Proposal for a regulation of the EUROPEAN PARLIAMENT AND OF THE COUNCIL laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006

29.9.2026

PROVISIONAL AGREEMENT RESULTING FROM INTERINSTITUTIONAL NEGOTIATIONS

Subject: Proposal for a regulation of the EUROPEAN PARLIAMENT AND OF THE COUNCIL laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006

(COM(2023)0193 – C90144/2023 – 2023/0131(COD))

The interinstitutional negotiations on the aforementioned proposal for a regulation have led to a compromise. In accordance with Rule 75(4) of the Rules of Procedure, the provisional agreement reproduced below is submitted to the Committee on Public Health for decision by way of a single vote.

Brussels,

24

February

2026

(

OR.

en

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6366

/

26

LIMITE

SAN 90

PHARM 14

MI 127

VETER 21

ENV 130

RECH 66

Brussels,

24

February

2026

(

OR.

en

)

6366

/

26

LIMITE

SAN 90

PHARM 14

MI 127

VETER 21

ENV 130

RECH 66

European Union

Interinstitutional File:

2023/0131 (COD)

COMPET 189

CODEC 236

PI 21

NOTE

Delegations will find in Annex the final compromise text of the Regulation laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency.

ANNEX

Proposal for a

REGULATION

OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

of

laying down Union procedures for the authorisation and supervision of medicinal products

Proposal for a

REGULATION

OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

of

laying down Union procedures for the authorisation and supervision of medicinal products

for human use and establishing rules governing the European Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty on the Functioning of the European Union, and in particular Article 114 and Article 168(4), point (c), thereof,

Having regard to the proposal from the European Commission,

After transmission of the draft legislative act to the national parliaments,

Having regard to the opinion of the European Economic and Social Committee,

Having regard to the opinion of the Committee of the Regions,

Acting in accordance with the ordinary legislative procedure,

Whereas:

(1) The Union pharmaceutical framework has enabled the authorisation of safe, efficacious

and high-quality medicines in the Union, contributing to a high level of public health and a smooth functioning of the internal market of these products.

(2) The Pharmaceutical Strategy for Europe marks a turning point with the addition of further

key objectives and by creatingaiming to create an attractive environment for research, development and production of medicinal products in the Union, along with a modern framework that makes innovative and established medicinal products available to patients and healthcare systems at affordable prices, while strengthening the fight against shortages of medicinal products and ensuring security of supply and addressing environmental concerns.

(2a) Ensuring that patients receive the medicines they need, when they need them, regardless

of where they live in the Union, is a central objective of the European Health Union. Ensuring the competitiveness of the European pharmaceutical industry, whilst providing better availability of medicines and more equal and timely access for patients, is a key objective of the Union pharmaceutical reform.

(2b) Published on 24 October 2023, the communication of the Commission entitled ‘Addressing medicine shortages in the EU’ outlined key measures aimed at aims to addressing critical shortages of medicines and strengthening security of supply in the Union in anticipation of the measures included in the pharmaceutical regulation. Among other things, this Communication foresaw a first informal Union list of critical medicines and the launch of a European voluntary solidarity mechanism for medicines allowing Member States to request support from another Member State and redistribution of available stocks in the event of shortage.

(3) Addressing unequal patient access of medicinal products has become a key priority of the

Pharmaceutical Strategy for Europe as has been highlighted by the Council and the European Parliament. Member States and the European Parliament have called for revised mechanisms and incentives for development of medicinal products tailored to the level of unmet medical need, while ensuring that the process is transparent, patient access and availability as well as affordability of medicinal products in all Member States.

(4) Previous amendments to the Union pharmaceutical legislation have addressed access to

medicinal products by providing for accelerated assessment for marketing authorisation applications or by allowing conditional marketing authorisation for medicinal products for unmet medical need. While these measures accelerated the authorisation of innovative and promising therapies in some areas, these medicinal products do not always reach the patient and patients in the Union still have different levels of access to medicines. In

addition, many unaddressed public health priorities remain.

(5) The COVID-19 pandemic has spotlightedfurther underlined critical issues, which require

a reform of the Union pharmaceuticals framework to strengthen its resilience, while improving the availability of medicinal products and to ensure that it contributes to public health needs and serves the people under all circumstances.

(6) For the sake of clarity, it is necessary to replace Regulation (EC) No 726/2004 of the European Parliament and of the Council with a new Regulation.

(7) Veterinary medicinal products are governed by Regulation (EU) No 2019/6 of the European Parliament and of the Council. These medicinal products are outside the scope of this Regulation, even if certain provisions regarding the governance and general tasks of the Agency set out in this Regulation apply to these medicinal products. The specific tasks of the Agency in respect to veterinary medicinal products are laid down in Regulation 2019/6 and Regulation 470/2009 of the European Parliament and of the Council.

(8) The scope of centrally authorised medicinal products has been adapted to the realities of

the market and technological development as well as the need to ensure a centralised assessment for certain categories of medicinal products. In the light of the Commission's report on the experience gained, it has proved necessary to improve the operation of the marketing authorisation procedures for the placing of medicinal products on the Union market and to amend certain administrative aspects of the European Medicines Agency. In addition, the regulatory framework should be adapted to the current market conditions and economic reality, while continuing to safeguard a high level of protection of public health and the environment. The conclusions of that report call for corrections to some of the operating procedures and require adaptations to take account of scientific and technological development. It also emerges from the report that the general principles previously established which govern the centralised marketing authorisation procedure ('centralised procedure’) should be maintained.

(9) As to the scope of this Regulation, the authorisation of antimicrobials is, in principle, in the

interest of patients' health at Union level and therefore it should be made possible to authorise them at Union level.

(10) With a view to maintain a high-level of scientific evaluation for new medicinal products

and medicinal products that will serve the entire Union population, the centralised procedure should be mandatory for high-technological medicinal products, particularly those resulting from biotechnological processes, for advanced therapy medicinal products, priority antimicrobials, orphan medicinal products, paediatric use medicinal products applying for paediatric use marketing authorisation and any medicinal product that includes ana new active substances not authorised before the last important change to thesubstance. In addition, the mandatory scope of the centralised procedure in 2004should reflect the scope provided for by Regulation (EC) 726/2004 and should therefore continue to apply to medicinal products authorised between 20 May 2004 and the date of entry into application of this Regulation, which contained a new active substance and for the indications listed in Annex I.

(11) As regards medicinal products for human use, optional access to the centralised procedure

should also be foreseen in cases where use of a single procedure produces added value for the patient. The centralised procedure should remain optional for medicinal products which, although not belonging to the categories of products to be authorised by the Union, are nevertheless therapeutically innovative. It is also appropriate to allow access to this procedure for medicinal products which, although not innovative, may be of benefit to society or to patients, including paediatric patients, if they are authorised from the outset at Union level, such as certain medicinal products which can be supplied without a medical prescription. This option may be extended to generic and biosimilar medicinal products authorised by the Union, provided that this in no way undermines either the harmonisation achieved when the reference medicinal product was evaluated or the results of that evaluation. At the same time, to ensure wide availability of generic medicinal products, those medicinal products may be authorised in any case by the competent authorities of the Member States, even if they are based on a centrally authorised reference medicinal product.

(11a) The Court of Justice of the European Union (hereafter “the Court”) has on numerous

occasions held that the health and life of humans rank foremost among the assets and interests protected by the Treaty. According to the Charter of Fundamental Rights, a high level of human health protection shall be ensured in the definition and implementation of all the Union's policies and activities. The centralised procedure ensures a high standard of scientific assessment and delivers significant benefits to the Union’s patient population, particularly regarding innovative medicines that can improve diagnosis, prevention and treatment of diseases and patients’ lives. In addition to its objective of guaranteeing a high level of protection of public health at Union level, the centralised procedure also brings greater clarity and efficiency to the Union’s authorisation system. This allows applicants of such products to benefit from easier and harmonised access to the European Union market. However, these innovative medicinal products are often unevenly available across the Union; this results in different levels of patient access depending on the Member State in which patients live. While fully respecting fundamental rights and without prejudice to the provisions of the Treaties, including provisions on the free movement of goods and competition, it is essential that marketing authorisation holders who obtain a centralised marketing authorisation for such medicinal products make every effort to place them on the market in all Member States.

In light of the fact that medicinal products are key for a broad and good therapeutic offer to patients in the EU, this is necessary to maintain a high level of public health protection across the EU, remove obstacles within the internal market and to strengthen Union-wide access to these products. Marketing authorisation holders should, in addition to established national legislation and procedures aiming at making available and supplying medicinal products at national level, also make their best efforts in complying with new mechanisms provided by the revised Directive that allow Member States to signal directly to companies their interest to have supply of a specific new medicinal product. Accordingly, a marketing authorisation holder for a medicinal product authorised through the centralised procedure which is subject to regulatory protection or intellectual property rights, should ensure that the medicinal product is made available and supplied in accordance with the needs of patient populations across all Member States. This obligation, however, should neither compromise the financial viability of the company nor be considered breached where external factors beyond the

company’s control make supply in all Member States impossible.

(12) The structure and operation of the various bodies making up the Agency should be

designed in such a way as to take into account the need to constantly renew scientific expertise, the need for cooperation between Union and national bodies, the need for adequate involvement of civil society, and the future enlargement of the Union. The various bodies of the Agency should establish and develop appropriate contacts with the parties concerned, in particular with representatives of patients, consumers and healthcare professionals.

(13) The chief task of the Agency should be to provide Union institutions and Member States

with the best possible scientific opinions to enable them to exercise the powers of authorisation and supervision of medicinal products conferred on them by Union legal acts in the field of medicinal products. Marketing authorisation should be granted by the Commission only after a single scientific evaluation procedure addressing the quality, safety and efficacy of high-technology medicinal products has been conducted by the Agency, applying the highest possible standards.

(13a) When assessing the marketing authorisation application of the medicinal product, the Agency should draw up the European assessment report on the quality, safety, efficacy, and the environmental risk assessment of the medicinal product and the reasons for its opinion. The Agency should make publicly available a summary of the European assessment report and a summary of the environmental risk assessment, after the deletion of any information of a commercially confidential nature and written in a manner that is understandable to the public.

(14) To ensure close cooperation between the Agency and scientists operating in Member States, the composition of the Management Board should be such as to guarantee that the competent authorities of the Member States are closely involved in the overall management of the Union system for authorising medicinal products.

(14a) To preserve the scientific integrity of the work and activities of the European Medicines Agency, the independence and impartiality of the members of the Management Board, the committees, rapporteurs and experts, who participate in meetings or working groups of the Agency, is crucial to avoid any conflict of interest. In implementing this objective, the Agency faces the challenge of balancing the need for specific expert input within tight timelines with the necessity of safeguarding the credibility of its decisions from being compromised by conflicts of interest. In certain fields, such as rare diseases, special populations, niche therapeutic indications and highly innovative technologies, the pool of experts is limited, and many are involved in clinical research on medicinal products. In situations where specific expertise is required and can be provided only by individuals with competing interests, which would normally disqualify or limit their involvement in the Agency’s activities as a member or expert, it may still be in the interest of public health to allow these individuals to provide observations before a scientific assessment is finalised, while excluding them from direct involvement in discussions or decision-making.

(15) The Agency's budget should be transparent and composed of fees and charges paid by the

private sector and contributions from the Union budget to implement Union policies and contributions paid from third countries, and in accordance, where applicable, with Regulation 2024/568. Although the majority of its funding comes from fees, the Agency is a public authority. It is of utmost importance to safeguard its integrity and impartiality in order to maintain public trust in its work and the Union regulatory framework.

(15a) The staff of the Agency, including the Executive Director and the Deputy Executive Director of the Agency, as officials or other servants of the Union, as are bound by independence , impartiality, integrity and other obligations provided for in the Staff Regulations and the Conditions of Employment of Other Servants and the rules adopted by agreement between the institutions of the Union, which include obligations after leaving the service such as engaging in lobbying or advocacy vis-à-vis staff of their former institution for their business, clients or employers on matters for which they were responsible. The Staff Regulations also lay down rules for those intending to engage in an occupational activity, whether gainful or not, after leaving the service and provides for the possibility for the Agency, having regard to the interests of the service, either forbid them from undertaking it or give its approval subject to any conditions it thinks fit.

(16) Exclusive responsibility for preparing the Agency's opinions on all questions concerning

medicinal products for human use should be vested in the Committee for Medicinal Products for Human Use.

(17) The creation of the Agency through Council Regulation (EEC) No 2309/931 which was

replaced by Regulation (EC) No 726/2004 has made it possible to reinforce the scientific evaluation and monitoring of medicinal products in the Union, in particular through its scientific bodies and committees for which competent authorities of the Member States provide experts and expertise, ensuring a high quality and independent assessment. This Regulation does not establish a new Agency. The Agency mentioned inAs this Regulation isreplaces Regulation 726/2004, the Agency, previously established by Regulation (EC) No 726/2004, should continue its functioning in accordance with this Regulation.

(18) The field of activity of the scientific committees should be enlarged and their operating

methods and composition modernised. In this regard it is important to ensure patient and healthcare professional representation in the Committee for Human Medicinal Products as it is the main evaluation committee of the Agency for medicinal products for human use.

(18a) The Commission should select, based on a public call for expression of interest,

representatives of patients and healthcare professionals to the Committee for Medicinal Products for Human Use and the Pharmacovigilance Risk Assessment Committee. Healthcare professionals can be represented by doctors and pharmacists. The appointment of such representatives should ensure there is a well-balanced representation of medical specialties and diseases amongst appointed members and alternates, and there are robust rules on the prevention of conflicts of interests including financial or other interests in the pharmaceutical or medical devices industry which could affect their impartiality.

(19) Scientific advice for future applicants seeking a marketing authorisation should be

provided more generally and in greater depth and should be adapted to the specificities of the medicinal product concerned. Similarly, structures allowing the development of advice for companies, in particular small and medium-sized enterprises (‘SMEs’) and notfor-profit entities, should be put in place. The Agency should also promote open and public exchanges about latest scientific developments and updates of scientific guidelines.

(20) Promising medicinal products that have the potential to significantly address patients’

unmet medical needs and are expected to be of major interest from the point of view of public health, in particular as regards therapeutical innovation, or are priority antimicrobials or are likely to target a neglected tropical disease, should benefit from early and enhanced scientific support. Such support will ultimately help patients benefit from new therapies as early as possible.

(20a) It is important to recognise that unmet medical needs also exist in the area of mental

health, and that promising medicinal products to address such unmet medical needs

should also benefit from early and enhanced scientific support.

(21) In order to allow for advice that is more informative and an exchange of information

between different bodies, scientific advice provided by the Agency should sometimes take place in parallel to scientific advice provided by other bodies. This should be the case for the joint scientific consultation carried out by the Member State Coordination Group on

Health Technology Assessment foreseen in Regulation (EU) 2021/2282 of the European Parliament and of the Council and, in cases of medicinal products involving a medical device, the consultation of the expert panels as described in Article 106 of Regulation (EU) No 2017/745 of the European Parliament and of the Council. Where parallel scientific advice consultation mechanisms are established under other relevant Union legal acts, a similar mechanism should apply.

(22) It is also necessary to reinforce the role of the scientific committees in such a way as to

enable the Agency to participate actively in international scientific dialogue and to develop certain activities that will be necessary, in particular regarding international scientific harmonisation and technical cooperation with the World Health Organization.

(23) Furthermore, without prejudice to the provisions laid down in Regulation (EU) 2019/6,

which remain applicable for veterinary medicinal products, in order to create greater legal certainty, it is necessary to define the responsibilities regarding the transparency rules for the Agency's work, to set certain conditions for the marketing of medicinal products authorised by the Union, to confer on the Agency powers to monitor the distribution of medicinal products authorised by the Union, to carry out inspections together with the Member States in third countries, and to specify the sanctions and the procedures for implementing them in the event of failure to observe the provisions of this Regulation and the conditions contained in the marketing authorisations granted under the procedures it establishes.

(24) In particularWithout prejudice to the powers of the national competent authorities and

without undermining their national inspection resources, the Agency should be empowered and given theprovided with the targeted inspection capacity to carry out inspections, where this iscontribute to the strenghtening of the supervision of the manufacturing of the medicinal products worldwide, in the interest of the Union and where the competent authorities of the Member States request support in carrying out their tasks under revised Directive 2001/83/EC of the European Parliament and of the Council. TheUnion.The interest of the Union may concern situations where, to ensure faster access to medicinal products, challenges with inspections capacities at national level have to be addressed in a timely manner or where a response to a public health emergency or a major event requires immediate action. ProvidingTherefore, the Agency with appropriate inspectionshould be empowered and given the capacity will also, in the interestto support Member States with regard to inspections in third countries. In particular, where the competent authorities of the Union, facilitate the dissemination of best practices, knowhow, and improve the oversight of manufacturing of medicinal products worldwide. Following theMember States request from asupport in carrying out their tasks under revised Directive 2001/83/EC of the European Parliament and of the Council, the Agency should be able to participate in inspections. Where the competent authority of thea Member State cannot carry out an inspection, the Agency, at its own discretion, can should facilitate the delegation of the inspection to another competent authority of a Member State. As a last resort, where no other competent authority of a Member State is able to accept to either provide support to the inspections of sites located in the Union orthe delegation to carry out inspections of sites located in third countriesan inspection, the competent authority concerned should be able to request the Agency to carry out the inspection.

(25) In certain cases, shortcomings in Member States’ system ofTo ensure consistency in

supervision and related enforcement activities could risk to substantially hinder the achievement of the objectives of this Regulation and those of revised Directive

2001/83/EC which could even lead to the emergence of risks to public health. To address these challengesin the Union, harmonised inspection standards should be ensured through the establishment of a joint audit programme within the Agency. This joint audit programme will also further harmonise the interpretation of good manufacturing and distribution practices on the basis of Union legislative requirements. As regards to its implementation, it takes into account the specific constitutional and administrative structures of each Member State pursuant to Article 4(2) TEU while ensuring the effectiveness of such implementation, in accordance with Article 4(3) of TEU.Moreover, it will support further mutual recognition of inspection outcomes between Member States and with strategic partners. Within the joint audit programme, the competent authorities are subject to regular audits conducted by other Member States to maintain an equivalent and harmonised quality system and to ensure an appropriate implementation of relevant good manufacturing and distribution practices into national laws and equivalence with other EEA inspectoratesMember States.

(26) An The inspection working groupgroups, which providesprovide input and

recommendations on all matters relating, directly or indirectly, to good clinical practice, good manufacturing practice and , good distribution practice and good

pharmacovigilance practice, irrespective of the marketing authorisation procedure through different reporting lines, should be established within the Agency. In particular, thatthe working group in charge of good manufacturing and good distribution practices should be responsible for the establishment, development and overall supervision of the joint audit programme.

(26a) Pharmaceutical research plays a decisive role in the continuing improvement in public

health and in ensuring the Union’s competitiveness. Medicinal products, in particular those that are the result of long, costly research will not continue to be developed in the Union unless they are covered by favourable rules that provide for sufficient protection to encourage such research. While such rules can contribute to the attractiveness of the Union market, they are however agnostic to the medicines’ geographical origin and medicines from third countries authorised in the Union are equally eligible to receive Union incentives.

(27) To promote innovation and the development of new medicinal products by SMEs within

the meaning of Commission Recommendation 2003/361/EC, and to reduce the cost of the placing on the market of medicinal products for human use authorised via the centralised procedure, these undertakings should benefit from a support scheme from the Agency.

(28) The support scheme should be composed of regulatory, procedural and administrative

support, and of a reduction, deferral or waiver of fees. The scheme should cover the various steps involved in pre-authorisation procedures, such as scientific advice, the submission of the marketing authorisation application, and post-authorisation procedures.

(29) LegalNot-for profit entities that are not engaged in an economic activity such as

universities, public bodies, research centres or not-for-profit organisations, represent an important source of innovationresearch in the area of unmet medical needs, research in different subpopulations, repurposing and treatment optimisation and should also benefit from this support scheme. Whereas it should be possible to take account of the particular situation of these entities on an individual basis, such support can best be achieved by means of a dedicated support scheme, including administrative support and through the reduction, deferral and waiver of fees.

(30) The Agency should be empowered to give scientific recommendations on whether a

product under development, which could potentially fall under the mandatory scope of the centralised procedure, meets the scientific criteria to be a medicinal product. Such an advisory mechanism would address, as early as possible, questions related to borderline cases with other areas such as substances of human origin, cosmetics or medical devices, which may arise as science develops. To ensure that recommendations given by the Agency take into account the views of equivalent advisory mechanisms in other legal frameworks, the Agency should consult the relevant advisory or regulatory bodies.

(31) To increase transparency of scientific assessments and all other activities, a European

medicines web-portal should be created and maintained by the Agency.

(31a) The Union Register of medicinal products lists all medicinal products for human use as

well as orphan medicinal products that have received a marketing authorisation by the

Commission through the centralised procedure. The information provided in the Union Register can be used to search for pertinent information on the medicinal product in question, including the active substance, and any post-authorisation requirements as well as applicable prolongations to regulatory protection periods.

(32) Experience with the functioning of the regulatory system has shown that the existing European Medicines Agency multi-scientific committee structure often creates complexity in the scientific assessment process among committees, duplication of work and nonoptimised use of expertise and resources. In addition, the Agency and the competent authorities of the Member States are confronted with challenges related to limited capacity and appropriate expertise to deal with increasing number of procedures related to existing medicinal products and assessment of new ones, in particular cutting edge innovative and complex medicinal products.

(33) To optimise the functioning and efficiency of the regulatory system, the structure of the Agency’s scientific committees is simplified and reduced to two main Committees for medicinal products for human use, the Committee for Medicinal Products for Human Use (CHMP) and Pharmacovigilance Risk Assessment Committee (PRAC).

(33a) The Agency and its committees should, where necessary, establish the appropriate

working parties to ensure the adequate expertise for the evaluation of medicines, including an Environmental Risk Assessment working party. That working party should have the scientific expertise necessary to characterise and assess the environmental risks, and the mitigation measures for such risks, related to the use and disposal of medicinal products.

(34) The simplification of procedures should not have an impact on standards or the quality of

scientific evaluation of the medicinal products to guarantee the quality, safety and efficacy of medicinal products. It should also allow for the reduction of the scientific evaluation period from 210 days to 180 days.

(35) The Agency’s scientific committees should be able to delegate some ofsupported, in

relation to their evaluation duties, by to working parties which should be open to experts from the scientific world and appointed for this purpose, whilst retaining complete responsibility for the scientific opinions issued by them.

(36) The expertise of the Committee for Advanced Therapies (CAT), the Committee for Orphan Medicinal Products (COMP), the Paediatric Committee (PDCO) and Committee for Herbal Medicinal Products (HMPC) is retained through working groups, working parties, advisory groups, and a pool of experts who are organised based on different domainsareas of expertise and who are giving input to the CHMP and PRAC. This structure gives the possibility for CHMP and PRAC to call upon additional scientific experts to provide specific input and advice on specific aspects raised during the evaluation. In addition, patients and healthcare professionals can be part of the pool of experts based on their expertise. The CHMP and PRAC consists of experts from all Member States while working parties and expert groups consist in majority of experts appointed by the Member States, based on their expertise, and, if necessary, of external experts. The model of rapporteurs remains unchanged. The efficiency gain, involvement of adequate scientific expertise and broad geographic representation of experts in the scientific committees, working parties and working groups will be ensured as part of the strategy for the organisational management and internal control systems. Representation of patients and health care professionals, with expertise in alla wide range of areas, including rare and paediatric diseases, is increasedassured at the CHMP and PRAC, in addition to the dedicated working groups representing patients and health care professionals. Information regarding the composition and work of the committees, working parties and working groups, should be publicly available.

(36a) It is crucial that the expertise of experts is not only preserved within working groups,

working parties, and a pool of experts, but also that the relevant expertise is expanded to cover emerging technologies, incorporates expertise from a broader range of Member States, and enables the Agency to continue fulfilling its obligations at the highest scientific level. It is also essential that experts can share knowledge, expand their skills through training programs, such as those offered by the EU Network Training Center (EUNTC), and engage in on-the-job learning activities, including shadowing rapporteurs, mentoring, and participating in discussions on topics of interest in working

parties, European Scientific Expert Groups (ESECs), and other relevant fora.

(37) Scientific committees, such as like the CAT have been instrumental to ensure expertise

and capacity building in an emerging technological field. However, after more than 15 years, advanced therapy medicinal products are now more common. The full integration of their assessment in the work of the CHMP will facilitate the assessment of medicinal products within the same therapeutic class, independent of the technology on which they are based. It will also ensure that all biological medicinal products are assessed by the same committee.

(38) To allow for more informative advice on clinical trial applications and therefore a more

integrated development advice in view of future data requirements for marketing authorisation applications, the Agency can engage in consultation with representatives from Member States with clinical trial expertise. Nevertheless, decisions on clinical trial applications should remain within the competence of the Member States, in accordance with Regulation (EU) No 536/2014 of the European Parliament and of the Council.

(39) To allow for a more informative decision making and for exchange of information and

pooling of knowledge on general issues of scientific or technical nature related to the tasks of the Agency regarding medicinal products for human use, in particular to scientific guidelines on unmet medical needs and the design of clinical trials, or other studies and the generation of evidence along the life cycle of medicinal product, the Agency should be able to have recourse to a consultation process of authorities or bodies active along the life cycle of medicinal products. These authorities could be, as appropriate, representatives from Heads of Medicines Agencies, the Clinical Trial Coordination and Advisory

Group, the SoHO Coordination Board, the Coordination Group on Health Technology Assessment, Medical Devices Coordination Group, medical devices national competent authorities, national competent authorities for pricing and reimbursement of medicines, national insurance funds or healthcare payers. The Agency should also be able to extend the consultation mechanism to consumers, patients, healthcare professionals, industry, associations representing payers, or other stakeholders, as relevant.

(40) Member States should ensure adequate funding of competent authorities to carry out their

tasks under this Regulation and under [revised Directive 2001/83/EC]. In addition, in line with the Joint Statement of the European Parliament, the Council of the EU and the European Commission on decentralised agencies, Member States should ensure adequate resources are assigned by the competent authorities of the Member States for the purpose of their contributions to the work of the Agency, taking into account the cost-based remuneration they receive from the Agency.

(41) In the context of cooperation with international organisations to support global public

health, it is important to leverage the scientific assessment performed by the Union and to promote reliance by third country regulatory authorities based on the use of certificates of medicinal products for authorised medicinal products in the Union. An applicant may request independently or as part of an application under the centralised procedure a scientific opinion from the Agency for the use of the medicinal product for markets outside the Union. The Agency should cooperate with the World Health Organization and relevant third country regulatory authorities and bodies to issue such scientific opinions.

(42) The Agency may cooperate with competent authorities of third countries in the context of

performing its tasks. Such regulatory cooperation should be coherent with the broader economic relationship of the Union with the third country concerned, taking account of the relevant international agreements between the Union and that third country.

(43) In the interest of public health, marketing authorisation decisions under the centralised

procedure should be taken on the basis of the objective scientific criteria of quality, safety and efficacy of the medicinal product concerned, to the exclusion of economic and other considerations. However, Member States should be able, exceptionally and temporarily, to prohibit the use in their territory of medicinal products for human use. Member States should provide justification for such prohibition of use to the Commission and the Agency.

(43a) The Union is required, pursuant to Article 208 of the Treaty on the Functioning of the European Union (TFEU), to take account of development objectives in policies that are likely to have an impact on low- and middle-income countries. Union pharmaceutical legislation has a role to play in the realisation of global public health objectives by promoting the development of efficacious, safe, accessible, and affordable innovations for antimicrobial resistance, poverty-related, emerging and re-emerging health threats, and neglected diseases, and other conditions of global public health interest. For example, as part of its Priority Medicines scheme, the Agency will offer dedicated support to medicine developments in the area of neglected tropical diseases. The Commission should continue to encourage research, development and innovation in areas of major global health interest, in line with its international commitments.

(44) The quality, safety and efficacy criteria of [revised Directive 2001/83/EC] should apply to

medicinal products authorised by the Union under the centralised procedure. The benefitrisk balance of all medicinal products will be assessed when they are placed on the market, and at any other time the competent authority deems appropriate.

(45) Marketing authorisation applications, like any other application submitted to the Agency,

should follow the digital by default principle and hence be sent to the Agency in electronic form. Applications should be assessed based on the file submitted by the applicant in accordance with the different legal basis provided by [revised Directive 2001/83/EC]. At the same time, the Agency and the relevant committees may take into account any information that is in its possession. Applicants shall be requested to generally submit raw data, in particular with regard to the clinical trials performed by the applicant in order to ensure a full assessment of the quality, safety and efficacy of the medicinal product.

However, this obligation to submit raw data should not be construed as obliging the Agency and the relevant committees to examine or make use of all such data during their scientific assessment. They should retain the discretion to determine in which cases such data are relevant and necessary for the purposes of assessing the application.

(45a) In the context of medicines development and authorisation, it is crucial that particular

attention is given to the composition of clinical trials, to ensure comprehensive clinical data and, where appropriate, gender-based equity.

(46) Directive 2010/63/EU of the European Parliament and of the Council on the protection of

animals used for scientific purposes1 lays down provisions on the protection of animals used for scientific purposes based on the principles of replacement, reduction and refinement. Any study involving the use of live animals, which provides essential information on the quality, safety and efficacy of a medicinal product, should take into account those principles of replacement, reduction and refinement, where they concern the care and use of live animals for scientific purposes, and should be optimised in order to provide the most satisfactory results whilst using the minimum number of animals. The procedures of such testing should be only used where necessary and be designed to avoid causing pain, suffering, distress or lasting harm to animals and should follow the available Agency and the International Committee for Harmonisation (ICH) guidelines. In particular, the marketing authorisation applicant and the marketing authorisation holder should take into account the principles laid down in Directive 2010/63/EU, including, where possible, use ofgiving priority to new approach methodologies in place of animal testing. These can include but are not limited to: in vitro models, such as microphysiological systems including organ-on-chips, (2D and 3D) cell culture models, organoids and human stem cells-based models; in silico tools, in chemico technologies and any combination thereof or read-across models. Ultimately, efforts should be made to fully replace procedures on live animals for scientific purposes.

(46a) This Regulation contributes to the implementation of the One Health Approach,

stressing the well-established interconnectedness between human, animal and ecosystem health, and the need to include those three dimensions when addressing public health threats. Environmental stress and degradation, including biodiversity loss, contribute to the transmission of diseases between, and the disease burden of, humans and animals. In addition, pollution from active pharmaceutical ingredients negatively affects the quality of waters and ecosystems, causes antimicrobial resistance to increase rapidly, posing risks to public health globally.

(47) Procedures should be in place to facilitate joint animal testing, wherever possible, in order

to avoid unnecessary duplication of testing using live animals covered by Directive 2010/63/EU. Marketing authorisation applicants and marketing authorisation holders should make all efforts to reuse animal study results and make the results obtained from animal studies publicly available. For abridged applications marketing authorisation applicants should refer to the relevant studies conducted for the reference medicinal product.

(48) The summary of product characteristics and the package leaflet should reflect the

assessment of the Agency and be part of its scientific opinion. The opinion may recommend certain conditions that should be part of the marketing authorisation, for example on the safe and efficacious use of the medicinal product or on post-authorisation obligations that have to be complied with by the marketing authorisation holder. Those conditions may include the requirement to conduct post-authorisation safety or efficacy studies or other studies that are considered necessary to optimise the treatment, for example where the proposed dose scheme by the applicant, whilst acceptable and justifying a positive benefit-risk balance, could be further optimised post-authorisation. Where the applicant disagrees with parts of the opinion, the applicant may request its reexamination.

(49) Due to the need to reduce overall approval times for medicinal products, the time between

the opinion of the Committee for Medicinal Products for Human Use (CHMP) and the final decision on the application for a marketing authorisation should in principle be no longer than 46 days.

(50) On the basis of the opinion of the Agency the Commission should adopt a decision on the

application by means of implementing acts. In justified cases, the Commission may return the opinion for further examination or deviate in its decision from the opinion of the Agency. Taking into account the need to make medicinal products swiftly available to patients, it should be acknowledged that the chairperson of the Standing Committee on

Medicinal Products for human use will use the available mechanisms under Regulation (EU) 182/2011 of the European Parliament and of the Council and notably the possibility to obtain the committee’s opinion by written procedure and within expeditious deadlines which, in principle, will not exceed 10 calendar days.

(51) As a general rule a marketing authorisation should be granted for an unlimited time;

however, one renewal may be decided only on justified grounds related to the safety of the medicinal product.

(52) There is a need to provide for the ethical requirements of Regulation (EU) No 536/2014 to

apply to medicinal products authorised by the Union. In particular, with respect to clinical trials conducted outside the Union on medicinal products destined to be authorised within the Union, at the time of the evaluation of the application for authorisation, it should be verified that these trials were conducted in accordance with the principles equivalent to these of Regulation (EU) No 536/2014 as regards the rights and safety of the subject and the reliability and robustness of the data generated in the clinical trial.

(53) Environmental risks may arise from medicinal products containing or consisting of

genetically modified organisms. It is thus necessary to subject such medicinal products to an environmental risk-assessment procedure similar to the procedure under Directive 2001/18/EC of the European Parliament and of the Council, to be conducted in parallel with the evaluation, under a single Union procedure, of the quality, safety and efficacy of the medicinal product concerned. The environmental risk-assessment should be conducted in accordance with the requirements set out in this Regulation and in [revised Directive 2001/83/EC] which are based on the principles set out in Directive 2001/18/EC but taking into account the specificities of medicinal products.

(54) [revised Directive 2001/83/EC] permits Member States to temporarily allow the use and

supply of unauthorised medicinal products for public health reasons or individual patient needs and that includes medicinal products to be authorised under this Regulation. It is also necessary, that Member States are allowed under this Regulation to make a medicinal product available for compassionate use prior to its marketing authorisation. In those exceptional and urgent situations, where there is a lack of a suitable authorised medicinal product, the need to protect public health or the health of individual patients must prevail over other considerations, in particular the need to obtain a marketing authorisation and consequently, to have available complete information about the risks posed by the medicinal product, including any risks to the environment from medicinal products containing or consisting of genetically modified organisms (GMOs). To avoid delays in making these products available or uncertainties as regards their status in certain Member States, it is appropriate, in those exceptional and urgent situations, that for a medicinal product containing or consisting of GMOs, an environmental risk assessment or consent in accordance with Directive 2001/18/EC or Directive 2009/41/EC of the European

Parliament and of the Council1 should not be a prerequisite. Nevertheless, in these cases, Member States should implement appropriate measures in line with the precautionary principle to minimise foreseeable negative environmental impacts resulting from the intended or unintended release of the medicinal products containing or consisting of GMOs into the environment.

(55) For medicinal products, the period for protection of data relating to non-clinical tests and

clinical trials should be the same as that provided for in [revised Directive 2001/83/EC].

(56) In order to meet, in particular, the legitimate expectations of patients and to take account of

the increasingly rapid progress of science and therapies, accelerated assessment procedures should be set up, reserved for medicinal products of major therapeutic interest, and procedures for obtaining conditional marketing authorisations subject to certain regularly reviewable conditions.

(57) Compassionate use programmes allow for an early access to medicinal products. Existing

provisions should be reinforced to ensure that a common approach is followed, whenever

(58) There is the possibility under certain circumstances for marketing authorisations to be

granted, subject to specific obligations or conditions, on a conditional basis or under exceptional circumstances. The legislation should allow under similar circumstances for medicinal products with a standard marketing authorisation for new indications to be authorised on a conditional basis or under exceptional circumstances. The medicinal products authorised on a conditional basis or under exceptional circumstances should in principle satisfy the requirements for a standard marketing authorisation with the exception of the specific derogations or conditions outlined in the relevant conditional or exceptional marketing authorisation and shall be subject to specific review of the fulfilment of the imposed specific conditions or obligations. It is also understood that the grounds for refusal of a marketing authorisation shall apply mutatis mutandis for such cases.

(59) In principle, only one marketing authorisation may be granted to an applicant for a

medicinal product. Duplicate marketing authorisations should only be granted in exceptional circumstances. When those exceptional circumstances are no longer present, notably as regards the protection by a patent or a supplementary protection certificate in one or more Member States, any potentially negative effects on markets from the existence of duplicate marketing authorisations should be minimised through a withdrawal of the initial or the duplicate marketing authorisation.

(60) Regulatory decision-making on the development, authorisation and supervision of

medicinal products may be supported by access and analysis of health data, including real world data, where appropriate, i.e. health data generated outside of clinical studies, and data generated via in silico methods, such as computational modelling and simulation, digital molecular representation and mechanistic modelling, digital twin technology and artificial intelligence (AI). The Agency should be able to use such data, including via the Data Analysis and Real World Interrogation Network (DARWIN) and the European Health Data Space interoperable infrastructure. Through these capabilities the Agency may take advantage of all the potential of supercomputing, artificial intelligence and big data science, to fulfil its mandate, without compromising privacy rights. The Agency should put in place sufficient, effective and specific technical and organisational measures to safeguard the fundamental rights and interests of data subjects in line with Union Law. Where necessary the Agency may cooperate with the competent authorities of the Member States towards this objective.

(61) The handling of health data requires a high level of protection against cyber attacks. It is

necessary for the Agency to be equipped with a high level of security controls and processes against cyber attacks to ensure that the Agency operates normally at all times. To that end, the Agency should establish a plan to prevent, detect, mitigate and respond to cyber attacks so that its operations are secure at all times, while preventing any illegal access to documentation held by the Agency.

(62) Due to the sensitive nature of health data, the Agency should safeguard its processing

operations and ensure that they respect the data protection principles of lawfulness, fairness and transparency, purpose limitation, data minimisation, accuracy, storage limitation, integrity and confidentiality. Where the processing of personal data is necessary for the purposes of this Regulation, such processing should be done in accordance with

Union law on the protection of personal data. Any processing of personal data under this

Regulation should take place in accordance with Regulation (EU) 2016/679 and Regulation (EU) 2018/1725 of the European Parliament and of the Council.

(63) Access to individual patient data from clinical studies in structured format allowing for

statistical analyses is valuable to assist regulators in understanding the submitted evidence and to inform regulatory decision-making on the benefit-risk balance of a medicinal product. The introduction of such possibility in the legislation is important to fosterfurther enable data-driven benefit-risk assessments at all stages of the life cycle of a medicinal product. This Regulation therefore empowers the Agency to requestreceive and use such data as part of the assessment of initial and post-authorisation applications.

(64) For generic and biosimilar medicinal products, as a general rule, risk management plans

should not be developed and submitted, also considering that the reference medicinal product has such a plan; however, in specific cases, a risk management plan for generic and biosimilar medicinal products should be developed and submitted to the competent authorities.

(65) In the preparation of scientific advice and in duly justified cases, the Agency should also

be able to consult authorities established in other relevant Union legal acts or other public bodies established in the Union, as applicable. These may include experts in clinical trials, medical devices, substances of human origin or any other as required for the provision of the scientific advice in question.

(66) Through the Priority Medicines (PRIME) scheme, the Agency has gained experience of the

provision of early scientific and regulatory support to developers of certain medicinal products that, based on preliminary evidence, are likely to address an unmet medical need and are considered promising at an early stage of development. It is appropriate to recognise this early support mechanism, including for priority antimicrobials and repurposed for medicinal products that have the potential to significantly address patients’ unmet medical needs and are expected to be of major interest from the point of view of public health, in particular as regards therapeutic innovation, or are antimicrobials addressing antimicrobial resistance or target a neglected tropical disease when they fulfil the criteria for the scheme, and allow. The Agency, in consultation with the Member States and the Commission, toshould establish selection criteria for promising medicinal products.

(67) The Agency, in consultation with the Member States and the Commission, should set the

scientific selection criteria for medicinal products that receive pre-authorisation support with priority to be given to the most promising developments in therapies. In the case of medicinal products for unmet medical needs, based on the scientific selection criteria set by the Agency, any interested developer can submit preliminary evidence to demonstrate that the medicinal product has the potential to provide a major therapeutic advancement with respect to theaddress an identified unmet medical need and be of major public health interest particularly regarding its therapeutic innovation.

(68) Before a medicinal product for human use is authorised for placing on the market of one or

more Member States, it generally has to undergo extensive studies to ensure that it is safe, of high quality and effective for use in the target population. However, in the case of certain categories of medicinal products for human use, in order to meet unmet medical needs of patients and in the interest of public health, it may be necessary to grant marketing authorisation on the basis of less complete data than is normally the case. Such marketing authorisation should be granted subject to specific obligations. The categories of medicinal products for human use concerned should be the medicinal products, including orphan medicinal products, that aim at the treatment, prevention or medical diagnosis of seriously debilitating or life-threatening diseases, or that are intended to be used in emergency situations in response to public health threats.

(69) The Union should have the means to carry out a scientific assessment of the medicinal

products presented in accordance with the decentralised marketing authorisation procedures. Moreover, with a view to ensuring the effective harmonisation of administrative decisions taken by Member States with regard to medicinal products presented in accordance with decentralised marketing authorisation procedures, it is necessary to endow the Union with the means to resolve disagreements between Member States concerning the quality, safety and efficacy of medicinal products.

(70) In the event of a risk to public health, the marketing authorisation holder or the competent

authorities should be able to make urgent safety or efficacy restrictions on their own initiative to ensure a swift adaption of the marketing authorisation to maintain the safe and efficacious use of the medicinal product by healthcare professionals and patients. If a review is launched on the same safety or efficacy concern addressed by urgent restrictions initiated by a competent authority, any written observations by the marketing authorisation holder should be considered in that review to avoid duplication of assessment.

(71) The terms of a marketing authorisation for a medicinal product for human use may be

varied. While the core elements of a variation are laid down in this Regulation, the Commission should be empowered to complement these elements by laying down further necessary elements, to adapt the system to technical and scientific progress, and to employ digitalisation measures to ensure that unnecessary administrative burden is avoided for marketing authorisation holders and competent authorities.

(71a) Competent authorities should have the power to evaluate additional evidence that may

affect the benefit-risk balance of medicinal products, beyond what is provided by marketing authorisation holders. When justified, competent authorities may recommend that the marketing authorisation holder varies the terms of its marketing authorisation.

(72) To avoid unnecessary administrative and financial burden both for the pharmaceutical

industry and the competent authorities, certain streamlining measures should be introduced. Electronic applications for marketing authorisations and for variations to the terms of the marketing authorisation should be made possible.

(73) To optimise the use of resources for both applicants for marketing authorisations and

competent authorities assessing such applications, a single assessment of an active substance master file should be introduced. The outcome of the assessment should be issued through a certificate. To avoid duplication of assessment, the use of an active substance master file certificate should be mandatory for subsequent applications or marketing authorisations for medicinal products for human use containing that active substance from an active substance master file certification holder. The Commission should be empowered to establish the procedure for the single assessment of an active substance master file. To further optimise the use of resources, the Commission should be empowered to extend the certification scheme to additional quality master files, e.g. in case of novel excipients, adjuvants, radiopharmaceutical precursors and active substance intermediates, when the intermediate is a chemical active substance by itself or used in conjugation with a biological substance.

(74) To avoid unnecessary administrative and financial burdens for applicants, marketing

authorisation holders and competent authorities, certain streamlining measures should be introduced. Electronic application for marketing authorisation and for variations to the terms of the marketing authorisation should be introduced. For generic and biosimilar medicinal products, except in specific cases, risk management plans do not need to be developed and submitted to the competent authorities.

(75) In a situation of public health emergency, it is of major interest for the Union that safe and

efficacious medicinal products can be developed and made available within the Union as soon as possible. Agile, fast and streamlined processes are of the essence. A range of measures already exists at Union level to facilitate, support and speed up the development of and granting marketing authorisations for treatments and vaccines during a public health emergency.

(76) It is considered appropriate to also have the possibility for the Commission to grant

temporary emergency marketing authorisations to address public health emergencies. Temporary emergency marketing authorisations may be granted provided that, having regard to the circumstances of the public health emergency, the benefit of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent to the fact that additional comprehensive quality, non-clinical, clinical data may still be required. A temporary emergency marketing authorisation should be valid only during the public health emergency. The Commission should be given the possibility to vary, suspend or revoke such marketing authorisations in order to protect public health or when the marketing authorisation holder has not complied with the conditions and obligations set out in the temporary emergency marketing authorisation.

(76a) It is appropriate to have in place transparency measures and standards regarding the Agency’s regulatory activities in relation to medicinal products, in particular those that receive a temporary emergency marketing authorisation. Those measures should include the timely publication of all relevant information on centrally approved medicinal products.

(77) The development of antimicrobial resistance is a growing concern and the pipeline of

effective antimicrobials is obstructed due to a market failure whereby antimicrobial research and development (R&D) is hampered by the low commercial value of the antimicrobial medicinal product market. It is therefore necessary to maintain the efficacy of existing antimicrobials for as long as possible and to consider a number of new measures to promote the development of priority antimicrobials that are effective against antimicrobial resistance and to support undertakings, often SMEs, and not-for-profit entities which choose to invest in this area. It is equally necessary to support research and development of novel antimicrobials including through the establishment of subscription models. Such models delink the volume of antimicrobial sales from the reward received, in particular through voluntary joint procurement and can help overcome such market failures. Such measures should facilitate the development of alternative treatments, such as bacteriophages, which can be effective against multi-drug resistant bacteria and can be used as an alternative treatment or together with antibiotics.

(77a) Reluctance to invest in the development of antimicrobials exists in part because the

development of antimicrobials is costly and many developers, often SMEs, cannot afford to proceed to the next stage of development. Additionally, when an antimicrobial is developed, the market is naturally limited by virtue of the need to use antimicrobials prudently. Therefore, it is necessary to consider further Union level action to support the development of antimicrobials and address existing market failures. Accordingly, a voluntary subscription model for the joint procurement of antimicrobials should be developed to ensure that a market exists for developers that delinks volumes sold from payment received.

(78) To be considered a ‘priority antimicrobial’, a medicinal product should represent a real

advancement against antimicrobial resistance and should therefore bring forward nonclinical and clinical data that underpin a significant clinical benefit with respect to antimicrobial resistance. When assessing the conditions for antibiotics, the Agency shall take into account the prioritisation of pathogens as regards the risk of antimicrobial resistance provided for in the ‘WHO priority pathogens list for R&D of new antibiotics’, specifically those listed as priority 1 (critical) or priority 2 (high) or in case there is an equivalent list of priority pathogens adopted at Union level, the Agency should take such Union list into account as a priority.

(79) The creation of a voucher rewarding the development of priority antimicrobials through an

additional year of regulatory data protection has the capacity to provide the needed financial support to developers of priority antimicrobials. However, in order to ensure that the financial reward which is ultimately borne by health systems is mostly absorbed by the developer of the priority antimicrobial and not the buyer of the voucher, the number of available vouchers on the market should be kept to a minimum. It is therefore necessary to establish strict conditions of granting, transfer and use of the voucher and to further give the possibility to the Commission to revoke the voucher under certain circumstances.

(80) A transferable data exclusivity voucher should only be available to those antimicrobial

products that bring a significant clinical benefit with respect to antimicrobial resistance, and which have the characteristics described in this Regulation. It is also necessary to ensure that an undertaking which receives this incentive is in turn capable to supply the medicinal product to patients across the Union in sufficient quantities and to provide information on all funding received for research related to its development in order to provide a full account of the direct financial support given to the medicinal product.

(81) To ensure a high level of transparency and complete information on the economic effect of

the transferable data exclusivity voucher, notably as regards the risk of overcompensation of investment, a developer of a priority antimicrobial is required to provide information on all direct financial support received for research related to the development of the priority antimicrobial. The declaration should include direct financial support received from any source worldwide.

(82) A transfer of a voucher for a priority antimicrobial may be conducted by sale and may only

be transferred once. The value of the transaction which may be monetary or otherwise agreed between the buyer and the seller, shall be made public so as to inform regulators and the public. The identity of the holder of a voucher that has been granted and not yet used should be publicly known at all times so as to ensure a maximum level of transparency and trust.

(83) The provisions related to transferable data exclusivity vouchers shall be applicable for a

specified period from the entry into force of this Regulation or until a maximum number of vouchers are granted by the Commission in order to limit the total cost of the measure to Member State health systems. The limited application of the measure will also provide the possibility to assess the effect of the measure in addressing the market failure in the development of new antimicrobials addressing antimicrobial resistance and assess the cost on national health systems. Such assessment will provide the necessary knowledge to decide whether to extend the application of the measure.

(84) The period of application of the provisions on transferable exclusivity vouchers for priority

antimicrobials and the total number of vouchers may be extended by the Parliament and the Council upon proposal by the Commission on the basis of the experience acquired.

(85) Where the Commission considers that there are reasons to believe that a medicinal product

could present a potential serious risk to human health, a scientific evaluation of the medicinal product should be undertaken by the Agency, leading to a decision whether to maintain, vary, suspend or revoke the marketing authorisation, and taken on the basis of an overall benefit-risk assessment. The Commission may also act on a centralised marketing authorisation where the conditions attached to it are not complied with.

