EN   EN 
 
 
 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 Regul ation (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}   EN 1  EN 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 
high-quality medicinal products. However, patient access to medicinal products 
across the EU and security of supply are growing concerns, mirrored by recent 
Council conclusions1 and resolutions of the European Parliam ent2. 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 professi onals, 
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 d o 
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 Europe3 
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 ensu ring EU’s supply of safe and affordable medicinal products and supporting 
the EU pharmaceutical industry’s innovation efforts4. Reviewing  the pharmaceutical 
legislation is key to achieving these objectives.  However,  innovation, access and 
affordability are  also influenced by factors outside the scope of th is 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 protecti on and harmonisation already achieved for the authorisation 
of medicinal products. The overarching aim of the re form  is to ensure that patients 
across the EU have timely and equitable access  to medicines . Another objective of 
the proposal is to enhance sec urity 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 
                                                 
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 fo r 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 f or 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) .  
3 Communication from the Commission, Pharmaceutical Strategy for Europe  (COM/2020/761 final), 
https://health.ec. europa.eu/medicinal -products/pharmaceutical -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)  EN 2  EN in advance of a foreseen interr uption 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 mea sures 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 re form  is comprehensive but targeted and focu ses 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 Council5 
and Regulation  (EC)  No 726/2004  of the European  Parliament  and of the Council6 
(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  
                                                 
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 us e (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 Age ncy (OJ L 136, 30.4.2004, p. 1).  EN 3  EN Regulation’7), medicinal  products  for children  (Regulation  (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 Council10 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 Regu lation 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 requiremen ts 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 th is regulation and th e 
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)11allows  for more  effici ent approval  of clinical  trials  in the EU. 
Regulation  (EU)  2022/12312 strengthens  the role of the European  Medicines  Agency  
in order  to facilitate  a coordinated  EU-level  response  to health  crises.  The EMA  fees 
                                                 
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 ). 
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 Regulat ion (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 2001/2 0/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).  EN 4  EN legislation13 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.  
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  devices15 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  Europe16, a key funding  programme  for 
EU research  and innovation , and Beating  Cancer  Plan17 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 Regulation18. The 
intellectual  property  action  plan19 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. 
                                                 
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 product s for human use  (OJ L 35, 15.2.1995, p. 1) . 
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, storag e 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 Directiv e 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 1 290/2013 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 potenti al. 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 . EN 5  EN Concer ning 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  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 Membe r 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 re form  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 com plements 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 re form  of the pharmaceutical 
legislation is therefore consis tent with the package of legislative initiatives related to 
health security under the European Health Union23. 
To address  environmental  challenges,  the proposed  reform  of the pharmaceutical  
legislation  will support  initiatives  under  the European  Green  Deal24. These  include  
the EU action  plan ‘Towards  Zero  Pollution  for Air, Water  and Soil’  and the revision  
of: (i) the Urban  Waste  Water  Treatment  Directive25, (ii) the Industrial  Emissions  
Directive26 and (iii) the list of surface  and groundwater  pollutants  under  the Water  
Framework  Directive27. The proposal  is also well aligned  with the Strategic  
Approach  to Pharmaceuticals  in the Environment28. 
                                                 
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 t heir inclusion in the scope of national 
health insurance systems  (OJ L 40, 11.2.1989, p. 8 ). 
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-
life/european -health -union_en . 
24 Communication from the C ommission. 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 , 
 EN 6  EN Finally,  on the use of health  data,  the European  Health  Data Space29 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.  
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 
establishmen t 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 eff icacy 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 a s 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 intra -EU trade for medicinal pr oducts 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 re form  are expected to reduce administrative burden for compa nies and 
authorities and hence improve the efficiency and attractiveness of the EU system. 
The re form  will also have a positive influence on the competitive functioning of the 
market through targeted incentives and other measures that facilitate early mark et 
entry of generic and biosimilar medicinal products, contributing to patient access and 
affordability. Nevertheless, the proposed re form  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.  
                                                                                                                                                         
  https://ec.europa.eu/environment/water/water -dangersub/pharmaceutica ls.htm . 
29 Comm unication from the Commission, A European Health Data Space: harnessing the power of health 
data for people, patients and innovation  (COM(2022) 196 final).  EN 7  EN 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 inno vation (promoting the development of new medicinal 
products) and the objective of affordability (which is often achieved by 
generic/biosimilar competition). The re form  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.  
3. RESULTS  OF EX-POST  EVALUATIONS,  STAKEHOLDER  
CONSULTATIONS  AND  IMPACT  ASSESSMENTS  
• Ex-post evaluations/fitness  checks  of existing  legislation  
For the re form  of the general pharmaceutical legislation, stakeholder consultation 
activities were carried out as part of  the ‘back -to-back’  evaluation s and impact  
assessment s of the general  pharmaceutical  legislation  and of the Orphan  and 
Paediatric  Regulations30. 
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 202031. 
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 ensur ing 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 t hat 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 reimburse ment 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; glob al are also the supply chains and manufacturing 
                                                 
30 Commission staff working document , Impact Assessment , Annex 5: Evaluation.   
31 Evalua tion of the medicines for rare diseases and children legislation,  
  https://health.ec.europa.eu/medicinal -produ cts/medicines -children/evaluation -medicines -rare-diseases -
and-children -legislation_en . EN 8  EN 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 H uman Use32. 
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 childr en, 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 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 u nequal 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 re form of the general pharmaceutical legislation, stakeholder consultation 
activities were carried out as part of the ‘back -to-back’ evaluation and impact 
assessment33. 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 re form . 
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 lear ned societies 
(academics); environmental organisations; the pharmaceutical industry and their 
representatives.  
                                                 
32 ICH – harmonisation for better health, https://www.ich.org/ .  
33 Commission staff working document , Impact Assessment , Annex 2: Stakeholder Consultation 
(Synopsis Report).  EN 9  EN 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 o n 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 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 additiona l 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 authori ties, 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 SM Es, 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 th e two pieces of legislation 
have had a positive effect on the development of medicinal products for children and EN 10  EN the treatment of rare diseases. However, concerning the Paediatric Regulation, all the 
current structure of the paediatric investigation plan a nd 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 an d 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 b etter 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) . 
– 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 legislation34 
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 alt ernatives.  
                                                 
34 Commission staff working document , Impact Assessment.  EN 11  EN 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. 
Compani es 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. 
Marke ting 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 hold ers 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 com plemented 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.  
The preferred option is based on option C and also includes the common el ements 
mentioned above. The preferred option was considered to be the best policy choice, 
taking into account the specific objectives of the re form  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 resi ding 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 authoriti es 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 EN 12  EN bacteria and current costs incurre d 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 incen tives 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 dur ation of market exclusivity of 10, 9 and 5 years, 
based on the type of orphan medicinal product (for HUMN, new active substances 
and well -established 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 legislat ion. 
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 
achievem ent of the four objectives of the revision. It will aim to refocus investments 
and boost innovation , in 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 an d 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, EN 13  EN but savings are expected for companies through the cross -cutting measures in the 
general pharma ceutical  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 th e 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, bu t 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 pro cedures 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. I t would also ensure a fair return of investment for medicinal products 
developers who fulfil the legal obligation to study medicin al 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 fo r 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 t o 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  and competent  authoritie s. 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  EN 14  EN 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  leaflet s) should  also lead to administrative  cost reductions.  
SMEs  and non-commercial  entities  involved  in the develop ment  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 optimis ing 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;  
– environmental  risk assessment  strengthening;  
– shortage  management  and security  of supply.  EN 15  EN 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 
10-15 years. Incentives and rewards therefore have an influence  many years after the 
marketing authorisation date. The benefit for patients also needs to be me asured 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 Committee35 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 legis lation 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 me dicinal 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 a n 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 living with rare diseases, and it targets more those areas of high 
                                                 
35 Council Decision of 20 May 1975 setting up a pharmaceutical committee (75/320/EEC) . EN 16  EN 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. T he 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 us e 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 medi cinal 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 m edicinal 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 plan s 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 expec ted 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 li nked to obligations to 
supply the priority antimicrobial in the EU. A sunset period of 15 years is proposed, EN 17  EN after which time the Parliament and the Council may decide to continue or review 
the measure, following a proposal by the Commission, based on expe rience gained 
during this period.  
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 resi stance 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 regulato ry 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 p andemic , 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 prod ucts 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 Devic e 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 cl inical 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 scientif ic 
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 consul ting 
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 
medicin al products.  
Temporary emergency marketing authorisation  EN 18  EN 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 si mplified 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 i ntroduces  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 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 st age).  
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 su pply 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 ha ve 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 distribut ion 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 EN 19  EN 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 co mponent 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 .  
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 rapp orteurs 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 effic ient 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 Commit tees: 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 Produc ts (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 Co -ordination Group for Mu tual 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 exper ts 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 a t 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 s cientific support for promising EN 20  EN 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 a reas 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 measur es 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.  
Among the m easures 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 interact ions 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, safe ty 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 (whe n a molecule has never 
been used before, for instance). With the concept of evolutionary PIP, certain type s 
of developments, like molecules used for the first time in humans, will be given the 
possibility to initially present a high level clinical developm ent 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.  EN 21  EN 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 rule s 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), thereo f, 
Having regard to the pr oposal 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 Committee1, 
Having regard to the opinion of the Committee of the Regions2, 
Acting in accordance with t he ordinary legislative procedure,  
Whereas:  
(1) The U nion 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 int ernal 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 be en 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 U nion pharmaceutical legislation have addressed access 
to medicinal products by providing for accelerated assessment for marketing 
authorisation applications or by allowing conditiona l marketing authorisation for 
                                                 
1 OJ C , , p. .  
2 OJ C , , p. .  EN 22  EN 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.  
(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 p eople under all cir cumstances.  
(6) For the sake of clarity, it is necessary to replace Regulation (EC) No 726/2004 of the 
European Parliament and of the Council3 with a new Regulation.   
(7) Veterinary medicinal products are governed by Regulation (E U) No 2019/6  of the 
Europ ean Parliament and of the Council4. 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 spe cific 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 Council5. 
(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 report6 on the experience gained, it has pr oved 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 v iew to maintain a high -level of scientific evaluation for new medicinal 
products and medicinal products that will serve the entire Union population, the 
                                                 
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 Agen cy (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 Parlia ment 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 acquire d 
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.  EN 23  EN 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 t he centralised procedure in 2004.  
(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 procedu re 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 prescript ion. 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 evalu ation. 
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 medicin al 
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 h ealthcare 
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 con ferred 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.  EN 24  EN (17) The creation of the Agency through Council Regulation (EEC) No 2309/937 which 
was replaced by Regulation (EC ) No 726/2004 has made it possible to reinforce the 
scientific evaluation and monitoring of medicinal products in the Union, in particular 
through its scientific bodies and committees for which competent authorities of the 
Member States provide experts and  expertise, ensuring a high quality and independent 
assessment. This Regulation does not establish a new Agency. The Agency mentioned 
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 com mittee 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 scientifi c 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 Ag ency 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 Regulat ion (EU) 2021/2282 of 
the European Parliament and of the Council8 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 an d of the 
Council9. 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 reg arding the 
transparency rules for the Agency's work, to set certain conditions for the marketing of 
                                                 
