(571) 447-5500

EAS independent consultant, Radhika Rajagopalan answers your questions on DMF submissions in Tablets and Capsules magazine.


Under the Generic Drug User Fees Act (GDUFA), the FDA applies a holistic, life-cycle approach to the evaluation of active pharmaceutical ingredients (APIs), featuring innovation, transparency, engagement of stake holders, communication, and collaboration. While the GDUFA program’s goals include communication and collaboration with the generic drug industry, those goals are achievable only through successful submissions and the engagement of industry and FDA scientific assessors.

Understand how to successfully submit a type 2 drug master file (DMF)—avoiding common chemistry, manufacturing, and control (CMC) issues—to obtain a fully adequate status. DMFs undergo a completeness assessment after filing, and an abbreviated new drug application (ANDA) allows issue of a letter of authorization. Technical review of the master file commences after the filing of the ANDA that has referred it. During the course of a review, FDA reviewers can issue deficiencies for the following reasons.

Facilities listed in DMFs

DMF holders need to list all facilities involved in manufacturing and routine testing of the drug substance in the DMF, as indicated under S.2.1 of the DMF. This includes intermediate sites where key intermediates are made; all testing sites—release, stability, and microbial; and secondary DMF information, such as DMF number and manufacturing-site information for the sites where key intermediates are made. Lack of information about facilities for critical intermediates or the addition of a new facility after the review has commenced usually results in major amendments during review.

Regulatory starting material

Often, review teams will disagree with the identified starting material in a DMF if it doesn’t allow for adequate evaluation of control of the process and/or provide the critical quality attributes of the drug substance.

Read More in Tablets and Capsules

Posted in Drugs, EAS in the News Drugs.