(86) Medicinal products for rare diseases and for children should be subject to the same

provisions as any other medicinal product concerning their quality, safety, and efficacy, for example for what concerns the marketing authorisation procedures, the pharmacovigilance and, quality, and environmental risk assessment requirements. However, specific requirements also apply to them. Such requirements, which are currently defined in separate legislations, should be integrated in this Regulation in order to ensure clarity and coherency of all the measures applicable to these medicinal products.

(87) Some orphan conditions occur so infrequently that the cost of developing and bringing to

the market a medicinal product to diagnose, prevent or treat the condition cannot be recovered by the expected sales of the medicinal product. However, patients suffering from rare conditions should be entitled to the same quality of treatment as other patients; it is therefore necessary to stimulate the research, development and placing on the market of appropriate medications by the pharmaceutical industry.

(88) Regulation (EC) No 141/2000 of the European Parliament and of the Council has proved

to be successful in boosting developments of orphan medicinal products in the Union, although more progress is needed, as a majority of rare diseases are still without an authorised treatment; therefore an action at Union level remains preferable to uncoordinated measures by the Member States which may result in distortions of competition and barriers to intra-Union trade.

(89) The open and transparent Union procedure for the designation of potential medicinal

products as orphan medicinal products established by Regulation (EC) No 141/2000 should be maintained. To increase legal clarity and simplification, the specific legal provisions applicable to these medicinal products should be integrated in this Regulation.

(90) Objective criteria for the orphan designation based on the prevalence of the life-threatening

or chronically debilitating condition for which diagnosis, prevention or treatment is sought and the existence of no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the Union should be maintained; a prevalence of not more than five affected persons per 10 000 is generally regarded as the appropriate threshold. The orphan designation criterion on the basis of return on investment has been abolished, since it has never been used.

(91) The criterion for orphan designation based on prevalence of a disease may, however, not

be appropriate to identify rare diseases in all cases. For example, for conditions which have a short duration and high mortality, measuring the number of people that acquired the disease during a specific time period would better reflect if it is rare within the meaning of this Regulation than measuring the number of people who are ‘affected by it’ in a specific moment of time. With the aim to better identify only those diseases which are rare, the Commission should be empowered to set up specific designation criteria for certain conditions if the one provided for are not appropriate due to scientific reasons and on the basis of a recommendation of the Agency.

(92) With the aim to better identify only those diseases which are rare, the Commission should

be empowered to supplement the designation criteria by a delegated act if they are not appropriate for certain conditions due to scientific reasons and on the recommendation of the Agency. In addition, the designation criteria require implementing measures to be adopted by the Commission.

(93) If a satisfactory method of diagnosis, prevention or treatment of the condition in question

has already been authorised in the Union, the orphan medicinal product will have to be of significant benefit to those affected by that condition. In this context, a medicinal product authorised in one Member State is generally deemed as being authorised in the Union. It is not necessary for it to have Union authorisation or to be authorised in all Member States to be considered as a satisfactory method. In addition, commonly used methods of diagnosis, prevention or treatment that are not subject to a marketing authorisation may be considered satisfactory if there is scientific evidence of their efficacy and safety. In certain cases, medicinal products prepared for an individual patient in a pharmacy according to a medical prescription, or according to the prescriptions of a pharmacopoeia and intended to be supplied directly to patients served by the pharmacy, may be considered as satisfactory treatment if they are well known and safe and this is a general practice for the relevant patient population in the Union.

(94) The competence to designate a medicinal product as an orphan medicinal product, in the

form of a decision, is accorded to the Agency. This is expected to facilitate and expedite the designation procedure, while ensuring high level of scientific expertise.

(95) In order to incite faster authorisation of designated orphan medicinal products, the validity

of orphan designation has been set at seven years, with the possibility of extension by the Agency under certain specified conditions; the orphan designation may be withdrawn at the request of the orphan medicine sponsor, who provides a reasoned justification for the withdrawal request. The Agency makes the reasoned justification for the withdrawal request, when provided by the sponsor, publicly available.

(96) The Agency is responsible for designation of an orphan medicinal product as well as for

the setting up and management of a register of designated orphan medicinal products. That register should be publicly available and the minimum data which should be included in the register have been specified in this Regulation with the empowerment for the Commission to amend or supplement this data by a delegated act.

(97) Sponsors of orphan medicinal products designated under this Regulation should be entitled

to the full benefit of incentives granted by the Union or by the Member States to support the research and development of medicinal products for the diagnosis, prevention or treatment of such conditions, including rare diseases.

(98) Patients suffering from orphan conditions deserve medicinal products of the same quality,

safety and efficacy as other patients; designated orphan medicinal products should therefore be submitted to the normal evaluation process carried out by the Committee of Medicinal Products for Human Use for the applicant to obtain ana marketing authorisation for those indications which fulfil the criteria for orphan medicinal productdesignation, while a separate marketing authorisation may be granted for indications not fulfilling the criteria of an orphan medicinal product. Those marketing authorisations should be

considered as belonging to the same global marketing authorisation.

(99) A vast percentage of rare diseases remains without treatment with research and

development clustered in the areas where profit is better assured. Therefore, there is a need to target those areas where research is mostly needed and where investments are most risky.

(100) Orphan medicinal products addressing a high unmet medical needare considered as

breakthrough orphan medicinal products when they prevent, diagnose or treat conditions where either no other method of prevention, diagnosis or treatment exists or, if such method already exists, they would bring exceptional therapeutic advancement. In both cases, the criterion of meaningfulexist and result in a clinically relevant reduction in disease morbidity or mortality for the relevant patient population should ensure that only most effective medicinal products are covered. The Agency should draw up scientific guidelines on the category of ‘orphan medicinal products addressing a high unmet medical need’.

(101) Experience since the adoption of Regulation (EC) No 141/2000 shows that the strongest

incentive for industry to invest in the development and making available of orphan medicinal products is where there is a prospect of obtaining market exclusivity for a certain number of years during which part of the investment might be recovered. In addition to the periods of market exclusivity, orphan medicinal products will benefit from the periods of regulatory protection set out in [revised Directive 2001/83/EC], including the prolongations of regulatory data protection. However, where an orphan medicinal product obtains an additional therapeutic indication it will benefit only from the prolongation of market exclusivity.

(102) In order to incentivise research and development of breakthrough orphan medicinal

products addressing high unmet needs, to ensure market predictability and to ensure a fair distribution of incentives, a modulation of market exclusivity has been introduced; breakthrough orphan medicinal products addressing high unmet medical needs benefit from the longest market exclusivity, while market exclusivity for well-established use orphan medicinal products, requiring less investment, is the shortest. In order to ensure increased predictability for developers, the possibility to review the eligibility criteria for market exclusivity after six years after the marketing authorisation has been abolished.

(103) In order to encourage faster and wider access also to orphan medicinal products, an

additional period of one year of market exclusivity is granted to orphan medicinal products for a Union market launch, with the exception of well-established use medicinal products.

(104) To maximise the potential benefit of clinical research, continued exploration of new

indications for orphan medicinal products should be encouraged. To reward research into and development of new therapeutic indications, an additional period of one year of market exclusivity is provided for a new therapeutic indication (with a maximum of two indications).

(105) This Regulation includes several provisions aimed to avoid not-justified benefits being

derived from the market exclusivity and to improve accessibility of medicinal products by ensuring faster entry of generics and biosimilars, and similar medicinal products on the market. It also clarifies the concurrence of market exclusivity with data protection and defines situations when a similar medicinal product may be granted a marketing authorisation, despite the ongoing market exclusivity.

(105b) In addition, the EU's strategic objective for rare diseases is to improve patient access to

diagnosis, information, and care. EU actions build on a supportive policy framework that encourages national plans and collaborative efforts among Member States. It has established European Reference Networks connecting healthcare providers across Europe to share expertise and provide consultations for patients suffering from rare diseases. Funding is provided through programs like Horizon Europe to support research on rare diseases. Moreover, efforts are made to enhance patient registries and data collection to support research and improve knowledge on rare diseases.

Additionally, the European Health Data Space is set to have a transformative impact on research, particularly for rare diseases. It will draw on the work of the European Platform on Rare Diseases Registration, to address the issue of fragmentation of patient data across Europe. In 2024 the Commission launched a new 7-year research partnership, the European Rare Diseases Research Alliance for better prevention, better diagnosis, and better treatment of rare diseases. With these comprehensive set of actions the EU aims to improve diagnosis, treatment, and quality of life and to better meet the unmet needs of people living with rare diseases and their carers.

(106) Before a medicinal product for human use is placed on the market in one or more Member States, it has to have undergone extensive studies, including non-clinical tests and clinical trials, to ensure that it is safe, of high quality and effective for use in the target population. It is important that such studies are undertaken also onin the paediatric population in order to ensure that medicinal products are appropriately authorised for use in the paediatric population, and to improve the information available on the use of medicinal products in the various paediatric population. It is also important that medicinal products are presented in dosages and formulations adequate for the use in children.

(107) Therefore, the development of medicinal products that could potentially be used for the

paediatric population should become an integral part of the development of medicinal products, integrated into the development programme for adults. Thus, paediatric investigation plans should be submitted early during medicinal product development, in time for studies to be conducted in the paediatric population, where appropriate, before marketing authorisation applications are submitted.

(108) As the development of medicinal products is a dynamic process dependent on the result of

ongoing studies, in certain cases, for example when limited information on the medicinal products are available because the medicinal products are tested for the first time in the paediatric population, a specific procedure allowing to progressively build up a paediatric investigation plan should be put in place.

(109) During public health emergencies, in order not to delay a prompt authorisation of a

medicinal product intended for the treatment or the prevention of a condition related to the public health emergency, there should be a possibility to temporarily waive the requirements concerning paediatric studies to be submitted at the moment of marketing authorisation.

(110) In order to not endanger the health of children and avoid to expose them to unnecessary

clinical trials, the obligation to agree and conduct paediatric studies in children should be waived when the medicinal product is likely to be ineffective or unsafe in part or all of the paediatric population, the specific medicinal product does not represent a significant therapeutic benefit over existing methods of diagnosis, prevention or treatments for children or the disease for which the medicinal product is intended occurs only in adult populations. Nevertheless, in the last case, if on the basis of existing scientific evidence, the medicinal product due to its molecular mechanism of action is expected to be effective against relevant for a different disease or condition in the same therapeutic area in children, the obligation should be maintained.

(111) To ensure that research in the paediatric population is only conducted to meet their

therapeutic needs, the Agency should agree and make public lists of waivers for medicinal products and for specific medicinal products or for classes or part of classes of medicinal products. As knowledge of science and medicine evolves over time, provision should be made for the lists of waivers to be amended. However, if a waiver is revoked, that requirement should not apply for a given period in order to allow time for at least a paediatric investigation plan to be agreed and studies in the paediatric population to be initiated before an application for marketing authorisation is submitted.

(112) With a view to ensuring that research is conducted only when safe and ethical and that the

requirement for study data in the paediatric population does not block or delay the authorisation of medicinal products for other populations, the Agency may defer, based on scientific or technical grounds or considerations related to public health, the initiation or completion of some or all of the measures contained in a paediatric investigation plan for a limited period of time. Such deferral should be extended only in duly justified cases.

(113) The possibility to modify an agreed paediatric investigation plan should be foreseen when

the applicant encounters such difficulties with its implementation as to render the plan unworkable or no longer appropriate.

(114) The Agency, after consultation of the Commission and of interested parties, should draw

up the details of the content of an application for agreement of a paediatric investigation plan, for its modification, for waivers and for deferral requests.

(115) For medicinal products intended to be developed for use only in children which would be

developed independently from the current provisions, simplified details of the paediatric investigation plan should be required.

(116) To ensure that the data supporting the marketing authorisation concerning the use of a

medicinal product in children to be authorised under this Regulation have been correctly developed, the Committee for Medicinal Products for Human Use should check compliance with the agreed paediatric investigation plan and any waivers and deferrals at the validation step for marketing authorisation applications.

(116a) Member States and marketing authorisation holders should operate a

pharmacovigilance system to collect information that is useful for the monitoring of medicinal products, including information on suspected adverse reactions arising from use of a medicinal product within the terms of the marketing authorisation as well as from use outside the terms of the marketing authorisation, including off-label use, overdose, misuse, abuse and medication errors by patients and healthcare professionals. Mistakes in the prescribing, dispensing, storing, preparation and administration of a medicine are common types of medication errors. Suspected adverse reactions should be recorded and reported by Member States and marketing authorisations holders to the Eudravigilance database for the monitoring of safety of medicinal products. The reports should be part of the continuous evaluation of the benefit-risk balance of the medicinal products. Summaries of data relevant to the benefit-risk balance should be included in periodic safety update reports. Marketing authorisation holders should also record and report information on adverse reactions occurring in the context of post-authorisation studies, including post authorisation studies in specific populations such as children, for evaluation of the benefit-risk balance.

(117) Free scientific advice should be provided by the Agency as an incentive to sponsors

developing medicinal products for the paediatric population.

(118) To provide healthcare professionals and patients with information on the safe and effective

use of medicinal products in the paediatric population, the results of the studies conducted in accordance with a paediatric investigation plan, independently from the fact that they support or not the use of the medicinal product in children, should be included in the summary of product characteristics and, if appropriate, in the package leaflet.

(119) To sustain the development of novel, paediatric only indications from authorised medicinal

products no longer covered by intellectual property rights, it is necessary to establish a specific type of marketing authorisation, the Paediatric Use Marketing Authorisation. A Paediatric Use Marketing Authorisation should be granted through existing marketing authorisation procedures but should apply specifically for medicinal products developed exclusively for use in the paediatric population. It should be possible for the name of the medicinal product that has been granted a Paediatric Use Marketing Authorisation to retain the existing brand name of the corresponding medicinal product authorised for adults, in order to capitalise on existing brand recognition, while benefiting from the regulatory protection associated with a new marketing authorisation.

(120) An application for a Paediatric Use Marketing Authorisation should include the submission

of data concerning use of the medicinal product in the paediatric population, collected in accordance with an agreed paediatric investigation plan. These data may be derived from the published literature or from new studies. An application for a Paediatric Use Marketing Authorisation should also be able to refer to data contained in the dossier of a medicinal product which is or has been authorised in the Union. This is intended to provide an additional incentive to encourage SMEs, including generic companies, to develop offpatent medicinal products for the paediatric population.

(121) Some paediatric investigation plans may be discontinued due to various reasons despite

possible positive results for the treatment of children obtained from the studies already conducted. The information of such discontinuations and their reasons should be collected by the Agency and made public in order to inform eventual third parties who may be interested in continuing the above-mentioned studies.

(122) To increase the transparency on clinical trials conducted in children in third countries and

referred to in a paediatric investigation plan or conducted from a marketing authorisation holder independently from a paediatric investigation plan, information on these clinical trials should be included in the European clinical trial database created by Regulation (EU) No 536/2014.

(123) The summary of the results of all the paediatric clinical trials included in the European

clinical trial database created by Regulation (EU) No 536/2014 should be made publicly available within 6 months after the end of the clinical trials unless this is not possible for justified scientific reasons.

(124) To discuss priority in medicinal product development, in particular in areas of unmet

medical need for children and to coordinate studies relating to paediatric medicinal products, the Agency should set up a European network composed of patient

representatives, academics, medicines developers, investigators and research centres based in the Union or in the European Economic Area.

(125) Union funding should be provided to cover all aspects of the work of the Agency resulting

from paediatric related activities, such as the assessment of paediatric investigation plans, fee waivers for scientific advice, and information and transparency measures, including the database of paediatric studies and the network.

(126) It is necessary to take measures for the supervision of medicinal products authorised by the Union, and in particular for the intensive supervision of undesirable effects of these medicinal products, and the collection of real-world data within the framework of Union pharmacovigilance activities, so as to ensure the rapid withdrawal from the market of any medicinal product presenting a negative benefit-risk balance under normal conditions of use.

(127) The main tasks of the Agency in the area of pharmacovigilance laid down in Regulation (EC) No 726/2004 should be maintained. This includes the management of the Union pharmacovigilance database and data-processing network (the ‘Eudravigilance database’), the coordination of safety announcements by the Member States and the provision to the public of information regarding safety issues. The Eudravigilance database should be the single point of receipt of pharmacovigilance information. Member States should therefore not impose any additional reporting requirements on marketing authorisation holders. The database should be fully and permanently accessible to the Member States, the Agency and the Commission, and accessible to an appropriate extent to marketing authorisation holders and the public.

(128) To enhance the efficiency of market surveillance, the Agency should be responsible for

coordinating Member States' pharmacovigilance activities. A number of provisions are required to put in place stringent and efficient pharmacovigilance procedures, to allow the competent authority of the Member State to take provisional emergency measures, including the introduction of amendments to the marketing authorisation and, finally, to permit a reassessment to be made at any time of the risk-benefit balance of a medicinal product.

(129) Scientific and technological progresses in data analytics and data infrastructure are

essential for the development, authorisation and supervision of medicinal products. The digital transformation has affected regulatory decision-making, making it more data-driven and multiplying the possibilities to access evidence and real-world data, across the life cycle of a medicinal product. This Regulation recognises the Agency’s experience and capacity to access and analyse data submitted independently from the marketing authorisation applicant or marketing authorisation holder. On this basis, the Agency should take initiative to updaterecommend the marketing authorisation holder to vary the summary of product characteristics in case new efficacy or safety data has an impact on the benefit-risk balance of a medicinal product, without excluding other actions that the competent authority may take.

(130) It is also appropriate to entrust the Commission, in close cooperation with the Agency and

after consultations with the Member States, with the task of coordinating the execution of the various supervisory responsibilities vested in the Member States, and in particular with the tasks of providing information on medicinal products and of checking the observance of good manufacturing, laboratory and clinical practices.

(131) It is necessary to provide for the coordinated implementation of Union procedures for the

marketing authorisation of medicinal products, and of the marketing authorisation procedures of Member States which have already been harmonised to a considerable degree by [revised Directive 2001/83/EC].

(132) The Union and Member States have developed a scientific evidence-based process that

allows competent authorities to determine the relative effectiveness of new or existing medicinal products. This process focuses specifically on the added value of a medicinal product in comparison with other new or existing health technologies However, this evaluation should not be conducted in the context of the marketing authorisation, for which it is agreed that the fundamental criteria should be retained. It is useful in this respect to allow for the possibility of gathering information on the methods used by the Member States to determine the therapeutic benefit obtained by each new medicinal product.

(133) Regulatory sandboxes can provide the opportunity for advancing regulation through

proactive regulatory learning, enabling regulators to gain better regulatory knowledge and to find the best means to regulate innovations based on real-world evidence, especially at a very early stage of development of a medicinal product, which can be particularly important in the face of high uncertainty and disruptive challenges, as well as when preparing new policies. Regulatory sandboxes provide a structured context for experimentation under a controlled framework, to enable where appropriate in a realworld environment the testing of innovative technologies, products, services or approaches

– at the moment especially in the context of digitalisation or the use of artificial intelligence and machine learning in the life cycle of medicinal products from drug discovery, development to the administration of medicinal products – for a limited time and in a limited part of a sector or area under regulatory supervision ensuring that appropriate safeguards are in place. In its conclusions of 23 December 2020 the Council has encouraged the Commission to consider the use ofparticular, SMEs and startups should have the possibility to participate in regulatory sandboxes on a case-bycase basis when drafting and reviewing legislationwhereby they can, as relevant contribute with their knowhow and experience.

(133a) The Commission should be empowered to establish a regulatory sandbox, based on the

recommendation of the Agency, when the development and authorisation of an innovative medicinal product or category of medicinal products cannot be achieved under the requirements applicable to medicinal products, due to methods related to those medicinal products or their inherent scientific or technical characteristics. A regulatory sandbox facilitates the development, validation and testing of the innovative element of the medicinal products under the supervision of the Agency and national regulators while allowing, where necessary and justified, the adaption of the regulatory requirements for those medicinal products. However, such adaptations should ensure that the principles of quality, safety and efficacy of medicinal products set in the Union legislation are respected. Regulatory sandboxes can also benefit patients’ access to groundbreaking new therapies without compromising the standards of quality, safety and efficacy. The outcome of regulatory sandboxes should guide the Commission in assessing if an adapted framework for the medicinal products in question is appropriate and should be pursued.

(134) In the area of medicinal products, a high level of protection of inter alia citizens,

consumers, health, as well as legal certainty, a level playing field and fair competition always need to be ensured and existing levels of protection need to be respected. (135) The establishment of a regulatory sandbox should be based on a Commission

implementing Decision, following a recommendation of the Agency. Such decision should be based on a detailed and comprehensive plan outlining the particularities of the sandbox as well as describing the products to be covered. A regulatory sandbox should be limited in duration and maycould be terminated at any time based on public health considerations. The learninglearnings stemming from a regulatory sandbox should informare capable of informing future changes to the legal framework to fully integrate the particular innovative aspects into the medicinal product regulation. Where appropriate, adapted frameworks maycould be developed by the Commission on the basis of the results of a regulatory sandbox. Marketing authorisations under a sandbox should ensure that the principles of quality, safety and efficacy are respected under this Regulation and [revised Directive]. The regulatory sandbox should not affect the supervisory and corrective powers of the competent authorities and the liability of the participants, such as clinical trial sponsors, marketing authorisation holders, applicants for marketing authorisation, or any entities

involved in the lifecycle of the medicinal product.

(136) Shortages of medicinal products represent a growing threat to public health, with potential

serious risks to the smooth functioning of the internal market, as well as the health of patients in the Union and impacts on thetheir right of patients to access appropriate medical treatment, including longer delays or interruptions in care or therapy, longer periods of hospitalisation, increased risks of exposure to falsified medicinal products, medication errors, adverse effects resulting from the substitution of unavailable medicinal products with alternative ones, significant psychological distress for patients and increased costs for healthcare systems. The root causes of shortages are

multifactorial, with challenges identified along the entire pharmaceutical value chain, from quality and manufacturing problems. In particular, shortages of medicinal products can result from supply chain disruptions and vulnerabilities affecting the supply of key ingredients and components. Member States, depending on their situation, have addressed this in different ways. Due to a lack of coordination of measures taken at national level, these efforts resulted in a fragmented response jeopardizing the availability of medicines across the European Union. Increased coordination is therefore, all marketing authorisation holders should have shortage prevention plans in place, to prevent shortages required at EU level. The Agency should provide guidance to marketing authorisation holders on approaches to streamline the implementation of those plans.

(136a) More often than in the past, Member States experience critical shortages of various

medicinal products, including certain antimicrobials, endangering the health of patients and risking the development of antimicrobial resistance. Those critical shortages of antimicrobials are the result of a multiplicity of factors, including changing infection patterns, which strongly increases demand. On the supply side, the long lead times needed to boost production makes it difficult to respond quickly. This experience underlines the need for a dedicated effort from all actors to address the issue of critical shortages.

(137) To achieve a better security of supply for medicinal products in the internal market and to

contribute thereby to a high level of public health protection, it is appropriate to approximate the rules on monitoring and reporting of supply disruptions and monitoring of expected or actual or potential shortages of medicinal products, including the procedures and the respective roles and obligations of concerned entities in this Regulation. It is important to ensure continued supply of medicinal products, which is often taken for granted across Europe. This is especially true for the most critical medicinal products which are essential to ensure the continuity of care, the provision of quality healthcare and guarantee a high level of public health protection in Europe within the Union.

(137a) A Member State should be able to decide to exempt a marketing authorisation holder

from complying with certain obligations under Chapter X where the medicinal product is

authorised by that Member State based on public health grounds.

(137b) Without affecting the rules laid down in this Regulation, Member States remain the sole

responsible for their own national security. They are responsible for defending their essential state functions, including ensuring their territorial integrity and safeguarding national security. In particular, under Article 346 TFEU, no Member State is obliged to supply information the disclosure of which it considers contrary to the essential interests of its security. For this reason, Member States should be able to waive some of the obligations applicable to marketing authorisation holders and other relevant actors only when the medicinal products are supplied for military and defence purposes and insofar as the application of such requirements imply a risk to national security and defence. For medicinal products that are supplied for military and defence purposes but also to cover the needs of patients, such exemptions should only target the specific batches that are supplied for military and defence purposes. Furthermore, Member States may also exempt national authorities from communicating information where such a requirement

would imply a risk to national security and defence.

(137c) To prevent or mitigate future shortages of medicines, marketing authorisation holders

should notify the concerned competent authorities and, where applicable, the Agency of any future withdrawal of a marketing authorisation, permanent cessation or temporary suspension of the marketing of a medicinal product and any supply disruption exceeding two weeks. Supply disruptions should be notified as soon as the marketing authorisation holder becomes aware of the situation, and at the latest 6 months in advance of the interruption, unless there are duly justified exceptional circumstances, to allow competent authorities to engage with relevant stakeholders and take the necessary mitigating actions. Furthermore, shortage prevention plans are key tools for the prevention of shortages given that they require marketing authorisation holders to identify risks in their supply chains and take the necessary mitigation measures to avoid shortages. Therefore, marketing authorisation holders should have shortage prevention plans in place for medicinal products subject to prescription and, where applicable, additional medicinal products identified by the Commission, taking into account recommendations from the Executive Steering Group on Shortages and Safety of medicinal products (MSSG), to prevent or mitigate shortages. The Agency should provide guidance to marketing authorisation holders on approaches to streamline the implementation of those plans. A documented risk assessment of supply chain risks should be required for other medicinal products. The Commission should be able to request the information of the shortage prevention plans of medical countermeasures in the context of crisis preparedness.

(137d) To ensure continuity of supply and availability of medicinal products identified as

critical at national level and other specific medicinal products on the market of any Member State where the medicinal product is authorised, rules for the transfer of the marketing authorisation or for the offer of a letter of access prior to the withdrawal of the marketing authorisation or the permanent market cessation, respectively, in Member States where the marketing authorisation is valid, should be laid down. Such transfer should not be considered to be a variation. Rules on wholesale distribution of medicinal products, marketed as a result of a marketing authorisation, whose data have been shared via a letter of access, do not affect the contractual arrangements between the marketing authorisation holders or wholesalers concerned.

(138) The national competent authorities should be empowered to monitor shortages of

medicinal products that are authorised through both national and centralised procedures, based on notifications of marketing authorisation holders. The Agency should be empowered to monitor shortages of medicinal products that are authorised through the centralised procedure, also based on notifications of marketing authorisation holders. When critical shortages of Union concern are identified, both national competent authorities and the Agency should work in a coordinated manner to manage those critical shortages, whether the medicinal product concerned by the critical shortage is covered by a centralised marketing authorisation or a national marketing authorisation and communicate the necessary information to patients, consumers and healthcare professionals. Marketing authorisation holders and other relevant entities mustshould provide the relevant information to inform the monitoring. Wholesale distributors and other persons or legal entities, including patient organisations or health care professionals, may also report a shortage of a given medicinal product marketed in the Member State concerned to the competent authority. The Executive Steering Group on Shortages and Safety of Medicinal Products (‘the Medicines Shortages Steering Group’ (MSSG))Agency, with the support of MSSG already established within the Agency pursuant to Regulation (EU) 2022/123 of the European Parliament and of the Council, should adoptestablish and, when necessary, update a list of critical shortages of medicinal products andUnion concern. The Agency, in coordination with the competent authority of the Member State concerned should ensure monitoring of those shortages by the Agency. The MSSG should also adopt a list of critical medicinal products authorised in accordance with [revised Directive 2001/83/EC] or this Regulation to ensure monitoring of the supply of those products. The MSSG may provide recommendations on measures to be taken by marketing authorisation holders, the Member States, the Commission and other entities to resolve any critical shortage or to ensure the security of supply of those critical medicinal products to the market. Implementing acts can be adopted by the Commission to ensure that appropriate measures, including the establishment or maintenance of contingency stocks, are taken by marketing authorisation holders, wholesale distributors or other relevant entities.

(138a) Parallel trade of medicinal products concerns medicinal products traded from one Member State to another Member State. Parallel trade facilitates the free movement of medicinal products due to the fact that the medicinal products are authorised in more Member States on the basis of the Union legislation. This situation is different from export, where the harmonised system of authorising and making medicinal products available on the market does not exist. While the Court of Justice has ruled that parallel trade fosters the free movement of medicinal products and is therefore beneficial to the internal market, it has also recognised the need to ensure that a country has reliable supplies for essential medical purposes, in particular a supply of medicinal products to the public that is reliable and of good quality. Therefore, it should be possible for a Member State to require, for certain medicinal products, to be informed by wholesale distributors whenever one of these products leaves the Member State in question to be distributed in another Member State. On the basis of this information and other information at its disposal, including shortage prevention plans, the Member State should be able to take measures to prevent or mitigate shortages and should notify to the Agency. These measures should also be appropriate and proportionate to such objectives and take into account that the principles of the free movement of goods are restricted only for the purpose of safeguarding public health, thus respecting the case law of the Court of Justice of the European Union and the Treaties, notably the provisions on free movement and competition. The information requirements set out in this Regulation do not affect existing obligations under Union law for the notification of technical regulations and technical barriers to the internal market, including those set out in Directive 2015/1535. It is important to recognise that parallel import can contribute to the objective of access to medicines, notably in smaller or vulnerable markets.

(138c) The voluntary mechanism can foster solidarity between Member States in the context of

critical shortages that require urgent collective action. The European Voluntary Solidary Mechanism, can be activated as a last resort mechanism, should aim at supporting Member States experiencing critical shortages that cannot be resolved at national level despite exhaustive short-term measures. Activation of such a mechanism should be contingent upon specific conditions, including the lack of therapeutic alternatives and insufficient quantities to cover critical indications and an imminent risk of stockout which underline the urgency of the situation. The Agency should facilitate communication and coordinate support responses, thereby also offering assistance in liaising with marketing authorisation holders when necessary. The MSSG should be responsible for establishing procedural rules to ensure the efficient operationalisation of the mechanism.

(138d) Based on a common Union methodology, national competent authorities should identify

medicinal products they consider as critical at national level. The resulting list of critical medicinal products identified by Member States ('Union long list') should be adopted and published by the Commission. The MSSG should also propose a Union list of critical medicinal products authorised in accordance with [revised Directive

2001/83/EC] or this Regulation to ensure monitoring of the supply of those products, to be adopted by the Commission. The MSSG, supported by the Agency, should undertake the vulnerability evaluation of critical medicinal products on the Union list following a defined prioritisation. The Commission should gradually, taking into account the outcome of the vulnerability evaluation, specify the critical medicinal product for which a vulnerability is established. Among these medicines the Commission should also specify those critical medicinal products, including their active substances, which are vulnerable due to a high level of dependency on a single or limited number of countries outside the Union. The MSSG may provide recommendations on measures to be taken by marketing authorisation holders, the Member States, the Commission and other entities to resolve any critical shortage or to ensure the security of supply of those critical medicinal products to the market. Where appropriate, those security of supply measures should also comprise the use of regulatory flexibilities such as on packaging and labelling requirements. However, such flexibility should not undermine the quality,

safety, and efficacy standards.

(139) To ensure continuity of supply and availability of critical medicinal products to the

market, rules on the transfer of the marketing authorisation prior to the permanent marketing cessation should be laid down. Such transfer should not be considered to be a variation.

(139a) Monitoring and prevention activities, together with targeted actions at national level,

have at times proven to be insufficient to prevent disruption of supply within the Union of critical medicinal products. Experience has shown that difficulties in the supply chain have led to uncoordinated approaches at company and governmental level, such as imposing contingency stocks requirements on actors in the supply chain, which led to restrictions in the internal market. Such restrictions are also likely to result in a suboptimal level of availability of critical medicines, due to the fact that a fragmented approach is jeopardising the availability throughout the European Union. It is necessary to ensure that tools for a Union approach are available to address such situations which are likely to lead to such restrictions, in specific circumstances, to ensure the free movement of medicines by safeguarding security of a safe and stable supply of them at Union level. The Commission should therefore be empowered to draw up recommendations on national measures, after having duly identified a serious risk of disruptions, to improve security of supply within the Union.

(140) It is recognised that improved access to information contributes to public awareness and

increases public trust, gives the public the opportunity to express its observations and enables authorities to take due account of those observations. The general public should therefore have access to information in the Union Register of medicinal products, the Eudravigilance database and the manufacturing and wholesale distribution database, after the deletion of any commercially confidential information by the competent authority., unless there is an overriding public interest in disclosure, in accordance with Regulation (EC) No 1049/2001 of the European Parliament and of the Council. Regulation (EC) No 1049/2001 gives the fullest possible effect to the right of public access to documents and lays down the general principles and limits on such access. The Agency should therefore give the widest possible access to the documents while carefully balancing the right for information with existing data protection requirements. Certain public and private interests, such as personal data and commercially confidential information, should be protected by way of exception in accordance with Regulation (EC) No 1049/2001.

(141) To ensure the enforcement of certain obligations relating to the marketing authorisation for

medicinal products for human use granted in accordance with this Regulation, the Commission should be able to impose financial penalties. When assessing the responsibility for failures to comply with those obligations and imposing such penalties, it is important that means exist to address the fact that marketing authorisation holders could be part of a wider economic entity. Otherwise, there is a clear and identifiable risk that the responsibility for a failure to comply with those obligations could be evaded, which might have an impact on the ability to impose effective, proportional and dissuasive penalties. The penalties imposed should be effective, proportionate and dissuasive, having regard to the circumstances of the specific case. For the purposes of ensuring legal certainty in the conduct of the infringement procedure, it is necessary to set maximum amounts for penalties. Those maximum amounts should not be linked to the turnover of a particular medicinal product but the economic entity involved.

(142) To supplement or amend certain non-essential elements of this Regulation, the power to

adopt acts in accordance with Article 290 of the Treaty on the Functioning of the European Union (‘TFEU’) should be delegated to the Commission in respect of determining the situations in which post-authorisation efficacy studies may be required; specifying the categories of medicinal products to which a marketing authorisation subject to specific obligations could be granted and specifying the procedures and requirements for granting such a marketing authorisation and for its renewal; specifying exemptions to variation and the categories in which variations should be classified and establishing procedures for the examination of applications for variations to the terms of marketing authorisations as well as specifying conditions and procedures for cooperation with third countries and international organisations for examination of applications for such variations; establishing procedures for the examination of applications for the transfer of marketing authorisations; laying down the procedure and rules for the imposition of fines or periodic penalty payments for a failure to comply with the obligations under this Regulation as well as the conditions and methods for their collection. The Commission should be empowered to adopt supplementary measures laying down the situations in which post-authorisation efficacy studies may be required. It is of particular importance that the Commission carries out appropriate consultations during its preparatory work, including at expert level, and that those consultations be conducted in accordance with the principles laid down in the

Interinstitutional Agreement between the European Parliament, the Council of the

European Union and the European Commission of 13 April 2016 on Better Law-Making.

In particular, to ensure equal participation in the preparation of delegated acts, the

European Parliament and the Council receive all documents at the same time as Member States’ experts, and their experts systematically have access to meetings of Commission expert groups dealing with the preparation of delegated acts.

(143) To ensure uniform conditions for the implementation of this Regulation in relation to

marketing authorisations for medicinal products for human use, implementing powers should be conferred on the Commission. The implementing powers related to the granting of centralised marketing authorisations and for suspending, revoking or withdrawing those authorisations, for granting vouchers, establishing and modifying regulatory sandboxes and decisions on the regulatory status of medicinal products should be exercised in accordance with Regulation (EU) 182/2011.

(144) Article 91 of Regulation (EU) No 536/2014 currently stipulates, amongst others, that it

applies without prejudice to Directives 2001/18/EC and 2009/41/EC.

(145) Experience shows that, in clinical trials with investigational medicinal products containing

or consisting of GMOs, the procedure to achieve compliance with the requirements of Directives 2001/18/EC and 2009/41/EC as regards the environmental risk assessment and consent by the competent authority of a Member State is complex and can take a significant amount of time.

(146) The complexity of that procedure increases greatly in the case of multi-centre clinical trials

conducted in several Member States, as sponsors of clinical trials need to submit multiple requests for authorisation to multiple competent authorities in different Member States in parallel. In addition, national requirements and procedures for the environmental risk assessment (ERA) and written consent by competent authorities under GMO legislation vary greatly from one Member State to another as some Member States apply Directive 2001/18/EC, others apply Directive 2009/41/EC and there are Member States that apply either Directive 2009/41/EC or 2001/18/EC depending on the specific circumstances of a clinical trial. It is therefore not possible to determine a priori the national procedure that is to be followed.

(147) Consequently, it is particularly difficult to conduct multi-centre clinical trials with

investigational medicinal products that contain or consist of GMOs involving several Member States.

(148) One of the objectives of Regulation (EU) No 536/2014 is that there will be a single

coordinated and harmonised assessment of the clinical trial application between the involved Member States, with one country leading the coordination of the assessment (the Reporting Member State).

(149) It is therefore appropriate to envisage a centralised assessment of the ERA involving

experts from the national competent authorities and where relevant the Environmental Risk Assessment working party.

(150) Article 5 of Directive 2001/18/EC provides that the authorisation procedures for the

deliberate release into the environment of GMOs and their related rules described in its Articles 6 to 11 do not apply for medicinal substances and compounds for human use if authorised by Union legal acts that fulfil the criteria listed in that Article.

(151) The requirement for the holding of authorisation of manufacturing and import of

investigational medicinal products in the Union in accordance with Article 61(2), point (a), of Regulation (EU) No 536/2014 should be extended to investigational medicinal products containing or consisting of GMOs in Directive 2009/41/EC.

(152) It is thus judicious, in order to ensure an efficient functioning of Regulation (EU) No 536/2014, to define a specific authorisation procedure for the deliberate release of medicinal substances and compounds for human use containing or consisting of GMOs fulfilling the requirements of Article 5 of Directive 2001/18/EC and taking into account the specific characteristics of medicinal substances and compounds.

(153) Detailed rules concerning financial penalties for failure to comply with certain obligations

laid down in this Regulation are specified in Commission Regulation (EC) No 658/2007. Those rules should be maintained, but it is appropriate to consolidate them by moving their core elements and the list specifying those obligations into this Regulation, while maintaining a delegation of powers that allows the Commission to supplement this Regulation by laying down procedures for imposing such financial penalties. It is appropriate, in order to provide for legal certainty, to clarify that Commission Regulation (EC) No 2141/96 remains in force and continues to apply unless and until repealed. For the same reason, it should be clarified that Regulations (EC) No 2049/2005,

No 507/2006, No 658/2007 and (EC) No 1234/2008 remain in force and continue to apply unless and until repealed.

(154) This Regulation is based on the double legal basis of Article 114 and Article 168(4), point (c), TFEU. It aims at achieving an internal market as regards medicinal products for human use, taking as a base a high level of protection of health. At the same time, this Regulation sets high standards of quality and safety for medicinal products in order to meet common safety concerns as regards these products. Both objectives are being pursued simultaneously. These two objectives are inseparably linked and one is not secondary to another. Regarding Article 114 TFEU, this Regulation establishes a European Medicines Agency and provides specific provision with regard to the central authorisation of medicinal products, therefore ensuring the functioning of the internal market and the free movement of medicinal products. Regarding Article 168(4), point (c), TFEU, this Regulation sets high standards of quality and safety for medicinal products.

(155) This Regulation respects the fundamental rights and observes the principles recognised in

particular by the Charter of Fundamental Rights of the European Union and notably human dignity, the integrity of the person, the rights of the child, respect for private and family life, the protection of personal data and the freedom of art and science. Similarly this

regulation integrates a high level of protection of the environment

(156) The objective of this Regulation is to ensure the authorisation of high quality medicinal

products, including for paediatric patients and patients suffering from rare diseases throughout the Union. Where this objective cannot be sufficiently achieved by the Member States but can rather, by reason of its scale, be better achieved at Union level, the Union may adopt measures, in accordance with the principle of subsidiarity as set out in Article 5 of the Treaty on European Union. In accordance with the principle of proportionality, as set out in that Article, this Regulation does not go beyond what is necessary in order to achieve that objective.

HAVE ADOPTED THIS REGULATION:

CHAPTER I SUBJECT MATTER, SCOPE AND DEFINITIONS

Article 1

Subject matter and scope

This Regulation lays down Union procedures for the authorisation, supervision and pharmacovigilance of medicinal products for human use at Union level, establishes rules and procedures at Union and at Member State level relating to the monitoring and management of shortages and critical shortages and the security of supply of medicinal products and lays down the governance provisions of the European Medicines Agency (‘the Agency’) established by Regulation (EC) No 726/2004 which shall carry out the tasks relating to medicinal products for human use that are laid down in this Regulation, Regulation (EU) No 2019/6 and other relevant Union legal acts.

This Regulation shall not affect the powers of Member States' authorities as regards setting the prices of medicinal products or their inclusion in the scope of the national health system or social security schemes on the basis of health, economic and social conditions. Member States may choose from the particulars shown in the marketing authorisation those therapeutic indications and pack sizes which will be covered by their social security bodies.

Article 2

Definitions

For the purposes of this Regulation, the definitions laid down in Article 4 of [revised Directive 2001/83/EC] shall apply.

The following definitions shall also apply:

(1) ‘veterinary medicinal product’ means a medicinal product as defined in Article 4, point (1),

of Regulation (EU) 2019/6;

(2) ‘designated orphan medicinal product’ means a medicinal product under development

which has been granted an orphan designation by a decision referred to in Article 64(4);

(3) ‘orphan medicinal products’ means a medicinal product which has been granted an orphan

marketing authorisation referred to in Article 69;

(4) ‘orphan medicinemedicinal product sponsor’ means any legal or natural person,

established in the Union, who submitted an application for or has been granted an orphan designation for a medicinal product by a decision referred to in Article 64(4);

(5) ‘similar medicinal product’ means a medicinal product containing a similar active

substance or substances as contained in a currently authorised orphan medicinal product, and which is intended for the same therapeutic indication;

(6) ‘similar active substance’ means an identical active substance, or an active substance with

the same principal molecular structural features (but not necessarily all of the same molecular structural features) and which acts via the same mechanism. In the case of advanced therapy medicinal products, for which the principal molecular structural features cannot be fully defined, the similarity between two active substances shall be assessed on the basis of the biological and functional characteristics;

(7) ‘significant benefit’ means a clinically relevant advantage or a major contribution to

patient care of an orphan medicinal product if such an advantage or contribution benefits a substantialrelevant part of the target population;

(8) ‘clinically superior’ means that a medicinal product is shown to provide a significant

therapeutic or diagnostic advantage above that provided by an orphan medicinal product in one or more of the following ways:

(a) greater efficacy than an authorised medicinal orphan medicinal product in a substantialthe relevant part of the target population;

(b) greater safety than an authorised orphan medicinal product in a substantialthe relevant part of the target population;

(c) in exceptional cases, where neither greater safety nor greater efficacy has been shown, demonstration that the medicinal product otherwise makes a major contribution to diagnosis or to patient care.

(9) ‘paediatric use marketing authorisation’ means a marketing authorisation granted in respect

of a medicinal product for human use which is not protected by a supplementary protection certificate under Regulation (EC) No 469/2009 of the European Parliament and of the Council concerning the supplementary protection certificate for medicinal products [OP please replace reference by new instrument when adopted], or by a patent which qualifies for the granting of the supplementary protection certificate, covering exclusively therapeutic indications which are relevant for use in the paediatric population, or subsets thereof, including the appropriate strength, pharmaceutical form or route of administration for that product.

(10) ‘regulatory sandbox’ means a regulatory framework during which it is possible to

develop, validate and test in a controlled environment innovative or adapted regulatory solutions that facilitate the development and authorisation of innovative products which are likely to fall in the scope of this Regulation, pursuant to a specific plan and for a limited time under regulatory supervision.

(11) ‘critical medicinal product’ means a medicinal product for which insufficient supply

results in serious harm or risk of serious harm to patients and identified using the methodology pursuant to Article 130(1), point (a).

(12) ‘shortage’ means a situation in which the supply of a medicinal product that is authorised

and placed on the market in a Member State does not meet the demand for that medicinal product in that Member State whatever the cause.

(13) ‘critical shortage in the Member State’ means a shortage of a medicinal product, which

may result in a significant impact on the healthcare system of a Member State or results in harm or risk of harm to patients and for which there is no appropriate alternative medicinal product available in sufficient quantities on the market in that Member State, and that shortage cannot be resolved.

(14) ‘critical shortage of Union concern’ means a critical shortage in the Member State that

cannot be resolved at Member State level and for which coordinated Union level action is considered necessary to resolve that shortage in accordance with this Regulation;

(14a) ‘demand’ means the request for a medicinal product by healthcare professionals or

patients in response to a clinical need; the demand is satisfactorily met when the medicinal product is acquired in appropriate time and in sufficient quantity to allow continuity of provision of the best care to patients;

(14b) ‘supply’ means the total volume of stock of a given medicinal product that is placed on

the market by a marketing authorisation holder or a manufacturer.

Article 3

Centrally authorised medicinal products

1. A medicinal product listed in Annex I shall only be placed on the Union market if a

marketing authorisation for that medicinal product has been granted by the Union in accordance with this Regulation (‘centralised marketing authorisation’).

2. Any medicinal product not listed in Annex I, may be granted a centralised marketing

authorisation in accordance with this Regulation, if the product meets at least one of the following requirements:

(a) the applicant shows that the medicinal product constitutes a significant therapeutic, scientific or technical innovation or that the granting of marketing authorisation in accordance with this Regulation is in the interest of patients' health at Union level, including as regards antimicrobial resistance and medicinal products for public health emergencies;

(b) it is a medicinal product intended solely for paediatric use.

(c) the applicant refers in the marketing authorisation application to a reference medicinal product that has been authorised through the centralised procedure;

(d) the medicinal product contains a new active substance, which on 20 May 2004 was not authorised in the Union.

3. Homeopathic medicinal products shall not be granted a marketing authorisation in

accordance with this Regulation.

4. The Commission shall grant and supervise centralised marketing authorisations for

medicinal products for human use in accordance with Chapter II.

5. The Commission is empowered to adopt delegated acts in accordance with Article 175 to

amend Annex I, in order to adapt it to technical and scientific and technological progress,. This empowerment shall be subject to the following conditions:

(a) The Commission shall justify, on the basis of scientific and technological evidence, the appropriateness of updating the description of the biotechnological processes in point 1 of Annex I. The delegated act shall also be based on an up-to date scientific literature review as regards the types and extent of developments that have occurred, including, where applicable international guidelines and comparative standards.

(b) Where applicable, the Commission shall take into account any relevant new or updated scientific opinions from the WHO or medicines agencies.

Article 4

Member State authorisation of generics of medicinal products referring to centrally authorised medicinal products

A generic medicinal product of a reference medicinal product authorised by the Union may be authorised byBy derogation to Article 3 the competent authorities of the Member States in accordance with [revised Directive 2001/83/EC2001/83] may authorise a medicinal product that refers to a reference medicinal product authorised by the Union under the following conditions:

(a) the application for marketing authorisation is submitted in accordance with Article 9 or 11

or, in justified cases, in accordance with Article 10 or 12 of [revised Directive

2001/83/EC];

(b) the summary of product characteristics and the package leaflet are in all relevant respects

consistent with that of the medicinal product authorised by the Union. including its

indications;

(c) the reference medicinal product is not a medicinal product referred to Annex I, points 1

or 2.

Where the application is submitted in accordance with Articles 10 or 12 of [revised Directive 2001/83/EC], the applicant shall demonstrate that all the indications covered by the application have been authorised by the Union for the active substance concerned

Point (b), first subparagraph, shall not apply to those parts of summary of product characteristics and package leaflet referring to indications, posologies, pharmaceutical forms, methods or routes of administration or any other way in which the medicinal product may be used which were still covered by a patent or a supplementary protection certificate for medicinal products at the time when the generic medicinal product for which a marketing authorisation have been requested under this Article, was marketed and where the applicant for the genericthis medicinal product has requested not to include this information in their marketing authorisation.

CHAPTER II GENERAL PROVISIONS AND RULES ON APPLICATIONS

Section 1

Application for centralised marketing authorisations

Article 5

Submission of applications for marketing authorisations

1. The marketing authorisation holder for medicinal products covered by this Regulation shall

be established in the Union. The marketing authorisation holder shall be responsible for the placing on the market of those medicinal products, whether done by that marketing authorisation holder or via one or more persons designated to that effect.

2. An applicant shall agree with the Agency the submission date of an application for a

marketing authorisation.

3. An applicant shall submit an application for a marketing authorisation electronically to the Agency and in the formats made available by the Agency.

4. The applicant shall be responsible for the accuracy and completeness of the information

and documentation submitted with respect to its application.

5. Within 20 days of receipt of an application, the Agency shall check whether all the

information and documentation required in accordance with Article 6 have been submitted, that the application does not contain critical deficiencies that may prevent the evaluation of the medicinal product and decide whether the application is valid.

