Five years as EMA Liaison at US FDA TOPRA Annual Human Medicines Symposium 2 4 October 2017 - Victoria Park Plaza Hotel, London Presented by Dr Sabine Haubenreisser on 2 October 2017 European Medicines Agency, International Affairs An agency of the European Union
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EU-EMA/FDA cooperation Long history of informal cooperation with FDA (EC and individual member states) before there was an EMA. Informal cooperation between EMA and FDA after creation of EMA. Cooperation formalised: Confidentiality Commitment 2003, updated 2010 and extended indefinitely Implementation Plan 2004, updated 2007 2
EMA/FDA confidentiality arrangement Legal basis: protection of non-public information provided in confidence Allows for sharing of non-public, pre-decisional information and draft legislation and guidance Foresees exchanges of staff (secondments, training), experts attendance and participation in scientific meetings Envisages information exchange in agreed areas, and types of exchange, eg, inspections, clusters Allows flexibility in dealing with ad hoc matters and broadening of fields of interest Provides for monitoring through yearly EU/FDA bilateral meeting A framework for regulatory cooperation, including exchange of information on advance drafts of legislation and regulatory guidance documents, as well as nonpublic information related to ensuring the quality, safety and efficacy of medicinal products for human and veterinary use, including orphan medicinal products, authorised or under review both in the USA and the EU 3
Practical experience of the confidentiality arrangements some thoughts Operate on basis of shared interests / mutual agreement on specified matters Legal constraints on information exchange (e.g. trade secret ) Arrangements are open to future development and broadening, without change to the implementation plan Key to working: cooperation, achieved through timely exchange of information and understanding, developing trust, building alliances 4
Role of the EMA liaison Facilitation of regulatory and scientific dialogue between EMA and FDA Identification of new and extended areas of cooperation Liaison with other relevant bodies and organisations Support awareness and understanding within FDA and amongst stakeholders of the regulatory cooperation To support and develop the regulatory cooperation between the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) 5
Some key responsibilities of the EMA Liaison Act as source of knowledge for FDA on EU and EMA regulatory matters Facilitate information exchange, attend cluster meetings, handle requests, overcome differences of understanding or position Propose, initiate and frame programme of fellowships (3-8 per year) of EMA staff at FDA, obtain buy-in from FDA hosts Ensure early heads up on regulatory decisions, including background information and draft public communications Prepare for and follow-up EMA-EU/ FDA bilateral meetings Identify and propose new areas for regulatory cooperation and ways to develop and extend existing areas Increase awareness of interaction with EMA, through presentations within FDA and participation at conferences, universities and educational programmes 6
Overview of current platforms for exchange: Clusters Increased to 14 clusters Advanced-therapy medicinal products (2008) Biosimilars (2011) Blood products (2010) Non-clinical oncology (2011) Oncology-haematology medicinal products (2004) Orphan medicinal products (2008) Paediatric medicinal products (2007) Patient engagement (2016) Pharmacogenomics (2005) Pharmacometrics / Modelling and simulation (2016) Pharmacovigilance (2013) Rare diseases (2016) Vaccines (2005) Veterinary medicinal products (2005) 7
Overview of current platforms for exchange: other platforms Formal platforms / interactions: International API Inspection Programme Teleconference (2012) EMA-FDA GCP initiative (2009) Bioequivalence (2014) Scientific Advice/Parallel Scientific Advice Interactions for medicines of human and veterinary use (2005) Shortages due to GMP non-compliance and quality defects (2013) Veterinary quarterly bilateral Informal bilateral teleconferences: Anti-infectives Cardiovascular Neurology/Psychiatry Pulmonary/Allergy/Rheumatology Veterinary novel therapies (2016) Veterinary pharmacovigilance (2016) 8
Advances in cooperation (1) Orphan medicines Single application form and annual report Paediatric medicines Increasing number of common commentaries Parallel EMA-FDA scientific advice Widened opportunities for parallel scientific advice and opened possibility of consultative advice Parallel submissions for qualification of Biomarkers or Clinical Outcome Measures Joint template agreed and published In all cases goals are the same: Support global development plans Scientific and public health convergence Reduce administrative burden 9
