An agency of the European Union

An agency of the European Union

Human medicines in 23 Research and development 473 overall number of scientific advice and protocol assistance requests received in 23 2.6% increase compared with 22 7 applications for parallel advice with health technology assessment bodies 36 orphan designations granted 97 positive opinions on paediatric investigation plans 23 recommendations on advanced therapy classifications 64% increase compared with 22 Authorisation phase 8 medicines recommended for marketing authorisation 2 advanced therapies orphan medicines 2 biosimilar monoclonal antibodies Immunotherapy and oncology Anti-infective Neurology/CNS Alimentary tract Cardiovascular Blood Genito-urinary Respiratory Musculoskeletal Sensory organs Dermatologicals Hormones Antiparasitic insecticides Various 2 4 3 9 6 4 3 3 2 2 2 Safety monitoring,,+ ADR reports received in 23 26.3% increase compared with 22 signals prioritised and analysed by the PRAC 43 referral procedures started

365 23 8 8 79 339 354 22 2 27% 52% 2% 23 22 2% 22% 63% 3% 3% 24% 62% % 2 2% 25% 6% 2% 23

Anti-neoplastic and immunomodulating agents Nervous system Alimentary tract and metabolism General anti-infectives for systemic use Blood and blood-forming organs Respiratory system Genito-urinary system and sex hormones Sensory organs Cardiovascular system Dermatologicals Various Musculoskeletal system Systemic hormonal preparations, excluding sex hormones Anti-parasitic products, insecticides, repellents Diagnostic agents 29 22 2 2 2 6 6 7 5 5 48 47 44 Annual report 23 36 Support to small and medium-sized enterprises The Agency put the SME initiative in place in December 25 to promote innovation and development of medicines by SMEs. This initiative provides active SME-related activites - requests received Requests for administrative assistance Requests for qualifications as an SME Requests for renewal as an SME 23 22 2 23 22 2 23 22 2 3 35 58 349 4 433 62 684 88 these companies in the development of their medicines. The support takes the form of individual guidance and more general advice through the SME user guide, topical workshops and a dedicated newsletter. In 23, the number of companies assigned SME status by the Agency increased by 4.6% in comparison with 22, with a cumulative total of,258 active SMEs registered at the end of the year. SMEs accounted for 24% of the requests for sciprotocol assistance received in 23. ions submitted to the Agency in 23 and one in two submitted by SMEs. Orphan-medicinal-product-designation procedures Submitted 23 22 2 66 2 97 Positive opinions 23 22 2 36 39 Negative opinions 23 22 2 2 Withdrawals 23 22 2 6 52 45 Commission decisions 23 22 2 7 36 48

4% 47% 39% 23 22 42% 3% 28% 4% 48% 38% 2 58 37 67 67 23 22 2 67 86 59% 7% 8% 6% 23

23 22 2 86 78 77 87 22 2 23 22 2 23 22 2 23 22 2 23 22 2 23 22 2 23 22 2 Positive on full waiver 4 3 3 3 2 6 4 9 52 47 45 Positive on PIP, including potential deferral Negative opinions adopted 97 87 7 Positive opinions adopted on modification of a PIP 86 65 53 Negative opinions adopted on modification of a PIP Positive opinions on compliance with a PIP 23 22 2 Negative opinions on compliance check with a PIP Cardiovascular diseases Endocrinology-gynaecology Infectious diseases Oncology Immunology-rheumatology-transplantation Neurology Gastroenterology-hepatology Haematology-haemostaseology Pneumology-allergology Dermatology Pain Uro-nephrology Psychiatry Neonatology-paediatric intensive care Diagnostic Ophthalmology Anaesthesiology Vaccines Other 5.3% 8.8% 6.2% 5.3% 6.3% 7.9% 3.% 5.3% 4.7% 5.3% 4.7% 4.4%.6% 2.6%.9%.6%.8%.8%.8% 7% 6.2% 5.8% 5.6% 5.8% 3.% 3.5%.6% 3.5% 3.% 3.5% 4.7% 3.% 34.4%

23 22 2 2 2 4 7 2 23 8 76 78 23 22 2 8 96 23 New medicinal products 22 (non-orphan) 2 48 47 48 23 Orphan medicinal 22 products 2 23 Similar biological 22 products 2 Generics, hybrid products etc. 23 22 2 23 Scientific opinions for 22 non-eu markets 2 3 8 2 4 8 9 2 34

Positive opinions Applications withdrawn prior to opinion Negative opinions 23 22 2 23 22 2 23 22 2 4 8 7 8 3 57 Positive opinions by type of procedure (2-23) New medicinal products (non-orphan) Orphan medicinal products Similar biological products Generic, hybrid and informed-consent applications 23 22 2 23 22 2 23 22 2 23 22 2 4 4 8 9 2 9 3 38 79 87 46 45 Immunotherapy and oncology Anti-infective Alimentary tract Neurology/CNS Respiratory Blood Cardiovascular Sensory organs Genito-urinary Hormones Musculoskeletal Dermatologicals Antiparasitic insecticides Various 9 2 4 9 4 3 8 3 7 4 3 6 5 2 3 3 2 2 5 2 Initial marketing-authorisation applications Positive opinions

