Your team has officially submitted a new drug application, biologics license application, or supplement for a new indication to the U.S. Food and Drug Administration (FDA). Congratulations! Now the review process starts and while waiting on the filing determination, you start diving into all the tasks you may have neglected in the final push to submit your application.
But be sure to monitor your inbox, because for certain applications the review division may request your participation in an application orientation meeting, or an AOM.
Haven’t heard of an AOM before? Neither had I, really.
I recently sat down with my colleague, Loren Reside, to get a better sense of why the FDA requests these meetings – and the role they play in the regulatory review process.
Loren, a veteran regulatory communications specialist, and the 3D team have partnered with leading pharma companies on their strategic approach to AOM requests and their preparation for these important interactions.
Penny: Loren, can you explain a little about the history of an AOM and the purpose of these meetings?
Loren: Well, the concept of an AOM came about as a component of PDUFA V, to broaden communication between FDA and applicants. Like an FDA Advisory Committee meeting, AOMs require sponsors to deliver a formal presentation that summarizes findings from their development program that support the marketing application. However, unlike an advisory committee meeting, AOMs are completely optional.
The FDA typically requests an AOM to directly discuss the content or format of the company’s application and to gain important insights early in the regulatory process.
Penny: And how many AOM meetings have you been involved in recently?
Four within the last year.
Penny: Four within just a year seems like a lot, is the FDA requesting these meetings more often?
Loren: Yes, in my experience we have seen an increase in requests over the past couple of years. This seems to be based on the heightened focus in drug development for orphan indications and breakthrough therapies, because these tend to be the applications that primarily receive requests. However, the agency may also request an AOM for non-priority applications that pose unique regulatory policy questions.
Penny: And as I understand it, the sponsor can request this meeting as well?
Loren: Yes, they can. We have largely been involved in AOMs that were requested by the FDA, but the sponsor can also request one should they see a need.
Penny: When does the FDA normally notify the sponsor that they’d like to hold an AOM?
Loren: Typically, they are requested and held within 45 days of submission. However, as you can imagine – it may take time from submission for the FDA to begin their review and determine the need for an AOM, so the sponsor may have very little time to prepare for the meeting.
We’ve worked with sponsors who received FDA’s request for a meeting as little as two weeks before the proposed meeting date.
Penny: Sounds like a difficult task to prepare for such an important meeting in such a short period of time.
Loren: Yes, it can be stressful, especially given everything else a team may have going on at the time. However, a professional presentation is critical since this is a sponsor’s first real opportunity to review data in detail with the agency.
Penny: Who typically attends an AOM?
Loren: Well, it depends. For the most part, it’s the FDA review team, including the regulatory project manager, the application review team, the cross-discipline team leader, and the review division and Office of New Drugs leadership. This is not exclusive though, as other members can be invited to join. If it is a Project Orbis application involving concurrent submission and review among international partners, then participating regulatory authorities like the Australian Therapeutic Goods Administration or Health Canada, for example, may join as well.
Penny: And is the structure of these meetings like other regulatory meetings with the FDA?
Loren: Actually, AOMs are typically two-part meetings. The first part is a one-hour meeting with 35 to 40 minutes allotted for a sponsor presentation and 25 to 20 minutes for a question-and-answer period immediately following. The second part includes a technical walkthrough, where the applicant may review the submission datasets with the FDA review team.
Penny: What can the sponsor expect in terms of meeting flow and the agenda?
Loren: For an AOM in the virtual setting, there is usually a technical check an hour before with the FDA regulatory project manager, to confirm who from the sponsor will share slides and to perform an audio check for presenters.
The FDA may choose to do brief introductions for review team participants – but from what we’ve seen, it varies.
In terms of the sponsor’s presentation, the FDA usually requests a long list of topics be covered. From the proposed indication and dosing recommendation, the risk/benefit profile and what makes the mechanism of action unique – to the regulatory history, study design, and key findings. In addition, depending on the product, the sponsor may need to cover topics like biomarker development, assay validation, chemistry, manufacturing, and control (CMC) issues, as well as other nonclinical, clinical pharmacology, or Risk Evaluation and Mitigation Strategy (REMS) details.
Penny: Seems like quite a lot to cover in less than 40 minutes.
Loren: Yes, sponsors must often cover more material than they would in an advisory committee meeting, but with less time to present and less time to prepare. That’s why having a solid strategy, clear messages, and a process for preparation and practice is so important.
Penny: So what happens after the presentation?
Loren: The FDA will open the floor to the team of reviewers and other FDA attendees for questions. And once the team is out of questions or the 20 to 25 minutes is up, the first part of the meeting concludes. The meeting is then followed by the second part, which is the “technical walkthrough” to review the datasets.
Penny: One final question comes to mind. Since this is not a mandatory meeting, do sponsors have to accept the invitation?
Loren: No, sponsors are not required to accept an invitation to participate in an AOM.
But I would strongly recommend that they do – even if given only two weeks to prepare.
In Part 2 of Penny’s interview, Loren will elaborate on why sponsors should accept an AOM meeting and importantly, how to prepare for success.