FDA/EC BILATERAL MEETING

SUMMARY

Representatives of FDA and the European Commission's Directorate General III held a Bilateral meeting on November 5, 9 and 10, 1998, in Bethesda, Maryland. Ms. Sharon Smith Holston, Deputy Commissioner for External Affairs, FDA, and Mr. J` rn Keck, Deputy Director General of DG III led the respective delegations. Representatives of DG XXIV and the Commission's U.S. delegation also attended.

Topics discussed in the opening plenary session were transmissible spongiform encephalopathies (TSEs), mutual recognition agreement implementation, chemical safety, antimicrobial resistance, and implementation of Directive 95/46 on personal data protection.

FDA described recent actions related to TSEs, and mentioned concerns with regard to BSE/new-variant CJD and iatrogenic transmission. DGIII described scientific opinions adopted in the past year, which identify measures and risks. New legislation is being developed to address prevention and control of all animal TSEs related to food and feed. Clarifications were requested and made. DGIII mentioned that it is expected that the SRM ban will not come into effect on January 1, 1999. Commission Decision 97/534/EC is likely to be either repealed or at least postponed. Within the Commission, work has begun on a new regulation which will exclude pharmaceuticals (including biologics), cosmetics and medical devices from its scope. However, given the legislative procedures and the fact that the regulation will have to be considered by the European Parliament and the Council of Ministers, this is not likely to be adopted in less than 24 months.

The US-EU Mutual Recognition Agreement (MRA) will enter into force on December 1. FDA discussed publication of its final regulation providing for implementation of the MRA, the plan for a framework for mutual recognition of GMPs required by FDAMA, and Congressional interest. Activities in the medical device area have started, with required documents having been published, and meetings held, including a very successful videoconference. Videoconferencing will also be considered for use in implementation of the pharmaceutical GMP annex. DGIII expressed concern about the possibility that not all member states would be assessed for equivalence by the end of the confidence-building period. FDA stated that it would do its best, within resource constraints, to accomplish as much as possible during the transition period. At the recent TABD meeting, it was reported that industry offered to support the process to the extent possible and had requested involvement in the process for determining equivalence.

FDA discussed chemical safety as it relates to inclusion of pharmaceutical products in the globally harmonized system during research, development and manufacturing. The issue is that OECD is working on guidelines that apply to pharmaceuticals and not considering data in the human use risk/benefit format that FDA and other regulatory agencies use. DGIII will look into the matter; they have corresponded with DGXI on the issue in the past.

On antimicrobial resistance, FDA described the national surveillance program to monitor changes in antimicrobial susceptibility, regulatory policy changes, work on "prudent use," research activities, coordination with CDC and NIH, and educational and labeling initiatives. The surveillance program links both animal and human health aspects, and is currently monitoring Campylobacter, Salmonella, and E. coli. Four different EC Directorates general are involved in work on antimicrobial resistance; the Scientific Steering Committee formed a working group last spring to look at human and animal prophylactic and therapeutic, feed enhancer, and phytosanitary uses of antimicrobials. Their first report is expected next spring. Both CPMP and CVMP are also working on related issues. Both sides agree that US/EU cooperation has been effective and should continue.

FDA described concerns relative to implementation of Directive 95/46 on personal data protection, and its potential impacts on clinical trial data, adverse event reports (AERs), epidemiological surveys and registries. The EC noted that there was evident public interest in ensuring that the Directive did not impede work in fields such as epidemiology, clinical trials on pharmaceutical products, and pharmacovigilance. To this end, there was considerable scope within the terms of the Directive for Member States to derogate such specific activities, notably where these activities used de-personalized data; met the substantial public interest provisions relating to exchange of data within the European Union; and/or met the provisions relating to data transferred to a third country. DGIII representatives stated that consideration is being given to the development of a document to clarify the handling in a pharmaceutical context of this Directive. The sides agreed to further followup to assure that the concerns are clarified and mechanisms identified for handling them.

