Memorandum of Understanding
Between The United States Department of Health and Human Services
National Institutes of Health
National Institute of Neurological Diseases and Stroke
Epilepsy Branch
and The United States Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research

 

I. PURPOSE

The purpose of the proposed Memorandum of Understanding (MOU) is to establish a relationship between the Center for Drug Evaluation and Research (CDER), Food and Drug Administration, and the Epilepsy Branch, National Institute of Neurological Disease and Stroke, so that joint experiments can be conducted relating to drug metabolism and drug-drug interactions.

 

II. BACKGROUND

Drug metabolism and drug-drug interactions represent significant issues for the FDA's mission to ensure safe and effective drugs with adequate instructions for use. For both metabolism and interactions, studies in vitro can provide substantial information needed for drug development and regulation. Review and laboratory scientist in CDER have become increasingly involved in the development of the technology for testing in vitro, and its application to modern drug development and regulation.

 

The Antiepileptic Drug Development (ADD) Program of the National Institute of Neurological Disorders and Stroke (NINDS) was established to collaborate with the private sector and academia effective and safe drugs for the treatment of seizures in epileptic patients. The ADD Program includes preclinical pharmacodynamic and pharmacokinetic as well as clinical investigations. The Preclinical Pharmacology Section of the Epilepsy Branch is responsible for identifying potential compounds through a multistage screening program. At present, drug-drug interactions are found by chance, as new therapeutic agents proceed through the developmental process and enter clinical trials with comedicated epileptic patients. A critical need exists to establish possible drug-drug interactions prior to the initiation of clinical trials.

 

III. SUBSTANCE OF AGREEMENT

Staff of both the FDA's Division of Clinical Pharmacology and the Preclinical Pharmacology Section, Epilepsy Branch, NINDS will collaborate in determining metabolic pathways and potential drug-drug interactions of ADD Program compounds. The basic technology for evaluating drug-drug interactions exists in the FDA's laboratory through the use of human liver slices and subcellular fractions. The division of labor for these studies are based on the expertise and equipment found in each laboratory. Analytical methods for the identification and quantification of metabolites of the experimental compounds and clinically effective antiepileptic drugs will be developed in both laboratories under a mutual agreement based on available resources. The compounds will be supplied by the Epilepsy Branch following an agreement with the pharmaceutical sponsor. All data from these studies will remain confidential as stipulated under the present NINDS ADD Program preclinical confidentiality agreement. Any information obtained or generated under this Memorandum of Understanding will not be disclosed by FDA staff to anyone outside FDA or NINDS without permission from NINDS or the pharmaceutical sponsor.

 

IV. PARTICIPATING PARTIES

Epilepsy Branch
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Federal Building, Rm. 118
Bethesda, MD 20892

Division of Clinical Pharmacology
Office of Research Resources
Center for Drug Evaluation and Research
Food and Drug Administration
4 Research Ct., Rm. 314
Rockville, MD 20850

 

V. LIAISON OFFICERS

For the Epilepsy Branch:

Harvey Kupferberg, Ph.D.
Epilepsy Branch, NINDS, NIH
Federal Bldg., Rm. 118
(301) 496-1846 [phone]
(301) 496-9916 [fax]

 

For the Division of Clinical Pharmacology:
John M. Strong, Ph.D.
Food and Drug Administration
4 Research Ct., Rm. 314
Rockville, MD 20850
(301) 427-1065 [phone]
(301 427-1026 [fax]

 

VI. PREIOD OF AGREEMENT

This agreement becomes effective upon acceptance by both parties and will continue in effect indefinitely. It may be modified by mutual written consent or terminated by either party at any time upon a 60-day advance written notice to the other party.

Approved and Accepted
for the Epilepsy Branch, NINDS
Signed by: Harvey Kupferberg
Chief, PPS, EB, DCDND
NINDS, NIH
Date: December 13, 1993

Approved and Accepted
for the Food and Drug Administration
Signed by: John M. Strong
Director, Office of Research
Resources, CDER/FDA
Date: December 1, 1993