1. Overview: Division of Cellular and Gene Therapies, Office of Cellular, Tissue and Gene Therapies
Raj K. Puri, M.D., Ph.D.
Director, DCGT
Office of Cellular, Tissue and Gene Therapies
FDA, CBER
Gene Transfer and Immunogenicity Branch Site Visit Report to
CTGTAC November 29, 2012
Good morning!
Before I begin, I like to thank the subcommittee and CTGT AC for their time and efforts in the evaluation of research program in DCGT

2. Division of Cellular and Gene Therapies (DCGT)
Raj Puri, M.D., Ph.D., Division Director
Kimberly Benton, Ph.D., Deputy Director
Gene Therapies Branch
Daniel Takefman, Ph.D., Chief
Gene Transfer and
Immunogenicity Branch
Andrew Byrnes, Ph.D., Chief
Cell Therapies Branch
Keith Wonnacott, Ph.D., Chief
Tumor Vaccines and
Biotechnology Branch
Raj Puri, M.D., Ph.D. Chief
DCGT is organized in five branches. Cell and gene therapy branches are comprised of regulatory scientists who not only review reg files but also participate and develop policy and guidance documents, do outreach activities and collaborations. Staff in other three branches, in addition to reg review and policy development, perform FDA mission relevant research to support development of OCTGT products.
Cellular and Tissue
Therapy Branch
Steven Bauer, Ph.D., Chief

3. DCGT Regulatory Activities
Ensure the safety of cellular, gene therapy and other products through:
Development and implementation of a comprehensive risk-based regulatory framework and review
Evaluation of new technologies for product characterization and rapid assessment of product safety
Development of FDA Policies and Guidances for the regulation of cellular and gene therapy, regenerative medicine, combination and other products

4. DCGT Regulatory Activities continued..
Inspections:
of manufacturing facilities, regulatory site visits
Consultation and Education:
Provide scientific and technical advice to other CBER Offices, FDA Centers, and Government Agencies
Information sharing and discussion with sponsors
Counterterrorism:
COOP Coordination and Laboratory Red Alert Plan
Participation in FDA’s CT exercise/simulations
DCGT staff participate in inspections….
We provide consultation and technical advice to colleagues in other CBER offices….
Perform counter terrorism activities including COOP.

5. DCGT Regulatory Activities continued..
Community Outreach: (seminars, panel discussions, round table, workshops)
Cell Therapy including stem cell
Tumor Vaccines and Immunotherapy
Gene Therapy
Regenerative Medicine
Xenotransplantation
Round Table (CIRM, JDRF, ARM and others)
Interaction/collaboration with NIH CRM
Patient advocacy groups
We perform outreach activities to…..
These are extremely important activities allowing our staff to interact with our stakeholders (sponsors and investigators) and work together addressing challenges for optimal development of these products.

6. DCGT Regulatory Activities continued..
Partnerships:
Development of Retrovirus and Adenovirus reference material
ASTM representation and STR profiling for cell line authentication
Workshops in collaboration with NIH “Pluripotent Stem Cells in Translation: Early Decisions” (March 21-22, 2011 and 2012)
MOU with NIH NINDS and NHLBI for sharing of information and expertise
ERCC and Fluorescence standards for microarray and flow technologies
Inter Agency Oncology Task Force between NCI and FDA for joint fellowship training program
Partnerships: National Toxicology Program, CDC, NIST, MATES, TERMIS, ASTM
Partnership with academia, government agencies and industry to help produce RV and ad vector reference standards - being distributed by ATCC.
Collaborated with NIH and held workshop on stem cells in 2011 and Additional workshop is planned
MOU with NINDS and NHLBI provide opportunities for joint workshops and other educational activities for grantees to facilitate both grant review and IND review.
Participation in ERCC consortium to develop internal and spike-in controls standards for microarray technology and developing fluorescence standard materials for flow cytometry technologies both being used for characterization of our products.
DCGT staff co-chair FDA/NCI IOTF Subcommittee for joint training and fellowship program.
Partnership with NTP, CDC, National Institute of Standards and Technology, Multi-Agency Tissue Engineering Science working group, Tissue Engineering and Regenerative Medicine International Society, ASTM (formerly American Society for Testing and Materials, a standards organization)

7. DCGT Regulatory Activities continued..
Participation in ICH (international conference on harmonization) – Regulators Forum on Cell Therapy and Regulator Forum on Gene Therapy
WHO
Liaison activities with professional societies (ISCT, ASGCT, SITC etc)
Publication of invited and peer-reviewed manuscripts on regulatory topics
OCTGT Learn webinar series on product manufacturing and testing, clinical, and preclinical topics.

