# Presentation: 507540

## Center for Biologics Evaluation and Research, FDA

- Site Visit Introduction
- Michael J. Brennan, Ph.D. for
- Kathryn M. Carbone, M.D.
- Associate Director for Research

## “The Researcher/Reviewer Model is essential to providing CBER with top-level expertise in a regulatory culture.”
           			 -Subcommittee for the External Review 
             				of CBER Research, 2/98

Work closely with Regulatory Scientists/Clinical Review Scientists to perform high quality evaluation of novel biological products

**           ****	****	****	**** ****-Subcommittee for the External Review **
**             ****	****	****	****	****of CBER Research, 2/98**
**Work closely with Regulatory Scientists/Clinical Review Scientists to perform high quality evaluation of novel biological products**

## Slide 3

## Evaluation of Research Program Achievements and Proposals

**Internal & External evaluation of past achievements and research proposals**
_**Internal**_ Management reviews: Yearly cycle using Annual Research Program Reporting
- Publications, Regulatory Policy/Guidances, Invited talks, Research QA/QC
_**External**_ Laboratory/Res-Reg/Office Site Visits:   4 yr cycle

## Site-Visit Team: To evaluate individual PI’s and Service Fellows in a Laboratory Unit

**RESEARCH accomplishments **_**since last review cycle **_
**RESEARCH proposals for next four years**
**Research Situation **
**Supervision Received **
**Guidelines and Originality **
**Qualifications and Contributions **
***Relative to time for research and research support available***
**Administrative/Management comments welcome**
**Regulatory activities and regulatory work quality NOT assessed by Site Visit Team**

## Site-Visit Team: Suggestions to get or continue “on the right track”

**Evaluation of the quality of science**
**New research directions and approaches to be considered**
**Needed laboratory expertise**
**Changes in laboratory organization**
**New collaborations**

## Site-Visit Report

**Oral summary is presented at end of review today to Research Management**
**Written report is prepared with:**
**Specific comments on each investigator**
**“****On target”, or, if **_**not**_** on target, detailed advice on improvement steps needed**
**Specific comments on Laboratory Program and Management issues**
**Specific comments on Personnel issues**
**Conversion Potential**
**Promotion Potential/Cyclical Review for Progress**

## Site-Visit Report

**Draft report is distributed to full Advisory Committee by Dr. Freas’ staff**
**Final report is approved by full Advisory Committee **
**Final report used for research evaluation and for Evaluation Committee (PCE) review for personnel actions**

## Slide 9

## OFFICE OF VACCINESRESEARCH AND REVIEWCenter for Biologics Evaluationand Research

**Michael J. Brennan, Ph.D.**
**Associate Director for Research**
** **
**VRBPAC Site Visit Review  November 14, 2007**

## OFFICE OF VACCINES RESEARCH AND REVIEW

**Division of Bacterial, Parasitic**
** ****and Allergenic Products.**
**Act. Dir.: Milan Blake, Ph.D.**
**Act. Deputy: Jay Slater, M.D.**

## OVRR’s Mission

**Review, evaluate and take appropriate action on INDs, BLAs, and amendments and supplements to these applications for vaccines and related products**
**Plan and conduct research related to the development, manufacture and testing of vaccines, and related products**
**Develop policy and procedures governing the pre-market review and evaluation of vaccines and related products **
**Evaluate and test licensed vaccines and related products as appropriate prior to release and distribution of these products into the market by manufacturers**
**Evaluate and monitor clinical experience and reports of adverse events as necessary in coordination with CBER’s Office of Biostatistics and Epidemiology**
**Participate in inspections of manufacturing facilities **
**Participate in national and international outreach activities, including collaborations with global National Regulatory Authorities **

## Major OVRR Research Priorities 2007

## Evaluation of OVRR Research Programs

** ****Performed on an annual basis using Office Research Priorities**
**  ****Process begins in Divisions**
**	****-Evaluation of  PI Res Prog by Lab Chief-Division Director**
**	****-Evaluates Research Progress (pubs; presentations; outreach) **
**	****  ****and Regulatory Workload (INDs, BLAs, Meetings w/ Pharma)**
**  ****Evaluation of Division Research Programs by OVRR through the  **
**   ****Scientific Management Committee to address:**
**	****- FDA regulatory needs**
**	****- Emerging issues**
**	****- Future issues ( 2 - 5 years )**
**	****- Budget issues**
** ****Individual Programs evaluated by VRBPAC (site visits) for progress**
** ****Individual PIs evaluated for promotions by CBER PCE committee**