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).  
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 Par liament 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).  EN 25  EN medicinal products authorised by the Union, to confer on the Agency powers to 
monitor the distribution of medicinal products authorised by the Union, to car ry 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 Sta tes request support in carrying out their tasks under 
revised Directive 2001/83/ EC of the European Parliament and of the Council10. The 
interest of the Union may concern situations where, to ensure faster access to 
medicin al products , challenges with inspec tions 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 ac cept to either provide support to the 
inspections of sites located in the U nion 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 U nion legislative requirem ents. 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 esta blished 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/EC11, and to reduce 
the cost of the placing on the market of medicinal products for human use authorised 
                                                 
10 Directive 200 1/83/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).  
11 Commission Recommendation of 6 May 2003 concerning the definition of micro, small a nd medium -
sized enterprises (OJ L 124, 20.5.2003, p. 36).  EN 26  EN 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 f ees. 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 par ticular 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 empower ed to give scientific recommendations on whether a 
product under development, which could potentially fall under the mandatory scope of 
the centralised procedure, meets the scientific criteria to be a medicinal product. Such 
an advisory mechanism would add ress, 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 t he 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 sh ould 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 pro cess among committees, duplication of 
work and non -optimised 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, th e 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 sc ientific 
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 EN 27  EN Committe e 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 
consist s of experts from all Memb er 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 exp ertise 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 therap y medicinal products are now more common. The full 
integration of their assessment in the work of the CHMP will facilitate the a ssessment 
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 adv ice on clinical trial applications and therefore a 
more integrated development advice in view of future data requirements for marketing 
authorisation applications, the Agency can engage in consultation with representatives 
from Member States with clinical trial expertise . Nevertheless, decisions on clinical 
trial applications should remain within the competence of the Member States, in 
accordance with Regulation (EU) No 536/2014  of the European Parliament and of the 
Council12.  
(39) To allow for a more infor mative 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 unm et 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 C oordination 
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 comp etent 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 agencies13, Member States 
should ensure adequate resources are assigned by the competent authorities of the 
                                                 
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 EN 28  EN 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 a n application under the centralised 
procedure a scientific opinion from the Agency for the use of the medicinal product 
for markets outside the U nion. 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 o f third countries in the context 
of performing its tasks. Such regulatory cooperation should be coherent with the 
broader economic relationship of the U nion with the third country concerned, taking 
account of the relevant international agreements between t he U nion 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 pro duct 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 -risk balance of all medicinal products will be assessed when they are 
placed on the market, and at any other time the com petent 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 ass essed 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 posses sion. 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 purposes14 lays down provisions on the protection of 
animals used for scientific purposes based on the principles of replacement, reduction 
and refinem ent. 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 ca re 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, 
                                                 
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 ). EN 29  EN suffering, di stress 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 accoun t 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 p ost-
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 optim ise 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 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 Medicin al Products  for human use will use the available 
mechanisms under Regulation (EU) 182/2011 of the European Parliament and of the 
Council15 and notably the possibility to obtain the committee’s opinion by written 
procedure and within expeditious deadli nes 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 produ ct.  
                                                 
15 Regulation (EU) No 182/2011 of the European Parliament and of the Counc il 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).  EN 30  EN (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 
right s 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 subje ct 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 Council16, 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 
principl es 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 reaso ns or individual 
patient needs and th at 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 particu lar the need to 
obtain a marketing authorisation and consequently, to have available complete 
information about the risks posed by the medicinal product, including any risks to the 
environment from medicinal products containing or consisting of genetically  modified 
organisms (GMOs). To avoid delays in making these products available or 
uncertainties as regards their status in certain Member States, it is appropriate, in those 
exceptional and urgent situations, that for a medicinal product containing or cons isting 
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 Council17 
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 pat ients and to take 
account of the increasingly rapid progress of science and therapies, accelerated 
                                                 
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).  
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).  EN 31  EN 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, reg arding 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 sh ould 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 o r 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 a nd 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 minimi sed through 
a withdrawal of the initial or t he 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. Through these capabilitie s 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 document ation 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 EN 32  EN necessary for the purposes of this Regulation, such processing should be done in 
accordance with Union law on the protection of personal dat a. Any processing of 
personal data under this Regulation should take place in accordance with Regulation 
(EU) 2016/67918 and Regulation (EU) 2018/172519 of the European Parliament and of 
the Council.  
(63) Access to individual patient data from clinical studi es 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 possibi lity 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 autho rities 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 th e 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 eviden ce, 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 medicinal products when they fu lfil 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 medicin al products  for unmet medical needs, based on the s cientific 
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 nee d. 
(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 
                                                 
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 ). EN 33  EN 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 t han 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 tr eatment, 
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 as sessment 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 observatio ns 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 lai d 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 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.  EN 34  EN (74) To avoid unnecessary admin istrative 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 marketi ng 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, i t 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 exist s at Unio n 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 ava ilability 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 an d 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 considere d a ‘priority antimicrobial ’, a medicinal product should  represent a real 
advancement against antimicrobial resistance and should therefore bring forward non-
clinical 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 U nion 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 financia l 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 nu mber 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 vouche r under ce rtain circumstances.  EN 35  EN (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 U nion 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 transpare ncy 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 financ ial 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 conduct ed 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 u sed 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 Regulati on 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 meas ure 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 applicati on 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 b y 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 condi tions attached to it are not 
complied with.  
(86) Medicin al 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.  EN 36  EN (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 necessar y 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 Council20 has 
proved to be successful in boosting developmen ts 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 transpare nt 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 t hese 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 appropria te 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 mean ing 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 th e 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 con dition. 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 satisfac tory method. In addition, 
                                                 
20 Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 19 99 on 
orphan medicinal products (OJ L 18, 22.1.2000, p. 1).  EN 37  EN commonly used methods of diagnosis, prevention or treatment that are not subject to a 
marketing authorisation may be considered satisfactory if there is scientific evidence 
of their efficacy and safety. In certain cases, medicinal  products prepared for an 
individual patient in a pharmacy according to a medical prescription, or according to 
the prescriptions of a pharmacopoeia and intended to be supplied directly to patients 
served by the pharmacy, may be considered as satisfactory treatment if they are well 
known and safe and this is a general practice for the relevant patient population in the 
Union. 
(94) The competence to designate a medicinal product as an orphan medicinal product, in 
the form of a decision, is accorded to the Ag ency. 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 medicin al products , the 
validity of orphan designation has be en 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 m edicinal product as well as 
for the setting up and management of a register of designated orphan medicinal 
products. Th at 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 evaluat ion 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 cri teria 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 alr eady 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 
medicin al products  are cove red. 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.  EN 38  EN In addition to the periods of ma rket exclusivity, o rphan 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 medicin al products  addressing high unmet needs, to ensure 
market predictability and to ensure  a fair distribution of incentives, a modulation of 
market exclusivity has been introduced; orphan medicinal products addressing high 
unmet medical needs benefit from the longest market exclusivity, while market 
exclusivity for well -established use orphan medicin al 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 t he concurrence of market exclusivity with data protection 
and defines situations when a similar medi cinal 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 formula tions 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 in vestigation 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 me dicinal 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.  EN 39  EN (109)  During public health emergencies, in order not to delay a prompt authorisation of a 
medicinal product intended for the treatme nt 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 en danger 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 th e 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 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 m edicinal 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 paed iatric 
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 difficultie s 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 th e Agency as an incentive to sponsors 
developing medicinal products for the paediatric population.  EN 40  EN (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 ap propriate, 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 author isation, 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 pa ediatric population. It 
should be possible for the name of the medicinal product that has been granted a 
Paediatric Use Marketing Authorisation to retain the existing brand name of the 
corresponding medicinal product authorised for adults, in order to capi talise 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 t he 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 Authorisatio n 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 m edicinal 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 informati on 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 continu ing 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 t he 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 
public ly 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 Economi c 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 EN 41  EN investigation plans, fee waivers for scientific advice, and information and tra nsparency 
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 effec ts 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 ma in 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 coo rdination 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 therefor e not impose any additional reporting 
requirements on marketing authorisation holders. The database should be fully and 
permanently accessible to the Member States, the Agency and the Commission, and 
accessible to an appropriate extent to marketing authori sation 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 efficien t 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 ti me 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 transformatio n 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 o n the benefit -risk 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 super visory 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 f or 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 20 01/83/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 EN 42  EN authorisation, for which it is agreed that the fundamental criteria should be retaine d. 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 opportuni ty 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 20 20 the Council has encouraged the 
Commission to consider the use of regulatory sandboxes on a case -by-case basis when 
drafting and reviewing legislation.  
(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 describ ing the 
products to be covered. A regulatory sandbox should be limited in duration and may 
be terminated a t 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 appropri ate, 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 
suppl y 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 re porting 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 tak en for granted across Europe. This is especially 
true for the most critical medicinal products which are essential to ensure the EN 43  EN 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 empower ed 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 hold ers 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 Parliament and of the Council21, 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 pro ducts 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 m arketing 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 permane nt 
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 a nd 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 datab ase, after the deletion 
of any commercially confidential information by the competent authority. Regulation 
(EC) No 1049/2001 of the European Parliament and of the Council22 gives the fullest 
possible effect to the right of public access to documents and la ys down the general 
principles and limits on such access. The Agency should therefore give the widest 
                                                 
21 Regulation (EU) 2022/123 of the European Parliament and of the Council o f 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 Counc il of 30 May 2001 
regarding public access to European Parliament, Council and Commission documents (OJ L 145, 
31.5.2001, p. 43).  EN 44  EN possible access to the documents while carefully balancing the right for information 
with existing data protection requirements. Certain public and privat e 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 
authoris ation 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 co uld 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 p urposes 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 inv olved.  
(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 o f 
determining the situations in which post -authorisation efficacy studies may be 
required; specifying the categories of medicinal products to which a marketing 
authorisation subject to specific obligations could be granted and specifying the 
procedures and  requirements for granting such a marketing authorisation and for its 
renewal; specifying exemptions to variation and the categories in which variations 
should be classified and establishing procedures for the examination of applications 
for variations to the terms of marketing authorisations as well as specifying conditions 
and procedures for cooperation with third countries and international organisations for 
examination of applications for such variations; establishing procedures for the 
examination of a pplications 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 con sultations 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 -Making23. 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 m edicinal products for human use, implementing  powers 
                                                 
23 OJ L 123, 12.5.2016, p. 1.  EN 45  EN 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 stipu lates, 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. I n 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 i s to be followed.  
(147)  Consequently, it is particularly difficult to conduct multi -centre clinical trials with 
investigational medicinal products that contain or consist of GMOs involving several 
Member States.  
(148)  One of the objectives of Regulation (E U) 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 environm ent 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 o f 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 failur e to comply with certain 
obligations laid down in this Regulation are specified in Commission Regulation (EC) EN 46  EN No 658/200724. Those rules should be maintained, but it is appropriate to consolidate 
them by moving their core elements and the list specifying th ose 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 2141/9625 remain s in force and continue s to apply 
unless and until repealed. For the same reason, it should be clarified that Regulations 
(EC) No 2049 /200526, No 507/200627, No 658/2007 and (EC) No 1234/200828 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 i nternal 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 spe cific provision with regard to the central 
authorisation of  medicinal products, therefore ensuring the functioning of the intern al 
market and the free movement of medicinal products. Regarding Article 168(4) , point 
(c), TFEU, this Regulation sets high stan dards 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 integri ty 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, in cluding 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 Europea n 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 . 
                                                 
