The GRx+Biosims Conference held in Baltimore, MD from September 5-7, had a session on the GDUFA II Pre-ANDA Program for Complex Products on the last day, presented by FDA.
The presenter, Kris Andre, Associate Director of Regulatory Affairs, Office of Research and Standards, Office of Generic Drugs (OGD), discussed in detail the logistics and agency’s expectations related to the meetings for complex generics. Currently, OGD has provisions for three types of meetings in relation to complex generics. The pre-ANDA Product Development (PDEV) meeting is a way for a sponsor to engage the Agency early in their complex generic product development program. The time of requesting of this meeting may be tricky. A sponsor should not do this too early in the process as they may not have enough information to help FDA provide them with advice on a path forward. At the same time, it should not be too late in the process, when a lot of resources have already been spent in performing studies. Re-doing any of the work based on FDA’s recommendation may be challenging. The pre-submission meetings (PSUB) are to be requested when the sponsor is about 6 months to a year from submitting the application. The last is the mid-review cycle meeting (MRCM) which is granted if the sponsor had a PDEV or PSUB meeting. This meeting is held after the ANDA is submitted, within 30 days of the mid-point of review cycle and will be more of a communication of what the FDA may have seen in the ANDA until then. The meeting goal dates based on GDUFA II are already discussed in FDA Guidance for Industry, “Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA” can be located here. The complex generic meetings can be face to face, via telephone or FDA may notify the applicant that they will provide a written response to their questions. The type of meeting depends on the specific product and the kind of discussion needed. The MRCM is typically a telephone meeting.
Discussed in the session was also the CDER Direct NextGen Collaboration Portal. The pre-ANDA meeting requests which were previously sent via the Generic Drugs email account can now be submitted to this portal. This portal is located at https://edm.fda.gov. The advice from FDA was that the sponsor should have a pre-ANDA number requested for their complex product and submit all their pre-ANDA meeting information to the portal with the pre-ANDA number. It was also recommended that controlled correspondence related to the complex generics should also reference the pre-ANDA number. FDA would also send their communications related to the complex product through the portal, along with an email notification to the sponsor. This would assure that all pre-submission communications regarding a specific product would be available in the portal for reviewers and sponsors to look at, even after the submission of the ANDA.
Ten months into the GDUF II, the agency had 65 meeting requests, out of which 45 were granted and 20 were refused. FDA stated that the possibility of having a meeting granted depends on whether the sponsor has something “original” to discuss regarding the product in question. It was mentioned that when a meeting is denied, FDA usually provides a path forward, which in most cases, comprises of using controlled correspondence to get discipline specific responses.
It was pointed out that a successful meeting depends on the kind of questions asked. Rather than asking general questions, a sponsor should decide what would be the most helpful for them to get clarification from FDA. Questions like, “Are the specifications acceptable?” would lead to general response that, “This is a review issue…” and would be a question not discussed. The take home message of the session was that a sponsor should do their homework and come to FDA with a clear purpose of negotiating a path forward with some original ideas. If they have some specific questions regarding disciplines, it is best to use the controlled correspondence.
Overall, it was a very informative session and based on the lively question and answer session, it appeared that the attendees benefited from it.