Generics Firms Improved Chances Of Winning Pre-ANDA Meetings For Complex Drugs Last Year

FDA officials said manufacturers of complex generic drugs submitted more approvable requests for pre-submission meetings for FY 2018. Official also clarifies at recent meeting when it's best to request a pre-ANDA meeting and when to submit a controlled correspondence.

It appears that generic drug manufacturers have figured out what it takes to get a pre-application meeting request approved by FDA for abbreviated new drug applications for complex generics.

At the end of fiscal year 2018, the agency approved more than two thirds of the requests for these meetings. That's an improvement over the beginning of the year when the agency approved only half of these requests. Many of the requests for meetings are from sponsors seeking clarification on the route of delivery, followed by questions related to drug and device combination products.

An FDA official also clarified when it is best to request a pre-ANDA meeting and when to instead submit a controlled correspondence.

Katherine Tyner, associate director of science for FDA’s Office of Pharmaceutical Quality, gave an update on the GDUFA II pre-ANDA program for complex generic products on March 5 at a meeting sponsored by the International Forum and Exhibition on Process Analytical Technology (Process Analyses & Control), or IFPAC, in North Bethesda, Md.

The pre-ANDA program was established by GDUFA II to clarify regulatory expectations for prospective applicants early in product development, to assist applicants to develop more complete submissions, to promote a more efficient and effective ANDA and to reduce the number of review cycles required to obtain ANDA approval, particularly for complex products. It was included among the FDA commitments for the renewed generic drug user fee program, which began in October 2017. (Also see "US FDA Commits To Meeting With Complex ANDA Sponsors, Works Hard To Avoid It" - Pink Sheet, 24 Oct, 2017.)

The GDUFA II agreement allows for three types of meetings: pre-ANDA submission meetings, product development meetings and mid-cycle review meetings.

Generic Industry Has Made Progress

Initially, pre-ANDA meetings were proving difficult to book, as about half of the requests were denied, often because the topic did not warrant an actual meeting, or the pre-meeting package was inadequate. (Also see "Pre-ANDA Meetings Proving Tough To Get – Nearly Half Of Requests Denied" - Pink Sheet, 24 May, 2018.)

Yet more recently in September, FDA officials told a generic drug meeting that more than two-thirds of the meetings requests were approved as sponsors and FDA grew more comfortable with the system and requirements. (Also see "FDA Approving Complex Generics Pre-ANDA Meeting Requests At Higher Rates " - Pink Sheet, 21 Sep, 2018.)

The industry has sustained its progress in getting meeting requests approved.

During the first year of the program in fiscal year 2018, FDA approved 57%, or 48 of the 83 requests for pre-ANDA meetings. Yet out of the 83 requests, 17 were cancelled at the sponsor’s request, and if the cancellations are not factored in, the approval rate is higher at 68% of meeting requests being approved. Sponsors cancelled meetings because the sponsor's questions were resolved by FDA in a preliminary written response.

Most of the requests for meetings center on questions related to the route of delivery at 42%, while 22% are related to drug and device combinations, and 13% on the active ingredient, 12% on the dosage form, 5% on the formulation and 4% for other reasons.

Tyner added that before submitting meeting requests for meetings on drug and device combination products, sponsors should first read FDA’s “Guidance on Comparative Analysis and Related Comparative Use Human Factor Studies for Drug-Device Combination Products Submitted in an ANDA.” Applicants of these products should also consider when and how to submit the device, as part of a meeting request or a controlled correspondence, and whether the product is a prototype of a final design.

Tyner said that requests are denied because either an incomplete meeting package was submitted, the product was not deemed a complex product, the wrong type of meeting was chosen, the request should have been subject to a controlled correspondence rather than a meeting, or a product-specific guidance was already available.

How To Determine Differences

Tyner said it is important to know the difference between a controlled correspondence and a request for a product development meeting so requests are not denied because sponsors asked for the wrong type of meeting.

She said that controlled correspondence should be reserved for clarifications on agency guidance, while pre-ANDA meetings are best for multidisciplinary questions. A controlled correspondence is best used for single questions or a small group of closely related questions.