1. An agency of the European Union The SME Office at the European Medicines Agency Constantinos Ziogas SME Office, Stakeholder & Communication Division, European Medicines Agency Open Info Day Horizon 2020 'Health, demographic change and wellbeing‘ Brussels 22 November 2013

2. How can regulators proactively support drug development? 1

3. Development challenges - seeing through the eye of the customer Issues: Solutions: Perceived barriers to engaging with regulators – small companies, start-ups, academic groups (main developers of ‘advanced therapies’) Easy access through ‘SME Office’ Early support from ‘Innovation Task Force’ 2

4. A proactive regulatory approach: “Be part of it and shape it together.” 3

5. Incentives/Assistance to drug development ITF Orphan Scientific Advice Advanced Therapies Paediatric SME 4

6. Orphan Designation Time Knowledge Medical Plausibility Pos Benefit-Risk Compliance with Ped Invest Plan Marketing Authorisation (To) (Clinical) Development Scientific Advice Benefit-Risk Mgt Plan Paediatric Invest. Plan Industry - Regulator interactions ITF 5

7. Support to small & medium sized enterprises (SMEs) 6

8. Tailoring assistance for SMEs To promote innovation & development of new medicinal products by SMEs 7

9. SME Office A single interface/’one-stop shop’ SME assignment, public SME register Fee incentives, regulatory assistance, translations Facilitate communication News bulletins, SME User Guide Workshops 8

10. Assignment of SME Status For applicants established in EEA SME criteria defined in Recommendation 2003/361/EC: Headcount < 250 and annual turnover not more than € 50 mil or balance sheet not more than € 43 mil Submit information to show compliance with criteria 9

11. Incentives for SMEs * Medicines based on genes / cells / tissues Regulatory, administrative and procedural assistance Fee reductions and deferrals Certification of Quality/Non-clinical data for advanced therapy medicinal products* Translation of product information 10

12. Fee Incentives for SMEs 90% reduction on : scientific advice GMP, GLP, GCP, PhVig inspections scientific services 100% ‘waiver’ on administrative services For MAA, SME fee deferral orphan medicine: 100% waiver to 1st year post-licensing paediatric use marketing autorisation: 50% fee reduction Conditional Fee Exemption Subject to EMA scientific advice – payment only for positive outcome 11

13. Experience with SMEs 2006-2012 1098 companies assigned SME status From 27 countries across EEA 41% micro, 38% small, 19% medium Majority human, 44 vet, 66 human/vet & 154 service providers Public register of companies launched in 2010 12

14. SME product pipeline – categories Therapeutics (84%), vaccines (7%), diagnostics/imaging (9%) Orphan medicines (20%) Nanotechnology (4%), pharmacogenomics/biomarkers (3%) Product development stages: 13

15. Regulatory Assistance for SMEs Direct assistance: Queries dealt with by SME office e-mail/telecon Briefing meetings/telecon on regulatory strategy Published SME User Guide on regulatory procedures SME News bulletin Annual training/workshops tailored for SMEs 14

16. Scientific advice 15

17. http://www.emea.europa.eu/index/indexh1.htm http://www.emea.europa.eu/index/indexh1.htm under Application Procedures Scientific advice and ‘protocol assistance’ EU advice on development & agreement of future strategy Working party of CHMP Note: Protocol assistance is scientific advice for orphan designated products, and does not only relate to clinical aspects. 16

18. Scope of scientific advice Scientific Advice can be provided on ANY scientific question - Quality, non-clinical and clinical At any time point of the development  Early advice with subsequent follow-up is recommended Not only product specific  Broad advice, Conditional approval/Exceptional circumstances - On the eligibility or on proposed development  Qualification of biomarkers and other novel methodologies Note: Clinical trial authorisation is handled at the national level 17

19. FAQs in Scientific Advice Quality/CMC comparability, stability, etc. Non-clinical in vivo pharmacology for innovative products animal models for products with human specific targets, animal models mimicking the human disease, surrogate molecules carcinogenicity and reprotoxicity waivers, etc. Clinical PK/PD, dose-finding, interactions exploratory & pivotal trials: study endpoints, population, comparator, blinding, statistics (interim A, adaptive/seamless design), safety DB 18

20. Key features of scientific advice Optional (upon company request) Strictly confidential Robust Short procedures 40 to 70 days ‘Pre-submission’ assistance Face-to-face meetings with scientific experts for 50% of advice Fee-related activity (significant fee waiver/reduction for orphan products/paediatrics/SMEs) Written responses adopted by the licensing Committee, sent to the company ie. the ‘scientific advice letter’ 19

21. Figures for scientific advice 20

22. Compliance with scientific advice is associated with positive MA outcome 21

23. Scientific advice and MA application outcome (2004-7; N=188) Who requests SA? Big pharma: 33% Who complies with SA? Company size is significantly associated with positive outcome of MA application: OR = 2.96 (95%CI: 1.92, 4.56) Obtaining and complying with SA appears to be a predictor of outcome [compliant with SA vs. no-SA: OR 14.71, 95% CI 1.95; 111.2; non-compliant with SA vs. no- SA: OR 0.17, 95% CI 0.06; 0.47, p<0.0001)]. Regnstrom et al; Eur J Clin Pharmacol. 2010 Jan;66(1):39-48 Big pharma: 84% Medium pharma: 60% Small pharma: 25% 22

24. Innovation Task Force (ITF) Multidisciplinary platform for preparatory dialogue and orientation on innovative medicines, technologies and methods 23

25. Purpose of Innovation Task Force (ITF): Provide a forum (soft landing zone) for innovation Complementary and preparatory to existing formal procedures Tools: Briefing meetings Scientific recommendations on classification Workshops (e.g. nano, stem-cell) 24

26. A platform for discussing a wide range of topics Preclinical and in vitro models Biomarker Qualification Adaptive designs “-omics” Methodologies and Statistics Epigenetics Synthetic Biology Nanopharmaceuticals Borderline products Advanced therapies 25

27. ITF briefing meetings Objective: facilitating the informal exchange of information and guidance in the development process, complementing and reinforcing existing formal procedures Scope: regulatory, technical and scientific issues arising from innovative medicines development, new technologies and borderline products Applicants: Consortia, Networks, Public/private partnerships, Learned societies, Pharmaceutical industry, Academia Free of charge Scientific discussions led by experts from the Agency network, working parties and committees For pharmacogenomics, with PG Working Party 26

28. ‘Mutually benefitting’ dialogue Starting the regulatory dialogue with the Agency early Facilitating knowledge exchange on innovative strategies: update on progress, address new science and questions to regulators, understand concerns and prepare for solutions Providing orientation on regulatory science topics in drug development Identify issue of particular interest to regulators in preparing for formal procedures (e.g. biomarkers qualifications, scientific advice, orphan medicines designation) 27

29. ITF briefing meetings 28

30. SMEs in ITF briefing meetings 29

31. Thank you for your attention 30