6. Where the Agency considers that the application is incomplete, or contains critical

deficiencies that may prevent the evaluation of the medicinal product, it shall inform the applicant accordingly and set a time limit for submitting the missing information and documentation. That time limit may be extended once by the Agency.

Upon receipt of the responses from the applicant to the request to submit the missing information and documentation, the Agency will determine whether the application can be considered valid. Where the Agency refuses to validate an application, it shall notify the applicant and state the reasons for such refusal.

If the applicant fails to provide the missing information and documentation within the time limit, the application shall be considered to have been withdrawn.

7. The Agency shall draw up scientific guidelines for the identification of critical deficiencies

that may prevent the evaluation of a medicinal product, in consultation with the European Commission and the Member States.

Article 5a

Obligation to supply for centrally authorised medicinal products

1. With a view to facilitating access to a medicinal product authorised under this Regulation and where such product is subject, as applicable, to regulatory protection pursuant to Article 80 of the [revised Directive], market exclusivity in accordance with Article 72, patent or a supplementary protection certificate, a Member State may request the marketing authorisation holder of that medicinal product to place it on the market and supply on the market of that Member State, either pursuant to the mechanism set out in Article 56a of [revised Directive], including the actions referred to in paragraph 2 of that Article, or independently. The marketing authorisation holder shall ensure, upon agreement with the respective Member State and within the limits of its responsibility, that such medicinal product is placed on the market and supplied so that the needs of patients in the Member State in question are covered.

The arrangements to implement the above obligations shall be proportionate to the objective pursued and in compliance with Union law

Marketing authorisation holders shall comply with the obligations set out in this Article, unless there are exceptional and unforeseeable circumstances, including those related to disruptions of supply, or duly justified circumstances fully outside the marketing authorisation holder’s control, the consequences of which could not have been avoided even if all best and reasonable measures had been taken. In such a case the marketing authorisation holder shall provide an explanation of the case and circumstances and

justify the reasons for non-compliance.

2. In case a Member State considers that a marketing authorisation holder referred to in

paragraph 1 has consistently failed to place a product on the market and supply it so that the needs of patients in the Member State in question are covered. it may inform the Commission. The Member State shall provide the Commission with a detailed description of the facts of the case and substantiate the marketing authorisation holders’ failure to place on the market and supply.

Prior to informing the Commission, the Member State shall notify the marketing authorisation holder concerned and invite it to provide written observations within four weeks from the notification. This period may be prolonged once. The written observations shall be attached to the information in accordance with the first subparagraph. When informing the Commission, the Member State shall duly consider the explanations provided by the marketing authorisation holder in its written observations.

3. Whenever more than one Member State invokes paragraph 2 first subparagraph, with

regards to the same medicinal product, the Commission shall require the marketing authorisation holder to enter into negotiations in good faith and make best efforts to ensure supply so that the needs of patients in the Member States in question are covered, within the meaning of paragraph 1.

4. By [OP please insert the date = 4 years from the date of application], the Commission

shall present a report to the European Parliament and the Council on the application of this Article. The report shall be based, among others, on information provided by Member States, and it shall include an assessment on whether the rules provided for in this Article ensure that the medicinal products concerned are placed on the market and supplied for use in patients in all Member States that have applied this Article. The Commission shall, if appropriate, present legislative proposals based on that evaluation notably with regard to remedial actions in the case of non-compliance, including the

possibility to impose penalties in accordance with Article 172.

Article 6

Centralised marketing authorisation application

1. Each application for a centralised marketing authorisation of a medicinal product for

human use shall specifically and completely include the particulars and documentation as referred to in Chapter II of [revised Directive 2001/83/EC]. In the case of applications in accordance with Article 6(2), Article 10 and Article 12 of [revised Directive 2001/83/EC], this shall include the electronic submission of raw data, in accordance with Annex II of that Directive.

The documentation shall include a declaration to the effect that clinical trials carried out outside the Union meet the ethical requirements of Regulation (EU) No 536/2014. Those particulars and documentation shall take account of the unique, Union nature of the authorisation requested and, otherwise than in exceptional cases relating to the application of the law on trademarks pursuant to Regulation (EU) 2017/1001 of the European Parliament and of the Council, shall include the use of a single name for the medicinal product. The use of a single name does not exclude the use of additional qualifiers where necessary to identify different presentations of the medicinal product concerned.

2. For medicinal products that are likely to offer an exceptional therapeutic advancement in

the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the Union,2. The Agency may, following the advice of the Committee for Medicinal Products for Human Use regarding the maturity of the data related to the development, offer to the applicant a phased review of complete data packages for individual modules of particulars and documentation as referred to in paragraph 1 for medicinal products which:

(a) are likely to address an unmet medical need as referred to in Article 83(1) of [revised Directive 2001/83/EC] and are expected to be of major interest from the point of view of public health, in particular as regards therapeutic innovation; or

(b) are antimicrobials with any of the characteristics mentioned in Article 40(3) or provided for in the ‘WHO priority pathogens list for R&D of new antibiotics’, specifically those listed as priority 1 (critical) or priority 2 (high), or taking into account as a priority any equivalent list of priority pathogens adopted at Union

level; or

(c) are intended to be used in relation to a potential or recognized public health emergency.

The Agency shall apply subparagraph 1 following the advice of the Committee for Medicinal Products for Human Use regarding the fulfilment of these criteria and the maturity of the data related to the development.

The Agency may at any stage suspend or cancel the phased review, where the Committee for Medicinal Products for Human Use considers that the submitted data are not of sufficient maturity or where it is considered that the medicinal product no longer fulfils an exceptional therapeutic advancementthe conditions referred to in the first subparagraph. The Agency shall inform the applicant accordingly.

3. A fee shall apply for a marketing authorisation application and shall be payable to the Agency for the examination of the application.

4. Where appropriate, the application may include an active substancesummary documents,

certificates, protocols or master file certificate or an application for an active substance master file or any other quality master file certificate or application as referred to in Article 25files in accordance with Chapter II section 4 and Annex II of [revised Directive 2001/83/EC].

5. The marketing authorisation applicant shall demonstrate that the principle of replacement,

reduction and refinement of animal testing for scientific purposes has been applied in compliance with Directive 2010/63/EU with regard to any animal study conducted in support of the application.

The marketing authorisation applicant shall not carry out animal tests in case scientifically satisfactory non-animal testing methods are available.

6. The Agency shall ensure that the opinion of the Committee for Medicinal Products for Human Use is given within 180 days after receipt of a valid application. In the case of a medicinal product for human use containing or consisting of genetically modified organisms, the opinion of that Committee shall take into account the evaluation of the environmental risk assessment in accordance with Article 8.

On the basis of a duly reasoned request, the Committee for Medicinal Products for Human Use may call for the duration of the analysis of the scientific data in the file concerning the application for marketing authorisation to be extended.

7. When an application is submitted for a marketing authorisation in respect of medicinal

products for human use which are of major interest from the point of view of public health and in particular from the viewpoint of therapeutic innovation, the applicant may request an accelerated assessment procedure. The same shall apply for products referred to in Article 60. The request shall be duly substantiated.

If the Committee for Medicinal Products for Human Use accepts the request, the time-limit laid down in Article 6(6), first subparagraph, shall be reduced to 150 days.

8. The adapted frameworks established in accordance with Art. 28 of [revised Directive 2001/83] may apply also for the for the purposes of obtaining a centralised marketing authorisation in accordance with this Regulation.

Article 7

Environmental risk assessment for medicinal products containing or consisting of genetically modified organisms

1. Without prejudice to Article 22 of [revised Directive 2001/83/EC], the marketing

authorisation application of a medicinal product for human use containing or consisting of genetically modified organisms as defined in Article 2(2) of Directive 2001/18/EC shall be accompanied by an environmental risk assessment identifying and evaluating potential adverse effects of the genetically modified organisms on human or animal health, and the environment.

2. The environmental risk assessment for the medicinal products referred to in paragraph 1

shall be conducted in accordance with the elements described in Article 8 and the specific requirements set out in Annex II to [revised Directive 2001/83/EC] based on the principles set out in Annex II to Directive 2001/18/EC taking into account the specificities of medicinal products.

3. Articles 13 to 24 of Directive 2001/18/EC shall not apply to medicinal products for human

use containing or consisting of genetically modified organisms.

4. Articles 6 to 11 of [revised Directive 2001/18/EC] as well as Articles 4 to 13 of Directive 2009/41/EC shall not apply to operations related to the supply and clinical use, including the packaging and labelling, distribution, storage, transport, preparation for administration, administration, destruction or disposal of medicinal products containing or consisting of genetically modified organisms, with the exception of their manufacture, in any of the following cases:

(a) where such medicinal products have been excluded from the provisions of [revised

Directive 2001/83/EC] by a Member State pursuant to Article 3(1) of that Directive;

(b) where the use and distribution of such medicinal products have been temporarily authorised by a Member State pursuant to Article 3(2) of [revised Directive

2001/83/EC]; or

(c) where such medicinal products are made available by a Member State pursuant to Article 26(1).

5. In the cases referred to in paragraph 4, Member States shall implement appropriate

measures to minimise foreseeable negative environmental impacts resulting from the intended or unintended release of the medicinal products containing or consisting of genetically modified organisms into the environment.

The competent authorities of the Member States shall ensure that information related to the use of medicinal products referred to in paragraph 4, is available and provided to the competent authorities established by Directive 2009/41/EC, when necessary and in particular in the event of an accident referred to in Article 14 and Article 15 of Directive 2009/41/EC.

Article 8

Content of the environmental risk assessment for medicinal products containing or consisting of genetically modified organisms

The environmental risk assessment referred to in Article 7(2) shall contain the following elements:

(a) description of the genetically modified organism and the modifications introduced as well

as characterisation of the finished product;

(b) identification and characterisation of hazards for the environment, animals and for human

health;

(c) exposure characterisation, assessing the likelihood or probability that the identified hazards

materialise;

(d) risk characterisation taking into account the magnitude of each possible hazard and the

likelihood or probability of that adverse effect occurring;

(e) risk minimisation and mitigation strategies proposed to address identified risks including

specific containment measures to limit contact withof the medicinal product with human beings other than the intended patient and its dissemination in the environment;

(f) overall risk evaluation and conclusions.

Article 9

Procedure for the environmental risk assessment for medicinal products containing or consisting of genetically modified organisms

1. The applicant shall submit an environmental risk assessment referred to in Article 7(1) to

the Agency.

The Committee for Medicinal Products for Human Use shall assess the environmental risk assessment.

2. In case of first-in-class medicinal products or when a novel question is raised during the

assessment of the submitted environmental risk assessment, the Committee for Medicinal Products for Human Use, or the rapporteur, shall carry out, as necessary, carry out consultations with bodies Member States have set up in accordance with Directive 2001/18/EC. They mayshall as necessary also consult with relevant Union bodies. Details on the consultation procedure shall be published by the Agency at the latest by [OJ:12

months after the date of entry into force of this Regulation].

Article 10

Committee assessment of an application for marketing authorisation

1. When preparing its opinion, the Committee for Medicinal Products for Human Use shall

verify that the particulars and documentation submitted in accordance with Article 6 comply with the requirements of [revised Directive 2001/83/EC], and shall examine whether the conditions specified in this Regulation for granting a marketing authorisation are satisfied. When preparing its opinion, the Committee for Medicinal Products for Human Use may make the following requests:

(a) that an Official Medicines Control Laboratory or a laboratory that a Member State has designated for that purpose tests the medicinal product for human use, its starting materials, ingredients and, where necessary, its intermediate products or other constituents in order to ensure that the control methods employed by the manufacturer and described in the application documents are satisfactory;

(b) that the applicant supplements the particulars accompanying the application within a specific time period. In case of such a request, the time-limit set out in Article 6(6), first subparagraph, shall be suspended until the supplementary information requested is provided. Likewise, this time-limit shall be suspended for the time allowed for the applicant to prepare oral or written explanations.

2. Where within 90 days of the date of validation of the marketing authorisation application

and during the assessment the Committee for Medicinal Products for Human Use considers that the submitted data are not of sufficient quality or maturity to complete the assessment, the assessment can be terminated. Prior to the termination, the Committee for Medicinal

Products for Human Use shall summarise the deficiencies in writing. On this basis, the Agency shall inform the applicant accordingly and set a time limit to address the deficiencies. The application shall be suspended until the applicant addresses the deficiencies. If the applicant fails to address those deficiencies within the time limit set by the Agency, the examination shall be terminated and the application shall be considered as withdrawn.

2b. The Committee for Medicinal Products for Human Use may consider and decide upon

additional evidence that is available to the Agency, independently from the data submitted by the marketing authorisation applicant.

Article 11

Certification of manufacturer

1. Upon receipt of a written request from the Committee for Medicinal Products for Human Use, a Member State shall forward the information demonstrating that the manufacturer of a medicinal product or the importer from a third country is able to manufacture the medicinal product concerned or carry out the necessary control tests, or both in accordance with the particulars and documents supplied by the applicant pursuant to Article 6.

2. The Committee for Medicinal Products for Human Use may, if it considers it necessary in

order to complete the assessment, require the applicant to undergo a specific inspection of the manufacturing site of the medicinal product concerned.

The inspection shall be carried out within the time-limit set out in Article 6(6), first subparagraph, by inspectors from the Member State holding the appropriate qualifications. Those inspectors may be accompanied by a rapporteur or an expert appointed by the Committee, or by one or more inspectors of the Agency. The inspections may be carried out unannounced.

For manufacturing sites located in third countries, the inspection may be carried out by the Agency, following a request by the Member States and based on the procedure set out in Article 52.

Article 12

Committee Opinion

1. The Agency shall without undue delay inform the applicant if the opinion of the Committee for Medicinal Products for Human Use is that:

(a) the application does not satisfy the criteria for marketing authorisation set out in this

Regulation;

(b) the application satisfies the criteria set out in this Regulation subject to changes required by the Agency to the summary of product characteristics are made;

(c) the application satisfies the criteria set out in this Regulation provided that changes required by the Agency, to the labelling or package leaflet of the medicinal product, are made to ensure compliance with Chapter VI of [revised Directive 2001/83/EC];

(d) where applicable, the application satisfies the criteria set out in Articles 18 and 19 subject to specific conditions therein.

2. Within 12 days of receipt of the opinion referred to in paragraph 1, the applicant may

request by written notice to the Agency a re-examination of the opinion. In that case, the applicant shall provide the Agency with the detailed grounds for the request within 60 days after receipt of the opinion.

The re-examination procedure may deal only with the points of the opinion initially identified by the applicant and may be based only on the scientific data available when the Committee for Medicinal Products for Human Use adopted the initial opinion.

Within 60 days following receipt of the grounds for the request, the Committee for Medicinal Products for Human Use shall re-examine its opinion. The reasons for the conclusion reached shall be annexed to the final opinion.

3. Within 12 days after its adoption, the Agency shall send the final opinion of the Committee

for Medicinal Products for Human Use to the Commission, to the Member States and to the applicant, together with a report describing the assessment of the medicinal product by the Committee for Medicinal Products for Human Use and stating the reasons for its conclusions.

4. If an opinion is favourable to the granting of the relevant marketing authorisation, the

following documents shall be annexed to the opinion:

(a) a summary of product characteristics referred to in Article 62 of [revised Directive

2001/83/EC] and corresponding to the assessment of the medicinal product;

(b) a recommendation on the frequency of submission of periodic safety update reports;

(c) details of any conditions or restrictions to be imposed on the supply or use of the medicinal product concerned, including the conditions under which the medicinal product may be made available to patients, in accordance with the criteria laid down in Chapter XII of [revised Directive 2001/83/EC];

(d) details of any recommended conditions or restrictions with regard to the safe and effective use of the medicinal product;

(e) details of any recommended measures for ensuring the safe use of the medicinal product to be included in the risk management system;

(f) where appropriate, details of any recommended obligation to conduct postauthorisation safety studies or to comply with obligations on the recording or reporting of suspected adverse reactions which are stricter than those referred to in

Chapter VIII;

(g) where appropriate, details of any recommended obligation to conduct postauthorisation efficacy studies where concerns relating to some aspects of the efficacy of the medicinal product are identified and can be resolved only after the medicinal product has been marketed. Such an obligation to conduct such studies shall be based on the delegated acts adopted pursuant to Article 21 while taking into account the scientific guidance referred to in Article 123 of [revised Directive 2001/83/EC];

(h) where appropriate, details of any recommended obligation to conduct any other postauthorisation studies to improve the safe and effective use of the medicinal product,

including treatment optimisation studies;

(i) in case of medicinal products for which there is substantial uncertainty as to the surrogate endpoint relation to the expected health outcome, where appropriate and relevant for the benefit-risk balance, a post-authorisation obligation to substantiate the clinical benefit;

(j) where appropriate, details of any recommended obligation to conduct additional post-authorisation environmental risk assessment studies, collection of monitoring data or information on use , or to implement appropriate risk mitigation measures, where concerns about risks to the environment or public health, including antimicrobial resistance need to be further investigated or mitigated after the medicinal product has been marketed;

(k) the text of the labelling and package leaflet, presented in accordance with Chapter VI of [revised Directive 2001/83/EC];

(l) the assessment report as regards the results of the pharmaceutical and non-clinical tests and of the clinical trials, and as regards the risk management system and the pharmacovigilance system for the medicinal product concerned;

(m) where appropriate, details of any recommended obligations to carry out medicinal product-specific validation studies to replace animal-based control methods with non-animal-based control methods.

(mb) where applicable, reasoning as to whether the medicinal product satisfies the criteria of Article 83 of [revised Directive 2001/83/EC] regarding medicinal products addressing an unmet medical need.

5. When adopting its opinion, the Committee for Medicinal Products for Human Use shall

include the criteria for the prescription or use of the medicinal products in accordance with Article 50(1) of [revised Directive 2001/83/EC].

Section 2 Marketing authorisation decisions

Article 13

Commission decision on the marketing authorisation

1. Within 12 days of receipt of the opinion of the Committee for Medicinal products for

Human Use the Commission shall submit to the Standing Committee on Medicinal Products for Human Use referred to in Article 173(1) a draft of the decision on the application.

In duly justified cases, the Commission may return the opinion to the Agency for further consideration.

Where a draft decision envisages the granting of a marketing authorisation, it shall include or make reference to the documents referred to in Article 12(4).

Where a draft decision envisages the granting of a marketing authorisation subject to the conditions referred to in Article 12(4), points (c) to (j), it shall lay down deadlines for the fulfilment of the conditions, where necessary.

Where the draft decision differs from the opinion of the Agency, the Commission shall provide a detailed explanation of the reasons for the differences.

The Commission shall send the draft decision to the Member States and the applicant.

2. The Commission shall, by means of implementing acts, take a final decision within 12

days after obtaining the opinion of the Standing Committee on Medicinal Products for Human Use. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173, paragraphs 2 and 3.

3. Where a Member State raises important new questions of a scientific or technical nature

that have not been addressed in the opinion delivered by the Agency, the Commission may refer the application back to the Agency for further consideration. In that case, the procedures set out in paragraphs 1 and 2, shall start again upon reception of the reply of the Agency.

4. The Agency shall disseminate the documents referred to in Article 12(4), points (a) to (e),

and, where relevant, the documents referred to in Article 12(4), points (f) to (ma), together with any deadlines laid down pursuant to paragraph 1, first subparagraph.

Article 14

Withdrawal of a marketing authorisation application

If an applicant withdraws an application for a marketing authorisation submitted to the Agency before an opinion has been given on the application, the applicant shall communicate its reasons for doing so to the Agency. The Agency shall make this information publicly available and shall publish the assessment report, if available, after deletion of all information of a commercially confidential nature.

After the opinion has been given on the application, the applicant is no longer in the position to

withdraw an application on its own initiative.

Article 15

Refusal of a centralised marketing authorisation

1. The marketing authorisation shall be refused if, after verification of the particulars and

documentation submitted in accordance with Article 6, the view is taken that:

(a) the benefit-risk balance of the medicinal product is not favourable;

(b) that the applicant has not properly or sufficiently demonstrated the quality, safety or efficacy of the medicinal product;

(c) its qualitative and quantitative composition is not as declared;

(d) the environmental risk assessment is incomplete or insufficiently substantiated by the applicant, or if the risks identified in the environmental risk assessment have not been sufficiently addressed by the applicant; including through risk mitigation measures, unless the applicant has duly justified and substantiated the reasons for the incomplete or insufficiently substantiated environmental risk assessment, and the competent authorities consider that the marketing authorisation can be granted subject to the conditions referred to in Article 12(4)(j) to conduct postauthorisation environmental risk assessment studies or to implement risk mitigation measures.

(e) particulars or documentation provided by the applicant in accordance with Article 6, paragraphs 1 to 4, are incorrect;

(f) the labelling and package leaflet proposed by the applicant are not in accordance with Chapter VI of [revised Directive 2001/83/EC].

2. The refusal of a Union marketing authorisation shall constitute a prohibition on the placing

on the market of the medicinal product concerned throughout the Union.

3. Information about all refusals and the reasons for them shall be made publicly available.

Article 16

Marketing authorisations

1. Without prejudice to Article 1, paragraphs 8 and 9 of [revised Directive 2001/83/EC], a

marketing authorisation which has been granted in accordance with this Regulation shall be valid throughout the Union. It shall confer the same rights and obligations in each of the Member States as a marketing authorisation granted by that Member State in accordance with Article 5 of [revised Directive 2001/83/EC].

The Commission shall ensure that authorised medicinal products for human use are added to the Union Register of Medicinal Products and that they are given a number, which shall appear on the packaging.

2. Notification of marketing authorisation shall be published in the Official Journal of the European Union, quoting the date of marketing authorisation and the registration number in the Union Register of Medicinal Products, any International Non-proprietary Name (INN) of the active substance of the medicinal product, its pharmaceutical form, and any Anatomical Therapeutic Chemical Code (ATC).

3. The Agency shall immediately publish the assessment report on the medicinal product for

human use and the reasons for its opinion in favour of granting marketing authorisation, after deletion of any information of a commercially confidential nature. The justification for a marketing authorisation issued under Articles 18, 19 and 30 shall be included in the assessment report.

The European public assessment report (EPAR) shall include:

- a summary of the assessment report written in a manner that is understandable to the public. The summary shall contain in particular a section relating to the conditions of use of the medicinal product;

- a summary of environmental risk assessment studies and their results as submitted by the marketing authorisation holder and the assessment of the environmental risk assessment and the information referred to in Article 22(5) of [revised Directive 2001/83/EC] by the Agency.

- for antimicrobials, the information referred to in Article 17 (1), point (a) and Annex I, 21 paragraph, point(a) to [revised Directive 2001/83/EC] as well as any other obligations imposed on the marketing authorisation holder.

4. After a marketing authorisation has been granted, the marketing authorisation holder shall

inform the Agency of the dates of actual marketing of the medicinal product for human use in the Member States, taking into account the various presentations authorised.

The marketing authorisation holder shall notify the Agency and the competent authority of the Member State concerned of the following:

(a) its intention to permanently cease the marketing of a medicinal product in that

Member State in accordance with Article 116(1), point (a); or

(b) its intention to temporarily suspend the marketing of a medicinal product in that

Member State in accordance with Article 116(1), point (c); or

(c) a potential or actual shortage in that Member State in accordance with Article 116(1), point (d); and its reasons for such action under points (a) and (b) in accordance with Article 24, as well as any other reason relating to precautionary actions with regard to quality, safety, efficacy and the environment.

Upon request by the Agency, particularly in the context of pharmacovigilance, the marketing authorisation holder shall provide the Agency with all data relating to the volume of sales of the medicinal product at Union level, broken down by Member State, and any data in the marketing authorisation holder's possession relating to the volume of prescriptions in the Union and its Member States.

Article 17

Validity and renewal of marketing authorisations

1. Without prejudice to paragraph 2, a marketing authorisation for a medicinal product shall

be valid for an unlimited period.

2. By way of derogation from paragraph 1, the Commission may decide when granting an

authorisation, on the basis of a scientific opinion by the Agency concerning the safety of the medicinal product, to limit the validity of the marketing authorisation to five years.

Where the validity of the marketing authorisation is limited to five years, the marketing authorisation holder shall apply to the Agency for a renewal of the marketing authorisation at least nine months before the marketing authorisation ceases to be valid.

Where a renewal application has been submitted in accordance with the second subparagraph, the marketing authorisation shall remain valid until a decision is adopted by the Commission in accordance with Article 13.

The marketing authorisation may be renewed on the basis of a re-evaluation by the Agency of the benefit-risk balance. Once renewed, the marketing authorisation shall be valid for an unlimited period.

Article 18

Marketing authorisation granted in exceptional circumstances

1. In exceptional circumstances where, in an application under Article 6 of [revised Directive 2001/83/EC] for a marketing authorisation of a medicinal product or a new therapeutic indication of an existing marketing authorisation under this Regulation, an applicant is unable to provide comprehensive data on the efficacy and safety of the medicinal product under normal conditions of use, the Commission may, by derogation to Article 6, grant an authorisation under Article 13, subject to specific conditions, where the following requirements are met:

(a) the applicant has demonstrated, in the application file, that there are objective and verifiable reasons not to be able to submit comprehensive data on the efficacy and safety of the medicinal product under normal conditions of use based on one of the grounds set out in Annex II to [revised Directive 2001/83/EC];

(b) except for the data referred to in point (a), the application file is complete and satisfies all the requirements of this Regulation;

(c) specific conditions are included in the decision of the Commission, in particular to ensure the safety of the medicinal product as well to ensure that the marketing authorisation holder notifies to the competent authorities any incident relating to its use and takes appropriate action where necessary.

2. The maintenance of the authorised new therapeutic indication and the validity of the

marketing authorisation granted in accordance with paragraph 1 shall be linked to the reassessment by the Agency of the conditions referred to in paragraph 1 after two years or at an earlier time as set out in the marketing authorisation, from the date when the new therapeutic indication was authorised or the marketing authorisation was granted, and thereafter at a risk-based frequency to be determined by the Agency and specified by the Commission in the marketing authorisation.

This reassessment shall be conducted on the basis of an application by the marketing authorisation holder to maintain the authorised new therapeutic indication or renew the marketing authorisation under exceptional circumstances.

Article 19

Conditional marketing authorisation

1. In duly justified cases, to meet an unmet medical need of patients, as referred to in Article 83(1), point (a), of [revised Directive 2001/83/EC], a conditional marketing authorisation or a new conditional therapeutic indication to an existing marketing authorisation authorised under this Regulation may be granted by the Commission to a medicinal product that is likely to address the unmet medical need in accordance with Article 83(1), point (b), of [revised Directive 2001/83/EC], prior to the submission of comprehensive clinical data provided that the benefit of the immediate availability on the market of that medicinal product outweighs the risk inherent in the fact that additional data are still required.

In emergency situations, a conditional marketing authorisation or a new conditional therapeutic indication referred to in the first subparagraph may be granted also where comprehensive non-clinical or pharmaceutical data have not been supplied.

2. Conditional marketing authorisations or a new conditional therapeutic indication referred

to in paragraph 1 may be granted only if the benefit-risk balance of the medicinal product is favourable and the applicant is likely to be able to provide comprehensive data.

3. Conditional marketing authorisations or a new conditional therapeutic indication granted

pursuant to this Article shall be subject to specific obligations. Those specific obligations and, where appropriate, the time limit for compliance shall be specified in the conditions to the marketing authorisation. Those specific obligations shall be reviewed annually by the Agency for the first three years after granting the authorisation and every two years thereafter.

4. As part of the specific obligations referred to in paragraph 3, the marketing authorisation

holder of a conditional marketing authorisation granted pursuant to this Article shall be required to complete ongoing studies, or to conduct new studies, with a view to confirming that the benefit-risk balance is favourable.

5. The summary of product characteristics and the package leaflet shall clearly mention that

the conditional marketing authorisation for the medicinal product has been granted subject to specific obligations as referred to in paragraph 3.

6. By way of derogation from Article 17(1), an initial conditional marketing authorisation

granted pursuant to this Article shall be valid for one year, on a renewable basis for the first three years after granting the authorisation and every two years thereafter..

7. When the specific obligations referred to in paragraph 3 have been fulfilled for a

conditional marketing authorisation granted pursuant to this Article, the Commission may, following an application by the marketing authorisation holder, and after having received a favourable opinion from the Agency, grant a marketing authorisation pursuant to Article

13.

8. The Commission is empowered to adopt delegated acts in accordance with Article 175 to

supplement this Regulation by establishing the following:

(a) the categories of medicinal products to which paragraph 1 applies;

(b) the procedures and requirements for granting a conditional marketing authorisation, for its renewal, and for adding a new conditional therapeutic indication to an existing marketing authorisation.

Article 20

Imposed post-authorisation studies

1. After the granting of a marketing authorisation, the Agency may consider that it is

necessary that the marketing authorisation holder:

(a) conducts a post-authorisation safety study if there are concerns about the risks of an authorised medicinal product. If the same concerns apply to more than one medicinal product, the Agency shall, following consultation with the Pharmacovigilance Risk Assessment Committee, encourage the marketing authorisation holders concerned to conduct a joint post-authorisation safety study;

(b) conducts a post-authorisation efficacy study when the understanding of the disease or the clinical methodology indicate that previous efficacy evaluations might have to be revised significantly. The obligation to conduct the post-authorisation efficacy study shall be based on the delegated acts adopted pursuant to Article 21 while taking into account the scientific guidance referred to in Article 123 of [revised Directive

2001/83/EC];

(c) conducts a post-authorisation environmental risk assessment study to further investigate the risks to the environment or public health, including antimicrobial resistance, due to the release of the medicinal product in the environment, if new concerns emerge on the authorised medicinal product, or other medicinal products containing the same active substance.

If this obligation applies to several medicinal products, the Agency shall encourage the marketing authorisation holders concerned to conduct a joint post authorisation environmental risk assessment study.

(d) conducts any other post-authorisation studies to improve the safe and effective use of the medicinal product, including treatment optimisation based on clinical experience.

If this obligation would apply to several medicinal products, the Agency shall encourage the marketing authorisation holders concerned to conduct a joint post authorisation environmental risk assessment study.

Where the Agency considers that any of the post-authorisations studies referred to in points (a) to (c)(d) is necessary, it shall inform the marketing authorisation holder thereof in writing, stating the grounds for its assessment and shall include the objectives and timeframe for submission and conduct of the study.

2. The Agency shall provide the marketing authorisation holder with an opportunity to

present written observations in response to its letter within a time limit which it shall specify, if the marketing authorisation holder so requests within 30 days of receipt of the letter.

3. On the basis of the written observations the Agency shall review its opinion.

4. Where the opinion of the Agency confirms the need for any of the post-authorisation

studies referred to in paragraph 1, points (a) to (c)(d), to be carried out, the Commission shall vary the marketing authorisation, by means of implementing acts, adopted pursuant to Article 13 to include the obligation as a condition of the marketing authorisation unless the Commission returns the opinion to the Agency for further consideration. For obligations under paragraph 1, points (a),and (b) and (d), the marketing authorisation holder shall update the risk management system accordingly.

Article 21

Post authorisation efficacy studies

The Commission is empowered to adopt delegated acts in accordance with Article 175, to supplement this Regulation by determining the situations in which post-authorisation efficacy studies may be required under Article 12(4), point (g), and Article 20(1), point (b).

Article 22

Risk management system

The marketing authorisation holder shall incorporate any condition of authorisation reflecting the elements referred to in Article 12(4), points (d) to (g)(i), or in Article 2020(1), points (a), (b) and (d), or in Article 18(1) and Article 19 in their risk management system.

Article 23

Liability of the marketing authorisation holder

The granting of a marketing authorisation shall not affect the civil or criminal liability of the manufacturer or of the marketing authorisation holder pursuant to the applicable national law in Member States.

Article 24

Suspension of marketing, withdrawal from the market of a medicinal product, withdrawal of a marketing authorisation by the marketing authorisation holder

1. In addition to the notification made pursuant to Article 116, The marketing authorisation

holder shall notify the Agency without undue delay of any action they take to suspend the marketing of a medicinal product, to withdraw a medicinal product from the market, to request the withdrawal of a marketing authorisation or not to apply for the renewal of a marketing authorisation, together with the reasonsa detailed reasoning for such action.

The marketing authorisation holder shall declare if such action is based on the following grounds:

(a) the medicinal product is harmful;

(b) it lacks therapeutic efficacy;

(c) the benefit-risk balance is not favourable;

(d) its qualitative and quantitative composition is not as declared;

(e) the controls on the medicinal product or on the ingredients and the controls at an intermediate stage of the manufacturing process have not been carried out or if some other requirement or obligation relating to the grant of the manufacturing authorisation has not been fulfilled; or

(f) a serious risk to the environment or to public health via the environment has been identified and not sufficiently addressed by the marketing authorisation holder.

(fa) commercial reasons.

Where the action referred to in the first subparagraph is to withdraw a medicinal product from the market, the marketing authorisation holder shall provide information on the impact of such withdrawal on patients who are already being treated.

The notification of the permanent withdrawal of a medicinal product from the market or of the temporary suspension of the marketing authorisation, or of the permanent withdrawal of a marketing authorisation or of the temporary disruption in supply of a medicinal product shall be made in accordance with Article 116(1).

The marketing authorisation holder shall make the notification electronically and in the formats made available by the Agency. The Agency shall consult the Member States

when drawing up the formats.

2. The marketing authorisation holder shall make the notification pursuant to paragraph 1 if

the action is taken in a third country and such action is based on any of the grounds set out

in Articles 195 or 196(1) of [revised Directive 2001/83/EC]paragraph 1(a) to (f).

3. In the cases referred to in paragraphs 1 and 2, the Agency shall forward the information to

the competent authorities of the Member States without undue delay.

3a. In the cases referred to in paragraph 1, second subparagraph, point (f), the Agency shall

immediately inform the Commission, and the Marketing Authorisation Holder shall

inform the relevant national and Union authorities without delay.

4. Where the marketing authorisation holder intends to permanently withdraw the marketing

authorisation for a critical medicinal product, the marketing authorisation holder shall, prior to the notification referred to in paragraph 1, offer, on reasonable terms, to transfer the marketing authorisation to a third party that has declared its intention to place that critical medicinal product on the market, or to use the pharmaceutical non-clinical and clinical documentation contained in the file of the medicinal product for the purposes of submitting an application in accordance with Article 14 of [revised Directive 2001/83/EC].

Article 25

Duplicate marketing authorisations

1. Only one marketing authorisation may be granted to an applicant for a specific medicinal

product.

By way of derogation from the first subparagraph, the Commission shall authorise the same applicant to submit more than one application to the Agency for that medicinal product in either of the following cases:

(a) if one of its indications or pharmaceutical forms, posologies, methods or routes of administration or any other way in which the medicinal product may be used is protected by a patent or a supplementary protection certificate in one or more

Member States;

(b) for reasons of co-marketing with a different undertaking not belonging to the same group as the marketing authorisation holder of the medicinal product for which a duplicate is requested.

As soon as the relevant patent or supplementary protection certificate referred to in point (a) expires, the marketing authorisation holder shall withdraw the initial or duplicate marketing authorisation as soon as possible.

2. As regards medicinal products for human use, Article 187(3) of [revised Directive 2001/83/EC] shall apply to medicinal products authorised under this Regulation.

3. Without prejudice to the unique Union nature of the content of the documents referred to in Article 12(4), points (a) to (k), this Regulation shall not prohibit the use of two or more commercial designs for a given medicinal product for human use covered by a single marketing authorisation.

Article 26

Medicinal products for compassionate use

1. By way of derogation from Article 5 of [revised Directive 2001/83/EC] Member States

may make available for compassionate use a medicinal product for human use belonging to the categories referred to in Article 3, paragraphs 1 and 2. This may include new therapeutic uses of an authorised medicinal product.

2. For the purposes of this Article, ‘compassionate use’ shall mean making a medicinal

product belonging to the categories referred to in Article 3, paragraphs 1 and 2 available for compassionate reasons to a single patient or group of patients with a chronically or seriously debilitating disease or whose disease is considered to be life-threatening, or impacting their mental health with severe psychological or emotional distress, leading to worsening of clinical symptoms and severely compromising the ability to function in daily life, and who cannot be treated satisfactorily by an authorised medicinal product. The medicinal product concerned mustshall either be the subject of an application for a marketing authorisation in accordance with Article 6 or the submission of such application is imminent, or it must beis undergoing clinical trials in the same indication.

3. When applying paragraph 1, the Member State shall notify the Agency, which shall make

the notification publicly available.

4. When compassionate use is envisaged by a Member State, the Committee for Medicinal Products for Human Use, after consulting the manufacturer or the applicant, may adopt opinions on the conditions for use, the conditions for distribution and, the patients targeted and the conditions of monitoring. The opinions shall be updated where necessary.

In the preparation of the opinion, the Committee for Medicinal Products for Human Use may request information and data from marketing authorisation holders and from developers and may engage with them in preliminary discussions. The Committee may also make use of health data generated outside of clinical studies, including real world data, where available, taking into account the reliability of those data.

The Agency may also liaise with the third country agencies for medicinal products with respect to additional information and data exchanges.

In the preparation of its opinion, the Committee for Medicinal Products for Human Use may consult the Member State concerned and request it to provide any available information or data that the Member State has in its possession relating to the medicinal product concerned.

5. When applying paragraph 1, Member States shall take account of any available opinion

and notify the Agency of the making available of products on the basis of the opinion in their territory. Member States shall ensure that pharmacovigilance requirements are applied for those products. Article 106, paragraphs 1 and 2, as regards the recording and reporting of suspected adverse reactions and the submission of periodic safety update reports respectively, shall apply mutatis mutandisare applied for those products.

6. The Agency shall keep an up-to-date list of the opinions adopted in accordance with

paragraph 4 and shall publish it on its website.

7. The opinions referred to in paragraph 4 shall not affect the civil or criminal liability of the

manufacturer or of the applicant for marketing authorisation.

8. Where a compassionate use programme has been set up in accordance with paragraphs 1

and 5, the applicant shall ensure thatthe supply of the medicinal product to patients taking part to such programme also have access to the new medicinal product during the, if necessary for a period betweenafter the marketing authorisation has been granted and until the medicine is made availableand placing on the market of the Member State concerned.

9. This Article shall be without prejudice to Regulation (EU) No 536/2014 and to Article 3 of [revised Directive 2001/83/EC].

10. The Agency mayshall adopt detailed guidelines laying down format and content of

notifications referred to in paragraphs 3 and 5, and data exchange under this Article.

Article 27

Request for opinion on scientific matters

At the request of the Executive Director of the Agency or the Commission, the Committee for Medicinal Products for Human Use shall draw up an opinion on any scientific matter concerning the evaluation of medicinal products for human use. That Committee shall take due account of any requests by Member States for an opinion.

The Agency shall publish the opinion after deletion of any information of a commercially confidential nature.

Article 28

Regulatory decisions on marketing authorisations

An authorisation to place a medicinal product covered by this Regulation on the market shall not be granted, refused, varied, suspended, withdrawn or revoked except through the procedures and on the grounds set out in this Regulation.

Article 29

Regulatory protection periods

Without prejudice to the law on the protection of industrial and commercial property, medicinal products for human use which have been authorised in accordance with this Regulation shall benefit from the periods of regulatory protection set out in Chapter VII of [revised Directive 2001/83/EC].

Section 3

Temporary emergency marketing authorisation

Article 30

Temporary emergency marketing authorisation

During a public health emergency, the Commission may grant a temporary emergency marketing authorisation (‘TEMA’) for medicinal products intended for the treatment, prevention or medical diagnosis of a serious or life-threatening disease or condition which are directly related to the public health emergency, prior to the submission of the complete quality, non-clinical, clinical data and environmental data and information.

Where medicinal products containing or consisting of genetically modified organisms in the sense of Article 2(2) of Directive 2001/18/EC are concerned, Articles 13 to 24 of that Directive shall not apply.

An application for a temporary emergency marketing authorisation shall be submitted in accordance with Articles 5 and 6.

Article 31

Criteria for granting a temporary emergency marketing authorisation

A temporary emergency marketing authorisation may be granted only after the recognition of a public health emergency at Union level in accordance with Article 23 of Regulation (EU) 2022/2371 of the European Parliament and of the Council and where the following requirements are met:

(a) there is no other satisfactory method of treatment, prevention or diagnosis authorised or

sufficiently available in the Union or, if such method is already available, the temporary emergency marketing authorisation of the medicinal product will contribute to address the public health emergency;

(b) based on the scientific evidence available, the Agency issues an opinion concluding that

the medicinal product could be effective in treating, preventing or diagnosing the disease or condition directly related to the public health emergency, and the known and potential benefits of the product outweigh the known and potential risks of the product, taking into consideration the threat posed by the public health emergency.

Article 32

Scientific opinion

1. The Agency shall ensure that the scientific opinion of the Committee for Medicinal Products for Human Use is given without undue delay, taking into account, the recommendation of the Emergency Task Force referred to in Article 38(1), second subparagraph. For the purpose of issuing its opinion, the Agency may consider any relevant data on the medicinal product concerned.

2. The Agency shall without undue delay review any new evidence provided by the

developer, the Member States or the Commission, or any other evidence that comes to its attention, in particular evidence that might influence the benefit-risk balance of the medicinal product concerned.

The Agency shall update its scientific opinion as necessary.

3. The Agency shall transmit without undue delay to the Commission the scientific opinion

and its updates and any recommendations on the temporary emergency marketing authorisation.

Article 33

Commission decision for a temporary emergency marketing authorisation

1. On the basis of the scientific opinion of the Agency or its updates referred to in Article 32,

paragraphs 1 and 2, the Commission shall, by means of implementing acts, take a decision without undue delay on the temporary emergency marketing authorisation of the medicinal product subject to the specific conditions set in accordance with paragraphs 2, 3 and 4. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2).

2. On the basis of the scientific opinion of the Agency referred to in paragraph 1, the Commission shall set specific conditions with respect to the temporary emergency marketing authorisation, in particular the conditions for manufacturing, use, supply and safety monitoring and the compliance with related good manufacturing, and pharmacovigilance practices. If necessary, the conditions may specify the batches of the medicinal product concerned by the temporary emergency marketing authorisation.

3. Specific conditions may be set to require the completion of ongoing studies or to conduct

new studies to ensure the safe and effective use of the medicinal product or minimise its impact on the environment. A time limit for the submission of those studies shall be set.

4. Those specific conditions and, where appropriate, the time limit for compliance shall be

specified in the conditions to the marketing authorisation and shall be reviewed annually by the Agency.

4a. The Agency shall immediately publish the assessment report on the medicinal product

for human use and the reasons for its opinion in favour of granting marketing authorisation, after deletion of any information of a commercially confidential nature.

Article 34

Validity of a temporary emergency marketing authorisation

The temporary emergency marketing authorisation shall cease to be valid when the Commission terminates the recognition of a public health emergency in accordance with Article 23(2) and (4) of Regulation (EU) 2022/2371.

Article 35

Variation, suspension or revocation of a temporary emergency marketing authorisation

The Commission may suspend, revoke or vary the temporary emergency marketing authorisation by means of implementing acts at any time in any of the following cases:

(a) the criteria laid down in Article 31 are no longer met;

(b) it is appropriate to protect public health;

(c) the marketing authorisation holder of a temporary emergency marketing authorisation has

not complied with conditions and obligations set out in the temporary emergency marketing authorisation;

(d) the marketing authorisation holder of a temporary emergency marketing authorisation has

not complied with the specific conditions set in accordance with Article 33.

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2).

Article 36

Granting of a marketing authorisation or conditional marketing authorisation after a temporary emergency marketing authorisation

As soon as sufficient data has been generated, the marketing authorisation holder of an authorisation in accordance with Article 33 mayshall submit an application in accordance with Articles 5 and 6 in order to obtainreplace the temporary emergency marketing authorisation by an authorisation in accordance with Articles 13, 1618 or 19.

For the purpose of regulatory data protection, the temporary emergency marketing authorisation and any subsequent marketing authorisation, as referred to in subparagraph 1, shall be considered as part of the same global marketing authorisation.

Article 37

Transitional period

When the temporary marketing authorisation of a medicinal product is suspended or revoked for reasons other than the safety of the medicinal product, or if that temporary emergency marketing authorisation ceases to be valid, Member States may, in exceptional circumstances, allow for a transitional period, the supply of the medicinal product to patients who are already being treated with it. In such cases, the Member State shall inform the Agency about the application of the transitional period. Conditions for manufacturing, use, supply and safety monitoring and the compliance with the related good manufacturing and pharmacovigilance practices shall continue to apply during that period.

Article 38

Relation with Article 18 of Regulation (EU) 2022/123

1. For medicinal products for which a temporary emergency marketing authorisation may be

considered by the Agency, Article 18(1) and (2) of Regulation (EU) 2022/123 shall apply.

The Emergency Task Force shall provide a recommendation for a temporary emergency marketing authorisation to the Committee for Medicinal Products for Human Use for an opinion in accordance with Article 32. To this purpose, the Emergency Task Force set up pursuant to Article 15 of Regulation (EU) 2022/123 may, where appropriate, perform the activities referred to in Article 18(2) of that Regulation prior to the recognition of a public health emergency.

2. 2. Where a request referred to in Article 18(3) of Regulation (EU) 2022/123 for a

recommendation has been made and there is an application for a temporary emergency marketing authorisation for the medicinal product concerned, the procedure for a recommendation under Article 18(3) of Regulation (EU) 2022/123 shall be stopped and the procedure for a temporary emergency marketing authorisation shall prevail. Any available data shall be considered under the temporary emergency marketing authorisation application.

Article 39

Withdrawal of authorisations granted in accordance with Article 3(2) of [revised Directive 2001/83/EC]

When the Commission has granted a temporary emergency marketing authorisation in accordance with Article 33, Member States shall, where possible and within a reasonable time limit, withdraw any authorisation granted in accordance with Article 3(2) of [revised Directive 2001/83/EC] for the use of medicinal products containing the same active substance for any indications that are subject to the temporary marketing authorisation.

CHAPTER III INCENTIVES FOR THE DEVELOPMENT OF ‘PRIORITY ANTIMICROBIALS’

Section 1

Transferable exclusivity vouchers for priority antimicrobials

Article 40

Granting the right to a transferable data exclusivity voucher

1. Following a request by the applicant when applying for a marketing authorisation, the Commission may, by means of implementing acts, grant a transferable data exclusivity voucher to a ‘priority antimicrobial’ referred to in paragraph 3, under the conditions referred to in paragraph 4 based on a scientific assessment by the Agency.

2. The voucher referred to in paragraph 1 shall give the right to its holder to an additional 12

months of data protection within the meaning of Article 80 paragraph 1 of [revised Directive 2001/83/EC] for one authorised medicinal product.

3. An antimicrobial shall be considered a ‘priority antimicrobial’ if it addresses a multi-drug

resistant organism and if the preclinical and clinical data underpindemonstrate a significant clinical benefit with respect to antimicrobial resistance and if it has at least one of the following characteristics:

(a) it represents a new class of antimicrobials;

(b) its mechanism of action is distinctly different from that of any authorised antimicrobial in the Union;

(c) it contains ana new active substance not previously authorised in a medicinal product in the Union thatthat when used either alone or in combination with other active substances addresses a multi-drug resistant organism and serious or life threatening infection.

In the scientific assessment of the criteria referred to in the first subparagraph, and in the case of antibiotics, the Agency shall take into account the ‘WHO priority pathogens list for R&D of new antibiotics’, or an equivalent list established at Union level.

4. To be granted the voucher by the Commission, the applicant shall:

(a) demonstrate capacity to supply the priority antimicrobial in sufficient quantities for the expected needs of the Union market;

(b) provide information on all direct financial support received for research related to the development of the priority antimicrobial.

(c) demonstrate that the application for granting a marketing authorisation of the priority antimicrobial has been first submitted to the Agency or has been submitted no later than 180 days after the submission of the application for the first marketing authorisation outside the European Union.

Within 30 days after the marketing authorisation is granted, the marketing authorisation holder shall make the information referred to in point (b) accessible to the public via a dedicated webpage and shall communicate, in a timely manner the electronic link to that webpage to the Agency.

5. Once the marketing authorisation is granted, the Agency shall inform without undue

delay the MSSG, in accordance with Article 131 paragraph 2 with a view to propose a potential inclusion of the priority antimicrobial on the Union list of critical medicinal products.

6 A priority antimicrobial shall be reserved for exclusive use for the treatment of humans

for a period of 10 years to preserve the efficacy of those antimicrobials.

The period referred to in the previous subparagraph may be prolonged based on an evaluation by the Agency on the basis of the criteria set in the Commission Delegated Regulation (EU) 2021/1760.

7 The Commission shall inform the Member States of the granting of the marketing

authorisation and include a recommendation inviting Member States to make use of the possibility of a voluntary subscription model for joint procurement referred to in Article 43a.

