1. DEPARTMENT OF HEALTH CENTER FOR BIOLOGICS AND HUMAN SERVICESEVALUATION and RESEARCH AND HUMAN SERVICES EVALUATION and RESEARCH Update on OCTGT Guidance Development Program Richard McFarland, PhD, MD Cellular, Tissue, and Gene Therapies Advisory Committee Meeting May 15, 2009

2. 2 FDA Good Guidance Practices (GGP) Ensures proper development, formatting, processing, routing, and use of FDA guidance documents  Mandated by “Food and Drug Administration Modernization Act of 1997" (FDAMA)  Administrative Practices and Procedures; Good Guidance Practices,” 21 CFR 10.115  CBER SOPP 8002  Annual Guidance Agenda published in Federal Register

3. 3 Guidance Documents Documents prepared for FDA staff, applicants/sponsors, and the public that:  Describe the agency’s interpretation of or policy on a regulatory issue;  Relate to the processing, content, and evaluation/approval of submissions;  Relate to the design, production, manufacturing, testing, labeling, and promotion of regulated products;

4. 4 Other Documents Guidance documents do NOT include documents related to:  Internal FDA procedures;  Agency reports;  General information provided to consumers or health professionals;  Speeches;  Journal articles and editorials;  Media interviews and press materials;  Warning letters;  Memoranda of understanding;  Other communications or actions taken by individuals at FDA or directed to individual persons or firms;  Documents directed at public health emergencies

5. 5 Guidance Documents Guidance documents are intended to represent our current thinking on matters discussed in the documents.  CBER staff may depart from guidance documents only with appropriate justification and supervisory concurrence (21 CFR 10.115(d)(3)).  Any consistent deviation from a guidance document indicates that we should revise it

6. 6 Level 1 Guidance Documents  Federal Register announcing the availability of the draft guidance for public comment  Placed on CBER web site  FDA offers a comment period (usually 60 to 90 days)  After reviewing the public comments, CBER will revise the guidance  Federal Register, announcing the availability of the final guidance.  The public may submit comments on the final guidance at any time.  CBER may issue a level 1 guidance for immediate implementation

7. 7 Level 2 Guidance Documents  All guidance documents not considered to be Level 1  Level 2 documents set forth existing practices or minor changes in interpretation or policy

8. 8 Communication with the Public During Guidance Development  When considering the development of guidance  CBER may freely discuss issues with the public.  If the issues to be addressed are particularly complex or controversial  Holding a public meeting  Holding advisory committee meeting on the issues  Before drafting the guidance  Once preparation of a draft guidance document has been initiated  Specifics of the guidance are not discussed with the public.  When the guidance has been issued in draft  Issues related to the draft guidance may be discussed  Issues related to specific intentions regarding the finalization of the guidance are not discussed  21 CFR 10.80  FDA may solicit information from the public at any time during the guidance development process.

9. 9 Published Final Guidances (April 2008-May 2009)   Content And Review Of Chemistry, Manufacturing, And Control (CMC) Information For Human Somatic Cell Therapy Investigational New Drug Applications (INDs)  Final 4/2008  CTGTAC Discussions- Topics included in discussion at numerous meetings   Content And Review Of Chemistry, Manufacturing, And Control (CMC) Information For Human Gene Therapy Investigational New Drug Applications (INDs )  Final 4/2008  CTGTAC Discussions- Topics included in discussion at numerous meetings

10. 10 Published HCT/P Guidances (April 2008-May 2009) (cont’d)  Current Good Tissue Practices (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) –  Draft- 1/16/2009  Comment Period- Recently Closed  CTGTAC Discussions-  Implementation of Tissue Rule  Certain Human Cells, Tissues, and Cellular and Tissue- Based Products (HCT/Ps) Recovered from Donors Who Were Tested for Communicable Diseases Using Pooled Specimens or Diagnostic Tests  Immediate Implementation- 4/16/2008

11. 11 Published Donor Eligibility Guidances (Office of Blood Lead) (April 2008-May 2009) (cont’d)   Use of Serological Tests to Reduce the Risk of Transmission of Trypanosoma cruzi Infection in Whole Blood and Blood Components for Transfusion and Human Cells, Tissues, and Cellular and Tissue- Based Products  Draft- 3/26/2009  BPAC Discussion- 4/26/2007   Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Whole Blood and Blood Components Intended for Transfusion and Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)  Draft- 4/25/2008  FDA Public Workshop Discussion- 11/4/2002  Proposed RCDAD for HCT/P in DE guidance  Draft 5/2004  Final 8/2007

12. 12 Published Draft Guidances (April 2008-May 2009)   Somatic Cell Therapy for Cardiac Disease  Written by Cross-Center Cardiovascular Team (CBER-CDRH)  Draft- 4/2/2009  Comment Period- Closes 7/1/2009  CTGTAC Discussions- 3/18/2004   Potency Tests for Cellular and Gene Therapy Products  Draft- 10/9/2008  Comment Period- Closed 1/7/2009  CTGTAC Discussions- 2/9/2006

13. 13 CVM Guidance on Genetically Engineered Animals  #187 - Regulation of Genetically Engineered Animals Containing Heritable rDNA Constructs  Draft- 1/15/2009  http://www.fda.gov/cvm/GEAnimals.htm

14. 14 CVM Guidance on Genetically Engineered Animals  Covers all GE animals with heritable rDNA constructs (including biopharm animals, knockouts)  Definition of “article”  rDNA construct intended to affect the structure or function of the animal  Case-by-case evaluation  Risk-based approach  Enforcement discretion and approval paths  NADA means mandatory approval prior to marketing  One existing approval

15. 15 Resources on the Web  Consolidation of OCTGT guidances  Cellular and Gene Therapies   http://www.fda.gov/cber/genetherapy/gtpubs.htm http://www.fda.gov/cber/genetherapy/gtpubs.htm  Tissues   http://www.fda.gov/cber/tissue/docs.htm http://www.fda.gov/cber/tissue/docs.htm  References for the Regulatory Process for the Office of Cellular, Tissue and Gene Therapies (OCTGT)  www.fda.gov/cber/genadmin/octgtprocess.htm www.fda.gov/cber/genadmin/octgtprocess.htm

16. 16 Summary  FDA guidance process to communicate with stakeholders  Good Guidance Practices (GGP)  Governed by regulations 21 CFR 10.115  OCTGT and CVM Recent Guidances  Current Annual Guidance Agenda  Additional Guidances to meet needs arising between Annual Guidance Agendas

17. 17 Conclusions  OCTGT has an active guidance development program that includes  Strategic Guidance Planning (Annual Agenda)  Responds to changing needs  OCTGT Guidance Program leverages  Input from CTGTAC meetings  Other public meetings (NIH RAC, Workshops, Scientific Meetings, Industry Liaison Meetings)  Cross-center efforts within FDA  Participation with Standards Development Organizations