1. Quality Regulation for Biological Products: Current and Future Sue Nie Park, Ph.D. Director, Division of Viral Products Center for Biologicals Evaluation Korea Food & Drug Administration

3. I. Current Regulation of Biological Products

11. Quality Regulation System Network Manufacturer NCL NRA RA * QA QC Production Final lot New drug approvals Changes to drugs Compliance with regulations Consequences of violations Do as a “gatekeeper” Inspection: regularly once every 2 years RA *: Regulatory Affair

12. The Process of Biological Products Licensure in Korea Pre-clinical & clinical reports Specifications & Test methods KFDA Simultaneously or separately application Licensure Market Submit a post-marketing surveillance report to KFDA by 5 years after approval Pre-approval Post-approval According to “Provision for Inspection of Request on Specifications and Test Methods of Drugs (No. 2001-9, Feb 16 2001 revised)

13. The Process of Biological Products Licensure in the US

14. Approval Process in Europe: Overview Determine Product Status Select a Rapporteur country (if France, AFSSAPS)) Apply to other EU members** Non Therapeutic Effect Submit to AAFSSAPS Therapeutic Effect Centralized Procedure Mutual Recognition Procedure * Based on rapporteur country’s authorization In France: additional submission to Transparency Commission Apply to EMEA

15. Overall relationship between NRA and Drug Manufacturer Unapproved Products IND initial CMC Amendments Annual Reports Lot Release Process Changes BLA (CMC) Inspections Inspections Regulatory Authority REVIEW REVIEW Compliance Action Approved Products Changes to Procedures Annual Reports Adverse Reactions License Updates Regulatory Affairs Legal Quality Control Marketing Customers Licensors Manufacturing Clinical Supplier Product Development Licenses Management Quality Assurance

16. Biological Products Regulated By KFDA

26. II. Current Approach To Regulation of Biological Products

27. Regulation of Biological Products Based on Sound Science, Law, and Public Health Impact Policy Compliance Surveillance Research Review

33. III. Registration Process of Biologicals

34. Licence for Pharmaceutical manufacturer Receipt Order & Review for Facility inspection Completion for Facility inspection & Review Proposal & Approval Issue of certificate for Pharmaceutical manufacture Report Facility inspection Order Fill-up of application form Release Transaction adminstration KFDA Via department (Regional KFDA) Applicant

35. Applicant Registration Process of NDA Safety & Efficacy application Specification and test methods application Safety Evaluation Office NITR Central Pharmaceutical Affair Council Evaluation Council In KFDA (If necessary) Review Result Notification Review Result Notification Applicant NDA Biologics Department NDA Action

36. IND Application Process PreIND Meeting Application IND Plan PreIND Meeting Notification of Application Eligiblity IND (or its amendment) Application 1 2 Was there a PreIND? Review Initiation at PreIND Meeting level Protocol No IND (or its amendment) Approval Yes Trial Ongoing Reporting of CT completion NDA Application Final PL Approval If necessary, forwarding to KCPAC IND Requisite Dossier

37. IV. Law and Ordinances Related to Biologicals Approval

38. System of and ordinances Pharmaceutical Affairs Law (PAL) Pharmaceutical Enforcement Ordinance(PEO) Pharmaceutical Enforcement Regulation(PER) Notice, Guidance’…etc

39. Laws and Regulations concerned with Biologicals Approval Article 85~88 Article 64 KFDA Notice 1999-39 Article 11.40 Article 19,31 Article 26-3 KFDA Notice 1999-11 Article 30,31 Article 26-2 Re-examination of New drug Re-evaluation of drug PMS Adverse reaction monitoring GMP Inspection Article 62~70 Article 45 Lot release KFDA Notice 2000-49, 1997-67, 1999-6, 2001-9, 2001-35 Article 23, 24, 27, 27-2 ,28,29,83 Article 26 Product Licence KFDA Notice 2000-49 Article 22 Article 26 Licence for Pharmaceutical manufacture Notice…etc PER PEO PAL

40. System to Regulate Biologicals

41. Licensing Process

46. V. Control of Viral Products August 2003 Division of Viral Products Center for Biologics Evaluation Korea Food and Drug Administration

49. Organization & Responsibilities QM Crosscheck QM Approval Hep B (plasma) HIV/HepB agn/aby test Hep A JE HFRS Influenza OPV IPV Interferon Clonorchis sinensis agn Paragonimus westermani agn MMR VZV

55. Test Items for Lot Release : Inactivated Vaccines or Antigens, 2003

56. Test Items for Lot Release : Live Attenuated Vaccines, 2003

59. Potency Standards / Reference Reagents for Viral Vaccines Manufacturer’s in house reference IPV Asan Institute for life science (WHO collaborating center for viral reference) HFRS 2001 (Established) Korea National Biological Standard JE (inactivated) NIBSC Influenza HA & Split " Hepatitis A vaccine Manufacturer’s in house reference Hepatitis B vaccine (plasma) Comment Sources Manufacturer’s in house reference Korea National Biological Standard " " OPV 2002 (Established) Varicella vaccine Mumps vaccine Measles vaccine Vaccines

61. Summary on Annual Activities (’96-’01) *1 Including 25 withdrawals *2 Including 2 withdrawals and 1 rejection

66. VI. Challenges