Source: EURLEX
Language: en
Format: md

**Council of the**
**European Union**

**Interinstitutional File:**

**2023/0131(COD)**

**COVER NOTE**

**Brussels, 28 April 2023**
**(OR. en)**

**8758/23**

**SAN 213**
**PHARM 59**
**MI 332**
**COMPET 362**
**VETER 45**
**ENV 418**
**RECH 146**
**CODEC 718**
**IA 82**

From: Secretary-General of the European Commission, signed by Ms Martine
DEPREZ, Director

date of receipt: 26 April 2023

To: Ms Thérèse BLANCHET, Secretary-General of the Council of the
European Union

No. Cion doc.: COM (2023) 193 final

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

Delegations will find attached document COM(2023) 193 finalCOM (2023) 193 final.

Encl.: COM (2023) 193 final

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EUROPEAN

COMMISSION

Brussels, 26.4.2023
COM(2023) 193 final

2023/0131 (COD)

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**

(Text with EEA relevance)

{SEC(2023) 390 final} - {SWD(2023) 192 final} - {SWD(2023) 193 final} 
{SWD(2023) 194 final}

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**EXPLANATORY MEMORANDUM**

**1.** **CONTEXT** **OF** **THE** **PROPOSAL**

**•** **Reasons for and objectives of the proposal**

EU pharmaceutical legislation has enabled the authorisation of safe, efficacious and highquality medicinal products. However, patient access to medicinal products across the EU
and security of supply are growing concerns, mirrored by recent Council conclusions [1] and
resolutions of the European Parliament [2] . There is also a growing problem of shortages of
medicinal products for many EU/EEA countries. Consequences of such shortages include
decreased quality of treatment received by patients and increased burden on health systems
and on healthcare professionals, who need to identify and provide alternative treatments.
While the pharmaceutical legislation creates regulatory incentives for innovation and
regulatory tools to support timely authorisation of innovative and promising therapies,
these products do not always reach the patient, and patients in the EU have differing levels
of access.

Moreover, innovation is not always focused on unmet medical needs, and there are market
failures, especially in the development of priority antimicrobials that can help address
antimicrobial resistance. Scientific and technological developments and digitalisation are
not fully exploited, while the environmental impact of medicinal products needs attention.
In addition, the authorisation system could be simplified to keep up with global regulatory
competition. The pharmaceutical strategy for Europe [3] is a holistic answer to the current
challenges of the pharmaceutical policy with legislative and non-legislative actions
interacting together to achieve its overall goal of ensuring EU’s supply of safe and
affordable medicinal products and supporting the EU pharmaceutical industry’s innovation
efforts [4] . Reviewing the pharmaceutical legislation is key to achieving these objectives.
However, innovation, access and affordability are also influenced by factors outside the
scope of this legislation, such as global research and innovation activities or national
pricing and reimbursement decisions. Hence, not all problems can be addressed by the
revision of the legislation alone. Despite this, EU pharmaceutical legislation can be an
enabling and connecting factor for innovation, access, affordability and environmental
protection.

The proposed revision of the EU pharmaceutical legislation builds on the high level of
public health protection and harmonisation already achieved for the authorisation of
medicinal products. The overarching aim of the reform is to ensure that patients across the
EU have timely and equitable access to medicines. Another objective of the proposal is to
enhance security of supply and address shortages through specific measures, including
stronger obligations on marketing authorisation holders to notify potential or actual
shortages and marketing withdrawals, cessations and suspensions in advance of a foreseen

1 Council conclusions on strengthening the balance in the pharmaceutical systems in the EU and its Member
States (OJ C 269, 23.07.2016, p. 31). Council conclusions on access to medicines and medical devices for a
stronger and resilient EU, 2021/C 269 I/02 (OJ C 269I, 7.7.2021, p. 3).
2 European Parliament resolution of 2 March 2017 on EU options for improving access to medicine
(2016/2057(INI), European Parliament resolution of 17 September 2020 on the shortage of medicines – how to
[address an emerging problem (2020/2071(INI).](https://oeil.secure.europarl.europa.eu/oeil/popups/ficheprocedure.do?lang=en&reference=2020/2071(INI))
3 Communication from the Commission, _Pharmaceutical Strategy for Europe_ (COM/2020/761 final),

                            -                            -                            https://health.ec.europa.eu/medicinal [products/pharmaceutical](https://health.ec.europa.eu/medicinal-products/pharmaceutical-strategy-europe_en) strategy europe_en.
4 Mission letter of the President of the European Commission to Stella Kyriakides,
[Commissioner for Health and Food Safety, mission-letter-stella-kyriakides_en.pdf (europa.eu)](https://commissioners.ec.europa.eu/system/files/2022-11/mission-letter-stella-kyriakides_en.pdf)

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interruption to continued supply of a medicinal product to the market. To support the
sector’s global competitiveness and innovative power, right balance needs to be struck
between giving incentives for innovation, with more focus on unmet medical needs, and
measures on access and affordability.

The framework needs to be simplified, adapted to scientific and technological changes, and
contribute to reducing the environmental impact of medicinal products. This proposed
reform is comprehensive but targeted and focuses on provisions relevant to achieving its
specific objectives; therefore it covers all provisions apart from those concerning
advertising, falsified medicinal products, and homeopathic and traditional herbal medicinal
products.

Therefore, the objectives of the proposal are the following:

_General objectives_

–
guarantee a high level of public health by ensuring the quality, safety and efficacy of
medicinal products for EU patients;

–
harmonise the internal market for the supervision and control of medicinal products
and the rights and duties incumbent upon the competent authorities of the Member
States.

_Specific objectives_

–
make sure all patients across the EU have timely and equitable access to safe,
effective, and affordable medicines;

–
enhance security of supply and ensure medicines are always available to patients,
regardless of where they live in the EU;

–
offer an attractive innovation-and competitiveness friendly environment for research,
development, and production of medicines in Europe;

–
make medicines more environmentally sustainable.

All the general and specific objectives set out above are also relevant for the areas of
medicinal products for rare diseases and for children.

**•** **Consistency with existing provisions in the policy area**

The current EU pharmaceutical legislation includes both general and specific legislation.
Directive 2001/83/EC of the European Parliament and of the Council [5] and Regulation (EC)
No 726/2004 of the European Parliament and of the Council [6] (together ‘general
pharmaceutical legislation’) lay down provisions related to medicinal products
authorisation and post-authorisation requirements, pre-authorisation support schemes,
regulatory incentives in terms of data and market protection, manufacturing and supply,
and the European Medicines Agency (EMA). The general pharmaceutical legislation is
complemented by specific legislation on medicinal products for rare diseases (Regulation
(EC) No 141/2000, the ‘Orphan Regulation’ [7] ), medicinal products for children (Regulation

5 Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community
code relating to medicinal products for human use (OJ L 311, 28.11.2001, p. 67).
6 Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down
Community procedures for the authorisation and supervision of medicinal products for human and veterinary
use and establishing a European Medicines Agency (OJ L 136, 30.4.2004, p. 1).
7 Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan
medicinal products (OJ L 18, 22.1.2000, p. 1).

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(EC) No 1901/2006, the ‘Paediatric Regulation’ [8] ) and advanced therapy medicinal
products (Regulation (EC) No 1394/2007, the ‘ATMP Regulation’ [9] ). The proposed
revision of the pharmaceutical legislation will consist of two legislative proposals:

–
a new directive, repealing and replacing Directive 2001/83/EC and Directive
2009/35/EC of the European Parliament and of the Council [10] and incorporating
relevant parts of the Paediatric Regulation (Regulation (EC) No 1901/2006)

–
a new regulation, repealing and replacing Regulation (EC) No 726/2004, repealing
and replacing the Orphan Regulation (Regulation (EC) No 141/2000) and repealing
and incorporating relevant parts of the Paediatric Regulation (Regulation (EC) No
1901/2006).

The merger of the Orphan Regulation and the Paediatric Regulation with the legislation
applicable to all medicinal products will allow for simplification and increased coherence.

Medicinal products for rare diseases and for children will continue to fall under the same
provisions as any other medicinal product concerning their quality, safety and efficacy, for
example concerning the marketing authorisation procedures, pharmacovigilance and
quality requirements. However, specific requirements will also continue to apply to these
types of medicinal products in order to support their development. This is because market
forces alone have proven insufficient to stimulate adequate research and development of
medicinal products for children and patients suffering from a rare disease. Such
requirements, which are currently laid down in separate legislative acts, should be
integrated into this regulation and the directive in order to ensure clarity and coherence of
all the measures applicable to these products.

**•** **Consistency with other Union policies**

The EU pharmaceutical legislation described above has close links with several other
related pieces of EU legislation. The ‘Clinical Trials Regulation’ (Regulation (EU) No
536/2014) [11] allows for more efficient approval of clinical trials in the EU. Regulation (EU)
2022/123 [12] strengthens the role of the European Medicines Agency in order to facilitate a
coordinated EU-level response to health crises. The EMA fees legislation [13] contributes to
providing adequate financing for the EMA's activities, including respective remuneration
to national competent authorities for their contribution to completing the EMA’s tasks.

8 Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on
medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC,
Directive 2001/83/EC and Regulation (EC) No 726/2004 (OJ L 378, 27.12.2006, p. 1).
9 Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on
advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004
(OJ L 324, 10.12.2007, p. 121).
10 Directive 2009/35/EC of the European Parliament and of the Council of 23 April 2009 on the colouring
matters which may be added to medicinal products (OJ L 109, 30.4.2009, p. 10).
11 Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical
trials on medicinal products for human use, and repealing Directive 2001/20/EC (OJ L 158, 27.5.2014, p. 1).
12 Regulation (EU) 2022/123 of the European Parliament and of the Council of 25 January 2022 on a reinforced
role for the European Medicines Agency in crisis preparedness and management for medicinal products and
medical devices (OJ L 20, 31.1.2022, p. 1).
13 Council Regulation (EC) No 297/95 of 10 February 1995 on fees payable to the European Agency for the
Evaluation of Medicinal Products, and Regulation (EU) No 658/2014 of the European Parliament and of the
Council on fees payable to the European Medicines Agency for the conduct of pharmacovigilance activities in
respect of medicinal products for human use (OJ L 35, 15.2.1995, p. 1).

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There are also links with EU regulatory frameworks for other health products. EU
legislation on blood, tissues and cells (BTC) [14] is relevant, as some substances of human
origin are starting materials for medicinal products. The EU regulatory framework for
medical devices [15] is also relevant, as there are products that combine medicinal products
and medical devices.

Futhermore, the objectives of the proposed reform of the pharmaceutical legislation are
consistent with those of a number of broader EU policy agendas and initiatives.

In terms of promoting innovation, Horizon Europe [16], a key funding programme for EU
research and innovation, and Beating Cancer Plan [17] both support research and development
of new medicinal products. In addition, innovation in the pharmaceutical sector is
promoted by the intellectual property frameworks, on patents under the national patent
laws, the European Patent Convention and the Trade-Related Aspects of Intellectual
Property Rights (TRIPS) agreement, and on supplementary protection certificates under
the EU SPC Regulation [18] . The intellectual property action plan [19] under the Industrial
Strategy includes modernising the system of supplementary protection certificates (SPCs).
SPCs extend certain patent rights to protect innovation and compensate for lengthy clinical
trials and marketing authorisation procedures. With regard to addressing unmet medical
needs in the area of antimicrobial resistance, the proposed reform of the pharmaceutical
legislation will contribute to the objectives of the European one health action plan against
antimicrobial resistance (AMR) [20] .

Concerning access to medicinal products, in addition to the pharmaceutical legislation, the
intellectual property frameworks, the Health Technology Assessment (HTA) Regulation
(Regulation (EU) 2021/2282) [21] and the Transparency Directive (Directive 89/105/EEC) [22]
also play a role. In addition to extending certain patent rights to protect innovation, SPCs
impact the effect of regulatory protection periods provided by the pharmaceutical

14 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, and 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 033, 8.2.2003, p.
30).
15 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) and Regulation (EU)
2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices
and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (OJ L 117, 5.5.2017, p. 176).
16 Regulation (EU) 2021/695 of the European Parliament and of the Council of 28 April 2021 establishing

–
Horizon Europe the Framework Programme for Research and Innovation, laying down its rules for
participation and dissemination, and repealing Regulations (EU) No 1290/2013 and (EU) No 1291/2013 (OJ L
170, 12.5.2021, p. 1).
17 Communication from the Commission, _Europe's Beating Cancer Plan_ (COM/2021/44 final).
18 Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the
supplementary protection certificate for medicinal products (OJ L 152, 16.6.2009, p. 1).
19 Communication from the Commission, _Making the most of the EU’s innovative_ _potential. An intellectual_
_property action plan to support the EU’s recovery and resilience_ (COM/2020/760 final).
20 Communication from the Commission, _A European One Health Action Plan against Antimicrobial Resistance_
_(AMR)_ [, https://ec.europa.eu/health/system/files/2020-01/amr_2017_action-plan_0.pdf.](https://ec.europa.eu/health/system/files/2020-01/amr_2017_action-plan_0.pdf)
21 Regulation (EU) 2021/2282 of the European Parliament and of the Council of 15 December 2021 on health
technology assessment and amending Directive 2011/24/EU (OJ L 458, 22.12.2021, p. 1).
22 Council Directive 89/105/EEC of 21 December 1988 relating to the transparency of measures regulating the
prices of medicinal products for human use and their inclusion in the scope of national health insurance
systems (OJ L 40, 11.2.1989, p. 8).

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legislation and therefore the entry of generic and biosimilar medicinal products and
ultimately patient access to medicinal products and affordability. Under the HTA
Regulation, national HTA bodies will conduct joint clinical assessments that compare new
medicinal products to existing ones. Such joint clinical assessments will help Member
States take more timely and evidence-based decisions on pricing and reimbursement.
Finally, the Transparency Directive regulates procedural aspects of the Member States’
pricing and reimbursement decisions but does not effect the level of price.

In order to enhance security of supply of medicinal products, the proposed reform of the
pharmaceutical legislation aims to address systemic shortages and supply chain challenges.
The proposed reform therefore complements and further develops the roles of the Member
States and competent authorities of the Member States as set out in the extension of the
EMA mandate (Regulation (EU) 2022/123), and is aimed at ensuring access to and
continued supply of critical medicinal products during health crises. It also complements
the mission of the Health Emergency Preparedness and Response Authority (HERA) to
ensure availability of medical countermeasures in preparation for and during health crises.
The proposed reform of the pharmaceutical legislation is therefore consistent with the
package of legislative initiatives related to health security under the European Health
Union [23] .

To address environmental challenges, the proposed reform of the pharmaceutical
legislation will support initiatives under the European Green Deal [24] . These include the EU
action plan ‘Towards Zero Pollution for Air, Water and Soil’ and the revision of: (i) the
Urban Waste Water Treatment Directive [25], (ii) the Industrial Emissions Directive [26] and
(iii) the list of surface and groundwater pollutants under the Water Framework Directive [27] .
The proposal is also well aligned with the Strategic Approach to Pharmaceuticals in the
Environment [28] .

Finally, on the use of health data, the European Health Data Space [29] will provide a
common framework across Member States for access to high-quality real world health
data. This will promote progress in research and development of medicinal products and
provide new tools for pharmacovigilance and comparative clinical assessments. By
facilitating access to and use of health data, the two initiatives together will support the
competitiveness and innovation capacity of the EU’s pharmaceutical industry.

23 European Health Union - Protecting the health of Europeans and collectively responding to cross-border health
crises,
[https://commission.europa.eu/strategy-and-policy/priorities-2019-2024/promoting-our-european-way-](https://commission.europa.eu/strategy-and-policy/priorities-2019-2024/promoting-our-european-way-life/european-health-union_en)
[life/european-health-union_en.](https://commission.europa.eu/strategy-and-policy/priorities-2019-2024/promoting-our-european-way-life/european-health-union_en)
24 Communication from the Commission. The European Green Deal. COM(2019) 640 final.
25 Council Directive 91/271/EEC of 21 May 1991 concerning urban waste-water treatment (OJ L 135, 30.5.1991,
p. 40).
26 Directive 2010/75/EU of the European Parliament and of the Council of 24 November 2010 on industrial
emissions (integrated pollution prevention and control) (OJ L 334 17.12.2010, p. 17).
27 Directive 2000/60/EC of the European Parliament and of the Council of 23 October 2000 establishing a
framework for Community action in the field of water policy (OJ L 327, 22.12.2000, p. 1) and Directive
2013/39/EU of the European Parliament and of the Council of 12 August 2013 amending Directives
2000/60/EC and 2008/105/EC as regards priority substances in the field of water policy Text with EEA
relevance (OJ L 226, 24.8.2013, p. 1).
28 Strategic Approach to Pharmaceuticals in the Environment,
[https://ec.europa.eu/environment/water/water-dangersub/pharmaceuticals.htm.](https://ec.europa.eu/environment/water/water-dangersub/pharmaceuticals.htm)
29 Communication from the Commission, _A European Health Data Space: harnessing the power of health data_
_for people, patients and innovation_ (COM(2022) 196 final).