22 6,468 2,889,2 2 23,26 2,875 873 3,958 2,922 96 6 22 88 87 2 39 2 79 73 8 22 23 2 57 87 22 28 9 2 3 94 23 23 364

23 22 Non-EEA ADRs 2 23 22 EEA ADRs 2 44,99 45,3 45,526 39,946 35,85 37,739 22 5 4 2 Herbal monographs Public statements 23 9 4 7 2 2 2 9,528 2 32,62 22 9,68 23 8,24 2,67 5,279 2 22 23 55,885 27,564 233,764 2 22 23 242,73 2 389,452 22 488,85 23

,,+ ADR reports received in 23 23 22 2,23 2,449 2,449 potential signals reviewed by EMA s signal-validation team 2,586 43 signals validated by the EMA and analysed by the PRAC In 23, 43 signals were detected and validated by the EMA and 57 signals were detected and validated by Member States. Among the 43 signals raised by the EMA, two had been under monitoring by the signal-validation team at the Agency in 22, eight were prompted by the scientific literature and five by information received from other regulatory authorities. 2 of the 43 signals validated by the EMA led to a recommendation for changes to the product information, either directly (n=7) or following a cumulative review (n=4), providing information to patients and healthcare professionals on the safe use of these products. For four signals, this also included the distribution of direct healthcare professional communications (DHPCs) to increase awareness about the new safety information.

Maintenance 36 Article 7i 5 CHMP variation 76 Suspension Article 2 Article 3Phv 6 7 Revocation Total outcomes 436

Veterinary medicines in 23 Research and development 4 scientific-advice applications received in 23 43% increase compared with 22 23 applications received for designation of minor-use minor-species (MUMS) classification 7 applications for maximum residue limits (MRLs) received for a new substance in 23 Authorisation phase 2 medicines recommended by the CVMP for marketing authorisation 23 applications for initial evaluation of new veterinary products received by CVMP in 23 3 for immunological products for food-producing species x2 increase compared with 22 8 relating to pharmaceuticals intended for companion animals generic pharmaceutical intended for both food-producing and non-producing species Safety monitoring 22,326 reports on suspected adverse reactions in relation to a veterinary medicine 6.% of reports concerned dogs referrals or arbitration procedures related to veterinary medicinal products started 9 food-producing animals companion animals

2 22 23 28 29 26 23 4 34 23 22 2 23 2 2 22 3 2 5 5 7 4 2 2 26 2 23

2 8 3 23 3 22 4 6 23 7 6 22 2 5 5 5 8

23 22 2 8 3 2 23 23 6 8 8 22 2 2 9 3 3 3 23 22 2 3 8 8 4 4 4 7 2 22 23 22 65 2 6 28 29 97 62 97

22 2 52 8 2 22 45 7 23 283 32 5 23 22 2 2, 2,869 5,86 2,592 3,598 4,568 8,59 6, 3,944 3,839 9,742 5,48 Canine/dog Feline/cat Bovine/cattle Ovine/sheep Porcine/pig Equine/horse European rabbit Caprine/goat Chicken 6.% 2.4% 9.3% 2.5% 2.8% 2.9%.5%.3%.3% 23 22 2 49 39 32

23 22 2 23 22 2 Started Finalised Re-examined Started Finalised Re-examined Started Finalised Re-examined 3 5 3 4 5 2 3 4 4 5 4 3 4 5 2 4 4 2 2 3

23 397 22 368 2 375 23 22 2 7 72 65 23 3 22 2 9 23 22 2

Number of quality defects There has been a progressive increase in the number of quality defects over the years. Causes for this increase are multifactorial and the Agency is studying the root causes in order to draw general lessons from these incidents which can be used to further improve the quality of medicines. Parallel distribution In May 23, a new procedure the annual upprocessed. Number of quality defects 23 78 23 2,532 2,563 22 48 22 2,388 3,264 2 54 2 2,5 2,55 53 Quality defects and recalls (23) Quality defects reported 78 Recalls (total) 9 Class recalls 5 Class 2 recalls Class 3 recalls 4 23 22 2 3,434 3,42 3,4 2,995 3,4 2,92 4 Inspections and compliance Requested Issued A new procedure was developed to handle urgent