## Summary

**The research-regulatory staff support the **
**  ****science-based review and regulation of  **
**  ****vaccines and related products.**
** ****OVRR’s research priorities focus upon our  **
**  ****mandate to assure the safety, purity, potency,  **
**  ****and effectiveness of vaccines and related **
**  ****products.**
** ****OVRR’s research program serves to recruit,**
**  ****train and retain highly qualified scientists.**

## Thank you

- To the Site Visit reviewers for their time, expertise and suggestions for continuing improvement of CBER research programs

## Slide 17

## Division of Viral ProductsOffice of Vaccines Research and Review

**Division of Viral Products****Office of Vaccines Research and Review**

**Jerry P. Weir, Ph.D., Director**
**Phil Krause, M.D., Deputy Director**

**Laboratory of Hepatitis Viruses**
**Steve Feinstone, M.D., Chief**

**Laboratory of DNA Viruses**
**Andrew Lewis, M.D., Chief**

**Laboratory of Respiratory Viral Diseases**
**Chief - Vacant**

**Laboratory of Immunoregulation**
**Ira Berkower, M.D., Chief**

**Laboratory of Method Development**
**Konstantin Chumakov, Ph.D., Chief**

## Division of Viral ProductsMission and Functions

**Regulate viral vaccines and related biological products, ensuring their safety and efficacy for human use**
**Facilitate the development, evaluation, and licensure of new viral vaccines that positively impact the public health**

## Division of Viral ProductsReview and Research Activities

**Investigational new drug (IND) application review**
**Biologics license application (BLA) and supplement review**
**Lot release review and testing**
**Post-marketing activities (e.g., Biological product deviations)**
**Manufacturer inspections**
**Consultation with other public health agencies (e.g., WHO, CDC, NIBSC)**

## Division of Viral ProductsReview and Research Activities (Cont.)

**Research activities related to development, manufacturing, and testing of viral vaccines**
- Viral pathogenesis
- Vaccine safety and efficacy (including cell substrates)
- Vaccine and viral vector evaluation
- Correlates of protection
- Reagent preparation (e.g., influenza vaccines)
- Methods development and evaluation
- Emerging issues (e.g., BSE, counter-terrorism)

## Laboratory of Method Development

**Laboratory Teams and their Research Programs**
- Evaluation of Safety and Potency of Viral Vaccines Based on Molecular Consistency
- Konstantin Chumakov, Ph.D., D.Sci., Team leader
- Microarray-Based Evaluation of Purity and Safety of Biological Products
- Vladimir Chizhikov, Ph.D, Team Leader
- Developing Tests to Evaluate Virus Vaccine Safety for the Nervous System
- Steven Rubin, M.S., Acting Team Leader

## Laboratory of MethodDevelopment (Cont.)

- Major Regulatory Responsibilities
- Poliovirus vaccines
- Measles, Mumps, Rubella virus vaccines
- Mycoplasma vaccine issues
- Other virus vaccines including parvovirus, varicella virus, ebola, influenza, etc.)
- Areas of Research
- Development of new methods to assess the consistency of viral vaccines
- Development of pre-clinical neurotoxicity assays for assuring the safety of live virus vaccines
- Development of methods for rapid accurate identification pf biological agents
- Evaluation of surrogate endpoints for vaccine safety
- Development of methods to detect extraneous agents in vaccines

## Slide 24

## Division of Bacterial, Parasitic and Allergenic Products (DBPAP)

**Laboratory of Mycobacterial Diseases and **
**Cellular Immunology**
**Sheldon Morris, Ph.D.-Chief**

## Laboratory Mission and Functions Dependent on Researcher/Reviewers

- Conduct regulatory review
- Conduct critical research: programmatic and special tasks
- Serve outside organizations as recognized subject matter experts
- Find outside resources to support research

**Responsibilities of Researcher/Reviewers**

## Regulatory Review and Laboratory Work: A Synergistic Combination

- Provide reagents/standards
- Assay development
- Improved technology
- Trouble-shooting
- Gain expertise to:
- Better anticipate issues/identify and fill knowledge gaps
- Provide expert input to vaccine community
- Provide guidance advice to industry

## DBPAP Research Priorities

**Improve or develop new methods that enhance  the safety of vaccines and related products**
**Improve or develop new methods that enhance the effectiveness of vaccines and related products**
**Facilitate the development of new biological products for high-priority public health threats,  including emerging diseases and BT agents**
**Develop and evaluate novel scientific technologies and standards to improve biological product regulatory pathways, availability and quality of vaccines and related products**

## The Laboratory of Mycobacterial Diseases and Cellular Immunology

**Areas of Research**
- Evaluation of protective innate and adaptive immune responses to intracellular bacteria
- Assessment of live attenuated TB vaccine strains and DNA vaccination strategies against tuberculosis
- Characterization of a unique family of tuberculosis proteins