Article 41

Transfer and use of the voucher

1. A voucher may be used to extendadd 12 months to the data protection for a period

referred to in Article 80 paragraph 1 of [revised Directive 2001/83/EC]of 12 months of the priority antimicrobial or of another medicinal product authorised in accordance with this Regulation of the same or different marketing authorisation holder.

A voucher shall only may be used once and in relation to a single centrally authorised medicinal product and only if that product is within its first four years of regulatory data protection..

In case of a medicinal product other than the priority antimicrobial concerned, the use of the voucher shall take place only in the fifth or sixth year of the regulatory data protection period and only if the marketing authorisation holder demonstrates that the annual gross sales of that medicinal product in the Union during any of the first four years after the granting of the marketing authorisation have not exceeded 490 million euros.

1a. The marketing authorisation holder shall demonstrate that information about the

annual gross sales referred to in paragraph (1) is accurate and complete and that it has been audited by an independent external auditor.

A voucher may only be used if the marketing authorisation of the priority antimicrobial for which the right was initially granted has not been withdrawn.

2. To use the voucher, its owner shall apply for a variation of the marketing authorisation

concerned in accordance with Article 47 to extend the data protection.

3. A voucher may be transferred to another marketing authorisation holder and shall not be

transferred further.

4. A marketing authorisation holder to whom a voucher is transferred shall notify the Agency

of the transfer within 30 days, stating the value of the transaction between the two parties.

The Agency shall make this information publicly available on its webpage.

Article 42 Validity of the voucher

1. A voucher shall cease to be valid in the following cases:

(a) where the Commission adopts a decision in accordance with Article 47 to extend the data protection of the receiving medicinal product;

(b) where it is not used within 5 years from the date it was granted.

2. The Commission may revoke the voucher prior to its transfer as referred to in Article 41(3)

if a request for supply by any Member State or the Commission, procurement or purchase of the priority antimicrobial in the Union has not been fulfilled.

3. Without prejudice to patent rights, or supplementary protection certificates34, if a priority

antimicrobial is withdrawn from the Union market prior to expiry of the periods of market and data protection laid down in Articles 80 and 81 of [revised Directive 2001/83/EC], those periods shall not prevent the validation, authorisation and placing on the market of a medicinal product using the priority antimicrobial as a reference medicinal product in accordance with Chapter II, Section 2 of [revised Directive 2001/83].

Article 43

Duration of application of Section I of Chapter III

This Chapter Section 1 shall apply, taking into account the outcome of the evaluation referred to in Article 170 paragraph 5a, until [Note to OP: insert the date of 15 years after the date of entry into force of this Regulation] or until the date when the Commission has granted a total of 105 vouchers in accordance with this Chapter, whichever date is the earliest.

34 Regulation (EC) No 469/2009 of the European Parliament and of the Council, (OJ L 152,

16.6.2009, p. 1).

Section 2

Voluntary subscription model for antimicrobials

Article 43a

Voluntary subscription model for the joint procurement of antimicrobials

1. Contracting authorities from different Member States may act jointly in the award of

public contracts pursuant to Article 39 of Directive 2014/24/EU with a view to purchasing antimicrobials.

2. For the purposes of paragraph 1, in addition to the elements in Article 39(4) of Directive 2014/24/EU, the agreement between the parties shall determine the practical arrangements governing the conditions for a subscription model system and other procedures, including, length of the subscription contract and the possibility of parallel procurement.

3. The contract to be awarded shall take the form of a multi-year subscription and include

at least the following conditions:

(a) delinkage or partial delinkage of funding from the volume of sales of the antimicrobial;

(b) arrangements regarding criteria to support continuous and sufficient supply in

pre-agreed quantities;

4. For the purpose of paragraphs 2 and 3, the Commission shall, in consultation with Member States and relevant parties, draw up guidelines to identify the relevant components for a subscription model system , including the methodology for valuing and remunerating products to ensure economic viability of their supply, and incentives to encourage investment in priority antimicrobial product development. The Commission shall upon request support Member States in the application of this Article. Member States may take such guidelines into account when they establish a subscription model system under this Article.

5. Member States may, where necessary, request the Commission to organise joint

meetings between the competent authorities of the Member States, the Agency, and any other relevant parties, as appropriate, including bodies responsible for pricing and reimbursement, to discuss issues related to the practical application of this Article.

Member States shall notify the Commission when applying this Article.

CHAPTER IV POST-MARKETING AUTHORISATION MEASURES

Article 44

Urgent safety or efficacy restrictions

1. If, in the event of a risk to public health, the marketing authorisation holder takes urgent

safety or efficacy restrictions on their own initiative, the marketing authorisation holder shall immediately inform the Agency and the competent authorities of the Member States where the medicinal product is placed on the market.

If the Agency has not raised objections within 24 hours following receipt of the information, the urgent safety or efficacy restrictions shall be deemed temporarily accepted.

The marketing authorisation holder shall submit the corresponding application for variation within 1512 days following initiation of that restriction in accordance with Article 47.

2. In the event of a risk to public health, the Commission may vary the marketing

authorisation to impose urgent safety or efficacy restrictions on the marketing authorisation holder.

The Commission shall take the decision to amend the marketing authorisation by means of implementing acts.

Where the Commission decision in accordance with this Article imposes restrictions with regard to the safe and effective use of the medicinal product, it may also adopt a decision addressed to the Member States pursuant to Article 57.

Where the marketing authorisation holder disagrees with the Commission decision, they may provide to the Agency written observations on the variation within 15 12 days of their receipt of the Commission decision. The Agency shall, based on the written observation, issue an opinion whether an amendment of the variation is required.

If an amendment of the variation is required, the Commission shall take a final decision in accordance with the examination procedure referred to in Article 173(2).

If a referral under Article 55 of this Regulation or under Article 95 or 114 of [revised Directive 2001/83/EC] is launched on the same safety or efficacy concern covered by this variation, any written observation provided by the marketing authorisation holder shall be considered in that referral.

Article 45

Update of a marketing authorisation related to scientific and technological developments

1. After a marketing authorisation has been granted in accordance with this Regulation, the

marketing authorisation holder shall, in respect of the methods of manufacture and control provided for in Annex I, points (6) and (10), to [revised Directive 2001/83/EC], take account of scientific and technical progress and introduce any changes that may be required to enable the medicinal product to be manufactured and checked by means of generally accepted scientific methods. The marketing authorisation holder shall apply for approval of corresponding variations in accordance with Article 47 of this Regulation.

2. The marketing authorisation holder shall without undue delay provide the Agency, the Commission and the Member States with any new information which might entail the amendment of the particulars or documentation referred to in Annex I, Articles 11, 28, 41

(5) or 62 of [revised Directive 2001/83/EC], in Annex II to that Directive, or in Article 12(4) of this Regulation.

The marketing authorisation holder shall without undue delay inform the Agency and, the Commission and the competent authorities of the Member States of any prohibition or restriction imposed on the marketing authorisation holder or any entity in contractual relationship with the marketing authorisation holder by the competent authorities of any country in which the medicinal product is marketed and of any other new information which might influence the evaluation of the benefits and risks of the medicinal product concerned. The information shall include both positive and negative results of clinical trials or other studies in all indications and populations, whether or not included in the marketing authorisation, as well as data on the use of the medicinal product where such use is outside the terms of the marketing authorisation.

3. The marketing authorisation holder shall ensure that the product information and the terms

of the marketing authorisation including the summary of product characteristics, the labelling and package leaflet are kept up to date with the current scientific knowledge including the conclusions of the assessment and recommendations made public by means of the European medicines web-portal set-up in accordance with Article 104.

4. The Agency may at any time request the marketing authorisation holder to submit data

demonstrating that the benefit-risk balance remains favourable. The marketing authorisation holder shall answer fully and promptlywithin the time limit set for any such request. The marketing authorisation holder shall also respond fully and within the time limit set to any such request of a competent authority regarding the implementation of any measures previously imposed, including risk minimisation measures.

The Agency may at any time ask the marketing authorisation holder to submit a copy of the pharmacovigilance system master file. The marketing authorisation holder shall submit that copy at the latest seven days after receipt of the request.

The marketing authorisation holder shall also respond fully and within the time limit set to any request of a competent authority regarding the implementation of any measures previously imposed with regard to risks to the environment or public health, including antimicrobial resistance.

4a. The Agency, through its scientific committees, may consider additional evidence

available, independently from the data submitted by the marketing authorisation holder. On that basis, if the additional evidence has an impact on the benefit-risk balance of a medicinal product, the Agency may recommend that the summary of product characteristics shall be updated, without excluding other actions that may be taken. In this case the marketing authorisation holder shall submit to the Agency an appropriate application for a variation, including an updated summary of product characteristics.

Article 46

Update of risk management plans

1. The marketing authorisation holder of a medicinal product referred to in Articles 9, and 11

of [revised Directive 2001/83/EC], who did not submit a risk management plan in accordance with Article 21 of [Revised Directive 2001/83/EC] shall submit to the Agency a risk management plan and a summary thereof, where the marketing authorisation for the reference medicinal product is withdrawn but the marketing authorisation for the medicinal product referred to in Articles 9 and 11 of [revised Directive 2001/83/EC] is maintained.

The risk management plan and the summary thereof shall be submitted to the Agency within 60 days of the withdrawal of the marketing authorisation for the reference medicinal product by means of a variation in accordance with Article 47.

2. The Agency may impose an obligation on a marketing authorisation holder for a medicinal

product referred to in Articles 9, 10, 11 and 12 and 11 of [revised Directive 2001/83/EC] to submit a risk management plan and summary thereof where:

(a) additional risk minimisation measures have been imposed concerning the reference medicinal product; or

(b) it is justified on pharmacovigilance grounds.

3. In the case mentioned referred to in paragraphparagraphs 1 and 2, point (a), the risk

management plan shall be aligned with the risk management plan for the reference medicinal product.

4. The imposition of the obligation referred to in paragraph 32, shall be duly justified in

writing, notified to the marketing authorisation holder and shall include the deadline for submission of the risk management plan and the summary by means of a variation in accordance with Article 47.

Article 47

Variation of marketing authorisation

1. An application for variation of a centralised marketing authorisation by the marketing

authorisation holder shall be made electronically in the formats made available by the Agency, unless the variation is an update by the marketing authorisation holder of their information held in a database.

2. Variations shall be classified in different categories depending on the level of risk to public

health and the potential impact on the quality, safety and efficacy of the medicinal product concerned. Those categories shall range from changes to the terms of the marketing authorisation that have the highest potential impact on the quality, safety or efficacy of the medicinal product, to changes that have no or minimal impact thereon and to administrative changes.

3. The procedures for examination of applications for variations shall be proportionate to the

risk and impact involved. Those procedures shall range from procedures that allow implementation only after approval based on a complete scientific assessment to procedures that allow immediate implementation and subsequent notification by the marketing authorisation holder to the Agency. Such procedures may also include updates by the marketing authorisation holder of their information held in a database.

4. The Commission is empowered to adopt delegated acts in accordance with Article 175 to

supplement this Regulation by establishing the following:

(a) the categories referred to in paragraph 2 in which variations shall be classified;

(b) procedures for the examination of applications for variations to the terms of marketing authorisations, including procedures for updates through a database;

(c) the conditions for submission of a single application for more than one change to the terms of the same marketing authorisation and for the same change to the terms of several marketing authorisations;

(d) specifying exemptions to the variation procedures where the update of information in the marketing authorisation referred to in Annex I of the [revised Directive 2001/83] may be directly implemented;

(e) the conditions and procedures for cooperation with competent authorities of third countries or international organisations on examination of applications for variations to the terms of marketing authorisation.

Article 48

Scientific opinion on data submitted from not-for-profit entities for repurposing of authorised medicinal products

1. An entity not engaged in an economic activity (‘A not-for-profit entity’) may submit to the Agency or to a competent authority of the Member State substantive non-clinical or clinical evidence for a new therapeutic indication that is expected to fulfil an unmet medical need.

The Agency may, at the request of a Member State, the Commission, or on its own initiative and on the basis of all available evidence, including any additional evidence that may be submitted by the marketing authorisation holders for the medicinal products concerned, make a scientific evaluation of the benefit-risk of the use of a medicinal product with a new therapeutic indication that concerns an unmet medical need. The

Agency shall draw up guidance on the consultation process.

The opinion of the Agency shall be made publicly available and the competent authorities of the Member States and the marketing authorisation holder shall be informed.

2. In cases where the opinion is favourable and the new therapeutic indication addresses an

unmet medical need, on the request of the Agency, the marketing authorisation holders of the medicinal products concerned shall submit a variation to update the product information with the new therapeutic indication.

3. Article 81(2), point (c)81(2a) and Article 84(1) of [revised Directive 2001/83/EC] shall

not apply for variations under this Article.

Article 49

Transfer of marketing authorisation

1. A marketing authorisation may be transferred to a new marketing authorisation holder. Such a transfer shall not be considered to be a variation. The transfer shall be subject to prior approval by the Commission, by means of implementing acts, following the submission of an application for the transfer to the Agency.

2. The Commission is empowered to adopt delegated acts in accordance with Article 175 to

supplement this Regulation by establishing procedures for the examination of applications to the Agency for the transfer of marketing authorisations.

Article 50

Supervisory authority

1. In the case of medicinal products manufactured within the Union, the supervisory

authorities for manufacturing shall be the competent authorities of the Member State or Member States which granted the manufacturing authorisation referred to in Article 142(1) of [revised Directive 2001/83/EC] in respect of the medicinal product concerned.

2. In the case of medicinal products imported from third countries, the supervisory authorities

for imports shall be the competent authorities of the Member State or Member States that granted the the manufacturing authorisation referred to in Article 142(3) of [revised Directive 2001/83/EC] to the importer, unless appropriate agreements have been made between the Union and the exporting country to ensure that those controls are carried out in the exporting country and that the manufacturer applies standards of good manufacturing practice at least equivalent to those laid down by the Unionholder that performs the certification.

A Member State may request assistance from another Member State or from the Agency.

3. The supervisory authority for pharmacovigilance shall be the competent authority of the Member State in which the pharmacovigilance system master file is located.

Article 51

Responsibilities of the supervisory authorities

1. The supervisory authorities for manufacturing and imports shall be responsible for

verifying on behalf of the Union that the marketing authorisation holder for the medicinal product or the manufacturer or importer established within the Union satisfies the requirements concerning manufacturing and imports laid down in Chapters XI and XV of [revised Directive 2001/83/EC].

When carrying out the verification referred to in the first subparagraph, the supervisory authorities may request to be accompanied by a rapporteur or expert appointed by the Committee for Medicinal Products for Human Use or by an inspector of the Agency.

The supervisory authorities for pharmacovigilance shall be responsible for verifying on behalf of the Union that the marketing authorisation holder for the medicinal product satisfies the pharmacovigilance requirements laid down in Chapters IX and XV of [revised Directive 2001/83/EC].

The supervisory authorities for pharmacovigilance may, if necessary, conduct preauthorisation inspections to verify the accuracy and successful implementation of the pharmacovigilance system as it has been described by the applicant in support of their application.

2. Where, in accordance with Article 202 of [revised Directive 2001/83/EC], the Commission

is informed of serious differences of opinion between Member States as to whether the marketing authorisation holder for the medicinal product for human use or a manufacturer or importer established within the Union satisfies the requirements referred to in paragraph 1, the Commission may, after consultation with the Member States concerned, request an inspector from the supervisory authority to undertake a new inspection of the marketing authorisation holder, the manufacturer or the importer.

The inspector in question shallmay be accompanied by up to two inspectors from Member States which are not party to the dispute or by two experts nominated by the Committee for Medicinal Products for Human Use.

3. Taking into accountWithout prejudice to any agreements which may have been concluded

between the Union and third countries in accordance with Article 50, the Commission may, following a reasoned request from a Member State or from the Committee for Medicinal Products for Human Use, or on its own initiative, require a manufacturer established in a third country to submit to an inspection.

The inspection shall be requested to the supervisory authority referred to in Article 50 (2). The inspection shall be undertaken by inspectors from the Member States who possess the appropriate qualifications. They may request to be accompanied by a rapporteur or expert appointed by the Committee for Medicinal Products for Human Use or by an inspector of the Agency. The report of the inspectors shall be made available electronically to the Commission, the Member States and the Agency.

Article 52

Inspection capacity of Cooperation between national competent authorities and the Agency for inspections in third countries

1. Without prejudice to the responsibilities of the competent authorities as defined in Article 188 (1) of [revised Directive 2001/83/EC], when an inspection, included in the system of supervision referred to in is needed as per Article 188(1), point (a) of [revised Directive 2001/83/EC] is or requested, as referred to in Article 11(2), for a site located in a third country, the national competent supervisory authority for this site may request the Agency to participate in the inspection or to carry out the inspection.concerned may:

2. The Agency, following a request in accordance with paragraph 1, may decide either of the

following:

(a) request the Agency to participate in the inspection. The Agency may to lend its assistance by participating in a joint inspection with the supervisory requesting authority of the site. In that case the supervisory requesting authority leads the inspection and the follow up thereof. After completion of the inspection, the supervisory authority grants the relevant good manufacturing practice (GMP) certificate and enters the certificate in the Union database; or

(aa) request the Agency to facilitate the cooperation among the competent authorities when a competent authority intends to delegate the inspection to another competent authority as referred to in Article 189 (6) of [revised Directive 2001/83/EC]; and

(b) if no national competent authority accepts the delegation to conduct the inspection as referred to under point (aa), request the Agency to carry out the inspection and the follow up thereof on behalf. If the inspection is in the interest of the supervisory authority Union defined in Annex III, the Agency shall accept the delegation and conduct the inspection. After completion of the inspection, the Agency grants the relevant GMP certificate and enters the certificate in the Union database referred to in Article 188(15) of [revised Directive 2001/83/EC].

Where the Agency decides to carry carries out the inspection, the Agency may request other Member States to participate in the inspection. To any such request, the provisions on joint inspections of Article 189 of [revised Directive 2001/83/EC] shall apply. In case the Agency carries out the inspection in form of a joint inspection, the Agency leads the inspection.

The Agency may also request to be accompanied by a rapporteur or expert appointed by the Committee for Medicinal Products for Human Use.

Where a follow-up inspection is required in view of a GMP non-compliance GMP certificate statement issued by the Agency, the supervisory Agency shall accept a request of the competent authority of the site will be in charge of its performance; the procedure of paragraph 2 shall apply if the supervisory authority for this site requests the Agency to participate in the to perform that follow up inspection or to take over the performance of the inspection.

3. The Agency shall take into account the criteria set out in Annex III when taking its

decision in accordance with paragraph 2.

4. Article 188, paragraph 6, and paragraphs 8 to 17 of [revised Directive 2001/83/EC] shall

apply mutatis mutandis to the inspections referred to in paragraph 21(b).

The Agency’s inspectors shall have the same powers conferred on official representatives of the competent authority pursuant to these provisions.

5. Following a request by a Member State, the inspectors of the Agency may provide support

to suchthat Member State when it performs inspections as referred to in Article 78 of Regulation (EU) 536/2014. The Agency shall take a decision whether to carry out itself such inspection based on the criteria set out in Annex III.

6. The Agency shall ensure that

(a) appropriate resources are made available for the performance of inspection tasks in accordance with the paragraphs 21 and 5;

(b) the inspectors of the Agency possess expertise, technical knowledge, and formal qualifications equivalent to those of the national inspectors as detailed in the compilation, published by the Commission, on Union procedures on inspections and exchange of information.

(c) it shall implement a quality system in accordance with the principles as referred to in Article 190(1)(a) of [revised Directive 2001/83/EC], to the extent applicable and participates as an inspectorate in the Joint Audit Programme and be subjected to periodic audits.

(d) the Agency shall review its inspectorate regularly to ensure that its resources are providing appropriate additional capacity to national competent authorities without undermining the national competent authority inspection resources.

Where needed, the Agency should take the necessary actions for improvement.

7. The cooperation between national competent authorities and the Agency for the

inspections of the interest of the Union shall be facilitated by the inspection working

groups referred to in Article 142, point (k).

Article 53

International Inspections

1. The Agency shall in consultation with the Commission and Member States, coordinate a

structured cooperation on inspections in third countries between Member States, and as relevant the European Directorate for the Quality of Medicines and Healthcare of the Council of Europe, the World Health Organisation and trusted international authorities, by means of international inspection programmes.

2. In cooperation with The Agency, in particular through its inspection working

group referred to in Article 142(k), in agreement with the Commission may adopt, shall draw up detailed guidelines laying down the principles applicable to those international inspection programmes.

Article 54

Joint Audit Programme

1. The inspection working group referred to in Article 142, point (k), shall ensure the

following:

(a) establish and develop the joint audit programme (‘JAP’) and supervise it;

(b) monitor any measure taken by the Member State and the Agency pursuant and limited to paragraph 4 and in cooperation with the concerned Member State or the

Agency;

(c) ensure cooperation with relevant international and Union level bodies to facilitate the work of the joint audit programme and to facilitate the recognition by international partners of the inspections carried out by the competent authorities.

For the purposes of the first subparagraph, the inspection working group may establish an operational subgroup.

2. For the purposes of paragraph 1, point (a), each Member State shall:

(a) provide trained auditors;

(b) accept that the competent authorityauthorities in charge of the implementation of good manufacturing and good distribution practice and related surveillance and enforcement activities applicable to medicinal products and active substances are audited, regularly and where appropriate, according to the joint audit programme.

3. The joint audit programme shall be considered an integral part of the quality system of the

inspectorates of competent authorities in accordance with the principles as referred to in

Article 3(3) of Commission190 (1) (a) of revised Directive (EU) 2017/1572 (EU) 2001/83/EC and ensure that adequate and equivalent quality standards are maintained within the Union network of national competent authorities.

4. Under the joint audit programme, the auditors shall issue an audit report after each audit. The audit report shall include, where relevant, appropriate recommendations on measures that the Member State concerned or the Agency shall consider to take to ensure that its relevant quality system and its enforcement activities are consistent with Union quality standards.

At the request of the Member State, the Commission or the Agency may support that Member State in taking the appropriate measures pursuant to the first subparagraph.

5. For the purposes of paragraph 4, the Agency in particular through its inspection working

group referred to in Article 142(k), shall:

(a) ensure the harmonisation of the assessment during the joint audit programme’s audits and the quality and consistency of the joint audit programme’s audit reports;

(b) establish the criteria for the provision of the joint audit programme’s recommendations.

6. The Agency, in particular through its inspection working group referred to in Article 142(k), shall update the compilation of Union procedures on inspections and exchange of information referred to in Article 3(1) of Directive 2017/1572 shall be updated by the Agency to cover rules applicable to the functioning, structure, and tasks of the joint audit programme.

7. The Union shall provide the financing for activities that support the work of the joint audit programme.

Article 55

Referral procedure

1. Where the supervisory authorities or the competent authorities of any other Member State

are of the opinion that the manufacturer or importer established within the Union territory is no longer fulfilling the obligations laid down in Chapter XI of [revised Directive 2001/83/EC], they shall without undue delay inform the Agency and the Commission, stating their reasons in detail and indicating the course of action proposed.

Similarly, where a Member State or the Commission considers that one of the measures envisaged in Chapters IX, XIV and XV of [revised Directive 2001/83/EC] is to be applied in respect of the medicinal product concerned or where the Committee for Medicinal Products for Human Use has delivered an opinion to that effect, they shall without undue delay inform each other, as well as the Committee for Medicinal Products of Human Use, stating their reasons in detail and indicating the course of action proposed.

2. In each of the situations described in paragraph 1, the Commission shall request the

opinion of the Agency within a time-limit which it shall determine having regard to the urgency of the matter, in order to examine the reasons advanced. Whenever practicable, the marketing authorisation holder for placing the medicinal product for human use on the market shall be invited to provide oral or written explanations.

3. At any stage of the procedure laid down in this Article, following appropriate consultation

of the Agency, the Commission may take temporary measures, by means of implementing acts. Those temporary measures shall be applied immediately.

Without undue delay, the Commission shall, by means of implementing acts, adopt a final decision concerning the measures to be taken in respect of the medicinal product concerned. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2).

The Commission may also, pursuant to Article 57, adopt a decision addressed to the Member States.

4. Where urgent action is essential to protect public health or the environment, a Member State may, on its own initiative or at the Commission's request, suspend the use in its territory of a medicinal product for human use which has been authorised in accordance with this Regulation.

When it does so on its own initiative, it shall inform the Commission and the Agency of the reasons for its action at the latest on the next working day following the suspension. The Agency shall inform the other Member States without delay. The Commission shall immediately initiate the procedure provided for in paragraphs 2 and 3.

5. In cases referred to in paragraph 4, the Member State shall ensure that healthcare

professionals are rapidly informed of its action and the reasons for the action. Networks set up by professional associations may be used to this effect. The Member States shall inform the Commission and the Agency of actions taken for this purpose.

6. The suspensive measures referred to in paragraph 4 may be maintained in force until such

time as a final decision has been adopted by the Commission in accordance with paragraph 3.

7. The Agency shall, upon request, inform any person concerned of the final decision and

make the decision publicly available immediately after it has been taken.

8. Where the procedure is initiated as a result of the evaluation of data relating to

pharmacovigilance, the opinion of the Agency, in accordance with paragraph 2, shall be adopted by the Committee for Medicinal Products for Human Use on the basis of a recommendation from the Pharmacovigilance Risk Assessment Committee and Article 115(2) of [revised Directive 2001/83/EC] shall apply.

9. By way of derogation from paragraphs 1 to 7, where a procedure under Article 95 or Articles 114, 115 and 116 of [revised Directive 2001/83/EC] concerns a range of medicinal products or a therapeutic class, medicinal products that are authorised in accordance with this Regulation and that belong to that range or class shall only be included in the procedure under Article 95, or Articles 114, 115 and 116 of that Directive.

Article 56

Action on conditional marketing authorisation, marketing under exceptional circumstances

Where the Agency concludes that a holder of a marketing authorisation granted in accordance with

ArticleArticles 18 and 19, including a new therapeutic indication granted referred to ArticleArticles

18 and 19, failed to comply with the conditions or obligations laid down in the marketing authorisation, the Agency shall inform the Commission accordingly.

The Commission shall adopt a decision to vary, suspend or revoke that marketing authorisation in accordance with the procedure set out in Article 13.

Article 57

Member State implementation of conditions or restrictions on a Union marketing authorisation

When the Committee for Medicinal Products for Human Use in its opinion refers to recommended conditions or restrictions as provided for in Article 12(4), points (d) to (g), the Commission may adopt a decision addressed to the Member States, in accordance with Article 13 for the implementation of those conditions or restrictions.

CHAPTER V PRE-AUTHORISATION REGULATORY SUPPORT

Article 58

Scientific advice

1. Undertakings or, as relevant, not-for-profit entities may request scientific advice as

referred to in Article 138(1), second subparagraph, point (p) , from the Agency.

Such advice can also be requested for medicinal products referred to in Articles 83 and 84 of [revised Directive 2001/83/EC].

2. In the preparation of the scientific advice referred to in paragraph 1 and upon request by

undertakings or, as relevant, not-for-profit entities that requested the scientific advice, the Agency may consult experts of the Member States with clinical trial or medical device expertise or the expert panels designated in accordance with Article 106(1) of Regulation (EU) 2017/745.

3. In the preparation of the scientific advice referred to in paragraph 1 and in duly justified

cases,of this Article the Agency may consult authorities established in other Union legal acts as relevant for the provision of the scientific advice in question or, other public bodies established in the Union, as applicable, and in duly justified cases public bodies established in third countries.

4. The Agency shall include in the European public assessment report the key areas of the

scientific advice once the corresponding marketing authorisation decision has been taken in relation to the medicinal product, after deletion of any information of a commercially confidential nature. For priority medicinal products the European public assessment report shall include the key areas of enhanced scientific and regulatory support provided by the Agency in accordance with Article 60, together with explanations how the conditions for the enhanced support have been fulfilled and, if applicable, the reasons why the enhanced support was stopped prior to the granting of the marketing authorisation.

4a. To support undertakings or, as relevant, not-for-profit entities, the Agency shall

develop guidelines on the design of studies in support of marketing authorisation applications. When developing such guidelines, it shall use, where relevant, the consultation mechanism referred to in Article 162.

Article 59

Parallel scientific advice

1. Undertakings or, as relevant, not-for-profit entities established in the Union may request

that the scientific advice referred to in Article 58(1) takes place in parallel to the joint scientific consultation carried out by the Member State Coordination Group on Health Technology Assessment, in line with Article 16(5) of Regulation (EU) 2021/2282.

2. In case of medicinal products involving a medical device, undertakings or, as relevant,

not-for profit not-for-profit entities may request scientific advice as referred to in Article

58(1) in parallel with the consultation of the expert panels referred to in Article 61(2) of Regulation (EU) 2017/745 and Article 48 (6) of Regulation (EU) 2017/746.

3. In the case of paragraph 2, the scientific advice, as referred to in Article 58(1), shall

involve exchanges of information between the respective authorities or bodies and, where applicable, have synchronised timing, while preserving the separation of their respective remits.

Article 60

Enhanced scientific and regulatory support for priority medicinal products (‘PRIME’)

1. The Agency may offer enhanced scientific and regulatory support, including as applicable

consultation with other bodies as referred to in Articles 58 and 59 and accelerated assessment mechanisms, for certain medicinal products that, based on preliminary evidence submitted by the developer fulfil at least one of the following conditions:

(a) are likely to address an unmet medical need as referred to in Article 83(1) of [revised Directive 2001/83/EC]; and are expected to be of major interest from the point of view of public health, in particular as regards therapeutic innovation, taking into account the early stage of development; or

(b) are orphan medicinal products and are likely to address a high unmet medical need as referred to in Article 70(1);

(c) are expected to be of major interest from the point of view of public health, in particular as regards therapeutic innovation, taking into account the early stage of development, or antimicrobials with any of the characteristics mentioned in Article 40(3). or provided for in the ‘WHO priority pathogens list for R&D of new

antibiotics’, specifically those listed as priority 1 (critical) or priority 2 (high), or taking into account as a priority any equivalent list of priority pathogens adopted at Union level; or

(d) are likely to target a neglected tropical disease (NTD).

2. The Agency, at the request of the Commission and after consulting the EMA Emergency Task Force, may offer enhanced scientific and regulatory support to developers of a medicinal product preventing, diagnosing or treating a disease resulting from serious cross border threats to health if access to such products is considered necessary to ensure high level of Union preparedness and response to health threats.

3. The Agency may stop the enhanced support if it is established that the medicinal product

will not address the identified unmet medical need or does not have the potential to enhance preparedness and response to serious cross border health threats to the anticipated extent.

4. The compliance of a medicinal product with the criteria set out in Article 83 of [revised Directive 2001/83/EC] shall be assessed on the basis of the relevant criteria, independently of whether it has received priority medicinal product support under this Article.

Article 61

Scientific recommendation on regulatory status

1. For products under development which may fall within the categories of medicinal

products to be authorised by the Union listed in Annex I, a developer or, a competent authority of the Member States or the Commission on its own initiative may submit a duly substantiated request to the Agency for a scientific recommendation with a view to determining on scientific grounds whether the concerned product is potentially a

‘medicinal product’, including an ‘advanced therapy medicinal product’ as defined in

Article 2 of Regulation (EC) No 1394/2007 of the European Parliament and of the Council. The Agency may rely on the relevant expertise of working parties and pools of experts when making its recommendation.

The Agency shall deliver its recommendation within 60 days of receiving such a request, which shall be extended by an additional 30 days where a consultation in accordance with paragraph 2 is required.

2. When forming the recommendation referred to in paragraph 1, the Agency shall consult,

where appropriate and where there is a doubt as to the regulatory status of a product under development, relevant advisory or regulatory bodies established in other Union legal acts in related fields. In particular, in the case of products which are based on substances of human origin, the Agency shall consult the Substances of Human Origin (SoHO) Coordination Board as established in Regulation (EU) No [reference to be added after

adoption cf. COM(2022)338 final].2024/1938.

The advisory or regulatory bodies consulted shall reply to the consultation within 30 days of receipt of the request.

The Agency shall annex to its scientific recommendation the opinions received from the relevant advisory or regulatory bodies referred to in the first subparagraph and shall publish summaries of the recommendations delivered in accordance with paragraph 1, after deletion of all information of a commercially confidential nature.

Article 62

Decision on regulatory status

1. In the case of duly substantiated disagreement with the Agency’s scientific

recommendation, in accordance with Article 61(2), a Member State may request the Commission to decide whether the product is a product referred to in Article 61(1).

The Commission may initiate the procedure referred to in the first subparagraph on its own initiative.

2. The Commission may ask the Agency for clarifications or refer the recommendation back

to the Agency for further consideration where a Member State's substantiated request raises new questions of a scientific or technical nature or on its own initiative.

3. The decision of the Commission referred to in paragraph 1 shall be adopted by means of

implementing acts, in accordance with the examination procedure referred to in Article 173(2), taking into account the scientific recommendation of the Agency.

CHAPTER VI ORPHAN MEDICINAL PRODUCTS

Article 63

Criteria for orphan designation

1. A medicinal product that is intended for the diagnosis, prevention or treatment of a life-

threatening or chronically debilitating condition shall be designated as granted an orphan designation where the orphan medicinal product where the orphan medicine sponsor can demonstrate that the following requirements are met:

(a) the condition affects not more than five in 10 000 persons in the Union when the application for an orphan designation is submitted and;

(b) there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the Union or, where such method exists, that the medicinal product would be of significant benefit to those affected by that condition.

2. By way of derogation from paragraph 1, point (a), and On the basis of a recommendation

from the Agency, when concluding that the requirements specified in paragraph 1, point (a), are not appropriate to identify an orphan condition within the scope of rarity in paragraph 1 point (a) due to the specific characteristics of certain conditions or any other scientific reasons, the Commission is empowered to adopt delegated acts in accordance with Article 175 in order to supplement paragraph 1, point (a), by setting specific criteria for certain conditions.

3. The Commission shall adopt the necessary provisions for implementing this Article by

means of implementing acts in accordance with the procedure laid down in Article 173(2) in order to further specify the requirements referred to in paragraph 1.

Article 64

Granting an orphan designation

1. The orphan medicinemedicinal product sponsor shall submit an application for granting

an orphan the designation of the orphan medicinal product to the Agency at any stage of the development of the medicinal product before the application for marketing authorisation referred to in Articles 5 and 6 is submitted.

2. The application of the for granting an orphan medicine sponsordesignation shall be

accompanied by the following particulars and documentation:

(a) name or corporate name and permanent address of the orphan medicinal product medicine sponsor;

(b) active substances of the medicinal product;

(c) proposed condition for which it is intended or the proposed therapeutic indication;

(d) justification that the criteria laid down in Article 63(1) or in the relevant delegated acts adopted in accordance with Article 63(2) are fulfilled and a description of the stage of development, including the expected therapeutic indication.

The orphan medicinemedicinal product sponsor shall be responsible for the accuracy of the particulars and documentation.

3. The Agency shall, in consultation with the Member States, the Commission and interested

parties, draw up detailed guidelines on the required procedure, format and content of applications for designation and for the transfer of the orphan designation pursuant to Article 65.

4. The Agency shall adopt a decision granting or refusing the orphan designation based on the

criteria referred to in Article 63(1) or in the relevant delegated acts adopted in accordance with Article 63(2) within 90 days of the receipt of a valid application. The Agency shall verify the validity of the application. The application is considered valid if it includes all the particulars and documentation referred to in paragraph 2.

When establishing whether the orphan designation criteria are met, the Agency may ask the orphan medicinal product sponsor to submit additional particulars and documents, within the deadline set by the Agency.

For the purpose of establishing whether the orphan designation criteria are fulfilled, the Agency may shall consult the Committee for Medicinal Products for Human Use or one of its . The Committee for Medicinal Products for Human Use shall ensure the appropriate involvement of the relevant scientific expertise through the working parties referred to in Article 150(2), first subparagraph150 or may delegate this task to one of those working parties. The outcome of such consultations, including information on the involvement of relevant scientific expertise, shall be annexed to the decision, as part of the scientific conclusions of the Agency which justify the decision.

The decision together with the Annexes referred to in this paragraph shall be notified to the applicant.

By way of derogation from the second subparagraph, the Committee for Medicinal Products for Human Use shall establish scientific principles to determine the situations

where consultation is not required.

4a. When the scientific conclusions referred to in paragraph 4 state that the application does

not satisfy the criteria set out in Article 63(1), they shall be transmitted without delay by the Agency to the orphan medicinal product sponsor before the adoption of the decision referred to in paragraph 4. Within 15 days following receipt of the scientific conclusions, the orphan medicinal product sponsor may request by written notice to the Agency a reexamination of the scientific conclusions together with the detailed grounds on which it is based. Following receipt of the grounds of the request the Agency shall reexamine its scientific conclusions within 30 days. The reasons for the conclusion reached shall be part of the final scientific conclusions. The time limit referred in paragraph 4 shall be suspended until the scientific conclusions become definitive. For the purpose of this paragraph, the Agency shall involve the Committee for Human Medicinal Product.

If the orphan medicinal product sponsor does not submit a written justified request for re-examination within 15 days following the receipt of scientific conclusions, they shall become definitive.

5. Decisions of the Agency on granting or refusing the orphan designation shall be made

public after deletion of any information of a commercially confidential nature.

Article 65

Transfer of orphan designation

1. The orphan designation may be transferred from a current orphan medicinal product

medicine sponsor to a new orphan medicinal product medicine sponsor. The transfer shall be subject to prior approval by the Agency, following the submission of an application for the transfer to the Agency.

2. The application of the current orphan medicinal product medicine sponsor shall be

accompanied by the following particulars and documentation:

(a) name or corporate name and permanent address of the current and new orphan medicine sponsor;

(b) decision on granting an orphan designation as referred to in Article 64(4); (c) designation number as referred to in Article 67(3), point (e).

(ca) reasons for the transfer of the orphan designation.

3. The Agency shall adopt a decision granting or refusing the transfer of the orphan

designation within 30 days of the receipt of a valid application by the current orphan medicinal product medicine sponsor. The application is considered valid if it includes all the particulars and documentation referred to in paragraph 2. The Agency shall address its decision to the current and new orphan medicinal product medicine sponsor.

Article 66

Validity of orphan designation

1. An orphan designation shall be valid for seven years. During this period, the orphan

medicinal product medicine sponsor shall be eligible for incentives referred to in Article

68.

2. By way of derogation from paragraph 1, on the basis of a justified request of the orphan

medicinemedicinal product sponsor, the Agency may extend the validity, where the orphan medicinemedicinal product sponsor can provide evidence that the relevant studies supporting the use of the designated orphan medicinal product in the applied conditions are ongoing and promising with regard to the filing of a future application. Such an extension shall be limited in time, taking into account the expected remaining time needed to file an application for marketing authorisation.

3. By way of derogation from paragraph 1, where an orphan designation is valid at the time

when a marketing authorisation application for an orphan medicinal product has been submitted in accordance with Article 5, the orphan designation shall remain valid until a decision is adopted by the Commission in accordance with Article 13(2).

4. An orphan designation ceases to be valid once an orphan medicinal product medicine

sponsor has obtained a marketing authorisation for a therapeutic indication covered under the orphan designation the relevant medicinal product in accordance with Article 13(2).

5. At any time, an orphan designation may be withdrawn at the request of the orphan

medicinemedicinal product sponsor. The orphan medicinal product sponsor shall provide the Agency with the reasons for such action. The Agency shall make this information publicly available.

Article 67

Register of designated orphan medicinal products

1. The register of designated orphan medicinal products shall list all designated orphan

medicinal products. It shall be set up and managed by the Agency and be publicly available.

2. Where an orphan designation ceases to be valid or is withdrawn pursuant to Article 66, the Agency shall make an entry in the register of designated orphan medicinal products.

3. The information on the designated orphan medicinal product entered in the register of

designated orphan medicinal products shall include at least the following:

(a) the information on the active substance;

(b) the name and address of the orphan medicinemedicinal product sponsor;

(c) the condition for which it is intended or the proposed therapeutic indication;

(d) the designation date;

(e) the designation number;

(f) the decision on granting the orphan designation.;

(g) the decision on transfer of the orphan designation.

(fb) where applicable, the decision extending the validity of the orphan designation in accordance with Article 66(2).

4. The Commission shall be empowered to adopt delegated acts in accordance with Article 175 in order to amend the information to be included in the register of designated orphan medicinal products referred to in paragraph 3 to ensure appropriate information of the users of that register.

Article 68

Protocol assistance and research support for orphan medicinal products

1. The orphan medicinemedicinal product sponsor may, prior to the submission of an

application for marketing authorisation, request advice from the Agency on the following:

(a) the conduct of the various tests and trials necessary to demonstrate the quality, safety and efficacy of the medicinal product, as referred to Article 138(1), second subparagraph, point (p); aa) the conduct of the various tests and trials necessary for the environmental risk assessment of the medicinal product.

(b) the demonstration of significant benefit within the scope of the designated orphan indicationcondition as set out in Article 63(1);

(c) the demonstration of similarity to or clinical superiority over other medicinal products, which have market exclusivity for the same indication.

2. Medicinal products designated as orphan medicinal products under the provisions of this Regulation shall be eligible for incentives made available by the Union and by the Member States to support research into, and the development and availability of, orphan medicinal products and in particular aid for research for small- and medium-sized undertakings and entities not engaged in economic activity provided for in framework programmes for research and technological development.

Article 69

Orphan marketing authorisation

1. Applications for an orphan marketing authorisation shall be submitted in accordance with Articles 5 and 6 and the related marketing authorisation shall be obtained in accordance with Articles 13(2).

2. In addition, the applicant shall demonstrate that the medicinal product has been granted an

orphan designation and that the criteria set out in Article 63(1) or in the relevant delegated acts adopted in accordance with Article 63(2) are fulfilled for the therapeutic indication sought.

Where appropriate, the applicant shall provide relevant evidence to demonstrate that the medicinal product addresses a high unmet medical need as specifiedmeets the conditions set out in Article 70(1).

3. The Committee for Medicinal Products for Human Use shall assess whether the medicinal

product fulfils the requirements set out in Article 63(1) or in the relevant delegated acts adopted in accordance with Article 63(2). In the situation referred in paragraph 2, subparagraph 2, that Committee shall also assess whether the medicinal product addresses a high unmet medical needis a breakthrough orphan medicinal product as specified in Article 70(1). The Committee for Medicinal Products for Human Use shall ensure the appropriate involvement of scientific expertise regarding orphan medicinal products.

Such assessment shall be subject to the same timelines as the application for the marketing authorisation itself and detailed conclusions of such assessment shall be part of the scientific opinion of the Committee for Medicinal Products for Human Use in accordance with Article 12(1).

The assessment and its conclusions shall be part of the opinion referred to in Article 12(1) and, where relevant, the opinion referred to in Article 12(3).

4. The orphan marketing authorisation shall cover only those therapeutic indications, which

fulfil the requirements set out in Article 63(1) or in the relevant delegated acts adopted in accordance with Article 63(2) at the time when the orphan marketing authorisation is granted.

5. If after the submission of an application for the orphan marketing authorisation and prior to

the opinion of the Committee for Medicinal Products for Human Use the orphan designation is withdrawn in accordance with Article 66(5), the application for the orphan marketing authorisation shall be treated as the application for a marketing authorisation in accordance with Article 6.

6. An applicant may submit an application for a separate marketing authorisation for other

indications which do not fulfil the requirements set out in Article 63(1) or in the relevant delegated acts adopted in accordance with Article 63(2).

Article 70

Breakthrough orphan medicinal products addressing a high unmet medical need

1. An orphan medicinal product shall be considered as addressing a high unmet medical

needa breakthrough orphan medicinal product where it fulfils the following requirements:

(a) there is no medicinal product authorised in the Union for such condition orwhere, despite medicinal products being authorised for such condition in the Union, the applicant demonstrates that the orphan medicinal product, in addition to having a significant benefit, will bring exceptional therapeutic advancement;condition; and

(b) the use of the orphan medicinal product results in a meaningful clinically relevant reduction in disease morbidity or mortality for the relevant patient population.

2. A medicinal product for which an application has been submitted in accordance with Article 13 of [revised Directive 2001/83/EC] shall not be considered as addressing a high unmet medical needto meet the conditions set out in paragraph 1.

3. Where the Agency adopts scientific guidelines for the application of this Article, it shall

consult the Commission and the authorities or bodies referred to in Article 162.

Article 71

Market exclusivity

1. Where an orphan marketing authorisation is granted and without prejudice to intellectual

property law, the Union and the Member States shall not grant a marketing authorisation or extend an existing marketing authorisation, for the same therapeutic indication, in respect of a similar medicinal product for the duration of market exclusivity set out in paragraph 2.

2. The duration of market exclusivity shall be as follows:

(a) nine years for orphan medicinal products other than those referred to in points (b) and (c);

(b) teneleven years for breakthrough orphan medicinal products addressing a high unmet medical need as referred to in Article 70;

(c) fivefour years for orphan medicinal products which have been authorised in accordance with Article 13 of [revised Directive 2001/83/EC].

3. Where a marketing authorisation holder holds more than one orphan marketing

authorisations for the same active substance, those authorisations shall not benefit from separate market exclusivity periods. The duration of the market exclusivity shall start from the date when the first orphan marketing authorisation was granted in the Union.

4. By way of derogation from paragraph 1, and without prejudice to intellectual property law,

the marketing authorisation may be granted, for the same therapeutic indication, to a similar medicinal product if:

(a) the marketing authorisation holder for the original orphan medicinal product has given consent to the second applicant, or

(b) the marketing authorisation holder for the original orphan medicinal product is unable to supply sufficient quantities of the medicinal product, or

(c) the second applicant can establish in the application that the second medicinal product, although similar to the orphan medicinal product already authorised, is safer, more effective or otherwise clinically superior.

5. The submission, validation and assessment of the application for the marketing

authorisation and granting the marketing authorisation for a generic or biosimilar product to the reference medicinal product for which market exclusivity has expired, shall not be prevented by the market exclusivity of a similar product to the reference medicinal product.

6. The market exclusivity of the orphan medicinal product shall not prevent the submission,

validation and assessment of an application for a a marketing authorisation, including to extend an existing marketing authorisation for a new therapeutic indication, of a similar medicinal product, including generics and biosimilars, where the remainder of the duration of the market exclusivity is less than two years. This may include the adoption of the corresponding decision provided that the decision granting or extending the marketing authorisation does not enter into force prior to the expiry of the market exclusivity period.

7. Where the Agency adopts scientific guidelines for the application of paragraphs 1 and 4, it

shall consult the Commission.

Article 72

Prolongation of market exclusivity

1. The periods of market exclusivity referred to in Article 71, paragraph 2, points (a) and (b),

shall be prolonged by 12 months, where the orphan marketing authorisation holder can demonstrate that the conditions referred to in Article 81(2), point (a), and Article 82(1) [of revised Directive 2001/83/EC] are fulfilled.

The procedures set out in Articles 82(2) to (5) [of revised Directive 2001/83/EC] shall accordingly apply to the prolongation of market exclusivity.

2. The period of market exclusivity shall be prolonged by an additional 12 months for orphan

medicinal products referred to in Article 71(2), points (a) and (b), if at least two years before the end of the exclusivity period, the orphan marketing authorisation holder obtains a marketing authorisation for one or more new therapeutic indications for a different orphan condition.

Such a prolongation may be granted twice, if the new therapeutic indications are each time for different orphan conditions.

3. The orphan medicinal products which benefit from the prolongation of market exclusivity

referred to in the paragraph 2 shall not benefit from the additional period of data market protection referred to in Article 81(2), point (d), 81(2a) of [revised Directive 2001/83/EC].

4. Article 71(3) equally applies to the prolongations of market exclusivity referred to in

paragraphs 1 and paragraph 2.

Article 73

Union financial contribution related to orphan medicinal products

The working arrangements referred to in Article 8 of [new fee Regulation]Regulation (EU)

2024/568 shall set out total or partial reductions for the applicable fees and charges payable to the European Medicines Agency as laid down in [new fee Regulation]. Such reductions shall be covered by the Union contribution provided for in Article 154(3), point (a) of this Regulation.

CHAPTER VII PAEDIATRIC MEDICINAL PRODUCTS

Article 74

Paediatric investigation plan

1. A paediatric investigation plan shall specify the timing and all the measures proposed to

assess the quality, safety and efficacy of the medicinal product in all subsets of the paediatric population that may be concerned. In addition, it shall describe any measures to adapt the pharmaceutical form, the strength, the route of administration and the eventual administration device of the medicinal product so as to make its use more acceptable, easier, safer or more effective for different subsets of the paediatric population.

2. By derogation from paragraph 1, in the following cases an applicant may submit only an

initial paediatric investigation plan as referred to in the second subparagraph:

(a) when the active substance concerned is not yet authorised in any medicinal product in the EU and is intended to diagnose, prevent or treat a novel paediatric condition or diagnose, prevent or treat an existing paediatric condition via a new mechanism of action; or;

(b) following the acceptance by the Agency of a duly justified request from an applicant in accordance with paragraph 3.

