Generic Drug Applications in the USA: Completeness Assessment of Drug Master Files for APIs by the FDA

The new Generic Drug User Fee Act (GDUFA) in the USA determines the fees to be paid by an applicant to the FDA as part of the application procedure. It also lists the types of services which have to be paid (see also our News dated 14 August 2012). Furthermore, the GDUFA also entails changes in the procedure of an application. This means that companies submitting an application have to adjust. One of the consequences is the completeness assessment of the Drug Master File (DMF) Type II (describing the active pharmaceutical ingredient of the generic drug). This completeness assessment is compulsory with immediate effect.


Until now, the common practice of application for a generic drug was as follows: The submitted application (ANDA) was assigned to a review process (and to a certain reviewer). Then the DMF and the application were reviewed together. The new FDA practice differs quite significantly from the procedure used so far and is described as preemptive review. Now the process takes place as follows:


  • Submission of application and DMF;

  • The DMF is assigned to a review team and assessed for completeness;

  • The DMF will possibly undergo several review cycles;

  • The application will only be reviewed after the DMF's completeness is confirmed;

  • The application will possibly undergo several cycles;

  • Authorisation will be granted after successful review of the application.


This new procedure means for the applicant that he should submit the DMF as complete and correct as possible in order to save unnecessary review cycles and valuable time. The review team will handle the DMF in a Question based Review (QbR). Such a Question based Review already is normal practice in the case of applications. The FDA has announced the publication of a list of questions and of a survey of points expected by the applicant for a complete DMF on its Website by autumn this year.


The generic drug industry not only has to adjust to a changed review procedure for applications - further costs also are to be expected: According to the GDUFA a DMF completeness assessment will account for 6% of the total costs for a generic drug application. But the generic drug application will only be handled in the USA if the relevant DMF has been deemed "available for reference". A DMF will obtain this status only if


  • the fee has been paid on time and

  • the assessment for completeness was passed successfully.

The list of questions will be of great importance for the generic drug industry because the FDA will require the industry to submit also a Quality Overall Summary (QOS) for a DMF in the QbR format no later than by the beginning of 2014.


Many colleagues of the department have contributed to the redesign of the review process and to the setting up of the DMF team at the Office of Generic Drugs (OGD). Representative for all those who contributed, two names will be mentioned: Dr. Aloka Srinivasan and Dr David Skanchy. Prior to recently leaving the FDA, Aloka Srinivasan has played a leading role in setting up the DMF team and David Skanchy actually is the DMF teamleader.


For further information please also read the interview with Aloka Srinivasan


Information: Dr. Aloka Srinivasan is speaker at the "15th APIC/CEFIC European Conference on Acitve Pharmaceutical Ingredients" in Budapest from 7 - 9 November 2012. She talks in detail about the DMF review, the GDUFA and the consequences for the generic drug and API industry.

This topic will also play an important role at the event event "Getting Approval of Generics in the EU and USA" taking place in Vienna on 15 and 16 November 2012. 


Dr Gerhard Becker

CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)

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