EU Update on Regulatory Developments

Transcription

1 EU Update on Regulatory Developments Pascal Venneugues European Medicines Agency CASSS CMC Strategy Forum Europe Copenhagen, 4-6 May 2015 An agency of the European Union

2 Overview International cooperation and globalisation challenges Lifecycle management (ICH Q12) Adaptive pathways and impact on CMC Update on BWP Process Validation Guideline Future directions 1

3 Why cooperate with international partners? Changing environment due to global nature of pharma R&D Movement of clinical trials outside of EU and US Increasing complexity of supply chains and manufacture of APIs outside of the EU increasing risks of falsification and concerns over data integrity Increasing needs for international collaboration, information sharing and work sharing reduce/avoid duplication, global strategic vision 2

4 Where do our active substances come from? Non-EU India & China ROW EU 1/3 of APIs come from EU 2/3 of APIs imported from non-eu countries India and China account for 70-80% of non-eu API supply Primary supplier in ROW is USA Source: EGA (2015) About 70% of inspections requested by EMA and about a third of national inspections take place in the USA but less than half of all EMA/national inspections are carried out in India & China. Mutual Reliance Initiative: Joint EMA-FDA initiative to accept each other s GMP inspections of manufacturing sites Better use of inspection resources 3

5 EU Directive on falsified medicines Medicine with a false representation of: - Identity (name, composition, strength, packaging, labelling) - Source (manufacturer, country of manufacturing, country of origin, MAH) - History (distribution records) Does not include - unintentional quality defects - Infringements of intellectual property rights Four pillars: 1. Safety features 2. Good Distribution Practices 4. Internet sales 3. Active substances 4

6 EU Directive on falsified medicines Ongoing work to implement the Directive Equivalence to EU GMP standards and practices of 3 rd countries exporting active substances to the EU: Written confirmations issued by competent authorities of 3 rd countries (e.g. India, China) Requirement waived for countries included in a list established by the Commission (USA, Japan, Switzerland, Australia) Assessment is ongoing for several countries (e.g. Israel, South Korea, Brazil) Exceptionally, requirement waived to ensure availability of a product, if the manufacturing site was inspected by a EU Member State. Legislation builds on cooperation activities with third countries 5

7 International cooperation (examples) ICMRA (International Coalition of Medicines Regulatory Authorities) Forum of Heads of Medicines Agencies aimed at providing strategic oversight on issues faced globally 19 countries plus EU (DG SANTE and EMA), across regions, and WHO as observer Working groups: governance, mapping, communication, information sharing, GMP inspections, generic medicinal products, capacity and competence building IPRF (International Pharmaceutical Regulators Forum) Discussions on high priority regulatory issues & challenges, regulatory operations to improve efficiency and effectiveness 10 countries plus EU (DG SANTE and EMA), across regions, and WHO as observer Working groups on gene and cell therapy, biosimilars, ICH E6 (GCP) TTIP (Transatlantic Trade and Investment Partnership) EMA supports Commission in several areas, e.g. GMP, biosimilars Tenth round of negotiations in July

8 EMA-FDA interactions interactions every month through confidentiality arrangements Many activities structured around thematic clusters: Orphan medicines, paediatric medicines, vaccines, oncology, blood products, biosimilars, ATMPs, pharmacovigilance, pharmacogenomics, veterinary medicines Interactions in other areas such as Quality by Design, shortages, antimicrobial resistance (TATFAR) EMA/FDA Parallel scientific advice Many of these interactions also involve Japan, Canada, Australia 7

9 Lifecycle management ICH Q12 Scope: framework to facilitate management of post-approval CMC changes in a more predictable and efficient manner Allow regulators to better understand and have more confidence and trust in the applicant s management of CMC changes Importance of transparency Key topics: Regulatory dossier: communication of information in the CTD (format, location), regulatory commitments PQS: change management, knowledge management Post-Approval Change Management Protocols (PACMPs) EWG face-to-face meeting on 6-11 June 2015 (Fukuoka, Japan) Proposal for BWP/QWP Workshop with Industry (27-28 October 2015) 8

10 ICH Q12 Information in the dossier, regulatory commitments Nowadays marketing authorisation applications include more development information and elements of enhanced approach How to effectively communicate important / relevant aspects of the development program in a submission? Summary of the story in the Quality Overall Summary with links to Module 3 The level of detail is not one size fits all ; it should consider the purpose / use of the studies Terminology matters: avoid terminology contradicting ICH principles Example of issue for biological products: non-cpps - Information in the dossier: which ones, ranges? - Reporting of post-authorisation changes 9

11 ICH Q12 Knowledge management Information in ICH Q10 is high level How to manage knowledge within a company? How to find a format to connect knowledge gain vs change being considered? How to communicate knowledge with regulators Is knowledge inspectable? Clear link with Annual Product Review: what has happened and what has been learnt 10

12 ICH Q12 Post-Approval Change Management Protocols The use of PACMPs relies on the scientific knowledge and understanding that a company has gained about a product and process Prediction of the impact of complex change(s) on product quality Benefits of using PACMPs: Faster and more predictable implementation of post-approval changes continuity of supply Input from regulators on the strategy before submitting the actual results Repetitive implementation of a specific change under a single PACMP More flexible and risk-based approach for managing changes post-approval Different regulatory frameworks between ICH regions 11

13 Adaptive pathways and impact on CMC Requires a well thought out plan in the marketing authorisation application to generate data post-approval. For example: Process validation: concurrent validation protocol New manufacturing site, scale up: opportunity to use PACMPs Specifications: review based on pre-defined criteria, reassessment of control strategy, submission of post-approval variations Shelf life: use of stability models, extrapolation,? Post-approval variation to extend shelf life Use of prior/platform knowledge to guide development An important CMC issue is limited data vs risk management Importance of Scientific Advice (including also EMA-HTA parallel advice) 12

14 Update on BWP Process Validation guideline Public consultation ended on 31/10/2014. Review of comments is ongoing Scope: - What to file in the dossier, not how to validate - Control strategy will not be addressed Distinction between process evaluation and verification is an important concept for biologicals and will be maintained Need to clarify where process development ends and where process evaluation starts 13

15 Update on BWP Process Validation guideline Differences in terminology with FDA guidance are acknowledged Terminology is aligned with existing EU guidance But no differences in concepts with FDA guidance Limited experience on continuous process verification for biologics No detailed guidance will be provided In the context of adaptive pathways, high level guidance on concurrent validation will be introduced Regulatory binding nature of information included in the dossier (e.g. S.2.2 and S.2.4 vs S.2.5 and S.2.6): Issue beyond the PV guideline. To be addressed in ICH Q12 14

16 Future directions Changing face of our international collaboration with regulators From information sharing to work sharing From bilateral to multilateral cooperation Key question is now how best to collaborate Need for continued dialogue and learning by both industry and regulators Support to global development Benefit to the patient Strong regulatory science is critical to innovation Supporting new approaches to improve product manufacturing and quality Ensuring regulators readiness to evaluate innovative emerging technologies EU Medicines Agencies network strategy to 2020: 15

17 Thank you Pascal Venneugues Quality of Medicines Human Medicines Evaluation Division 30 Churchill Place, Canary Wharf, London E14 5EU 16