24 Commission Regulation (EC) No 658/2007 of 14 June 2007 concerning financial penalties for 
infrin gement 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 conce rning 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 Decemb er 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).  
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).  EN 47  EN HAVE ADOPTED THIS REGULATION:  
CHAPTER I  
SUBJECT MATTER, SCOPE AND DEFINITION S 
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 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/EC29] 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 t o 
in Article 64(4); 
(3) ‘orphan medicinal products’ means a medicinal product which  has been granted  an 
orphan marketing authoris ation 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 ha s 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 substa nce’ 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 therap y medicinal products, for which the principal molecular 
                                                 
29 [Name of revised Directive 2001/83/EC, date (OJ L XX, XX.XX.XXX, p. X).]  EN 48  EN 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’ mea ns a clinically relevant advantage or a major contribution to 
patient care of an orphan medicinal product if such an advantage or contribution  
benefits a substantia l 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 pr otection certificate under Regulation (EC) No 469/2009 of the 
European Parliament and of the Council concerning the supplementary protection 
certificate for medicinal products30 [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 develop ment 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 i nsufficient 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 p laced 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 pr oduct available on the market 
in that Member State, and that shortage cannot be resolved.  
                                                 
30 Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009 
concerning the supplementary pr otection certificate for medicinal products  (OJ L 152, 16.6.2009, p. 1 ). EN 49  EN (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  (‘central ised marketing authorisation’) . 
2. Any medicinal product not listed in Annex I, may be granted a central ised marketing 
authorisation in accordance with this Regulation, if the product meets at least one of 
the follo wing 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 patient s' 
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 . 
4. The Commission  shall grant and supervise central ised marketing authorisations for 
medicinal products for human use in accordance with Chapter II.  
5. The Commission is empowered to adop t delegat ed 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 f or 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 protecti on 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 . EN 50  EN Chapter II  
GENERAL P ROVISIONS AND RULES ON APPLICATIONS  
SECTION 1 
APPLICATION FOR CENTR ALISED  MARKETING AUTHORISATI ONS  
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 documenta tion required in accordance with  Article 6 have been 
submitted , that the application does not contain critical deficiencies that may prevent 
the evaluation of the medicinal product  and decide  whether the application is valid.  
6. Where the Agency considers that the application is incomplete, or contains critical 
deficiencies that may prevent the evaluation of the medicinal product , it shall inform 
the applicant accordingly and set a time limit for submitting the missing information  
and documentation. That time limit may be extended once by the Agency.  
Upon receipt of the responses from the applicant to the request to submit the missing 
information and documentation, the Agency will determine whether the application 
can be considere d 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  
Central ised marketing authorisation application  
1. Each application for a central ised 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 EN 51  EN 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 o f 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 uni que, 
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 Council31, 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 particular s 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 con sidered 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 examin ation of the application.  
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 en sure 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 opin ion of that Committee shall take into account the 
evaluation of the environmental risk assessment  in accordance with Article 8. 
                                                 
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).  EN 52  EN On the basis of a duly reasoned request, the Committee for Medicinal Products for 
Human Use may call for the duration of the ana lysis 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 su bstantiated.  
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 m edicinal product s 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 environment al 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 s et 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 organi sms. 
4. Articles 6 to 11 of [revised Directive 2001/18/EC ] as well as Articles 4 to 13 of 
Directive 2009/41/EC shall not apply to operations related to the supply and clinical 
use, including  the packaging and labelling, distribution, storage, transport, 
preparation for administration, administration , destruction or disposal of medicinal 
products containing or consisting of genetically modified organisms, with the 
exception of their manufactur e, 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 product s containing or consisting of 
genet ically modified organisms into the environment.   EN 53  EN 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 establ ished 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 product s 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, assess ing 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 m easures 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 a n 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 su bmitted environmental risk assessment, the Committee  for 
Medicinal 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  prepar ing 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 EN 54  EN 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 test s the medicinal product for human 
use, its starting materials , ingredients  and, where necessary , its intermediate 
products or other constituent s in order to ensure that the control methods 
employed by the manufacturer and described in the application documents are 
satisfactory;  
(b) that the applicant supplement s 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 Produc ts 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 th is 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 t he medicinal product concerned or carry out the necessary control tests, 
or both in accordance with the particulars and documents supplied by the applicant 
pursuant to  Article 6.  
2. The Committee for Medicinal Products for Human Use may, if  it considers it  
necessary in order to complete the assessment , require the applicant to undergo a 
specific inspection of the manufacturing site of the medicinal product concerned.  
The inspection shall be carried out within the time -limit set out  in Article 6(6), first 
subparagraph, by inspectors from the Member State holding the appropriate 
qualifications . Those inspectors  may be accompanied by a rapporteur or an expert 
appointed by the Committee , or by one or more inspectors of the Agency . The 
inspections may be carried  out unannounced.  
For manufacturing  sites located  in third  countries,  the inspection  may be carried  out 
by the Agency,  following  a request  by the Member  States  and based  on the procedure  
set out in Article  52. 
Article 12  
Committee Opinion  EN 55  EN 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 applic ation 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 th e 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 Article s 18 and 
19 subject to specific conditions therein . 
2. Within 1 2 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, th e Committee for 
Medicinal Products for Human Use shall re -examine its opinion. The reasons for the 
conclu sion 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 f avourable 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 assess ment 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 conditi ons under which the 
medicinal product may be made available to patients, in accordance with the 
criteria laid down in  Chapter XII  of [revised Directive 2001/83/EC] ; 
(d) details of any recommended conditions or restrictions with regard to the safe 
and effec tive 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;  EN 56  EN (f) where  appropriate, details of any recommended obligation to conduct post -
authorisation 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 post -
authorisation 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 
post-authorisation 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 
surro gate 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 conduc t 
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 a fter 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] . 
SECTION 2 
MARKETING AUTHORISATI ON DECISIONS  
Article 13  
Commission decision  on the marketing authorisation  
1. Within 12 days of receipt of the opinion  of the Committee for Medicinal products for 
Human Use  the Commission shall  submit to the Standing Committee on Medicinal 
Products for Human Use  referred to in Article 173(1) a draft of the decision on the 
application.  EN 57  EN 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 conditio ns 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 t he 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 Co mmittee 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 pa ragraph 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 informati on 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 suffici ently 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 ; EN 58  EN (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 medici nal 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 m edicinal products for human use  are 
added to the Union Reg ister of Medicinal Products and  that they are given a number, 
which shall ap pear 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 Int ernational 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 produc t; 
– a summary of environmental risk assessment studies and their results as 
submitted by th e 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 EN 59  EN (b) its intention to temporarily suspend the marketing of a medicinal product in 
that Member State in accordance with Article 116(1), point (c ); or 
(c) a potential or actual shortage in that Member State in accordance with Article 
116(1), point ( d); and  
its reasons for such action under points (a) and (b) in accordance with  Article 24 , as 
well as any other reason relating to precautionary actions with regard to quality, 
safety, efficacy and the environment . 
Upon request by the Agency, particularly in the cont ext 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 aut horisation 
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 ci rcumstances  
1. In exceptional circumstances where, in an application under Article 6 of [revised 
Directive 2001/83/EC]  for a marketing authorisation of a medi cinal  product or a new  
therapeutic  indication of an existing marketing authorisation  under this Re gulation, 
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 EN 60  EN 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 o f this Regulation;  
(c) specific conditions are included in the decision of the Commission, in 
particular to ensure the safety of the medicinal product as well to ensure that 
the marketing authorisation holder notifies to the competent authorities any 
incid ent relating to its use and takes appropriate action where necessary.  
2. The maintenance of the a uthorised 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 ren ew 
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 medic al 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 th at 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 sub paragraph may be gra nted 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 m arketing authorisations or a new conditional therapeutic indication 
granted pursuant to this Article shall be subject to specific obligati ons. 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 g ranting 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 EN 61  EN Article shall be required to c omplete ongoing studies, or to conduct new studies, with 
a view to confirming that the benefit -risk balance is favourable.  
5. The summary of product characteristics and the package leaflet shall clearly mention 
that the conditional marketing authorisation for the medicinal product has been 
granted subject to specific obligations as referred to in  paragraph  3. 
6. By way of derogation from Article 17(1), an initial conditional marketing 
authorisation granted pursuant to this Article shall be valid for one year, on a 
renewable basis for the first three years after granting the authorisation and every two 
years thereafter.  
7. When the specific obligations referred to in paragraph  3 have been fulfilled for a 
conditional  marketing authorisation granted pursuant  to this Article, the Commission 
may, following an application by the marketing authorisation holder, and after  
having  receiv ed 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) conduct s 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 shal l, following consultation with the 
Pharmacovigilance Risk Assessment Committee, encourage the marketing 
authorisation holders concerned to conduct a joint post -authorisation safety 
study;  
(b) conduct s a post -authorisation efficacy study when the understand ing 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) conduct s a post -authorisation environmental risk assessment study to further 
investigate the risks to the environment or public healt h 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.  EN 62  EN Where the Agency considers that any of the post -authorisations studies referred to in 
points (a) to (c) is n ecessary, 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 author isation holder with an opportunity to 
present written observations in response to its letter  within a time limit which it shall 
specify, if the marketing authorisation holder so requests within 30 days of receipt of 
the letter . 
3. On the basis of the writt en 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 au thorisation , 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 incorporat e 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 authorisatio n, together with the reasons 
for such action.  EN 63  EN 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 oth er 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 alr eady being 
treated . 
The notification of the permanent withdrawal of a medi cinal  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 disruptio n 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 Article s 195 or 196(1) of [revised Directive 2001/83/EC] . 
3. In the cases referred to in paragraph s 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 ; EN 64  EN (b) for reasons of co -marketing with a different undertaking  not belonging to the 
same group as the marketing a uthorisation 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 
dupli cate 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 commercial designs for a given medicinal product for human use 
covered by a single marketing authorisation.  
Article  26 
Medic inal 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 , para graphs 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 
medici nal product concerned must either be the subject of an application for a 
marketing a uthorisation 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 applyi ng 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 author isation 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 ma y 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 . EN 65  EN 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 a nd 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 referre d to in  paragraph  4 shall not affect the civil or criminal liability 
of the manufacturer or of the applicant for marketing authorisation.  
8. Where a compassionate use programme has been set up  in accordance with 
paragraph s 1 and 5 , the applicant shall ensu re 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. Th at Committee sha ll 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 authorisation s  
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 pr otection 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] . EN 66  EN SECTION 3 
TEMPORARY EMERGENCY M ARKETING AUTHORISATI ON 
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 comple te 
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 tha t 
Directive shall not apply.  
An application for a temporary emergency marketing authorisation shall be submitted in 
accordance with Article s 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 Council32 and where  the foll owing 
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 conclud ing 
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 considerati on 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.  
                                                 