An initial paediatric investigation plan shall contain only the details and the timing of the measures proposed to assess the quality, safety and efficacy of the medicinal product in all subsets of the paediatric population that may be concerned, that are known at the moment of the submission of the request for agreement mentioned in Article 76(1).

This initial paediatric investigation plan shall also provide a precise timing of when updated versions of the paediatric investigation plan are to be submitted and when a final paediatric investigation plan complying with all the particulars described in paragraph 1, is expected to be submitted to the Agency.

3. When it is not possible, on the basis of scientifically justified reasons, to have a complete

paediatric developmentinvestigation plan in accordance with the timing given in Article 76(1) an applicant may submit a duly justified request to the Agency to utilise the procedure mentioned in paragraph 2. The Agency has 20 days to accept or refuse the request and shall immediately inform the applicant and state the reasons for refusal.

4. On the basis of the experience acquired as a result of the operation of this Article or of

scientific knowledge, the Commission is empowered to adopt delegated acts in accordance with Article 175 to amend the grounds for granting the possibility to utilise the adapted procedure foreseen in paragraph 2.

Article 75

Waivers

1. In accordance with the procedure set out in Article 78, the Agency may decide that the

production of the information referred to in, Article 6(5), point (a), of [revised Directive 2001/83], shall be waived for products or for classes of medicinal products, if there is evidence showing any of the following:

(a) that the specific medicinal product or class of medicinal products is likely to be ineffective or unsafe in part or all of the paediatric population;

(b) that the disease or condition for which the specific medicinal product or class is intended occurs only in adult populations, unless except when the product displays a mechanism of action, including where its action is directed at a specific molecular target or biological pathway, that on the basis of existing scientific data, is responsible relevant for a different disease or condition in the same therapeutic area in children than the one for which the specific medicinal product or class of medicinal products is intended for in the adult population;

(c) that the specific medicinal product is likely to not represent a significant therapeutic benefit over existing methods of diagnosis, prevention or treatments for paediatric patients, except when the product displays a mechanism of action, including where its action is directed at a specific molecular target or biological pathway, that on the basis of existing scientific data, is relevant for a different disease or condition in the same therapeutic area in children than the one for which the specific medicinal product or class of medicinal products is intended for in the adult population.

2. The waiver provided for in paragraph 1 may be issued with reference either to one or more

specified subsets of the paediatric population, or to one or more specified therapeutic indications, or to a combination of both.

3. On the basis of the experience acquired as a result of the operation of this Article or of

scientific knowledge the Commission is empowered to adopt delegated acts in accordance with Article 175 to amend the grounds for granting a waiver detailed in paragraph 1.

3a. The Agency shall, in consultation with the Commission, the competent authorities of the Member States and relevant interested parties, draw up guidelines for the application of

this Article.

Article 76

Validation of a paediatric investigation plan or of a waiver

1. A paediatric investigation plan or an application for waiver shall be submitted to the Agency with a request for agreement, except in duly justified cases, before the initiation of safety and efficacy clinical studies so as to ensure that a decision on use in the paediatric population of the medicinal product concerned can be given at the time of the marketing authorisation or other application concerned.

2. Within 30 days following receipt of the request referred to in paragraph 1, the Agency shall

verify the validity of the request and communicate the result to the applicant.

3. Whenever appropriate, the Agency may ask the applicant to submit additional particulars

and documents, in which case the time-limit of 30 days shall be suspended until the supplementary information requested has been provided.

4. In consultation with the Commission, the competent authorities of the Member States and

with interested parties, the Agency shall draw up and publish guidelines for the practical application of this Article.

Article 77

Agreement on a paediatric investigation plan

After the validation of the proposed paediatric investigation plan referred to in Article 74(1).which is valid in accordance with the provisions of Article 76(2), the Agency shall adopt within 90 days a decision as to whether or not the proposed studies will ensure the generation of the necessary data determining the conditions in which the medicinal product may be used to treat the paediatric population or subsets thereof, and as to whether or not the expected therapeutic benefits, where appropriate also over existing treatments, justify the studies proposed. When adopting its decision, the Agency shall consider whether or not the measures proposed to adapt the pharmaceutical form, the strength, the route of administration and the eventual administration device of the medicinal product for use in different subsets of the paediatric population are appropriate.

2. After the validation of the proposed initial paediatric investigation plan prepared in

accordance with the adapted procedure referred to in Article 74(2) first subparagraph, which is valid in accordance with the provisions of Article 76(2), the Agency shall adopt a decision within 70 days as to whether or not the paediatric investigation plan is expected to ensure the generation of the necessary data determining the conditions in which the medicinal product may be used to treat the paediatric population or subsets thereof, and as to whether or not the expected therapeutic benefits, where appropriate also over existing treatments, justify the studies envisaged.

3. After receiving an updated version of the paediatric investigation plan referred to in Article 74(2), third subparagraph, the Agency shall review it within 3060 days.

After the timeframe laid down in the first subparagraph, without any request from the Agency in accordance with paragraph 5, the updated version of the paediatric investigation plan shall be considered as agreed.

4. When the final paediatric investigation plan referred to in Article 74(2), third

subparagraph, is received, the Agency shall adopt within 60 days a decision on the paediatric investigation plan considering all the updated reviews eventually conducted and of the initial decision in accordance with paragraphs 2 and 3.

5. Within time periods referred to in paragraphs 1, 2, 3 or 4 the Agency may request the

applicant to propose modifications to the plan or ask for additional information, in which case the time-limits referred to in paragraphs 1, 2, 3 and 4 shall be extended for a maximum of the same number of days. These time-limits shall be suspended until the supplementary information requested has been provided.

6. The procedure laid down in Article 87 shall apply for the adoption of decisions by the Agency.

Article 78

Granting of a waiver

An applicant may, on the grounds set out in Article 75(1), apply to the Agency for a product-specific waiver.

2. Following the receipt of a valid application in accordance with the provisions of Article 76(2), the Agency shall within 90 days adopt a decision as to whether or not a productspecific waiver shall be granted.

Whenever appropriate, the Agency may request the applicant to supplement the particulars and documents submitted. Where the Agency avails itself of this option, the 90-day timelimit shall be suspended until such time as the supplementary information requested has been provided.

3. When appropriate, the Agency may of its own motion adopt decisions, on the basis of the

grounds set out in Article 75(1), to the effect that a class or a product-specific waiver, as referred to in Article 75(2), should be granted.

4. The Agency may, at any time adopt a decision reviewing an already granted waiver.

5. If a particular product-specific or class waiver is revoked, the requirement set out in Article 6(5) of [revised Directive 2001/83/EC] shall not apply for 36 months from the date of its removal from the list of waivers.

6. The procedure laid down in Article 87 shall apply for the adoption of decisions by the Agency.

7. In consultation with the Commission, the competent authorities of the Member States,

and with interested parties, the Agency shall draw up and publish guidelines for the practical application of this Article.

Article 79

List of waivers

The Agency shall maintain a list of all waivers granted. The list shall be updated regularly and made available to the public.

Article 80

Waivers granted following a negative decision on a paediatric investigation plan

If, having considered a paediatric investigation plan, the Agency concludes that Article 75(1), points (a), (b) or (c), applies to the medicinal product concerned, it shall adopt a negative a decision under Article 77, paragraphs 1, 2 or 4.

In such cases, the Agency shall adopt a decision in favour of a waiver under Article 78(3). The two decisions shall be adopted at the same time by the Agency.

The procedure laid down in Article 87 shall apply for the adoption of decisions by the Agency.

Article 81

Deferrals

At the same time as the application for a paediatric investigation plan is submitted under Article 76(1) or during the assessment for a paediatric investigation plan, the applicant may also make a request for deferral of the initiation or completion of some or all of the measures set out in that plan. Such deferral shall be justified on scientific and or technical grounds or on grounds related to public health.

In any event, a deferral shall be granted when it is appropriate to conduct studies in adults prior to initiating studies in the paediatric population or when studies in the paediatric population will take longer to conduct than studies in adults.

2. The Agency shall adopt a decision on the request referred to in paragraph 1 and inform the

applicant thereof. The Agency shall adopt such decision at the same time as the adoption of the positive decision under Article 77, paragraphs 1 or 2.

A decision in favour of a deferral shall specify the time-limits for initiating or completing the measures concerned.

3. The length of the deferral shall be specified in a decision of the Agency and shall be

substantiated by scientific or technical grounds or by considerations pertaining to public health and not exceed five years.

4. On the basis of the experience acquired as a result of the operation of this Article, the Commission is empowered to adopt delegated acts in accordance with Article 175 to amend the grounds for granting a deferral referred to in paragraph 1.

Article 82

Prolongation of deferrals

1. In duly justified cases, a request for a prolongation of the deferral, may be submitted, at

least 6 months before the expiry of the deferral period. A prolongation of the derogation deferral shall not exceed the duration of the deferral period given under Article 81(3).

The Agency shall decide on the prolongation within 60 days.

2. Whenever appropriate, the Agency may ask the applicant to submit, within the deadline

set by the Agency, additional particulars and documents, in which case the time-limit of 60 days shall be suspended until the supplementary information requested has been provided.

3. The procedure laid down in Article 87 shall apply for the adoption of decisions by the Agency.

Article 83

Waivers during a public health emergency

1. The decision by the Agency referred to in Article 6(5), point (e) of [revised Directive 2001/83/EC] shall concern only medicinal products intended for the treatment, prevention or medical diagnosis of a serious or life-threatening disease or condition which are directly related to the public health emergency.

2. The decision mentioned under paragraph 1 shall include the grounds for providing such

derogation and its duration.

3. At the latest at the date of expiry of the derogation referred to in paragraph 2, the applicant

shall submit to the Agency a paediatric investigation plan or an application for a waiver with a request for agreement in accordance with the provisions of Article 76(1).

Article 84

Modification of a paediatric investigation plan

1. If, following the decision agreeing the paediatric investigation plan, the applicant

encounters such difficulties with its implementation as to render the plan unworkable or no longer appropriate, the applicant may propose changes or request the Agency to issue a deferral in accordance with Article 81 or a waiver in accordance with Article 75. The

Agency shall adopt within 90 days a decision on the basis of the procedure laid down in Article 87. When appropriate, the Agency may request the applicant to supplement the particulars and documents submitted. Where the Agency avails itself of this option, the time-limit shall be suspended until such time as the supplementary information requested has been provided.

1a.

2. If, following the decision agreeing the paediatric investigation plan referred to in Article 77, paragraphs 1, 2 and 4, or on the basis of the updated paediatric investigation plan received in accordance with Article 77(3), the Agency, on the base of new scientific information available, considers that the agreed plan or any of its elements are no longer appropriate, it shall request, based on scientific grounds, that the applicant to propose changes to the paediatric investigation plan.

The applicant shall submit the changes requested within 60 days.

Within 30 days, the Agency shall review these changes and adopt a decision on their refusal or acceptance.

3. Within the time period referred to in paragraph 2, third subparagraph, the Agency may

request the applicant for additional modifications to the submitted changes or to submit additional information, in those cases the time-limits referred to in paragraph 2, third subparagraph, shall be extended by another 30 days. This time-limit shall be suspended until the supplementary information requested or the additional modifications have been provided.

4. The procedure laid down in Article 87 shall apply for the adoption of decisions by the Agency.

Article 85

Detailed arrangements for applications in relation to paediatric investigation plans, waivers and deferrals

1. In consultation with the Member States, the Commission and interested parties, the Agency

shall draw up the detailed arrangements concerning the format and content which applications for agreement or modification of a paediatric investigation plan, and requests for waivers or deferrals are to follow in order to be considered valid and concerning the operation of the compliance check referred to in Articles 48, 49(2), 86 and 90(2) of [revised Directive 2001/83/EC], and Articles 86 and 90(2).

2. The detailed arrangement concerning the format and content of applications for agreement

of a paediatric investigation plan mentioned in paragraph 1 shall:

(a) specify which information should be included in an application for agreement or modification of a paediatric investigation plan or requests for a waiver in the cases referred to in Article 75(1);

(b) be adapted to take into account the specificities of:

(i) adapted procedure for paediatric investigation plans as referred to in Article

74(2);

(ii) products intended to be developed only for use in children;

(iii) products intended to be submitted under the procedure referred to in Article 92.

Article 86

Compliance with the paediatric investigation plan

Where the application for marketing authorisation or variation is submitted in accordance with the procedures set out in in this Regulation, the Committee for Medicinal Products for Human Use shall verify whether anthe application for marketing authorisation or variation complies with the requirements laid down in Article 6(5) of [revised Directive 2001/83/EC].

Article 87

Procedure for adopting a decision in relation to paediatric investigation plans, a waiver or a deferral

1. Decisions referred to in Articles 77, 78, 80, 81, 82 and 84 adopted by the Agency shall be

supported by scientific conclusions which shall be annexed to the decision.

2. Where The Agency considers it necessary, it may shall consult the Committee for Medicinal Products for Human Use or the appropriate working parties when preparing the above mentioned scientific conclusions. The Committee for Medicinal Products for Human Use shall ensure, as necessary, the appropriate involvement of the relevant scientific expertise through at least one the working parties established under Article 150 or may delegate this task to one of those working parties. The outcome of such consultations shall be annexed to the decision.

2a. By derogation from paragraph 2, the Committee for Medicinal Products for Human Use

shall establish scientific principles to determine the situations when consultation is not required.

2b. The scientific conclusions mentioned in paragraph 1 shall be transmitted without delay

by the Agency to the applicant before the adoption of the decisions referred to in Articles 77, 78, 80, 81, 82 and 84. Within 15 days following receipt of the scientific conclusions, the applicant may request by written notice to the Agency a re-examination of the scientific conclusions together with the detailed grounds on which it is based. Following receipt of the grounds of the request the Agency shall reexamine its scientific conclusions within 30 days. The reasons for the conclusion reached shall be part of final scientific conclusions. The time limit referred to in Articles 77, 78, 82 and 84 will be suspended until the scientific conclusions become definitive. For the purpose of this paragraph, the Agency shall consult the Committee for Human Medicinal Products.

If the applicant does not submit a written justified request for re-examination within 15 days following the receipt of scientific conclusions, they shall become definitive.

3. Decisions of the Agency shall be made public after deletion of any information of a

commercially confidential nature.

Article 88

Discontinuation of a paediatric investigation plan

Where a paediatric investigation plan, agreed in accordance with the provisions of Article 77, paragraphs 1, 2 and 4, is discontinued, the applicant shall notify the Agency of its intention to discontinue the conduct of the paediatric investigation plan and provide the reasons for such discontinuation without undue delay and in any case no less than six months before the discontinuation.

The Agency shall publish this information after removing personal or commercially sensitive information.

Article 89

Scientific advice for paediatric developments

Any legal or natural person developing a medicinal product intended for paediatric use or intended for in utero treatment may, prior to the submission of a paediatric investigation plan and during its implementation, request advice from the Agency on the design and conduct of the various tests and studies necessary to demonstrate the quality, safety and efficacy of the medicinal product in the paediatric population in accordance with Article 138(1), point (za).

The Agency shall provide advice under this Article free of charge.

Article 90

Data deriving from a paediatric investigation plan

1. Where a marketing authorisation or a variation of a marketing authorisation, is granted in

accordance with this Regulation:

(a) the results of all clinical studies conducted in compliance with an agreed paediatric investigation plan as referred to in Articles 6(5), point (a), of [revised Directive 2001/83/EC] shall be included in the summary of product characteristics and, if appropriate, in the package leaflet; or

(b) any agreed waiver as referred to in Articles 6(5), points (b) and (c) of [revised Directive 2001/83/EC], shall be recorded in the summary of product characteristics and, if appropriate, in the package leaflet of the medicinal product concerned.

2. If the application complies with all the measures contained in the agreed completed

paediatric investigation plan and if the summary of product characteristics reflects the results of studies conducted in compliance with that agreed paediatric investigation plan, the Commission shall include within the marketing authorisation a statement indicating compliance of the application with the agreed completed paediatric investigation plan.

Article 91

Variation of marketing authorisations on the basis of paediatric studies

1. Any clinical study which involves the use in the paediatric population of a medicinal

product covered by a marketing authorisation and is sponsored by the marketing authorisation holder, whether or not it is conducted in compliance with an agreed paediatric investigation plan, shall be submitted to the Agency or to the Member States in which have previously authorised the medicinal product concerned is authorised within six months of completion of the studies concerned.

2. Paragraph 1 shall apply independent of whether or not the marketing authorisation holder

intends to apply for a marketing authorisation of a paediatric indication.

3. When products are authorised in accordance with the provisions of this Regulation, the Commission may update the summary of product characteristics and package leaflet, and may vary the marketing authorisation accordingly.

Article 92

Paediatric use marketing authorisation

1. An application for a paediatric use marketing authorisation shall be submitted in

accordance with Articles 5 and 6 and shall be accompanied by the particulars and documents necessary to establish quality, safety and efficacy in the paediatric population, including any specific data needed to support an appropriate formulation, pharmaceutical form, strength, route of administration and eventual administration device for the product, in accordance with an agreed paediatric investigation plan. The application shall also include the decision of the Agency agreeing the paediatric investigation plan concerned.

2. Where a medicinal product is or has been authorised in a Member State or in the Union,

data contained in the dossier on that product may, where appropriate, be referred to, in accordance with Article 29 of this Regulation or Article 9 of [revised Directive 2001/83/EC], in an application for a paediatric use marketing authorisation.

The medicinal product in respect of which a paediatric use marketing authorisation is granted may retain the name of any medicinal product which contains the same active substance and in respect of which the same marketing authorisation holder has been granted authorisation for use in adults.

4. Submission of an application for a paediatric use marketing authorisation shall in no way

preclude the right to apply for a marketing authorisation for other therapeutic indications.

Article 93

Rewards for products authorised under the paediatric use marketing authorisation procedure

Where a paediatric use marketing authorisation referred to in Article 92 is granted and includes the results of all studies conducted in compliance with an agreed paediatric investigation plan, the product shall benefit from independent data and marketing protection periods referred to in Articles 80 and 81 of [revised Directive 2001/83/EC].

Article 94

Paediatric clinical trials

1. The EU database created by Article 81 of Regulation (EU) No 536/2014 shall include

clinical trials carried out in third countries which are:

(a) contained in an agreed paediatric investigation plan;

(b) submitted following the provisions of Article 91.

2. For the clinical trials mentioned in paragraph 1 which are conducted in third countries, the

description of the following elements shall be entered into the EU database prior to the start of the trial by the clinical trial sponsor, the addressee of the Agency's decision on a paediatric investigation plan referred to in Article 77, or by the marketing authorisation holder as appropriate:

(a) the clinical trial protocol;

(b) the investigational medicinal products used;

(c) the therapeutic indications covered; (d) details of the trial population.

Irrespective of the outcome of a clinical trial within 6 months from the end of the trial the clinical trial sponsor, the addressee of the Agency's decision on a paediatric investigation plan or the marketing authorisation holder as appropriate, shall submit to the EU database a summary of the results of the trial which shall be uploaded in the database.

If for justified scientific reasons it is not possible to submit the summary of the result of the trial within 6 months it shall be submitted to the EU database at the latest within twelve months after the trial has ended. The justification for the delay needs also to be submitted in the EU database.

In consultation with the Commission, Member States and interested parties, the Agency shall draw up guidance on the nature of the information referred to in paragraph 2.

4. On the basis of the experience acquired as a result of the operation of this Article, the Commission may adopt implementing acts in accordance with the examination procedure referred to in Article 173(2) to amend the details concerning clinical trials conducted in third countries to be submitted to the EU database and referred to in paragraph 2.

Article 95

European network

1. The Agency shall develop a European network of patient representatives, academics,

medicines developers, investigators and centres with expertise in the performance of studies in the paediatric population.

2. The objectives of the European network shall be, inter alia, to discuss priorities in the

clinical development of medicines for children, in particular in areas of unmet medical need, to coordinate studies relating to paediatric medicinal products, to build up the necessary scientific and administrative competences at European level, and to avoid unnecessary duplication of studies and testing in the paediatric population.

Article 96

Incentives for research in medicinal products for children

Paediatric medicinal products shall be eligible for incentives made available by the Union and by the Member States to support research into, and the development and availability of, paediatric medicinal products.

Article 97

Fees and Union contribution for paediatric activities

1. Where an application for a paediatric use marketing authorisation is submitted in

accordance with the procedure laid down in Article 92, the amount of the reduced fees for the examination of the application and the maintenance of the marketing authorisation shall be fixed in accordance with Article 6 of [new fee Regulation].

2. Assessments of the following by the Agency shall be free of charge:

(a) applications for waivers;

(b) applications for deferrals;

(c) applications for paediatric investigation plans;

(d) compliance with the agreed paediatric investigation plan.

The Union contribution provided for in Article 154 shall cover the work of the Agency, including the assessment of paediatric investigation plans, scientific advice and any fee waivers provided for in this Chapter, and shall support the Agency's activities under Articles 94 and 95.

Article 98

Yearly reporting on paediatric activities

At least on an annual basis, the Agency shall make public:

(a) a list of the companies entities and of the products that have benefited from any of the

rewards and incentives in this Chapter of the Regulation;

(b) the companies entities that have failed to comply with any of the obligations in this

Chapter of the Regulation;

(c) the number of paediatric investigation plans agreed in accordance with Article 74;

(d) the number of waivers agreed, providing also a summary of their reasons;

(e) a list of deferrals agreed;

(f) the number of paediatric investigation plans completed;

(g) the renewals prolongations of the deferrals beyond five years and the detailed reasons

provided as mentioned in Article 82;

(h) the scientific advice provided for the development of medicinal products addressed to

children, requested in accordance with Article 89.

CHAPTER VIII VIII PHARMACOVIGILANCE

Article 99

Pharmacovigilance

1. The obligations of marketing authorisation holders laid down in Articles 99 and 100(1) of [revised Directive 2001/83/EC] shall apply to marketing authorisation holders for medicinal products for human use authorised in accordance with this Regulation.

2. The Agency may impose an obligation on a holder of a centralised marketing authorisation

to operate a risk management system, as referred to in Article 99(4), point (c) of [revised Directive 2001/83/EC], if there are concerns about the risks affecting the benefit-risk balance of an authorised medicinal product. In that context, the Agency shall also oblige the marketing authorisation holder to submit a risk management plan for the riskmanagement system that they intend to introduce for the medicinal product concerned.

The obligation referred to in paragraph 2 shall be duly justified, notified in writing, and shall include the timeframe for submission of the risk-management plan.

3. The Agency shall provide the marketing authorisation holder with an opportunity to submit

written observations in response to the imposition of the obligation referred to in paragraph 2 within a time limit which it shall specify, if the marketing authorisation holder so requests within 30 days of receipt of the written notification of the obligation.

On the basis of the written observations submitted by the marketing authorisation holder, the Agency shall review its opinion.

4. Where the opinion of the Agency confirms the obligation referred to in paragraph 2 and

unless the Commission returns the opinion to the Agency for further consideration, the marketing authorisation shall be varied accordingly by the Commission in accordance with the procedure set out in Article 13, to:

(a) include the obligation as a condition of the marketing authorisation and the risk management system shall be updated accordingly.

(b) include the measures to be taken as part of the risk management system as conditions of the marketing authorisation referred to in Article 12(4), point (e).

Article 100

Safety announcements

The obligations of marketing authorisation holders laid down in Article 104(1) 104, paragraphs 1 and 2 of [revised Directive 2001/83/EC], and the obligations of the Member States, the Agency and the Commission laid down in paragraphs 2, 3 and 4 of that Article shall apply to the safety announcements referred to in Article 138(1), point (f), of this Regulation concerning medicinal products for human use authorised in accordance with this Regulation.

Article 101

Eudravigilance database

1. The Agency shall, in collaboration with the Member States and the Commission, set

up and maintain a database and data processing network (‘Eudravigilance database’) to collate pharmacovigilance information regarding medicinal products authorised in the Union and to allow competent authorities to access that information simultaneously and to share it.

In justified cases, The Eudravigilance database may shall include pharmacovigilance information with regard to medicinal products used under compassionate use referred to in Article 26 or early access schemes.

The Eudravigilance database shall contain information on suspected adverse reactions in human beings arising from use of the medicinal product within the terms of the marketing authorisation as well as from uses outside the terms of the marketing authorisation, and on those occurring in the course of post-authorisation studies with the medicinal product or associated with occupational exposure.

2. The Agency shall, in collaboration with the Member States and the Commission, draw

up the functional specifications for the Eudravigilance database, together with a timeframe for their implementation.

The Agency shall prepare an annual report on the Eudravigilance database and send it to the European Parliament, the Council and the Commission.

Any substantial change to the Eudravigilance database and the functional specifications shall take into account the recommendations of the Pharmacovigilance Risk Assessment Committee.

The Eudravigilance database shall be fully accessible to the competent authorities of the Member States and to the Agency and the Commission. It shall also be accessible to marketing authorisation holders and marketing authorisation applicants to the extent necessary for them to comply with their pharmacovigilance obligations.

The Agency shall ensure that healthcare professionals and the public have appropriate levels of access to the Eudravigilance database, and that personal data is protected in accordance with Union law. The Agency shall work together with all stakeholders, including research institutions, healthcare professionals, and patient and consumer organisations, in order to define the ‘appropriate level of access’ for healthcare professionals and the public to the Eudravigilance database.

The data held on the Eudravigilance database shall be made publicly available in an aggregated and anonymised format together with an explanation of how to interpret the data.

3. The Agency shall, in collaboration either with the marketing authorisation holder or with

the Member State that submitted an individual suspected adverse reaction report to the Eudravigilance database, be responsible for operating procedures that ensure the quality and integrity of the information collected in the Eudravigilance database.

4. Individual suspected adverse reaction reports and follow-ups submitted to the

Eudravigilance database by marketing authorisation holders and marketing authorisation applicants shall be transmitted electronically upon receipt to the competent authority of the Member State where the reaction occurred.

Article 102

Forms for reporting suspected adverse reactions

The Agency shall, in collaboration with the Member States, develop standard web-based structured forms for the reporting of suspected adverse reactions by healthcare professionals and patients in accordance with the provisions referred to in Article 106 of [revised Directive 2001/83/EC].

Article 103

Periodic safety update reports repository

The Agency shall, in collaboration with the competent authorities of the Member States and the Commission, set up and maintain a repository for periodic safety update reports ( ‘repository’) and the corresponding assessment reports regarding medicinal products authorised in the Union so that they are fully and permanently accessible to the Commission, the competent authorities of the

Member States, the Pharmacovigilance Risk Assessment Committee, the Committee for Medicinal

Products for Human Use and the coordination group referred to in Article 37 of [revised Directive 2001/83/EC] (‘coordination group’).

The Agency shall, in collaboration with the competent authorities of the Member States and the Commission, and after consultation with the Pharmacovigilance Risk Assessment Committee, draw up the functional specifications for the repository.

Any substantial change to the repository and the functional specifications shall always take into account the recommendations of the Pharmacovigilance Risk Assessment Committee.

Article 104

European medicines web-portal and register of studies for environmental risk assessment

1. The Agency shall, in collaboration with the Member States and the Commission, set

up and maintain a European medicines web-portal for the dissemination of information on medicinal products authorised or to be authorised in the Union. That web-portal shall be easily accessible and user-friendly. By means of that portal, the Agency shall make public the following:

(a) the names of members of the Committees referred to in Article 142, points (d) and (e), and the members of the coordination group, together with their professional qualifications and with the declarations referred to in Article 147(2);

(b) agendas and minutes from each meeting of the Committees referred to in Article 142, points (d) and (e), and of the coordination group as regards pharmacovigilance activities;

(c) a summary of the risk management plans for medicinal products authorised in accordance with this Regulation;

(d) a list of the locations in the Union where pharmacovigilance system master files are kept and contact information for pharmacovigilance enquiries, for all medicinal products authorised in the Union;

(e) information about how to report to competent authorities of the Member States suspected adverse reactions to medicinal products and the standard structured forms referred to in Article 102 for their web-based reporting by patients and healthcare professionals, including links to national websites;

(f) Union reference dates and frequency of submission of periodic safety update reports established in accordance with Article 108 of [revised Directive 2001/83/EC];

(g) protocols and public abstracts of results of the post-authorisation safety studies referred to in Articles 108 118 and 120 of [revised Directive 2001/83/EC];

(h) the initiation of the procedure provided for in Article 41(2)55 of this Regulation, and Articles 95, 114, 115 and 116 of [revised Directive 2001/83/EC], the active substances or medicinal products concerned and the issue being addressed, any public hearings pursuant to that procedure and information on how to submit information and to participate in public hearings;

(i) conclusions of assessments, recommendations, opinions, approvals and decisions taken by the Agency and its Committees under this Regulation and [revised Directive 2001/83/EC], unless it is required that this information is made public by the Agency by other means;

(j) conclusions of assessments, recommendations, opinions, approvals and decisions taken by the coordination group, the competent authorities of the Member States and the Commission in the framework of the procedures set out in Articles 16, 106, 107 and 108 of this Regulation and of Chapter IX, Sections 3 and 7 of [revised Directive 2001/83/EC].

The summaries referred to in point (c) shall include a description of any additional risk minimisation measures.

2. In the development and review of the web portal, the Agency shall consult relevant

stakeholders, including patient and consumer groups, healthcare professionals, not-forprofit entities and industry representatives.

Article 104a

European register of studies for environmental risk assessment

3. The Agency shall, in collaboration with the Member States and the Commission, set

up and maintain a register of results of environmental risk assessment studies conducted for the purpose of supporting an environmental risk assessment for medicinal products authorised in the Union, unless such information relevant data is made public in the Union

by different means accordance with Regulation 2025/2455.

Information in such register shall be publicly available, unless restrictions are necessary to protect commercially confidential information. For the purpose of setting up such register, the Agency may request marketing authorisation holders and competent authorities to submit results of any such study already completed for products authorised in the Union within [OP please add the date = 24 months after the date of application of this Regulation].

Article 105

Literature monitoring

1. The Agency shall monitor selected medical literature for reports of suspected adverse

reactions to medicinal products containing certain active substances. It shall publish the list of active substances being monitored and the medical literature subject to this monitoring.

2. The Agency shall enter into the Eudravigilance database relevant information from the

selected medical literature.

3. The Agency shall, in consultation with the Commission, Member States and interested

parties, draw up a detailed guide regarding the monitoring of medical literature and the entry of relevant information into the Eudravigilance database.

Article 106

Monitoring of safety of medicinal products

1. The obligations of marketing authorisation holders and of Member States laid down in Article 105 and Article 106 of [revised Directive 2001/83/EC] shall apply to the recording and reporting of suspected adverse reactions for medicinal products for human use authorised in accordance with this Regulation.

2. The obligations of marketing authorisation holders laid down in Article 107 of [revised Directive 2001/83/EC] and the procedures under Articles 107 and 108 of that Directive shall apply to the submission of periodic safety update reports, the establishment of Union reference dates and changes to the frequency of submission of periodic safety update reports for medicinal products for human use authorised in accordance with this Regulation.

The provisions applicable to the submission of periodic safety update reports laid down in the of Article 108(2), second subparagraph, of that Directive shall apply to marketing authorisation holders of marketing authorisations which were granted before 2 July 2012 and for which the frequency and dates of submission of the periodic safety update reports are not laid down as a condition to the marketing authorisation until such time as another frequency or other dates of submission of the reports are laid down in the marketing authorisation or are determined in accordance with Article 108 of that Directive.

3. The assessment of the periodic safety update reports shall be conducted by a rapporteur

appointed by the Pharmacovigilance Risk Assessment Committee. The rapporteur shall closely collaborate with the rapporteur appointed by the Committee for Medicinal Products for Human Use or the Reference Member State for the medicinal products concerned.

The rapporteur shall prepare an assessment report within 60 days of receipt of the periodic safety update report and send it to the Agency and to the members of the

Pharmacovigilance Risk Assessment Committee. The Agency shall send the report to the marketing authorisation holder.

Within 30 days of receipt of the assessment report, the marketing authorisation holder and the members of the Pharmacovigilance Risk Assessment Committee may submit comments to the Agency and to the rapporteur.

Following the receipt of the comments referred to in the third subparagraph, the rapporteur shall within 15 days update the assessment report taking into account any comments submitted, and forward it to the Pharmacovigilance Risk Assessment Committee. The Pharmacovigilance Risk Assessment Committee shall adopt the assessment report with or without further changes at its next meeting and issue a recommendation. The recommendation shall mention the divergent positions with the grounds on which they are based. The Agency shall include the adopted assessment report and the recommendation in the repository set up under Article 103, and forward both to the marketing authorisation holder.

4. In the case of an assessment report that recommends any action concerning the marketing

authorisation, the Committee for Medicinal Products for Human Use shall, within 30 days of receipt of the report by the Pharmacovigilance Risk Assessment Committee, consider the report and adopt an opinion on the maintenance, variation, suspension or revocation of the marketing authorisation concerned, including a timetable for the implementation of the opinion. Where this opinion of the Committee for Medicinal Products for Human Use differs from the recommendation of the Pharmacovigilance Risk Assessment Committee, the Committee for Medicinal Products for Human Use shall attach to its opinion a detailed explanation of the scientific grounds for the differences together with the recommendation.

Where the opinion states that regulatory action concerning the marketing authorisation is necessary, the Commission shall adopt a decision, by means of implementing acts, to vary, suspend or revoke the marketing authorisation in accordance with Article 13. Where the Commission adopts such a decision, it may also adopt a decision addressed to the Member States pursuant to Article 57.

5. In the case of a single assessment of periodic safety update reports concerning more than

one marketing authorisation in accordance with Article 110(1) of [revised Directive 2001/83/EC] which includes at least one marketing authorisation granted in accordance with this Regulation, the procedure laid down in Article 107110 and Article 109112 of that Directive shall apply.

6. The final recommendations, opinions and decisions referred to in paragraphs 3, 4 and 5

shall be made public by means of the European medicines web-portal referred to in Article 104.

Article 107

Agency pharmacovigilance related activities

1. Regarding medicinal products for human use authorised in accordance with this

Regulation, the Agency shall, in collaboration with the Member States, take the following measures:

(a) monitor the outcome of risk minimisation measures contained in risk management plans and of conditions referred to in Article 12, paragraph 4, points (d) to (g)(i), or in Article 20, paragraph 1, points (a), (b) and (d) and (b), and in Articles 18(1), 19, and in Article 33(2) and (3). and 19;

(b) assess updates to the risk management system;

(c) monitor the data in the Eudravigilance database to determine whether there are new risks or whether risks have changed and whether those risks impact on the benefitrisk balance.

2. The Pharmacovigilance Risk Assessment Committee shall perform the initial analysis and

prioritisation of signals of new risks or risks that have changed or changes to the benefitrisk balance. Where it considers that follow-up action may be necessary, the assessment of those signals and agreement on any subsequent action concerning the marketing authorisation shall be conducted in a timescale commensurate with the extent and seriousness of the issue. Where appropriate, the assessment of those signals may be included in a pending assessment of a periodic safety update report or a pending procedure in accordance with Articles 95 and 114 to 116 of [revised Directive 2001/83/EC] or ArticleArticles 47 and 55 of this Regulation.

3. The Agency and competent authorities of the Member States and the marketing

authorisation holder shall inform each other in the event of new risks or risks that have changed or changes to the benefit-risk balance being detected.

Article 108

Non-interventional post-authorisation safety studies

1. For non-interventional post-authorisation safety studies concerning medicinal products for

human use authorised in accordance with this Regulation which have been imposed in accordance with Articles 13 and 20, the procedure provided for in Article 117, paragraphs 3 to 7, Articles 118, 119, 120 and 121(1) of [revised Directive 2001/83/EC] shall apply.

2. Where, in accordance with the procedure referred to in paragraph 1, the Pharmacovigilance Risk Assessment Committee issues recommendations for the variation, suspension or revocation of the marketing authorisation, the Committee on Medicinal Products for

Human Use shall adopt an opinion taking into account the recommendation, and the Commission shall adopt a decision in accordance with Article 13.

Where the opinion of the Committee for Medicinal Products for Human Use differs from the recommendation of the Pharmacovigilance Risk Assessment Committee, the Committee for Medicinal Products for Human Use shall attach to its opinion a detailed explanation of the scientific grounds for the differences, together with the recommendation.

Article 109

Exchange of information with other organisations

1. The Agency shall collaborate with the World Health Organization in matters of

pharmacovigilance and shall take the necessary steps to submit to it, promptly, appropriate and adequate information regarding the measures taken in the Union which could have a bearing on public health protection in third countries.

The Agency shall make available promptly all suspected adverse reaction reports occurring in the Union to the World Health Organization.

2. The Agency and the European Monitoring Centre forUnion Drugs and Drug

AddictionAgency shall exchange information that they receive on the abuse of medicinal products including information related to illicit drugs.

Article 110

International collaboration

At the request of the Commission, the Agency shall participate in collaboration with the Member States in international harmonisation and standardisation of technical measures in relation to pharmacovigilance.

Article 111

Cooperation with Member States

The Agency and the Member States shall cooperate to continuously develop pharmacovigilance systems capable of achieving high standards of public health protection for all medicinal products, regardless of the routes of marketing authorisation, including the use of collaborative approaches, to maximise use of resources available within the Union.

Article 112

Reports on pharmacovigilance tasks

The Agency shall perform regular independent audits of its pharmacovigilance tasks and report the results to its Management Board on a 2-yearly basis. The results shall be subsequently published.

CHAPTER IX REGULATORY SANDBOX

Article 113

Regulatory sandbox

1. The Commission may set up on a case-by-case basis a regulatory sandbox pursuant to a

specific sandbox plan, based on a recommendation of the Agency and pursuant to the procedure set out in paragraphs 4 to 7in accordance with this Chapter, where all of the following conditions are met:.

(a) it is not possible to develop and authorise the medicinal product or category of medicinal products in full compliance with the requirements applicable to medicinal products set out in this Regulation and [revised Directive 2001/83/EC] due to scientific or regulatory challenges arising from characteristics or methods related to the medicinal product or due to the scientific or technical characteristics inherent to the medicinal product, for which certain targeted and technical adaptations to the requirements laid down in this Regulation and [revised Directive 2001/83/EC] are considered indispensable ;

(b) the characteristics or methods referred to in point (a) are likely to, based on available scientific evidence, positively and distinctively contribute to the quality, safety or efficacy of the medicinal product or category of medicinal products as provided for in this Regulation and [revised Directive] or provide a major advantage contribution to patient access to prevention, diagnosis, treatment, or patient care.

2. The regulatory sandbox shall set out a controlled regulatory framework, including

scientific consisting of specific requirements, for and technical adaptations necessary during the development and, where appropriate clinical trialsphase, authorisation and placing on the market of a product referred to in paragraph 1 under the conditions set out in this Chapter . The regulatory sandbox may allow targeted derogations toadaptations to certain requirements of this Regulation, [revised Directive 2001/83/EC] or Regulation (EC) 1394/2007 under the conditions set out inwhich are necessary for the purposes of assessing whether an authorisation can be granted for a product referred to in paragraph 1 and its life cycle management in accordance with Article 114 and which ensure that the principles of quality, safety and efficacy set out by this Regulation and [revised Directive 2001/83/EC] are respected.

A regulatory sandbox shall take effectoperate under direct supervision of the competent authorities of the Member States concerned with a view to ensuring compliance with the requirements of this Regulation and, where relevant, other Union and Member State legislation concerned by the sandbox for activities that take place on their territory. Any violation of the conditions set out in the decision referred to in paragraph 6 and the identification of any risks to health and to environment shall be immediately notified to the Commission and to the Agency.

3. The Agency shall monitor the field of emerging medicinal products and may request

information and data from the national competent authorities of the Member States, marketing authorisation holders, developers, independent experts and researchers, and representatives of healthcare professionals and of patients and may engage with them in preliminary discussions.

4. Where, based on available scientifc evidence the Agency considers it appropriate to set

up a regulatory sandbox for medicinal products which are likely to fall under the scope of this Regulation and meet the conditions set out in paragraph 1, it shall providesubmit a recommendation to the Commission, following appropriate consultations, including consultation with the competent authorities of the Member States or, where appropriate, other competent authorities responsible for the setting up of regulatory sandboxes under other relevant regulatory frameworks. The recommendation of the Agency shall list eligible products or category of products in that recommendation and shalland include thea recommended sandbox plan referred to in paragraph 15 .

The Agency shall not recommend to set up a regulatory sandbox for a medicinal product that is already advanced in its development programme.

5. The Agency shall be responsible for developing adevelop the sandbox plan based on data

submitted by developers of eligible products and following appropriate consultations. The.. The sandbox plan shall set out clinical, scientific and regulatory justification for the necessity to establish a regulatorya sandbox, including the identification of the requirements of this Regulation, [revised Directive 2001/83/EC] and Regulation (EC) 1394/2007 that cannot be complied with and a proposalwhose adaptations are considered indispensable from a technical and scientific viewpoint for the development and authorisation of such medicinal product while ensuring that the principles of quality, safety and efficacy set out in this Regulation and [revised Directive 2001/83/EC] are respected . The sandbox plan shall also provide recommendations for alternative or mitigation measures, where appropriate. The sandbox plan shall also include a proposed timeline for the duration of the sandbox. Where appropriate, the Agency shall also proposerecommend measures in order to mitigate any possible distortion of market conditions as a consequence of establishing a regulatory sandbox. The Agency shall levy a

fee for activities under this Article.

6. The Commission shall, by means of implementing acts, takeadopt a decision on the set

up ofestablishing a regulatory sandbox for the eligible medicinal products or category of medicinal products taking into account the recommendation of the Agency and the sandbox plan pursuant to paragraph 4. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2).

7. Decisions establishing a regulatory sandbox under paragraph 56 shall be limited in time

and shall set out detailed conditions for its implementation. These Decisions shall include:

(a) include the proposedthe final sandbox plan, taking into account the recommended sandbox plan of the Agency, specifying the specific requirements and the targeted technical adaptations, in accordance with paragraphs 2 and 5, to the requirements of this Regulation and of [revised Directive 2001/83/EC] and, Regulation (EC) 1394/2007;

(b) include the duration of the regulatory sandbox and its expiry taking into account the duration for development, and, if applicable, for obtaining a marketing authorisation and placing on the market of the medicinal products concerned;

(c) include as partthe participants of the regulatory sandbox plan the requirements of this Regulation and of [revised Directive 2001/83/EC] that cannot be complied with and shall include appropriate measures to mitigate potential risks to health and to the environment.

8. The Commission may, by means of implementing acts, suspend or revoke a regulatory

sandbox at any time. in any of the following cases:

(a) the requirements and conditions laid down in paragraphs 6 and 7 are no longer met;

(b) it is appropriate to protect public health. , or to avoid serious risks for the

environment,

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2).

Where the Agency receives information that one of the cases referred to in the first subparagraph may be fulfilled, it shall inform the Commission accordingly.

9. Where after the decision to establish the regulatory sandbox in accordance with

paragraph 6, risks to health are identified but these risks can be fully mitigated by the adoption of supplementary conditions, the Commission may, after consultation of the Agency, amend its decision referred to in paragraph 6 and, where applicable, revoke a suspension decision adopted under paragraph 8 by means of implementing acts. The Commission may also prolong the duration of a regulatory sandbox by means of implementing acts. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2).

10. This Article shall not exclude the setting up of time limited pilot projects to test different

ways of implementing the applicable legislation.

Article 114

Products developed under a sandbox

1. When authorising a clinical trial application for products covered by a regulatory sandbox, Member States shall take the sandbox plan referred to in Article 113(1) into consideration.

2. A medicinal product developed as part of a regulatory sandbox mayshall be placed on the

market only when authorised in accordance with Article 13, 18 or 19 of this Regulation. Such authorisation may be granted only if the benefit-risk balance of the medicinal product is favourable. The initial validity of such authorisation shall not exceed the duration of the regulatory sandbox as specified in the implementing act referred to in Article 113(6) and (7). The authorisation may be prolongedrenewed at the request of the marketing authorisation holder in accordance with Article 17. The marketing authorisation holder shall submit the request for a renewal to the Agency at least nine

months before the marketing authorisation ceases to be valid.

3. In duly justified cases,Where necessary the marketing authorisation adopted in

accordance with Article 13, 18 or 19 of a medicinal product developed under the regulatory sandbox may include derogations from the requirements set out in this Regulation and [revised Directive 2001/83/EC]. Those derogations may entail adapted, enhanced, waived or deferred requirements. Each derogation shall specify in its conditions the adaptations that apply to the specific medicinal product pursuant to Article 113 (7). Each adaptation shall be limited to what is apt and strictly necessary to attain the objectives pursued, duly justified and specified. It shall not exceed the adaptations specified in the conditions to the marketing authorisationdecision referred to in Article 113(6) and (7) establishing the regulatory sandbox concerned.

4. For medicinal products developed as part of a regulatory sandbox for which a marketing

authorisation has been granted in accordance with paragraph 2 and where appropriate paragraph 3, the summary of product characteristics and the package leaflet shall indicate that the medicinal product has been developed as part of a regulatory sandbox. This

condition shall apply for the duration of the regulatory sandbox.

5. Without prejudice to Article 195 of [revised Directive 2001/83/EC], the Commission shall

suspend or revoke a marketing authorisation granted in accordance with paragraph 2, where the regulatory sandbox has been suspended or revoked in accordance with Article 113(7)113(8).

6. The Commission shall immediately vary the marketing authorisation to take account of the

mitigation measures taken in accordance with Article 115.

6a. In addition to Articles 55 and 56, where the Agency concludes that a holder of a

marketing authorisation granted under a regulatory sandbox, failed to comply with the specific conditions laid down in the marketing authorisation in accordance with paragraph 3, the Agency shall inform the Commission accordingly. The Commission shall adopt a decision to vary, suspend or revoke that marketing authorisation in accordance with the procedure set out in Article 13.

Article 115

General sandbox provisions

1. The regulatory sandboxes shall not affect the supervisory and corrective powers of the

competent authorities. In case of identification of risks to public health or safety concerns associated with the use of products covered by a sandbox, competent authorities shall take immediate and adequate temporary measures in order to suspend or restrict their use and inform the Commission and the Agency in accordance with Article 113(2).

Where such mitigation is not possible or proves to be ineffective, the development and testing process shall be suspended without delay until an effective mitigation takes place. If no effective mitigation plan can be provided, the Agency shall recommend to the

Commission to suspend or revoke a regulatory sandbox in accordance with Article

113(8). If applicable, the marketing authorisation provided for in accordance with Article 114 shall be suspended or revoked accordingly.

2. Participants in the regulatory sandbox, in particularincluding the marketing authorisation

holder of the medicinal product concerned, shall remain liable under applicable Union and Member States liability legislation for any harm inflicted on third parties as a result from the testing taking place in the sandbox. They shall inform the Agency without undue delay of any information which might entail the amendment of the regulatory sandbox or concerns the quality, safety or efficacy of products developed as part of a regulatory sandbox.

3. The modalities and the conditions of the operation of the regulatory sandboxes, including

the eligibility criteria and the procedure for the application, selection, participation and exiting from the sandbox, and the rights and obligations of the participants shall be set out in implementing acts. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2).

4. The Agency with input from Member States shall submit annual reports to the Commission, the European Parliament and the Council, on the results from the implementation of a regulatory sandbox, including a breakdown on the number of sandboxes granted, trends on medicinal products eligible for a regulatory sandbox, good practices, difficulties encountered, lessons learnt, reflections on possible future adaptations to the regulatory framework and recommendations on their setup and, where relevant, on the application of this Regulation and other Union legal acts supervised within the sandbox. These reports as well as lay summaries shall be made publicly available by the Commission.

5. The Commission shall review the reports and put forward, as appropriate, legislative

proposals with a view to update the regulatory framework referred to in Article 113(2) or delegated acts in accordance with Article 28 of [revised Directive 2001/83/EC].

CHAPTER X AVAILABILITY AND SECURITY OF SUPPLY OF MEDICINAL PRODUCTS

Section 1

Monitoring and management of shortages and critical shortages

Article 115a

Derogations on the provisions of this Chapter

1. Member States may waive the application of Articles 116(3a), 117(1b), Articles 120(2), 121(5a), 127(4), 129, 130(2) point (c), 130(4) point (c) when: (a) the batches of medicinal products concerned are supplied for military and defence purposes; or (b) when the medicinal products are manufactured for military and defence use only; and (c) insofar as the application of such requirements for these medicinal products imply a risk to national security and defence.

2. Member States may exempt authorities within their territory of the obligation to

communicate information for the medicinal products referred to in paragraph 1 in accordance with Articles 121 and 127 insofar as such requirements imply a risk to national security and defence.

3. Member States may exempt a marketing authorisation holder in possession of a

marketing authorisation for a medicinal product authorised in that Member State in accordance with article 205 of [revised Directive 2001/83/EC] from complying with the obligations set out in the articles 116, 117, 119, 125, 128 and 133.

