FDA Brings its Formal Meetings Guidance Up to Date: What You Need to Know About Type D, INTERACT, and “In-Person” Meetings Under PDUFA
Much has changed since the long-gone days of 2017. The Washington Nationals won the World Series, Presidential administrations have come and gone, and FDA has added new meeting types and formats to its menu. And so, FDA has issued a new draft guidance to bring everyone up to speed on formal meetings under PDUFA. While the Nats being replaced by the Orioles as the dominant home team did not get a mention in the new Draft Guidance, there were plenty of other interesting changes made to the old 2017 draft guidance. Many of these changes are not specifically “new,” but the draft guidance formalizes them to a certain extent and puts them all in one place – until more changes are made, that is.
The biggest changes are the addition of Type D and Initial Targeted Engagement for Regulatory Advice on CDER and CBER ProducTs (INTERACT) meetings to the four types already present (Types A, B, B (end of phase), and C), and the addition of additional meeting formats.
Type D Meetings
Type D meetings were first introduced in the PDUFA VII goals letter, and much of the language from that letter is repeated verbatim in the new draft guidance. A Type D meeting is a meeting focused on a narrow set of issues (not more than two topics and associated questions) that are used to discuss issues at key decision points. Examples of Type D meeting requests are described in the new draft guidance:
- A follow-up question raising a new issue after a formal meeting (not just a clarifying question – more on that later)
- A narrow issue on which the sponsor is seeking input with only a few (3-5) associated questions
- A general question about an innovative development approach that does not require extensive, detailed advice
Also, the issues should not require input from more than three disciplines or divisions. The meeting package for Type D meetings should be included with the meeting request. The new draft guidance warns that sponsors should not request several Type D meetings in temporal proximity instead of a single Type C meeting. If the request does not fit into the narrow Type D window, a Type C meeting is generally the appropriate meeting type. FDA will convert the meeting to the appropriate meeting type (B or C) if the sponsor submits an inappropriate Type D meeting request, and the sponsor can either withdraw their request or accept the conversion without submitting a new meeting request. The draft guidance helpfully adds a few examples of appropriate Type D meeting scenarios, and they are:
- A specific question about an aspect of a complex or innovative trial design (e.g., innovative pediatric design approach)
- A specific question about presenting data following a pre-BLA/NDA meeting
- A specific follow-up question about a new idea stemming from a Type C meeting
The timelines for Type D meetings were added to the very helpful tables in the draft guidance. FDA intends to respond to a Type D meeting request within 14 days from receipt and to schedule a meeting or issue written responses within 50 days of receipt of a request. FDA intends to provide preliminary responses to Type D meeting packages no later than 5 calendar days before the meeting date. The goal for meeting minutes is the same as all other meeting types – 30 days after the meeting.
In our experience, Type D meetings are being granted as written responses only (WRO), so no videoconference/teleconference option. So, these do not seem to be a suitable place for topics that, while narrow, would benefit from a dialogue with FDA. In fact, it seems to us that the Type D meeting provides an opportunity to elicit iterative input from the Agency given that many Type C meetings and even some Type B meetings are being granted as WRO in recent years. With the live discussion by phone or video, it had been difficult for sponsors to ensure their briefing materials, often consisting of complex data and issues, were understand and that they had clarity around FDA’s written feedback.
INTERACT meetings have a bit of a longer history than Type D meetings, but not much (although they replaced the older “pre-pre-IND meetings”). INTERACT meetings are for novel products and development programs that present unique challenges early in development (before filing an IND or having a pre-IND meeting) and are intended to facilitate IND-enabling efforts where there are novel or challenging issues. The issues appropriate for an INTERACT meeting typically relate to IND requirements, such as questions about IND-enabling studies, complex manufacturing technologies or processes, development of innovative devices used with a drug or biologic, or the use of New Approach Methodologies (methods to be used in place of traditional animal testing). The sponsor needs to have selected a specific investigational product or have a product-derivation strategy to evaluate in a clinical study before requesting an INTERACT study. Like with Type D meetings (and Type A meetings and Type C meetings about a novel surrogate endpoint), the meeting package should be included with the meeting request.
The new draft guidance also describes some questions and topics that would be appropriate for an INTERACT meeting:
- Choice of appropriate preclinical models or toxicology studies for novel drug platforms or drug candidates
- CMC issues or testing strategies aimed to demonstrate safety adequate to support a first-in-human (FIH) study
- Advice related to the design of proof-of-concept or other pilot safety/biodistribution studies necessary to support a FIH trial
- General recommendations about a future FIH trial where the population is novel and there is no prior precedent or guidance
- Recommendations on approach for further development of an early-stage product with limited CMC; pharmacology/toxicology; and/or clinical data that were collected outside of a U.S. IND
For INTERACT meetings, FDA intends to respond to a meeting request within 14 days of receipt and to schedule a meeting or issue written responses within 75 days from receipt of the meeting request. FDA intends to provide preliminary responses to INTERACT meeting packages no later than 5 calendar days before the meeting date. For INTERACT meetings, in lieu of meeting minutes, preliminary responses will be annotated and resent within 30 days if the advice provided changes as a result of the meeting.