Four working group sessions were held: foodstuffs, agrifood/biotech, human pharmaceuticals including biologics, and cosmetics. Following are general summaries of these sessions:

Foodstuffs

The foodstuffs group agreed to continue collaboration where possible and beneficial to both sides. Topics discussed were patulin, lead in juices, research plans of the Joint Institute for Food Safety and Applied Nutrition, and dietary supplement good manufacturing practices. It was noted that the EC Scientific Committee is currently considering upper safety levels for vitamins and minerals, a subject also reviewed by official US scientific bodies.

Agrifood/biotech

This was the first time that agrifood/biotech was discussed under the FDA-EU bilateral discussions. The working group felt that the discussion was timely and that it provided a unique opportunity to discuss mutually important issues regarding agrifood/biotech. The working group had a fruitful update on the procedures used by each side for agrifood/biotech products and on the products that have been examined or are under examination on both sides. Moreover, an update took place on the existing scientific guidance for biotech food safety assessment. The group also had an exchange on the structures available for using scientific advice. The working group found similarities in the underlying principles for safety assessment and thought that regulatory cooperation in this area would be useful. Possibilities for further informal exchanges will be explored, such as exchanges through video conference and joint activities in the form of Workshop(s) or concurrent reviews of case studies.

Pharmaceuticals including human biologics

The pharmaceuticals/biologics session was characterized as "remarkably good." The group further addressed TSE, and the need to establish links with the DG XXIV scientific committees and to involve CPMP/EMEA in future meetings. FDA will explore extending the existing US/Canada postmarket drug risk assessment videoconference to include EC/EMEA. Xenotransplantation and vaccines were identified as further opportunities for collaboration. Contact points were set up for internet promotion issues, and further exchanges will occur in conjunction with the DIA meeting to be held in Baltimore in June, 1999. Information will continue to be shared on direct to consumer advertising and off-label promotion. There has been good communication on the trademark issue, with both sides having issued guidelines; contact points were identified. The issue of exclusivity needs more discussion. The possibility of allocating one day during the next ICH meeting to allow the regulatory agencies (FDA, EMEA and other EU agencies and their Japanese counterpart) to discuss regulatory practice and science was discussed and welcomed in principle.

Cosmetics

Cosmetics was a fairly new substantive agenda item. The discussion of animal testing revealed that additional information needed to be exchanged, in particular with regard to validation and regulatory acceptance of different test methods. DG III outlined the provisions of the proposed 7^th Amendment (and committed to send the final version of the proposed 7^th Amendment to the FDA for information) and described the lead role that the EU will take in the validation of alternative methods. The mutual acceptance of in vitro/in vivo data was tabled. The EU explained that all in vivo data generated in the US would be accepted for the demonstration of safety for products marketed within the community. With regard to US acceptance of in vitro data from EU-validated alternatives, DG III committed to submit all files on validation programs for review by FDA/ICCVAM (Interagency Centre for the Evaluation of Alternative Toxicological Methods.) The dossiers will be reviewed and the methods assessed for their acceptability for the safety assessment of cosmetics by the FDA. The issue of harmonization of cosmetic ingredient lists is complicated by differences in regulatory categories (cosmetics, over-the-counter drugs, color additives) and other FDA Centers and Offices will have to be brought into the discussions. FDA has had considerable correspondence with industry concerning harmonization of cosmetic ingredient nomenclature, and will share that with the EC. Further discussion of acceptance of foreign market data and approvals is needed. Approval packages for color additives and UV filters will be exchanged, after legal issues relating to confidentiality of data are resolved, so that both sides can get a better idea of the processes used and investigate the feasibility of functional equivalence for such reviews. Formal cooperation on cosmetic regulation with Japan (similar to ICH) will be explored.

Both sides agreed to maintain the Bilateral meeting as the basis for their discussions of regulatory issues and as a collaboration mechanism. The format and length of the meeting were appropriate; this large meeting should be held once a year although various sectors may need to meet more frequently by teleconference, videoconference, or in conjunction with other meetings, such as ICH, in which both sides already participate. Exchanges of information on approaches to carrying out our responsibilities and experiences were identified as important activities. While FDA and DGIII remain the principals, representatives of other agencies, or parts of the Commission, such as DG XXIV, DG VI, EMEA/CPMP, USDA, or U.S. EPA, will be invited to participate depending on the subject matter to be discussed.

