US FDA has issued a set of guidelines to assist pharma companies preparing to submit prior approval supplements (PASs). These are also amendments to PASs for abbreviated new drug applications (ANDAs).

The guidance elucidates how the Generic Drug User Fee Amendments of 2012 (GDUFA) relates to PAS submissions. It also describes the performance metric goals, outlined in the GDUFA Commitment Letter, that FDA has agreed to meet. It also clarifies how FDA will handle a PAS and its amendments for an ANDA.
 
Specifically, this guidance makes it clear  how the GDUFA and its performance metric goals apply to a PAS subject to the refuse-to-receive (RTR) standards which require an inspection or not.
 
The Commitment Letter outlines the performance metric goals FDA agreed to meet for reviewing and acting on PASs submitted between FY 2015 and FY 2017. Specifically, FDA agreed to review and act on 60 per cent of the complete PASs that do not require inspection within 6 months from the date of submission for receipts in FY 2015. It would also look into 75 per cent of complete PASs that do not require inspection within 6 and 10 months from the date of submission for receipts in FY 2016.
 
Further, the Commitment Letter defines the submission date for an ANDA or a Type II API (active pharmaceutical ingredient) drug master file (DMF) to be dispatched via the Electronics Submissions Gateway (ESG) of FDA. If a submission arrives in physical media form in an electronic common technical document (eCTD) format, it is deemed to be submitted on the day it arrives at FDA’s appropriate designated document room.
 
The regulatory authority’s performance goal obligations under GDUFA would begin on the submission date of a PAS. An applicant may request reconsideration of FDA’s supplement reporting category determination. These requests will be reviewed and managed on a case-by-case basis. If an applicant is requesting reconsideration of a supplement reporting category, then he should submit a written request for reconsideration within 10 business days of FDA’s notice. If an applicant disagrees with the outcome of the reconsideration, the applicant may initiate a formal appeal if the submission was not accepted as a changes-being-effected (CBE) supplements to FDA.
 
Grouped supplements are multiple supplements submitted to ANDAs by a single applicant for the same chemistry, manufacturing and controls (CMC). Although the submissions are considered a group, each supplement in the group is considered its own individual submission and therefore would require a GDUFA PAS fee for each ANDA identified in the group.

Thus, for example, if a group PAS change is submitted to 10 ANDAs, then 10 GDUFA PAS fees should be remitted. Because the grouped supplements are being reviewed together, and they will have the same GDUFA goal date, stated the regulatory authority.
 
Commenting on behalf of the industry Kaushik Desai, pharma consultant and general secretary Indian Pharmaceutical Association said, “This is the guidance of the future. It brings in clarity on the submissions and may speed up the approvals. The only area of concern is that it GDUFA and PAS would have an additional financial impact for the companies.