Advances in cooperation (2) Prime / Breakthrough Therapy Quarterly meetings comparing (Oncology pilot, engaging experts as early as possible for dual designated applications) New clusters: Patient engagement Rare diseases Pharmacometrics Increased cooperation in Biosimilars FDA gives advance notice on planned communications including Drug Safety Communications Awareness of ongoing evaluations, opportunity for discussion, exchange of views Advance notice of important regulatory action Understanding in case of different outcomes 10 10
International exchange on shortages Reinstated quarterly teleconference on shortages due to manufacturing quality issues Follows from EU initiative on minimising and preventing shortages relating to manufacturing and quality issues Raising awareness of existing shortages in different regions Update on programs within regions to prevent shortages Discuss reasons for shortages and ways to address them Rapid alert on identified shortages 11
GMP inspection initiatives API inspection programme Fosters greater international cooperation and information sharing to help to better distribute inspection capacity, allowing more sites to be monitored and reducing unnecessary duplication Involves WHO, EDQM, several EU Member States, FDA, TGA, Health Canada and PMDA EU/US Mutual Recognition Agreement Signed March 1st, 2017 Better use of inspection resources, avoiding duplication, increased inspection coverage Signature of Super CC (confidentiality arrangement allowing FDA to share full inspection reports, including trade secret information with EU regulators) August 3 rd, 2017 12
GCP inspection initiatives GCP inspection initiative improved communications between agencies and strengthened trust in each other s efforts Covers new chemical entities and biologics and FDA-EMA inspections Conduct information exchanges on GCP-related information Conduct collaborative GCP inspections and share information on GCP inspections and interpretation of GCP Facilitates both agencies inspection coverage and decision-making GCP bioequivalence inspection initiative involves inspections within national programmes (UK, IT, DE, FR, NL, ES) Exchange of planned and conducted bioequivalence inspections Possibility of joint (system related) or observed inspections Aims to streamline inspection resources for bioequivalence studies 13
Fellowships Aim: advance scientific and regulatory understanding, usually a 2-week exchange 22 EMA fellowships at FDA in the last 4 years 5 more this year 2 currently in progress (MRA, Combination products) 14 This year: GMP inspections Extrapolation Regulatory procedures Combination products ISO standardisation Past years: GMP inspections (x2) Risk communication Raw data analysis (x2) Pharmacovigilance Qualification of clinical outcome measures ISO standardisation Patient engagement Veterinary medicines (x3) Legal aspects PhV inspections Accelerated access to medicines Rheumatology and gastroenterology Quality of medicines Transparency Communications Real world data and big data Orphan medicines Paediatric medicines
Progress supported by fellowships Creation of Patient Engagement cluster MRA on GMP inspections (3 related fellowships) Signing of Super CC confidentiality commitment allowing FDA to share trade secret information Increased heads up from FDA on advance notice of communications, alignment of messages / timing and lines to take Exchange on PRIME/ Breakthrough Therapy designation Oncology pilot Discussions on novel veterinary therapies and veterinary pharmacovigilance 15
Conclusion strong support for continuity Regulatory cooperation essential to meet challenges of globalisation on bilateral as well multilateral level EMA/FDA cooperation addresses relevant aspects of EU Medicines Agencies Network Strategy 2020 Assuring product supply chain and data integrity Convergence of global standards and contribution to international fora Ensuring best use of resources through promoting mutual reliance and work-sharing Supporting training and capacity building and promoting the EU regulatory model Sharing of expertise to meet challenges of globalisation 20 years experience of interactions and regular exchanges has led to better understanding and more readiness to engage on both sides Has established global pool of expertise and increased readiness to strive towards convergence 16
Conclusion looking ahead Need to join forces in: Addressing quality issues currently bottleneck for accelerated approvals Supporting innovation facilitating early access to medicines, development of ATMPs, making use of real world data Implementation of the MRA 17
Conclusion experience of last 5 years Liaison presence within hosting agency is invaluable feeding information in both directions, providing background, facilitating interactions, anticipating and acting on differences, finding common ground, overcoming hurdles Takes time to get to know colleagues, build trust, develop culture of cooperation, mutual reliance and strive systematically for convergence 18
Thank you for your attention Sabine Haubenreisser, MSc, PhD European Medicines Agency, International Affairs +44 (0) 20 3660 8653 sabine.haubenreisser@ema.europa.eu European Medicines Agency 30 Churchill Place Canary Wharf London E14 5EU United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact Follow us on @ EMA_News