Today, the FDA released Revision 1 to the Draft Guidance to Industry: Generic Drug User Fee Amendment of 2012: Questions and Answers.  This 36 page document contains additional questions and answers (as well as clarifications) to some of the issues raised in the original draft guidance issued on August 22, 2012.  A complete copy of the new guidance can be found here.

Here are some of the highlights:

In question 32, FDA explains when a fee for a serially submitted application is due.  First, a serially submitted application is one that references a New Drug Application (NDA) subject to new chemical entity exclusivity (NCE), where four years has passed since approval of the NDA, and the ANDA applicant is aware of a patent that has been recently issued, but has not yet been submitted to the NDA for listing in the Orange Book.  Since an ANDA referencing an NDA subject to NCE cannot be submitted to FDA until the expiration of 5 years (unless a patent is listed in the Orange Book, in which case it may be submitted after 4 years if a Paragraph IV certification challenging the patent is in the submitted ANDA), then the applicant (in anticipation of the patent being listed) will submit its ANDA every day until the patent appears in the Orange Book.  If a fee was required each time the application was submitted, this would cause significant administrative issues for the Agency.  Thus, FDA advises that no fee should be submitted with such an ANDA, until such time as the Office of Generic Drugs advises the applicant that the application is valid, i.e., the patent has been listed.  Once the FDA advises the firm its submission is valid, they then have 20 days to pay the required fee.

The 2013 and 2014 GDUFA fees are listed in question 33 and have also been provided in our blog here .

There are a significant number of questions in the Draft Guidance clarifying when a facility fee payment is required when a firm taking part in the manufacture is referenced in an ANDA (see questions 36-42).  Fee assessments are keyed to the date the facility fees are mandated.

Questions 43 and 44 further clarify when a packager is required to pay a fee.

Questions 59 through 61 explain the consequences of being on the arrears list, and also explain that, if a sponsor has an affiliate on the arrears list, the FDA will refuse to receive their applications for filing until such time as the outstanding obligation of the affiliate is satisfied.

Question 72 clarifies that a contract organization that is used for sterilization of the FDF or API are considered to be part of the manufacturing process and are, therefore, required to pay a facility fee.

Questions 75 and 76 identify self-identification reporting schedules for facilities and obligations for fee payment are described.

In the answer to question 83, the FDA explains that they will issue a complete response letter (CRL), even if the inspectional information has not been completed.  This represents a welcome change from the original view that had been expressed during the beginning months of GDUFA.  Thus, if there is a delay in scheduling an inspection, the FDA will issue the CRL so the applicant can begin remediation of the issues identified in the letter.  FDA also notes that such a CRL without inspection information will not count towards meeting the FDA’s GDUFA goals.

The guidance addresses the impact of amendments on the GDUFA review clock and further clarifies some of the more confusing Tier Amendment discussions that appeared in the FDA’s GDUFA Commitment Letter.

The Q&A document provides many clarifications to questions that have been swirling around since the implementation of GDUFA.  We commend the Agency for its proactive approach to responding to many of the issues raised by industry, and look forward to their further updates to this document as new situations arise.

For questions relative to GDUFA please contact Joan Janulis at or one of your regulatory contacts at Lachman.