FDLI: BIOLOGICS UPDATE

1. FDLI: BIOLOGICS UPDATE Kathryn C. Zoon, PhD Director Center for Biologics Evaluation and Research July 14, 1998 Washington, DC

4. Forces Shaping Pharmaceutical Medicine in 1998 New Discovery Research and Technology Demand for New Medicines and Faster Access Mergers, Reorganizations, Process Changes Global Market: International Harmonization and Competition Changing Health Care Environment New Laws

5. Regulation of Biological Products

6. FY98Major Initiatives & Action Plans Performance FDAMA PDUFA II CBER Strategic Plan 2004 Xenotransplantation Action Plan Tissue Action Plan Blood Action Plan Team Biologics ICH

8. CBER User Fee Review PerformanceLicense Applications and Supplements% of First Actions Within Goal*By Completed Fiscal Year 1993-1996

13. CBER Product License ApplicationsAverage Time To Approval#FY 1989 - FY 1997 User Fee and Non-User Fee##

14. FDA Modernization Actof 1997(FDAMA) Signed into law November 21, 1997 Amends the Food, Drug & Cosmetic Act Amends the Public Health Service Act Renews the Prescription Drug User Fee Program with amendments (PDUFA 2) Effective 90 days after enactment unless otherwise specified

15. FDA MODERNIZATION ACTDRUG PROVISIONS Fast Track Products Manufacturing Changes Biologics Modernization Postmarketing Studies Reporting Clinical Investigations

16. FDA MODERNIZATION ACTDRUG PROVISIONS Streamlining Clinical Research Data Requirements Content and Review of Applications Scientific Advisory Panels Radiopharmaceuticals

17. FDA MODERNIZATION ACTGENERAL PROVISIONS Dissemination of Information - Proposed Rule 6/8/98 Expanded Access to Investigational Therapies Supplemental Applications - Guidance 5/15/98 Dispute Resolution Informal Agency Statements Interstate Commerce Intramural Research Training Authority

18. CBER LEAD IN FDAMA REGULATION/GUIDANCE INITIATIVES RADIOPHARMACEUTICALS - New requirements for review of Radiopharmaceuticals (122) PR - May 20, 1998, (Posted May 22, 1998) FR - May 20, 1999 POSTMARKETING STUDIES - revise 314 and 601 to require annual progress reports (130) BIOLOGICS MODERNIZATION - regulations for BLAs (123) FAST TRACK - policies and procedures on fast track products (112) Nov. 21, 1998 (under review)

19. CBER LEAD IN OTHER FDAMA ACTIVITIES Postmarketing Studies-Publish Status Annually (130) Fast Track: disseminate to physicians and others a description of the provisions applicable to fast track products (112) Modernization of regulation: MAPP/SOP to minimize differences between CDER and CBER review and approval (123) PDUFA II Implementation: CBER/CDER co-lead

20. IMPLEMENTATION OF PDUFA II Review Performance Discipline Reviews/Informational Request Letters Two Level Resubmissions Class 1 and 2 (Posted 5/14/98) Meeting Management Clinical Hold Responses (Posted 5/14/98) Major Dispute Resolution Special Protocol Agreements Electronic Submissions

21. FDA Modernization Act of 1997 (FDAMA) Section 406 (b): consult with �appropriate scientific and academic experts, health care professionals, representatives of patient and consumer advocacy groups and the regulated industry.� open to constructive input and proposals no preconceived conclusion process will continue in years ahead

22. FDA Modernization Act of 1997 (FDAMA) Section 406 (b): consult with �appropriate scientific and academic experts, Health care professionals, representatives of patient and consumer advocacy groups� Docket Number 98N-0339

24. FDA GAP ANALYSIS Injury Reporting Product Quality Assurance Enforcement Food Safety Outreach Scientific Research Application Reviews Tobacco DOCKET 98N-0339

28. CBER Strategic Plan: 2004Vision Statement CBER advances the public health and merits the public trust through high quality science-based regulation to ensure that safe and effective products reach the public as rapidly as possible. CBER demonstrates international leadership in regulation through development of innovative regulatory strategies and standards, a managed regulatory process, coordinated research, and the use of partnerships.

29. CBER Vision: 2004 To that end: We will have implemented a managed and integrated regulatory process from discovery to postmarketing. Our research will serve as a critical public health resource which is linked to scientific evaluation of traditional and novel products.

30. CBER Strategic Goals2004 A high quality regulatory process which is managed and integrated from discovery through post marketing A high quality research program which contributes directly to the regulatory mission A high quality diverse work force Interactive information systems that are integral to all CBER activities Leveraged resources

31. Project Plan Develop a business model of CBER�s regulatory process - DONE Identify weaknesses/bottlenecks in the current regulatory process - DONE Propose and evaluate solutions to overcome these weaknesses/bottlenecks - DONE Design a new, streamlined Managed Review Process (MRP) - DONE Identify performance goals in order to expand the MRP - DONE Implementation

32. 6/1/98

34. Impact of Research

35. Significant Accomplishments in Information Technology Desktop Standardization Electronic Submissions - BLAs, INDs Document Management Technology Regulatory Management System Electronic Lot Release (note: 26% reduction in Review Days)

36. Xenotransplantation Action Plan Develop a comprehensive Public Health Policy: Tools Emerging Infectious Diseases Notification and Look-back FDA Response to Emergencies Ensuring Compliance International Collaboration Workshops and Public Education

37. Tissue Action Plan Issuing Guidance Documents Promulgating Tissue Regulations Inspections and Compliance Coordinating Scientific and Regulatory Policy

38. Blood Action Plan Updating Blood Regulations Reinvention of Blood Regulation Emerging Infectious Diseases Insuring Compliance of Plasma Fractionation Establishments Notification and Lookback FDA Response to Emergencies and Class I recalls Affecting Blood Safety

39. TEAM BIOLOGICS A plan for Reinventing FDA�s Ability to Optimize Compliance of Regulated Biologics Industries Joint effort of CBER and the Office of Regulatory Affairs Capitalize on diverse skills and knowledge Focus on inspectional and compliance issues

40. TEAM BIOLOGICS (con�t) Transfer of lead responsibility for biennial inspections Reduce inconsistency Cadre of specialized biologics inspectors Inspections will include Lead investigator CBER staff Specialized training

41. Implementation Schedule October 1, 1997: Plasma Fractionation Products April 1, 1998: Licensed In Vitro Diagnostic Products October 1, 1998: Allergenic & Biotech Products October 1, 1999: Vaccines

42. International HarmonizationPriorities International Conference on Harmonization World Health Organization National Institute of Biological Standardization and Control Mutual Recognition Agreements

43. CBER�s Biotech Leadership Q5A - Quality of Biotechnological Products: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin - Final March, 1997 Q5B - Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products - Final November, 1995 Q5C - Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products - Final November, 1995

44. CBER�s Biotech Leadership Q5D - Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/ Biological Products - Final July, 1997 Q6B - Specifications: Test Procedures and Acceptance Criteria for Biotechnological/ Biological Products - Draft February 1998 S6 - Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals - Final July, 1997

45. ICH FUTURE DIRECTIONS

46. HOW TO GET INFORMATION FROM CBER Visit CBER�s home page: �www.fda.gov/cber/� Send e-mail to: �CBER_INFO@A1.CBER.FDA.GOV� For a list of documents: �DOC_LIST@A1.CBER.FDA.GOV� FAX Information System: 1-888-CBER-FAX (301-827-3844 outside of U.S.) Telephone: 1-800-835-4709 (301-827-1800 outside of U.S.)