In Part 1, we focused on drafting the Controlled Correspondence and tips for formatting and presenting the correspondence, but, after submission, the CC must be accepted by the coordinator to be placement in the queue for review. The office has been very strict, perhaps rightly so, but there have been a few headscratchers too. Some examples follow below with some suggestions on how to hopefully avoid roadblocks to acceptance.

It can be frustrating when trying to request verification that a formulation is Q1/Q2 (QQ) when being QQ to the RLD is not required and when there is a bioequivalence (BE) pathway described in the Product Specific Guidance (PSG) based on the ANDA product being Q1/Q2 to the RLD. If not properly phrased, this type of CC can be rejected simply because the product in question is not required to be QQ. Beware, these are not straight QQ questions and, if asked as such, they will be rejected as the product is not required to be QQ. These questions, instead, are for verification of the correct generic product formulation to be able to use the BE pathway described in the PSG. It’s a subtle but important distinction that can be frustratingly nuanced when trying to phrase this type of question to avoid rejection.

There are occasions when someone at the FDA requests that a CC be submitted in response to something discussed in a meeting. Even when this is explained in the background and when referencing the meeting by date, the subject of the meeting, and including the name of the FDA attendee who requested the CC submission, the CC may still be rejected. The only way we have found to resolve this is to send an email or make a call to the Office of Regulatory Operations in the OGD to help smooth the path for resubmission and acceptance. To these authors, this seems like an easy point to train the CC coordinators to allow as such CCs are being submitted in response to direct requests.

Asking questions that the CC coordinator perceives to be directed at more than one discipline is also grounds for rejection (see draft guidance, Section IV. C. 5). Do not list multiple disciplines in the CC, even if you aren’t sure; instead, list the primary discipline knowing that the FDA can always request a consultation if the Agency feels it is needed. Alternative BE format questions seem to be the biggest challenge in this case; we advise you only to request the Division of Bioequivalence for such questions. Be precise when there is more than one strength as some questions can be misinterpreted as asking product quality questions rather than BE questions, and the CC may be rejected. This seems to be another type of situation that could be improved by better training of the CC staff.

Once you have submitted your CC through the Portal, you just need to wait for the acceptance, right? Well, in our experience, you are not out of the woods; things can still go wrong. CCs can get lost or misdirected before being acknowledged and accepted/rejected, and, in one case, even be lost after being accepted! Alternately, we have experienced CCs that were accepted and then received missed goal date notifications and remained pending for months with no feedback as to why they are pending or when they might be answered. There is a general email box for inquiries about CC status, but responses are usually the same: the CC is still under review with no timeline as to when you can expect a response. If this continues, it may be an opportunity to approach the ombudsman for some assistance.

While some of these issues are out of the CC author’s control, and some of these items are better addressed by the Office of Regulatory Operations, which oversees the CC staff, the author of a CC can still take steps to afford their CC the best chance at being accepted. Authors should read the December 2022 draft guidance before drafting a CC, read it again after the CC is drafted, then read it one more time once the CC is finalized before submission. Take every opportunity to make sure that the question is clear, the correct format is used to present the information, and that attachments and supporting documentation are provided appropriately. When possible, consider having someone else familiar with the draft guidance review the CC. Though there are opportunities to revise and resubmit a CC, you are losing time every time you need to go through that process. Submitting a CC is a mine field of potential rejection these days, but these tips may help save you from feeling like you’re stuck in a loop, repeating the same submission over and over and over…

If your firm needs help submitting a Controlled Correspondence or you have any questions regarding the best strategy for approaching the FDA with what you think might be answered by a CC, we are here to help! Please send us an email at and we will help you navigate the process.