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**2.** **LEGAL** **BASIS,** **SUBSIDIARITY** **AND** **PROPORTIONALITY**

**•** **Legal basis**

The proposal is based on Articles 114(1) and 168(4), point (c), of the Treaty on the
Functioning of the European Union (TFEU). This is consistent with the legal basis of
existing EU pharmaceutical legislation. Article 114(1) has as its object the establishment
and functioning of the internal market, while Article 168(4), point (c), relates to the setting
of high standards for the quality and safety of medicinal products.

**•** **Subsidiarity (for non-exclusive competence)**

Common standards of quality, safety and efficacy for the authorisation of medicinal
products constitute a cross-border public health issue that affects all Member States and
thus can be regulated effectively only at EU level. EU action relies also on the single
market to achieve a stronger impact as regards access to safe, effective and affordable
medicinal products, and with regard to the security of supply across the EU. Uncoordinated
measures by Member States may result in distortions of competition and barriers to intraEU trade for medicinal products that are relevant for the entire EU, and would also likely
increase administrative burden for pharmaceutical companies, which often operate in more
than one Member State.

A harmonised approach at EU level also provides greater potential for incentives to
support innovation and for concerted action to develop medicinal products in areas of
unmet medical needs. Moreover, simplification and streamlining of processes under the
proposed reform are expected to reduce administrative burden for companies and
authorities and hence improve the efficiency and attractiveness of the EU system. The
reform will also have a positive influence on the competitive functioning of the market
through targeted incentives and other measures that facilitate early market entry of generic
and biosimilar medicinal products, contributing to patient access and affordability.
Nevertheless, the proposed reform of the pharmaceutical legislation respects Member
States’ exclusive competence in the provision of health services, including pricing and
reimbursement policies and decisions.

**•** **Proportionality**

The initiative does not go beyond what is necessary to achieve the objectives of the reform.
It does so in a way that is conducive to national action, which would otherwise not be
sufficient to achieve those objectives in a satisfactory way.

The principle of proportionality has been reflected in the comparison of different options
evaluated in the impact assessment. For example, trade-offs are inherent between the
objective of innovation (promoting the development of new medicinal products) and the
objective of affordability (which is often achieved by generic/biosimilar competition). The
reform maintains the incentives as a key element for innovation, but they are adapted to
better encourage and reward product development in areas of unmet medical needs and to
better address timely patient access to medicinal products in all Member States.

**•** **Choice of the instrument**

The proposed regulation introduces a large number of amendments to Regulation (EC) No
726/2004. It also incorporates part of the current provisions and amendments to Regulation
(EC) No 1901/2006, as well as current provisions and amendments to Regulation (EC) No
141/2000. A new regulation repealing Regulation (EC) No 726/2004, Regulation (EC) No
141/2000 and Regulation (EC) No 1901/2006 (rather than an amending regulation) is
therefore considered the appropriate legal instrument.

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**3.** **RESULTS** **OF** **EX-POST** **EVALUATIONS,** **STAKEHOLDER** **CONSULTATIONS**
**AND** **IMPACT** **ASSESSMENTS**

**•** **Ex-post evaluations/fitness checks of existing legislation**

For the reform of the general pharmaceutical legislation, stakeholder consultation activities
were carried out as part of the ‘back-to-back’ evaluations and impact assessments of the
general pharmaceutical legislation and of the Orphan and Paediatric Regulations [30] .

For medicinal products for rare diseases and for children a joint evaluation on the
functioning of the two pieces of legislation was carried out and published in 2020 [31] .

For the general pharmaceutical legislation the evaluation of the legislation showed that the
legislation continues to be relevant for the dual overarching objectives of protecting public
health and harmonising the internal market for medicinal products in the EU. The
legislation delivered on the objectives of the 2004 revision, albeit not to the same extent for
all. The objective of ensuring quality, safety and efficacy of medicinal products was
achieved to the largest extent, while patient access to medicinal products in all Member
States was achieved only to a limited extent. As to ensuring the competitive functioning of
the internal market and attractiveness in a global context, the legislation has performed to a
moderate extent. The evaluation found that the achievements or shortcomings of the 2004
revision vis-a-vis its objectives depend on many external factors outside the remit of the
legislation. These include R&D activities and international location of R&D clusters,
national pricing and reimbursement decisions, business decisions and market size. The
pharmaceutical sector and the development of medicinal products are global; research and
clinical trials conducted on one continent will support development and authorisation in
other continents; global are also the supply chains and manufacturing of medicinal
products. International cooperation to harmonise requirements to support authorisation
exists, e.g. the International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use [32] .

The evaluation identified the main shortcomings that the pharmaceutical legislation has not
adequately addressed, while recognising that these also depend on factors outside its remit.
These main shortcomings are as follows:

–
Medical needs of patients are not sufficiently met.

–
Affordability of medicinal products is a challenge for health systems.

–
Patients have unequal access to medicinal products across the EU.

–
Shortages of medicinal products are an increasing problem in the EU.

–
The medicinal product life cycle can have negative impacts on the environment.

–
The regulatory system does not sufficiently cater for innovation and in some
instances creates unnecessary administrative burden.

Concerning medicinal products for rare diseases and for children, the evaluation showed
that overall the two specific pieces of legislation have achieved positive results by allowing
more medicinal products to be developed for these two population groups. However, it also

30 Commission staff working document, Impact Assessment, Annex 5: Evaluation.
31 Evaluation of the medicines for rare diseases and children legislation,
[https://health.ec.europa.eu/medicinal-products/medicines-children/evaluation-medicines-rare-diseases-and-](https://health.ec.europa.eu/medicinal-products/medicines-children/evaluation-medicines-rare-diseases-and-children-legislation_en)
[children-legislation_en.](https://health.ec.europa.eu/medicinal-products/medicines-children/evaluation-medicines-rare-diseases-and-children-legislation_en)
32 [ICH – harmonisation for better health, https://www.ich.org/.](https://www.ich.org/)

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identified important shortcomings, which are similar to the ones identified for the general
pharmaceutical legislation:

–
Medical needs of patients with rare diseases and of children are not sufficiently met.

–
Affordability of medicinal products is a growing challenge for health systems.

–
Patients have unequal access to medicinal products across the EU.

–
The regulatory system does not sufficiently cater for innovation and in some
instances creates unnecessary administrative burden.

**•** **Stakeholder consultations**

For the reform of the general pharmaceutical legislation, stakeholder consultation activities
were carried out as part of the ‘back-to-back’ evaluation and impact assessment [33] . A single
consultation strategy was prepared for this exercise, including consultation activities
looking backward and forward. It aimed to collect inputs and perspectives of all
stakeholder groups both on the evaluation of the legislation and for the impact assessment
of different possible policy options for the reform.

The following key stakeholder groups were identified as priority groups in the consultation
strategy: the public; organisations representing patients, consumers and civil society active
in public health and social issues (‘CSOs’); healthcare professionals and healthcare
providers; researchers, academia and learned societies (academics); environmental
organisations; the pharmaceutical industry and their representatives.

As part of the internal policy work process supporting the revision, the Commission
collaborated with the European Medicines Agency (EMA) and the competent authorities of
the Member States (NCAs) dealing with the regulation of medicinal products. Both actors
play a pivotal role in implementing the pharmaceutical legislation.

Information was collected through consultations that took place between 30 March 2021
and 25 April 2022. These consisted of:

– feedback on the Commission’s combined evaluation roadmap/inception impact
assessment (30 March-27 April 2021);

–
Commission online public consultation (28 September-21 December 2021);

–
targeted stakeholder surveys with public authorities, the pharmaceutical industry
including SMEs, academia, civil society representatives and healthcare providers
(survey) (16 November 2021-14 January 2022);

–
interviews (2 December 2021-31 January 2022);

–
a validation workshop on the evaluation findings (workshop-1) on 19 January 2022;

–
a validation workshop on the impact assessment findings (workshop 2) on 25 April
2022.

There was broad consensus among stakeholders that the current pharmaceutical system
guarantees a high level of patient safety on which the revision can build to address new
challenges and improve supply of safe and affordable medicinal products, patient access
and innovation, especially in areas where the medical needs of patients are not met. The
public, patients and civil society organisations expressed their expectation of equitable

33 Commission staff working document, Impact Assessment, Annex 2: Stakeholder Consultation (Synopsis
Report).

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access to innovative therapies across the EU, including for unmet medical needs, and
continuous supply of their medicinal products. Public authorities and patient organisations
opted for a variable duration for the current main incentives, as reflected in the preferred
option. The pharmaceutical industry argued against any introduction of variable incentives
or the shortening of existing ones and favoured the introduction of additional or novel
incentives. Industry also highlighted the need for stability in the current legal framework
and predictability for incentives. The elements on the environment, regulatory support for
non-commercial entities and repurposing of medicinal products included in the preferred
option were supported by key stakeholders such as healthcare providers, academia and
environmental organisations.

Concerning the revision of the legislation on medicinal products for children and for rare
diseases, specific consultation activities were carried out in the context of the impact
assessment procedure: a public consultation ran from 7 May to 30 July 2021. Furthermore,
targeted surveys, including a costing survey both for pharmaceutical companies and public
authorities, were conducted from 21 June to 30 July 2021 (late responses were accepted
until the end of September 2021, due to the summer break). An interview programme with
all relevant stakeholder groups (public authorities, pharmaceutical industry including
SMEs, academia, civil society representatives and healthcare providers) was conducted at
the end of June 2021, while focus groups met on 23 February 2022 to discuss some of the
main issue of the revision.

There was broad consensus among stakeholders that the two pieces of legislation have had
a positive effect on the development of medicinal products for children and the treatment
of rare diseases. However, concerning the Paediatric Regulation, all the current structure of
the paediatric investigation plan and of the condition allowing the waiver of the obligation
to draw up such a plan were considered as possible obstacles to the development of certain
innovative products. All stakeholders highlighted that for both the medicinal products for
rare diseases and the medicinal products for children, medicinal products addressing unmet
medical needs of patients should be better supported. Public authorities supported a
variable duration for market exclusivity for medicinal products for rare diseases as a tool to
better focus development in areas where treatments are not available. The pharmaceutical
industry argued any introduction of variable incentives or the shortening of existing ones
and favoured the introduction of additional or novel incentives. As for the revision of the
general pharmaceutical legislation, industry also highlighted the need for stability in the
current legal framework and predictability for incentives.

**•** **Collection and use of expertise**

In addition to the extensive stakeholder consultation described in previous sections, the
following external studies were conducted to support the ‘back-to-back’ evaluation and
impact assessment of the general pharmaceutical legislation and the evaluation and impact
assessment of the orphan and paediatric legislation:

–
_Study supporting the Evaluation and Impact Assessment of the general_
_pharmaceutical legislation. Evaluation Report_, Technopolis Group (2022).

–
_Study supporting the Evaluation and Impact Assessment of the general_
_pharmaceutical legislation. Impact Assessment Report_, Technopolis Group (2022).

– _Future-proofing pharmaceutical legislation - Study on medicine shortages_,
Technopolis Group (2021).

–
_Study to support the evaluation of the EU Orphan Regulation_, Technopolis Group
and Ecorys (2019).

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–
_Study on the economic impact of supplementary protection certificates,_
_pharmaceutical incentives and rewards in Europe_, Copenhagen Economics (2018).

–
_Study on the economic impact of the Paediatric Regulation, including its rewards_
_and incentives_, Technopolis Group and Ecorys (2016).

**•** **Impact assessments**

_**General pharmaceutical legislation**_

The impact assessment for the revision of the general pharmaceutical legislation [34] analysed
three policy options (A, B and C).

–
Option A builds on the status quo and achieves the objectives mainly through new
incentives.

–
Option B reaches the objectives through more obligations and oversight.

–
Option C adopts a ‘quid pro quo’ approach in the sense that positive behaviour is
rewarded and obligations are only used when there are no alternatives.

Option A maintains the current system of regulatory protection for innovative medicinal
products and adds additional conditional periods of protection. Priority antimicrobials
benefit from a transferable exclusivity voucher. Current requirements on security of supply
are retained (notification of withdrawal at least 2 months in advance). The existing
requirements on the environmental risk assessment continue with additional information
obligations.

Option B provides for a variable duration of regulatory data protection periods (split into
standard and conditional periods). Companies must either have an antimicrobial in their
portfolio or pay into a fund to finance the development of new ones. Companies are
obliged to launch medicinal products with an EU-wide authorisation in the majority of
Member States (small markets included) and to provide information on public funding
received. Current requirements on security of supply are retained and companies are
obliged to offer their marketing authorisation for transfer to another company before
withdrawal. The environmental risk assessment results in additional responsibilities for
companies.

Option C provides for a variable duration of regulatory data protection (split into standard
and conditional periods), striking a balance between providing attractive incentives for
innovation and supporting timely patient access to medicinal products across the EU.
Priority antimicrobials can benefit from a transferable exclusivity voucher subject to strict
eligibility criteria and conditions for use of the voucher, while prudent-use measures
further contribute to addressing antimicrobial resistance. Marketing authorisation holders
are required to ensure transparency on public funding for clinical trials. Reporting of
shortages is harmonised and only critical shortages are brought to the attention of
authorities at the EU level. Marketing authorisation holders are obliged to notify possible
shortages earlier and to offer their marketing authorisation for transfer to another company
before withdrawal. Requirements on the environmental risk assessment and conditions of
use are strengthened.

All options are complemented by a set of common elements aimed at simplifying and
streamlining regulatory procedures and future-proofing the legislation with a view to
accommodating novel technologies.

34 Commission staff working document, Impact Assessment.

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The preferred option is based on option C and also includes the common elements
mentioned above. The preferred option was considered to be the best policy choice, taking
into account the specific objectives of the reform and the economic, social and
environmental impacts of the proposed measures.

The preferred option and its introduction of variable incentives is a cost-effective way of
achieving the objectives of improved access, addressing unmet medical need and
affordability for health systems. It is expected to provide 8% increased access, meaning 36
million more people residing in the EU who can potentially benefit from a new medicinal
product, EUR 337 million in annual gains for public payers, and more medicinal products
addressing unmet medical needs. In addition, savings are expected for companies and
regulatory authorities through the cross-cutting measures that would allow for better
coordination, simplification and accelerated regulatory processes.

Measures to incentivise the development of priority antimicrobials are estimated to entail
costs for public payers and the generic industry but could be effective against antimicrobial
resistance if applied under strict conditions and with tight measures for prudent use. These
costs must also be seen in the context of the threat of resistant bacteria and current costs
incurred from antimicrobial resistance including deaths, healthcare costs and productivity
losses. The principal costs for industry are associated with shorter default regulatory data
protection period and conditions for extensions of regulatory data protection, and with
increased reporting on shortages and environmental risks. Regulatory authorities will incur
costs to perform additional tasks in the areas of shortage management, strengthened
environmental risk assessment and enhanced pre-authorisation scientific and regulatory
support.

_**Orphan and paediatric legislation**_

The impact assessment on the revising of the _orphan_ and _paediatric_ legislation also
analysed three policy options (A, B and C) per legislative act. The different policy options
vary as to the incentives or rewards to which medicinal products for rare diseases and for
children would be entitled. In addition, the revision will include a series of common
elements present in all options.

For medicinal products for _rare diseases_, option A keeps the 10 years of market
exclusivity and adds - as an additional incentive - a transferable regulatory protection
voucher for products addressing a high unmet medical need (HUMN) of patients. Such a
voucher allows for a one-year extension in the length of regulatory protection or can be
sold to another company and used for a product in that company’s portfolio.

