# Presentation: 012302

## Division of Cellular and Gene Therapies (DCGT)Overview of Activities

- Raj K. Puri, M.D., Ph.D.
- Division Director,
- Division of Cellular and Gene Therapies
- FDA, Center for Biologics Evaluation and Research

## Outline

- Mission and organizational structure
- Regulatory scope
- Approach to research
- Tumor Vaccines Biotechnology Branch (TVBB) Site Visit September, 2006

## OCTGT Structure

## DCGT Structure 

**Raj Puri, Ph.D., M.D., Division Director**
**Kimberly Benton, Ph.D.,**** Deputy Director**

**Cellular and Tissue **
**Therapy Branch**
**Steven Bauer, Ph.D.,  Chief***

**Tumor Vaccines and **
**Biotechnology Branch**
**Raj Puri, Ph.D., M.D., Chief***

**Cell Therapies Branch**
**Keith Wonnacott, Ph.D., Chief**

**Gene Therapies Branch**
**Daniel Takefman, Ph.D., Chief**

**Gene Transfer and **
**Immunogenicity Branch**
**Eda Bloom, Ph.D., Chief**

- DCGT Structure

- *Acting

## Products Evaluated  by DCGT

- Cellular therapies
- Gene therapies
- Tumor vaccines and immunotherapy
- Tissue engineered products
- Xenotransplantation products
- Combination products
- Devices used with cells/tissue

## DCGT regulatory portfolio and activities

-  Over 1100 active INDs, IDEs, and master files, several
-     thousand amendments per year, consult reviews
-  One licensed product, a growing number of products in 	phase 3
-  Devices: 510ks, PMAs, HDEs
- Pre-INDs, pre-pre-IND advice
-  Advisory committee meetings
-  Inspections
-  Enforcement actions

## Additional DCGT regulatory portfolio and activities

** **Partnerships: National Toxicology Program, NIH, CDC, NCI/IOTF program, NIH stem cell task force, NIST, MATES
-  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 papers on regulatory topics

## Roles and work of researcher-reviewers 

-  Product application review, policy and guidance development, regulatory outreach, regulatory mentoring, advisory committee preparation, enforcement, international activities
-  Research, training/mentoring
-  Administrative: branch chief duties, CBER peer review and coordinating committees, research management
-  Grant writing
- Participation in the scientific community: scientific talks, chairing of conference sessions, editing, peer reviewing manuscripts and grant applications

## Approach to research: Stay ahead of the curveas products and technologies evolve

-   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.

- Approach to research: Stay ahead of the curveas products and technologies evolve

## Research Strategy in DCGT

- DCGT products are diverse and rapidly evolving. They require new regulatory paradigms which are developing rather than established
- Critical Path: fill gaps, deal with scientific challenges, figure out what is important
- Sponsors study individual products, results often proprietary
- CBER scientists perform studies relevant to entire product classes, make results public, and thus accessible to all sponsors, to advance the entire field

## DCGT Research Priorities:Led by Critical Path Challenges

- Virology
- Retroviruses, adeno, herpes, filo
- Immunology
- Anti-viral immunity, immunobiology of cell therapy and xenotransplantation
- Cell biology
- Control of differentiation in animal models,
- stem cell biology
- Cancer biology
- Molecular biomarkers, animal models
- Biotechnology
- 	 Genomics, flow cytometry, proteomics

## PIs Reviewed in TVBB

**Raj K. Puri, M.D., Ph.D.**** **
*Cancer Biology and Genomics Program*
**   ****Michail Alterman, Ph.D.  **
*Proteomics Program*

## Public Health Issue and Regulatory Challenges

- Cancer, a most difficult public health problem*
- Biology of cancer – appropriate targets
- Appropriate tests and biomarkers for purity, identity and potency
- Animal models – safety and efficacy
- Biomarkers for disease monitoring and response

**	*********1,372,910 New Cases of Cancer in 2005**
**	****570,280 Cancer Deaths in 2005**
- 	**Source:  Cancer Facts and Figures, 2005 (American Cancer Society)**

## Critical Path Scientific Research Addressing Regulatory Challenges

**Specific Aims: **
- Characterization of tumor associated cell surface proteins (antigens or receptors) to establish identity of tumor vaccines and target for cancer therapy
- Establish animal models of human cancer to assess safety and efficacy of tumor targeted agents and gene therapy products
- Characterization of tumor vaccines and stem cells by genomics technology to identify biomarkers of purity, identity and potency and cancer stem cells

## Characterization of tumor associated cell surface receptors and antigens 

**Discovery of Th-2 derived cytokine receptors**
- Interleukin-4 receptors
- Renal cell carcinoma, head and neck cancer, malignant glioma, AIDS-Kaposi’s tumors, colon cancer, breast carcinoma, NSCLC, prostate cancer, pancreatic cancer, ovarian cancer, mesothelioma, and hematological malignancies (CLL-B)
- Interleukin-13 receptors
- Renal cell carcinoma, malignant glioma, ovarian carcinoma, AIDS-associated Kaposi’s sarcoma, pediatric glioma, and head and neck tumors

## Animal models of human cancer to assess safety, toxicity and effectiveness of cancer targeted agents

- Ovarian Cancer
- Pancreatic cancer
- Glioblastoma multiforme
- SCCHN
- Mesothelioma
- Lung cancer
- AIDS-associated Kaposi’s tumors
- Breast cancer
- Hodgkin’s lymphoma

- Serous adeno             Clear cell CA

## Analytical proteomics for the characterization of biologic products and discovery of biomarkers

- Michail Alterman, Ph.D.

## Specific Aims 

- Development of mass spectrometry-based analytical tools for testing of biological product quality and identity;
- Identification of proteomics-based cellular molecular signatures to be tested as predictors of therapeutic success;
- Characterization of cell substrates used to produce gene therapy products and preventive and therapeutic vaccines.
- Proteomic characterization (profiling) of different cell lines with emphasis on stem cell lines.
- Proteomic profiling of cytochrome P450 isozymes expression in tumors as potential biomarkers of cancer.

## Expected Outcome and Deliverables

- Proteomic profiling of MDCK and MRC-5 cells and other cell substrates
- Identification of a unique protein signature (biomarkers) of hESC and CD34+ cells and analysis of quantitative and qualitative changes during the differentiation of hESC to CD34+ cells.
- The discovery of new CYP isozymes in tumors may lead to new biomarkers and development of new anti-cancer drugs and therapies.

## Regulatory outcome

- Identification of new antigens for cancer vaccines characterization and target for cancer therapy
- Developing animal models for a variety of human cancer to test safety and efficacy of targeted agents
- Promote development of novel technologies (e.g., genomics, proteomics) for product characterization (e.g., biomarker for identity, purity, and potency) and safety
- Unique opportunity to identify molecular markers with *in vivo* outcomes