OCTGT Research

1. OCTGT Research Suzanne Epstein, Ph.D. Associate Director for Research, OCTGT 12-14-2010

2. OCTGT Mission Facilitate development of, approval of, and access to safe and effective CTGT products

3. Cellular therapies Tumor vaccines and immunotherapy Gene therapies Tissue and tissue-based products Xenotransplantation products Combination products Devices used for cells/tissues Cord blood Products Regulated by OCTGT

4. CBER Office of Cellular, Tissue, and Gene Therapies Office of the Director Celia M.Witten, Ph.D., M.D., Director Stephanie Simek, Ph.D. Deputy Director Suzanne Epstein, Ph.D. Associate Director of Research Richard McFarland, M.D., Ph.D., Associate Director of Policy Division of Cellular and Gene Therapies Raj Puri, M.D., Ph.D., Director Kimberly Benton, Ph.D., Deputy Director Division of Human Tissues Ellen Lazarus, M.D., Director Division of Clinical Evaluation and Pharmacology/Toxicology Vacant Wilson Bryan, M.D., Clinical Branch Chief Mercedes Serabian, MS., Pharm/Tox Branch Chief

5. OCTGT regulatory portfolio and activities • Over 1350 active INDs and IDEs, over 4500 IND amendments in 2009, plus consult reviews • Two licensed products, a growing number of IND products in advanced development • Devices: 510ks, PMAs, HDEs • Tissue regulations • Pre-INDs, pre-pre-IND advice • Policy and guidance, advisory committee meetings • Inspections, regulatory site visits • Enforcement actions, international activities

6. Guidance Examples • Potency testing for cell and gene therapies • Therapeutic cancer vaccines • Allogeneic pancreatic islet cell products • Cell therapy for cardiac disease • Cord Blood • Good Tissue Practices • International Harmonization on Genomic Biomarkers

7. Additional DCGT regulatory portfolio and activities • Partnerships: National Toxicology Program, NIH, CDC, NCI/IOTF program, NIH stem cell task force, NIST, MATES, TERMIS, ASTM • Participation in international conference on harmonization (ICH), WHO • Outreach talks at conferences, academic institutions, consumer and patient advocacy group meetings • Liaison activities with professional groups • Publication of manuscripts on regulatory topics

8. OCTGT research: Stay ahead of the curve as products and technologies evolve • For this wide spectrum, cannot have research related to each product. • If research addressed only the products and assays of today, we would already be obsolete. We must guide pre-IND work, prepare the way for anticipated products.

9. OCTGT research: Stay ahead of the curve as products and technologies evolve • For this wide spectrum, cannot have research related to each product. • If research addressed only the products and assays of today, we would already be obsolete. We must guide pre-IND work, prepare the way for anticipated products.

10. Research Strategy in OCTGT OCTGT products are diverse and rapidly evolving. They use new regulatory paradigms, developing rather than established • Fill scientific gaps, deal with barriers • Perform studies relevant to entire product classes (sponsors study individual products) • Make results public, and thus accessible to all sponsors, to advance the entire field • Perform horizon scanning to choose priorities Scientific areas emphasized will be covered in the Division Director summary

11. Roles of researcher-reviewer PIs • Regulatory: product/CMC review (IND, 510k, IDE, BLA), policy and guidance development, pre-application consultation, regulatory outreach, inspections, mentoring, advisory committee preparation, enforcement, international activities • Administrative: branch chief duties, emergency preparedness, CBER coordinating committees, research management • Research: including lab management, training/mentoring • Grant writing: increasing role of competitive resources • Peer review: manuscripts, grant applications, PCE • Participation in the scientific community: scientific talks, chairing conference sessions, editing

12. Investigator recruitment • Scientific gap identified with input from staff, field of expertise endorsed by Center Director's office • Open, public recruitment with search committee. PI recruitments in DCGT in recent years: Field: Investigator recruited from: • Organ development Jackson Lab. • Proteomics Univ. of Kansas • Retrovirology Louisiana State University • Tissue safety Armed Forces Institute of Pathology • Immunity and tolerance Scripps Research Institute • Ongoing: iPS cells ?

13. OCTGT Research Management • Announcement of regulatory/public health goals • PI annual reports address research goals and progress, describe periodic refocusing/adjustment • Analysis of productivity and alignment with OCTGT goals • Horizon scanning for gaps, to guide recruitment • Increasing role of targeted intramural funding allocated by peer review of proposals • Tracking of outside resources • Communication tools: work in progress seminars, annual report summaries. CBER expertise database being developed.

14. 2009 OCTGT Research Priorities(responsive to CBER priorities) • Chemistry, manufacturing, controls: Development and evaluation of methods and standards for improved product characterization and lot release testing, including definition of product markers predictive of safe, effective, and consistent product performance. • Pharmacology, toxicology, product rationale: Development and evaluation of preclinical/nonclinical in vitro and in vivo methods and studies informative about the safety and efficacy of OCTGT products. • Participation in CBER-, FDA-, and DHHS-wide initiatives including risk assessment, clinical trial design and monitoring, development of markers, counterterrorism, pandemic influenza preparedness, and HIV/AIDS programs, as well as OCTGT-specific initiatives in these areas. • Improvement of the microbial safety of human tissue products by development and evaluation of methods for better processing conditions, pathogen inactivation, and/or pathogen detection.

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