Option B abolishes the current market exclusivity of 10 years for all orphan medicinal
products.

Option C provides for a variable duration of market exclusivity of 10, 9 and 5 years, based
on the type of orphan medicinal product (for HUMN, new active substances and wellestablished use applications respectively). A ‘bonus’ market exclusivity extension of 1 year
can be granted, based on patient accessibility in all relevant Member States, but only for
HUMN products and new active substances.

All options are complemented by a set of common elements aimed at simplifying and
streamlining regulatory procedures and future-proofing the legislation.

Option C was considered to be the best policy choice, taking into account the specific
objectives and the economic and social impacts of the proposed measures. This option is
expected to provide a balanced positive outcome contributing to the achievement of the
four objectives of the revision. It will aim to refocus investments and boost innovation, in

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particular in products addressing HUMN, without undermining the development of other
medicinal products for rare diseases. The measures provided for under this option are also
expected to improve the competitiveness of EU pharmaceutical industry, including of
SMEs, and will lead to the best results in terms of patient access (due to: (i) the possibility
for generics and biosimilars to enter the market earlier than they do today; and (ii) the
proposed access conditionality for extending the market exclusivity). Furthermore, more
flexible criteria to better define an orphan condition will make the legislation more ‘fit’ to
accommodate new technologies and reduce administrative burdens.

The total balance of yearly costs and benefit calculated per interested stakeholder group for
this preferred option compared to the baseline are: EUR 662 million cost savings for public
payers from accelerated generic entry and a EUR 88 million profit gain for the generic
industry. The public will benefit from additional 1 or 2 HUMN medicinal products and
overall broader and faster access for patients. Originators will see an estimated EUR 640
million gross profit loss from earlier generic entry, but savings are expected for companies
through the cross-cutting measures in the general pharmaceutical legislation that would
allow for better coordination, simplification and accelerated regulatory processes.

For medicinal products _for children_, in option A the 6-month supplementary protection
certificate (SPC) extension is kept as a reward for all medicinal products completing a
paediatric investigation plan (‘PIP’). Furthermore, an extra reward benefiting products
addressing unmet medical needs of children is added. This will consist of either 12 extra
months of SPC extension or a regulatory protection voucher (duration 1 year), which could
be transferred to another product (possibly of another company) against payment, allowing
the receiving product to benefit from extended regulatory data protection (+1 year). In
option B, the reward for completing a PIP is abolished. Developers of every new medicinal
product would continue to be obliged to agree with the EMA and conduct a PIP, but the
extra costs incurred would not be rewarded. In option C, like today, the 6-month SPC
extension remains the main reward for completing a PIP. All options are complemented by
a set of common elements aimed at simplifying and streamlining regulatory procedures and
future-proofing the legislation .

Option C was considered the best policy choice, taking into account the proposed
measures’ specific objectives and economics and social impacts. Option C is expected to
yield to an increased number of medicinal products, in particular in areas of unmet medical
needs of children, which are expected to reach children faster than today. It would also
ensure a fair return of investment for medicinal products developers who fulfil the legal
obligation to study medicinal products in children, as well as reduced administrative costs
linked to the procedures that follow from the obligation.

New simplification measures and obligations (for example those linked to medicinal
product’s mechanism of action) are expected to cut time to access to children’s versions of
medicinal products by 2-3 years and to bring three more new medicinal products for
children yearly compared to the baseline, which in turn results in additional rewards for
developers. These new medicinal products for children will result, on a yearly basis, in
costs for the public estimated EUR 151 million, while originator companies would gain
EUR 103 million in gross profits to compensate their efforts. Thanks to simplification of
the rewards scheme linked to the study of medicinal products for use in children, generic
companies will find it easier to predict when they will be able to enter the market.

**•** **Regulatory fitness and simplification**

The proposed revisions aim to simplify the regulatory framework and improve its
effectiveness and efficiency, thereby reducing the administrative costs borne by companies

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and competent authorities. Most of the envisaged measures will act on core procedures for
the authorisation and life cycle management of medicinal products.

Administrative costs will fall for competent authorities, business and other relevant
entities, for two overarching reasons. Firstly, procedures will be streamlined and
accelerated, for example in connection with the renewal of marketing authorisations and
the submission of variations or the transfer of the responsibility for orphan designations
from the Commission to the EMA. Secondly, there will be enhanced coordination of the
European medicines regulatory network, for example in terms of the work of different
EMA committees and interactions with related regulatory frameworks. Further
contributions to cost reductions for business and administrations are expected to come
from adaptations to accommodate new concepts such as adaptive clinical trials, a
medicinal product’s mechanism of action, use of real world evidence, and new uses of
health data within the regulatory framework.

Enhanced digitisation will facilitate the integration of regulatory systems and platforms
across the EU and support for the re-use of data, and is expected to reduce costs for
administrations over time (although it may induce initial one-off costs). For example,
electronic submissions by industry to the European Medicines Agency and competent
authorities of the Member States will deliver cost savings to industry. Moreover, the
envisaged use of the electronic product information (as opposed to paper leaflets) should
also lead to administrative cost reductions.

SMEs and non-commercial entities involved in the development of medicinal products are
expected to benefit in particular from the envisaged simplification of procedures, wider use
of electronic processes and reduction of administrative burden. The proposal also aims at
optimising the regulatory support (e.g. scientific advice) to SMEs and non-commercial
organisations, resulting in additional reductions of administrative costs for these parties.

Overall, the envisaged measures for simplification and burden reduction are expected to
reduce costs for businesses, supporting the ‘one in one out’ approach. In particular, the
proposed streamlining procedures and enhanced support are expected to yield cost savings
for EU pharmaceuticalindustry.

**•** **Fundamental rights**

The proposal contributes to achieving a high level of human health protection and is
therefore consistent with Article 35 of the Charter of Fundamental Rights of the European
Union.

**4.** **BUDGETARY** **IMPLICATIONS**

The budgetary implications are set out in the legislative financial statement attached to the
proposal.

Budgetary implications are mainly related to additional tasks to be carried out by the
European Medicines Agency in terms of providing scientific, administrative and IT support
in the following main areas:

–
enhanced pre-authorisation scientific and regulatory support;

–
decision-making on orphan designations and management of the Union Register of
designated orphan medicinal products;

–
active substance master file assessment and certification;

–
inspection capacities for inspections in third countries and support to Member States;

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–
environmental risk assessment strengthening;

–
shortage management and security of supply.

**5.** **OTHER** **ELEMENTS**

**•** **Implementation plans and monitoring, evaluation and reporting arrangements**

The development of new medicinal products can be a long process that can take up to 1015 years. Incentives and rewards therefore have an influence many years after the
marketing authorisation date. The benefit for patients also needs to be measured over a
period of at least 5-10 years after a medicinal product is authorised. The Commission
intends to monitor relevant parameters that enable assessment of progress of the proposed
measures with a view to reaching their objectives. The majority of indicators are already
collected at the EMA level. Furthermore, the Pharmaceutical Committee [35] will provide a
forum for discussing issues related to the transposition and monitoring progress. The
Commission will report on the monitoring periodically. A meaningful evaluation of the
results of the revised legislation can only be envisaged after at least 15 years from its entry
into application.

**•** **Detailed explanation of the specific provisions of the proposal**

The proposed revision of the pharmaceuticals legislation consists of a proposal for a new
regulation and a proposal for a new directive (see previous section ‘Consistency with
existing provisions in the policy area’), which will also cover orphan and paediatric
medicinal products. Provisions for orphan medicinal products have been integrated in the
proposed regulation. For paediatric medicinal products, procedural requirements applicable
to these products are primarily integrated in the proposed regulation, while the general
framework for the authorisation and rewarding of these products has been included in the
new directive. The main areas of revision under the proposed new directive are covered by
the explanatory memorandum for the accompanying proposal for a directive.

The proposed regulation includes the following main areas of revision:

_**Promoting innovation and access to affordable medicines creating a balanced**_
_**pharmaceutical**_ _**ecosystem**_

To enable innovation and promote the competitiveness of the EU pharmaceutical industry,
in particular small and medium-sized firms, the provisions of the proposed regulation work
in synergy with those of the proposed directive.

In this respect, a balanced system of incentives is proposed. The system rewards
innovation, especially in areas of unmet medical need, and innovation reaches patients and
improves access across the EU, including for medicines for rare diseases. To make the
regulatory system more efficient and innovation-friendly, measures are proposed to
simplify and streamline procedures and to create an agile and future-proof framework (see
the measures proposed further below under ‘ _Reducing regulatory burden and providing a_
_flexible regulatory framework to support innovation and competitiveness’_ and in the
proposed directive).

_Modulation of the length of the market exclusivity for orphan medicinal products_

The proposed regulation continues to provide measures to promote research, development
and authorisation for medicinal products to address the unmet medical needs of people

35 Council Decision of 20 May 1975 setting up a pharmaceutical committee (75/320/EEC).

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living with rare diseases, and it targets more those areas of high unmet medical needs
(HUMN), where research is most needed and investment is riskier. Criteria to identify
medicinal products addressing HUMN are set out in the regulation. The duration of market
exclusivity is set at [nine] years, except for: (i) orphan medicinal products addressing
HUMN, which will get [ten] years, and (ii) well-established use orphan medicinal
products, which will be granted [five] years of market exclusivity. A ‘bonus’ market
exclusivity extension of [one] year can be granted, based on patient access in all relevant
Member States.

To continue supporting further development of an already authorised orphan medicinal
product, while avoiding ever-greening, the first two new indications of an orphan
medicinal product will be rewarded with [one] year of exclusivity each. The extension will
apply to the entire medicinal product.

Therefore, the modulation of market exclusivity, while keeping the orphan medicinal
products reward system very competitive compared to other regions, will better reward
medicinal products that will address diseases for which no treatment is available or
medicinal products that will bring exceptional advances in treatment. Furthermore, the new
system will also promote faster generic/biosimilar competition improving affordability and
patient access to orphan medicinal products.

_Paediatric investigation plans for medicinal products for children, based on a medicinal_
_product’s mechanism of action_

Currently, the obligation to conduct a paediatric investigation plan (PIP) for studies in
children is waived in certain situations, for example when an adult product is intended for a
disease not existing in children. However, in certain cases the molecule in question, due to
its molecular mechanism of action, may be efficacious against a disease in children that is
different from the one for which it was initially designed for use in adults.

The proposal envisages that in such cases, the product will have to be studied for use in
children too. This requirement, apart from increasing the number of medicinal products
adequately studied for use in children, is also expected to promote innovation and research.

_Measures related to antimicrobials_

To promote the development of priority antimicrobials that can address antimicrobial
resistance, transferable data exclusivity vouchers are introduced. To this end, strict criteria
are laid down for defining the categories of priority antimicrobials eligible to receive the
voucher.

Such a voucher will grant an additional year of regulatory data protection to the developer
of the priority antimicrobial, which the developer can either use for any product in their
own product portfolio or sell it to another marketing authorisation holder.

The number of vouchers will be limited to a maximum of 10 over a 15 year period.
Transparency regarding any contribution to the research & development costs for priority
antimicrobials will be ensured. Strict conditions are also introduced for the transfer and use
of the voucher to extend the data protection period of another product within a certain
period, to ensure predictability for competitor products, including generics and biosimilars.

Eligibility criteria and the validity of the voucher are also linked to obligations to supply
the priority antimicrobial in the EU. A sunset period of 15 years is proposed, after which
time the Parliament and the Council may decide to continue or review the measure,
following a proposal by the Commission, based on experience gained during this period.

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Antimicrobial prudent use measures require that antimicrobials are placed under
prescription status in the EU. Antimicrobial marketing authorisation holders are required to
develop a stewardship plan for antimicrobial resistance which includes information on risk
mitigation measures, monitoring and reporting of resistance to the medicinal product.

The environmental fate of the antimicrobial, including through its manufacture and
disposal, becomes a factor to be assessed in the environmental risk assessment. The
proposal reinforces its provisions on package sizes, educational measures and proper
disposal of unused and expired antimicrobials.

_Enhanced pre-authorisation scientific and regulatory support_

Scientific and regulatory support by the European Medicines Agency will be strengthened,
in particular for developers of medicinal products that address unmet medical needs, e.g.
by building on the experience gained with the PRIME scheme and procedures used during
the COVID-19 pandemic, such as a phased review of data. It will provide an enhanced
legal framework for such scientific support and accelerated assessment and authorisation
of medicinal products that offer an exceptional therapeutic advancement in areas of unmet
medical needs including orphan medicinal products in particular for HUMN.

Small and medium-sized firms and not-for-profit entities will benefit from a dedicated
support scheme composed of regulatory, procedural and administrative support, which will
also include a reduction, deferral or waiver of fees. In addition, the regulation facilitates
the translation of robust research results, carried out by not-for-profit entities, onto the
label, allowing new promising therapeutic indications of off-patent medicinal products for
unmet medical needs.

Moreover, the European Medicines Agency will be able to provide scientific advice to
developers in parallel with the scientific advice given by HTA bodies under the ‘HTA
Regulation’ or by expert panels under the ‘Medical Device Regulation’. The European
Medicines Agency will also be able to consult other relevant Member State authorities
(e.g. with clinical trial expertise) in its scientific advice activities.

These measures are designed to help medicine developers generate clinical evidence that
meets the needs of the different authorities along the medicinal products’ life cycle, while
respecting the different remits of the legal frameworks concerned.

In addition, the European Medicines Agency will be able to provide scientific opinions
related to the classification of products, thereby advising developers and regulators on
whether a particular product under development is a medicinal product or not.

Finally, the European Medicines Agency will coordinate a mechanism for consulting
public authorities active along the medicinal product life cycle, to promote the sharing of
information and the pooling of knowledge on general issues of scientific or technical
nature that are relevant for developing, evaluating and accessing medicinal products.

_Temporary emergency marketing authorisation_

In a public health emergency, it is of major interest for the EU that safe and efficacious
medicinal products can be developed and made available within the EU as soon as
possible. Agile, fast and simplified processes are of the essence. A range of measures
already exist at EU level to facilitate, support and speed up the development of and
marketing authorisation for treatments and vaccines during a public health emergency.

The proposed regulation introduces the possibility to grant temporary emergency
marketing authorisations to address public health emergencies. Such authorisations should
be granted provided that the benefit of the immediate availability of the medicinal product

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in question on the market, with regard to the circumstances of the public health emergency,
outweighs the risk inherent in the fact that additional comprehensive quality, non-clinical,
clinical data may not yet be available (though they should still be required at a later stage).

_**Improving security of supply of medicines**_

_Addressing shortages of medicines_

The proposal sets out a framework for the activities to be deployed by the Member States
and the Agency to improve the EU’s capacity to react efficiently and in a coordinated
manner to support shortage management and security of supply of medicinal products, in
particular critical medicinal products, to EU citizens, at all times. The provisions to
strengthen the security of supply of medicines in the EU were, in part, informed by a
structured dialogue with and between the actors in the pharmaceuticals manufacturing
value chain and public authorities.

This proposal complements and further develops the core tasks already given to the
Agency in the extension of its mandate (Regulation (EU) 2022/123) which was introduced
as part of the EU’s overall health response to the COVID-19 pandemic and the improved
crisis management framework. It also complements Health Emergency Preparedness and
Response Authority’s (HERA) mission to ensure availability of medical countermeasures
in preparation for and during crises.

_EMA capacity to inspect sites located in non-EU countries_

Challenges in inspection capacity and capability in the EU network have been evident and
these gaps have been further exacerbated because of the COVID-19 pandemic. In some
cases, the lack of resources has led to delayed inspections of EU interest. Solutions are
needed to promote and support extra inspection capacity and build inspector capability, to
strengthen the oversight of compliance with good practice by sites located outside the EU.
Changes to the legal framework will allow the European Medicines Agency to have the
necessary authority and expertise to conduct certain inspections of EU interest also in
emergency situations, and when specific capacity and expertise is required.

_Joint Audit Programme_

To maintain an equivalent and harmonized implementation of the EU legislation on good
manufacturing, clinical and distribution practices, and the corresponding enforcement
activities, the new legal framework establishes, within the EMA, the Joint Audit
Programme (JAP) to ensure that the Member States’ inspectorates are subject to regular
audits conducted by other Member States.