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 ). EN 67  EN 2. The Agency shall review any new evidence provided by the developer, the Member 
States or the Commission, or any other evidence that come s to its attention, in 
particular evidence that might influence the benefit -risk balance of the medicinal 
product concer ned. 
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  paragraph s 2, 3  and 4. Those implementing acts shall be adopted in 
accordance with the examination procedure referred to in  Article 173(2). 
2. On the basis of the scientific opinion of the Agency referred to in paragraph  1, the 
Commi ssion 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 th ose 
studies shall be set.  
4. Those specific conditions and, where appropriate, the time limit for compliance shal l 
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 r evocation  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 3 1 are no longer met;  
(b) it is appropriate to protect public health;  EN 68  EN (c) the marketing authorisation holder of a temporary emergency marketing 
authorisation has not complied with conditions and obligations set out in the 
temporary emergency market ing 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 exam ination 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 Article s 5 and 6 in order to obtain an authorisation 
in accordance with Article s 13, 16 or 19.  
For the purpose of regulatory d ata 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 te mporary marketing author isation 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) 
2022/12333 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, w here 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 
                                                 
33 Regulation (EU) 2022/123 of the European Parliament and of the Council of 25 Jan uary 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).  EN 69  EN emerge ncy 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 avai lable 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 
product s containing the same active substance  for any indications that are subject to the 
temporary marketing authorisation.  
CHAPTER III  
INCENTIVES FOR THE DEVELOPMENT OF ‘ PRIORITY 
ANTIMICROBIALS’  
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 act s, 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 ‘pri ority 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, t he applicant shall :  
(a) demonstrate capacity to supply the priority antimicrobial in sufficient 
quantities for the expected needs of the Union  market;  EN 70  EN (b) provid e 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 referr ed 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 . 
A voucher may only be used if the market ing authorisation of the priority 
antimicrobial for which the righ t 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 protecti on 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 certificates34, if a 
priority antimicrobial  is withdrawn from the Union  market prior to expiry of the 
periods of market and data protection laid down in Article s 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 
                                                 
34 Regulation (EC) No 469/2009 of the European Parliament and of the Council , (OJ L  152, 16.6.2009, p. 
1). EN 71  EN 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 t he Agency.  
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 appl ication 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 r equired, 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 th e 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  EN 72  EN 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 D irective 
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 
authorisa tion 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 informa tion 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 hold er by the competent authorities of any country in which the 
medicinal product is marketed and of any other new information which might 
influence the evaluation of the benefits and risks of the medicinal product concerned. 
The information shall include both  positive and negative results of clinical trials or 
other studies in all indications and populations, whether or not included in the 
marketing authorisation, as well as data on the use of the medicinal product where 
such use is outside the terms of the ma rketing 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 authorisa tion 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 antimicr obial resistance.  
Article  46 
Update of risk management plans  
1. The marketing authorisation holder of a medicinal product referred to in Article s 9, 
and 11 of [revised Directive 2001/83/EC]  shall submit to the Agency a risk EN 73  EN 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 Article s 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 conce rning 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 authorisa tion holder and shall include the deadline 
for submission of the risk management plan and the summary  by means of a 
variation in accordance with Article 47. 
Article 47 
Variation of marketing authorisation  
1. An application for variation of a centralised marketing authorisation by the 
marketing authorisation holder shall be made electronically  in the formats made 
available by the Agency, unless the variation is an update by the marketing 
authorisation holder of their information held in a database.  
2. Variations shall be classified in different categories depending on the level of risk to 
public health and the potential impact on the quality, safety and efficacy of the 
medicinal product concerned. Those categories shall range from changes to the terms 
of th e 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 a nd 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 de legated acts i n 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 ; EN 74  EN (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 s everal 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 no t-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 medici nal product with a new therapeutic indication that 
concerns an unmet medical need.  
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 
autho rities for manufacturing shall be the competent authorities of the Member State 
or Member States which granted the manufacturing authorisation referred to  in EN 75  EN 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 
Direc tive 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 manufactur ing 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] . 
When carry ing 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 superviso ry 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 Direct ive 2001/83/EC] . 
The supervisory authorities for pharmacovigilance  may, if necessary, conduct pre -
authorisation inspections to verify the accuracy and successful implementation of the 
pharmacovigilance system as it has been described by the applicant in su pport 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 pr oduct 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 authori ty 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.  EN 76  EN 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 
posses s 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 electronic ally 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 comp letion of the inspection, the supervisory 
authority grants the relevant good manufacturing practice (GMP) certificate 
and enters the certificate in the Union database; or  
(b) to carry out the inspection and the follow up thereof on behalf of the 
supervisor y 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] .  
Whe re the Agency decides to carry out the in spection, 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 f orm 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.  
Whe re 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. EN 77  EN The Agency’s inspectors shall have the same powers conferred on official 
representatives of the competent authority pursuant to these provisions.  
5. Following a reque st 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 bas ed 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 paragraph s 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 participate s as an inspectorat e 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 Organi sation and trusted international authorities, by 
means of international inspection program mes. 
2. In cooperation with the A gency, 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 o f 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 activitie s applicable to medicinal products and active substances EN 78  EN 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 refe rred to in Article 3(3) of Commission Directive (EU) 
2017/157235 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 inspe ctions 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 f or activities that support the work of the joint 
audit programme . 
Article 55 
Referral procedure  
1. Where the supervisory authorities or the competent authorities of any other Member 
State are of the opinion that the manufacturer or importer established within the 
Union territory is no longer fulfilling the obligations laid down in Chapter  XI of 
[revised  Directive 2001/83/EC] , they shall without undue delay  inform the Agency 
and the Commission, stating their reasons in detail and indicating the course of 
action proposed.  
Similarly, where a Member State or the Commission considers that one of the 
measures envisaged in Chapters IX, XIV  and X V 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 Medi cinal  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 
                                                 
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 produc ts for human use (OJ L 238, 16.9.2017, p. 44).  EN 79  EN 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 u se 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 ac ts. 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 implementin g 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 heal th 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 par agraph s 2 
and 3 . 
5. In case s 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 ha s been adopted by the Commission in accordance 
with paragraph 3.  
7. The Agency shall, upon request, inform any person concerned of the final decision 
and make the decision publicly available immediately after it has been taken.  
8. Where the procedure is initiated as a result of the evaluation of data relating to 
pharmacovigilance, the opinion of the Agency, in accordance with paragraph 2, shall 
be adopted by the Committee for Medicinal Products for Human Use on the basis of 
a recomm endation from the Pharmacovigilance Risk Assessment Committee and 
Article 115(2) of [revised Directive 2001/83/EC]  shall apply.  
9. By way of derogation from paragraph s 1 to 7, where a procedure under Article 95 or 
Articles 114, 115 and 116 of [revised Dire ctive 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 A rticles  114, 115 and 116 of that 
Directive.  
Article 56 
Action on conditional marketing authorisation  EN 80  EN 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.  
CHAPTE R 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 Article s 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.  
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.  EN 81  EN 2. In case of medicinal products involvi ng a medical device, undertakings or, as 
relevant, not -for-profit entities may request scientific advice as referred to in  Article 
58(1) in parallel with the consultation of the expert panels referred to in Article 61(2) 
of Regulation (EU) 2017/745.  
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  Article s 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 Artic le 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 antimicrobial s 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 cr oss 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 . 
Article 61 
Scientific recommendation on r egulatory 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’ , EN 82  EN including an ‘advanced therapy medicinal product’ as defined in  Article 2 of 
Regulation (EC) No 1394/2007 of the European Parliament and of the Council36.  
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 o f 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 subs tantiated 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.  
CHAPTER VI  
ORPHAN MEDICINAL PRODUCTS  
Article 63 
Criteria for orphan designation  
1. A medicinal product that is intended for the diagnosis, prevention or treatment of a 
life-threatening or chronically debilitating condition shall be designated as an orphan 
                                                 
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 ). EN 83  EN medicinal product where the orphan medicine sponsor can demonstrate that the 
follow ing 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 
conditi on 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, w hen the requirements specified in paragraph  1, 
point (a ), are not appropriate due to the specific characteristics of certain condition s 
or any other scientific reasons, the Commission is empowere d 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 p aragraph 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 med icine 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 inten ded 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 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. EN 84  EN 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  referre d 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 gran ting 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 particular s 
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 6 8. 
2. By way of derogation from paragraph 1, o n 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 ext ension shall be 
limited in time, taking into account the expected remaining time needed to file an 
application for marketing authorisation.  
3. By way of derogation from paragraph 1, w here an orphan designation is valid at the 
time when a marketing authoris ation for an orphan medicinal product has been EN 85  EN 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 onc e 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 
medi cinal  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 ind ication; 
(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 ef ficacy 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  indic ation ; 
(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 Regulatio n shall be eligible for incentives made available by the Union and by EN 86  EN 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 Article s 5 and 6 and the related marketing authorisation shall be obtained  in 
accordance with Article s 13(2). 
2. In addition, t he 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). I n 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 a pplication for the 
marketing authorisation itself  and d etailed 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 op inion 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  
1. An orphan medicinal product shall be considered as addressing a high unmet medical 
need where it fulfils the following requirements:  EN 87  EN (a) there is no medicinal product authorised  in the Union for such con dition  
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 re sults 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. Wher e 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 a n 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 tha n 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 1 3 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 gr anted, 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 ori ginal 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 auth orised, 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 EN 88  EN product to the  reference  medicinal product for which market exclusivity has expired, 
shall not be prevented by the market exclusivity of a similar product to the reference 
medicinal product.  
6. The market exclusivity of the orphan medicinal product shall not prevent the 
submission, validation and assessment of an application for a marketing authorisation 
for a similar medicinal product, including generics and biosimilars, where the 
remainder of the duration of the market exc lusivity is less than two years.   
7. Where the Agency adopts scientific guidelines for the application of paragraphs 1 
and 4 , it shall consult the Commissio n. 
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 ma rketing 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 
paragraph s 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 R egulation (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 ]. EN 89  EN 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 paedia tric 
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 o nly 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 an d 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 
accordanc e 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 p roduction of the informat ion 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:  EN 90  EN (a) that the specific medicinal product or class of m edicinal products is likely to be 
ineffective or unsafe in part or all of the paediatric population;  
(b) that the disease or condition for which the specific medicinal product or class is 
intended occurs only in adult populations , unless 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 produc ts 
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 de legated 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 th e 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 supplement ary 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 investigati on 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 appropr iate 
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 EN 91  EN admini stration 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 shal l 
adopt a decision within 70 days as to whether or not the paediatric investigation plan 
is expected to ensure the generation of the necessary data determining the conditions 
in which the medicinal product may be used to treat the paediatric population or 
subsets thereof, and as to whether or not the expected therapeutic benefits, where 
appropriate also over existing treatments, justify the studies envisaged.  
3. After receiving an updated version of the paediatric investigation plan referred to in 
Article 74(2), third subparagraph , the Agency shall review it within 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 shal l 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 revi ews 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 proc edure 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 
product -specific waiver shall be granted.  
Whenever appropriate, the Agency may request the applicant to supp lement the 
particulars and documents submitted. Where the Agency avails itself of this option, 
the 90 -day time -limit 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 alr eady  granted waiver . EN 92  EN 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.  
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 7 7, paragraph s 1, 2 or 4 . 
In such cases, the Agency s hall 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 som e 
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 the reof. 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.  EN 93  EN 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 pe riod given under  Article 
81(3). 
The Agency shall decide on the prolongation within 60 days.  
2. Whenever appropriate, the Agency may ask the applicant to submit 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 emergenc y 
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 
whic h 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 7 6(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 supp lement 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 paedia tric 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 ch anges requested within 60 days.  EN 94  EN 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. Th is time-limit shall be 
suspended until the supplemen tary information requested  or the additional 
modifications have  been provided . 
4. The procedure laid down in Article 87 shall apply for the adoption of decisions by 
the Agency . 
Article 85 
Detailed arrangements for applications  in relation to paediatric investigation plan s, 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 Article s 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 applicatio n 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 ref erred to in  
Article 74(2); 
(ii) products intended to be dev eloped 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 procedure s 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 do wn 
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.  EN 95  EN 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 m entioned 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 . 
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 pa ediatric 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 d esign 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 Art icle 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 appro priate, 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 m edicinal 
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 a pplication with the agreed completed 
paediatric investigation plan.  EN 96  EN Article 91 
Variation of marketing authorisations on the basis of paediatric studies  
1. Any clinical study which involve s 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.  
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  Article s 5 and 6 and shall be  accompanied by the particulars and 
documents necessary to establish quality, safety an d 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 paedi atric 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 do ssier 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 gra nted 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 9 3 
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 
investigatio n plan , the product shall benefit from independent data and marketing protection 
periods referred to in Article s 80 and 81 of [revised Directive 2001/83/EC] . EN 97  EN Article 94 
Paediatric clinical trials  
1. The EU database created by Article 81 of Regulation ( EU) No 536/2014 shall 
include clinical trials carried out in third countries  which are : 
(a) contained in an agreed paediatric investigation plan ; 
(b) submitted following the provisions of  Article 91. 
2. For the clinical trials mentioned in paragraph  1 which are conducted in third 
countries, the description of the following elements shall be entered into the EU 
database  prior to the start of the trial by the clinical trial sponsor, the addressee of the 
Agency's decision on a paediatric investigation plan  referred to in Article 77, or by 
the marketing authorisation holder as appropriate : 
(a) the clinical trial protocol ; 
(b) the investigational medicinal products used ; 
(c) the therapeutic indications covered ; 
(d) details of the trial population.  
Irrespective  of the outcome of a clinical trial within 6 months from the end of the 
trial the clinical trial sponsor, the addressee of the Agency's decision on a paediatric 
investigation plan or the marketing authorisation holder as appropriate , shall subm it 
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  Articl e 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 medic ines 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.  EN 98  EN 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 Regulation38]. 
2. Assessments of the following by the Agency shall be free of charge:  
(a) applications for waiver s; 
(b) applications for deferral s; 
(c) applications for paediatric investigation plans;  
(d) compliance with the agreed paediatric investigation plan.  
3. The Un ion 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 suppor t the Agency's 
activities under  Article s 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 waiver s agreed, providing also a summary of their reasons ; 
(e) a list of def errals  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; 
                                                 
