Murray M. Lumpkin, M.D., M.Sc. Deputy Commissioner International Programs

1. VIEWING THE WORLDTHROUGH THE FDA INTERNATIONAL LENSAdvancing Domestic Public Health through International Engagement Murray M. Lumpkin, M.D., M.Sc. Deputy Commissioner International Programs U.S. Food and Drug Administration

2. Globalization and the US FDAThemes You’ve Probably Heard • Globalization and the global supermarket have multiplied the scale of our responsibilities and the challenges we face. • Globalization has fundamentally changed the environment for regulating food and medical products used by Americans • Created unique regulatory challenges for FDA and our regulatory partners around the world

3. Main Lessons Learned • All – In the world of sourcing our food and drugs and clinical trials data, – it’s a GLOBAL SUPERMARKET – and people are shopping everywhere. • The United States imports approximately US$2 billion worth of FDA-regulated products, from roughly 200 countries, using 825,000 importers, through over 300 U.S. ports–of-entry.

4. The Global SupermarketThe Challenges • More foreign facilities and clinical trials sites supplying primary data for US marketing applications • Increasing volume of imported finished products and components • More outsourcing of manufacturing and clinical trials to local entities not historically engaged with FDA • Greater complexity in supply chains • Imports of products and data coming from countries with less well developed regulatory systems

5. The Global SupermarketThe Challenges • Some of these products come from countries with governments that do not wish us well • Some come from countries with little ability to provide the regulatory oversight needed to assure the safety of products or robustness of clinical data exported from their country.

6. The Global SupermarketThe Challenges • Lax oversight in many foreign locales presents opportunities for contamination, counterfeiting, or economic “gain” by cutting corners • Food, cosmetics, and medical products could all be used as unsuspected offensive weapons against a large part of the US population

7. FDA’s Present International Lens • Fundamentally missioned as a domestic public health protection and promotion mission • this hasn’t changed • how do we focus on a domestic mission while thinking global without appearing self-serving, self-centered, or arrogant • FDA is not missioned or funded as a development agency • but not everyone understands this • only around 450 people at FDA out of 12,000 focus full time on international issues (OIP, border staff, others) • how can we leverage our meager resources with development agencies and others to actually leave a footprint (technical expertise to the table -> translate it)

8. FDA’s Present International Lens • In order to accomplish our mission and be even more effective at home today we have to engage more effectively abroad • but what we need to do, we cannot do alone • what are the appropriate metrics by which we measure the domestic impact of our international work

9. FDA’s Present International Lens • International engagement is no longer discretionary; it is an integral, daily part of how we accomplish our domestic mission – part of global regulatory community • but parts of our Agency is still in the process of embracing this • explore ways to get that embrace / ownership / recognition of value added to their daily work • how do we get from “receiving” information from trusted regulators to “relying” on the information to make our own regulatory decisions – true leveraging / work sharing – next big hurdle

10. FDA Current Global Engagements • What already is in place • What we do at present • Why we do it

11. FDA’s Statutory Mission • SEC. 903. [ 21 U.S.C. 393] FOOD AND DRUG ADMINISTRATION. • (b) MISSION.—The Administration shall— • (1) promote the public health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely manner; • (2) with respect to such products, protect the public health by ensuring that— • (A) foods are safe, wholesome, sanitary, and properly labeled; • (B) human and veterinary drugs are safe and effective; • (C) there is reasonable assurance of the safety and effectiveness of devices intended for human use; • (D) cosmetics are safe and properly labeled; and • (E) public health and safety are protected from electronic product radiation;

12. FDA’s Statutory Mission • (3) participate through appropriate processes with representatives of other countries to reduce the burden of regulation, harmonize regulatory requirements, and achieve appropriate reciprocal arrangements;

13. FSMA – Section 305 The Secretary shall, not later than 2 years of the date of enactment of this Act, develop a comprehensive plan to expand the technical, scientific, and regulatory food safety capacity of foreign governments, and their respective food industries, from which foods are exported to the United States.