Furthermore, the JAP will be an essential tool for mutual recognition agreements and other
international agreements, as it gives evidence of a regulatory system for medicinal
products based on a network of EU agencies that operate to consistent best practice
standards.

_**Reducing regulatory burden and providing a flexible regulatory framework to support**_
_**innovation and competitiveness**_

_Improved structure and governance of EMA and the regulatory network_

The agility of the European regulatory system is a key component for attracting applicants
and developers of medicinal products, from generics and biosimilars to cutting edge
medicines. The evaluation and assessment of medicinal products in the EU relies on the
EMA, competent authorities of the Member States and their experts who are present in the
scientific committees of the EMA.

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Both EMA scientific committees and competent authorities of the Member States are faced
with an increasing number of procedures, which require additional resources to ensure that
rapporteurs and assessors continue to be available to conduct assessment within the
appropriate timeframe. Moreover, new challenges arise from the assessment of innovative
and complex medicinal products. Capacity limitations that were observed during the
COVID-19 pandemic risk becoming more frequent.

It is therefore essential to continue to optimise the functioning and efficiency of the
regulatory system. In this regard, duplication of work needs to be avoided and procedures
should be handled in the most efficient way.

However, the current structure of the EMA means that in some cases up to five scientific
committees are involved in assessing a single medicinal product. Therefore, the structure
of the EMA scientific committees is simplified and reduced to two main Committees: the
Committee for Medicinal Products for Human Use (CHMP) and the Pharmacovigilance
Risk Assessment Committee (PRAC) as the main safety committee.

The expertise of the Committee for Advanced Therapies (CAT), the Committee for Orphan
Medicinal Products (COMP), the Paediatric Committee (PDCO) and the Committee for
Herbal Medicinal Products (HMPC) will be retained and reorganised in the form of
working parties and a pool of experts who will give input to the CHMP, PRAC and the Coordination Group for Mutual Recognition and Decentralised Procedures -Human (CMDh).

The CHMP and PRAC will consist, like today, of experts from all Member States, and
especially in the CHMP, the voice of patients will be strengthened by appointing patient
representatives to this committee for the first time.

Working parties will support the work of the committees and will mostly consist of experts
appointed by the Member States based on their expertise and of external experts. This will
ensure a continuous link between the experts in the competent authorities of the Member
States and the EMA. The model of rapporteurs remains unchanged.

Representation of patients and health care professionals with expertise in all areas,
including rare and paediatric diseases, will be increased at the CHMP and PRAC, in
addition to the dedicated working parties that represent patients and health care
professionals.

This simplified structure is expected to free up resources for the network to focus on new
activities, in particular regarding early scientific support for promising medicinal products
and repurposing, as well as activities related to more of a life cycle approach to authorising
medicinal products.

Training opportunities will be provided so that all Member States build expertise in new
areas of science and technology, so they can actively contribute to the work of the
regulatory network in assessing and monitoring medicinal products, including cutting edge
innovative and complex medicinal products.

Responsibility for adopting decisions on orphan designations will be transferred from the
Commission to the Agency to provide a more effective and efficient procedure.

_Other simplification, streamlining and future proofing measures_

Reduction of the regulatory burden will be facilitated by measures to simplify regulatory
procedures and increased digitalisation, including provisions related to the electronic
submission of applications for marketing authorisation and electronic product information
(ePI) on authorised medicinal products.

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Among the measures to reduce the regulatory burden are the abolishment of the renewal
and the sunset clause. The simplification of the structure of the scientific committees at the
EMA should also reduce the regulatory burden for companies and simplify their
interactions with the EMA.

The reduction of administrative burden through simplification and digitalisation measures
will benefit in particular small and medium-sized firms and not-for-profit entities involved
in the development of medicinal products. Moreover, a number of measures will contribute
to ensuring that the regulatory framework will be able to deal with emerging developments
in science. This includes provisions related to adapted clinical trials, use of real-world
evidence, secondary use of health data and regulatory sandboxes.

A regulatory sandbox can under certain conditions be linked to an adapted framework,
tailored to the characteristics or methods inherent to certain, especially novel medicines,
without lowering the high standards of quality, safety and efficacy. Measures for adapted
frameworks are provided for in the proposed Directive.

Taken together, the various measures in the proposed regulation and directive addressing
simplification to support innovation, future proofing and reduction of the regulatory burden
will strengthen the competitiveness of the pharmaceutical sector.

_Evolutionary and simplified Paediatric Investigation Plans (PIPs)_

For certain type of paediatric developments, the necessity to submit and agree with the
EMA, at a very early stage, a full clinical development plan for studies in children, is
problematic. In certain cases, this obliges developers to make assumptions about the
expected results.

This results in the subsequent need to modify the PIP (when a molecule has never been
used before, for instance). With the concept of evolutionary PIP, certain types of
developments, like molecules used for the first time in humans, will be given the
possibility to initially present a high level clinical development plan.

The EMA will agree that this development plan will be completed and new information
submitted at precise stages in the development. This will reduce administrative burden and
create, where appropriate, a more agile PIP system.

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2023/0131 (COD)

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**

(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 [1],

Having regard to the opinion of the Committee of the Regions [2],

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 creating a modern framework that makes innovative and established
medicinal products available to patients and healthcare systems at affordable prices, while
ensuring security of supply and addressing environmental concerns.

(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 have called for revised mechanisms and incentives for
development of medicinal products tailored to the level of unmet medical need, while
ensuring patient access and availability 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, these medicinal products do not always reach the patient and patients in
the Union still have different levels of access to medicines.

1 OJ C,, p. .
2 OJ C,, p. .

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(5) The COVID-19 pandemic has spotlighted critical issues which require a reform of the Union
pharmaceuticals framework to strengthen its resilience and to ensure that it 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 [3] with a new Regulation.

(7) Veterinary medicinal products are governed by Regulation (EU) No 2019/6 of the European
Parliament and of the Council [4] . 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 [5] .

(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 [6] 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, priority antimicrobials, orphan medicinal products,
paediatric use medicinal products and any medicinal product that includes an active
substances not authorised before the last important change to the scope of the centralised
procedure in 2004.

3 Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down
Community procedures for the authorisation and supervision of medicinal products for human and veterinary
use and establishing a European Medicines Agency (OJ L 136, 30.4.2004, p. 1).
4 Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary
medicinal products and repealing Directive 2001/82/EC (OJ L 4, 7.1.2019, p. 43).
5 Regulation (EC) No 470/2009 of the European Parliament and of the Council of 6 May 2009 laying down
Community procedures for the establishment of residue limits of pharmacologically active substances in
foodstuffs of animal origin, repealing Council Regulation (EEC) No 2377/90 and amending Directive
2001/82/EC of the European Parliament and of the Council and Regulation (EC) No 726/2004 of the European
Parliament and of the Council (OJ L 152, 16.6.2009, p. 1).
6 Report from the Commission to the European Parliament and the Council on the experience acquired with the
procedures for authorising and supervising medicinal products for human use, in accordance with the
requirements set out in the EU legislation on medicinal products for human use, COM(2021)497 final.

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(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.

(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 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.

(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.

(15) The Agency's budget should be 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.

(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 2309/93 [7] 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

7 Council Regulation (EEC) No 1647/2003 of 18 June 2003 amending Regulation (EEC) No 2309/93 laying
down Community procedures for the authorisation and supervision of medicinal products for human and
veterinary use and establishing a European Agency for the evaluation of Medicinal Products (OJ L 245,
29.9.2003, p. 19).

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Regulation does not establish a new Agency. The Agency mentioned in this Regulation is
the Agency established by Regulation (EC) No 726/2004.

(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.

(19) Scientific advice for future applicants seeking a marketing authorisation should be provided
more generally and in greater depth. Similarly, structures allowing the development of
advice for companies, in particular small and medium-sized enterprises (‘SMEs’), should be
put in place.

(20) Promising medicinal products that have the potential to significantly address patients’ unmet
medical needs should benefit from early and enhanced scientific support. Such support will
ultimately help patients benefit from new therapies as early as possible.

(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 [8] 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 [9] . 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 particular, the Agency should be empowered and given the capacity to carry out
inspections, where this is 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 [10] . The interest of the Union may

8 Regulation (EU) 2021/2282 of the European Parliament and of the Council of 15 December 2021 on health
technology assessment and amending Directive 2011/24/EU (OJ L 458, 22.12.2021, p. 1).
9 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).
10 Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community
code relating to medicinal products for human use (OJ L 311, 28.11.2001, p. 67).

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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. Providing
the Agency with appropriate inspection capacity will also, in the interest of the Union,
facilitate the dissemination of best practices, know-how, and improve the oversight of
manufacturing of medicinal products worldwide. Following the request from a competent
authority of the Member State, the Agency, at its own discretion, can accept to either
provide support to the inspections of sites located in the Union or to carry out inspections of
sites located in third countries.

(25) In certain cases, shortcomings in Member States’ system of 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 challenges, 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.
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 inspectorates.

(26) An inspection working group, which provides input and recommendations on all matters
relating, directly or indirectly, to good manufacturing practice and good distribution practice
irrespective of the marketing authorisation procedure through different reporting lines,
should be established within the Agency. In particular, that working group should be
responsible for the establishment, development and overall supervision of the joint audit

programme.

(27) To promote innovation and the development of new medicinal products by SMEs within the
meaning of Commission Recommendation 2003/361/EC [11], 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) Legal 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
innovation 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

11 Commission Recommendation of 6 May 2003 concerning the definition of micro, small and medium-sized
enterprises (OJ L 124, 20.5.2003, p. 36).

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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.

(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).

(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 of their evaluation
duties 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 and a pool
of experts who are organised based on different domains and who are giving input to the
CHMP and PRAC. The CHMP and PRAC consists of experts from all Member States while
working parties consist in majority of experts appointed by the Member States, based on
their expertise, and of external experts. The model of rapporteurs remains unchanged.
Representation of patients and health care professionals, with expertise in all areas,
including rare and paediatric diseases, is increased at the CHMP and PRAC, in addition to
the dedicated working groups representing patients and health care professionals.

(37) Scientific committees 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

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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 [12] .

(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 [13], 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, to prohibit the use in
their territory of medicinal products for human use.

(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 benefit
12 Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical
trials on medicinal products for human use, and repealing Directive 2001/20/EC (OJ L 158, 27.5.2014, p. 1).
13 https://europa.eu/european
[union/sites/europaeu/files/docs/body/joint_statement_and_common_approach_2012_en.pdf](https://europa.eu/european-union/sites/europaeu/files/docs/body/joint_statement_and_common_approach_2012_en.pdf)

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risk 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.

(46) Directive 2010/63/EU of the European Parliament and of the Council on the protection of
animals used for scientific purposes [14] 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 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 of 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 or read-across
models.

(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 re-examination.

(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

14 Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection
of animals used for scientific purposes (OJ L 276, 20.10.2010, p. 33).

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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 [15] 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 [16], 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

15 Regulation (EU) No 182/2011 of the European Parliament and of the Council of 16 February 2011 laying
down the rules and general principles concerning mechanisms for control by Member States of the
Commission’s exercise of implementing powers (OJ L 55, 28.2.2011, p. 13).
16 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
(OJ L 106, 17.4.2001, p. 1).

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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 Council [17] should not be a prerequisite. Nevertheless, in these cases, Member
States should implement appropriate measures 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
possible, regarding the criteria and conditions for the compassionate use of new medicinal
products under Member States' legislation. Moreover, it is important to allow for data on
such uses to be collected to inform decisions regarding the benefit-risk balance of the
medicinal products concerned.

(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. 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.

17 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).

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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. 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 [18] and Regulation (EU)
2018/1725 [19] 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 foster data-driven
benefit-risk assessments at all stages of the life cycle of a medicinal product. This
Regulation therefore empowers the Agency to request 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

18 Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection
of natural persons with regard to the processing of personal data and on the free movement of such data, and
repealing Directive 95/46/EC (General Data Protection Regulation) (OJ L 119, 4.5.2016, p. 1).
19 Regulation (EU) 2018/1725 of the European Parliament and of the Council of 23 October 2018 on the
protection of natural persons with regard to the processing of personal data by the Union institutions, bodies,
offices and agencies and on the free movement of such data, and repealing Regulation (EC) No 45/2001 and
Decision No 1247/2002/EC (OJ L 295, 21.11.2018, p. 39).

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medicinal products when they fulfil the criteria for the scheme, and allow the Agency, in
consultation with the Member States and the Commission, to 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 the identified unmet medical need.

(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.

(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

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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.

(77) The development of antimicrobial resistance is a growing concern and the pipeline of
effective antimicrobials is obstructed due to a market failure; it is therefore necessary to
consider new measures to promote the development of priority antimicrobials that are
effective against antimicrobial resistance and to support undertakings, often SMEs, which
choose to invest in this area.

(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

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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. 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 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.

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(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 [20] has proved
to be successful in boosting developments of orphan medicinal products in the Union;
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,

20 Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan
medicinal products (OJ L 18, 22.1.2000, p. 1).

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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.

(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; 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 an marketing authorisation for orphan
medicinal product, while a separate marketing authorisation may be granted for indications
not fulfilling the criteria of an orphan medicinal product.

(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 need 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 meaningful 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 orphan medicinal
products addressing high unmet needs, to ensure market predictability and to ensure a fair

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distribution of incentives, a modulation of market exclusivity has been introduced; 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 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.

(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 on 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 treatments for children or the disease for which the
medicinal product is intended occurs only in adult populations. Nevertheless, in the last

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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 a different disease 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 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.

(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

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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 off-patent
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 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

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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, 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 update the summary
of product characteristics in case new efficacy or safety data has an impact on the benefitrisk balance of a medicinal product.

(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, enable
where appropriate in a real-world 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 of regulatory sandboxes on a case-bycase basis when drafting and reviewing legislation.

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(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 Decision

following a recommendation of the Agency. Such decision should be based on a detailed
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 may be terminated at any
time based on public health considerations. The learning stemming from a regulatory
sandbox should inform future changes to the legal framework to fully integrate the particular
innovative aspects into the medicinal product regulation. Where appropriate, adapted
frameworks may be developed by the Commission on the basis of the results of a regulatory
sandbox.

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

serious risks to the health of patients in the Union and impacts on the right of patients to
access appropriate medical treatment. 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. Therefore, all marketing authorisation holders should have shortage prevention
plans in place, to prevent shortages. The Agency should provide guidance to marketing
authorisation holders on approaches to streamline the implementation of those plans.

(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 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.

(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 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. Marketing authorisation holders and other relevant entities
must 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)) already
established within the Agency pursuant to Regulation (EU) 2022/123 of the European

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Parliament and of the Council [21], should adopt a list of critical shortages of medicinal
products and 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.

(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.

(140) It is recognised that improved access to information contributes to public awareness, 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. Regulation (EC) No
1049/2001 of the European Parliament and of the Council [22] 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

21 Regulation (EU) 2022/123 of the European Parliament and of the Council of 25 January 2022 on a reinforced
role for the European Medicines Agency in crisis preparedness and management for medicinal products and
medical devices (OJ L 20, 31.1.2022, p. 1).
22 Regulation (EC) No 1049/2001 of the European Parliament and of the Council of 30 May 2001 regarding
public access to European Parliament, Council and Commission documents (OJ L 145, 31.5.2001, p. 43).

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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 [23] . 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.

23 OJ L 123, 12.5.2016, p. 1.

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(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.

(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 [24] .
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 [25] 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 [26], No 507/2006 [27],

24 Commission Regulation (EC) No 658/2007 of 14 June 2007 concerning financial penalties for infringement of
certain obligations in connection with marketing authorisations granted under Regulation (EC) No 726/2004 of
the European Parliament and of the Council (OJ L 155, 15.6.2007, p. 10).
25 Commission Regulation (EC) No 2141/96 of 7 November 1996 concerning the examination of an application
for the transfer of a marketing authorization for a medicinal product falling within the scope of Council
Regulation (EC) No 2309/93 (OJ L 286, 8.11.1996, p. 6).
26 Commission Regulation (EC) No 2049/2005 of 15 December 2005 laying down, pursuant to Regulation (EC)
No 726/2004 of the European Parliament and of the Council, rules regarding the payment of fees to, and the
receipt of administrative assistance from, the European Medicines Agency by micro, small and medium-sized
enterprises (OJ L 329, 16.12.2005, p. 4).
27 Commission Regulation (EC) No 507/2006 of 29 March 2006 on the conditional marketing authorisation for
medicinal products for human use falling within the scope of Regulation (EC) No 726/2004 of the European
Parliament and of the Council (OJ L 92, 30.3.2006, p. 6).