In our experience with INTERACT meetings prior to their formalization as part of PDUFA, these meetings were often limited to very early development where there were novel CMC/manufacturing issues. Meeting questions pertaining to proposed, novel nonclinical development plan or any clinical development issues were explicitly excluded as being premature for an INTERACT meeting. So, it will be interesting to see whether FDA’s practices change given how their own guidance explicitly includes those very topics as within the scope of an INTERACT meeting.
New Meeting Formats
Back in the old days of 2017, everyone knew that face-to-face meant your face was in the same room as the other faces. Now, we know better. As such, the new draft guidance breaks down face-to-face into “In person face-to-face” and “Virtual face-to-face (video conference).” Moreover, for in-person face-to-face meetings, “core” attendees (those with primary speaking roles) will participate in-person with the sponsor/applicant at FDA, but there will be a hybrid virtual component for “non-core” participants. The new draft guidance states that individuals expected to have a more peripheral role (such as to answer one possible question) may participate virtually to save room for the “core” attendees. The “core” sponsor personnel should plan to attend in person (or otherwise a virtual face-to-face meeting should be requested), but “core” attendees may join virtually if they are suddenly unable to attend in-person.
That brings us to virtual face-to-face meetings, where attendees participate remotely on a virtual meeting platform, with “core” attendees’ cameras on. In the previous draft guidance, teleconference/videoconference meeting formats were combined in the same category, but now that face-to-face means face-to-webcam as well, the new draft guidance distinguishes between the two. However, it is possible that the only difference between a teleconference and a “virtual face-to-face” conference is that the cameras on Zoom (or other platform) are off.
This is understandably very confusing terminology. You may have even had to reread what we wrote a couple of times just to make sure you understood. So, we encourage sponsors requesting meetings to be clear and not use “face-to-face” alone if trying to request an “in person” meeting, as FDA could interpret that as a request for a “virtual cameras on” meeting.
The new draft guidance makes various other changes as well.
For meeting requests, it specifies that there should be generally no more than 10 total consecutively numbered questions in a meeting request and that meeting requesters should not submit subquestions (1a, 1b, etc.) – these will be counted toward the overall number of questions regardless. The new draft guidance also includes Type D, INTERACT, and all Type C meetings along with the previous draft guidance’s inclusion of pre-IND and Type C meetings other than those for a new surrogate endpoint as the types where FDA may convert to written response.
The new draft guidance states that requestors are “encouraged” to include their meeting packages for all meeting types, if possible. For both meeting requests and meeting packages, the new draft guidance also removes descriptions of old-fashioned paper submissions to FDA for meetings – everything should be submitted electronically, though, if necessary, noncommercial IND holders may also submit via the appropriate center’s document room.
In responding to meeting requests, FDA still reserves the right to determine what format is most appropriate. If WRO is the type granted, FDA will notify the requester of the date it intends to send the written response in its response to the meeting request. The new draft guidance also explicitly encourages sponsors to submit a rationale in a follow-up correspondence if they believe a meeting is needed instead of written responses, and FDA may or may not convert it back to a live meeting format.
Finally, the new draft guidance adds a paragraph to the end of the draft guidance stating that sponsors may submit a “follow-up opportunity/clarifying questions” correspondence in formal submission to their application to ensure their understanding of FDA feedback. Such correspondence should be sent as a “Request for Clarification” within 20 calendar days following receipt of meeting minutes or written responses (or preliminary comments if the meeting is cancelled), and FDA intends to respond within 20 calendar days of receipt. This correspondence should only include questions of a clarifying nature, not new issues or proposals (or a Type D meeting could be appropriate). However, even if this correspondence is out of scope, if the issue is narrow and focused, the review division may provide a response as soon as reasonably possible. We are relieved to see this opportunity to ask follow-up clarifying questions after an FDA meeting was not eliminated with the advent of the Type D meeting, as they both seek to serve similar goals. Often, timely clarification can be the difference between a sponsor being able to submit a final study protocol and initiating recruitment or being able to finalize an NDA/BLA submission – where every day is material to the company.
P.S. – As this post publishes, the Orioles may have just cemented the AL East Division title. Something we would have never imagined given the rebuild that started back in the long-gone days 2017. Let’s go O’s!