Update on the Somatic Cell Therapy Letter

1. Update on the Somatic Cell Therapy Letter Cellular, Tissue, and Gene Therapies Advisory Committee Meeting April 11, 2008

2. Somatic Cell Therapy Letter (SCTL) • Letter issued as of June 2002 • Requested submission of information on • product manufacturing • quality control procedures • product testing • clinical trial oversight and monitoring practices

3. Goals of SCTL • Ensure ongoing trials meet current expectations for • Product release testing & characterization • Identify lapses in product testing • Product characterization & manufacturing processes • Clinical trial oversight & monitoring • Encourage Good Clinical Practice

4. Goals of SCTL (cont.) • Gather information on need for additional guidance other regulatory documents • Determine need for other forms of outreach to SCT field • Enhance the safety of cellular products • Facilitate product development

5. Somatic Cell Therapy Letter • Consisted of 8 multi-part Chemistry, Manufacturing, and Control (CMC) questions and 3 multi-part Clinical questions • Requested date for response was 60 days from anniversary date of the file • Lack of response was not considered a cause for placing the file on clinical hold

6. CMC Question Topics • QC/QA program- • description, procedures, personnel, audits • Qualification of starting cells, reagents, equipment • Tracking, segregation, labeling • Cleaning and sanitization • Control of contamination & cross contamination

7. CMC Question Topics (cont.) • Processing and testing timeline • Product testing methods • In-process, final product • Sterility validation, aseptic processing • Product characterization • Stability program • Cross referenced files

8. Clinical Question Topics • A complete description of the clinical monitoring program including: • A description of the personnel responsible for monitoring • A summary of the procedures for clinical study conduct monitoring and auditing • A request final study reports be submitted for all studies

9. Review Summary • Responses reviewed by IND review team • ensure ongoing clinical trials met current expectations • identify lapses in product safety testing • Identified safety issues in low number of INDs • Safety issues in a specific IND were addressed between review team and sponsor • Observed broad differences in status of product characterization • Identified need for additional CMC guidance documents and outreach to SCT field

10. CMC- Published Guidance

11. CMC- Published Draft Guidance

12. GMP Guidances with Sections on SCT products

13. Clinical Guidances • Good Clinical Practice is addressed in “ICH E6 Good Clinical Practice: Consolidated Guidance”

14. CMC Guidance in Development • Potency Measurements for Cell and Gene Therapy Products • Topic of CTGTAC meeting on February 9, 2006 • Guidance document is under development

15. Outreach • OCTGT gives regulatory presentations at numerous conferences each year • broad audiences across SCT field • Liaison Meetings • CMC talks commonly focus on product characterization and potency • CMC talks also address 21 CFR 1271, (Tissue Rules)

16. HCT/P Regulations and Guidance • 21 CFR 1271, “Tissue Rules” • In effect in May 2005 • Focus on the prevention of transmission of infectious disease • Parts A-D apply to SCT products

17. Resources on the Web • Consolidation of relevant information onto CBER website • References for the Regulatory Process for the Office of Cellular, Tissue and Gene Therapies (OCTGT) • www.fda.gov/cber/genadmin/octgtprocess.htm

18. Summary • CBER experience from SCTL responses contributed to: • multiple guidance documents • issued and in preparation • numerous ongoing outreach activities broadly applicable to the field of cell therapies

19. Conclusions • Guidances are now available to address our expectations for IND submissions and clinical trial conduct • It is not necessary to convey these expectations and request responses in a separate format • OCTGT will discontinue issuing the SCTL and no longer request that sponsors provide updates in the format of the SCTL questions • IND Sponsors may provide information updates in amendments and annual reports, as appropriate

20. Thank you • Somatic cell therapy IND sponsors • CTGTAC members