14. FSMA – Section 305 • The plan developed under subsection (a) shall include, as appropriate, the following: • (1) Recommendations for bilateral and multilateral arrangements and agreements, including provisions to provide for responsibility of exporting countries to ensure the safety of food. • (2) Provisions for secure electronic data sharing. • (3) Provisions for mutual recognition of inspection reports. • (4) Training of foreign governments and food producers • on United States requirements for safe food. • (5) Recommendations on whether and how to harmonize • requirements under the Codex Alimentarius. • (6) Provisions for the multilateral acceptance of laboratory • methods and testing and detection techniques.

15. FSMA – Section 308 The Secretary shall establish offices of the Food and Drug Administration in foreign countries selected by the Secretary, to provide assistance to the appropriate governmental entities of such countries with respect to measures to provide for the safety of articles of food and other products regulated by the Food and Drug Administration exported by such country to the United States, including by directly conducting risk-based inspections of such articles and supporting such inspections by such governmental entity.

16. International Work - Past Decade Covers the full scope of all FDA-related products: • Regulatory and Enforcement Cooperation • Harmonization of Regulatory Policy and Science-based Standards • Scientific Collaboration and Exchange • Technical Assistance and Training • Outreach and Education about FDA expectations • Technical Assistance to USG agencies involved in Trade Negotiations and Trade Agreements • Emergency Response and Preparedness

17. 2008 – 2009- 2010 Budgets • $30.9 M to stand up overseas offices and expand international program • Prior to 2008 - $4.6M • $35M - base for our international programs

18. Primary International Engagement PurposeBetter Information • Through several broad initiatives, many of which are specific to certain areas, obtain better and more robust information to help FDA officials in the centers and at the borders make better entry decisions about the products that are presented for entry into the US

19. Primary International Engagement PrincipalLeveraging of Resources • Bilateral and multilateral efforts to leverage the human, scientific, financial, and inspectional resources of and the knowledge and experience of other key regulatory authorities and others so as to avoid duplication of effort, to make our activities more efficient, and to allow us to focus our limited resources on higher-risk areas of concern.

20. International Engagement Styles • Bilaterally • Multilaterally • Multilateral International Organizations • Harmonization Initiatives • Product Specific Regulatory Alliances

21. Bilaterally • Topic Specific Workshops (ex. GCP – Vietnam, India, China, Russia, S Africa) • Meetings with delegations • Temporary Staff secondments • Confidentiality Arrangements • Daily exchanges embedded officials • Work plans / Specific Initiatives • FDA Foreign Offices

22. FDA’s Collaborations (Agreements) • Over 100 bilateral agreements • Confidentiality Commitments • 20 Countries • European Commission (DG - SANCO) • EMA and EFSA • EDQM • World Health Organization (drugs / biologics) • Most tools for information exchange; others developed affirmative collaborations.

23. Australia Austria Belgium Brazil Canada Denmark EDQM EFSA EMA EU – SANCO France Germany Ireland Israel Italy Japan Mexico Netherlands New Zealand Singapore Sweden Switzerland South Africa United Kingdom World Health Organization Confidentiality Commitments

24. Confidentiality Arrangements • Legal Framework • Commercial confidential • Pre-decisional • Investigative – compliance • NOT Trade Secret • NO requirement to exchange anything

25. Specific Initiatives • Depends on country and issues being addressed • level of capability, • history of interactions, • level of confidence • bilateralism • is the juice worth the squeeze? • API with TGA and EMA • GCP with EMA • Medical Devices with COFEPRIS

26. FDA Foreign Posts • Response to the Problems of 2007 • Special Congressional Appropriation in 2008 • Stood up from zero in 12 months • Now mandated in FSMA • Chosen strategically based on problems in the past and on ability to leverage expertise and to build on past experiences

