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The Complexity of Complex – Explained at Least in Part

On Wednesday afternoon at AAM’s GRx+Biosimilars Conference in Bethesda, MD, the FDA held a valuable workshop on Complex Generic Drug Products.  The workshop opened with a general session explaining the opportunities for interacting with the FDA to get guidance and input while developing your complex generic and preparing your ANDA and how to get the most out of these interactions.

As agreed to during the GDUFA-II negotiations, sponsors of Complex Generic Drugs can request a Product Development Meeting with the FDA to discuss plans and proposals for developing the product and demonstrating bioequivalence.  Generally speaking, the FDA will grant such meetings if there is no Product-Specific Guidance for the reference product published on the FDA’s website here, or if you are proposing to use a different method for demonstrating bioequivalence than the method described in an existing PSG.  Furthermore, the meeting request must be prepared in accordance to the FDA’s draft guidance for Formal Meeting Between FDA and ANDA Applicants of Complex Products Under GDUFA <here>.

A successful request for a product Development meeting must include a pre-assigned ANDA file number.  If you don’t have one, this can be requested via the CDER’s NextGen Portal.  Also, your meeting request will need to include specific plans that you propose for developing your product and for demonstrating sameness and bioequivalence.  Your development plans should be supported by scientific data and the questions you wish to get answers to should include background information and data to support discussion points.

A project manager will be assigned from OGD’s Office of Research & Standards and, if necessary, your meeting request will be assessed by both OGD and OBP.

The FDA recommends that sponsors who would like to have a pre-submission meeting submit their meeting request approximately ten months before they plan to submit their ANDA.  This will allow time for the Agency to assess the meeting request, hold the meeting at least six months before the ANDA is to be submitted, and for the sponsor to address the Agency’s feedback in their application.  Details on preparing a pre-submission meeting request can be found in the FDA’s guidance <here>.  One significant bonus of requesting a pre-submission meeting is that it makes you eligible for a Mid-Review-Cycle Meeting by which the FDA meets with you (via teleconference) to provide a progress report on the review of your application.

Following the introductory session, I attended a breakout session at which the FDA discussed how to prepare a product development meeting request and what to expect from the meeting.  This breakout session used a mock topical ophthalmic liposomal eyedrop product as an example.  This was very informative, as the FDA session leaders provided a mock RLD package insert, several potential product formulations, possible analytical methods for product characterization and sameness demonstration, and a variety of proposed BE study designs.  The audience was expertly guided through the process of considering each of these topics and learning how to use them to develop a complex nano-liposomal topical product and to present the information in a pre-development meeting request package.  The details of this exercise are too extensive to go through here but suffice it to say that the audience learned a great deal and I encourage the FDA to repeat this workshop at future conferences.