Drug Master file Review Issues at the Office of Generic Drugs

Abstract

The Office of Generic Drugs (OGD) in the US Food and Drug Adminstration's (FDA) Center for Drug Evaluation and Research (CDER) has recently been receiving unprecedented numbers of abbreviated new drug applications (ANDAs); currently, more than 700 per year. Each ANDA is supported by drug master files (DMFs), which are separate proprietary documents describing the chemistry, manufacture and associated controls for the active pharmaceutical ingredients (APIs). Usually, the firm submitting the ANDA purchases the API from a fine chemicals producer who has filed a DMF with the FDA. A Letter of Authorisation (LOA) from the DMF holder allows the FDA staff to review the DMF in conjunction with review of the ANDA. An adequate DMF is one requirement for approval of an ANDA. To date, over 18,000 DMFs have been submitted to the FDA. Very few of these are found to be adequate in an initial review and, consequently, approvals of ANDAs are delayed as additional information and data are needed from the DMF holder to ensure consistent production of high-quality APIs. Illustrative examples of typical DMF deficiencies are presented in this paper and suggestions for improved DMF submissions are given.