27. FDA In-Country Presence Locations • China – Beijing, Shanghai, Guangzhou • India – New Delhi, Mumbai • Latin America – San Jose, Santiago, Mexico City – just gotten DOS permission for Brasilia • Europe – Brussels, EFSA / EMA (FDA embeds) • The Middle East - Amman, Jordan • South Africa – Pretoria

29. Breakdown of New Hires • 50 US Nationals – new FDA FTEs • 4 Regional/Country Directors, 2 Special Reps • 21 Senior Technical Experts in foods, medicines, or devices • 9 inspectors with expertise in either food/feed or medical products • 14 support personnel at Headquarters • 19 Locally employed staff

30. Present In-Country FocusBetter Information • Through several broad initiatives, many of which are specific to certain areas, obtain better and more robust information to help FDA officials in the centers and at the borders make better entry decisions about the products that are presented for entry into the US

31. Present In-Country FocusBetter Collaboration • Through several broad initiatives, many of which are specific to certain areas, initiate and strengthen areas in which we can better collaborate with our counterpart agencies • Have people in-country whose “full time, day job” it is to foster these relationships and to champion these collaborative efforts 

32. FDA In-Country Presence:Activities • (1) Working with counterpart agencies in-country / full time focus on the country’s issues / championing agreed initiatives • (2) “Environmental scanning” to gather better knowledge about issues that may affect the quality and availability of products to be exported to the US  Analytical papers • (3) Engage with mature counterpart agencies overseas to leverage/create synergies with scientific, inspectional, and other resources

33. FDA In-Country Presence:Activities • (4) When requested, engage with counterpart agencies in specific technical cooperation projects • (5) Engage private- and public-sector trusted third parties to provide helpful information about regulated industry compliance with FDA standards (third party auditors)

34. FDA In-Country Presence:Activities • (6) Engage with regulated industry to provide greater information about expectations and standards for their products to be admitted to the USA • (7) Engage with USG agencies already in-country with complementary missions

35. FDA In-Country Presence:Activities • (8) Have the capacity to perform more overseas inspections of high risk facilities

36. Multilateral Cooperation • PEPFAR • WHO Prequalification • IICA • CDER/CBER/CDRH Fora • Latin America Pharmacogenomics • East African Community Regulatory Harmonization • WHO/Gates/DFID/Quadrilateral (FDA/TGA/HC/EMA) • PIC/S (GMP Inspectorates)

37. Cooperative Agreements(Multilateral) • Global surveillance and monitoring system for combating falsified medicines and supply chain threats – WHO ($1M) • Regional info hub related to medical products to promote regional cooperation and data utilization/sharing – PAHO ($1M)

38. Cooperative Agreements(Multilateral)improve collaboration, surveillance, and information detection through new global and regional information platforms and networks of regulators/ scientists • Global Food-borne Infections Network and its surveillance advisory committee (WHO - $850K) • Global integrated food safety information platform to facilitate data sharing (WHO - $400K) • Regulatory capacity strengthening and adoption of intl standards (IOE - $565K)

39. Contracts(Better evidence for decision making) • Analysis of Global Supply chain risks and formulation of strategies to address weaknesses ($1.7M) • IOM Study ($1.1M) • Global assessment of training institutions, capacities, and approaches in regulatory affairs to identify gaps and niches FDA can uniquely fill and where we can leverage with other regulatory authorities ($1M) • Leveraging a pharmacovigilance contract with USAID in Africa (($150K)

40. What We’ve Learned • None of us has the financial, human, or scientific resources to do all that our parliaments and people ask and expect of us • Cannot meet our mission by only looking within one’s own borders

41. No national or regional regulatory authority has a monopoly on good science or good regulatory practices. • The sum of our parts (as regulatory authorities) is clearly superior to their individual value.

42. Regulatory cooperation is no longer discretionary. • Regulatory cooperation must become the standard operating procedure of 21st century medicinal and food products regulatory authorities

43. Further information: www.fda.gov/InternationalPrograms/default/htm