Mr. Keck extended an invitation to FDA to come to Europe for next year's meeting.

FDA DELEGATION

Sharon Smith Holston, Head of Delegation
Deputy Commissioner for External Affairs

Walter M. Batts
Director, Office of International Affairs

C. Michelle Limoli, Pharm.D.
Assistant to the Director

Marilyn E. Veek
Associate Director for Communications

Patrick Wilson
Acting Associate Director for Europe

Linda R. Horton
Director, International Policy

Eric Flamm, Ph.D.
Senior Policy Adviser, International Policy Staff

Gary J. Dykstra
Deputy Associate Commissioner for Regulatory Affairs

Kathryn C. Zoon, Ph.D.
Director

Elaine C. Esber, M.D.
Associate Director for Medical and International Affairs

David M. Asher
Chief, Laboratory Methods Development

Joan W. Blair
Office of the Associate Director for Medical and International Affairs

Janice F. Oliver
Deputy Director for Systems and Support

Terry C. Troxell, Ph.D.
Director, Division of Programs and Enforcement, Office of Plant and Dairy Foods and Beverages

Samuel W. Page, Ph.D.
FDA Scientific Director, Joint Institute for Food Safety and Applied Nutrition

James H. Maryanski, Ph.D.
Biotechnology Coordinator

Nega Beru, Ph.D.
Consumer Safety Officer, Office of Premarket Approval

Charles W. Cooper
Director, International Activities Staff

Carolyn Miles
Nutritionist, Office of Special Nutritionals

John Bailey, Ph.D.
Director, Office of Cosmetics and Colors

Roger L. Williams, M.D.
Deputy Director for Pharmaceutical Science

Justina A. Molzon, S. Pharm., J.D.
Special Assistant to the Deputy Center Director for Pharmaceutical Science and Acting International Affairs Officer

Minnie V. Baylor Henry
Director, Division of Drug Marketing, Advertising and Communications

Yuan-Yuan Chiu, Ph.D.
Deputy Director, Office of New Drug Chemistry

Ralph B. Lillie, R.Ph., M.P.H.
Deputy Director, Office of Postmarket Drug Risk Assessment

Gary K. Chikami, M.D.
Division of Anti-infective Drug Products

Daniel L. Boring, R.Ph., Ph.D.
Division of New Drug Chemistry III, Office of Pharmaceutical Science

Donald B. Hare
Special Assistant, Office of Generic Drugs

Melissa Moncavage
Public Health Advisor, Division of Drug Marketing, Advertising and Communications

Sharon R. Thompson, DVM
Associate Director for Veterinary Medical and International Affairs

Robert C. Livingston, Ph.D.
Codex and JECFA Liaison

John Honstead, DVM
Division of Animal Feeds

John O'Rangers, Ph.D.
Office of New Animal Drug Evaluation

William Price, Ph.D.
Special Assistant, Office of Surveillance & Compliance

Michael H. Thomas
Director, Division of Residue Chemistry, Office of Research

Joanne Kla
Office of the Director

Margaret Hare

EC DELEGATION

Patrick Deboyser
Head of Unit, DG III/E/3, Pharmaceuticals and cosmetics

Lee Bansil
DG III/E/3, Pharmaceuticals and cosmetics

Emer Cooke
DG III/E/3, Pharmaceuticals and cosmetics

Gwenole Cozigou
Head of Unit, DG III/E/2, Food production and biotechnology

Joanna Kioussi
DG III/E/2, Food production and biotechnology

Basil Mathioudakis
DG III/E/1, Foodstuffs

Tanagiotis Daskaleros
DG XXIV

Catherine Bunyan
EC Delegation, Washington D.C.

Anna Snow
EC Delegation, Washington D.C.

(Hypertext updated by jch 1999-MAR-08)