Commenters on FDA’s PSG meeting guidance want better alignment with GDUFA commitments

The US Food and Drug Administration’s (FDA) draft guidance on product-specific guidance (PSG) meetings for abbreviated new drug application (ANDA) applicants under the reauthorization of the Generic Drug User Fee Amendments (GDUFA III) garnered few comments from stakeholders, but those who did choose to weigh in are concerned that the agency may be proposing processes inconsistent with the goals of its GDUFA III commitment letter.

The draft guidance outlines FDA’s thinking on how ANDA applicants can request and conduct PSG-specific meetings with the agency, detailing information on teleconferences as well as pre-submission and post-submission PSG meetings.

FDA’s guidance is “intended to provide procedures that will promote well-managed PSG meetings and help ensure that such meetings are scheduled and conducted in accordance with the time frames set forth in the GDUFA III commitment letter,” the agency wrote. (RELATED: Guidance: FDA details ANDA PSG meetings under GDUFA III, Regulatory Focus 20 February 2023)

AAM: FDA is interpreting GDUFA III too narrowly

Commenting on the draft guidance, the Association for Accessible Medicines (AAM) said they were concerned FDA was reading the GDUFA III commitments in a way that would deter their use.

“FDA seems to be reading the commitments more narrowly than intended and imposing restrictions and limitations that will make it more difficult for applicants to request and receive timely PSG teleconferences and pre- and post-submission PSG meetings,” they wrote. “As a result, ongoing development programs or pending ANDAs could be adversely affected, and approvals delayed, because applicants will not have clear direction on whether and if so how the new or revised PSGs will affect their ANDAs.”

AAM disagreed with FDA’s proposal to limit discussion within PSG teleconferences to only PSG approaches, rather than having the option to also discuss alternative approaches within the meeting. The current proposal for PSG teleconferences also does not describe a situation where FDA could theoretically agree with a sponsor’s approach and offer feedback.

“This limitation will negate the utility of the teleconference and likely guarantee that a further communication will be required, which could unnecessarily consume both applicant and FDA resources,” they said. “Determining the impact of a new or revised PSG on the applicant’s development program will require discussion of an approach other than the approach recommended in the PSG, i.e., the study that the applicant has already begun or completed.”

AAM said FDA should “implement the Commitment Letter as it was written, and, to the extent possible, reduce the obstacles that can hinder timely, meaningful communication about PSGs and delay applications.” This includes not distinguishing between pre-submission and post-submission teleconferences and applying a 30-day timeframe for holding a PSG conference as outlined in GDUFA III “even if the request for a teleconference is submitted more than 60 days after the new or revised PSG is published.”

“The guidance provides too much discretion to FDA to deny PSG teleconferences and meetings, raising the concern that applicants are going to be shut out of meaningful communication with FDA about PSGs despite the GDUFA III commitments,” AAM wrote.

Teva: Guidance inconsistent with GDUFA III commitment letter

Noting similar concerns, Teva Pharmaceuticals highlighted the historical problem of FDA issuing PSGs for bioequivalence studies and active ingredient sameness and device comparability, sometimes revising the PSGs one or more times while generic drug manufacturers have dedicated “extensive development work” on a proposed product. When FDA requires ANDA applicants to adhere to new PSGs in the middle of a proposed generic product’s development, it can add to the expense and delays in ANDA approvals.

“The PSG teleconference and meeting process was negotiated as part of GDUFA III specifically to ameliorate this problem,” Teva said. However, the current draft guidance “will not serve the intended purpose of mitigating the 'moving target' problem” and is overly burdensome and inconsistent in places, which may discourage sponsors from using it.

Citing the example of mid-cycle review meetings under GDUFA II, Teva said “FDA restricted the interaction during those meetings so much that they became of little value,” but acknowledged the agency made significant changes in this area under GDUFA III.

Teva agreed with AAM that FDA should revise PSG meeting guidance so that other issues related to scientific or regulatory bioequivalence can be discussed during teleconferences, calling the current proposal a “one-sided communication” where FDA offers their feedback on the impact of PSG recommendations without further discussion.

“Teva believes this proposed one-sided communication is unnecessarily restrictive, not useful, and inconsistent with the process agreed to during the GDUFA III negotiations, as set forth in the Goals Letter,” they said. “The parties who proposed and negotiated this process envisioned PSG Teleconferences as an efficient way for ANDA sponsors to engage in a two-way dialogue with FDA about the potential effects of a new or revised PSG.”

The company said the proposal as currently written is likely to discourage use of PSG teleconferences and meetings. Teva agreed with AAM that the draft guidance distinguishing between pre-submission and post-submission PSG teleconferences, and its proposal to not honor a 30-day timeline for holding a teleconference if the sponsor does not submit a request within 60 days of receiving a new or revised PSG are both “inconsistent with the GFUFA III Goals Letter.”

Further, Teva noted the requirement for submitting a protocol summary for PSG teleconferences is also inconsistent with GDUFA III. “While this may not be a major burden to some sponsors, it highlights again the fact that the draft guidance is inconsistent with the GDUFA III Goals Letter and suggests again that the only appropriate subject of discussion at a PSG Teleconference is the in vivo work, which is not the case,” they said.

Viatris: More detail on when PSG meetings are appropriate

International pharmaceutical and healthcare company Viatris asked FDA to provide more detail on when PSG teleconferences and meetings should be used, rather than other methods of communication such as controlled correspondence (CC).

“[T]he Draft Guidance states that a pre-submission or post-submission PSG meeting may be denied if the inquiry would be appropriately addressed through a controlled correspondence,” they said. “Yet, there is no granularity as to how FDA makes this determination. If an applicant mistakenly submits a request for a PSG meeting in lieu of CC due to lack of clarification around when a CC or another meeting type is more appropriate, then time may be wasted as the timelines for each option differ.”

To reduce ambiguity in the draft guidance and lower the likelihood of sponsors submitting multiple meeting or communication requests, Viatris requested FDA “address specific instances where inquiries appropriate for PSG meetings are better suited for a controlled correspondence or another type of communication and consider expediently notifying applicants when a PSG meeting request is denied because the inquiry is more appropriate for another communication method.”

“Clarity on FDA’s thinking will bring greater predictability and efficiency to generic drug review, which ultimately will help ensure patients have access to quality, safe, and effective generic drugs,” they wrote.

Draft guidance

Commenters on FDA’s PSG meeting guidance want better alignment with GDUFA commitments

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