8. Regulatory Science Related Research
DCGT Research-Regulators perform mission relevant research to facilitate development of safe and effective cutting edge medical products

9. Current DCGT Research Areas
Virology
Retroviruses, Lentivirus, adenovirus
Immunology
Immune responses to viral and plasmid vectors,
autoimmunity and immune regulation
Cell and developmental biology
Control of differentiation in animal models:
cell fate and survival, stem cell biology
Cancer biology/Immunology
Cancer vaccines, immunotherapy, animal models Molecular biomarkers,
Biotechnology
Genomics, flow cytometry, proteomics, transgenics
Microbiology of tissue safety
Pyrosequencing and whole genome sequencing

10. Identification and correlation of MSC attributes with in vivo and in vitro assays of safety and efficacy: DCGT MSC consortium

11. Researcher Reviewer Model
Cellular, tissue engineering, and gene therapies evolve rapidly and continually present new regulatory challenges
These novel products raise extraordinarily complex issues
DCGT seeks to foster a cadre of Researcher Reviewer scientists who :
perform regulatory review and identify regulatory science related research needs to enhance and promote product development and patient safety
perform research in key areas to support the FDA mission and help sponsors solve product development problems to advance cellular, gene therapy and other products to the market place
We are not trying to reproduce industry or NIH expertise here. However, we need scientists in key areas that can engage in constructive and informed evaluations of files and productively interact with industry and academia including their cutting edge scientists.

12. Types of Researcher Reviewers
Principle investigators (PIs) – tenured or tenure track researcher reviewers
Staff Scientists – tenured researcher reviewers supporting PIs program: do both review and research
Technicians: do primarily research, lab management, some also do limited regulatory review work
Staff Fellows: do both review and research work
Postdoctoral fellows funded as ORISE: do primarily research
Note: Resources are provided to PIs
PIs tenured or tenure track scientists and located in 3 branch structure. Individual groups within these branches are headed by PIs, who are expected to build and lead FDA mission relevant research programs.
Resources flow to lab activities and support through PIs.

13. Responsibilities of PIs
Product review INDs, IDEs, PMA, 510k, HDEs, licenses, master files, inspections - regulatory mentoring by branch chiefs Policy development working groups, guidance development, advisory committees Outreach presubmittal advice, scientific and regulatory talks, refereeing and editing for journals, chairing sessions at scientific conferences, scientific collaborations relevant to the regulatory science Research lab management, training/mentoring/supervising, publishing papers, grant writing, leveraging/collaboration
PIs responsibilities include product review of ….. however, their regulatory workload is approximately half of the reg scientists.

14. Research Assessment/Management
Publications (including research articles, guidance documents, and regulatory articles)
Regulatory workload and quality
Success in securing internal and external funding
National and International recognition of scientific expertise
Site visit and CBER Advisory Committee recommendations
Promotion and Conversion Evaluation (PCE) Committee review
At the division level: Each year, OCTGT ADR collects information on PIs accomplishments
Division uses this information for resource distribution to PIs.
In addition, PIs write projects for special funding request. These proposals are generally reviewed internally before funding decisions are made from ADR’s office based on available funds.
PIs research programs are reviewed by external site visit committee every 4 years and approved by CTGT advisory committee.
Internally, PCE reviews for tenure, promotion and cyclical review – evaluates research and regulatory work

15. DCGT Research Regulatory PIs
GTIB:
Andrew Byrnes, Ph.D.
Suzanne Epstein, Ph.D.
Jacob Reiser, Ph.D.
Cheng-Hong Wei, Ph.D.
Carolyn Wilson, Ph.D.
CTTB
Steve Bauer, Ph.D.
Deborah Hursh
Brent McCright, Ph.D.
Malcolm Moos, M.D., Ph.D.
TVBB
Michail Alterman, Ph.D.
Shyh-Ching Lo, M.D., Ph.D.
Raj K. Puri, M.D., Ph.D.

16. Thank you
We appreciate your feedback and recommendations for research program in DCGT GTIB
Once again, thank you for your time and efforts. We look forward to your feedback and recommendations for research projects in GTIB.
I will take any questions that you may have.