38 Regulation [ XXX ] of the European Parliament and of the Council on fees and charges payable to the 
European Medicines Agency, a mending 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 ]. EN 99  EN (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 Article s 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 central ised marketing 
authorisation to operate a risk management system, as referred to in Article 99(4), 
point (c) of [revised Directive 2001/83/EC] , if there are concerns about the risks 
affecting the benefit -risk balance of an authorised medicinal product. In that context, 
the Agency shall also oblige the marketing authorisation holder to submit a risk 
manage ment plan for the risk -management 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 acc ordingly.  
(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 paragraph s 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.  EN 100  EN 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 sh are 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 in formation 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 o f 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, togeth er with a 
timeframe for their implementation.  
The Agency shall prepare an annual report on the Eudravigilance database and send 
it to the European Parliament, the Council and the Commission.  
Any substantial change to the Eudravigilance database and the fun ctional 
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 Commiss ion. 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 
protec ted. The Agency shall work together with all stakeholders, including research 
institutions, healthcare professionals, and patient and consumer organisations, in 
order to define the ‘appropriat e 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 
electro nically upon receipt to the competent authority of the Member State where the 
reaction occurred.  EN 101  EN 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 prod ucts 
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 co ordination 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 Pharmacovigilanc e Risk Assessment 
Committee, draw up the functional specifications for the repository.  
Any substantial change to the repository and the functional specifications shall always take 
into account the recommendations of the Pharmacovigilance Risk Assessment Committee.  
Article 104 
European medicines web -portal  and register of studies for environmental risk assessment  
1. The Agency shall, in collaboration with the Member States and the Commission, set 
up and maintain a European medicines web -portal for the diss emination 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 p roducts 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;  EN 102  EN (f) Union reference dates and frequency of submission of periodic safety upda te 
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 Article s 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 proced ure 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 2 001/83/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 Article s 16, 106, 107 and 108 of this Regulation and of  Chapter IX , Sections 
3 and 7  of [revised Directive 2001/83/EC ]. 
The summaries referred to in point (c) shall  include a description of any additional 
risk minimisation measures.  
2. In the development and review of the web portal , the Agency shall consult relevant 
stakeholders, including patient and consumer groups, healthcare professionals 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 envir onmental 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 commerc ially 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 liter ature.  EN 103  EN 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 adv erse 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 Article s 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 i n 
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 authoris ations 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 su bmission of the 
reports are laid down in the marketing authorisation or are determined in accordance 
with Article 108 of that Directive.  
3. The assessment of the periodic safety update reports shall be conducted by a 
rapporteur appointed by the Pharmacovig ilance 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 referre d 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 
assess ment report and the recommendation in the repository set up under  Article 103, 
and forward both to the marketing authorisation holder.  EN 104  EN 4. In the case of an assessment report that recommends any action concerning the 
marketing authorisation, the Committee f or 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 authori sation 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 Me dicinal 
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 nece ssary, 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 Me mber 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 mar keting 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  
1. Regarding medicinal products for human use authorised in accordance with this 
Regulation, the Agenc y 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  
Article s 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 whet her those risks impact on the 
benefit -risk 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 benefit -risk 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. Wh ere 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  Article s 95 and 114 
of [revised Directive 2001/83/EC]  or Article 55 of this Regulation . EN 105  EN 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-interventi onal 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 Article s 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 d ecision in accordance with  
Article 13.  
Where the opinion of the Committee for Medicinal Products for Human Use differs 
from the recommendation of the Pharmacovigilance Risk Assessment Committee, 
the Committee for Medicinal Products for Human Use shall attach to its opinion a 
detailed explanation of the scientific grounds for the differences, together with the 
recommendation.  
Article 109 
Exchange of information with other organisations  
1. The Agency shall collaborate with the World Health Organization in matters of 
pharmacovigilance and shall take the necessary steps to submit to it, promptly, 
appropriate and adequate information regarding the measures taken in the Union 
which could  have a bearing on public health protection in third countries.  
The Agency shall make available promptly all suspected adverse reaction reports 
occurring in the Union to the World Health Organization.  
2. The Agency and the European Monitoring Centre 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 collabo ration with the 
Member States in international harmonisation and standardisation of technical measures in 
relation to pharmacovigilance.  
Article 111 
Cooperation with Member States  EN 106  EN 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 publi shed.  
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 charact eristics 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 trial s and placing 
on the market of a product referred to i n paragraph 1 under the conditions set out in 
this Chapter. 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 legisl ation 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 ma y engage with them in preliminary discussions.  EN 107  EN 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 Commissi on. 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 sh all 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 a lternative 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 a ny possible distortion 
of market conditio ns 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 paragraph s 6 and 7 are no longer 
met; 
(b) it is appropriate to protect public health.  
Those implementing acts shall be ado pted 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). EN 108  EN 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 accor dance 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 produc ts 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 medic inal 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 grant ed 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 cover ed 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). 
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, sha ll 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 EN 109  EN Agency without undue delay  of any information which migh t 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 th e 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 re commendations 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 a nd put forward, as appropriate, legislative 
proposals with a view to update the regulatory framework  referred to in Article 
113(2) or delegated acts in accordance with  Article 28 of [revised Directive 
2001/83/EC] . 
CHAPTER X  
AVAILABILITY AND SECURITY OF SUPPLY  OF 
MEDICINAL PRODUCTS  
SECTION 1 
MONITORING AND MANAGE MENT OF SHORTAGES AN D 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 medic inal 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 n o 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 authori sed 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;  EN 110  EN (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 medicin al 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 accordanc e 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 ho lder 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 paragra ph. 
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 holde rs 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 
recommen dations 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). EN 111  EN 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 collab oration 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 
referre d 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 EN 112  EN and take into account the guidance drawn up by the Agency according to Article 
122(4), point  (c). 
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 define d 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 re port 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 representativ e 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 th at 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 
availabl e 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 EN 113  EN reporting established pursuant to Article 122(4), point (b), by the deadline set 
by the Agency;  
(b) where necessary, provide updates to the information provided in accordance 
with point (a) to the Agency;  
(c) justify any failure to provide any of the information referred to in point (a) to 
the Agency;  
(d) where necessary, submit a request to the Agency to extend the deadline set by 
the Agency referred to in point (a);  
(e) indicate whether the marketing authorisation holder as defined in Article 
116(1) has indicated the existence of any commercially confidential 
information and provide the m arketing 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 refe rred 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 A rticle 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 provi de 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 EN 114  EN 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 infor m the MSSG of the shortages of the medicinal products that 
have been identified pursuant to paragraph 2.  
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 th e 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’) , establish ed 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 prov ision of recommendations referred to in Article 
123(4); 
(e) publish information covered by points (a)  to (d) on a dedicated webpage on its 
web-portal referred to in Article 104. 
5. For the duration of the critical shortage and until the MSSG considers it t o 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 Re gulation 
(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 impl ementing 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 rep orting.  
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 ’). EN 115  EN 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 th is 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 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 purp oses 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 reques ted. 
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 pro vided 
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 addi tional relevant information to the Agency;  EN 116  EN (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 point s (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  
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 prov ide recommendations referred to in 
Article 123(4). 
SECTION 2 
SECURITY OF SUPPLY  
Article  127 
Identification and management of critical medicinal products by the competent authority of 
the Member State  
1. The competent authority of the Member State shall 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 
referre d 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 enti ties 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.  EN 117  EN 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 compe tent 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 pr ovided in accordance with point s (a) and 
(b) to the Agency where necessary;  
(d) justify any failure to provide any  of the requested information;  
(e) indicate the existence of any commercially confidential information reported as 
such by the marketing auth orisation 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 accordanc e 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 rele vant information to the Agency;  
(c) comply and coo rdinate 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 : EN 118  EN (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 monitori ng 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 wheth er 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 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) speci fy 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) ; EN 119  EN (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.  
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 th e 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 inform ation 
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 EN 120  EN 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 im plementing 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 thi s list and any updates to 
this list on its web -portal referred to in Article 104. 
Article  132 
Role of the MSSG  
1. Following the adoption of the Union list of critical medicinal products pursuant to 
Article 131(3), in consultation with the Agency and the working party referred to in 
Article 121(1), point (c), the MSSG may provide recommendations, in accordance 
with the methods referred to in Article 130(1), point (d), on appropriate security of 
supply measures to marketing authorisation holders as defined in Article 116(1), the 
Member States, the Commission or other entities. Such measures may include 
recommendations on diversification of suppliers and inventory management.  
2. The MSSG shall amend its rules of proc edure, 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 medici nal 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  
Follo wing 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 refe rred 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);  EN 121  EN (e) inform the Agency of any measures taken and report on the result s 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 requirem ents 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). 
CHAPTER XI  
EUROPEAN MEDICINES AGENCY  
SECTION 1 
TASKS OF THE AGENCY  
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 i ts 
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 State s, 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.  EN 122  EN Article 137 
Seat 
The seat of the Agency shall be established in Amsterdam, the Netherl ands.  
Article 138 
Objectives and tasks of the Agency  
1. The Agency shall provide the Member States and the institutions of the Union with 
the best possible scientific opinion on any question relating to the evaluation of the 
quality, safety and efficacy of medicinal products for human use, veterinary 