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No 658/2007 and (EC) No 1234/2008 [28] 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.

(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 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

28 Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations
to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal
products (OJ L 334, 12.12.2008, p. 7).

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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 [29] ] 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 medicine sponsor’ means any legal or natural person, established in the Union,
who submitted an application for or has been granted an orphan designation 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
substantial 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
substantial part of the target population;

(b) greater safety than an authorised medicinal product in a substantial 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.

(11) ‘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

29 [Name of revised Directive 2001/83/EC, date (OJ L XX, XX.XX.XXX, p. X).]

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certificate under Regulation (EC) No 469/2009 of the European Parliament and of the
### Council concerning the supplementary protection certificate for medicinal products [30] [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.

(12) ‘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.

(13) ‘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).

(14) ‘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.

(15) ‘critical shortage in the Member State’ means a shortage of a medicinal product, for which
there is no appropriate alternative medicinal product available on the market in that
Member State, and that shortage cannot be resolved.

(16) ‘critical shortage’ means a critical shortage in the Member State for which coordinated
Union level action is considered necessary to resolve that shortage in accordance with this
Regulation.

_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.

3. Homeopathic medicinal products shall not be granted a marketing authorisation in
accordance with this Regulation.

30 Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the
supplementary protection certificate for medicinal products (OJ L 152, 16.6.2009, p. 1).

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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 to adapt it to technical and scientific progress.

_Article 4_

_Member State authorisation of generics of centrally authorised medicinal products_

A generic medicinal product of a reference medicinal product authorised by the Union may be
authorised by the competent authorities of the Member States in accordance with [revised Directive
2001/83/EC] under the following conditions:

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

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 was marketed and where the applicant for the generic medicinal
product has requested not to include this information in their marketing authorisation.

## **Chapter II** **GENERAL PROVISIONS AND RULES ON APPLICATIONS**

### **S ECTION 1** **A PPLICATION 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 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.

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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 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 [31], 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, 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.

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 advancement. 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.

31 Regulation (EU) 2017/1001 of the European Parliament and of the Council of 14 June 2017 on the European
Union trade mark (OJ L 154, 16.6.2017, p. 1).

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4. Where appropriate, the application may include an active substance 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 25 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.

_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 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

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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 strategies proposed to address identified risks including specific
containment measures to limit contact with the medicinal product.

_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

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Products for Human Use, or the rapporteur, shall carry out necessary consultations with
bodies Member States have set up in accordance with Directive 2001/18/EC. They may
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 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. 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 application shall be
considered as withdrawn.

_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.

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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];

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(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;

(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, where concerns about risks to the environment or public
health, including antimicrobial resistance need to be further investigated 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, to carry out medicinal product-specific validation studies to

replace animal-based control methods with non-animal-based control methods.

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].

### **S ECTION 2** **M ARKETING 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

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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),
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.

_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;

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(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 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.

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

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(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;

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(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
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.

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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 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 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) 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.

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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), 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), 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), or in Article 20, 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 reasons 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

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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.

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).

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].

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.

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 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.

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

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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 group of patients with a chronically or seriously debilitating
disease or whose disease is considered to be life-threatening, and who cannot be treated
satisfactorily by an authorised medicinal product. The medicinal product concerned must
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 be undergoing
clinical trials in the same indication.

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

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.
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, 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. 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 mutandis_ .

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.

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8. Where a compassionate use programme has been set up in accordance with paragraphs 1
and 5, the applicant shall ensure that patients taking part also have access to the new
medicinal product during the period between authorisation and placing on the market.

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 may 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].

### **S ECTION 3** **T EMPORARY 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.

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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 [32] 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 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.

32 Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on serious
cross-border threats to health and repealing Decision No 1082/2013/EU (OJ L 314, 6.12.2022, p. 26).

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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.

_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_

The marketing authorisation holder of an authorisation in accordance with Article 33 may submit an
application in accordance with Articles 5 and 6 in order to obtain an authorisation in accordance
with Articles 13, 16 or 19.

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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.

_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 [33] 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. 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 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.

33 Regulation (EU) 2022/123 of the European Parliament and of the Council of 25 January 2022 on a reinforced
role for the European Medicines Agency in crisis preparedness and management for medicinal products and
medical devices (OJ L 20, 31.1.2022, p. 1).

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## **CHAPTER III** **INCENTIVES FOR THE DEVELOPMENT OF ‘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 for one authorised medicinal product.

3. An antimicrobial shall be considered ‘priority antimicrobial’ if preclinical and clinical data
underpin a significant clinical benefit with respect to antimicrobial resistance and 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 an active substance not previously authorised in a medicinal product in the
Union that 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.

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.

_Article 41_

_Transfer and use of the voucher_

1. A voucher may be used to extend the data protection for a period of 12 months of the
priority antimicrobial or another medicinal product authorised in accordance with this
Regulation of the same or different marketing authorisation holder.

A voucher shall only 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.

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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.

_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, procurement or purchase of the priority antimicrobial in the Union
has not been fulfilled.

3. Without prejudice to patent rights, or supplementary protection certificates [34], 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 Chapter III_

This Chapter shall apply 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 vouchers
in accordance with this Chapter, whichever date is the earliest.

## **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.

34 Regulation (EC) No 469/2009 of the European Parliament and of the Council, (OJ L 152, 16.6.2009, p. 1).

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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 15 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 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
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 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

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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 promptly any such 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,
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.

_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] 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 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 paragraph 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 3, 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.

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_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 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 (‘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 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.

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The opinion of the Agency shall be made publicly available and the competent authorities
of the Member States shall be informed.

2. In cases where the opinion is favourable, 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) 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 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 Union.

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].

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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 shall be accompanied by 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 account 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 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 the Agency_

1. When an inspection, included in the system of supervision referred to in Article 188(1),
point (a) of [revised Directive 2001/83/EC] is requested, as referred to in Article 11(2), for
a site located in a third country, the supervisory authority for this site may request the
Agency to participate in the inspection or to carry out the inspection.

2. The Agency, following a request in accordance with paragraph 1, may decide either of the
following:

(a) to lend its assistance by participating in a joint inspection with the supervisory
authority of the site. In that case the supervisory 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

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(b) to carry out the inspection and the follow up thereof on behalf of the supervisory
authority. 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 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 non-compliance GMP certificate
issued by the Agency, the supervisory 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 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 to the inspections referred to in paragraph 2.

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 such Member State when it performs inspections 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 2 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 participates as an inspectorate in the Joint Audit Programme and be subjected to
periodic audits.

_Article 53_

_International Inspections_

1. The Agency shall in consultation with the Commission, 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.

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2. In cooperation with the Agency, the Commission may adopt 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 pursuant and limited to paragraph 4;

(c) ensure cooperation with relevant international and Union level bodies to facilitate the
work of the joint audit programme.

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 authority 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 referred to in Article 3(3) of Commission Directive (EU) 2017/1572 [35] 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 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 shall:

(a) ensure 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 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.

35 Commission Directive (EU) 2017/1572 of 15 September 2017 supplementing Directive 2001/83/EC of the
European Parliament and of the Council as regards the principles and guidelines of good manufacturing
practice for medicinal products for human use (OJ L 238, 16.9.2017, p. 44).

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_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.

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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_

Where the Agency concludes that a holder of a marketing authorisation granted in accordance with
Article 19, including a new therapeutic indication granted referred to Article 19, failed to comply
with the 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, 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.

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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.

_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, notfor-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.

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 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];

(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).

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 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.

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_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 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 [36] .

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, relevant advisory or regulatory bodies established in other Union legal
acts in related fields. 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_ ].

The advisory or regulatory bodies consulted shall reply to the consultation within 30 days
of receipt of the request.

The Agency 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 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.

36 Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on
advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004
(OJ L 324, 10.12.2007, p. 121).

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## **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 lifethreatening or chronically debilitating condition shall be designated as an 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;

(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 the requirements specified in paragraph 1, point (a), are not
appropriate 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 medicine sponsor shall submit an application for 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 orphan medicine sponsor shall be accompanied by the following
particulars and documentation:

(a) name or corporate name and permanent address of the orphan 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 medicine 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

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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 application is
considered valid if it includes all the particulars and documentation referred to in
paragraph 2.

For the purpose of establishing whether the orphan designation criteria are fulfilled, the
Agency may consult the Committee for Medicinal Products for Human Use or one of its
working parties referred to in Article 150(2), first subparagraph. The outcome of such
consultations 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.

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 medicine sponsor to a
new orphan 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 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).

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
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 medicine sponsor.

_Article 66_

_Validity of orphan designation_

1. An orphan designation shall be valid for seven years. During this period, the orphan
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
medicine sponsor, the Agency may extend the validity, where the orphan medicine 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

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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 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 medicine sponsor has obtained a
marketing authorisation for 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
medicine sponsor.

_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 medicine 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.

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 medicine 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);

(b) the demonstration of significant benefit within the scope of the designated
[orphan indication;](https://www.ema.europa.eu/en/glossary/indication)

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(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
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 specified 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 need as specified in Article 70(1).

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).

5. 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.

6. 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.

7. 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_

_Orphan medicinal products addressing a high unmet medical need_

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1. An orphan medicinal product shall be considered as addressing a high unmet medical need
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;

(b) the use of the orphan medicinal product results in a meaningful 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 need.

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) ten years for orphan medicinal products addressing a high unmet medical need as
referred to in Article 70;

(c) five 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

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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 marketing authorisation for a similar
medicinal product, including generics and biosimilars, where the remainder of the duration
of the market exclusivity is less than two years.

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 protection
referred to in Article 81(2), point (d), of [revised Directive 2001/83/EC].

4. Article 71(3) equally applies to the prolongations of market exclusivity referred to in
paragraphs 1 and 2.

_Article 73_

_Union financial contribution related to orphan medicinal products_

The working arrangements referred to in Article 8 of [new fee Regulation] [37] 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.

37 Regulation [XXX] of the European Parliament and of the Council on fees and charges payable to the European
Medicines Agency, amending Regulation (EU) 2017/745 of the European Parliament and of the Council and
repealing Council Regulation (EC) No 297/95 and Regulation (EU) 658/2014 of the European Parliament and
of the Council [OJ L X, XX.XX.XXXX, p. X].

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## **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 treat a novel paediatric condition;

(b) following the acceptance by the Agency of a 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 development plan in accordance with the timing given in Article 76(1) an
applicant may submit a 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;

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(b) that the disease or condition for which the specific medicinal product or class is
intended occurs only in adult populations, unless when the product is directed at a
molecular target that on the basis of existing scientific data, is responsible 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 treatments for paediatric patients.

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.

_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 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_

1. 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

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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 30 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_

1. 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 and with interested parties, the Agency shall draw up
and publish guidelines for the practical application of this Article.

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_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 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_

1. 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 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 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
shall not exceed the duration of the deferral period given under Article 81(3).

The Agency shall decide on the prolongation within 60 days.

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2. Whenever appropriate, the Agency may ask the applicant to submit 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.

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 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.

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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].

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 is submitted in accordance with the procedures set out in in this Regulation,
the Committee for Medicinal Products for Human Use shall verify whether an 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 consult the Committee for Medicinal
Products for Human Use or the appropriate working parties when preparing the above
mentioned scientific conclusions. The outcome of such consultations shall be annexed to

the decision.

3. Decisions of the Agency shall be made public after deletion of any information of a
commercially confidential nature.

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_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 no less than six months before the discontinuation.

The Agency shall publish this 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
which have previously authorised the medicinal product concerned 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.

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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 or Article 9 of [revised Directive 2001/83/EC], in an
application for a paediatric use marketing authorisation.

3. 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;

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(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 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.

3. 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 **[38]** ].

38 Regulation [XXX] of the European Parliament and of the Council on fees and charges payable to the European
Medicines Agency, amending Regulation (EU) 2017/745 of the European Parliament and of the Council and

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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.

3. 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_

At least on an annual basis, the Agency shall make public:

(a) a list of the companies and of the products that have benefited from any of the rewards and
incentives in this Regulation;

(b) the companies that have failed to comply with any of the obligations in this 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 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.

## **CHAPTER 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

repealing Council Regulation (EC) No 297/95 and Regulation (EU) 658/2014 of the European Parliament and
of the Council [OJ L X, XX.XX.XXXX, p. X].

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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 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 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) 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 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.

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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 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. 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 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 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.

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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. 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 and 120 of [revised Directive 2001/83/EC];

(h) the initiation of the procedure provided for in Article 41(2), and Articles 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.

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2. In the development and review of the web portal, the Agency shall consult relevant
stakeholders, including patient and consumer groups, healthcare professionals and industry
representatives.

3. The Agency shall, in collaboration with the Member States and the Commission, set up
and maintain a register 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 is made public in the Union by different means.

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.

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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 107 and Article 109 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_

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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), or in
Article 20, paragraph 1, points (a) and (b), and in Articles 18(1) 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 of [revised Directive 2001/83/EC] or Article 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

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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 for Drugs and Drug Addiction 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 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 7, where all the following conditions are met:

(a) it is not possible to develop the medicinal product or category of products in
compliance with the requirements applicable to medicinal products due to scientific
or regulatory challenges arising from characteristics or methods related to the
product;

(b) the characteristics or methods referred to in point (a) positively and distinctively
contribute to the quality, safety or efficacy of the medicinal product or category of
products or provide a major advantage contribution to patient access to treatment.

2. The regulatory sandbox shall set out a regulatory framework, including scientific
requirements, for the development and, where appropriate clinical trials and placing on the
market of a product referred to in paragraph 1 under the conditions set out in this Chapter.

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The regulatory sandbox may allow targeted derogations to this Regulation, [revised
Directive 2001/83/EC] or Regulation (EC) 1394/2007 under the conditions set out in
Article 114.

A regulatory sandbox shall take effect 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. 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 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 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, it shall provide a
recommendation to the Commission. The Agency shall list eligible products or category of
products in that recommendation and shall include the sandbox plan referred to in
paragraph 1.

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 a sandbox plan based on data submitted by
developers of eligible products and following appropriate consultations. The plan shall set
out clinical, scientific and regulatory justification for a 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 proposal for alternative or
mitigation measures, where appropriate. The plan shall also include a proposed timeline for
the duration of the sandbox. Where appropriate, the Agency shall also propose measures in
order to mitigate any possible distortion of market conditions as a consequence of
establishing a regulatory.

6. The Commission shall, by means of implementing acts, take a decision on the set up of a
regulatory sandbox 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 5 shall be limited in time and
shall set out detailed conditions for its implementation. These Decisions shall:

(a) include the proposed sandbox plan;

(b) include the duration of the regulatory sandbox and its expiry;

(c) include as part of the 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.

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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 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 may be placed on the
market only when authorised in accordance with this Regulation. The initial validity of
such authorisation shall not exceed the duration of the regulatory sandbox. The
authorisation may be prolonged at the request of the marketing authorisation holder.

3. In duly justified cases, the marketing authorisation 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 be limited to what is apt
and strictly necessary to attain the objectives pursued, duly justified and specified in the
conditions to the marketing authorisation.

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.

5. Without prejudice to Article 195 of [revised Directive 2001/83/EC], the Commission shall
suspend a marketing authorisation granted in accordance with paragraph 2, where the
regulatory sandbox has been suspended or revoked in accordance with Article 113(7).

6. The Commission shall immediately vary the marketing authorisation to take account of the
mitigation measures taken in accordance with Article 115.

_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 in accordance with Article 113(2).

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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.

2. Participants in the regulatory sandbox, in particular 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
on the results from the implementation of a regulatory sandbox, including good practices,
lessons learnt 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
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**

### **S ECTION 1** **M ONITORING AND MANAGEMENT OF SHORTAGES AND CRITICAL SHORTAGES**

_Article 116_

_Marketing authorisation holder notifications_

1. The marketing authorisation holder of a medicinal product in possession of a centralised
marketing authorisation or a national marketing authorisation (‘the marketing authorisation
holder’) shall notify 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

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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 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 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).

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.

