1. Implementation of the CTD: CBER’S Perspective May 8, 2001 Joan Wilmarth Blair, M.A. International Affairs Advisor CBER/FDA May 8, 2001 Joan Wilmarth Blair, M.A. International Affairs Advisor CBER/FDA CBER

2. International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use

3. International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use

4. BIOLOGICAL PRODUCTS REGULATED BY CBER Whole Blood Somatic Cell & Gene Therapy Blood Components Allergenic Extracts Plasma Derivatives Vaccines Monoclonal Antibodies Biotech Derived Therapeutics TissuesXenotransplantation Blood Related Devices PeptidesPeptides

5. Q6B: Specifications,Test Procedures & Acceptance Criteria for Biotechnological/ Biological Products Q6B: Specifications,Test Procedures & Acceptance Criteria for Biotechnological/ Biological Products Scope: “…apply to proteins & polypeptides, their derivatives, & products of which they are components (e.g., conjugates)” “…does not cover antibiotics, synthetic peptides & polypeptides, heparins, vitamins, cell metabolites, DNA products, allergenic extracts, conventional vaccines, cells, whole blood, and cellular blood components” Scope: “…apply to proteins & polypeptides, their derivatives, & products of which they are components (e.g., conjugates)” “…does not cover antibiotics, synthetic peptides & polypeptides, heparins, vitamins, cell metabolites, DNA products, allergenic extracts, conventional vaccines, cells, whole blood, and cellular blood components”

6. BIOLOGICAL PRODUCTS REGULATED BY CBER Whole Blood Somatic Cell & Gene Therapy Blood Components Allergenic Extracts Plasma Derivatives Vaccines Monoclonal Antibodies Biotech Derived Therapeutics TissuesXenotransplantation Blood Related Devices ICH PeptidesPeptides

7. Whole Blood Somatic Cell & Gene Therapy Blood Components Allergenic Extracts Plasma Derivatives Vaccines Monoclonal Antibodies Biotech Derived Therapeutics TissuesXenotransplantation Blood Related Devices ICH CTD? PeptidesPeptides CTD application format only applicable to BLAs for this subset of products? CTD application format only applicable to BLAs for this subset of products?

8. BLA - Section 601.2 Application for Biologics Licenses l Describes content of application l Describes procedures for filing

9. NDA - Section 314.50 Content and Format of Application l Describes form and content, e.g., – Application form – Numbers of copies (archival copy) – Index – Summaries – Case report tabulations – Case report forms – Labeling – etc.

10. The question is NOT “Will CBER be accepting the CTD instead of the BLA?” The question being asked is “Will the CTD application format be applicable to all BLAs?”

11. Application Format - Regulatory Requirements? NDA - Section 314.50 l Describes content of application l Describes procedures for filing l Describes format BLA - Section 601.2 l Describes content of application l Describes procedures for filing l DOES NOT describe format

12. BLA req’ments and Form 356h format BLA req’ments and Form 356h format ELA/PLA Req’ments ELA/PLA Req’ments Migration from ELA/PLA to BLA Construct Issue guidance for content & format for product categories Issue guidance for content & format for product categories

13. BLA/Form 356h  Issuance of Guidances l 8/96: Therapeutic rDNA-derived products and monoclonal antibody products for in vivo use l 1/97: Autologous somatic cell therapy products l 1/99: Vaccines & related products l 2/99: Plasma derivatives, animal plasma, serum-derived products l 3/99: Biological in-vitro diagnostics l 4/99: Allergenic extracts or allergen patch tests l 5/99: Human blood & blood components

14. CTD BLA BLA Content Req’ments “CMC” guidance BLA Content Req’ments “CMC” guidance Formatting of BLA to CTD Construct Revise guidance for new format Revise guidance for new format

15. CBER’s Acceptance of CTD l Question of acceptance of CTD format prior to issuance of guidance l Use of CTD format not precluded in advance of guidance l URGE early communication -- assure all required content included in submission

16. CBER’s CTD Implementation Process l Revise “CMC” guidances to map CTD to BLA l “Specified Products” currently in process l Staff training l Workshops likely

17. Integration of CTD with Applications for Product Approval