4.4 The European medicines regulatory network Annual report 23 54 The European medicines regulatory network a partnership between the European Medicines Agency, the European Commission and 5 medicines regulatory authorities in the European Union (EU) and the European Economic Area (EEA) is the basis of the Agency's success. The network gives the Agency access to a pool of over 4,5 experts, allowing it to regulation of medicines in the EU. Experts participate in the work of the Agency as members of its seven advisory groups and a number of other ad hoc advisory groups, as well as members of the assessment teams carrying out the evaluation of medicines. Payment to national competent authorities for evaluation activities The overall payment to national competent authorities (NCAs) remained stable in 23 compared to 22. There was a decrease in marketing-authorisation-related payments to national competent authorities in 23 compared with 22 due to the decrease in the number of initial applications received. Rapporteurships/co-rapporteurships Some of the EMA s committees appoint a member to as the rapporteur for the procedure. The rapporteur works to an agreed timetable and prepares an assessment report for the committee. For certain procedures, the committee also appoints a corapporteur to consider the matter in parallel to, and independently from, the rapporteur. The rapporteur and co-rapporteur are supported by an assessment team to provide the necessary expertise and resources. Rapporteurs and assessment teams are selected based on criteria aimed at ensuring the high use of resources. Opposite is an overview of the rapporteurships/co-rapporteurships of the CHMP and the CVMP, the two committees that are responsible for providing recommendations on marketing authorisation for medicines. Payment to NCAs for evaluation activities (EUR ) 23 4,496 3,789,775 2,85 7,85 3,957 22 3,723 3,554 6,43 6,38 2,853 29,32 2 3,799 4,38,944 4,64,82 24,594 Type-II variations Marketing authorisations Annual fee Inspections Other

CHMP rapporteurships/co-rapporteurships (23) Austria Belgium Bulgaria Croatia Cyprus Czech Republic 2 Denmark Estonia Finland France Germany Greece Hungary Iceland Ireland 2 2 2 3 3 3 3 3 4 5 5 6 6 Italy Latvia Lithuania Luxembourg Malta Netherlands Norway Poland Portugal Romania Slovakia Slovenia Spain Sweden United Kingdom * 2 3 3 3 * Corrected on 22 July 24. 5 5 7 7 9 3 3 4 6 Rapporteur Co-rapporteur 55 Austria Belgium Bulgaria Croatia Cyprus Czech Republic Denmark 2 Estonia Finland France Germany Greece Hungary Iceland Ireland 2 2 3 CVMP rapporteurships/co-rapporteurships (23) CVMP rapporteurship / co-rapporteurship 23 Italy Latvia Lithuania Luxembourg Malta Netherlands Norway Poland Portugal Romania Slovakia Slovenia Spain Sweden United Kingdom 2 2 4 The European medicines regulatory network Rapporteur Rapporteur Co-rapporteur Co-rapporteur

4.5 Administrative aspects Annual report 23 56 Access-to-document requests EU citizens have a right to access documents held European Medicines Agency grants this access according to the principles and further conditions as policy on access to documents. While complying with the initial halt imposed by the interim rulings of the General Court on the release of clinical study reports, in 23 the Agency received 293 requests for access to documents and released a total of 3,48 pages in response to requests. quester by request. Pharmaceutical industry Legal Media Academia/research institute Consultant Healthcare professional EU NCA General public EU institution (Commission etc) Regulator outside EU Patient s organisation Not-for-profit organisation Affiliation Number of requests received Other Total 2 7 7 3 3 2 7 293 37 34 67 3 Budget composition: revenue The outturn of the Agency in 23 was 24,387,, representing a 7.5% increase compared with 22. The EU general contribution represented 3.6% of the budget in 23, compared with 9.6% in 22. 6,59 23 22 2 2 29 2,466 7,49 9,875 4,72 5,477 32,63 28,42 24,533 7,988 4,532 5,632 4,9 36,32 Revenue EUR 42,283 6,7 62,47 General EU contribution (excluding orphan medicines contribution) Orphan medicines contribution Surplus from year N-2 Fees and other income 84,696 2,248 Budget composition: expenditure The considerable increase in the cost for infrastructure in 23 is due to investment costs for the relocation of the Agency in 24. These investment and 24. Expenditure EUR 23 62,56 77,552 3,8 22 3,87 75,25 2,79 2 3,63 72,539 97,92 2 52,883 67,695 82,234 29 57,742 5,28 78,67 Staff expenditure Infrastructure Operational expenditure

Temporary agents 94 Contract agents 6 Interim staff National experts Trainees Men 6 7 5 Women 389 76 3 9 43 Total 583 Grand total 238 547 785 Ratio men/women for temporary agents Ratio men/women for contract agents Total Category AD (administrators) 56 (49%) 5 (33%) 7 (47%) 6 (5%) 3 (67%) 92 (53%) 92 36 6 58 Category AST (assistants) Men Women Men Women 38 (4%) (2%) 39 (2%) 228 (86%) 45 (98%) 273 (88%) <3 3-4 4-45 45-5 5-55 55-6 >6 Austria.48% Belgium 3.56% Bulgaria.33% Czech Republic 3.26% Denmark Estonia Finland France Germany Greece Hungary Ireland Italy Latvia Lithuania Malta Netherlands Poland Portugal Romania Slovakia Slovenia Spain Sweden United Kingdom % 7% 4% % 8% 4% 46%.93%.33%.33% 4.52% 7.7% 5.33% 3.% 2.7%.67%.9%.48%.5%.74% 6.37% 4.74%.93% 3.%.3%.26% 2.52% 8.3%