Member States shall notify the Commission of the use of the derogations referred to in paragraph 1, 2 and 3 without undue delay.

Article 116

Marketing authorisation holder notifications

1. Without prejudice to the rules on notification referred to in Article 24 of this Regulation

and Article 203 of [the revised Directive 2001/83/EC] the marketing authorisation holder of a medicinal product in possession of a centralised marketing authorisation or a national marketing authorisation (‘these are referred to in this chapter as the marketing authorisation holder’) shall notify and explain the reasons to the competent authority of the Member State where the medicinal product has been placed on the market and, in addition, the Agency for a medicinal product covered by a centralised marketing authorisation (these are referred to in this Chapter as ‘the competent authority concerned’) of the following:

(a) its decision to permanently cease the marketing of a medicinal product in that Member State no less than twelve months before the last supply of that medicinal product into the market of a given Member State by the marketing authorisation holder;

(b) its request to permanently withdraw the marketing authorisation for that medicinal product authorised in that Member State no less than twelve months before the last supply of that medicinal product into the market of a given Member State by the marketing authorisation holder;

(c) its decision to temporarily suspend the marketing of a medicinal product in that Member State as soon as possible and no less than six months before the start of the temporary suspension of supply of that medicinal product into the market of a given

Member State by the marketing authorisation holder;

(d) a temporary disruption in supply of a medicinal product in a given Member State, of an expected duration of in excess of two weeks or, based on the demand forecast of the marketing authorisation holder, as soon as possible and in any event no less than six months before the start of such temporary disruption of supply or, if this is not possible and where duly justified, as soon as they become aware of such temporary disruption, to allow the Member State to monitor any potential or actual shortage in accordance with Article 118(1).

By way of derogation to paragraph 1, point (d), the marketing authorisation holder shall notify the temporary disruption in supply of a medicinal product in a given Member State as soon as they become aware of such temporary disruption where exceptional circumstances directly related to the supply disruption, which shall be duly identified and substantiated to the competent authority concerned, prevented the marketing authorisation holder from complying with the deadlines laid down therein.

The marketing authorisation holder shall make the notification electronically and in the formats made available by the Agency. The Agency shall consult the Member States when drawing up the formats.

2. For the purposes of the notification made in accordance with paragraph 1, points (a), (b)

and (c), the marketing authorisation holder shall provide the information set out in Part I of Annex IV.

For the purpose of notifications made in accordance with the paragraph 1, point (d), the marketing authorisation holder shall provide the information set out in Part III of Annex IV.

The marketing authorisation holder shall immediately notify the competent authority concerned, as appropriate, of any relevant changes to the information provided according to this paragraph.

3. The Commission is empowered to adopt delegated acts, in accordance with Article 175 in

order to amend Annex IV as regards the information to be provided in case of a temporary disruption of supply, information to be provided in case of a suspension or cessation of marketing of a medicinal product or withdrawal of the marketing authorisation of a medicinal product, or the content of the shortage prevention plan referred to in Article 117. 3a. Where the marketing authorisation holder intends to withdraw the marketing

authorisation or permanently cease to market in one or more Member States where the marketing authorisation is valid for a critical medicinal product identified by the competent authority of a Member State pursuant to Article 127(1), medicinal products identified in accordance with 126(2b) or a priority antimicrobial pursuant to Article 40

(3), the marketing authorisation holder shall, prior to the notification referred to in Article 116(1), point a or b, as applicable:

(a) publish a declaration of its intention to offer to transfer the marketing authorisation or its intention to issue a letter of access as referred to in Article 14 of [revised Directive 2001/83] via a dedicated webpage on its website and communicate the electronic link to such webpage to the competent authority of the Member State and the Agency. The Agency shall publish and compile a list of such electronic links.

(b) offer, on reasonable terms, to transfer the marketing authorisation or the letter of access to a third party that has declared its intention to place that medicinal product or to allow the use of the pharmaceutical non-clinical and clinical documentation contained in the file of that medicinal product for the purposes of submitting an application in accordance with Article 14 of [revised Directive 2001/83/EC].

(c) inform the competent authority concerned on the outcome of the negotiations with the third party or parties.

For the purpose of this paragraph, the marketing authorisation holder shall provide as part of the notification referred to in article 116 (1) point (a) and (b) information proving that they have taken steps to make the marketing authorisation available to third parties on reasonable terms.

Article 117

The shortage prevention plan

1. The marketing authorisation holder as defined in Article 116(1) shall have in place and

keep up to date a shortage prevention plan, for any for medicinal product placed on the marketproducts subject to prescription and for medicinal products identified in accordance with Article 126 (2b). To put in place the shortage prevention plan, the marketing authorisation holder shall include the minimum set of information set out in Part V of Annex IV and take into account the guidance drawn up by the Agency according to paragraph 2.

1a. The Agency, in collaboration with the working party referred to in Article 121(1), point (c), shall draw up guidance for marketing authorisation holders to put in place the shortage prevention plan. The guidance shall, in particular, indicate the relevant type and detail of information for the shortage prevention plan according to the different level of risk, including descriptions of the relevant shortage management measures.

1b. Whenever a medicinal product is subject to a shortage prevention plan in accordance

with this Article, the national competent authority, the Agency at any time or the Commission in accordance with Article 126 (2a) may request the marketing authorisation holder to submit that shortage prevention plan at any time. The marketing authorisation holder shall submit that copy at the latest two days after receipt of such request.

2. The Agency, in collaboration with the working party referred to in Article 121(1), point (c), shall draw up guidance to marketing authorisation holders as defined in Article 116(1) to put in place the shortage prevention plan.

3. Where relevant, the marketing authorisation holder as defined in Article 116(1) shall

update the shortage prevention plan to include additional information, based ontaking into account recommendations of the Executive Steering Group on Shortages and Safety of Medicinal Products (also referred to as the Medicine Shortages Steering Group – ‘MSSG’, established in Article 3(1) of Regulation (EU) 2022/123, in accordance with Articles 123(4) and 132(1).

Article 118

Shortage monitoring by the competent authority of the Member State or the Agency

1. Based on the reports referred to in Articles 120(1) and 121(1), point (c), information

referred to in Articles 119, 120(2) and 121 and the notification made pursuant to Article

116(1), points (a) to (d) and 120(1a), the competent authority concerned as referred to in Article 116(1) shall continuously monitor any potentialexpected or actual shortage of those medicinal products. In addition, the competent authority concerned may use information contained in the repositories in Article 67(2), second subparagraph, point (e), of [revised Directive 2001/83/EC] or in a national repository.

The Agency shall carry out that monitoring in collaboration with the relevant competent authority of the Member State whenwhere those medicinal products are authorised under this Regulation or when coordinated EU action is required.

2. For the purposes of paragraph 1, the competent authority concerned as defined in Article 116(1) may request any additional information from the marketing authorisation holder as defined in Article 116(1). In particular, it may request the marketing authorisation holder to submit a shortage mitigation plan in accordance with Article 119(2), a risk assessment of impact of suspension, cessation or withdrawal in accordance with Article 119(3), or the shortage prevention plan referred to in Article 117. The competent authority concerned mayshall set a deadline for the submission of the information requested.

Article 119

Obligations on the marketing authorisation holder

1. The marketing authorisation holder as defined in Article 116(1) shall:

(a) submit the information requested in accordance with Article 118(2) or, Article 124(2), point (b), or Article 117(1b) to the competent authority concerned as defined in Article 116(1), without undue delay, using the tools, methods of and criteria for the monitoring and reporting established pursuant to Article 122(4), point (b), by the deadline set by that competent authority;

(b) provide updates to the information provided in accordance with point (a), where necessary;

(c) justify any failure to provide any of the requested information;

(d) where necessary, submit a request to the competent authority concerned as defined in Article 116(1) for an extension of the deadline set by that competent authority in accordance with point (a), and

(e) indicate whether the information provided in accordance with point (a) contains any commercially confidential information, identify the relevant parts of that information having a commercially confidential nature and explain why that information is of such nature.

2. To prepare the shortage mitigation plan referred to in Article 118(2), the marketing

authorisation holder as defined in Article 116(1) shall include the minimum set of information set out in Part IV of Annex IV and take into account the guidance drawn up by the Agency according to Article 122(4), point (c).

3. To prepare a risk assessment of impact of suspension, cessation or withdrawal referred to

in Article 118(2), the marketing authorisation holder as defined in Article 116(1) shall include the minimum set of information set out in Part II of Annex IV and take into account the guidance drawn up by the Agency according to Article 122(4), point (c).

3a. In case of medicinal products that are not subject to the obligation of preparing a

shortage prevention plan the marketing authorisation holder shall carry out a regular documented risk assessment of potential supply chain risks and, where necessary, take mitigating measures.

The national competent authority of the Member State or the Agency may request the marketing authorisation holder to submit that document at any time. The marketing authorisation holder shall submit that copy at the latest two days after receipt of such request.

4. The marketing authorisation holder as defined in Article 116(1) shall be responsible for

providing correct, not misleading, and complete information as requested by the competent authority concerned.

5. The marketing authorisation holder as defined in Article 116(1) shall cooperate with that

competent authority and disclose, on their own motion, any relevant information to that authority and update the information as soon as new information becomes available.

Article 120

Obligations on other actors

1. Wholesale distributors and other persons or legal entities that are authorised or entitled to

supply medicinal products authorised to be placed on the market of a Member State pursuant to Article 5 of [revised Directive 2001/83/EC] to the public may report a shortage of a given medicinal product marketed in the Member State concerned to the competent authority in that Member State.

1a. Member States may require for centrally or nationally authorised medicinal products,

that a wholesale distributor that is not the marketing authorisation holder who intends to distribute the medicinal product to another Member State informs the competent authority of the source Member State of this intention. This information shall include:

(a) The name of the medicinal product and authorisation number;

(b) Active substance(s);

(c) Pharmaceutical form;

(d) Strength;

(e) Pack size;

(f) The quantity of the medicinal product which shall be taken out from the source Member State.

Based on the information provided by the wholesaler and on the information available pursuant to this Chapter, the source Member State may take measures to prevent or to mitigate shortages in the source Member State. The Member State shall notify the Agency of the measures referred to in this subparagraph.

The information requirement referred to in the first subparagraph and measures referred to in the third subparagraph shall, moreover, be justified on grounds of public health protection and be proportionate in relation to the objective of such protection, in compliance with the Treaty rules.

2. For the purposes of Article 118(1), where relevant, upon request from the competent

authority concerned as defined in Article 116(1), entities including other marketing authorisation holders as defined in Article 116(1), importers and manufacturers of medicinal products or active substances and relevant suppliers of these, wholesale distributors, stakeholder representative associations or other persons or legal entities that are authorised or entitled to supply medicinal products to the public shall provide any information requested in a timely mannerwithin the timeframe specified by the competent authority concerned.

Article 121

Role of the competent authority of the Member State

1. The competent authority of the Member State shall:

(-a) collect and assess information received in accordance with Articles 116(1), points (a) to (d), 119, 120 in order to continuously monitor any expected or actual shortages pursuant to article 118(1).

(a) assess the merits of each confidentiality claim made by the marketing authorisation holder as defined in Article 116(1) in accordance with Article 119(1), point (e), and shall protect information which that competent authority considers to be commercially confidential against unjustified disclosure;

(b) publish information and provide regular updates on actual shortages of medicinal products, in cases in which that competent authority has assessed the shortage, on a publicly available and user-friendly website and ensure such information, including regarding available alternatives, has been actively communicated to representatives of healthcare professionals and patients;

(c) report to the Agency, through the single point of contact working party referred to in Article 3(6) of Regulation (EU) 2022/123, any shortage of a medicinal product that it identifies as a critical shortage in that Member State to the Agency without undue delay.

(cb) consider the use of appropriate regulatory measures to mitigate the shortage.

2. Following the reporting referred to in paragraph 1, point (c), and to facilitate the

monitoring referred to in Articles 118(1), the competent authority of the Member State shall, through the working party referred to in paragraph 1, point (c):

(a) submit to the Agency the information referred to in Articles 122(1) or 124(2), point (a), using the tools, methods of and criteria for the monitoring and reporting established pursuant to Article 122(4), point (b), by the deadline set by the Agency;

(b) where necessary, provide updates to the information provided in accordance with point (a) to the Agency;

(c) justify any failure to provide any of the information referred to in point (a) to the

Agency;

(d) where necessary, submit a request to the Agency to extend the deadline set by the

Agency referred to in point (a);

(e) indicate whether the marketing authorisation holder as defined in Article 116(1) has indicated the existence of any commercially confidential information and provide the marketing authorisation holder’s explanation of why that information is of a commercially confidential nature, in accordance with Article 119(1), point (e);

(f) inform the Agency of any actions foreseen or taken by that Member State to mitigate the shortage at national level without undue delay.

2a. After the expansion of the ESMP referred to in Article 122(6) and for the purpose of Article 118(1) and Article 121(2), point (a), competent authorities of the Member States shall make reasonable efforts that their national IT systems are gradually made interoperable with the ESMP and allow for the automated exchange of information with the ESMP while avoiding duplication of reporting.

3. Where the competent authority of the Member State has any information in addition to the

information to be provided pursuant to this Article, it shall immediately provide such information to the Agency through the working party referred to in paragraph 1, point (c).

4. Following the addition of a medicinal product on the list of critical shortages of medicinal

products referred to in Article 123(1)122(2), the competent authority of the Member State shall, through the working party referred to in paragraph 1, point (c), provide any information requested pursuant to Article 124(2), point (a), to the Agency.

5. Following any MSSG recommendations provided in accordance with Article 123(4), the

competent authority of the Member State shall, through the working party referred to in paragraph 1, point (c):

(a) report to the Agency on any information received from the marketing authorisation holder as defined in Article 116(1) of the medicinal product concerned or from other actors pursuant to Article 120(2)120(1a) and (2);

(b) comply and coordinate with any relevant measures taken by the Commission pursuant to Article 126(1), point (a);

(c) take into account any MSSG recommendations referred to in Article 123(4);

(d) inform the Agency of any actions foreseen or taken by that Member State in accordance with points (b) and (c) and report on any other actions taken to mitigate or resolve the critical shortage in the Member State, as well as the results of these actions, without undue delay.

(da) Where Member States take an alternative course of action which is not in line with the recommendations of the MSSG at national level, they shall communicate the reasons for doing so to the MSSG in a timely manner.

5a. The competent authority of the Member State may require wholesale distributors and

other persons or legal entities that are authorised or entitled to supply to the public medicinal products authorised to be placed on the market of a Member State pursuant to Article 5 of [revised Directive 2001/83/EC] to report a shortage of a medicinal product marketed in the Member State concerned.

6. The Member States may request that the MSSG provide further recommendations, referred

to in pursuant to Article 123(4).

Article 121a

National websites on medicines shortages

The website referred to in Article 121(1), point (b), shall include at least the following information:

(a) trade name of the medicinal product and international non-proprietary name, for

interoperability purposes;

(b) the therapeutic indication for the medicinal product of which there is a shortage;

(c) reasons for the shortages and mitigation measures taken to address the shortages, after

the deletion of any commercially confidential information

(d) the start and expected end dates of the shortage;

(e) where relevant, other information for healthcare professionals and patients, including

information about available alternative medicinal products.

Article 122

Role of the Agency concerning shortages

1. For the purposes of Article 118(1), the Agency may request additional information from

the competent authority of the Member State, through the working party referred to in Article 121(1), point (c). The Agency may set a deadline for the submission of the information requested.

2. On the basis of Article 118(1), the Agency, in collaboration with the working party

referred to in Article 121(1), point (c), shall establish and update a list of critical shortages of Union concern whenever a Member State requests to do so for identify the medicinal products for which the shortage cannot be resolved without EU coordination.

3. The Agency shall inform the MSSG of the shortages of the medicinal products that have

been identifiedlisted pursuant to paragraph 2.

3b. The Agency shall establish within its web-portal referred to in Article 104 a publicly

available and user-friendly webpage that provides information on actual critical shortages of Union concern of medicinal products. This webpage shall also provide references to the lists of actual shortages published by the competent authorities of the Member States pursuant to Article 121(1), point (b).

4. For the purposes of fulfilling the tasks referred to in Articles 118(1), 123 and 124, the Agency shall ensure the following, in consultation with the working party referred to in Article 121(1), point (c):

(a) set the criteria to adopt and review the list of critical shortages referred to in Article

123(1);

(b) specify the tools, including the European Shortages Monitoring Platform (‘ESMP’), established by Regulation (EU) 2022/123, once the scope is expanded pursuant to paragraph 6, the methods of and criteria for the monitoring and reporting provided for in Articles 119(1), point (a), and 121(2), point (a);

(c) draw up guidance to allow marketing authorisation holders as defined in Article 116(1) to put in place the risk assessment of impact of suspension, cessation or withdrawal and the shortage mitigation plan as referred to in Article 118(2);

(d) specify the methods for the provision of recommendations referred to in Article

123(4);

(e) publish information covered by points (a) to (d) on a dedicated webpage on its webportal referred to in Article 104.

5. For the duration of the critical shortage and until the MSSG considers it to be resolved,of Union concern the Agency shall regularly report on the results of the monitoring referred to in Article 124 to the Commission and the MSSG, and in particular, it shall report any event that is likely to lead to a major event, as defined in Article 2 of Regulation (EU)

2022/123. Where a public health emergency is recognised in accordance with Regulation (EU) 2022/2371 or an event is recognised as a major event, in accordance with Regulation (EU) 2022/123, that Regulation appliesprevails.

6. For the purposes of implementing this Regulation, the Agency shall expand the scope of

the ESMP by one year after the entry into force, including the information exchange for the purpose of the vulnerability evaluation. The Agency shall ensure that, where relevant, data is interoperable between the ESMP, Member States’ IT systems and other relevant IT systems and databases, while avoiding without duplication of reporting.

Article 123

Role of the MSSG and the list of critical shortages of medicinal products

1. Based on the monitoring referred to in Article 118(1), and following consultation with the Agency and the working party referred to in Article 121(1), point (c), the MSSG shall adopt a list of critical shortages of medicinal products authorised to be placed on the market of a Member State pursuant to Article 5 of [revised Directive 2001/83/EC]and for which co-ordinated Union level action is necessary (‘the list of critical shortages of medicinal products’).

1a. The MSSG, following consultation of the working party referred to in Article 121(1),

point (c), shall review the status of the critical shortage of Union concern whenever necessary and shall recommend the Agency to update the list in accordance with Article 122, paragraph 2.

2. The MSSG shall review the status of the critical shortage whenever necessary and shall

update the list when it considers that a medicinal product needs to be added or that the critical shortage has been resolved based on the report pursuant to Article 122(5).

3. In addition, The MSSG shall amend its rules of procedure, and the rules of procedure of

the working party referred to in Article 121(1), point (c), in accordance with the roles set out in this Regulation.

4. The MSSG may provide recommendations on measures to resolve or to mitigate the

critical shortage of Union concern, in accordance with the methods referred to in Article

122(4), point (d), to relevant marketing authorisation holders, the Member States, the

Commission, the Agency, the representatives of healthcare professionals or other entities. The MSSG may recommend Member States to forecast and monitor demand for medicinal products on the list of critical shortages of Union concern, taking into account the demand forecast from the marketing authorisation holder.

4a. The MSSG shall provide recommendations to the Commission regarding the possibility,

pursuant to Article 117 paragraph 1, to require a shortage prevention plan for a medicinal product that is not subject to prescription. In doing so, the MSSG shall take

into account the criteria set out in Article 126, paragraph 2b.

Article 124

Management of the critical shortage of Union concern

1. Following the addition of a medicinal product to the list of critical shortages of Union

concern pursuant to Article 123, paragraphs 1 and 2,122(2) and based on the continuous monitoring carried out in accordance with Article 118(1), the Agency, in coordination with the competent authority of the Member State concerned, shall continuously monitor the critical shortage of Union concern of that medicinal product.

2. For the purposes of paragraph 1, wherethe Agency may, if that information is not already

available to the Agency, the Agency may request relevant information on that critical shortage of Union concern from:

(a) the competent authority of the Member State concerned through the working party referred to in Article 121(1), point (c);

(b) the marketing authorisation holder as defined in Article 116(1); (c) the other actors listed in Article 120(2).

For the purposes of this paragraph, the Agency mayshall set a deadline for the submission of the information requested.

3. The Agency shall establish within its web-portal referred to in Article 104 a publicly

available webpage that provides information on actual critical shortages of medicinal products in cases in which the Agency has assessed the shortage and has provided recommendations to healthcare professionals and patients. This webpage shall also provide references to the lists of actual shortages published by the competent authorities of the Member State pursuant to Article 121(1), point (b).

Article 125

Obligations on the marketing authorisation holder in case of a critical shortage of Union concern

1. Following the addition of a medicinal product to the list of critical shortages of Union

concern of medicinal products in accordance with Article 123, paragraphs 1 and122, paragraph 2, or recommendations provided in accordance with Article 123(4), the marketing authorisation holder as defined in Article 116(1) and subject to those recommendations shall:

(a) provide any additional information that the Agency may request, including regular information on the available stocks of the concerned medicinal product;

(b) provide additional relevant information to the Agency;

(c) take into account the recommendations referred to in Article 123(4);

(d) comply with any measurestake into account the actions taken by the Commission pursuant to Article 126(1), point (a), or actions taken by the Member State pursuant to Article 121(5), point (d)126 (1) ;

(e) inform the Agency of any measures taken pursuant to points (c) and (d) and the report on results of such measures;

(f) inform the Agency and the competent authority of the Member State of the end date of the critical shortage of Union concern without undue delay.

Article 125a

Voluntary Solidarity Mechanism for Medicinal products

1. In order to mitigate critical shortages of medicinal products, Member States may, on a

voluntary basis and as a last resort, request to the MSSG the activation of the Voluntary

Solidarity Mechanism for Medicinal products. The Voluntary Solidarity Mechanism for Medicinal products shall be coordinated by the MSSG and supported by the Agency.

2. The Voluntary Solidarity Mechanism for Medicinal products referred to in paragraph 1

may be activated by the MSSG on behalf of a requesting Member State where the following conditions are met:

(a) The Agency has been notified of the critical shortage in accordance with Article 121(1)(c), and the shortage has been brought to the attention of the single point of contact working party referred to in Article 3(6) of Regulation (EU) 2022/123;

(b) There are no or insufficient therapeutic alternatives available in the Member State concerned;

(c) There are insufficient quantities of the medicinal product available in the Member State concerned to treat critical indications;

(d) Import of stocks from third countries or other short-term measures do not provide a solution in a timely manner or in sufficient quantities;

(e) There is a risk of stockout in the Member State concerned within one month or

less.

3. The MSSG shall establish rules of procedure to facilitate the use of The Voluntary Solidarity Mechanism in accordance with this article.

4. Where any Member State is ready to provide assistance, the Agency shall put the

requesting Member State in contact with the volunteering Member States.

5. The Agency shall facilitate the exchange of information between Member States,

coordinate requests for support, and, where necessary, liaise with marketing

authorisation holders.

Article 126

Role of the Commission

1. The Commission shall, where it considers it appropriate and necessary:

(a) take into account the MSSG recommendations and implement relevant measures;

(aa) take any actions, within the limits of the powers conferred on the Commission;

(b) inform the MSSG of those measures actions taken by the Commissionpursuant to

letter (aa).

2. The Commission may request the MSSG to provide recommendations referred to in Article 123(4).

2a. The Commission may request the information gathered by the Agency in accordance

with Section 2 of Chapter X and, where relevant in the context of crisis preparedness, may request the Marketing Authorisation holder to submit relevant information, including the Shortage Prevention Plan referred to in Article 117. The Commission shall protect any information that is commercially confidential against unjustified disclosure.

2b. The Commission is empowered to adopt a delegated act supplementing this Regulation to

identify additional medicinal products that require a shortage prevention plan, in accordance with the requirements set out in Article 117.

Those delegated acts shall be adopted taking due account of the likelihood of shortages, relevance for public health and patient needs relating to such medicinal products. To this end, the following criteria shall guide the identification of these medicinal products:

(a) The number and frequency of past critical shortages reported to the MSSG;

(b) The specific characteristics of the medicinal products concerned and the existence of

available alternative authorised medicinal products;

(c) The therapeutic relevance of the medicinal product and the conditions intended to be

treated;

(d) Potential risks to public health, including crisis preparedness.

When the Commission adopts a delegated act pursuant to this paragraph, it shall take into account MSSG recommendations adopted in accordance with Article 123(4a).

Section 2

Security of supply

Article 127

Identification and management of critical medicinal products by the competent authority of the Member State

1. The competent authority of the Member State shall consult, where relevant with

healthcare professionals and patient organisations, and shall identify critical medicinal products in that Member State, using the methodology set out in Article 130(1), point (a).

1a. The Commission shall adopt and update the list of critical medicinal products identified

by the competent authorities of the Member States according to paragraph 1 ('Union long list') by means of an implementing act and communicate the adoption of the list and any updates to the Agency and the MSSG. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2).

2. The competent authority of the Member State acting through the working party referred to

in Article 121(1), point (c), shall report to the Agency the critical medicinal products in that Member State identified pursuant to the paragraph 1, first subparagraph, and all available data relevant for the vulnerability evaluation referred to in Article 132 paragraph 1a, as well as the information received from the marketing authorisation holder. The Agency shall inform the Commission on the critical medicinal products identified as critical by Member States pursuant to paragraph 1 as defined in Article 116(1).

3. For the purposespurpose of the identification of critical medicinal products referred to in

paragraph 1, first subparagraph, using the methodology pursuant to Article 130(1), point (a), and for the purpose of the vulnerability evaluation referred to in Article 132

paragraph 1a, using the methodology pursuant to Article 130(1), point (aa), the competent authority of the Member State may request relevant information including the shortage prevention plan referred to in Article 117 from the marketing authorisation holder as defined in Article 116(1).

4. For the purposes of the identification of critical medicinal products referred to in

paragraph 1, using the methodology pursuant to Article 130(1), point a, and of the vulnerability evaluation referred to in Article 132 paragraph 1a, using the methodology pursuant to Article 130(1), point aa, the competent authority of the Member State may request relevant information from other entities including other marketing authorisation holders, importers and manufacturers of medicinal products or active substances and relevant suppliers of these, wholesale distributors, stakeholder representative associations or other persons or legal entities that are authorised or entitled to supply medicinal products to the public.

5. The competent authority of the Member State shall assess the merits of each confidentiality

claim made by the marketing authorisation holder pursuant to Article 128(1), point (e), and shall protect any information that is commercially confidential against unjustified disclosure.

6. For the purposes of the adoption of the Union list of critical medicinal products pursuant to Article 131, each Member State shall, through the competent authority of the Member State concerned:

(a) submit to the Agency the information referred to in Article 130(2), point (a), using the tools, methods of and criteria for the monitoring and reporting established pursuant to Article 130(1), point (c), by the deadline set by the Agency;

(b) provide any relevant information to the Agency, including information on measures that have been taken by the Member State to strengthen the supply of that medicinal product;

(c) provide updates to the information provided in accordance with points (a) and (b) to the Agency where necessary;

(d) justify any failure to provide any of the requested information;

(e) indicate the existence of any commercially confidential information reported as such by the marketing authorisation holder pursuant to Article 128(1), point (e), and provide the marketing authorisation holder’s explanation of why that information is of a commercially confidential nature.

Where necessary, the competent authority of the Member State may request an extension of the deadline set by the Agency to comply with the request for information in accordance with point (a) of the first subparagraph.

7. Following the addition of a medicinal product to the Union list of critical medicinal

products in accordance with Article 131 or any recommendations provided in accordance with Article 132(1), the Member States shall:

(a) provide any additional information that the Agency may request;

(b) provide additional relevant information to the Agency;

(c) comply and coordinate with any measures actions taken by the Commission pursuant to Article 134(1), point (a)(aa);

(d) take into account any MSSG recommendations referred to in Article 132(1);

(e) inform the Agency of any actions foreseen or taken in accordance with point (c) and (d) by that Member State, as well as the results of these actions.

8. Member States that take an alternative course of action in respect of paragraph 7, points (c)

and (d), shall share the reasons for doing so with the Agency in a timely manner.

Article 128

Obligations of the marketing authorisation holder with regard to critical medicinal products

1. For the purposes of Article 127, paragraphs 1 and 3, and Article 131(1), the marketing

authorisation holder as defined in Article 116(1) shall:

(a) submit the information requested in accordance with Articles 127(3), 130(2), point

(b), and 130(4), point (b), to the competent authority concerned as defined in Article 116(1), without undue delay, using the tools, methods of and criteria for the monitoring and reporting established pursuant to Article 130(1), point (c), by the deadline set by that competent authority concerned;

(b) provide updates to the information provided in accordance with point (a) where necessary;

(c) justify any failure to provide any of the requested information;

(d) where necessary, submit a request to the competent authority concerned as defined in Article 116(1) for an extension of the deadline set by that competent authority in accordance with point (a), and

(e) indicate whether the information provided in accordance with point (a) contain any commercially confidential information, identify the relevant parts of that information having a commercially confidential nature and explain why that information is of such nature.

2. The marketing authorisation as defined in Article 116(1) authorisationholder shall be

responsible for providing correct, not misleading, and complete information as requested by the competent authority concerned as defined in Article 116(1) and shall have the duty to cooperate and to disclose on their own motion any relevant information without undue delay to that competent authority and to update the information as soon as that information becomes available.

Article 129

Obligations on other actors

For the purposes of Article 127(4) and Article 130(2), point (c), and Article 130(4), point (c), where relevant, upon request from the competent authority concerned as defined in Article 116(1), entities including other marketing authorisation holders as defined in Article 116(1), importers and manufacturers of medicinal products or active substances and relevant suppliers of these, wholesale distributors, stakeholder representative associations or other persons or legal entities that are authorised or entitled to supply medicinal products to the public shall provide any information requested in a timely manner within the timeframe specified by the competent authority concerned and provide updates whenever necessary.

Article 130

Role of the Agency

1. The Agency shall, in collaboration with the MSSG and the working party referred to in Article 121(1), point (c), ensure the following:

(a) develop a common methodology to identify critical medicinal products, including the evaluation of vulnerabilities with respect to the supply chain on the basis of their therapeutic relevance and availability of appropriate alternatives of those medicines,medicinal products in consultation, where appropriate, with relevant stakeholders;

(aa) develop a common methodology to evaluate the vulnerabilities with respect to the supply chains of critical medicinal products listed on the Union list of Critical Medicinal Products as referred to in Article 131 including, but not limited to the lack of supply chain diversification or the level of dependency on countries outside the Union with respect to these critical medicinal products or their active substances or both, in consultation, where appropriate, with relevant stakeholders;

(b) specify the procedures and criteria for establishing and reviewing the Union list of critical medicinal products referred to in Article 131, and the procedures and criteria for prioritising the vulnerability evaluation of such medicinal products;

(c) specify the tools, including the European Shortages Monitoring Platform (ESMP), established by Regulation (EU)2022/123, once the scope is expanded pursuant to Article 124(6), methods of and criteria for the monitoring and reporting provided for in Articles 127(6), point (a), and 128(1), point (a);

(d) specify the methods for the provision and review of MSSG recommendations referred to in Article 132, paragraphs 1 and 3.

The Agency shall publish the information referred to in points (b), (c) and (d) on a dedicated webpage on its web-portal.

2. Following the reports and information provided by the Member States and marketing

authorisation holders in accordance with Article 127, paragraphs 2 and 6, and Article 128(1), the Agency, may request the relevant information from:

(a) the competent authority of the Member State concerned;

(b) the marketing authorisation holder of the medicinal product, including the shortage prevention and the shortage mitigation plan, respectively referred to in Article 117 and Article 118(2);

(c) other entities including other marketing authorisation holders, importers and manufacturers of medicinal products or active substances and relevant suppliers of these, wholesale distributors, stakeholder representative associations or other persons or legal entities that are authorised or entitled to supply medicinal products to the public.

The Agency, in consultation with the working party referred to in Article 121(1), point (c), shall report the information referred to in Article 127, paragraphs 2 and 6, and Article 128(1) to the MSSG.

3. For the purposes of Article 127(6), point (e), and Article 128(1), point (e), the Agency

shall assess the merits of each confidentiality claim and protect commercially confidential information against unjustified disclosure.

4. Following the adoption of the Union list of critical medicinal products in accordance with Article 131, the Agency may request additional information from:

(a) the competent authority of the Member State concerned;

(b) the marketing authorisation holder as defined in Article 116(1);

(c) other entities including other marketing authorisation holders, importers and manufacturers of medicinal products or active substances and relevant suppliers of these, wholesale distributors, stakeholder representative associations or other persons or legal entities that are authorised or entitled to supply medicinal products to the public.

5. Following the adoption of the Union list of critical medicinal products in accordance with Article 131, the Agency shall report to the MSSG onassess any relevant information received from the marketing authorisation holder pursuant to Article 133 and the competent authority of the Member State in accordance with Article 127, paragraphs 7 and 8 and report on that information to the MSSG.

6. The Agency shall make publicly available via the web-portal referred to in Article 104 the MSSG recommendations referred to in Article 132(1).

Article 131

The Union List of Critical Medicinal Products

1. Following the reporting referred to in Article 130, paragraph 2, second subparagraph, and Article 130(5), the MSSG shall consult the working party referred to in Article 121(1), point (c). Based on this consultation, the MSSG shall propose a Union list of critical medicinal products authorised to be placed on the market of a Member State pursuant to Article 5 of [revised Directive 2001/83/EC] and for which the coordinated Union level action foreseen in this chapter is necessary (“the Union list of critical medicinal products”).

2. The MSSG mayshall propose updates to the Union list of critical medicinesmedicinal

products to the Commission, where necessary., in particular taking into account the outcome of vulnerability evaluations referred to in Article 132(1a)

The first revision of the Union list of critical medicinal products shall take place no later than one year after the date of entry into force of this Regulation. Where the results of the vulnerability evaluation are available in line with the prioritisation criteria referred to in Article 130, paragraph 1(b), the revision shall include an update of the list taking

into account the results of the vulnerability evaluation.

3. The Commission, taking into account the proposal of the MSSG, shall adopt and update

the Union list of critical medicinal products by means of an implementing act and communicate the adoption of the list and any updates to the Agency and the MSSG. On the Union list of critical medicinal products, to the extent possible, the Commission shall specify the critical medicinal products for which a vulnerability in the supply chains is established, taking into account the vulnerability evaluation referred to in Article 132(1a) and prioritisation criteria referred to in Article 130 (1b). Among these medicines the Commission shall also specify those critical medicinal products, including their active substances, which are vulnerable due to a high level of dependency on a single or limited number of countries outside the Union Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2).

4. Following the adoption of the Union list of critical medicinal products in accordance with

paragraph 3, the Agency shall immediately publish this list and any updates to this list on its web-portal referred to in Article 104.

Article 132

Role of the MSSG

1. Following the adoption of the Union list of critical medicinal products pursuant to Article

131(3), in consultation with the Agency and the working party referred to in Article 121(1), point (c), the MSSG may provide recommendations, in accordance with the methods referred to in Article 130(1), point (d), on appropriate security of supply measures to marketing authorisation holders as defined in Article 116(1), the Member States, the Commission, the Agency or other entities. Such measures may include, inter alia, recommendations on diversification of suppliers and, inventory management and regulatory flexibilities.

1a. The MSSG, relying on the information referred to Article 130, paragraph 2 and on the

basis of methodology set out in Article 130(1) point (aa), shall evaluate the vulnerability with respect to the supply chains of the medicinal products listed on the Union list of critical medicinal products and according to prioritisation criteria referred to in Article 130(1)(b).

2. The MSSG shall amend its rules of procedure, and the rules of procedure of the working

party referred to in Article 121(1), point (c), in accordance with the tasks set out in this section.

3. Following the report pursuant to Article 130(5), the MSSG shall review its

recommendations in accordance with the methods referred to in Article 130(1), point (d).

4. The MSSG may request the Agency to request further information from the Member States

or marketing authorisation holder of the medicinal product as defined in Article 116(1) and included on the Union list of critical medicinal products or other relevant entities referred to in Article 129.

Article 133

Obligations on the marketing authorisation holder after the MSSG recommendations

Following the addition of a medicinal product to the Union list of critical medicinal products in accordance with Article 131(3) or following any recommendations provided in accordance with Article 132(1), the marketing authorisation holder as defined in Article 116(1) of a medicinal product on that list or subject to those recommendations shall:

(a) provide any additional information that the Agency may request;

(b) provide additional relevant information to the Agency;

(c) take into account the recommendations referred to in Article 132(1);

(d) comply with any measures take into account the actions taken by the Commission in

accordance with Article 134(1), point (a), or by the Member State pursuant to Article

127(7), point (e);

(e) inform the Agency of any measures taken and report on the results of such measures.

Article 134

Role of the Commission

1. The Commission may, where it considers it appropriate and necessary:

(a) shall take into account the MSSG recommendations and implement the relevant measures;

(aa) shall take, if appropriate, any necessary actions within the limits of the powers conferred on the Commission, including the development of guidelines to improve the security of supply;

(ab) may foster coordination of Member State measures aimed at ensuring security of

supply within their territories.

(b) shall inform the MSSG of those measures actions taken by the Commission.

(c) may request the MSSG to provide information or an opinion or further recommendations referred to in Article 132(1).

2. If necessary to ensure the smooth functioning of the internal market, the Commission

may, taking into consideration the information or the opinion,recommendations referred to in paragraph 1, or MSSGdraw up recommendations, may decide to adopt an implementing act for national measures to improve security of supply. The implementing act may impose contingency stock requirements of active pharmaceutical ingredient or finished dosage forms, or other relevant measures required to improve security of supply, on marketing authorisation holders, wholesale distributors or other relevant entities of

medicinal products included in the Union list of critical medicinal products.

2a. The adoption of these recommendations shall be limited to cases where the Commission

identifies a highly likely disruption of the internal market which strongly and negatively affects the security of supply of critical medicinal products. They shall take into account:

(a) the severity of the disruption of the internal market, or the risk thereof;

(b) the causes of the disruption to security of supply;

(c) the existence of other available measures under this Regulation to mitigate or resolve the disruption;

(d) the gravity and scope of risks to public health.

(e) The recommendations shall be based on objective, factual, measurable and substantiated data, including from the Agency and its preparatory bodies, national competent authorities and relevant economic operators.

3. The implementing act referred to in paragraph 2 shall be adopted in accordance with the

examination procedure referred to in Article 173(2).

CHAPTER XI EUROPEAN MEDICINES AGENCY

Section 1

Tasks of the Agency

Article 135

Establishment

The functioning of The European Medicines Agency is hereby established by Regulation (EC) No 726/2004 (the ‘‘the Agency’) shall continue in accordance with the present Regulation..

The functioning of the Agency, as previously established in Regulation (EC) 726/2004 shall continue in accordance with the provisions set out in this Regulation.

The Agency shall be responsible for coordinating the existing scientific resources put at its disposal by Member States for the evaluation, supervision and pharmacovigilance of medicinal products for human use and of veterinary medicinal products.

Article 136 Legal status

1. The Agency shall have legal personality.

2. In each of the Member States, the Agency shall enjoy the most extensive legal capacity

accorded to legal persons under their laws. It may, in particular, acquire or dispose of movable and immovable property, and be party to legal proceedings.

3. The Agency shall be represented by an Executive Director.

Article 137

Seat

The seat of the Agency shall be established in Amsterdam, the Netherlands.

Article 138

Objectives and tasks of the Agency

1. The Agency shall provide the Member States and the institutions of the Union with the

best possible scientific opinion on any question relating to the evaluation of the quality, safety and efficacy of medicinal products for human use, veterinary medicinal products, which is referred to it in accordance with the Union legal acts relating to medicinal products for human use or veterinary medicinal products.

The Agency, acting particularly through its Committees, shall carry out the following tasks:

(a) coordinating the scientific evaluation of the quality, safety and efficacy of medicinal products for human use, which are subject to Union marketing authorisation procedures;

(b) coordinating the scientific evaluation of the quality, safety and efficacy of veterinary medicinal products, which are subject to Union marketing authorisation procedures in accordance with Regulation (EU) 2019/6 and the performance of other tasks set out in Regulation (EU) 2019/6 and Regulation (EC) 470/2009;

(c) transmitting on request and making publicly available assessment reports, summaries of product characteristics, labels and, package leaflets and AMR awareness cards, where applicable, for the medicinal products for human use;

(ca) coordinating the environmental risk assessment and where relevant providing scientific opinions related to medicinal products for human use which are subject to Union marketing authorisation procedures in accordance with this Regulation or investigational medicinal products for human use containing or consisting of genetically modified organisms (GMOs);

(d) coordinating the monitoring of medicinal products for human use which have been authorised in the Union and providing advice on the measures necessary to ensure the safe and effective use of those products, in particular by coordinating the evaluation and implementation of pharmacovigilance obligations and systems and the monitoring of such implementation;

(e) ensuring the collation and dissemination of information on suspected adverse reactions to medicinal products for human use authorised in the Union by means of databases that are permanently accessible to all Member States;

(f) assisting Member States with the rapid communication of information on pharmacovigilance concerns relating to medicinal products for human use to healthcare professionals and coordinating the safety announcements of the competent authorities of the Member States;

(g) distributing appropriate information on pharmacovigilance concerns relating to medicinal products for human use to the general public, in particular by setting up and maintaining a European medicines web-portal;

(h) coordinating, as regards medicinal products for human use and veterinary medicinal products, the verification of compliance with the principles of good manufacturing practice, good laboratory practice, good clinical practice, good pharmacovigilance practice and, as regards medicinal products for human use, the verification of compliance with pharmacovigilance obligations;

(i) ensuring the secretariat of the Joint Audit Programme referred to in Article 54;

(j) upon request, providing technical and scientific support in order to improve cooperation between the Union, its Member States, international organisations and third countries on scientific and technical issues relating to the evaluation and monitoring of medicinal products for human use and of veterinary medicinal products, in particular in the framework of the International Council for

Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and the Veterinary International Conference on Harmonization;

(k) coordinating as referred to in Article 53 a structured cooperation on inspections in third countries between Member States, the European Directorate for the Quality of Medicines and Healthcare of the Council of Europe, the World Health Organization or trusted international authorities, by means of international inspection programmes;

(l) conducting or participating in inspections with Member States to verify the compliance with the principles of good manufacturing practice, including issuing GMP certificates and good clinical practice at the request of the Supervisory Authority referred to inin accordance with Article 50(2) whenever additional capacity is needed to carry out inspection of Union interest including in response of public health emergencies;52.

(m) recording the status of marketing authorisations for medicinal products for human use granted in accordance with Union marketing authorisation procedures;

(n) creating and maintaining a user-friendlya database on medicinal products for human use, to be accessible to the general public, and ensuring that it is updated, and managed independently of pharmaceutical companies; the database is to facilitate the search for product information already authorised for, including the electronic version of the package leafletsleaflet; it is to include a section on medicinal products for human use authorised for the treatment of children; the information provided to the general public is to be worded in an appropriate and comprehensible manner;

(o) assisting the Union and its Member States in the provision of information to healthcare professionals and the general public about medicinal products for human use and about veterinary medicinal products evaluated by the Agency;

(p) providingcoordinating the provision of scientific advice to undertakings or, as relevant, not-for-profit entities on the conduct of the various tests and trials necessary to demonstrate the quality, safety and efficacy of medicinal products for human use;

(q) supporting, through enhanced scientific and regulatory advice, the development of medicinal products which are of major interest from the point of view of public health, including antimicrobial resistance, and in particular from the viewpoint of therapeutic innovation and unmet medical needs (priority medicines);

(r) checking that the conditions laid down in Union legal acts on medicinal products for human use and on veterinary medicinal products and in the marketing authorisations are met in the case of parallel distribution of medicinal products for human use and on veterinary medicinal products authorised in accordance with this Regulation or, as applicable, Regulation (EU) 2019/6;

(s) drawing up, at the Commission’s request, any other scientific opinion concerning the evaluation of medicinal products for human use and of veterinary medicinal products or the starting materials used in the manufacture of medicinal products for human use;

(t) with a view to the protection of public health, compiling scientific information concerning pathogenic agents which might be used in biological warfare, including the existence of vaccines and other medicinal products for human use and other veterinary medicinal products available to prevent or treat the effects of such agents;

(u) coordinating the supervision of the quality of medicinal products for human use and of veterinary medicinal products placed on the market by requesting testing of compliance with their authorised specifications to the European Directorate for the Quality of Medicines and Healthcare that coordinates with the Official Medicines Control Laboratory or by a laboratory that a Member State has designated for that purpose. The Agency and the European Directorate for the Quality of Medicines and

Healthcare shall enter into a written contract for the provision of services to the

Agency under this subparagraph;

(v) forwarding annually to the budgetary authority aggregated information on procedures for medicinal products for human use and veterinary medicinal products;

(w) taking decisions as referred to in Article 6(5) of [revised Directive 2001/83/EC];

(x) contributing to the joint reporting with the European Food Safety Authority and European Centre for Disease Prevention and Control on the sales and use of antimicrobials in human and veterinary medicine as well as on the situation as regards antimicrobial resistance in the Union based on contributions received by

Member States, taking into account the reporting requirements and periodicity in Article 57 of Regulation (EU) 2019/6. Such joint reporting shall be carried out at least every three years;

(y) adopting a decision granting, refusing or transferring or extending the validity of an orphan designation;

(z) adopting decisions on paediatric investigation plans, their modifications, waivers and deferrals in relation to medicinal products;

(za) providing regulatory support and coordinating the provision of scientific advice for the development of orphan and paediatric medicinal products;

(zb) coordinating assessment of and certifying quality master files for medicinal products for human use as well as, where necessary, coordinating inspections of manufacturers applying for or holding a certificate for a quality master file;

(zc) establishing a mechanism of consultation of authorities or bodies active along the life cycle of medicinal products for human use for exchange of information and pooling of knowledge on general issues of scientific or technical nature related to the tasks of the Agency, notably where relevant with the SoHO Coordination Board, Medical Devices Coordination Group, the Member State Coordination Group on Health

Technology Assessment and national pricing and reimbursement authorities;

(zd) developing coherent scientific assessment methodologies in the fields falling within its mission;

(ze) (ze) cooperating with EU decentralised agencies and other scientific authorities and bodies established under Union law, notably the European Chemicals Agency, the European Food Safety Authority, the European Centre for Disease Prevention and Control and the European Environment Agency as regards the scientific assessment of relevant substances, exchange of data including submission of data to the

Common Data Platform on Chemicals pursuant to [add final OJ reference for COM(2023) 779 final] and information and development of coherent scientific methodologies, including replacing, reducing or refining animal testing, and, where possible, prioritising replacement strategies such as non-animal in vitro and in silico approaches, taking into account the specificities of the assessment of medicinal products;

(zf) coordinating the monitoring and management of critical shortages of medicinal products included in the list referred to in Article 123(1);

(zg) coordinating the identification and management of the Union list of critical medicinal products referred to in Article 131;

(zh) supporting the Commission and Member States in relation to critical shortages and critical medicinal products through the working party referred to in Article 121(1), point (c), and the MSSG in their tasks in relation to critical shortages and critical medicines;

(zi) providing regulatory support and scientific advice for, and facilitate the development, validation and regulatory uptake of new-approach methodologies that replace the use of animals in testing and report regularly on best practices and key observations on the replacement, reduction and refinement of animal testing submitted by applicants;

(zj) facilitating joint non-clinical studies between applicants and holders to avoid unnecessary duplication of tests using live animals;

(zk) facilitating data sharing of results from non-clinical studies on live animals;

(zl) drawing up scientific guidelines to facilitate the implementation of the definitions established in this Regulation and in [revised Directive 2001/83], and for the environmental risk assessment of medicinal products for human use, in consultation with the Commission and the Member States;

(zla) support regulatory decision making on the development, authorisation and supervision of medicinal products by accessing and analysing health data,

including real world data, where appropriate;

(zlb) where scientific guidelines are provided, the Agency shall ensure that such

guidelines are kept up-to-date and based on the latest scientific developments.

2. The database provided for in paragraph 1, point (n), shall include all medicinal products for

human use authorised in the Union together with the summaries of product characteristics, the package leaflet and the information shown on the labelling. Where relevant, it shall include the electronic links to the dedicated webpages where the marketing authorisation holders have reported the information pursuant to Article 40(4), point (b), and Article 57 of [revised Directive 2001/83/EC] and to Article 40(4), point (b).

For the purposes of the database, the Agency shall set up and maintain a list of all medicinal products for human use authorised in the Union. To this effect:

(a) the Agency shall make public a format for the electronic submission of information on medicinal products for human use;

(b) marketing authorisation holders shall electronically submit to the Agency information on all medicinal products for human use authorised in the Union and shall inform the Agency of any new or varied marketing authorisations granted in the Union, using the format referred to in point (a).

(ba) marketing authorisation holders of centrally authorised medicinal products shall electronically submit to the Agency information concerning the Member States in which the medicinal products have been placed on the market.

