FDA defines Goal Dates for the Processing of Changes in Generics Authorisation Applications

Recommendation

6/7 September 2023
Vienna, Austria

Drug Master File Procedures in the EU, the US and Japan
Taking into account the guidance on metal impurities (ICH Q3D) and genotoxic impurities (ICH M7)

The FDA recently published a new guideline draft for review. This draft refers to changes in generic drug applications. The document is entitled "ANDA Submissions - Prior Approval Supplements under GDUFA" and describes how the FDA processes Prior Approval Supplements (PAS) in the context of the legal framework GDUFA (Generic Drug User Fee Act) which became effective on 9 July 2012.  GDUFA is based on an agreement that was negotiated by the FDA and representatives of the generics industry. Purpose of this Act is the accelerated processing of generics' authorisation applications to ensure the adequate supply of the population with high-quality, safe and cost-saving generic pharmaceuticals. To finance the required human resources, the FDA has set up a system of fees for the processing of PAS and Drug Master Files (DMFs).  A detailed description of the target agreements in connection with GDUFA can be found in the FDA "Commitment Letter" entitled "Generic Drug User Fee Act Program Performance Goals and Procedures". 

The Guidance sets two time periods for processing Prior Approval Supplements (PAS): 

•  6 months if no inspection is required 
•  10 months, if an external inspection has to be conducted

The period begins on the day on which the PAS was submitted via the electronic FDA portal.  The 10-month period may be shortened to six months if the authority subsequently determines that no inspection is necessary.

Another category of documents for which the FDA has fixed specific goal dates for processing are amendments to marketing authorisation applications (ANDAs) or to PASs. These amendments are response letters which the applicant obtained following the authority's deficiency letter - the so-called "complete response letter". For the processing of these amendments, the FDA has further published a guidance entitled "ANDA Submissions - Amendments and Easily Correctable deficiencies under GDUFA". This Guideline draft describes in great detail the handling of the different types of amendments and their review times.  Amendments are divided into three main categories and several subcategories:

• Solicited Amendment
   - Major amendment (e.g. new analytical methods, new bioequivalence studies, new validation methods)
   - Minor amendments (e.g. small changes to a validated method of analysis, additional stability data)
   - Easily correctable deficiency (e.g. lack of information which, however, the applicant has available; misplacement of information in the amendment 
• Unsolicited  Amendment
   - Delaying amendment (actions of third parties which the applicant has no control of, such as the revision of a monograph by the USP)
   - Nondelaying  amendment (unsolicited submission of new data, for example on a new strength of the drug or with regard to a new production site) 
• Administrative Amendments (general correspondence with the authority which is not subject to review, and does not affect the goal dates)

For the major and minor amendments as well as for the easily correctable deficiencies the the Guidance's Annexes A to C each provide a number of concrete examples.

The various amendments are then processed in a three-level tier system, in which different amendment types and goal dates are assigned to each tier. Annex D of the Guidance contains a flowchart of the various amendments associated with the system.

It should be noted that the review times may add up. That means that an original goal date for the processing of a PAS may be extended, depending on the type of amendment submitted in the meantime. To this end, the Guidance "Prior Approval Supplements and GDUFA" lists some examples.

The 3-tier system for the processing of amendments is quite complex and yet can lead to unforeseen delays in spite of defined review times. In the approval process applicants should seek to keep the number of amendments as low as possible by submitting high-quality applications in order to rapidly obtain the authorisation and also to save fees.

The goal dates for PASs described in the two Guidances will become effective on 1 October 2014. The procedures / goal dates for amendments will only be applicable to those referring to authorisation applications (ANDAs) on 1 October 2014 or thereafter. Therefore, the generics industry remains some time to adjust to the new regulations.