Of the many benefits that have come from the Generic Drug User Fee Act (GDUFA) over the years, one has been the addition of response times for the FDA to answer Controlled Correspondences (CCs) that were first negotiated under GDUFA II. The Agency issued an FDA CC guidance, which was finalized in December 2020. Having a clock with a defined response time has allowed CC to become a more predictable and useful tool for pharmaceutical companies developing generic products. However, with the updates in GDUFA III that clarified the two levels of CCs and expanded the scope of questions that can be submitted as CCs, the burden on the FDA’s Controlled Correspondence Coordinators may have increased, which has led to an increased level of scrutiny that CCs undergo before being accepted for review. The enhancements also triggered a new draft guidance, which was released in December 2022, to coordinate with the CC program under GDUFA III (currently, both guidances are listed on the FDA’s site). Since the release of the December 2022 draft guidance, the rejection rate of CCs has noticeably increased. There are some measures that industry can take to increase the acceptance rate, but there is also room for improvement by the FDA as well.

In order to help guide yourself and your firm through these new GDUFA III additions, we recommend that authors of CCs verify against the December 2022 draft guidance that all new requirements have been met. Among the new requirements that came about in the December 2022 draft guidance is that CCs can no longer be submitted anonymously; the CC must have a named sponsor, either the product developer or an appointed U.S. Agent, and if it is submitted by a U.S. Agent, the Agent must identify the company for which it is the agent and provide a Letter of Authorization dated within the past year for each CC submitted (see draft guidance Section IV. B). The cover letter and the letter of appointment for the U.S. Agent must both be on company letterhead that includes the company’s address. Don’t forget to explicitly state that the correspondence is in relation to a specific drug product and for support of a future or current ANDA as such an omission can be cause for rejection as well.

Proper use of attachments is also critical. Be sure to include only attachments that are relevant. There is a separate place in the CDER NextGen Portal now for attaching related CCs and responses but be sure that the referenced correspondence is actually related. Also, be sure that you do not provide the related correspondence as an attachment to the cover letter. Since the enactment of GDUFA III, we have experienced rejections of CCs for many reasons. For example:

  • If the related correspondence is still pending, this is grounds for rejection (see draft guidance, Section IV C. 1).
  • If the attachments are not provided in the correct place, this may be grounds for rejection.
  • If the CC coordinator doesn’t think the attachments are related, the CC may be rejected, and, on the flip side, if CCs aren’t attached that the FDA thinks should have been, the CC may be rejected as well.

Our feeling is that if the CC is not deemed related by the review team, this should not be grounds for rejection; the CC coordinator can just ignore it. Should the CC coordinator be the one to make such a decision if the author thought it was relevant to attach?

Once the administrative details have been worked out, take a hard look at the content and the way the information and question(s) are presented. Review the December 2022 draft guidance again and make sure that nothing is included that the guidance says to leave out, such as providing the full product formulation when asking for IID level confirmation of one or only a few ingredients (see Section IV. C of the draft guidance). Is there enough detail for the Agency to respond to the question or might anything be seen as confusing? Is information provided in a narrative that would be provided in a tabular format if it were being submitted in an ANDA? If providing information such as a product formulation, do you have the grades of the excipients listed as requested in the guidance? You cannot read the guidance too many times when drafting a CC, and your ANDA authorship experience will also come in handy. These are the same reviewers so organize and present the information in the format in which they would expect to see it.

Stay tuned for more information in Part 2…