_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 medicinal product placed on the
market. 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.

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 on
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).

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_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), the competent authority concerned as referred to in Article 116(1)
shall continuously monitor any potential or actual shortage of those medicinal products.

The Agency shall carry out that monitoring in collaboration with the relevant competent
authority of the Member State when those medicinal products are authorised under this
Regulation.

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
may 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) 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).

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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.

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 manner.

_Article 121_

_Role of the competent authority of the Member State_

1. The competent authority of the Member State shall:

(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 on actual shortages of medicinal products, in cases in which that
competent authority has assessed the shortage, on a publicly available website;

(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.

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;

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(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.

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), 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);

(b) comply and coordinate with any 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.

6. The Member States may request that the MSSG provide further recommendations, referred
to in Article 123(4).

_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 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 identified pursuant to paragraph 2.

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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, 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 applies.

6. For the purposes of implementing this Regulation, the Agency shall expand the scope of
the ESMP. The Agency shall ensure that, where relevant, data is interoperable between the
ESMP, Member States’ IT systems and other relevant IT systems and databases, 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’).

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, in accordance with the methods referred to in Article 122(4), point (d), to

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relevant marketing authorisation holders, the Member States, the Commission, the
representatives of healthcare professionals or other entities.

_Article 124_

_Management of the critical shortage_

1. Following the addition of a medicinal product to the list of critical shortages pursuant to
Article 123, paragraphs 1 and 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, shall continuously monitor the critical shortage of that medicinal
product.

2. For the purposes of paragraph 1, where that information is not already available to the
Agency, the Agency may request relevant information on that critical shortage 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 may 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_

1. Following the addition of a medicinal product to the list of critical shortages of medicinal
products in accordance with Article 123, paragraphs 1 and 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;

(b) provide additional relevant information to the Agency;

(c) take into account the recommendations referred to in Article 123(4);

(d) comply with any measures 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);

(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 of the end date of the critical shortage.

_Article 126_

_Role of the Commission_

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1. The Commission shall, where it considers it appropriate and necessary:

(a) take into account the MSSG recommendations and implement relevant measures;

(b) inform the MSSG of those measures taken by the Commission.

2. The Commission may request the MSSG to provide recommendations referred to in Article
123(4).

### **S ECTION 2** **S ECURITY 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 identify critical medicinal products in
that Member State, using the methodology set out in Article 130(1), point (a).

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, as well as the information
received from the marketing authorisation holder as defined in Article 116(1).

3. For the purposes of the identification of critical medicinal products referred to in paragraph
1, 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, 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;

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(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 taken by the Commission pursuant to
Article 134(1), point (a);

(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) authorisation 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

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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.

_Article 130_

_Role of the Agency_

1. The Agency shall, in collaboration with 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 of those medicines, 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;

(c) specify the tools, 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 plan, referred to in Article 117;

(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.

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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 on 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.

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 coordinated Union level action
is necessary (“the Union list of critical medicinal products”).

2. The MSSG may propose updates to the Union list of critical medicines to the Commission,
where necessary.

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. 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

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to marketing authorisation holders as defined in Article 116(1), the Member States, the
Commission or other entities. Such measures may include recommendations on
diversification of suppliers and inventory management.

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 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 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) take into account the MSSG recommendations and implement the relevant measures;

(b) inform the MSSG of those measures taken by the Commission.

(c) request the MSSG to provide information or an opinion or further recommendations
referred to in Article 132(1).

2. The Commission, taking into consideration the information or the opinion, referred to in
paragraph 1, or MSSG recommendations, may decide to adopt an implementing act 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.

3. The implementing act referred to in paragraph 2 shall be adopted in accordance with the
examination procedure referred to in Article 173(2).

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## **CHAPTER XI** **EUROPEAN MEDICINES AGENCY**

### **S ECTION 1** **T ASKS OF THE A GENCY**

_Article 135_

_Establishment_

The functioning of the European Medicines Agency established by Regulation (EC) No 726/2004
(the ‘Agency’) shall continue in accordance with the present 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

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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 for the medicinal products for
human use;

(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 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 in
Article 50(2) whenever additional capacity is needed to carry out inspection of Union
interest including in response of public health emergencies;

(m) recording the status of marketing authorisations for medicinal products for human

use granted in accordance with Union marketing authorisation procedures;

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(n) creating a 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 information
already authorised for package leaflets; 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) providing 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 (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

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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 an orphan designation;

(z) adopting decisions on paediatric investigation plans, waivers and deferrals in relation
to medicinal products;

(za) providing regulatory support and 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;

(zd) developing coherent scientific assessment methodologies in the fields falling within

its mission;

(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 and information and development of
coherent scientific methodologies, including replacing, reducing or refining animal
testing, 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 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;

(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.

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

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holders have reported the information pursuant to Article 40(4), point (b), and Article 57 of

[revised Directive 2001/83/EC].

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).

Where appropriate, 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.

_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 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 body or
agency 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 Agency or a scientific committee, the Agency and the body
concerned shall cooperate to resolve the divergence, and inform the Commission without
undue delay.

4. The Commission may ask the Agency to conduct an assessment as regards specifically the
use of the substance concerned in 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 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 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

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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 Agency shall ensure that it is not seen as representing the Union position to an outside
audience or as 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.

### **S ECTION 2** **S TRUCTURE AND OPERATION**

_Article 142_

_Administrative and management structure_

The Agency shall comprise:

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(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 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'
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

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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 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 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);

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(c) adopt procedures for the performance of scientific services regarding medicinal products
for human use (Article 152);

(d) appoint the 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 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;

(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’) **[39]** 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;

(q) adopt a strategy for the organisational management and internal control systems.

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 defining the conditions under which that delegation of powers can be suspended. The
Executive Director shall be authorised to sub-delegate those powers.

39 Regulation No 31 (EEC), 11 (EAEC) by the Council of the European Economic Community and by the
Council of the European Atomic Energy Community, laying down the Staff Regulations of Officials and the
Conditions of Employment of Other Servants of the European Economic Community and the European
Atomic Energy Community (OJ 45, 14.6.1962, p. 1385).

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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;

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(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;

(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 and the coordination group 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 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.

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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 Use may, if they consider it
appropriate, seek guidance on important questions of a general scientific or ethical nature.

8. The scientific committees and any working parties and scientific advisory groups
established in accordance with this Article 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_

_Conflict of interest_

1. Members of the Management Board, members of the committees, rapporteurs and experts
shall not have financial or other interests in the pharmaceutical 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 interests. All indirect

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interests which could relate to this industry shall be entered in a register held 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 with respect to the items on the agenda. These declarations shall be made
available to the public.

_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. 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) four members and one 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;

(c) four members and four 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
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.

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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, advance therapy medicinal products, biological and
biotechnological products, in order to guarantee the highest levels of specialist
qualifications and a broad spectrum of relevant expertise. 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 thee 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;

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(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.

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.

_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 may establish an Environmental Risk Assessment working party and other
scientific working parties, as necessary.

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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. 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.

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.

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 necessary, for the nomination of other experts the Agency may 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 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

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remuneration of such accredited expert shall be deducted from the remuneration due to the
rapporteurs.

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 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 co-rapporteur. 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 in the financial arrangements established by the Management
Board/mechanism under the new fee legislation].

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 as regards the fulfilment of its
tasks in accordance with Articles 108, 110, 112, 116 and 121 of [revised Directive
2001/83/EC].

_Article 1_

_Methods to determine added therapeutic value_

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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.

### **S ECTION 3** **F INANCIAL 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 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 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 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.

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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.

Where a branch of the budgetary authority has notified its intention to deliver an opinion, it
shall forward its opinion to the Management Board within a period of six weeks from the
date of notification of the project.

_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 [40] .

40 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).

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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.

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 [41] 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 [42] shall apply
without restriction.

41 Commission Delegated Regulation (EU) 2019/715 of 18 December 2018 on the framework financial
regulation for the bodies set up under the TFEU and Euratom Treaty and referred to in Article 70 of Regulation
(EU, Euratom) 2018/1046 of the European Parliament and of the Council (OJ L 122, 10.5.2019, p. 1).
42 Regulation (EU, Euratom) No 883/2013 of the European Parliament and of the Council of 11 September 2013
concerning investigations conducted by the European Anti-Fraud Office (OLAF) and repealing Regulation

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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 [43] 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 [44] .

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 [45], 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 [46] .

### **S ECTION 4** **G ENERAL PROVISIONS GOVERNING THE A GENCY**

_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.

(EC) No 1073/1999 of the European Parliament and of the Council and Council Regulation (Euratom) No
1074/1999 (OJ L 248, 18.9.2013, p. 1).
43 Interinstitutional Agreement of 25 May 1999 between the European Parliament, the Council of the European
Union and the Commission of the European Communities concerning internal investigations by the European
Anti-fraud Office (OLAF) (OJ L 136, 31.5.1999, p. 15).
44 Council Regulation (Euratom, EC) No 2185/96 of 11 November 1996 concerning on-the-spot checks and
inspections carried out by the Commission in order to protect the European Communities' financial interests
against fraud and other irregularities (OJ L 292, 15.11.1996, p. 2).
45 **C** ouncil Regulation (EU) 2017/1939 of 12 October 2017 implementing enhanced cooperation on the
establishment of the European Public Prosecutor’s Office (‘the EPPO’) (OJ L 283, 31.10.2017, p. 1).
46 Directive (EU) 2017/1371 of the European Parliament and of the Council of 5 July 2017 on the fight against
fraud to the Union's financial interests by means of criminal law (OJ L 198, 28.7.2017, p. 29).

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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 [47] and 2015/444 [48] . The security rules

47 Commission Decision (EU, Euratom) 2015/443 of 13 March 2015 on Security in the Commission (OJ L 72,
17.3.2015, p. 41).
48 Commission Decision (EU, Euratom) 2015/444 of 13 March 2015 on the security rules for protecting EU
classified information (OJ L 72, 17.3.2015, p. 53).

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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 may 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.

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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] [49] .

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 10 and Article 12 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.

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.

49 Council Regulation (EC) No 297/95 of 10 February 1995 on fees payable to the European Agency for the
Evaluation of Medicinal Products (OJ L 35, 15.2.1995, p. 1).

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_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 implement
cybersecurity best practices adopted within Union institutions, bodies, offices and agencies 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 [50], and existing national provisions and 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 [51], 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_

50 Directive (EU) 2019/1937 of the European Parliament and of the Council of 23 October 2019 on the protection
of persons who report breaches of Union law (OJ L 305, 26.11.2019, p. 17).
51 Directive (EU) 2016/943 of the European Parliament and of the Council of 8 June 2016 on the protection of
undisclosed know-how and business information (trade secrets) against their unlawful acquisition, use and
disclosure (OJ L 157, 15.6.2016, p. 1).

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1. The Agency may process personal data, including personal health data, for the
performance of its tasks as referred to in Article 135, in particular 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 include 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.

_Article 170_

_Evaluation_

1. Not later than [ _note 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.

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

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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.

## **CHAPTER XII** **GENERAL PROVISIONS**

_Article 171_

_Penalties at national level_

1. 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.

_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

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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.

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.

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## **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 214 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;

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(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), 75(3), 81(4) 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 fiveyear 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),
75(3), 81(4) 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 21, 19(8), 47(4), 49(2) and 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 8, 17 and 20 to 23 are deleted;

(2) in Article 9(3), the fourth subparagraph is replaced by the following:

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‘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).’

_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) 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 paragraph 5.

6. To obtain and review the additional information referred to in paragraph 6, 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

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period set by the Agency, the application referred to in paragraph 1 shall be deemed
to have expired in all Member States concerned.

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
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).’;

(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:

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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.’;

(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

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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/Euratom [52], Council
Directive 96/29/Euratom [53], Directive 2004/23/EC of the European Parliament and of the
Council [54], Directive 2002/98/EC of the European Parliament and of the Council [55] and
Directive 2010/53/EU of the European Parliament and of the Council [56] .

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.’

_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_

52 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).
53 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).
54 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).
55 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).
56 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).

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1. Regulations (EC) No 141/2000, (EC) No 726/2004 and (EC) No 1901/2006 are repealed.

References to the repealed Regulations shall be construed as references to this Regulation
and shall be read in accordance with the correlation table in Annex V.

2. Commission Implementing Regulation (EU) No 198/2013 [57] 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_ ].

2. The procedures concerning the applications for marketing authorisations for medicinal
products for human use that have been validated, 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.

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.

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.

57 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).

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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]._

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 [58] 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 vouchers
in accordance with Chapter III, whichever date is the earliest, shall continue to be valid
according to the conditions set out in Chapter III.

_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 18 months after its entry into force._
_The date should be identical to the date for the application of the Directive_ ].

58 Commission Regulation (EC) No 847/2000 of 27 April 2000 laying down the provisions for implementation of
the criteria for designation of a medicinal product as an orphan medicinal product and definitions of the
concepts 'similar medicinal product' and 'clinical superiority' (OJ L 103, 28.4.2000, p. 5).

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However, Article 67 shall apply from [ _Note to the OP: Please insert the date of 2 years after the_
_date of adoption/entry into force/application 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_
_The President_ _The President_

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**LEGISLATIVE FINANCIAL STATEMENT**

**1.** **FRAMEWORK** **OF** **THE** **PROPOSAL/INITIATIVE**

**1.1. Title of the proposal/initiative**

**1.2. Policy area(s) concerned**

**1.3. The proposal/initiative relates to:**

**1.4. Objective(s)**

_1.4.1. General objective(s)_

_1.4.2. Specific objective(s)_

_1.4.3. Expected result(s) and impact_

_1.4.4. Indicators of performance_

**1.5. Grounds for the proposal/initiative**

_1.5.1. Requirement(s) to be met in the short or long term including a detailed timeline for_
_roll-out of the implementation of the initiative_

_1.5.2. Added value of Union involvement (it may result from different factors, e.g._
_coordination gains, legal certainty, greater effectiveness or complementarities). For the_
_purposes of this point 'added value of Union involvement' is the value resulting from Union_
_intervention which is additional to the value that would have been otherwise created by_
_Member States alone._

_1.5.3. Lessons learned from similar experiences in the past_

_1.5.4. Compatibility with the Multiannual Financial Framework and possible synergies_
_with other appropriate instruments_

_1.5.5. Assessment of the different available financing options, including scope for_
_redeployment_

**1.6. Duration and financial impact of the proposal/initiative**

**1.7. Management mode(s) planned**

**2.** **MANAGEMENT** **MEASURES**

**2.1. Monitoring and reporting rules**

**2.2. Management and control system(s)**

_2.2.1. Justification of the management mode(s), the funding implementation mechanism(s),_
_the payment modalities and the control strategy proposed_

_2.2.2. Information concerning the risks identified and the internal control system(s) set up_
_to mitigate them_

_2.2.3. Estimation and justification of the cost-effectiveness of the controls (ratio of "control_
_costs ÷ value of the related funds managed"), and assessment of the expected levels of risk_
_of error (at payment & at closure)_

**2.3. Measures to prevent fraud and irregularities**

**3.** **ESTIMATED** **FINANCIAL** **IMPACT** **OF** **THE** **PROPOSAL/INITIATIVE**

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**3.1. Heading(s) of the multiannual financial framework and expenditure budget**
**line(s) affected**

**3.2. Estimated financial impact of the proposal on appropriations**

_3.2.1. Summary of estimated impact on operational appropriations_

_3.2.2. Estimated output funded with operational appropriations_

_3.2.3. Summary of estimated impact on administrative appropriations_

_3.2.4. Compatibility with the current multiannual financial framework_

_3.2.5. Third-party contributions_

**3.3. Estimated impact on revenue**

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**LEGISLATIVE FINANCIAL STATEMENT**

**1.** **FRAMEWORK** **OF** **THE** **PROPOSAL/INITIATIVE**

**1.1.** **Title of the proposal/initiative**

Proposal for a revision of

Regulation (EC) No 726/2004 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 a European Medicines Agency and

Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use
and

Regulation (EC) No 141/2000 of the European Parliament and of the Council on orphan medicinal products and

Regulation (EC) No 1901/2006 of the European Parliament and of the Council on medicinal products for paediatric use [1] .