If a competent authority of a Member State identifies incorrect data in the database against the data they keep regarding medicinal products authorised according to [revised Directive 2001/83/EC], it shall inform the Agency.

Where appropriateavailable, the database shall also include references to clinical trials currently being carried out or already completed, contained in the clinical trials database provided for in Article 81 of Regulation (EU) No 536/2014.

The Commission is empowered to adopt delegated acts in accordance with Article 175, to supplement this Regulation by adding further information contained in the database, as well as by specifying the rules of updating and maintaining the data in the database. When adopting the delegated act, the Commission shall take into account internationally recognised standards.

Article 139

Coherence of scientific opinions with other Union bodies

1. The Agency shall take the necessary and appropriate measures to monitor and identify at

an early stage any potential source of divergence between its scientific opinions and the scientific opinions issued by other Union bodies and, agencies or independent scientific committees carrying out similar tasks in relation to issues of common concern.

2. Where the Agency identifies a potential source of divergence, it shall contact the Union

body,body or agency or independent scientific committee in question to ensure that all relevant scientific or technical information is shared and in order to identify potentially contentious scientific or technical issues.

3. Where a substantive divergence over scientific or technical issues is identified and the

body concerned is a Union Body or Agency or a scientific committee, the Agency and the body or independent scientific committee concerned shall cooperate to resolve the divergence, and inform the Commission without undue delay and the Commission shall facilitate to resolve the divergence in question.

4. The Commission may ask the Agency to conduct an assessment as regards specifically the

use of the substance concerned in medicinal products and in veterinary medicinal products. The Agency shall make public its assessment stating clearly the reasons for its specific scientific conclusions.

5. To enable coherence between scientific opinions and to avoid duplication of tests, the Agency shall make arrangements with other bodies or agencies established or designated under Union law for cooperation on scientific assessments and methodologies. The Agency shall also make arrangements for the exchange of data and information on relevant substances with the Commission, Member States’ authorities and other Union Agencies, in particular for environmental risk assessments, non-clinical studies and, when applicable, maximum residue limits.

These arrangements shall seek to ensure that exchanges of data and information are made available in electronic formats and shall protect the commercially confidential nature of the information exchanged and be without prejudice to the provisions on regulatory protection.

Article 140

Scientific opinions in the context of international collaboration

1. The Agency may give a scientific opinion, in particular in the context of cooperation with

the World Health Organization, for the evaluation of certain medicinal products for human use intended for markets outside the Union. For this purpose, an application shall be submitted to the Agency in accordance with the provisions of Article 6. Such application may be submitted and assessed together with a marketing authorisation application or any subsequent variation for the EU. The Agency may, after consulting the World Health Organization, and as appropriate other relevant organisations, draw up a scientific opinion in accordance with Articles 6, 10 and 12. The provisions of Article 13 shall not apply.

2. The Agency shall establish specific procedural rules for the implementation of

paragraph 1, as well as for the provision of scientific advice.

Article 141

International regulatory cooperation

1. In so far as is necessary in order to achieve the objectives set out in this Regulation, and

without prejudice to the respective competences of the Member States and the institutions of the Union, the Agency may cooperate with the competent authorities of third countries and/or with international organisations.

To this end, the Agency may, subject to prior approval by the Commission, establish working arrangements with the authorities of third countries and international organisations, with regard to:

(a) the exchange of information, including non-public information, where relevant jointly with the Commission;

(b) sharing of scientific resources and expertise, with a view to facilitating collaboration, while maintaining independent assessment in full compliance with the provisions of this Regulation and [revised Directive 2001/83/EC] and under conditions determined beforehand by the Management Board, in agreement with the Commission;

(c) the participation in certain aspects of the Agency's work, under conditions determined beforehand by the Management Board, in agreement with the Commission.

These arrangements shall not create legal obligations incumbent on the Union and its Member States.

2. The arrangements and cooperation carried out by the Agency shall ensure that it is not

seen asnot amount to representing thea Union position to an outside audience or as to committing the Union to international cooperation.

3. The Commission may, in agreement with the Management Board and the relevant

committee, invite representatives of international organisations with an interest in the harmonisation of technical requirements applicable to medicinal products for human use and to veterinary medicinal products to participate as observers in the work of the Agency.

The conditions for participation shall be determined in advance by the Commission.

Section 2

Structure and operation

Article 142

Administrative and management structure

The Agency shall comprise:

(a) a Management Board, which shall exercise the functions set out in Articles 143, 144 and 154.

(b) an Executive Director, who shall exercise the responsibilities set out in Article 145;

(c) a Deputy Executive Director who shall exercise the responsibilities set out in Article

145(7);

(d) the Committee for Medicinal Products for Human Use;

(e) the Pharmacovigilance Risk Assessment Committee;

(f) the Committee for Veterinary Medicinal Products set up pursuant to Article 139(1) of

Regulation (EU) 2019/6;

(g) the Herbal Medicinal Products working group set up pursuant to Article 141 of [revised

Directive 2001/83/EC];

(h) the Emergency task force set up pursuant to Article 15 of Regulation (EU) 2022/123;

(i) the MSSG set up pursuant to Article 3 of Regulation (EU) 2022/123;

(j) the Medical Device Shortages Steering Group, set up pursuant to Article 21 of Regulation

(EU) 2022/123;

(k) the inspection working group;

(l) a Secretariat, which shall provide technical, scientific and administrative support to all

bodies of the Agency and ensure appropriate coordination between them, and which shall provide technical and administrative support for the coordination group referred to in

Article 37 of [revised Directive 2001/83/EC] and for the coordination group referred to in Article 142 of Regulation (EU) 2019/6 and ensure appropriate coordination between it and the Committees. It shall also undertake the work required of the Agency under the procedures for the assessment and preparations of decisions for paediatric investigation plans, waivers, deferrals or orphan designations.

Article 143

Management Board

1. The Management Board shall be composed of one representative from each Member State,

two representatives of the Commission and two representatives of the European Parliament, all with voting rights.

In addition, two representatives of patients' organisations, one representative of doctors'healthcare professionals’ organisations and one representative of veterinarians' organisations, all with voting rights, shall be appointed by the Council in consultation with the European Parliament on the basis of a list drawn up by the Commission which includes appreciably more names than there are posts to be filled. The list drawn up by the Commission shall be forwarded to the European Parliament, together with the relevant background documents. As quickly as possible, and at the latest within three months of notification, the European Parliament may submit its views for consideration to the Council, which shall then appoint these representatives to the Management Board.

The members of the Management Board shall be appointed in such a way as to guarantee the highest levels of specialist qualifications, a broad spectrum of relevant expertise and the broadest possible geographic spread within the European Union.

2. Members of the Management Board and their alternates shall be appointed on the basis of

their knowledge, recognised experience and commitment in the field of medicinal products for human or veterinary use, taking into account relevant managerial, administrative and budgetary expertise [which are to be used to further the objectives of this Regulation].

All parties represented in the Management Board shall make efforts to limit turnover of their representatives, in order to ensure continuity of the work of the Management Board. All parties shall aim to achieve a gender balanced representation between men and women on the Management Board.

3. Each Member State and the Commission shall appoint their members of the Management Board as well as an alternate who will replace the member in their absence and vote on their behalf.

4. The term of office for members and their alternates shall be four years. That term shall be

extendable.

5. The Management Board shall elect a chairperson and a Deputy chairperson from among its members.

The chairperson and the Deputy chairperson shall be elected by a majority of two-thirds of the members of the Management Board with voting rights.

The Deputy chairperson shall automatically replace the chairperson if they are prevented from attending to their duties.

The term of office of the chairperson and the deputy chairperson shall be four years. The term of office may be renewed once. If however, their membership of the Management Board ends at any time during their term of office, their term of office shall automatically expire on that date.

6. Without prejudice to paragraph 5 and Article 144, points (e) and (g), the Management Board shall take decisions by absolute majority of its members with voting rights.

7. The Management Board shall adopt its rules of procedure.

8. The Management Board may invite the chairpersons of the scientific committees to attend

its meetings, but they shall not have the right to vote.

9. The Management Board may invite any person whose opinion may be of interest to attend

its meetings as an observer.

10. The Management Board shall approve the annual work programme of the Agency

programme and forward it to the European Parliament, the Council, the Commission and the Member States.

11. The Management Board shall adopt the annual report on the Agency's activities and

forward it by 15 June of each year at the latest to the European Parliament, the Council, the Commission, the European Economic and Social Committee, the Court of Auditors and the Member States.

Article 144

Tasks of the Management Board

The Management Board shall:

(a) give the general orientations for the Agency's activities;

(b) adopt an opinion on the rules of procedures of the Committee for Medicinal Products for

Human Use (Article 148) and the Committee for Veterinary Medicinal Products (Article

139 of Regulation (EU) 2019/6);

(c) adopt procedures for the performance of scientific services regarding medicinal products

for human use (Article 152);

(d) appoint the Executive Director and the Deputy Executive Director, and where relevant

extend their term of office or remove them from office, in accordance with Article 145;

(e) adopt yearly the Agency’s draft single programming document before its submission to the Commission for its opinion, and the Agency's single programming document by a majority of two-thirds of members entitled to vote and in accordance with Article 154;

(f) assess and adopt a consolidated annual activity report on the Agency's activities and send it

by 1 July of each year to the European Parliament, the Council, the Commission and the

Court of Auditors. The consolidated annual activity report shall be made public;

(g) adopt the annual budget of the Agency by a majority of two-thirds of the members entitled

to vote and in accordance with Article 154;

(h) adopt the financial rules applicable to the Agency in accordance with Article 155;

(ha) adopt procedures for the reimbursement by the Agency of expenses of members of bodies

of the Agency, including civil society representatives;

(i) exercise, with respect to the staff of the Agency, the powers conferred by Regulation No 31 by the Council of the European Economic Community, and Regulation No 11 and by the Council of the European Atomic Energy Community (‘Staff Regulations’ and

‘Conditions of Employment of Other Servants’) on the Appointing Authority and on the Authority Empowered to Conclude a Contract of Employment (‘the appointing authority powers’);

(j) adopt implementing rules for giving effect to the Staff Regulations and the Conditions of

Employment of Other Servants in accordance with Article 110 of the Staff Regulations;

(k) develop contacts with stakeholders and stipulate the conditions applicable as mentioned in

Article 163;

(l) adopt an anti-fraud strategy, proportionate to risks of fraud taking into account the costs

and benefits of the measures to be implemented;

(m) ensure adequate follow-up to findings and recommendations stemming from the internal or

external audit reports and evaluations, as well as from investigations of the European Antifraud Office (‘OLAF’) and the European Public Prosecutor’s Office (‘EPPO’);

(n) adopt rules to ensure the availability to the public of information concerning the

authorisation or supervision of medicinal products for human use as mentioned in Article 166;

(o) adopt an efficiency gains and synergies strategy;

(p) adopt a strategy for cooperation with third countries or international organisations within

the limits of the Agency’s mandate;

(q) adopt and implement a strategy for the organisational management and internal control

systems. including on the operation of the Committees, scientific working parties and scientific advisory groups in relation to efficiency as well as scientific expertise and

geographic representation of experts;

(qa) assess and adopt a report regarding the performance of the strategy referred in point q

four and ten years following the entry into application of this Regulation and send it to the European Parliament, the Council and the Commission. The report shall, amongst others, contain quantitative data on the involvement of scientific expertise related to marketing authorisation application assessment and the provision of regulatory and scientific advice for paediatric and orphan medicinal products, ATMPs and evaluation of environmental risks assessment as well as on the work-share and task distribution between experts nominated by the national competent authorities and external experts. Subsequent reports shall be prepared to support the evaluation referred to in Article 170(1).

The Management Board shall adopt, in accordance with Article 110 of the Staff Regulations, a decision based on Article 2(1) of the Staff Regulations and on Article 6 of the Conditions of

Employment of Other Servants, delegating relevant appointing authority powers to the Executive Director and Deputy Executive Director and defining the conditions under which that delegation of powers can be suspended. The Executive Director shall be authorised to sub-delegate those powers.

Where exceptional circumstances so require, the Management Board may, by way of a decision, temporarily suspend the delegation of the appointing authority powers to the Executive Director and those sub-delegated by the latter and exercise them itself or delegate them to one of its members or to a staff member other than the Executive Director.

Article 145

Executive Director

1. The Executive Director shall be engaged as a temporary agent of the Agency under Article 2, point (a), of the Conditions of Employment of Other Servants.

2. The Executive Director shall be appointed by the Management Board from a list of

candidates proposed by the Commission following an open and transparent selection procedure.

For the purpose of concluding the contract with the Executive Director, the Agency shall be represented by the Chairperson of the Management Board.

Before appointment, the candidate nominated by the Management Board shall be immediately invited to make a statement to the European Parliament and to answer any questions put by its Members.

3. The term of office of the Executive Director shall be five years. By the end of that period

the Commission shall undertake an assessment that takes into account an evaluation of the Executive Director's performance and the Agency's future tasks and challenges.

4. The Management Board, acting on a proposal from the Commission that takes into account

the assessment referred to in paragraph 3, may extend the term of office of the Executive Director once, for no more than five years.

An Executive Director whose term of office has been extended may not participate in another selection procedure for the same post at the end of the overall period.

5. The Executive Director may be removed from office only upon a decision of the Management Board acting on a proposal from the Commission.

6. The Management Board shall reach decisions on appointment, extension of the term of

office or removal from office of the Executive Director on the basis of a two-thirds majority of its members with voting rights.

7. The Executive Director will be assisted by a Deputy Executive Director. If the Executive Director is absent or indisposed, the Deputy Executive Director shall take their place.

8. The Executive Director shall manage the Agency. The Executive Director shall be

accountable to the Management Board. Without prejudice to the powers of the

Commission and of the Management Board, the Executive Director shall be independent in the performance of their duties and shall neither seek nor take instructions from any government or from any other body.

9. The Executive Director shall report to the European Parliament on the performance of their

tasks when invited to do so. The Council may invite the Executive Director to report on the performance of those tasks.

10. The Executive Director shall be the legal representative of the Agency. The Executive Director shall be responsible for:

(a) the day-to-day administration of the Agency;

(b) implementing decisions adopted by the Management Board;

(c) managing all the Agency resources necessary for conducting the activities of the Committees referred to in Article 142, including making available appropriate scientific and technical support to those Committees, and for making available appropriate technical support to the coordination group referred to in Article 37 of

[revised Directive 2001/83/EC] and to the coordination group referred to in Article 142 of Regulation (EU) 2019/6;

(d) ensuring that the time-limits laid down in Union legal acts for the adoption of opinions by the Agency are complied with;

(e) ensuring appropriate coordination between the Committees referred to in Article 142 and, where necessary, between those Committees, the coordination group referred to in Article 37 of [revised Directive 2001/83/EC] and the coordination group referred to in Article 142 of Regulation (EU) 2019/6; or other working groups of the Agency;

(f) the preparation of the draft statement of estimates of the Agency's revenue and expenditure, and execution of its budget;

(g) the preparation of the draft single programming document and the submission it to the Management Board after consulting the Commission;

(h) implementing the single programming document and report to the Management

Board on its implementation;

(i) preparing the Agency’s consolidated annual activity report on the Agency's activities and presenting it to the Management Board for assessment and adoption;

(j) all staff matters;

(k) providing the secretariat for the Management Board;

(l) without prejudice to the competences of OLAF and EPPO, protecting the financial interests of the Union by applying preventive measures against fraud, corruption and any other illegal activities, by effective checks and, if irregularities are detected, by recovering amounts wrongly paid and, where appropriate, by imposing effective, proportionate and dissuasive administrative and financial penalties;

(m) reporting, on the basis of key performance indicators agreed by the Management board, on the IT infrastructure developed by the Agency by means of implementation of legislation, in term of timing, budgetary compliance and quality.

11. Each year the Executive Director shall submit a draft report covering the activities of the

Agency in the previous year and a draft work programme for the coming year to the Management Board for approval, making a distinction between the Agency's activities concerning medicinal products for human use, those concerning herbal medicinal products and those concerning veterinary medicinal products.

The draft report covering the activities of the Agency in the previous year shall include information about the number of applications evaluated by the Agency, the time taken for completion of the evaluation, and the medicinal products for human use and veterinary medicinal products authorised, rejected or withdrawn.

Article 145a

Deputy Executive Director

On the proposal of the Executive Director, the Management Board shall appoint the Deputy Executive Director. The Deputy Executive Director shall be appointed on the grounds of merit and appropriate administrative and management skills, including relevant professional experience. The Executive Director shall, following consultation with the Commission, propose two candidates for the post of Deputy Executive Director. The Management Board shall take its decision by a two-thirds majority of its members with a right to vote. The Management Board shall have the power to dismiss the Deputy Executive Director by means of a decision adopted by a two-thirds majority of its members with a right to vote.

The term of office of the Deputy Executive Director shall be five years. The Management Board may extend that term once, for a period of no more than five years. The Management Board shall adopt such a decision by a two-thirds majority of its members with the right to vote.

Article 146

Scientific Committees – General provisions

1. The scientific committees shall be responsible for providing the scientific opinions or

recommendations of the Agency, each within their own spheres of competence, and shall have the possibility, where necessary of organising public hearings.

2. The membership of the scientific committees shall be made public. When each

appointment is published, the professional qualifications of each member shall be specified.

3. The Executive Director of the Agency or their representative and representatives of the Commission shall be entitled to attend all meetings of the scientific committees referred to in Article 142, working parties and scientific advisory groups and all other meetings convened by the Agency or its scientific committees.

4. Members of the scientific committees and experts responsible for evaluating medicinal

products and nominated by Member States shall rely on the scientific evaluation and resources available to national competent authorities responsible for marketing authorisation, and on external experts proposed by Member States or selected by the Agency. Each competent national authority shall monitor the scientific level and independence of the evaluation carried out and facilitate the activities of nominated members of the Committees and experts. Member States shall refrain from giving those members and experts any instruction which is incompatible with their own individual tasks or with the tasks and responsibilities of the Agency.

5. The members of the scientific committees may be accompanied by experts in specific

scientific or technical fields.

6. When preparing any opinion or recommendation, the scientific committees shall use their

best endeavours to reach a scientific consensus. If such a consensus cannot be reached, the opinion shall consist of the position of the majority of members and divergent positions, with the grounds on which they are based.

7. The Committee for Medicinal Products for Human Usescientific committees may, if they

consider it appropriate, seek guidance on important questions of a general scientific or ethical nature.

8. The scientific committees and any scientific working parties and scientific advisory

groups established in accordance with this Article 150 shall in general matters establish contacts, on an advisory basis, with parties concerned with the use of medicinal products for human use, in particular patient and consumer organisations and healthcare professionals’ associations. For that purpose working groups of patient and consumer organisations and healthcare professionals’ associations shall be established by the Agency. They shall ensure a fair representation of healthcare professionals, patients and consumers covering a wide range of experience and disease areas, including orphan, paediatric and geriatric diseases and advanced therapy medicinal products, and a broad geographical range.

Rapporteurs appointed by the scientific committees may, on an advisory basis, establish contacts with representatives of patient organisations and healthcare professionals’ associations relevant to the therapeutic indication of the medicinal product for human use.

9. The Committee for Veterinary Medicinal Products shall operate in accordance with Regulation (EU) No 2019/6 and paragraphs 1, 2 and 3.

Article 147

Impartiality and conflict of interest

1. Members of the Management Board, members of the committees, rapporteurs and, experts

and inspectors of the Agency shall not have financial or other interests in the pharmaceutical and medical devices industry which could affect their impartiality. They shall undertake to act in the public interest and in an independent manner, and shall make an annual declaration of their financial and other interests. All including indirect interests which could relate to this industry. The annual declarations shall be entered in a register heldmade publicly available by the Agency which is accessible to the public, on request, at the Agency's offices..

The Agency's code of conduct shall provide for the implementation of this Article with particular reference to the acceptance of gifts.

2. Members of the Management Board, members of the committees, rapporteurs and experts

who participate in meetings or working groups of the Agency shall declare, at each meeting, any specific interests which could be considered to be prejudicial to their independence or impartiality with respect to the items on the agenda. These declarations shall be made available to the public.

3. Where a declared interest is considered by the Agency to be prejudicial to the

independence or impartiality with respect to an item on the agenda, the member of the Management Board, member of the committee or expert concerned shall not have any involvement and not take part in the discussions or decision-making with respect to that

item.

4. By way of derogation from paragraphs 1 and 3, experts who declare an interest that

would prevent them from participating in the work of the Agency’s scientific committees and other bodies may in exceptional and justified cases be called upon, in the interest of public health, to provide written or oral observations. These observations shall be

separated from the discussion or decision-making with respect to the concerned item.

5. The Agency shall establish procedures with regard to the application of the provisions

on conflict of interest and impartiality, to be adopted by its Management Board.

6. The Executive Director shall after leaving the service continue to be bound by the rules

of the Staff Regulations as regards the acceptance of certain appointments or benefits and engaging in an occupational activity for the period referred to in the staff regulations. Prior to engaging in any such activity, the former executive director shall inform the Agency and its Management Board to verify whether those actions are in line with the Staff Regulations and its implementing rules adopted in accordance with Article 144.

Article 148

Committee for Medicinal Products for Human Use activities

1. The Committee for Medicinal Products for Human Use shall be responsible for drawing

up the opinion of the Agency on any matter concerning the admissibility of the files submitted in accordance with the centralised procedure, the granting, variation, suspension or revocation of an authorisation to place a medicinal product for human use on the market in accordance with the provisions of this Chapter, and pharmacovigilance and scientific advice. For the fulfilment of its pharmacovigilance tasks, including the approval of risk management systems and monitoring their effectiveness provided for under this Regulation, the Committee for Medicinal Products for Human Use shall rely on the scientific assessment and recommendations of the Pharmacovigilance Risk Assessment Committee referred to in Article 142, point (e).

2. In addition to their task of providing objective scientific opinions to the Union and Member States on the questions which are referred to them, the members of the Committee for Medicinal Products for Human Use shall ensure that there is appropriate coordination between the tasks of the Agency and the work of competent national authorities, including the consultative bodies concerned with the marketing authorisation.

3. The Committee for Medicinal Products for Human Use shall be composed of the

following:

(a) one member and one alternate member appointed by each Member State, in accordance with paragraph 6;

(b) fourtwo members and onetwo alternate members appointed by the Commission, on the basis of a public call for expressions of interest, after consulting the European

Parliament, in order to represent healthcare professionals’ organisations;

(c) fourtwo members and fourtwo alternate members appointed by the Commission, on the basis of a public call for expressions of interest, after consulting the European Parliament, in order to represent patient organisations.

4. The Committee for Medicinal Products for Human Use may co-opt a maximum of five

seven additional members chosen on the basis of their specific scientific competence. Those members shall be appointed for a term of three years, which may be renewed, and shall not have alternates.

With a view to the co-opting of such members, the Committee for Medicinal Products for Human Use shall identify the specific complementary scientific competence of the additional member or members. Co-opted members shall be chosen among experts nominated by Member States or the Agency.

4a Members appointed under paragraph 3, point (b), shall jointly be entitled to one vote,

and members appointed under paragraph 3, point (c), shall jointly be entitled to one vote.

5. The alternates shall represent and vote for the members in their absence and may also be

appointed to act as rapporteurs in accordance with Article 152.

Members and alternates shall be chosen for their role and experience in the evaluation of medicinal products for human use as appropriate and shall represent the competent authorities of the Member States.

6. The members and alternate members of the Committee for Medicinal Products for Human Use shall be appointed on the basis of their relevant expertise in the assessment of medicinal products which should cover all types of medicinal products covered by [revised Directive 2001/83/EC] and this Regulation and which include medicinal products for rare and paediatric diseases, advanceadvanced therapy medicinal products, biological and biotechnological products, in order to guarantee the highest levels of specialist qualifications and a broad spectrum of relevant expertise. This expertise shall also cover the environmental risk assessment. The Member States shall cooperate in order to ensure that the final composition of the Committee for Medicinal Products for Human Use provides appropriate and balanced coverage of all scientific areas relevant to its tasks taking into account scientific developments and new types of medicinal products. For this purpose, Member States shall liaise with the Management Board and the Commission.

7. The members and alternate members of the Committee for Medicinal Products for Human Use shall be appointed for a term of theethree years, which may be renewed following the procedures referred to in paragraph 6. The Committee shall elect its chairperson and vicechairperson from among its members for a term of 3 years, which may be prolonged once.

8. The Committee for Medicinal Products for Human Use shall establish its own rules of

procedure.

These rules shall, in particular, lay down:

(a) procedures for appointing and replacing the chairperson;

(b) procedures relating to working parties and scientific advisory groups; and

(c) a procedure for the urgent adoption of opinions, particularly in relation to the provisions of this Regulation on market surveillance and pharmacovigilance.

They shall enter into force after receiving a favourable opinion from the Commission and the Management Board.

Article 149

Pharmacovigilance Risk Assessment Committee activities

1. The mandate of the Pharmacovigilance Risk Assessment Committee shall cover all aspects

of the risk management of the use of medicinal products for human use including the detection, assessment, minimisation and communication relating to the risk of adverse reactions, having due regard to the therapeutic effect of the medicinal product for human use, the design and evaluation of post-authorisation safety studies and pharmacovigilance audit.

2. The Pharmacovigilance Risk Assessment Committee shall be composed of the following:

(a) one member and one alternate member appointed by each Member State, in accordance with paragraph 3;

(b) six members appointed by the Commission, with a view to ensuring that the relevant expertise is available within the Committee, including clinical pharmacology and pharmacoepidemiology, on the basis of a public call for expressions of interest;

(c) two members and two alternate members appointed by the Commission, on the basis of a public call for expressions of interest, after consulting the European Parliament, in order to represent healthcare professionals;

(d) two members and two alternate members appointed by the Commission, on the basis of a public call for expressions of interest, after consulting the European Parliament, in order to represent patient organisations.

Members appointed under paragraph 2 (c) shall jointly be entitled to one vote and, members appointed under paragraph 2 (d) shall jointly be entitled to one vote

The alternate members shall represent and vote for the members in their absence. The alternate members referred to in point (a) may be appointed to act as rapporteurs in accordance with Article 152.

3. A Member State may delegate its tasks in the Pharmacovigilance Risk Assessment Committee to another Member State. Each Member State may represent no more than one other Member State.

4. The members and alternate members of the Pharmacovigilance Risk Assessment

Committee shall be appointed on the basis of their relevant expertise in pharmacovigilance matters and risk assessment of medicinal products for human use, in order to guarantee the highest levels of specialist qualifications and a broad spectrum of relevant expertise. For this purpose, Member States shall liaise with the Management Board and the Commission in order to ensure that the final composition of the Committee covers the scientific areas relevant to its tasks.

5. The members and alternate members of the Pharmacovigilance Risk Assessment Committee shall be appointed for a term of 3 years, which may be renewed following the procedures referred to in paragraph 1. The Committee shall elect its chairperson and vicechairperson from among its members for a term of three years, which may be prolonged once.

5a. The Pharmacovigilance Risk Assessment Committee shall establish its own rules of

procedure, laying down in particular:

(a) procedures for appointing and replacing the chairperson;

(b) procedures relating to working parties and scientific advisory groups; (c) a procedure for the urgent adoption of recommendations.

They shall enter into force after receiving a favourable opinion from the Commission and the Management Board.

Article 150

Scientific working parties and scientific advisory groups

1. The scientific committees referred to in Article 146 may establish scientific working

parties and scientific advisory groups in connection with the performance of their tasks.

The scientific committees may rely on scientific working parties for the performance of certain tasks. The scientific committees shall retain the final responsibility for the assessment or any scientific opinion related to these tasks.

Working parties established by the Committee for Veterinary Medicinal Products are governed by Regulation (EU) 2019/6.

2. The Committee for Human Medicinal Products shall establish for the evaluation of specific

types of medicinal products or treatments, working parties with scientific expertise in the fields of pharmaceutical quality, methodologies, non-clinical and clinical evaluations.

For the provision of scientific advice the Committee for Human Medicinal Products shall establish a scientific advice working party.

The Committee mayshall, where necessary, establish an Environmental Risk Assessment working party, working parties with scientific expertise on paediatric medicinal products and orphan medicinal products and other scientific working parties, as necessary..

3. The composition of the working party and the selection of members shall be based on the

following criteria:

(a) a high level of scientific expertise;

(b) meeting the needs for the specific multi-disciplinary expertise of the working party to which they will be appointed.

The majority of the members of the working parties shall consist of experts from the competent authorities of the Member States by ensuring the broadest possible geographical distribution. Where appropriate, the Committee for Human Medicinal Products may, following consultation with the Management Board, set a minimum number of experts from the competent authorities in a working party. Where a specific area for expertise can be fulfilled by an expert nominated by a competent authority of a Member State, this expert shall have priority over external experts.

3a. Representatives of patients, healthcare professionals and academia may as appropriate

and based on their expertise be included as members of the working parties.

4. Competent authorities of the Member States that are not represented in a working party

may request to attend meetings of working parties as an observer.

5. The Agency shall make documents discussed in working parties accessible to all

competent authorities of the Member States.

5a. The scientific committees may seek advice from scientific advisory groups in connection

with the evaluation of specific medicinal products and treatments.

6. When establishing working parties and scientific advisory groups, the scientific

committees shall in their rules of procedures provide for:

(a) the appointment of members of these working parties and scientific advisory groups on the basis of the lists of experts referred to in Article 151(2); and

(b) consultation of these working parties and scientific advisory groups.

Article 151

Scientific experts

1. The Agency or any of the committees referred to in Article 142 may use the services of

experts and service providers for the discharge of specific tasks for which they are responsible.

2. Member States shall transmit to the Agency the names of national experts with proven

experience in the evaluation of medicinal products for human use and veterinary medicinal products who, taking into account conflicts of interest pursuant to Article 147, would be available to serve on working parties or scientific advisory groups of any of the committees referred to in Article 142, together with an indication of their qualifications and specific areas of expertise.

3. Where necessaryappropriate, for the nomination of other experts the Agency mayshall

publish a call for expression of interest after endorsement by the Management Board of the necessary criteria and fields of expertise, in particular to ensure a high level of public health and animal protection.

The Management Board shall adopt the appropriate selection procedures on a proposal from the Executive Director.

4. The Agency shall establish and maintain a pool of accredited experts. That expert pool

shall include the national experts referred to in paragraph 2 and any other experts appointed by the Agency or the Commission, and shall be updated.

5. Accredited Experts shall have access to training provided by the Agency, as appropriate.

6. Rapporteurs of any of the committees referred to in Article 142 may use the services of

accredited experts for the fulfilment of their tasks in accordance with Article 152. Any remuneration of such accredited expert shall be deducted from the remuneration due to the rapporteurs. The use of the services of national experts referred to in paragraph 2 by rapporteurs shall be subject to the agreement of the relevant competent authorities. The Agency may facilitate those agreements in accordance with Article 152(2).

7. The remuneration of experts and service providers for services used by the Agency under

paragraph 1 shall be financed through the Agency’s budget, in accordance with the financial rules applicable to the Agency.

Article 152

Rapporteurship

1. Where, in accordance with this Regulation, any of the Committees referred to in Article 142 is required to evaluate a medicinal product for human use, it shall appoint, with the exception of members representing healthcare professionals’ organisations and patients organisations, one of its members to act as rapporteur, taking into account existing expertise in the Member State. The Committee concerned may appoint a second member to act as co-rapporteur.

A member of a Committee shall not be appointed rapporteur for a particular case if they declare, in accordance with Article 147 any interest that might be, or might be perceived as, prejudicial to the impartial assessment of that case. The Committee concerned may replace the rapporteur or co-rapporteur by another member at any time, if they are unable to fulfil their duties within the prescribed time limits, or if an actual or potential prejudicial interest is detected.

A rapporteur appointed for that purpose by the Pharmacovigilance Risk Assessment

Committee shall closely collaborate with the rapporteur appointed by the Committee for Medicinal Products for Human Use or the Reference Member State for the medicinal product for human use concerned.

When consulting the scientific advisory groups referred to in Article 150, the Committee shall forward to them the draft assessment report or reports drawn up by the rapporteur or the corapporteur. The opinion issued by the scientific advisory group shall be forwarded to the chairperson of the relevant committee in such a way as to ensure that the deadlines laid down in Article 6 are met.

The substance of the opinion shall be included in the assessment report published pursuant to Article 16(3).

2. Without prejudice to Article 151(7), the provision of services by rapporteurs or experts

shall be governed by a written contract between the Agency and the person concerned, or where appropriate between the Agency and its employer.

The person concerned, or their employer, shall be remunerated in accordance with [a scale of fees to be included inpursuant to the financial arrangements established by the Management Board/mechanism under the new fee legislation]Board in accordance with Regulation (EU) 2024/568 of the European Parliament and of the Council.

The first and second subparagraphs shall also apply:

(a) to the services provided by the chairpersons of the scientific committees of the

Agency; and

(b) to the work of rapporteurs in the coordination group referred to in Article 37 of [revised Directive 2001/83/EC] as regards the fulfilment of its tasks in accordance with Articles 108, 110, 112, 116 and 121 of [revised Directive 2001/83/EC].

Article 153

Methods to determine added therapeutic value

At the request of the Commission, the Agency shall, in respect of authorised medicinal products for human use, collect any available information on methods that Member States' competent authorities use to determine the added therapeutic value that any new medicinal product for human use provides.

Section 3

Financial provisions

Article 154

Adoption of the budget of the Agency

1. Estimates of all the revenue and expenditure of the Agency shall be prepared for each

financial year, corresponding to the calendar year, and shall be shown in the budget of the Agency.

2. The revenue and expenditure shown in the budget shall be in balance.

3. The Agency’s revenue shall consist of:

(a) a contribution from the Union;

(b) a contribution from third countries participating in the work of the Agency with which the Union has concluded international agreements for that purpose;

(c) fees paid by undertakings and entities not engaged in an economic activity:

(i) for obtaining and maintaining Union marketing authorisations for medicinal products for human use and for veterinary medicinal products and for other services provided by the Agency, as provided for in this Regulation and in

Regulation (EU) 2019/6; and

(ii) for services provided by the coordination group referred to in Article 37 of [revised Directive 2001/83/EC] as regards the fulfilment of its tasks in accordance with Articles 108, 110, 112, 116 and 121 of [revised Directive

2001/83/EC];

(d) charges for other services provided by the Agency;

(e) Union funding in the form of contribution agreements or grants for participation in research and assistance projects, in accordance with the Agency’s financial rules referred to in Article 155(11) and with the provisions of the relevant instruments supporting the policies of the Union.

The European Parliament and the Council (‘the budgetary authority’) shall re-examine, when necessary, the level of the Union contribution, referred to in the first subparagraph, point (a), on the basis of an evaluation of needs and by taking account of the level of revenue provided by the sources referred to in the first subparagraph, points (c), (d) and (e).

4. Activities relating to the assessment of marketing authorisation applications, subsequent

variations, pharmacovigilance, to the operation of communications networks and to market surveillance shall be under the permanent budgetary control of the Management Board in order to guarantee the independence of the Agency. This shall not preclude the Agency from charging fees to marketing authorisation holders for performing these activities by the Agency on the condition that its independence is strictly guaranteed.

5. The expenditure of the Agency shall include staff remuneration, administrative and

infrastructure costs, and operational expenditure. In respect of operational expenditure, budgetary commitments for actions which extend over more than one financial year may be broken down over several years into annual instalments, as necessary.

The Agency may award grants related to the fulfilment of the tasks incumbent upon it under this Regulation or other relevant Union legal acts or related to the fulfilment of other entrusted tasks.

6. Each year the Management Board, on the basis of a draft drawn up by the Executive Director, shall produce an estimate of revenue and expenditure for the Agency for the following financial year. That estimate, which shall include a draft establishment plan, shall be forwarded by the Management Board to the Commission by 31 March at the latest.

7. The estimate shall be forwarded by the Commission to the budgetary authority together

with the preliminary draft general budget of the European Union.

8. On the basis of the estimate, the Commission shall enter in the preliminary draft general

budget of the European Union the estimates it deems necessary for the establishment plan and the amount of the subsidy to be charged to the general budget, which it shall place before the budgetary authority in accordance with Article 272 of the Treaty.

9. The budgetary authority shall authorise the appropriations for the subsidy to the Agency.

The budgetary authority shall adopt the establishment plan for the Agency.

10. The budget shall be adopted by the Management Board. It shall become final following

final adoption of the general budget of the European Union. Where appropriate, it shall be adjusted accordingly.

11. Any modification of the establishment plan and of the budget shall be the subject of an

amending budget, which is forwarded for the purposes of information to the budgetary authority.

12. The Management Board shall, as soon as possible, notify the budgetary authority of its

intention to implement any project which may have significant financial implications for the funding of its budget, in particular any projects relating to property such as the rental or purchase of buildings. It shall inform the Commission thereof.

43

43

Article 155

Implementation of the Agency’s budget

1. The Executive Director shall implement the budget of the Agency in accordance with

Regulation (EU, Euratom) 2018/1046 of the European Parliament and of the Council .

2. By 1 March of financial year n+1, the Agency’s accounting officer shall send the

provisional accounts for year n to the Commission’s accounting officer and to the Court of Auditors.

3. By 31 March of financial year n+1, the Executive Director shall send the report on the

budgetary and financial management for year n to the European Parliament, to the Council, to the Commission and to the Court of Auditors.

4. By 31 March of financial year n+1, the Commission’s accounting officer shall send the Agency’s provisional accounts for year n, consolidated with the Commission’s provisional accounts, to the Court of Auditors.

43 Regulation (EU, Euratom) 2018/1046 of the European Parliament and of the Council of 18

July 2018 on the financial rules applicable to the general budget of the Union, amending

Regulations (EU) No 1296/2013, (EU) No 1301/2013, (EU) No 1303/2013, (EU)

No 1304/2013, (EU) No 1309/2013, (EU) No 1316/2013, (EU) No 223/2014, (EU) No 283/2014, and Decision No 541/2014/EU and repealing Regulation (EU, Euratom) No 966/2012 (OJ L 193, 30.7.2018, p. 1).

On receipt of the Court of Auditors’ observations on the Agency’s provisional accounts pursuant to Article 246 of Regulation (EU, Euratom) 2018/1046, the Agency’s accounting officer shall draw up the Agency’s final accounts and the Executive Director shall submit them to the Management Board for an opinion.

5. The Management Board shall deliver an opinion on the Agency’s final accounts for year n.

6. The Agency’s accounting officer shall, by 1 July of financial year n+1, send the final

accounts, together with the Management Board’s opinion, to the European Parliament, to the Council, to the Court of Auditors and to the Commission’s accounting officer.

7. The final accounts for year n shall be published in the Official Journal of the European Union by 15 November of financial year n+1.

8. The Executive Director shall send to the Court of Auditors a reply to its observations by 30 September of financial year n+1. The Executive Director shall also send that reply to the Management Board.

9. The Executive Director shall submit to the European Parliament, at the latter’s request, any

information required for the smooth application of the discharge procedure for the financial year concerned, as laid down in Article 261(3) of Regulation (EU, Euratom) 2018/1046.

10. The European Parliament, upon a recommendation from the Council, shall, before 15 May

of financial year n+2, give a discharge to the Executive Director in respect of the implementation of the budget for year n.

11. The financial rules applicable to the Agency shall be adopted by the Management Board

after the Commission has been consulted. They shall not depart from Commission Delegated Regulation (EU) 2019/715 unless specifically required for the Agency’s operation and with the Commission’s prior consent.

Article 156

Fraud prevention

1. In order to combat fraud, corruption and other unlawful activities, the Regulation (EU, Euratom) No 883/2013 of the European Parliament and of the Council shall apply without restriction.

2. The Agency shall accede to the Interinstitutional Agreement of 25 May 1999 between the

European Parliament, the Council of the European Union and the Commission of the European Communities and shall adopt, without delay, the appropriate provisions applicable to all the employees of the Agency using the template set out in the Annex to that Agreement.

3. The European Court of Auditors shall have the power of audit, on the basis of documents

and on the spot, over all grant beneficiaries, contractors and subcontractors who have received Union funds from the Agency.

4. OLAF may carry out investigations, including on-the-spot checks and inspections with a

view to establishing whether there has been fraud, corruption or any other illegal activity affecting the financial interests of the Union in connection with a grant or a contract funded by the Agency, in accordance with the provisions and procedures laid down in Regulation (EU, Euratom) No 883/2013 and Council Regulation (Euratom, EC) No 2185/96.

5. Working agreements with third countries and international organisations, contracts, grant

agreements and grant decisions of the Agency shall contain provisions expressly empowering the European Court of Auditors and OLAF to conduct such audits and investigations, according to their respective competences.

6. In accordance with Council Regulation (EU) 2017/1939, the EPPO may investigate and

prosecute fraud and other illegal activities affecting the financial interests of the Union as provided for in Directive (EU) 2017/1371 of the European Parliament and of the Council.

Section 4

General provisions governing the Agency

Article 157

Liability

1. The contractual liability of the Agency shall be governed by the law applicable to the

contract in question. The Court of Justice of the European Union shall have jurisdiction pursuant to any arbitration clause contained in a contract concluded by the Agency.

2. In the case of non-contractual liability, the Agency shall, in accordance with the general

principles common to the laws of the Member States, make good any damage caused by it or by its staff in the performance of their duties.

The Court of Justice shall have jurisdiction in any dispute relating to compensation for any such damage.

3. The personal liability of its staff towards the Agency shall be governed by the provisions

laid down in the Staff Regulations or Conditions of Employment of Other Servants applicable to them.

Article 158

Access to documents

Regulation (EC) No 1049/2001 shall apply to documents held by the Agency.

The Agency shall set up a register pursuant to Article 2(4) of Regulation (EC) No 1049/2001 to make available all documents that are publicly available pursuant to this Regulation.

The Management Board shall adopt the arrangements for implementing Regulation (EC) No 1049/2001.

Decisions taken by the Agency pursuant to Article 8 of Regulation (EC) No 1049/2001 may give rise to the lodging of a complaint with the Ombudsman or form the subject of an action before the Court of Justice, under the conditions laid down in Article 228 and Article 263 of the Treaty respectively.

Article 159

Privileges

Protocol No 7 on the Privileges and Immunities of the European Union annexed to the Treaty on the Functioning of the European Union shall apply to the Agency and its staff.

Article 160

Staff

The Staff Regulations and the rules adopted by agreement between the institutions of the Union for giving effect to those Staff Regulations and Conditions of Employment of Other Servants shall apply to the staff of the Agency.

The Agency may make use of seconded national experts or other staff not employed by the Agency.

The Management Board, in agreement with the Commission, shall adopt the necessary implementing provisions.

Article 161

Security rules on the protection of classified and sensitive non-classified information

The Agency shall adopt own security rules equivalent to the Commission's security rules for protecting European Union Classified Information (EUCI) and sensitive non-classified information, as set out in Commission Decisions (EU, Euratom) 2015/443 and 2015/444. The security rules of the Agency shall cover, inter alia, provisions for the exchange, processing and storage of such information.

Members of the Management Board, the Executive Director, members of the committees, external experts participating in ad hoc working groups, and members of the staff of the Agency shall comply with the confidentiality requirements under Article 339 TFEU, even after their duties have ceased.

The Agency may take the necessary measures to facilitate the exchange of information relevant to its tasks with the Commission and the Member States and, where appropriate, the relevant Union institutions, bodies, offices and agencies. Any administrative arrangements concluded to that end with regard to the sharing of EU classified information (EUCI) or, in the absence of such arrangements, any exceptional ad hoc release of EUCI, shall have received the Commission’s prior approval.

Article 162

Consultation process

1. The Agency shall establish a consultation process with relevant national authorities or

bodies for the exchange of information and pooling of knowledge on general issues of scientific or technical nature related to the tasks of the Agency, in particular guidelines on unmet medical needs and the design of clinical trials, other studies and the generation of evidence along the life cycle of medicinal products.

The consultation process shall include bodies responsible for health technology assessment as referred to in Regulation (EU) 2021/2282 and national bodies responsible for pricing and reimbursement.

The conditions of participation shall be set by the Management Board in agreement with the Commission.

2. The Agency mayshall, where appropriate, extend the consultation process to patients,

medicine developers, healthcare professionals, industries or other stakeholders, as relevant.

Article 163

Contacts with civil society representatives

The Management Board shall, in agreement with the Commission, develop appropriate contacts between the Agency and the representatives of the industry, consumers and patients and the healthcare professions. These contacts may include the participation of observers in certain aspects of the Agency's work, under conditions determined beforehand by the Management Board, in agreement with the Commission.

Article 164

Support to SMEs and to not-for profit entities

1. The Agency shall ensure that micro, small and medium-sized enterprises (‘SMEs’) and

not-for-profit entities are offered a support scheme.

2. The support scheme shall be comprised of regulatory, procedural and administrative

support and reduction, deferral or waivers of fees.

3. The scheme shall cover the various steps involved in pre-authorisation procedures, and in

particular scientific advice, the submission of the marketing authorisation application, and the post-authorisation procedures.

4. SMEs shall benefit from the incentives laid down in Commission Regulation (EC) No 2049/2005 and [revised Council Regulation (EC) No 297/95].

5. For not-for-profit entities, the Commission shall adopt specific provisions clarifying the

definitions, establishing waivers, reductions or deferrals of fees, as appropriate, in accordance with the procedure referred to in Article 1011 and Article 1213 and Annex V of [revised Regulation (EC) No 297/95].

Article 165

Transparency

To ensure an appropriate level of transparency, the Management Board shall, on the basis of a proposal by the Executive Director and in agreement with the Commission, adopt rules to ensure the availability to the public of regulatory, scientific or technical information concerning the authorisation or supervision of medicinal products for human use which is not of a confidential nature.

The internal rules and procedures of the Agency, its committees and its working groups shall be made available to the public at the Agency and on the Internet.

The Agency may engage in communication activities on its own initiative within its field of competence. The allocation of resources to communication activities shall not be detrimental to the effective exercise of the tasks of the Agency. Communication activities shall be carried out in accordance with relevant communication and dissemination plans adopted by the Management Board.

Article 166

Personal health data

1. To support its public health tasks and in particular the evaluation and monitoring medicinal

products or the preparation of regulatory decisions and scientific opinions, the Agency may process personal health data, from sources other than clinical trials, for the purpose of improving the robustness of its scientific assessment or verifying claims of the applicant or marketing authorisation holder in the context of the evaluation or supervision of medicinal product.

1a.

2. The Agency may consider and decide upon additional evidence available, independently

from the data submitted by the marketing authorisation applicant or marketing authorisation holder. On that basis, the summary of product characteristics shall be updated if the additional evidence has an impact on the benefit-risk balance of a medicinal product.

3. The Agency shall adopt adequate data governance practices and the required standards to

ensure the appropriate use and protection of personal health data, in accordance with this Regulation and Regulation (EU) 2018/1725.

Article 167

Protection against cyber attacks

The Agency shall equip itself with a high level of security controls and processes against cyber attacks, cyber espionage and other data breaches to ensure the protection of health data and the normal functioning of the Agency at all times, especially during public health emergencies or major events at Union level.

For the purposes of the first subparagraph, the Agency shall actively identify and implementtake measures to ensure its compliance with a high common level of cybersecurity best practices adopted within Union institutions, bodies, offices and agencies, and identify and implement up-todate cybersecurity best practices for preventing, detecting, mitigating, and responding to cyber attacks.

Article 168

Confidentiality

1. Unless otherwise provided for in this Regulation and without prejudice to Regulation (EC)

No 1049/2001 and Directive (EU) 2019/1937 of the European Parliament and of the

Council, and existing national provisions and existing national legal practices in the Member States on confidentiality, all parties involved in the application of this Regulation shall respect the confidentiality of information and data obtained in carrying out their tasks in order to protect the commercially confidential information and trade secrets of natural or legal persons in accordance with Directive (EU) 2016/943 of the European Parliament and of the Council, including intellectual property rights.

2. Without prejudice to paragraph 1, all parties involved in the application of this Regulation

shall ensure that no commercially confidential information is shared in a way which has the potential to enable undertakings to restrict or distort competition within the meaning of Article 101 TFEU.

3. Without prejudice to paragraph 1, information exchanged on a confidential basis between

competent authorities of the Member States and between competent authorities of the Member States and the Commission and the Agency shall not be disclosed without the prior agreement of the authority from which that information originates.

4. Paragraphs 1, 2 and 3 do not affect the rights and obligations of the Commission, the Agency, Member States or other actors identified in this Regulation with regard to the exchange of information and the dissemination of warnings, nor do they affect the obligations of the persons concerned to provide information under criminal law.

5. The Commission, the Agency, and Member States may exchange commercially

confidential information with regulatory authorities of third countries with which they have concluded bilateral or multilateral confidentiality arrangements.

