# Presentation: 079383

## Simple Complexity in an Evolving World: Rising to the Challenge

**Science Board Advisory Committee, 25 October 2002**
**Philip D. Noguchi, M.D.**
**Acting Director**
**Office of Cellular, Tissue, and Gene Therapies**
**CBER, FDA**

## Office of Cellular, Tissue and Gene Therapies	

**Efforts in counterterrorism**
**Repair, Replace, Restore, Regenerate**
**Human Tissues**
**Finalize rules for framework **
**Hematopoetic Stem cell transplantation**
**Reviewing data for possible ‘deemed’ licensing for stem cell facilities **
**Other Stem Cells (Neural, pancreatic, mesenchymal)**
**Guidance for stem cells**
**Outreach to stem cell providers**
**Tumor vaccines**
**International Workshop, April 2003**
**Development of guidance**

## Office of Cellular, Tissue and Gene Therapies	

**Federal “Stone Soup”**
**Education**
**Comprehensive Clinical Course, ASGT**
**ICH Gene Therapy Workshop**
**Partnerships**
**Adenovirus Standard (finished and shipping, 2002)**
**NIH Stem cell task force (ongoing)**
**Xenotransplantation Assay development (ongoing)**
**Patient Centered Therapies**

## “PATIENT CENTERED THERAPIES”

**Patient defines therapy**
**Market share/niche**
**Delivery infrastructure evolving**
**Financing, product development evolving**
**Patient need drives the process**

## Prototype Patient Centered Therapy

**X-linked Severe Combined Immunodeficiency Syndrome (X-SCID)**
**Lack of gamma-c chain with consequent lack of cytokine receptors needed for T-cell function**
**Death within first year of life from severe recurrent infections**
**Transplant of HLA-identical marrow >90 % survival; haploidentical transplant 50-70 %**
**Survivors may still need gamma globulin, unknown long term survival**

## Gene Therapy For X-SCID	

**In France, 9/11 children showed evidence of immune reconstitution following gene therapy**
**Late August 2002, one successfully treated child developed leukemia-like symptoms**
**FDA Biologics Response Modifier Advisory Committee (BRMAC) reviewed case on 10 October 2002**
**Consensus of BRMAC**
**Gene insertion gave both therapeutic effect and caused insertional mutagenesis**
**Because of potential superior immune reconstitution with gene therapy, studies should proceed with caution with stringent testing for clonal expansion of T-lymphocytes**
**Revision of informed consent process for ALL retroviral gene therapies**

## Complexity of  (a) Gene Therapy Product

- Ex Vivo Transduced CD34+ Cells Expressing GammaC-R for X-SCID

## Complexity continued...

**Cord Blood**
**Donor screening, adventitious agents, purity, potency**
**Devices**
**Monoclonal antibodies, surface markers, extracellular matrix**
**Retroviral Vectors**
**Cell substrates, adventitious agents, reversion to wild type**
**Specified Products (SCF, Flt-3, etc)**
**Purity, potency, novel use (ancillary, not as primary effector)**
**Cellular Product**
**Characterization, potency, evidence of gene transduction**

## ...learning the lessons of the past 	will enable the future:“What can be imagined, will be done”

***	****** ...******humility***
***	******	******...******patience ***
***	******	******	******...******compassion***

**...****learning the lessons of the past ****	****will enable the future:*****“What can be imagined, will be done”***