**1.2.** **Policy area(s) concerned**

Heading 2: Cohesion, Resilience and Values

Activity: Health

**1.3.** **The proposal/initiative relates to:**

◻ **a new action**

◻ **a new action following a pilot project/preparatory action** [2]

**X** **the extension of an existing action**

**X** **a merger or redirection of one or more actions towards another/a new action**

1 Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation
(EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004 (OJ L 378, 27.12.2006, p. 1).
2
As referred to in Article 58(2) **, point** (a) or (b) **,** of the Financial Regulation.

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**1.4.** **Objective(s)**

_1.4.1._ _General objective(s)_

The general objective of the revision is to guarantee a high level of public health by ensuring the quality, safety and efficacy of medicines for
EU patients and harmonise the internal market.

_1.4.2._ _Specific objective(s)_

Specific objectives

1. Promote innovation, in particular for unmet medical needs, including for rare disease patients and children.

2. Create a balanced system for pharmaceuticals in the EU that promotes affordability for health systems while rewarding innovation.

3. Ensure access to innovative and established medicines for patients, with special attention to enhancing security of the supply across the EU.

4. Reduce the environmental impact of the pharmaceutical product life cycle.

5. Reduce the regulatory burden and provide a flexible regulatory framework.

_1.4.3._ _Expected result(s) and impact_

_Specify the effects which the proposal/initiative should have on the beneficiaries/groups targeted._

The initiative builds on the high level of public health protection and harmonisation achieved for the authorisation of medicines, so that
patients across the EU have timely and equitable access and a reliable supply of the medicines they need. Additional obligations and
incentives should ensure that patients with rare diseases and children have access to high quality medicines and to safe and effective therapies
to address their specific medical needs.

The sector’s global competitiveness and innovative power should be supported by striking a balance between giving incentives for innovation,
including for unmet medical needs, and measures on access and affordability,. as well as simplification and future-proofing through a
framework that is adaptable to scientific and technological change and environmentally sustainable.

_1.4.4._ _Indicators of performance_

_Specify the indicators for monitoring progress and achievements._

The following core indicators will generate information in a continuous and systematic way on implementation and performance.

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For promoting innovation to address unmet medical needs:

–
Number of authorised medicines addressing unmet medical needs or high unmet medical needs.

– Number of authorised novel antibiotics

For improving access to patients:

–
Average time from authorisation to market launch for newly authorised medicines

–
Number of member states in which new medicines launched within 2 years from authorisation

–
Number of medicine shortages reported by member states

For environmental impact:

– Presence of medicines residues in the environment

For a flexible and attractive regulatory system:

– Number of authorised medicines with new active substance

–
Average assessment time of newly authorised innovative medicines

**1.5.** **Grounds for the proposal/initiative**

_1.5.1._ _Requirement(s) to be met in the short or long term including a detailed timeline for roll-out of the implementation of the initiative_

Upon the entry into force of the Regulation, the Agency should put in place the framework which will be used to enhance regulatory support
and accelerated assessment, to address medicine shortages and supply chain challenges and to strengthen the environmental risk assessment
under the marketing authorisation.

Regarding the enhanced regulatory support, the Agency shall set up within 6 months of adoption a coordination mechanism to enable parallel
scientific advice with health technology assessment and regulatory bodies for medical devices. Within the same period, the Agency shall
create an Academia Office, a secretariat to support not-for-profit entities by providing them free of charge early scientific advice.
Furthermore, the Agency shall establish an EU inspectorate within the Agency, to strengthen the network’s inspection capacity and deal with
emergencies, similar what was needed during the pandemic.

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For addressing medicine shortages the Agency shall extend the monitoring and management capacity for all shortages, with a focus on critical
shortages, and extend the EMA capacity to support availability of critical medicinal products. This would facilitate appropriate availability
and access to medicinal products which may have a serious impact on public health.

The Agency shall also extend its capacity to support the enhanced environmental risk assessments.

_1.5.2._ _Added value of Union involvement (it may result from different factors, e.g. coordination gains, legal certainty, greater effectiveness or_
_complementarities). For the purposes of this point 'added value of Union involvement' is the value resulting from Union intervention which is_
_additional to the value that would have been otherwise created by Member States alone._

Reasons for action at European level (ex-ante): Ensuring access to medicines is a clear public health interest in the EU. The current level of
harmonisation shows that the authorisation of medicines can be effectively regulated at EU level. Uncoordinated measures by Member States
may result in distortions of competition and barriers to intra-Union trade for products that are relevant for the entire EU. The initiative respects
national exclusive competence in health services and pricing and reimbursement of medicines.

Expected generated Union added value (ex-post)

Currently there is no Union intervention to increase patient access to newly authorised medicines, and there is a significant variation between
Member States in terms of access, especially the smaller markets are disadvantaged. The Union intervention will rely on the combined EU
market power in encouraging companies to serve all Member States and in a timely fashion.

Most authorised innovative medicines are authorised through the centralised procedure, at EU level. Therefore, enhancing regulatory support
is not only more effective at EU-level than at Member State level but also probably the only feasible option.

A coordinated response at Union-level to monitoring and mitigating the risk of shortages can help to avoid actions such as uncoordinated
stockpiling being taken and therefore have both a positive impact on public health and maintain the smooth functioning of the single market.

Environmental hazards know no borders, therefore only an EU-level coordinated and standardised mitigation of environmental risks stemming
from pharmaceuticals manufacturing, use and disposal can be effective.

_1.5.3._ _Lessons learned from similar experiences in the past_

The EU pharmaceutical legislation roots back to 1961, the first common EU rules for authorisation. Much of the impetus behind the adoption
of the legal framework stemmed from the determination to prevent a recurrence of the thalidomide disaster of the late 1950s, when thousands
of babies were born with limb deformities as a result of their mothers taking a medicinal product during pregnancy. This experience, which
shook public health authorities and the general public, made it clear that to safeguard public health, no medicinal product must ever again be
marketed without prior authorisation.

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Since then, a large body of legislation has been developed around this principle, with the progressive harmonisation of requirements for the
granting of marketing authorisation, and post-marketing monitoring, implemented across the entire European Economic Area (EEA).

Beyond safety, and harmonised rules for medicinal products to enable a single market, incentives have been introduced to support innovation.
Dedicated incentives for medicines for rare diseases and medicines for children have boosted research and innovation in these areas, leading to
scientific breakthroughs and life-saving new products.

Both the obligations and incentives have proven to be largely effective, and the lessons learned from their application drove the current
revision. Revision and modulation of existing obligations and incentives and adding new ones will serve new and recurring goals:

–
Promoting innovation and addressing unmet medical needs

–
Promoting access to affordable medicines

–
Enhancing security of supply of medicines

–
Reducing the environmental impact of medicines

– Reducing regulatory burden and providing a flexible and future-proof regulatory framework

_1.5.4._ _Compatibility with the Multiannual Financial Framework and possible synergies with other appropriate instruments_

The Agency should cooperate and promote synergies with other Union bodies, such as the European Centre for Disease and Control (ECDC),
European Food Safety Authority (EFSA) and take full advantage and ensure consistency with the EU4Health programme and other EU
programmes financing actions in the domain of public health.

_1.5.5._ _Assessment of the different available financing options, including scope for redeployment_

The overall budgetary impact of the revision to the Pharma legislation is 17.8 million EUR for the period 2024-2027 (excluding the costs for
fee-financed staff). This amount will cover the development and the maintenance of the data register from Environmental Risk Assessment
studies; activities related to shortage management and security of supply; the development of a new IT module for third-country inspections of
decentralised manufacturing, development and maintenance of the union register of orphan designations and the support to “not-for-profit”
entities. Most of these budgetary needs will be covered by EMA fees therefore the impact on the EU budget amounts to 4.4 million EUR. The
4.4 million EUR that will result in an increase of the EMA annual subsidy for the current MFF period will be redeployed internally within
Heading 2b, by a corresponding reduction of the EU4Health programme’s budgetary envelope in years 2026 and 2027.

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**1.6.** **Duration and financial impact of the proposal/initiative**

◻ **limited duration**

– ◻ in effect from [DD/MM]YYYY to [DD/MM]YYYY

– ◻ Financial impact from YYYY to YYYY for commitment appropriations and from YYYY to YYYY for payment appropriations.

🗹 **unlimited duration**

–
Implementation with a start-up period from 2023 to 2024,

–
followed by full-scale operation.

**1.7.** **Management mode(s) planned** **[3]**

🗹 **Direct management** by the Commission

– ◻ by its departments, including by its staff in the Union delegations;

– ◻ by the executive agencies

◻ **Shared management** with the Member States

🗹 **Indirect management** by entrusting budget implementation tasks to:

– ◻ third countries or the bodies they have designated;

– ◻ international organisations and their agencies (to be specified);

– ◻ the EIB and the European Investment Fund;

– 🗹 bodies referred to in Articles 70 and 71 of the Financial Regulation;

– ◻ public law bodies;

– ◻ bodies governed by private law with a public service mission to the extent that they provide adequate financial guarantees;

– ◻ bodies governed by the private law of a Member State that are entrusted with the implementation of a public-private partnership and that

provide adequate financial guarantees;

3 Details of management modes and references to the Financial Regulation may be found on the BudgWeb site:
[https://myintracomm.ec.europa.eu/budgweb/EN/man/budgmanag/Pages/budgmanag.aspx](https://myintracomm.ec.europa.eu/budgweb/EN/man/budgmanag/Pages/budgmanag.aspx)

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– ◻ persons entrusted with the implementation of specific actions in the CFSP pursuant to Title V of the TEU, and identified in the relevant

basic act.

–
_If more than one management mode is indicated, please provide details in the ‘Comments’ section._

Comments

**2.** **MANAGEMENT** **MEASURES**

**2.1.** **Monitoring and reporting rules**

_Specify frequency and conditions._

All Union agencies work under a strict monitoring system involving an internal control coordinator, the Internal Audit Service of the
Commission, the Management Board, the Commission, the Court of Auditors and the Budgetary Authority. This system is reflected and laid
down in the EMA’s founding regulation. In accordance with the Joint Statement on the EU decentralised agencies (the ‘Common Approach’),
the framework financial regulation (2019/715) and related Commission Communication C(2020)2297, the annual work programme and Single
Programming Document of the Agency comprise detailed objectives and expected results, including a set of performance indicators. The
Single Programming Document combines multiannual and annual programming as well as “strategy documents”, e.g. on independence. DG
SANTE comments through the Agency’s Management Board and prepares a formal Commission Opinion on the Single Programming
Document. The activities of the Agency will be measured against these indicators in the Consolidated Annual Activity Report.

The Agency will monitor periodically the performance of its internal control system to ensure that data is collected efficiently, effectively and
timely and to identify internal control deficiencies, register and assess the results of controls, control deviations and exceptions. The results of
the internal control assessments, including significant weaknesses identified and any differences as compared to internal and external audit
findings will be disclosed in the Consolidated Annual Activity report.

**2.2.** **Management and control system(s)**

_2.2.1._ _Justification of the management mode(s), the funding implementation mechanism(s), the payment modalities and the control strategy proposed_

The annual EU subsidy will be transferred to the Agency in accordance with its payment needs and upon its request. The Agency will be
subject to administrative controls including budgetary control, internal audit, annual reports by the European Court of Auditors, the annual
discharge for the execution of the EU budget and possible investigations conducted by OLAF to ensure, in particular, that the resources
allocated to the Agency are put to proper use. Through its representation in the Agency's Management Board and Audit Committee, the

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Commission will receive audit reports and ensures that adequate actions are defined and timely implemented by the Agency to address the
issues identified. All payments will remain pre-financing payments until the Agency’s accounts have been audited by the European Court of
Auditors and the Agency has submitted its final accounts. If necessary, the Commission will recover unspent amounts of the instalments paid
to the Agency.

The activities of the Agency will also be subject to the supervision of the Ombudsman in accordance with Article 228 of the Treaty. These
administrative controls provide a number of procedural safeguards to ensure that account is taken of the interests of the stakeholders.

_2.2.2._ _Information concerning the risks identified and the internal control system(s) set up to mitigate them_

The main risks relate to the Agency’s performance and independence in implementing the tasks entrusted to it. Underperformance or impaired
independence could hamper the achievement of the objectives of this initiative and also reflect negatively on the Commission’s reputation.

The Commission and the Agency have put in place internal procedures that aim at covering the risks identified above. The internal procedures
are in full compliance with the Financial Regulation and include anti-fraud measures and cost-benefit considerations.

First and foremost, sufficient resources should be made available to the Agency in both financial and staffing terms to achieve the objectives
of this initiative.

Furthermore, quality management will include both the integrated quality-management activities and risk-management activities within the
Agency. A risk review is conducted annually, with risks being assessed at a residual level, i.e. taking into account controls and mitigations
already in place. Conducting self-assessments (as part of the EU Agencies benchmarking programme), annual reviews of sensitive functions
and ex-post controls also fall within this area, as does maintain a register of exceptions.

To preserve impartiality and objectivity in every aspect of the Agency’s work, a number of policies and rules on management of competing
interests have been put in place and will be regularly updated, describing specific arrangements, requirements and processes applying to the
Agency’s Management Board, scientific committee members and experts, the Agency’s staff and candidates, as well as consultants and

contractors.

The Commission will be informed timely of relevant management and independence issues encountered by the Agency and will react upon
notified issues timely and adequately.

_2.2.3._ _Estimation and justification of the cost-effectiveness of the controls (ratio of "control costs ÷ value of the related funds managed"), and_
_assessment of the expected levels of risk of error (at payment & at closure)_

The Commission’s and the Agency’s internal control strategies take into consideration the main cost drivers, and the efforts already taken over
several years to reduce the cost of controls, without compromising the effectiveness of controls. The existing control systems proved to be
able to prevent and/or to detect errors and/or irregularities, and in case of errors or irregularities, to correct them.

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In the past five years, the Commission’s yearly costs of controls under indirect management represented less than 1% of the annual budget
spent on subsidies paid to the Agency. The Agency allocated less than 0,5% of its total annual budget on control activities centering around
integrated quality management, audit, anti-fraud measures, finance and verification processes, corporate risk management and self-assessment
activities.

**2.3.** **Measures to prevent fraud and irregularities**

_Specify existing or envisaged prevention and protection measures, e.g. from the Anti-Fraud Strategy._

As for its activities in indirect management, the Commission shall take appropriate measures ensuring that the financial interests of the
European Union are protected by the application of preventive measures against fraud, corruption and any other illegal activities, by effective
checks and, if irregularities are detected, by the recovery of the amounts wrongly paid and, where appropriate, by effective, proportional and
deterrent penalties.

To this effect, the Commission adopted an anti-fraud strategy, latest update of April 2019 (COM(2019)176), covering preventive, detective
and corrective measures.

The Commission or its representatives and the European Court of Auditors shall have the power of audit, on the basis of documents and onthe-spot, over all grant beneficiaries, contractors and subcontractors who have received Union funds. OLAF shall be authorised to carry out
on-the-spot checks and inspections on economic operators concerned indirectly by such funding.

As regards the European Medicines Agency, the anti-fraud measures are provided for in Article 69 of Regulation (EC) No 726/2004 and the
framework financial Regulation (2019/715). The Executive Director and the Management Board of the Agency will take the appropriate
measures in accordance with the Internal Control Principles applied across all EU institutions. In line with the Common Approach and Article
42 of the framework financial Regulation, an anti-fraud strategy has been developed and is followed by the Agency.

The Agency’s Anti-fraud strategy covers 3-year period and is accompanied by a corresponding action plan, outlining both specific focus areas
and actions for the next years, and several continuous actions that are carried out every year, such as a specific standalone fraud risk
assessment, with the identified fraud risks included in the overall Agency risk register. Anti-fraud trainings are organised as part of the
induction training and via mandatory anti-fraud e-learning training for newcomers. Staff are made aware of how to report any suspects of
wrongdoings and disciplinary procedures are in place as per the rules of the Staff Regulations.

