# Presentation: 212714

## The Division of Monoclonal Antibodies

**Kathleen A. Clouse, Ph.D., Director**
**CTGTAC - July 26, 2007  **

## Mission of the DMA

**... ****to ensure that safe, efficacious, and high quality **
**	****monoclonal antibody and related products are ****	****available to the American people to diagnose, ****	****prevent and treat the illnesses that afflict them.**
**    ... ****to maintain and retain a diverse, knowledgeable,  **
**         ****scientifically based and dedicated staff actively **
**         ****involved in research and regulatory review**

## Clinical Success of Monoclonal Antibodies

**Clinical Success of Monoclonal Antibodies**

***Janice Reichert, Tufts University Center for the Study of Drug Development***
***Nature Biotechnology, September 2005***

## The Division of Monoclonal Antibodies

## Dr. David Frucht

**  ****Established an independent research program to characterize **
**    ****the activity of anthrax lethal toxin *****in vitro***** and *****in vivo***
**  ****Reviews products for infectious diseases, including antibodies**
**    ****under consideration for inclusion in the SNS under Emergency**
**    ****Use Authorization**
**  ****Reviews monoclonal antibodies or related molecules that **
**    ****function as agonists or antagonists for hematologic indications**
**  ****Participates in pre-approval inspections for MoAb products**
**  ****Serves on working groups for guidance document development **
**   ****(anthrax therapeutics development, drug-drug interactions)**
**  ****Co-Chair, CDER/CBER Inter-Center Biotechnology Counter-**
**    ****Terrorism Working Group**
**  ****Chair, CMC session of the FDA-sponsored workshop on **
**    “****Immune Therapies for Anthrax Infection”**

## Dr. David Frucht

**  ****Board certified in Internal Medicine & Infectious Diseases **
**  ****Performs weekly clinical rounds at NIH**
**  ****Serves on Editorial Boards for **_**The Journal of Immunology**_** and **
**    **_**The Journal**_** **_**of Biological Chemistry**_** **
**  ****Awarded competitive HHS grants (2006 & 2007) and **
**   ****CBER/FDA grants (2002 & 2003) for CBT research efforts**
**  ****Duties as  a Commissioned Officer, U.S. Public Health Service**
**      ****- Incident Response Coordination Team, on-call every 5 **
**         ****months for deployment (six deployments in 3 years)**
**      ****- Selected for the Physicians’ Professional Advisory Committee**
**         ****to the Surgeon General**

## David Frucht, M.D.

**Research Program Objectives**

**  ****Identify biological markers for the activity of anthrax lethal toxin **
**   ****(LT) in humans and animal models**
**  ****Assess the biological significance of these markers in the **
**    ****pathology of toxemia and/or anthrax infection**
**  ****Establish the scientific basis for development of more relevant **
**    ****bioassays to assess product potency**
***Important for addressing issues relevant to seeking approval for **
**  ****these products under the “Animal Rule” (i.e., efficacy testing in **
**  ****animal models and not in humans)**

## David Frucht, M.D.

**Research Program Milestones**

**  ****Anthrax LT activates murine macrophages, leading to release of **
**    ****IL-1******** and IL-18 (**_**J Biol Chem**_**, 2004) - Identification of new **
**    ****biomarkers & strain susceptibility factors**
**  ****Anthrax LT targets human T cells, leading to a blockade in **
**    ****proliferation and cytokine production (**_**J Immunol**_**, 2005) - A **
**    ****pathogenic mechanism and basis for new bioassays **
**  ****Anthrax LT blocks B cell proliferation and immunoglobulin **
**    ****production (**_**J Immunol**_**, 2006) - A pathogenic mechanism and **
**    ****basis for new bioassay**