Article 169

Processing of personal data

1. To support its public health tasks and in particular the evaluation and monitoring of

medicinal products or the preparation of regulatory decisions and scientific opinions, the Agency may process personal data, including personal health data, for the performance of its tasks as referred to in Article 135, in particular from clinical trials and other sources including real world data for the purpose of improving the robustness of its scientific assessment or verifying claims of the applicant or marketing authorisation holder in the context of the evaluation or supervision of medicinal products.

Additionally, the Agency may process such data for the performance of regulatory science activities, as defined in paragraph 2, provided that the processing of those personal data:

(a) is strictly required and duly justified to achieve the objectives of the project or of the horizon scanning activities concerned;

(b) as regards special categories of personal data, is strictly necessary and subject to appropriate safeguards, which may includeand protect the rights of data subjects in accordance with Union Law, including technical and organisational measures such as pseudonymisation.

2. For the purpose of this Article, ‘regulatory science activities’ shall mean scientific projects

to complement available scientific evidence with regard to diseases or horizontal questions related to medicinal products, to fill evidence gaps that cannot be fully addressed through data in the possession of the Agency, or to support horizon scanning activities.

3. The processing of personal data by the Agency in the context of this Article shall be guided

by the principles of transparency, explainability, fairness, and accountability.

4. The Management Board shall establish the general scope for the regulatory science

activities in consultation with the Commission and the European Data Protection Supervisor.

5. The Agency shall keep documentation containing a detailed description of the process and

of the rationale behind the training, testing and validation of algorithms to ensure transparency of the process and the algorithms, including their compliance with the safeguards provided for in this Article, and to allow for verification of the accuracy of the results based on the use of such algorithms. Upon request, the Agency shall make relevant documentation available to interested parties, including Member States.

6. If the personal data to be processed for the regulatory science activities have been directly

provided by a Member State, a Union body, a third country or an international organisation, the Agency shall request authorisation from that provider of data, unless the provider of data has granted its prior authorisation to such processing for the purpose of regulatory science activities, either in general terms or subject to specific conditions.

7. Processing of personal data under this Regulation shall be subject to Regulations (EU) 2016/679 and (EU) 2018/1725, as applicable. The Agency shall adopt adequate data governance practices and the required standards to ensure the appropriate use and protection of personal health data in accordance with Union Law.

Article 170

Evaluation

1. Not later than [note to OP = five years after the date of entry into applicationnote to OP =

five years after the date of entry into application], and every 10 years thereafter, the Commission shall commission an evaluation of the Agency's performance in relation to its objectives, mandate, tasks, governance and location(s) in accordance with Commission's guidelines. The evaluation shall include, amongst others, based on the reports referred to in Articles 144 point q and qa, a quantitative assessment of the efficiency gain, the appropriate involvement of scientific expertise in particular regarding orphan, paediatric medicinal products and ATMPs as well as the broad geographical representation of national experts in the work of the scientific committees, advisory groups and working parties.

2. The evaluation shall, in particular, address the possible need to modify the mandate of the Agency, and the financial implications of any such modification.

3. On the occasion of every second evaluation, there shall be an assessment of the results

achieved by the Agency having regard to its objectives, mandate, governance and tasks, including an assessment of whether the continuation of the Agency is still justified with regard to these objectives, mandate, governance and tasks. This assessment shall also include the experience acquired as a result of the operation of the procedures laid down in this Regulation and in Chapter III, Sections 4 and 5 of [revised Directive 2001/83/EC] on the basis of input from Member States and the Coordination group referred to in Article 37 of [revised Directive 2001/83/EC].

4. The Commission shall report to the European Parliament, the Council and the Management Board on the evaluation findings. The findings of the evaluation shall be made public.

5. By 10 years following the entering into application, the Commission shall assess the

application of this Regulation and produce an evaluation report on the progress towards achievement of the objectives contained herein including an assessment of the resources required to implement this Regulation.

5a. The Commission shall, following the use of the first two vouchers pursuant to Article 41,

paragraph 2, or five years after the date of application of this Regulation, whichever is the earliest, and every 5 years thereafter, carry out an evaluation of Articles 40 to 43 and present a report on the main findings of that evaluation to the European Parliament and the Council. The evaluation shall include an assessment of the effectiveness of the voucher as a measure, taking into account also other existing Union level market incentives for authorised priority antimicriobials, to address the market failure in the development of priority antimicrobials addressing antimicrobial resistance and assess the actual and expected costs, as well as an assessment of whether the value of the annual gross sales referred to in Article 41(1) should be adjusted to inflation and whether it is appropriate to increase the number of vouchers granted referred to in Article 43. The Commission shall, if appropriate, present a legislative proposal, based on the evaluation, in order to amend this Regulation.

5b. The Commission shall, five years after [the date of application of this Regulation], carry

out an evaluation of the voluntary subscription model referred to in Article 43a and present a report on the main findings of that evaluation to the European Parliament and the Council. That evaluation shall cover at least the following:

(a) the implementation and uptake of the voluntary subscription model by Member

States;

(b) the impact of the voluntary subscription model on the development and supply of antimicrobials;

(c) the effectiveness and appropriateness of the voluntary subscription model set out in Article 43a, including an assessment of whether that model could be improved by introducing a voluntary Union level subscription model for the purchase of antimicrobials.

The evaluation shall be based on information provided by Member States related to the practical application of Article 43a. The Commission shall, if appropriate, present a legislative proposal, based on the evaluation, in order to amend this Regulation.

CHAPTER XII

GENERAL PROVISIONS

Article 171

Penalties at national level

1. By 6 months before the date of application of this Regulation, Member States shall lay

down the rules on penalties applicable to infringements of this Regulation and shall take all measures necessary to ensure that they are implemented. The penalties provided for shall be effective, proportionate and dissuasive. Member States shall, without delay, notify the Commission of those rules and of those measures and shall notify it, without delay, of any subsequent amendment affecting them.

2. Member States shall inform the Commission immediately of any litigation instituted for

infringement of this Regulation regarding centrally authorised medicinal products.

Article 172

Union penalties

1. The Commission may impose financial penalties in the form of fines or periodic penalty

payments on the marketing authorisations holder granted under this Regulation if they fail to comply with any of the obligations laid down in Annex II in connection with the marketing authorisations.

2. The Commission may, insofar as specifically provided for in the delegated acts referred to

in paragraph 10, point (b), impose the financial penalties referred to in paragraph 1 on a legal entity or legal entities other than the marketing authorisation holder provided that such entities form part of the same economic entity as the marketing authorisation holder and that such other legal entities:

(a) exerted a decisive influence over the marketing authorisation holder; or

(b) were involved in, or could have addressed, such failure to comply with the obligation by the marketing authorisation holder.

3. Where the Agency or a competent authority of a Member State is of the opinion that a

marketing authorisation holder has failed to comply with any of the obligations, referred to in paragraph 1, it may request the Commission to investigate whether to impose financial penalties pursuant to that paragraph.

4. In determining whether to impose a financial penalty and in determining its appropriate

amount, the Commission shall be guided by the principles of effectiveness, proportionality and dissuasiveness and take into consideration, where relevant, the seriousness and the effects of the failure to comply with the obligations.

5. For the purposes of paragraph 1, the Commission shall take into account:

(a) any infringement procedure initiated by a Member State against the same marketing authorisation holder on the basis of the same legal grounds and the same facts;

(b) any sanctions, including penalties, already imposed on the same marketing authorisation holder on the basis of the same legal grounds and the same facts.

(ba) the nature, gravity and duration of the infringement and its consequences;

(bb) the intentional or negligent character of the infringement;

(bc) any action taken by the infringing party to mitigate the damage caused by the infringement;

(bd) the risk to public health.

6. Where the Commission finds that the marketing authorisation holder has failed,

intentionally or negligently, to comply with its obligations, as referred to in paragraph 1, it may adopt a decision imposing a fine not exceeding 5 % of the marketing authorisation holder’s Union turnover in the business year preceding the date of that decision.

Where the marketing authorisation holder continues to fail to comply with its obligations referred to in paragraph 1, the Commission may adopt a decision imposing periodic penalty payments per day not exceeding 2,5 % of the marketing authorisation holder’s average daily Union turnover in the business year preceding the date of that decision.

Periodic penalty payments may be imposed for a period running from the date of notification of the relevant Commission's decision until the failure to comply with the obligation by the marketing authorisation holder, as referred to in paragraph 1, has been brought to an end.

7. When conducting the investigation on a failure to comply with any of the obligations

referred to in paragraph 1, the Commission may cooperate with competent authorities of the Member States and rely on resources provided by the Agency.

8. Where the Commission adopts a decision imposing a financial penalty, it shall publish a

concise summary of the case, including the names of the marketing authorisation holders involved and the amounts of and reasons for the financial penalties imposed, having regard to the legitimate interest of the marketing authorisation holders for the protection of their business secrets.

9. The Court of Justice of the European Union shall have unlimited jurisdiction to review

decisions whereby the Commission has imposed financial penalties. The Court of Justice of the European Union may cancel, reduce or increase the fine or periodic penalty payment imposed by the Commission.

10. The Commission is empowered to adopt delegated acts in accordance with Article 175 in

order to supplement this Regulation by laying down:

(a) procedures to be applied by the Commission when imposing fines or periodic penalty payments, including rules on the initiation of the procedure, measures of inquiry, rights of the defence, access to file, legal representation and confidentiality;

(b) further detailed rules on the imposition by the Commission of financial penalties on legal entities other than the marketing authorisation holder;

(c) rules on duration of procedure and limitation periods;

(d) elements to be taken into account by the Commission when setting the level of and imposing fines and periodic penalty payments, as well as the conditions and methods for their collection.

CHAPTER XIII DELEGATED AND IMPLEMENTING ACTS

Article 173

Standing Committee on Medicinal Products for Human Use and examination procedure

1. The Commission shall be assisted by the Standing Committee on Medicinal Products for Human Use established by Article 214 of [revised Directive 2001/83/EC]. That committee shall be a committee within the meaning of Regulation (EU) No 182/2011.

2. Where reference is made to this paragraph, Article 5 of Regulation (EU) No 182/2011 shall

apply.

3. Where the opinion of the Committee is to be obtained by written procedure and reference

is made to this paragraph, that procedure shall be terminated without result only when, within the time-limit for delivery of the opinion, the chair of the Committee so decides.

4. The Standing Committee on Medicinal Products for Human Use shall ensure that its rules

of procedure are adapted to the need to make medicinal products swiftly available to patients.

Article 174

Implementing measures related to authorisation and pharmacovigilance activities

1. In order to harmonise electronic transmissions provided for in this Regulation, the Commission may adopt implementing measures covering the format and content of electronic transmissions by marketing authorisation holders.

Those measures shall take account of the work on international harmonisation carried out in the area and shall, where necessary, be revised to take account of technical and scientific progress. Those measures shall be adopted in accordance with the examination procedure referred to in Article 173(2).

2. In order to harmonise the performance of the pharmacovigilance activities provided for in

this Regulation, the Commission shall adopt implementing measures as provided for in Article 214122 of [revised Directive 2001/83/EC] covering the following areas:

(a) the content and maintenance of the pharmacovigilance system master file kept by the marketing authorisation holder;

(b) the minimum requirements for the quality system for the performance of pharmacovigilance activities by the Agency;

(c) the use of internationally agreed terminology, formats and standards for the performance of pharmacovigilance activities;

(d) the minimum requirements for the monitoring of data included in the Eudravigilance database to determine whether there are new risks or whether risks have changed;

(e) the format and content of electronic transmission of suspected adverse reactions by

Member States and marketing authorisation holders;

(f) the format and content of electronic periodic safety update reports and risk management plans;

(g) the format of protocols, abstracts and final study reports of the post-authorisation safety studies.

Those measures shall take account of the work on international harmonisation carried out in the area of pharmacovigilance and shall, where necessary, be revised to take account of technical and scientific progress. Those measures shall be adopted in accordance with the examination procedure referred to in Article 173(2).

Article 175

Exercise of the delegation

1. The power to adopt delegated acts is conferred on the Commission subject to the

conditions laid down in this Article.

2. The power to adopt delegated acts referred to in Articles 3(5), 19(8), 21, 47(4), 49(2), 63(2), 67(4), 74(4), 75(3), 81(4), 116(3), 126(2b), 138(2) and 172(10) shall be conferred on the Commission for a period of five years from [date of entry into force]. The Commission shall draw up a report in respect of the delegation of power not later than nine months before the end of the five-year period. The delegation of power shall be tacitly extended for periods of an identical duration, unless the European Parliament or the Council opposes such extension not later than three months before the end of each period.

3. The delegation of power referred to in Articles 3(5), 19(8), 21, 47(4), 49(2), 63(2), 67(4), 74(4), 75(3), 81(4), 116(3), 126(2b), 138(2) and 172(10) may be revoked at any time by the European Parliament or by the Council. A decision to revoke shall put an end to the delegation of the power specified in that decision. It shall take effect the day following the publication of the decision in the Official Journal of the European Union or at a later date specified therein. It shall not affect the validity of any delegated acts already in force.

4. Before adopting a delegated act, the Commission shall consult experts designated by each Member State in accordance with the principles laid down in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making.

5. As soon as it adopts a delegated act, the Commission shall notify it simultaneously to the European Parliament and to the Council.

6. A delegated act adopted pursuant to Articles 3(5),21, 19(8), 21, 47(4), 49(2), 63(2), 67(4), 74(4), 75(3), 81(4), 116(3), 126(2b), 138(2) and 172(10)175 shall enter into force only if no objection has been expressed either by the European Parliament or by the Council within a period of two months of notification of that act to the European Parliament and to the Council or if, before the expiry of that period, the European Parliament and the Council have both informed the Commission that they will not object. That period shall be extended by three months at the initiative of the European Parliament or of the Council.

CHAPTER XIV AMENDMENTS TO OTHER LEGAL ACTS

Article 176

Amendments to Regulation (EC) No 1394/2007

Regulation (EC) No 1394/2007 is amended as follows:

(1) Articles 5, 8, 17 and 20 to 23 are deleted;

(2) in Article 9(3), the fourth subparagraph is replaced by the following:

‘If the application does not include the results of the assessment, the Agency shall seek an opinion on the conformity of the device part with Annex I to Regulation (EU) 2017/745 of the European Parliament and of the Council* from a notified body identified in conjunction with the applicant, unless the Committee for Medicinal Products for Human Use advised by its experts for medical devices decides that involvement of a notified body is not required.

_____________________

* Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (OJ L 117, 5.5.2017, p. 1).

(3) the following Article 7a is inserted:

‘Article 7a Adapted frameworks for ATMPs The adapted frameworks established in accordance with Article 28 of [revised Directive 2001/83/EC] may apply also for the purposes of obtaining a centralised marketing authorisation in accordance with [revised Regulation 726/2004/EC].’’

Article 177

Amendments to Regulation (EU) No 536/2014

Regulation (EU) No 536/2014 is amended as follows:

(1) the following Article 5a is inserted:

‘Article 5a

Environmental risk assessment for investigational medicinal products for human use containing or consisting of genetically modified organisms

1. Where the application according to Article 5 of this Regulation concerns clinical trials with investigational medicinal products for human use containing or consisting of genetically modified organisms (GMOs) within the meaning of Article 2 of Directive 2001/18/EC of the European Parliament and of the Council*, the sponsor shall submit an environmental risk assessment (ERA) in the EU portal (CTIS).

2. The ERA referred to in paragraph 1 shall be conducted in accordance with the principles set out in Annex II to Directive 2001/18/EC and the scientific guidelines developed by the Agency in coordination with the competent authorities of the Member States, established according to Directive 2001/18/EC for this purpose and the delegated act referred to in paragraph 8.

3. Articles 6 to 11 of Directive 2001/18/EC shall not apply to investigational medicinal products for human use containing or consisting of genetically modified organisms.

4. The Committee for Medicinal Products for Human Use (CHMP) referred to in Article 148 [revised Regulation No (EC) 726/2004] shall assess the ERA referred to in paragraph 1 in the form of a scientific opinion. The CHMP shall submit its opinion to the competent authority of the Reporting Member State within 45 days from the validation date referred to in Article 5(3). Where appropriate, the opinion shall include risk mitigation measures. The sponsor shall provide evidence to the Reporting Member State and the Member States Concerned that these measures will be implemented.

5. The CHMP may request, with justified reasons, via the EU portal (CTIS) additional information from the sponsor regarding the assessment referred to in paragraph 1, which shall be provided only within the period referred to in Article 6, paragraph 5.

6. To obtain and review the additional information referred to in paragraph 65, the

Agency may extend the period referred to in paragraph 5 by a maximum of 31 days. The sponsor shall submit the requested additional information within the period set by the Agency. Where the sponsor does not provide additional information within the period set by the Agency, the application referred to in paragraph 1 shall be deemed to have expired in all Member States concerned. The Agency shall inform the reporting Member State via the CTIS and the Member States concerned about the extension of the period referred to in paragraph 5 in accordance with this paragraph as well as the period set for the sponsor to submit the requested information.

7. In case of first-in-class products or when a novel question arises during the assessment of the submitted ERA as referred to in paragraph 1, the Agency shall, if necessary, consult with bodies that Member States have set up in accordance with Directive 2001/18/EC or Directive 2009/41/EC of the European Parliament and of the Council**. If a consultation is necessary, the technical dossier addressing in sufficient detail the information specified in Annex III to Directive 2001/18/EC should be included to support the ERA where appropriate.

8. The Commission shall be empowered to adopt a delegated act in accordance with Article 89 to amend the Annexes to this Regulation in order to specify the procedure for the submission and the harmonized assessment of the ERA for investigational medicinal products containing or consisting of GMOs as set out in paragraphs 1 to 8.

The delegated act referred to in the first subparagraph shall establish that the ERA is an independent part of the application.

The delegated act referred to in the first subparagraph shall specify the content of the ERA taking into account the common application forms and Good Practice Documents for genetically modified human cells and for adeno-associated viral vectors that were published by the Agency.

The delegated act referred to in the first subparagraph shall contain a provision to update the ERA requirements for investigational medicinal products containing or consisting of GMOs following scientific developments and changes of (Directive

2001/18/EC).’;

* Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC - Commission Declaration (OJ L 106,

17.4.2001, p. 1).

** Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained use of genetically modified micro-organisms (Recast) (OJ L 125,

21.5.2009, p. 75).’;’

(1a) in Article 6(1) point c is replaced by the following:

‘(c) Compliance with the requirements concerning the manufacturing and import of investigational medicinal products and auxiliary medicinal products set out in Chapter IX.

‘If requested by an applicant, whether the investigational medicinal product can be manufactured through decentralised manufacturing.

When assessing a request to use decentralised manufacturing, the principles expressed in paragraph 1 of Article 26b [of the revised Directive] apply mutatis mutandis. The Commission may specify by means of an implementing act, the detailed arrangements for the application of these principles. This implementing act shall be adopted in accordance with the

examination procedure referred to in Article 88(2).’

(2) in Article 25(1), point (d), is replaced by the following:

‘(d) measures to protect subjects, third persons and the environment;;’

(3) Article 26 is replaced by the following:

‘Article 26

Language requirements

The language of the application dossier, or parts thereof, shall be determined by the Member State concerned.

The language for the environmental risk assessment (ERA) shall preferably be English.

Member States, in applying the first subparagraph, shall consider accepting, for the documentation not addressed to the subject, a commonly understood language in the medical field.;’

(4) in Article 37(4), the following subparagraph is inserted after the first subparagraph:

‘In the case of a clinical trial which involves the use of a medicinal product in the paediatric population, the timeline referred to in the first subparagraph to submit to the EU database a summary of the results of the clinical trial shall be 6 months.’;’

(5) in Article 61(2), point (a), is replaced by the following:

‘(a) it shall have at its disposal, for manufacture or import, suitable and sufficient premises, technical equipment and control facilities complying with the requirements set out in this Regulation and, where appropriate, in case of investigational medicinal products containing or consisting of GMOs, in Directive 2009/41/EC;;’

(6) in Article 66(1), point (c), is replaced by the following:

‘c) information to identify the medicinal product, including, where appropriate, ‘This

IMP contains genetically modified organisms;’;’

(7) in Article 76, paragraph (1) is replaced by the following:

‘1. Member States shall ensure that systems for compensation for any damage suffered by a subject resulting from the participation in a clinical trial or caused to third persons or the environment during such trial conducted on their territory are in place in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extent of the risk.’;’

(7a) in Article 61, paragraph 1 is replaced by the following:

‘‘1. The manufacturing and import of investigational medicinal products in the Union shall be subject to the holding of an authorisation.

The manufacturing authorisation shall not be required for decentralised sites carrying out manufacturing or testing steps, in accordance with Article 6(1)(c) under the responsibility of the qualified person of a central site referred to in Article 61(2)(b).

The holder of the manufacturing authorisation for a central site responsible for decentralised manufacturing of the investigational medicinal products shall ensure that the activities of the central site and decentralised sites are compliant with the good manufacturing practice for investigational medicinal products referred to in Article

63(1).’;’

(7b) in Article 61 in paragraph 3a is added:

‘‘3a. The Commission shall adopt delegated acts supplementing this Regulation by specifying the particulars required in an application for a manufacturing authorisation for a central site responsible for decentralised manufacturing of the investigational medicinal products, in accordance with Article 61 and Article 6, paragraph 1, point (c), as well as the modalities of the registration process for these decentralised sites and clarifying the arrangements of the manufacturing authorisation holder for a central site as well as sponsors as regards the registration and oversight of the decentralised manufacturing sites.’;’

(7c) in Article 61 paragraph 4 is replaced by the following:

‘‘4. Article 142(1), (2), (4), (5) Articles 144 to 146, Article 147(1) points (a) to (b), (d) to (f), Article 148(6) to (11) of [revised Directive 2001/83/EC] shall apply mutatis mutandis to the authorisation referred to in paragraph 1.’;’

(8) Article 89 is replaced by the following:

‘Article 89

Exercise of the delegation

1. The power to adopt delegated acts is conferred on the Commission subject to the conditions laid down in this Article.

2. The power to adopt delegated acts referred to in Articles 5a, 27, 39, 45, 63(1) and 70 shall be conferred on the Commission for a period of five years from the date referred to in Article 99(2). The Commission shall draw up a report in respect of the delegated powers not later than nine months before the end of the five year period. The delegation of powers shall be tacitly extended for periods of an identical duration, unless the European Parliament or the Council opposes such extension not later than three months before the end of each period.

3. The delegation of power referred to in Articles 5a, 27, 39, 45, 63(1), and 70 may be revoked at any time by the European Parliament or by the Council. A decision to revoke shall put an end to the delegation of the power specified in that decision. It shall take effect the day following the publication of the decision in the Official Journal of the European Union or at a later date specified therein. It shall not affect the validity of any delegated acts already in force.

4. Before adopting a delegated act, the Commission shall consult experts designated by each Member State in accordance with the principles laid down in the

Interinstitutional Agreement of 13 April 2016 on Better Law-Making.

5. As soon as it adopts a delegated act, the Commission shall notify it simultaneously to the European Parliament and to the Council.

6. A delegated act adopted pursuant to Articles 5a, 27, 39, 45, 63(1), and 70 shall enter into force only if no objection has been expressed either by the European Parliament or the Council within a period of two months of notification of that act to the

European Parliament and the Council or if, before the expiry of that period, the European Parliament and the Council have both informed the Commission that they will not object. That period shall be extended by two months at the initiative of the

European Parliament or the Council.;’

(9) Article 91 is replaced by the following:

‘Article 91

Relation with other Union legal acts

‘This Regulation shall be without prejudice to Council Directive 97/43/Euratom1, Council

Directive 96/29/Euratom2, Directive 2004/23/EC of the European Parliament and of the Council3, Directive 2002/98/EC of the European Parliament and of the Council4 and Directive 2010/53/EU of the European Parliament and of the Council5.

In the context of inspections referred under Articles 52(5) of [revised Regulation 726/2004] and Article 78 of this Regulation and the criteria set out in Annex III of [revised Regulation 726/2004] apply mutatis mutandis.

_________________

1. Council Directive 97/43/Euratom of 30 June 1997 on health protection of individuals against the dangers of ionizing radiation in relation to medical exposure, and repealing Directive 84/466/Euratom (OJ L 180, 9.7.1997, p. 22).

2. Council Directive 96/29/Euratom of 13 May 1996 laying down basic safety standards for the protection of the health of workers and the general public against the dangers arising from ionizing radiation (OJ L 159, 29.6.1996, p. 1).

3. Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (OJ L 102, 7.4.2004, p. 48).

4. Directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001/83/EC (OJ L 033, 8.2.2003, p. 30).

5. Directive 2010/53/EU of the European Parliament and of the Council of 7 July 2010 on standards of quality and safety of human organs intended for transplantation (OJ L 207, 6.8.2010, p. 14).’

(10) In Annex I point B, a new paragraph 8a is added:

‘‘The cover letter shall indicate whether, and if yes why, the decentralised manufacturing of investigational medicinal products has been proposed by the sponsor.’’

Article 178

Amendments to Regulation (EU) 2022/123

Regulation (EU) No 2022/123 is amended as follows:

1. In Article 18, the following paragraph (7) is added:

‘(7) Where a request has been made in accordance with Article 18(3) of Regulation (EU) 2022/123 and there is an application for a temporary emergency marketing authorisation for the medicinal product concerned in accordance with Article 30 of Regulation [Note to OP: Please fill in with the number of this Regulation]*, the procedure initiated under that Regulation shall prevail.’

__________________

* [OP: Insert the full title of that Regulation and the OJ reference, please]’

2. Articles 33 and 34 are deleted.

CHAPTER XV FINAL PROVISIONS

Article 179

Repeals

1. Regulations (EC) No 141/2000, (EC) No 726/2004 and (EC) No 1901/2006 are repealed.

55

55

2. Commission Implementing Regulation (EU) No 198/2013 is repealed.

Article 180

Transitional provisions

1. The provisions of Article 117 of this Regulation shall also apply to marketing

authorisations of medicinal products for human use granted in accordance with Regulation (EC) No 726/2004 and in accordance with Directive 2001/83/EC before [Note to the OP:

Please insert the date = date of entry into application of this Regulation].

55 Commission Implementing Regulation (EU) No 198/2013 of 7 March 2013 on the selection of a symbol for the purpose of identifying medicinal products for human use that are subject to additional monitoring (OJ L 65, 8.3.2013, p. 17).

2. The procedures concerning the applications for marketing authorisations for medicinal

products for human use that have been validatedsubmitted, in accordance with Article 5 of Regulation (EC) No 726/2004, before [Note to the OP: Please insert the date = date of entry into application of this Regulation] and that were pending on [Note to the OP: Please insert the date = the day before the date of application of this Regulation] shall be completed in accordance with Article 10 of Regulation (EC) No 726/2004.

3. Procedures concerning imposed post-authorisation studies that were initiated in accordance

with Article 10a of Regulation (EC) No 726/2004, before [Note to the OP: Please insert the date = date of entry into application of this Regulation] and that were pending on [Note to the OP: Please insert the date = the day before the date of application of this Regulation] shall be completed in accordance with Article 20 of this Regulation.

3a. For medicinal products authorised before [OP: Please insert the date = the day before

the date of application of this Regulation] and for which the validity expires after that date, the renewal of the marketing authorisation shall follow the procedures referred to

in Article 17.

4. By way of derogation, the periods of regulatory protection referred to in Article 29 shall

not apply to reference medicinal products for which an application for marketing authorisation has been submitted before [Note to the OP: Please insert the date of application of this Regulation]. Article 14(11) of Regulation (EC) No 726/2004 shall continue to apply to them.

4a. By way of derogation, the reporting obligations as referred to in Article 57 of [the revised Directive 2001/83/EC], shall not apply with regards to medicinal products authorised in accordance with [revised Regulation 726/2004/EC] before [OP please insert the date = 36 months after the date of entering into force of this Regulation].

5. Orphan designations granted before [Note to the OP: Please insert the date of application

of this Regulation], entered in and not removed from the Community Register of Orphan Medicinal Products in accordance with Article 5, paragraphs 8 and 12, respectively, of Regulation (EC) No 141/2000 and not granted a marketing authorisation in accordance with Article 7(3) of Regulation (EC) No 141/2000 corresponding to the orphan designation shall be considered to comply with this Regulation and shall be entered in the Register of Designated Orphan Medicinal Products.

6. Orphan designations granted before [Note to the OP: Please insert the date of application

of this Regulation] which are either removed from the Community Register of Orphan Medicinal Products in accordance with Article 5(12) of Regulation (EC) No 141/2000 or granted a marketing authorisation in accordance with Article 7(3) of Regulation (EC) No 141/2000 shall not be considered as orphan designations and shall not be entered in the Register of Designated Orphan Medicinal Products.

7. The 7-year validity of an orphan designation referred to in Article 66 of this Regulation for

orphan medicinal products granted before [Note to the OP: Please insert the date of application of this Regulation], entered in and not removed from the Community Register of Orphan Medicinal Products in accordance with Article 5 (8) and (12), respectively, of Regulation (EC) No 141/2000 and not granted a marketing authorisation in accordance with those Article 7(3) of Regulation (EC) No 141/2000 corresponding to the orphan designation shall begin to run from [Note to the OP: Please insert the date of application of this Regulation].

7a. By way of derogation, the periods of market exclusivity referred to in Article 71(2) shall

not apply for orphan medicinal products for which an application for marketing authorisation has been submitted before [Note to the OP: Please insert the date of application of this Regulation]. Those orphan medicinal products shall benefit from the period referred to in Article 8(1) of Regulation (EC) No 141/2000. This derogation shall only apply to the initial marketing authorisation.

However, any other application for an orphan medicinal product containing the same active substance submitted before [Note to the OP: Please insert the date of application of this Regulation], shall be subject to the provisions of this Regulation with regard to the market exclusivity periods, in particular Articles 71(3) and 72.

8. The procedures concerning orphan designations which were initiated in accordance with

Article 5, paragraphs 1, 11 or 12 of Regulation (EC) No 141/2000 before [Note to the OP: Please insert the date of application of this Regulation] and were pending on [OP please insert the date = the day before the date of application], shall be completed in accordance with Article 5, paragraphs 1, 11 or 12 of Regulation (EC) No 141/2000 as applicable on [OP please insert the date = the day before the date of application].

9. When a paediatric investigation plan, a waiver or a deferral has been granted in accordance

with Regulation (EC) No 1901/2006 before [Note to the OP: Please insert the date of application of this Regulation], it shall be considered to comply with this Regulation.

The procedures concerning the application for a paediatric investigation plan, a waiver or a deferral submitted before [date of entry into application], shall be completed in accordance with Regulation (EC) No 1901/2006.

10. Regulations (EC) No 2141/96, (EC) No 2049/2005, (EC) No 507/2006 and (EC)

No 658/2007 shall remain in force and continue to apply unless and until repealed.

11. Regulation (EC) No 1234/2008 shall continue to apply unless and until repealed as regards

medicinal products for human use that are covered by Regulation (EC) No 726/2004 and

Directive 2001/83/EC and that are not excluded from the scope of Regulation (EC)

No 1234/2008 pursuant to Article 23b, paragraphs 4 and 5 of Directive 2001/83/EC.

12. Commission Regulation (EC) No 847/2000 shall continue to apply unless and until

repealed as regards orphan medicinal products that are covered by this Regulation.

13. By way of derogation from Article [Duration of application of Chapter III] vouchers

granted until [Note to OP: insert the date of 15 years after the date of entry into force of this Regulation] or until the date when the Commission has granted a total of 10 5vouchers in accordance with Chapter III, whichever date is the earliest, shall continue to be valid according to the conditions set out in Chapter III.

14. Marketing authorisations of human medicinal products authorised in accordance with Article 6(1) of Directive 2001/83/EC shall be deemed to have been issued in accordance with Article 5(1) [revised Directive 2001/83/EC], irrespective of whether those products

are covered by Annex I to [Revised Regulation (EC) No 726/2004.

Article 181

Entry into force

This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union.

It shall apply from [Note to the OP: Please insert the date of 1824 months after its entry into force.

The date should be identical to the date for the application of the Directive].

However, Article 67 shall apply from [Note to the OP: Please insert the date of 2 years6 months after the date of adoption/entry into force/applicationapplication of this Regulation].

Articles 40 to 43a, Articles 113 to 115, Article 115a, Articles 127 to 134 and Articles 141 and

154(5), shall apply from its entry into force and Articles 116 to 126 shall apply from [Note to the OP: Please insert the date of 6 months after the date of entry into force of this Regulation].

This Regulation shall be binding in its entirety and directly applicable in the Member States in accordance with the Treaties.

Done at Brussels,

For the European Parliament For the Council

ANNEX I

MEDICINAL PRODUCTS TO BE AUTHORISED BY THE UNION

1. Medicinal products developed by means of one of the following biotechnological

processes:

- recombinant nucleic acid technology;

- controlled expression of genes coding for biologically active proteins in prokaryotes and eukaryotes including transformed mammalian cells.

2. Advanced therapy medicinal products as defined in Article 2 of Regulation (EC) No 1394/2007.

3. Medicinal products for human use containing ana new active substance which on 20 May 2004[date of application of this Regulation] was not authorised in the Union, excluding allergen medicinal products or herbal medicinal products, which shall in any case not be authorised by the Union..

3a. Medicinal products for human use containing a new active substance, which on 20 May 2004 was not authorised in the Union and which is not covered by point 3, for which the therapeutic indication is the treatment of any of the following diseases:

- acquired immune deficiency syndrome,

- cancer,

6366/26

ANNEX I

- neurodegenerative disorder,

- diabetes,

- auto-immune diseases and other immune dysfunctions, - viral diseases.

4. Medicinal products that are designated as orphan medicinal products pursuant to this Regulation.

5. Medicinal products authorised in accordance with a paediatric use marketing authorisation.

6. Priority antimicrobials as referred to in Article 40.

6366/26

ANNEX I

ANNEX II

LIST OF THE OBLIGATIONS REFERRED TO IN ARTICLE 172

(1) the obligation to submit complete and accurate particulars and documentation in an

application for marketing authorisation submitted to the Agency or in response to obligations laid down in this Regulation to the extent that the failure to comply with the obligation concerns a material particular;

(2) the obligation to comply with conditions or restrictions included in the marketing

authorisation and concerning the supply or use of the medicinal product for human use, as referred to in Article 12 (4), point (c) and in Article 13(1) fourth subparagraph;

(3) the obligation to comply with conditions or restrictions included in the marketing

authorisation with regard to the safe and effective use of the medicinal product for human use as referred to in Article 12(4), points (b), (d), (e), (f) and (g) and in Article 13(1);

(4) the obligation to introduce any necessary variation to the terms of the marketing

authorisation to take account of technical and scientific progress and enable the medicinal products for human use to be manufactured and checked by means of generally accepted scientific methods, as provided for in Article 45(1);

(5) the obligation to supply any new information which may entail a variation to the terms of

the marketing authorisation, to notify any prohibition or restriction imposed by the competent authorities of any country in which the medicinal product for human use is marketed, or to supply any information that may influence the evaluation of the risks and benefits of the product, as provided for in Article 45(2);

(6) the obligation to keep product information up to date with current scientific knowledge,

including the conclusions of the assessment and recommendations made public on the

European medicines web-portal, as provided for in Article 45(3);

(7) the obligation to provide, at the request of the Agency, any data demonstrating that the

benefit-risk balance remains favourable, as provided for in Article 45(4);

(8) the obligation to place the medicinal product for human use on the market in accordance

with the content of the summary of product characteristics and the labelling and package leaflet as contained in the marketing authorisation;

(9) the obligation to comply with the conditions referred to in Article 18(1) and Article 19;

(10) the obligation to notify the Agency of the dates of actual marketing and of the date when

the medicinal product for human use ceases to be on the market, and to provide to the Agency data relating to the volume of sales and the volume of prescriptions of the medicinal product for human use, as provided in Article 16(4);

(11) the obligation to operate a comprehensive pharmacovigilance system for the fulfilment of

pharmacovigilance tasks, including the operation of a quality system, maintenance of a pharmacovigilance system master file and performance of regular audits, in accordance with Article 99 in conjunction with Article 99 of [revised Directive 2001/83/EC];

(12) the obligation to submit, at the request of the Agency, a copy of the pharmacovigilance

system master file, as provided for in Article 45(4);

(13) the obligation to operate a risk management system as provided for in Article 22 and

Article 99(2) in conjunction with Article 99(4) of [revised Directive 2001/83/EC];

(14) the obligation to record and report suspected adverse reactions for medicinal products for

human use, in accordance with Article 106 (1) in conjunction with Article 105 of [revised

Directive 2001/83/EC];

(15) the obligation to submit periodic safety update reports, in accordance with Article 106(2)

in conjunction with of [revised Directive 2001/83/EC];

(16) the obligation to conduct post-marketing studies, including post-authorisation safety

studies and, post-authorisation efficacy studies and post-authorisation environmental risk assessment studies, and to submit them for review, as provided for in Article 20;

(17) the obligation to ensure that public announcements relating to information on

pharmacovigilance concerns are presented objectively and are not misleading and to notify them to the Agency, as provided for in Articles 104 of [revised Directive 2001/83/EC];

(18) the obligation to comply with the time limits for initiating or completing measures

specified in the Agency’s decision on deferral following the initial marketing authorisation of the medicinal product for human use concerned and in accordance with the definitive opinion referred to in Article 81(2);

(19) the obligation to submit to the Agency an updated version of the paediatric investigation

plan in accordance with the agreed timing as provided for in Article 74(2) and Article

74(3);

(20) the obligation to place the medicinal product for human use on the market within two years

of the date on which the paediatric indication is authorised, as provided for in Article 59 of [revised Directive 2001/83/EC];

(21) the obligation to notify the Agency the intention to discontinue the placing on the market

of the product no less than six12 months before the discontinuation as provided for in

Article 60 of [revised Directive 2001/83/EC];

(22) the obligation to transfer the marketing authorisation or to allow a third party to use

documentation contained in the file of the medicinal product, as provided for in Article 60 of [revised Directive 2001/83/EC];

(23) the obligation to notify the Agency of the intention to discontinue the conduct of an agreed

paediatric investigation plan and provide the reasons for such discontinuation no less than six months before the discontinuation as provided in Article 88;

(24) the obligation to submit paediatric studies to the Agency or to the Member States,

including the obligation to enter information on third country clinical trials into the

European database, as provided for in Articles 91Article 94;

(25) the obligation to submit to the Agency a paediatric investigation plan with a request for

agreement or an application for a waiver from it, not later than upon completion of the human pharmaco-kineticbefore the initiation of safety and efficacy clinical studies in adults, except in duly justified cases, as provided for in Article 76(1).;

26. the obligations in accordance with Article 116, paragraph 1, points (a), (b), (c) and (d),

Article 117, Article 119, Article 125, Article 128, Article 133

(25b) the obligations to report on financial support and research and development costs as laid

down in Article 57 of [revised Directive 2001/83/EC].

ANNEX III

PROCEDURE AND CRITERIA GOVERNING INSPECTIONS CARRIED OUT BY THE

AGENCY IN THE INTEREST OF THE UNION

Reasoned request by the competent authority

The supervisory authority may submit after consultation with the Agency, a reasoned request to the Agency to carry out an inspection or to participate with its inspectors to an inspection carried out of a site located in a third country. The reasoned request should specify:

- The precise identification of the site, the scope of the inspections and if relevant the

concerned products;

- The timeline for this inspection to be completed;

- The reasons for requesting the support of the Agency, by reference to the criteria set out in

this Annex.

The Agency may refuse an inspection request after consideration of the request, the scope and availability of internal inspection capacity.

Assessment by the Agency

The Agency decides whether it accepts to carry out such inspection or to participate with its inspectors in such inspection, based on the following criteria:

- The site is located in a non-EU/EEA country;

- The inspection is in the interest of the Union, when one or more of the following situations

apply to ensure faster or continuous access to medicines of patients:

- to prevent, mitigate or address shortages of medicinal products or their active substances or

other supply issues;

- to prevent, mitigate or address a possible threat to public health, a public health emergency

or a major event which requires immediate action;

- to address a suspicion of non-compliance of the manufacturing site;

- to enable the process of granting of the marketing authorisation for centrally authorised

products/emergency use authorisation and for their active substance master files;

- to improve the oversight of medicines production worldwide;

- to address serious challenges of an unexpected and temporary nature with inspections

capacities at national level;

- other relevant situations.

The compilation of Union procedures on inspections and exchange of information referred to in Article 3(1) of Directive 2017/1572 might be updated to cover rules applicable to situations where the Agency may be requested to carry out an inspection or to participate in a joint inspection.

In the context of inspections referred under Article 78 of Regulation (EU) 536/2014, the above criteria apply mutatis mutandis.

An inspection is in the interest of the Union when there is a need to ensure faster or continuous access to medicines for patients and when the inspection is justified based on at least one of the following grounds:

(a) to prevent, mitigate or address shortages of medicinal products, or their active substances or other supply issues, or

(b) to prevent, mitigate or address a possible threat to public health, a public health emergency or a major event which requires immediate action, or

(c) to address a suspicion of non-compliance of the manufacturing site, or

(d) to enable the process of granting the marketing authorisation for centrally authorised products/emergency use authorisation and for their active substance master files.

ANNEX IV

AVAILABILITY

Part I

Information to be provided in case of a suspension or cessation of marketing of a medicinal product or withdrawal of the marketing authorisation of a medicinal product

For the purpose of the notification in accordance with Article 116(1), points (a), (b) and (c), the marketing authorisation holder shall notify the following minimum set of information:

(1) Product details:

(a) Product name;

(b) Active substance(s) and active substance supplier(s);

(c) Finished product manufacturer;

(d) Anatomical Therapeutic Chemical (ATC)code;

(e) Therapeutic indication(s);

(f) Pharmaceutical form;

(g) Strength(s);

(h) Route(s) of administration;

(i) Affected pack size(s);

(j) Alternative, pharmaceutical form, strength, route of administration or pack size, not affected by the suspension, cessation or withdrawal;

(k) Details of authorisation: procedure type (national (including Member State(s) involved)/ centralised marketing authorisation) and referencemarketing authorisation number;

(l) Member States in which the product is placed on the market.

(2) Details of action (suspension, cessation or withdrawal):

(a) Category of action (suspension, cessation or withdrawal);

(b) Available stock up to start date of action;

(c) Start date of action, per Member State;

(d) Reason for action and information on alternative medicinal product(s), where relevant;

(e) Impacted EU/ EEA countries;

(f) Reference to pending regulatory action, Rapid Alert (quality/ safety) or Quality

Defect Report related to the action, if relevant;

(g) Other competent authorities notified;

(h) Any actions completed or planned based on a request of the competent authorities of the Member State concerned.

(3) Contact details

(a) Marketing authorisation holder name and address; (b) Name and contact details of person notifying.

Part II

Risk assessment of impact of suspension, cessation or withdrawal

For the purpose of the request made by the competent authority concerned in accordance with Article 118(2), the marketing authorisation holder shall notify at least the following information:

(1) Risk assessment of impact of suspension, cessation or withdrawal, including:

(a) Potential alternative medicinal products;

(b) Estimated market share per Member State in previous 12 months;

(c) Quantities delivered per month per Member State in previous 12 months;

(d) Manufacturing capacity globally per manufacturing site;

(e) Forecast of supply per month and per Member State until suspension, cessation or withdrawal occurs;

(f) Forecast of demand per month and per Member State in next 6 months;

(g) Impact on the supply of other medicinal products from the same marketing authorisation holder;

(h) Potential impact on the consumption of or demand for other medicinal products.

(2) Any risk-mitigating measures taken by the marketing authorisation holder to address the

shortage.

Part III

Information to be provided in case of a temporary disruption of supply (to monitor potential or actual shortage)

For the purpose of the notification in accordance with Article 116(1), point (d) the marketing authorisation holder shall notify the following information:

(1) Product details

(a) Product name;

(b) Active substance(s) and active substance manufacturer(s);

(c) Finished product manufacturer;

(d) Therapeutic indication(s);

(e) ATC code;

(f) Pharmaceutical form;

(g) Strength(s);

(h) Route(s) of administration;

(i) Affected pack size;

(j) Alternative, pharmaceutical form, strength, route of administration or pack size, not affected by the supply disruption;

(k) Details of authorisation: procedure type (national (including Member State(s) involved)/ centralised marketing authorisation) and referencemarketing authorisation number;

(l) Member States in which the product is placed on the market.

(2) Details of supply disruption

(a) Shortage status (actual, expected or potential);

(b) Available stock per month

(c) Expected start date of shortage by Member State;

(d) Expected end date of shortage by Member State; (e) Reason for shortage; providing information on:

(i) Manufacturing issues including, but not limited to:

- Unavailability of active pharmaceutical ingredient

- Unavailability of excipients

- Unavailability of other raw materials

- Issues with the equipment,

- Delay in the release of the finished product,

- GMP non–compliance,

- Manufacturing site transfer

- Capacities issues

- Other manufacturing issues

(ii) Quality issues;

(iii) Distribution issues, including but not limited to:

- Export restrictions/bans

- Import/export delays

- Transport issues

- GDP non-compliance

- Other distribution issues

(iv) Unexpected increase in demand, including but not limited to:

- Changes in prescribing behaviour

- Unavailability from other MAHs - Other issues related to increased demand

(v) Commercial reasons; including but not limited to:

- Change of the MAH Business strategy

- Insolvency proceedings of the manufacturer or MAH

- Other commercial reasons

(vi) Regulatory issues; including but not limited to: Pending variation to the terms of the marketing authorisation Other regulatory issues

(vii) any other reasons.

(f) Impacted EU/ EEA countries and where available other impacted countries;

(g) Reference to pending regulatory action, Rapid Alert (quality/ safety) or Quality

Defect Report related to the action, if relevant;

(h) Other competent authorities notified;

(i) Any actions completed or planned based on a request of competent authorities of Member State concerned.

(3) Contact details

(a) Marketing authorisation holder name and address; (b) Name and contact details of person notifying.

Part IV

The Shortage Mitigation Plan

For the purpose of the request made by the competent authority concerned in accordance with

Article 118(2), the marketing authorisation holder shall notify at least the following information:

1. Shortage mitigation plan, detailing the risk assessment of impact of shortage, including,

where available:

(a) Potential alternative medicinal products;

(b) Estimated market share by Member State in previous 12 months;

(c) Quantities delivered per month per Member State, in previous 12 months;

(d) Manufacturing capacity globally per manufacturing site;

(e) Forecast of supply per month and per Member State for the duration of the shortage,

(f) Forecast of demand per month and per Member State for the duration of the shortage;

(g) Impact on the supply of other medicinal products from the same marketing authorisation holder;

(h) Potential impact on the consumption of or demand for other medicinal products;

(i) Any risk-mitigating measures taken or planned by the marketing authorisation holder to address the shortage.

Part V

The shortage prevention plan

The Shortage Prevention Plan referred to in Article 117 shall contain the following minimum set of information:

(1) Product details:

(a) Product name;

(b) Active substance(s) and active substance manufacturer(s);

(c) Finished product manufacturer;

(d) ATC code;

(e) Therapeutic indication(s);

(f) Pharmaceutical form;

(g) Strength(s);

(h) Route(s) of administration;

(i) Pack size(s);

(j) Details of authorisation: procedure type (national (including Member State(s) involved)/ centralised marketing authorisation) and referencemarketing authorisation number;

(k) Member States in which the product is placed on the market.

(2) Shortage prevention measures and supply chain risk assessment:

(a) Patient impact of potential supply disruptions, considering therapeutic indication and alternative marketed medicinal products and estimated market share by

Member States in the previous 12 months;

(b) Supply chain map, with risk identification and analysis with particular attention to

supply chain vulnerabilities;

risk assessment ,

to include:

)

i

(

Supply chain map,

including the list of manufacturing sites, their location

and share of production volumes per manufacturing site at the different

steps

of manufacturing process with particular attention to supply chain

vulnerabilities an

d dependencies;

(

ii

)

A record of root causes of resolved shortages and mitigation measures taken

(

ba

)

Final risk classification (low, medium, high) covering both supply chain

supply chain vulnerabilities;

risk assessment ,

to include:

)

i

(

Supply chain map,

including the list of manufacturing sites, their location

and share of production volumes per manufacturing site at the different

steps

of manufacturing process with particular attention to supply chain

vulnerabilities an

d dependencies;

(

ii

)

A record of root causes of resolved shortages and mitigation measures taken

(

ba

)

Final risk classification (low, medium, high) covering both supply chain

vulnerability and public health impact, with separate risk classification if necessary.

(c)(2a) Shortage management measures, to include:

(i)(a) a risk control strategy in place, to include information on strategies to minimise risks of shortages and how these are implemented;

(ii)(b) a process for the detection and notification of supply disruptions and

(iii) a record of root causes of resolved shortages and mitigation measures taken for those shortages.

(d)(2b) Process for check of effectiveness, review and update of the shortage prevention plan.

(2c) methodology for establishing the demand forecast;

(3) Contact details

(a) Marketing authorisation holder name and address; (b) Name and details of contact person.