medicinal products, which is referred to it in accordance with the Union legal acts  
relating to medicinal products for human use or veterinary medicinal products.  
The Agency, acting particularly through its Committees, shall carry out the following 
tasks:  
(a) coordinating the scientific evaluation of the quality, safety and efficacy of 
medicinal products for human use,  which are subject to Union marketing 
authorisation procedures;  
(b) coordinating the scientific evaluation of the quality, safety and efficacy of  
veterinary medicinal products, which are subject to Union marketing 
authorisation procedures in accordance with Regulation (EU) 2019/6 and the 
performance of other tasks set out in Regulation (EU) 2019/6 and Regulation 
(EC) 470/2009;  
(c) transmitting on r equest 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 authori sed 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 pr oducts 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;  EN 123  EN (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 
cooperat ion 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 i n 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 accorda nce with Union marketing authorisation 
procedures;  
(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 
health -care 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 therap eutic 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;  EN 124  EN (s) drawing up, at the Commission’s request, any other scientific opinion 
concerning the evalu ation 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 
conce rning 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) coordina ting 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 Medici nes and Healthcare that coordinates with 
the Official Medicines Control Laboratory or by a laboratory that a Member 
State has designated for that purpose. The Agency and the European 
Directorate for the Quality of Medicines and Healthcare shall enter into a 
written contract for the provision of services to the Agency under this 
subparagraph ; 
(v) forwarding annually to the budgetary authority aggregated information on 
procedures for medicinal products for human use and veterinary medicinal 
products;  
(w) taking decisions as referred to in  Article 6(5) of [revised Directive 
2001/83/EC] ; 
(x) contributing to the joint reporting with the European Food Safety Authority 
and European Centre for Disease Prevention and Control on the sales and use 
of antimicrobials in human and veterinary medicine as well as on the situation 
as regards antimicrobial resistance in the Union based on contributions 
received by Member States, taking into account the reporting requirements and 
periodicity in Article 57 of Regulation (EU) 201 9/6. Such joint reporting shall 
be carried out at least every three years ; 
(y) adopt ing a decision granting , refusing or transferring  an orphan designation ; 
(z) adopt ing decisions on paediatric investigation plans, waivers and deferrals in 
relation to medicinal products ; 
(za) provid ing regulatory support and scientific advice for the development of 
orphan an d 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;  EN 125  EN (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 A rticle 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 p ackage leaflet and the information shown on the 
labelling. Where relevant, it shall include the electronic links to the dedicated 
webpages where the marketing authorisation holders have reported the information 
pursuant to Article 40( 4), point (b) , and Article 57 of [revised Directive 
2001/83/EC] . 
For the purposes of the database, the Agency shall set up and maintain a list of all 
medicinal products for human use authoris ed in the Union. To this effect:  
(a) the Agency shall  make public a format for the e lectronic 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 o f 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 th e clinical trials 
database provided for in Article 81 of Regulation (EU) No 536/2014.  
Article 139 
Coherence of scientific opinions  with other Union bodies  EN 126  EN 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 so urce 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 wit hout undue delay . 
4. The Commission may ask the Agency to conduct a n 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 
regulat ory protection.  
Article  140 
Scientific opinions in the context of international collaboration  
1. The Agency may give a scientific opinion, in particular  in the context of cooperation 
with the World Health Organization, for the evaluation of certain medicinal products 
for human use intended for markets outside the Union. For this purpose, an 
application shall be submitted to the Agency in accordance with t he 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 Article s 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 p rovision 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 EN 127  EN 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 compli ance 
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 condi tions 
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 co nditions for participation shall be determined in advance by the 
Commission.  
SECTION 2 
STRUCTURE AND OPERATI ON  
Article 142 
Administrative and management structure  
The Agency shall comprise:  
(a) a Management Board, which shall exercise the functions set ou t 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 ; EN 128  EN (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 appropriat e 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 als o 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 m ore 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 o f 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, recognise d experience and commitment in the field of 
medicinal products for human or veterinary use, taking into account relevant 
managerial, administrative and budgetary expertise [which are to be used to further 
the objectives of this Regulation].  
All parties rep resented 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 Manag ement Board.  EN 129  EN 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 e lected 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 ); 
(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; EN 130  EN (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 s hall 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 ‘ Conditi ons 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 
Cond itions 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 r isks 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 o f 
the European Anti -fraud 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 menti oned 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 po wers 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. 138 5). EN 131  EN 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 th e 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 o f 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 ma y 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 Manageme nt 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 pre judice 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 Dir ector 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 o f the Agency. The 
Executive Director shall be responsible  for: EN 132  EN (a) the day -to-day administration of the Agency;  
(b) implementing decisions adopted by the Management Board ; 
(c) managing all the Agency resources necessary for conducting the activities of 
the Committees referred to in  Article 142, including making available 
appropriate scientific and technical support to those Committees, and for 
making available appropriate technical support to the coordination group;  
(d) ensuring that the time -limits laid do wn 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 th ose 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) witho ut prejudice to the  competences of OLAF and EPPO,  protecting the 
financial interests of the Union by applying preve ntive 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 administrativ e 
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 qua lity. 
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 ab out 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  EN 133  EN 1. The scientific committees shall be responsible for providing the scientific opinions or 
recommendations of the Agency, each within their own spheres of competence, and 
shall have the possibility, where necessary of organising public hearings.  
2. The membership of the scientific  committees shall be made public. When each 
appointment is published, the professional qualifications of each member shall be 
specified.  
3. The Executive Director of the Agency or their representative and repres entatives 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. Memb ers 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 authorisat ion, 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 th e Committee s 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 committee s 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, t he 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 qu estions 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 parti es 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 adva nced 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 relev ant 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. EN 134  EN 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 indep endent manner, and shall make an annual declaration of their 
financial interests. All indirect 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 of fices.  
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 meeting s 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 acc ordance 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 fulfilm ent 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 reco mmendations 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 app ointed 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.  EN 135  EN 4. The Committee for Medicinal Products for Human Use may co -opt a maximum of 
five additional members chosen on the b asis 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.  
5. The alternates shall represent and vote for the members in thei r 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 
comp etent 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 ty pes of medicinal products 
covered by [revised Directive 2001/83/EC]  and this Regulation and which  includ e 
medicinal products for rare and paediatric diseases, advance therapy medicinal 
products, biological and biotechnological products, in order to guarant ee 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 vic e-chairperson 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 appoin ting 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 EN 136  EN risk of adverse reactions, having due regard to the therapeutic effe ct 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 m ember appointed by each Member State, in 
accordance with  paragraph 3; 
(b) six members appointed by the Commission, with a view to ensuring that the 
relevant expertise is available within the Committee, including clinical 
pharmacology and pharmacoepidemiolo gy, on the basis of a public call for 
expressions of interest;  
(c) two member s and two alternate member s 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 member s and two alternate member s 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 alternat e 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 Ris k 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 e xpertise 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 wi th 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 ap pointed 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 vice -chairperson from among its members for a term of three  years, which may 
be prolonged once.  
Article 150 
Scientific w orking parties  and scientific advisory groups  
1. The scientific  committees referred to in  Article 146 may establish scientific w orking 
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.  EN 137  EN Working parties estab lished 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 s cientific 
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 Comm ittee may establish an Environmental Risk Assessment working party and 
other scientific working parties, as necessary.   
3. The composition  of the working par ty 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 th e Member States.  Where appropriate, the Committee for 
Human Medicinal Product s 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 estab lishing 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 re ferred 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 
veterinar y 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 th eir 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 EN 138  EN 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. T hat expert 
pool shall include the national experts referred to in paragraph 2 and any other 
experts appointed by the Agency or the Commission, and shall be updated.  
5. Accredited experts shall have access to training provided by the Agency , as 
appropriate . 
6. Rapporteurs of any of the committees referred to in Article 142 may use the services 
of accredited experts for the fulfilment of their tasks in accordance with  Article 152. 
Any remuneration of such accredited  expert shall be deducted from the remuneration 
due to the rapporteurs.  
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 r ules 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 a s 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 accor dance 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 a ppointed 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 t he 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 do wn 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), t he 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.  EN 139  EN 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  
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 me dicinal 
product for human use provides.  
SECTION 3 
FINANCIAL PROVISIONS  
Article 154 
Adoption of the budget of the Agency  
1. Estimates of all the revenue and expenditure of the Agency shall be prepared for 
each financial year, corresponding to the calendar year, and shall be shown in the 
budget of the Agency.  
2. The revenue and expenditure shown in the budget shall be in balance.  
3. The Agency’s revenue shall consist of:  
(a) a contribution from the Union;  
(b) a contribution from third countries participating  in the work of the Agency with 
which the Union has concluded international agreements for th at 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 EN 140  EN 155(11) and with the provisions of the relevant instruments supporting the 
policies of the Union.  
The European Par liament 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  revenu e provided by the sources referred to in the first subparagraph, 
point s (c), (d) and (e) . 
4. Activities relating to the assessment of marketing authorisation applications, 
subsequent variations, pharmacovigilance, to the operation of communications 
network s 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 ac tivities by the Agency on the condition that its independence is 
strictly guaranteed.  
5. The expenditure of the Agency shall include staff remuneration, administrative and 
infrastructure costs, and operational expenditure. In respect of operational 
expendi ture, 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 t his 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 bas is 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 bu dget 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 EN 141  EN 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 no tified 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 
Council40. 
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 Com mission 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 wi th 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 Nove mber 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 Directo r shall submit to the European Parliament, at the latter’s 
request, any information required for the smooth application of the discharge 
                                                 