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**3.** **ESTIMATED** **FINANCIAL** **IMPACT** **OF** **THE** **PROPOSAL/INITIATIVE**

**3.1.** **Heading(s) of the multiannual financial framework and expenditure budget line(s) affected**

    - Existing budget lines

_In order of multiannual financial framework headings and budget lines._

|Heading of<br>multiannual<br>financial<br>framework|Budget line|Type of<br>expenditure|Contribution|Col5|Col6|Col7|
|---|---|---|---|---|---|---|
|Heading of<br>multiannual<br>financial<br>framework|Number <br>|Diff./Non-<br>diff.4|from<br>EFTA<br>countries5 <br>|from<br>candidate<br>countries6 <br>|from third<br>countries|within the<br>meaning of<br>Article 21(2)(b) of<br>the Financial<br>Regulation|
|2|06.100302 Special contribution for<br>orphan medicinal products|Non-diff.|YES|NO|NO|NO|

**3.2.** **Estimated financial impact of the proposal/initiative**

_3.2.1._ _Summary of estimated impact on operational appropriations_

– ◻ The proposal/initiative does not require the use of operational appropriations

– 🗹 The proposal/initiative requires the use of operational appropriations, as explained below:

EUR million (to three decimal places)

**Heading of multiannual financial**

2 Cohesion, Resilience and Values
**framework**

4 Diff. = Differentiated appropriations / Non-diff. = Non-differentiated appropriations.
5 EFTA: European Free Trade Association.
6 Candidate countries and, where applicable, potential candidates.

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|DG: SANTE|Col2|Col3|Col4|Year<br>2024|Year<br>2025|Year<br>2026|Year<br>2027 and<br>subsequent<br>years|TOTAL7|
|---|---|---|---|---|---|---|---|---|
|• Operational appropriations|• Operational appropriations|• Operational appropriations|• Operational appropriations||||||
|06.100302 Special contribution for<br>orphan medicinal products|Commitments|(1b)|(1b)|||1.172|3.196|4.368|
|06.100302 Special contribution for<br>orphan medicinal products|Payments|(2b)|(2b)|||1.172|3.196|4.368|
|Appropriations of an administrative nature financed from the<br>envelope of specific programmes8  <br>|Appropriations of an administrative nature financed from the<br>envelope of specific programmes8  <br>|Appropriations of an administrative nature financed from the<br>envelope of specific programmes8  <br>|Appropriations of an administrative nature financed from the<br>envelope of specific programmes8  <br>||||||
|Budget line||(3)|(3)||||||
|**TOTAL appropriations** <br>**for DG**SANTE|Commitments|=1a+1b<br>+3|=1a+1b<br>+3|||1.172|3.196|4.368|
|**TOTAL appropriations** <br>**for DG**SANTE|Payments|=2a+2b<br>+3|=2a+2b<br>+3|||1.172|3.196|4.368|

|• TOTAL operational appropriations|Commitments|(4)|Col4|Col5|1.172|3.196|4.368|
|---|---|---|---|---|---|---|---|
|• TOTAL operational appropriations|Payments|(5)|||1.172|3.196|4.368|
|• TOTAL appropriations of an administrative nature<br>financed from the envelope for specific programmes|• TOTAL appropriations of an administrative nature<br>financed from the envelope for specific programmes|(6)||||||
|**TOTAL appropriations** <br>**under HEADING <2b>** <br>of the multiannual financial framework|Commitments|=4+ 6|||1.172|3.196|4.368|
|**TOTAL appropriations** <br>**under HEADING <2b>** <br>of the multiannual financial framework|Payments|=5+ 6|||1.172|3.196|4.368|

7 For 2026 the total amount covers the costs for 6 TAs. For 2027 the total amount covers the costs for 6 TAs (1.196 million EUR) and the costs for the incentives to “not-forprofit” entities (2 million EUR).
8 Technical and/or administrative assistance and expenditure in support of the implementation of EU programmes and/or actions (former ‘BA’ lines), indirect research, direct research.

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**Heading of multiannual financial**

**7** ‘Administrative expenditure’
**framework**

[This section should be filled in using the 'budget data of an administrative nature' to be firstly introduced in the Annex to the Legislative Financial](https://myintracomm.ec.europa.eu/corp/budget/financial-rules/legal-framework/internal-rules/Documents/2021-5-legislative-financial-statement-ann-en.docx)
[Statement](https://myintracomm.ec.europa.eu/corp/budget/financial-rules/legal-framework/internal-rules/Documents/2021-5-legislative-financial-statement-ann-en.docx) (Annex V to the internal rules), which is uploaded to DECIDE for interservice consultation purposes.

EUR million (to three decimal places)

|Col1|Col2|Year<br>2024|Year<br>2025|Year<br>2026|Year<br>2027 and<br>subsequent<br>years|Enter as many years as<br>necessary to show the<br>duration of the impact (see<br>point 1.6)|Col8|Col9|TOTAL|
|---|---|---|---|---|---|---|---|---|---|
|DG: SANTE||||||||||
|• Human resources|• Human resources|||||||||
|• Other administrative expenditure|• Other administrative expenditure|||||||||
|**TOTAL DG**<…….>|Appropriations|||||||||

EUR million (to three decimal places)

|Col1|Col2|Year<br>2024|Year<br>2025|Year<br>2026|Year<br>2027|Enter as many years as<br>necessary to show the duration<br>of the impact (see point 1.6)|Col8|Col9|TOTAL|Col11|
|---|---|---|---|---|---|---|---|---|---|---|
|**TOTAL appropriations** <br>**under HEADINGS 1 to 7** <br>of the multiannual financial framework|Commitments|||1.172|3.196||||4.368|4.368|
|**TOTAL appropriations** <br>**under HEADINGS 1 to 7** <br>of the multiannual financial framework|Payments|||1.172|3.196||||4.368|4.368|

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_3.2.2._ _Estimated output funded with operational appropriations_

Commitment appropriations in EUR million (to three decimal places)

|Indicate<br>objectives and<br>outputs<br>⇩|Col2|Col3|Year<br>2024|Col5|Year<br>2025|Col7|Year<br>2026|Col9|Year<br>2027 and<br>subsequent years|Col11|TOTAL|Col13|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|**Indicate**<br>**objectives and**<br>**outputs**<br> <br>⇩|**OUTPUTS**|**OUTPUTS**|**OUTPUTS**|**OUTPUTS**|**OUTPUTS**|**OUTPUTS**|**OUTPUTS**|**OUTPUTS**|**OUTPUTS**|**OUTPUTS**|**OUTPUTS**|**OUTPUTS**|
|**Indicate**<br>**objectives and**<br>**outputs**<br> <br>⇩|Type9 <br>|Avera<br>ge<br>cost|No<br>Cost|No<br>Cost|No<br>Cost|No<br>Cost|No<br>Cost|No<br>Cost|No<br>Cost|No<br>Cost|Tota<br>l No<br>Total<br>cost|Tota<br>l No<br>Total<br>cost|
|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients<br>and children.|<br> <br>|<br> <br>|
|Support to “not-<br>for-profit”<br>entities|||<br>|<br>|<br>|<br>|<br>1.172|<br>1.172|<br>3.196|<br>3.196||4.368|
|Subtotal for specific objective No 1|Subtotal for specific objective No 1|Subtotal for specific objective No 1||||||1.172||3.196||4.368|
|**TOTALS**|**TOTALS**|**TOTALS**||||||1.172||3.196||4.368|
|- Output|||||||||||||
||||||||||||||
||||||||||||||

9 Outputs are products and services to be supplied (e.g.: number of student exchanges financed, number of km of roads built, etc.).

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_3.2.3._ _Estimated impact on EMA’s human resources_

– ◻ The proposal/initiative does not require the use of appropriations of an

administrative nature

– ◻ The proposal/initiative requires the use of appropriations of an administrative nature,

as explained below:

EUR million (to three decimal places)

|Temporary agents (AD Grades)|Col2|Col3|0.781|0.797|1.578|
|---|---|---|---|---|---|
|Temporary<br>agents<br>(AST<br>grades)|||0.391|0.399|0.790|
|Contract staff||||||
|Seconded National Experts||||||

Staff requirements (FTE): Total posts Union funded and funded from fees

|Temporary agents (AD Grades)|13|22|33|40|40|
|---|---|---|---|---|---|
|Temporary agents (AST grades)|6|15|19|20|20|
|Contract staff||||||
|Seconded National Experts||||||

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The appropriations required for human resources and other expenditure of an administrative nature will be met by appropriations
from the DG that are already assigned to management of the action and/or have been redeployed within the DG, together if necessary
with any additional allocation which may be granted to the managing DG under the annual allocation procedure and in the light of
budgetary constraints.

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3.2.3.1. Estimated requirements of human resources

– ◻ The proposal/initiative does not require the use of human resources.

– ◻ The proposal/initiative requires the use of human resources, as explained below:

_Estimate to be expressed in full time equivalent units_

|Col1|Col2|Year<br>2024|Year<br>2025|Year<br>2026|Year<br>N+3|Enter as many years as<br>necessary to show the duration<br>of the impact (see point 1.6)|Col8|Col9|
|---|---|---|---|---|---|---|---|---|
|•** Establishment plan posts (officials and temporary staff)**|•** Establishment plan posts (officials and temporary staff)**|•** Establishment plan posts (officials and temporary staff)**|•** Establishment plan posts (officials and temporary staff)**|•** Establishment plan posts (officials and temporary staff)**|•** Establishment plan posts (officials and temporary staff)**|•** Establishment plan posts (officials and temporary staff)**|•** Establishment plan posts (officials and temporary staff)**|•** Establishment plan posts (officials and temporary staff)**|
|20 01 02 01 (Headquarters and Commission’s Representation<br>Offices)|20 01 02 01 (Headquarters and Commission’s Representation<br>Offices)||||||||
|20 01 02 03 (Delegations)|20 01 02 03 (Delegations)||||||||
|01 01 01 01 (Indirect research)|01 01 01 01 (Indirect research)||||||||
|01 01 01 11 (Direct research)|01 01 01 11 (Direct research)||||||||
|Other budget lines (specify)|Other budget lines (specify)||||||||
|•** External staff (in Full Time Equivalent unit: FTE)103 **<br>|•** External staff (in Full Time Equivalent unit: FTE)103 **<br>|•** External staff (in Full Time Equivalent unit: FTE)103 **<br>|•** External staff (in Full Time Equivalent unit: FTE)103 **<br>|•** External staff (in Full Time Equivalent unit: FTE)103 **<br>|•** External staff (in Full Time Equivalent unit: FTE)103 **<br>|•** External staff (in Full Time Equivalent unit: FTE)103 **<br>|•** External staff (in Full Time Equivalent unit: FTE)103 **<br>|•** External staff (in Full Time Equivalent unit: FTE)103 **<br>|
|20 02 01 (AC, END, INT from the ‘global envelope’)|20 02 01 (AC, END, INT from the ‘global envelope’)||||||||
|20 02 03 (AC, AL, END, INT and JPD in the delegations)|20 02 03 (AC, AL, END, INT and JPD in the delegations)||||||||
|**XX** 01 xx**yy zz** **_104_ **<br>|- at Headquarters <br>||||||||
|**XX** 01 xx**yy zz** **_104_ **<br>|- in Delegations||||||||
|01 01 01 02 (AC, END, INT - Indirect research)|01 01 01 02 (AC, END, INT - Indirect research)||||||||
|01 01 01 12 (AC, END, INT - Direct research)|01 01 01 12 (AC, END, INT - Direct research)||||||||
|Other budget lines (specify)|Other budget lines (specify)||||||||
|**TOTAL**|**TOTAL**||||||||

**XX** is the policy area or budget title concerned.

The human resources required will be met by staff from the DG who are already assigned to management of the action
and/or have been redeployed within the DG, together if necessary with any additional allocation which may be granted to
the managing DG under the annual allocation procedure and in the light of budgetary constraints.

Description of tasks to be carried out from the FTE, funded by Union contribution:

|Officials and temporary staff|The requested FTE (4 AD and 2 AST) are necessary to set up the<br>Academia Office at EMA that will be managing the procedures. The<br>tasks of the office will be similar to the tasks of the SME office and will<br>include procedural and administrative assistance to “not-for-profit”<br>entities, including direct assistance and briefing meetings on regulatory<br>strategy, providing fee waivers and reductions to eligible entities,<br>provide free-of-charge translations of the product information in all EU<br>languages for initial EU marketing authorisations, provide training and<br>education to “not-for-profit” entities, etc|
|---|---|
|External staff||

103 AC= Contract Staff; AL = Local Staff; END= Seconded National Expert; INT = agency staff; JPD= Junior
Professionals in Delegations.
104 Sub-ceiling for external staff covered by operational appropriations (former ‘BA’ lines).

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_3.2.4._ _Description of tasks to be carried out from the FTE, funded by EMA fees:_

|Officials and temporary staff|The requested staff (54 FTE) will be:<br>• managing (AD profiles) and providing support (AST profiles) to<br>operational expert groups in the area of the Environmental Risk<br>Assessment (ERA);<br>• with a scientific and regulatory profile to work in the shortages<br>management and security of supply;<br>• Good Manufacturing Practice and Good Clinical Practice<br>inspectors (AD) necessary to establish an EU inspectorate<br>resourced by EMA staff that would provide help to the<br>inspections done by Member States (lacking resources), and deal<br>with emergency situations which require dedicated and<br>dependable intervention (e.g., similar to inspections required<br>during the pandemic);<br>• Legal officers (AD profiles), needed in the field of orphan<br>designations that are already today a litigious topic and so it is<br>assumed the proposed changes in the decision making on orphan<br>designation would generate an increased in workload for even<br>more legal queries and litigations;<br>• defining business requirements for the data register, following<br>up on the implementation and perform the related scientific<br>activities when the register is live;, develop trainings on ERA,<br>etc.;<br>• providing administrative support to the operational expert<br>groups;<br>• working in the area of inspection planning;<br>• general assistants, assistants, supporting on procedural aspects or<br>working on document creation.|
|---|---|
|External staff||

_3.2.5._ _Compatibility with the current multiannual financial framework_

The proposal/initiative:

– 🗹 can be fully financed through redeployment within the relevant heading of the

Multiannual Financial Framework (MFF).

The increase of appropriations for EMA budget line 06.100302 in years 2026 and 2027 by 4.4 million EUR,
will be done via internal redeployment within heading 2b, i.e. by an equal reduction of the EU4Health
budget line 06.0601 for this period.

– ◻ requires use of the unallocated margin under the relevant heading of the MFF and/or

use of the special instruments as defined in the MFF Regulation.

Explain what is required, specifying the headings and budget lines concerned, the corresponding amounts,
and the instruments proposed to be used.

– ◻ requires a revision of the MFF.

Explain what is required, specifying the headings and budget lines concerned and the corresponding amounts.

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_3.2.6._ _Third-party contributions_

The proposal/initiative:

– 🗹 does not provide for co-financing by third parties

– ◻ provides for the co-financing by third parties estimated below:

Appropriations in EUR million (to three decimal places)

|Col1|Year<br>2024|Year<br>2025|Year<br>2026|Year<br>2027<br>and<br>subsequ<br>ent<br>years|Enter as many years as necessary<br>to show the duration of the<br>impact (see point 1.6)|Col7|Col8|Total|
|---|---|---|---|---|---|---|---|---|
|Specify the co-financing<br>body|||||||||
|TOTAL appropriations<br>co-financed|||||||||

**3.3.** **Estimated impact on revenue**

– 🗹 The proposal/initiative has no financial impact on revenue.

– ◻ The proposal/initiative has the following financial impact:

– ◻ on own resources

– ◻ on other revenue

– please indicate, if the revenue is assigned to expenditure lines ◻

EUR million (to three decimal places)

|Budget revenue line:|Appropriations<br>available for<br>the current<br>financial year|Impact of the proposal/initiative105|Col4|Col5|Col6|Col7|Col8|Col9|
|---|---|---|---|---|---|---|---|---|
|Budget revenue line:|Appropriations<br>available for<br>the current<br>financial year|Year <br>**2024**|Year <br>**2025**|Year <br>**2026**|Year <br>**2027 and**<br>**subseque**<br>**nt years**|Enter as many years as necessary to show<br>the duration of the impact (see point 1.6)|Enter as many years as necessary to show<br>the duration of the impact (see point 1.6)|Enter as many years as necessary to show<br>the duration of the impact (see point 1.6)|
|Article ………….|||||||||

For assigned revenue, specify the budget expenditure line(s) affected.

Other remarks (e.g. method/formula used for calculating the impact on revenue or any other information).

105 As regards traditional own resources (customs duties, sugar levies), the amounts indicated must be net
amounts, i.e. gross amounts after deduction of 20 % for collection costs.

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