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). EN 142  EN 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 Agen cy shall be adopted by the Management 
Board after the Commission has been consulted. They shall not depart from 
Commission Delegated Regulation (EU) 2019/71541 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 Council42 shall 
apply without restriction.  
2. The Agency shall accede to the I nterinstitutional Agreement of 25  May 1999 
between the European Parliament, the Council of the European Union and the 
Commission of the European Communities43 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 Uni on 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 i n 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  2185/9644. 
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 co mpetences.  
                                                 
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 Parliam ent 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 Regulat ion (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 ins pections 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).  EN 143  EN 6. In accordance with Council Regulation (EU) 2017/193945, 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 Parlia ment and 
of the Council46. 
SECTION 4 
GENERAL PROVISIONS GO VERNING THE AGENCY  
Article 157 
Liability  
1. The contractual liability of the Agency shall be governed by the law applicable to the 
contract in question. The Court of Justice of the European Union shall have 
jurisdiction pursuant to any arbitration clause contained in a contract concluded by 
the Agency.  
2. In the c ase of non -contractual liability, the Agency shall, in accordance with the 
general principles common to the laws of the Member States, ma ke good any 
damage caused by it or by its staff in the performance of their duties.  
The Court of Justice shall have jurisdiction in any dispute relating to compensation 
for any such damage.  
3. The personal liability of its staff towards the Agency shall be governed by the 
provisions laid down in the Staff Regulations or Conditions of Employment of Other 
Servants applicable to them.  
Article 158 
Access to documents  
Regulation (EC) No  1049/2001 sha ll 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 C ourt of Justice, under the conditions laid down in Article 228 and Article 263 of 
the Treaty respectively.  
Article 159 
Privileges  
                                                 
45 Council Regulation (EU) 2017/1939 of 12 October 2017 implementing enhanced coope ration 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 in terests by means of criminal law (OJ L 198, 28.7.2017, p. 29).  EN 144  EN 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) 2015/44347 and 2015/44448. 
The security rules of the Agency shall cover, inter alia, provisions for the exchange, 
processing and storage of such information.  
Members of the Management Boa rd, 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 c eased.  
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 administr ative 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 A gency, 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 . 
                                                 
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 sec urity rules for protecting 
EU classified information (OJ L 72, 17.3.2015, p. 53).  EN 145  EN The consultation process  shall include bodies responsible for health technolo gy 
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, 
health care 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 health care professions. These contacts may include the participation of observers in 
certain aspects of the Agency's wor k, under conditions determined beforehand by the 
Management Board, in agreement with the Commission.  
Article 164 
Support to SMEs and to not -for profit entities  
1. The Agency shall ensure that micro, small and medium -sized enterprises ( ‘SMEs ’) 
and not-for-profit entities are offered a support scheme.  
2. The support scheme shall be comprised of regulatory, procedural and administrative 
support and reduction, deferral or waivers of fees.  
3. The scheme shall cover the various steps involved in pre -authorisation procedures, 
and in particular scientific advice, the submission of the marketing authorisation 
application, and the post -authorisation procedures.  
4. SMEs shall benefit from the incentives laid down in Commission Regulation (EC) 
No 2049/2005 and [revised Council Regulation (EC) No 297/95 ]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.  
                                                 
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).  EN 146  EN 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 th e 
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 o f 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 character istics 
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 per sonal health data , in 
accordance with this Regulation and Regulation (EU) 2018/1725.  
Article 167 
Protection against cyber attacks  
The Agency shall equip itself with a high level of security controls and processes against 
cyber attacks, cyber espionage and other data breaches to ensure the protection of health data 
and the normal functioning of the Agency at all times, especially during public health 
emergencies or major events at Union level.  
For the purposes of the first subparagraph, the Agency shall actively identify and 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 Council50, and existing national provisions and practices in the Member States 
on confidentiality, all parties in volved in the application of this Regulation shall 
respect the confidentiality of information and data obtained in carrying out their tasks 
                                                 
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).  EN 147  EN in order to protect the commercially confidential information and trade secrets of 
natural or legal persons in accor dance with Directive (EU) 2016/943 of the European 
Parliament and of the Council51, including intellectual property rights.  
2. Without prejudice to  paragraph  1, all parties involved in the application of this 
Regulation shall ensure that no commercially con fidential 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 co mpetent 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. Paragraph s 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 t he 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 m ultilateral confidentiality arrangements.  
Article 169 
Processing of personal data  
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 perfo rmance 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 A rticle , ‘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.  
                                                 
51 Directive (EU) 2016/943 of the European Parliament and of the Council o f 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).  EN 148  EN 4. The Management Board shall establis h the general scope for the regulatory science 
activities in consultation with the Commission and the European Data Protection 
Supervisor.  
5. The Agency shall keep document ation  containing a detailed description of the 
process and of the rationale behind t he 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 t he 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 M ember 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 sh all be an assessment of the 
results achieved by the Agency having regard to its objectives, mandate, governance 
and tasks, including an assessment of whether the continuation of the Agency is still 
justified with regard to these objectives, mandate, govern ance 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.  EN 149  EN 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 a ll 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, with out 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 tha n the marketing authorisation 
holder provided that such entities form part of the same economic entity as the 
marketing authorisation holder and that such other legal entities:  
(a) exerted a decisive influence over the marketing authorisation holder; or  
(b) were involved in, or could have addressed, such failure to comply with the 
obligation by the marketing authorisation holder.  
3. Where the Agency or a competent authority of a Member State is of the opinion that 
a marketing authorisation holder has failed  to comply with any of the obligations, 
referred to in paragraph  1, it may request the Commission to investigate whether to 
impose financial penalties pursuant to that paragraph.  
4. In determining whether to impose a financial penalty and in determining its 
appropriate amount, the Commission shall be guided by the principles of 
effectiveness, proportionality and dissuasiveness and take into consideration, where 
relevant, the seriousness and the effects of the failure to comply with the obligations.  
5. For the purposes of paragraph  1, the Commission shall take into account:  
(a) any infringement procedure initiated by a Member State against the same 
marketing authorisation holder on the basis of the same legal grounds and the 
same facts;  
(b) any sanctions, including penalties, already imposed on the same marketing 
authorisation holder on the basis of the same legal grounds and the same facts.  EN 150  EN 6. Where the Commission finds that the marketing authorisation holder has failed, 
intentionally or negligently, to co mply 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 authori sation 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 turnov er 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 th e 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 met hods for their collection.  
CHAPTER XIII   
DELEGATED AND IMPLEMENTING ACTS  
Article  173 
Standing Committee on Medicinal Products for Human Use  and examination procedure  EN 151  EN 1. The Commission shall be assisted by the Standing Committee on Medicinal Products 
for Hu man 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 
Committe e 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  authorisatio n 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 accoun t 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 Ar ticle 173(2). 
2. In order to harmonise the performance of the pharmacovigilance activities provided 
for in this Regulation, the Commission sh all adopt implementing measures as 
provided for in Article 214 of [revised Directive 2001/83/EC]  covering the follo wing 
areas:  
(a) the content and maintenance of the pharmacovigilance system master file kept 
by the marketing authorisation holder;  
(b) the minimum requirements for the quality system for the performance of 
pharmacovigilance activities by the Agency;  
(c) the use of internationally agreed terminology, formats and standards for the 
performance of pharmacovigilance activities;  
(d) the minimum requirements for the monitoring of data included in the 
Eudravigilance database to determine whether there are new risks or whether 
risks have changed;  
(e) the format and content of electronic transmission of suspected adverse 
reactions by Member States and marketing authorisation holders;  
(f) the format and content of electronic periodic safety update reports and risk  
management plans;  
(g) the format of protocols, abstracts and final study reports of the post -
authorisation safety studies.  
Those measures shall take account of the work on international harmonisation carried 
out in the area of pharmacovigilance and shall,  where necessary, be revised to take EN 152  EN 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  Article s 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 i nto force] . The Commission shall draw up a 
report in respect of the delegation of power not later than nine months before the end 
of the five -year period. The delegation of power shall be tacitly extended for periods 
of an identical duration, unless the European Parliament or the Council opposes such 
extension not later than three months before the end of each period.  
3. The delegation of power referred to in  Article s 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 effec t 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 Commiss ion 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 simulta neously to 
the European Parliament and to the Council.  
6. A delegated act adopted pursuant to  Article s 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 peri od, 
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 AC TS 
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 : 
‘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 EN 153  EN 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 o f 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 va lidation 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 EN 154  EN information within the period set by the Agency, the application referred to in  
paragraph 1 shall be deemed to have expired in all Member States concerned.  
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 Counc il**. 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 adop t 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 paragraph s 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 ta king 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 Counc il 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. ’; EN 155  EN (4) in Article 37(4) , the following subparagraph is inserted after the first subparagraph : 
In the case of a clinical trial which involve s 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 facilitie s 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 compensatio n 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 
arrang ement 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 th e 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 Articl e 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 decis ion. 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 d elegated 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 Commissio n shall notify it 
simultaneously to the European Parliament and to the Council.  EN 156  EN 6. A delegated act adopted pursuant to Articles  5a, 27, 39, 45, 63(1), and 70 shall 
enter into force only if no objection has been expressed either by the European 
Parliament or the Council within a period of two months of notification of that 
act to the European Parliament and the Council or if, before the expiry of that 
period, the European Parliament and the Council have both informed the 
Commission that they will not object . That period shall be extended by two 
months at the initiative of the European Parliament or the Council. ’; 
(9) Article 91 is replaced by the following : 
‘Article 91  
Relation with other Union legal acts  
‘This Regulation shall be without prejudice to Council Directive 97/43/Euratom52, 
Council Directive 96/29/Euratom53, Directive 2004/23/EC of the European 
Parliament and of the Council54, Directive 2002/98/EC of the European Parliament 
and of the Council55 and Directive 2010/53/E U of the European Parliament  and of 
the Council56. 
In the context of inspections referred under Article s 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 Regulatio n shall prevail.’  
* [OP: Insert the full title of that Regulation and the OJ reference, please]  
2. Articles 33 and 34 are deleted.  
                                                 
52 Council Directive 97/43/Euratom of 30 June 1997 on health protection of i ndividuals 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 radiati on (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 safe ty 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 ). EN 157  EN CHAPTER XV  
FINAL PROVISIONS  
Article 179 
Repeals  
1. Regulations (EC) No 141/2000, (EC) No 726/2004 and (EC) No 1901/2006 are 
repealed . 
References to the repealed Regulation s 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  198/201357 is repealed.  
Article  180 
Transitional provisions  
1. The provisions of Article 117 of this Regulation shall also apply to m arketing 
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 wit h 
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: P lease 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 
                                                 
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).  EN 158  EN authorisation in accordance with Article 7(3) of Regulation (EC) No 141/2000  
corresponding to the orphan designation  shall be considered to comply wi th this 
Regulation  and shall be entered in the Register of Designated Orphan Medicinal 
Products . 
6. Orphan designations granted before  [Note to the OP: Ple ase 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 consi dered as orphan 
designations and shall not be entered in the Register of Designated Orphan Medicinal 
Products.  
7. The 7-year validity of an orph an designation referred to in Article 66 of this 
Regulation for orphan medicinal products granted befor e [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 applic ation of this Regulation].  
8. The procedures concerning orphan designation s which were initi ated 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: Plea se 
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 applica tion], 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 pur suant to Article 23b , paragraphs 4 and 5  of 
Directive 2001/83/EC.  
12. Commission Regulation (EC) No 847/200058 shall continue to apply unless and until 
repealed as regards orphan medicinal products that are covered by this Regulation.  
                                                 
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 pr oduct as an orphan medicinal product 
 EN 159  EN 13. By way of derogati on 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 acco rdance 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 shoul d be identical to the date for the application of the Directive ]. 
However , Article 67 shall apply from [ Note to the OP: Please insert the date of 2 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  
                                                                                                                                                         
and definitions of the concepts 'similar medicinal product' and 'clinical superiority' (OJ L 103, 
28.4.2000, p. 5).  EN 160  EN 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 in volvement (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 i s 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. Monitori ng 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 identi fied 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  EN 161  EN  3.1. Heading(s) of the multiannual financial framework and expenditure 
budget line(s) affected  
 3.2. Estimated fin ancial 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 
EN 162  EN 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 h uman 
use and  
Regulation (EC) No 141/2000 of the European Parliament and of the Council on orphan medicinal pro ducts and  
Regulation (EC) No 1901/2006 of the European Parliament and of the Council on medicinal products for paediatric use1.  
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 action2  
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 med icinal products for paediatric use and amending 
Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Re gulation (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 Regu lation.   
EN 163  EN 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 innova tion, 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 inno vation.  
3. Ensure access to innovat ive 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 regula tory 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 obligati ons 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 u nmet 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.   
EN 164  EN The following core indicators will generate information in a continuous and systematic way on implementation and performance.   
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 syst em:  
– 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 timelin e 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 regul atory 
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 en able 
parallel scientific advice with health technology assessment and regulatory bodies for medical devices. Within the same perio d, the 
Agency shall create an Academia Office, a secretariat to support not -for-profit entities by providing them free of charge e arly 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.   
EN 165  EN 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 ac cess 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 inter vention 
which is additional to the value that would have been othe rwise 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 serv ices 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 i n 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 au thorised 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 monitori ng 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 func tioning 
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 pharmac eutical 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 lat e 1950s, 
when t housands 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 me dicinal 
product must ever again be marketed without prior authorisation.   
EN 166  EN Since then, a large body of legislation has been developed around this principle, with the progressive harmonisation of requi rements for 
the granting of marketing authorisation, and p ost-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 supp ort 
innovation. Dedicated incentives for med icines 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 les sons 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 goa ls:  
– 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 Contro l 
(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 Environme ntal 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 des ignations 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 subsid y 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 . 
  
EN 167  EN 1.6. Duration and financial impact of the proposal/initiative  
 limited dur ation  
–  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) planned3  
 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/ma n/budgmanag/Pages/budgmanag.aspx    
EN 168  EN –  persons entrusted with the implementation of specific actions in the CFSP pursuant to Title V of the TEU, and identified in t he 
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 Servic e of the 
Commission, the Management Board, the Commission, the Court of Auditors and the Budgetary Authority. This system is reflec ted and 
laid down in the EMA’s founding regulation. In accordance with the Joint Statement on the EU decentralised agencies (the ‘Com mon 
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 
docu ments”, 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 An nual Activity Report.  
The Agency will monitor periodically the performance of its internal control system to ensure that data is collected efficien tly, 
effectively and timely and to identify internal control deficiencies, register and assess the results o f 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.   
EN 169  EN 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 stra tegy 
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 Audit ors, 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 Audi t 
Committee, the Commission will re ceive 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 w ith Article 228 of the Treaty. 
These administrative controls provide a number of procedural safeguards to ensure that account is taken of the interests of t he 
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. Underperformanc e or 
impaired independence could hamper the achievement of the objectives of this initiative and also re flect 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 inte rnal 
procedures are in full compliance with the Financial Regulation and include a nti-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 achie ve the 
objectives of this initiative.  
Furthermore, quality management will inc lude 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 cont rols 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  
EN 170  EN applying to the Agency’s Management B oard, 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 reac t 
upon n otified 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 cl osure)  
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 c ontrol systems 
proved to be able to prevent and/or to detect errors and/or irregularities, and in case of errors or irregularities, to corre ct them.  
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 activ ities 
centering around integrated quality management, audit, anti -fraud measures, finance and verificati on 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 indire ct 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 activi ties, by 
effective check s 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 docum ents and 
on-the-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 pro vided 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 ap plied across all EU institutions. In line with the Common  
EN 171  EN 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 stan dalone fraud 
risk assessment, with the identified fraud r isks 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 di sciplinary procedures are in place as per the rules of the Staff Regulations.  
   
EN 172  EN 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 
multiannual 
financial 
framework  Budget line  Type of  
expenditure  Contribution  
Number  
 Diff./Non -
diff.4 from 
EFTA 
countries5 
 from 
candidate 
countries6 
 from third 
countries  within the 
meaning of 
Article  21(2)(b) of 
the Financial 
Regulation  
2 06.100302 Special contribution for 
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  
framework  2 Cohesion, Resilience and Values  
 
                                                 
4 Diff. = Differentiated appropriations / Non -diff. = Non -differentiated appropriations.  
5 EFTA: European Free Trade Association.  
6 Candidate countries and, where applicable, potential candidates.   
EN 173  EN DG: SANTE    
Year 
2024  Year 
2025  Year 
2026  Year 
2027 and 
subsequent 
years  TOTAL7 
 Operational appropriations       
06.100302 Special contribution for 
orphan medicinal products  Commitments  (1b)   1.172 3.196 4.368 
Payments  (2b)   1.172 3.196 4.368 
Appropriations of an administrative nature financed from the 
envelope of specific programmes8  
      
Budget line   (3)      
TOTAL appropriations  
for DG SANTE  Commitments  =1a+1b 
+3   1.172 3.196 4.368 
Payments  =2a+2b  
+3   
1.172 3.196 4.368 
 
 
 TOTAL operational appropriations  Commitments  (4)   1.172 3.196 4.368 
Payments  (5)   1.172 3.196 4.368 
 TOTAL appropriations of an administrative nature 
financed from the envelope for specific programmes  (6)      
TOTAL appropriations  
under HEADING <2b>  Commitments  =4+ 6    1.172 3.196 4.368 
Payments  =5+ 6    1.172 3.196 4.368 
                                                 
7 For 2026 the total amo unt 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 th e incentives to 
“not-for-profit” 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.   
EN 174  EN of the multiannual financial framework  
 
   
EN 175  EN Heading of multiannual financial  
framework  7 ‘Administrative expenditure’  
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 Statement  (Annex V to the internal rules), which is up loaded to DECIDE for interservice consultation purposes.  
EUR million (to three decimal places)  
   
Year 
2024  Year 
2025  Year 
2026  Year 
2027 and 
subsequent 
years  Enter as many years as 
necessary to show the 
duration of the impact (see 
point 1.6)  TOTAL  
DG: SANTE  
 Human resources          
 Other administrative expenditure          
TOTAL DG <…….>  Appropriations          
 
TOTAL appropriations  
under HEADING  7 
of the multiannual financial framework   (Total commitments = 
Total payments)          
EUR million (to three decimal places)  
   Year 
2024  Year 
2025  Year 
2026  Year 
2027  Enter as many years as 
necessary to show the duration 
of the impact (see point 1.6)  TOTAL  
TOTAL appropriations  
under HEADINGS 1 to 7  
of the multiannual financial framework   Commitments    1.172 3.196    4.368 
Payments    1.172 3.196    4.368 
  
EN 176  EN 3.2.2.  Estimated output funded with operational appropriations  
Commitment appropriations in EUR million (to three decimal places)  
Indicate 
objectives and 
outputs  
 
   Year 
2024  Year 
2025  Year 
2026  Year 
2027 and 
subsequent years  TOTAL  
OUTPUTS  
Type9 
 Avera
ge 
cost 
No 
Cost 
No 
Cost 
No 
Cost 
No 
Cost Tota
l No Total 
cost 
Specific objective 1. Promote innovation, in particular for unmet medical needs, including for rare disease patients 
and children.          
Support to “not -
for-profit” 
entities  
        1.172  3.196  4.368 
Subtotal for specific objective No 1       1.172  3.196  4.368 
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, et c.).  
EN 177  EN 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)  
 
Year 
2024  Year 
2025  Year 
2026  Year 
2027 and 
subsequent 
years  TOTAL  
 
 
Temporary agents (AD Grades)  
  0.781 0.797 1.578 
Temporary agents (AST 
grades)    0.391 0.399 0.790 
Contract staff  
     
Seconded National Experts  
     
 
 
TOTAL  
  1.172  1.196  2.368  
 
Staff requirements (FTE): Total posts Union funded and funded from fees  
 
 
Year 
2024  Year 
2025  Year 
2026  Year 
2027 and 
subsequent 
years  TOTAL  
 
Temporary agents (AD Grades)  13 22 33 40 40 
Temporary agents (AST grades)  6 15 19 20 20 
Contract  staff      
Seconded National Experts       
  
EN 178  EN TOTAL  19 37 52 60 60 
 
 
 
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.   
EN 179  EN 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  
 
Year 
2024  Year 
2025  Year 
2026  Year 
N+3 Enter as many years as 
necessary to show the duration 
of the impact (see point 1.6)  
 Establishment plan posts (officials and temporary staff)  
20 01 02 01  (Headquarters and Commission’s Representation 
Offices)         
20 01 02 03 (Delegations)         
01 01 01 01   (Indirect research)         
 01 01 01 11 (Direct research)         
Other budget lines (specify)         
 External staff (in Full Time Equivalent unit: FTE)103 
 
20 02 01  (AC, END, INT from the ‘global envelope’)         
20 02 03 (AC, AL, END, INT and JPD in the delegations)         
XX 01  xx yy zz  104 
 - at Headquarters  
        
- in Delegations         
01 01 01 02  (AC, END, INT - Indirect research)         
 01 01 01 12 (AC, END, INT - Direct research)         
Other budget lines (specify)         
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 b e 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 
Academia Office at EMA that will be managing the procedures. The 
tasks of the office will be similar to t he tasks of the SME office and will 
include procedural and administrative assistance to “not -for-profit” 
entities, including direct assistance and briefing meetings on regulatory 
strategy, providing fee waivers and reductions to eligible entities, 
provide free-of-charge translations of the product information in all EU 
languages for initial EU marketing authorisations, provide training and 
education to “not -for-profit” entities, etc  
External staff   
                                                 
103 AC= Contrac t 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).   
EN 180  EN 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:  
 managing (AD profiles) and providing support (AST profiles) to 
operational expert groups in the area of the Environmental Risk 
Assessment ( ERA);  
 with a  scientific and regulatory profile to work in the shortages 
management and security of supply;  
 Good Manufacturing Practice and Good Clinical Practice 
inspectors (AD) necessary to establish an EU inspectorate 
resourced by EMA staff that would provide help to the 
inspections done by Member States (lacking resources), and deal 
with emergency situations  which require dedicated and 
dependable intervention (e.g., similar to inspections required 
during the pandemic);  
 Legal officers (AD profiles), needed in the field of orphan 
designations that are already today a litigious topic and so it is 
assumed the pr oposed changes in the decision making on orphan 
designation would generate an increased in workload for even 
more legal queries and litigations;  
 defining business requirements for the data register, following 
up on the implementation and perform the relat ed scientific 
activities when the register is live; , develop trainings on ERA, 
etc.;  
 providing administrative support to the operational expert 
groups;  
 working in the area of inspection planning;  
 general assistants, assistants, supporting on procedural aspects or 
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 Financia l 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.   
EN 181  EN 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)  
 
Year 
2024  Year 
2025  Year 
2026  Year 
2027 
and 
subsequ
ent 
years  Enter as many years as ne cessary 
to show the duration of the 
impact (see point 1.6)  Total  
Specify the co -financing 
body           
TOTAL appropriations 
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 
available for 
the current 
financial year  Impact of the proposal/initiative105 
Year 
2024  Year 
2025  Year 
2026  Year 
2027 and 
subseque
nt years  Enter as many years as necessary to show 
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 (cus toms duties, sugar levies), the amounts indicated must be net 
amounts, i.e. gross amounts after deduction of 20 % for collection costs.