How to successfully navigate through Type B and C meetings with the FDA
by Annegret Vaggelas and Gabriele Dallmann
At Biopharma Excellence we are frequently involved in scientific advice procedures, going up to as much as six agency meetings a month covering FDA, EMA and national agencies in the EU. Depending on the agency, timetables, meeting structure and conduct itself vary considerably. In this article we give some hands-on advice on how to successfully navigate through Type B and C meetings with FDA based on our recent experience with FDA.
In September our team has been involved in six scientific advice procedures covering FDA, EMA and national agencies in the EU. These agency interactions were prepared with different clients for two ATMPs, two recombinant protein, one vaccine and a small molecule. The aim of a scientific advice is to present your envisaged development program to the agency and to obtain relevant feedback for preparation of the next milestones (e.g. CTA or IND submission prior to start of the first-in human study, overall clinical development program).Scientific advice can help to prepare a smooth CTA/ IND authorization and to help planning of the clinical development, especially if the product is innovative, if it is a first-in-class product or if not much experience is available from past clinical studies. The six meetings in September included three pre-IND Type B meetings with FDA where we discussed the CMC, nonclinical package and clinical study protocols intended for the submission of the respective INDs (two for Phase 1 and one or the pivotal study of the respective products). At EMA, we presented the total clinical program for approval of a recombinant protein via centralized procedure. In the national procedures, we discussed the CTA package for a vaccine derived from a novel expression system and presented the repurposing strategy for a small molecule following a rarely used regulatory pathway.
Depending on the agency chosen, the procedures and timetables for obtaining scientific advice but also the meeting structure and conduct itself vary. From our recent experience with FDA we specifically want to give some hands-on advice on how to successfully navigate through Type B and C meetings with FDA.
According to the FDA guidance, the meeting request for a Type B meeting has to be sent 60 days (for type C 75 days) in advance of the envisaged meeting date. But it very much depends on the availability of the required FDA staff if a meeting date is actually granted within this timeframe. Based on our recent experience CBER granted one Type B meeting up to a month later than the 60 days given by the guidance whereas another one was granted exactly at one of the proposed dates. If the meeting is requested for the summer months, the postponement might be due to the popular vacation period, however, we feel that there are simply a lot of meeting requests arriving at CBER, which limits their availability. Thus, companies should be prepared for delays in the meeting schedule and rather plan in some flexibility.
The meeting confirmation, in our case, was received in all cases in the time period defined by the 21-day timeframe given in the guidance, i.e. ~2.5-3 weeks after submission of the meeting request. Still in the worst case, this could mean that the briefing package has to be submitted just ~1 week after receipt of meeting confirmation (30 days prior to the meeting). Thus, the briefing package should be prepared well ahead and latest as soon as the request is sent out to FDA. But of course, if the meeting date is later than envisaged, the submission of the briefing package will also get postponed.
The next important milestone on the way to an FDA meeting is the receipt of the preliminary FDA responses. According to FDA guidance, the preliminary response should arrive 5 days prior to the meeting and the requester has to notify FDA not later than 3 days before the meeting if meeting is still needed. In reality, FDA did not adhere to this timeline and the preliminary responses were received only 2 days before the meeting and due to the time difference between EU and US it effectively arrived in the EU at EOB, which further adds complexity to the process. Thus, the teams are ultimately left with one day for the assessment of the preliminary responses, the decision making if a meeting is still required, and the preparation of the agenda with the topics to be discussed during the meeting, including the required brief rationale for requiring further discussion. This agenda has to be sent 24 hours before the meeting to the FDA. This tight schedule requires quick action and can be quite challenging for teams with e.g. little experience of agency interaction or with team members in different time zones. Therefore, the process should be clearly discussed upfront, responsibilities assigned and timeslots for discussion reserved. In general, there is the option to resolve only minor clarification points regarding the FDA responses/comments via email, but also this requires fast decisions.
In case it was decided to proceed with the meeting as scheduled, the preparation for the FDA meeting continues. The next steps on the team’s agenda should be the preparation of a presentation to facilitate the discussion during the meeting as well as a rehearsal with the team, where clear roles & responsibilities are defined. The presentation should be sent a couple of hours before the meeting to the FDA project manager. Thus, very structured and focused work is required to achieve this in the little time left. The slides should focus on the points for discussion and no time should be spent on introductory slides. A meeting lasts ~50 minutes but actually there is much less time for the discussion of the topics due to the new pilot for capturing meeting summaries in real time. This means that the FDA team captures the meeting minutes during the meeting, which cuts the total discussion time to 30-40 minutes at best. For this, following discussion of each question or comment FDA will mute the phone while they internally summarize the text of the final FDA response or comment. One person from FDA will then read the captured summary and inquire whether any additional clarification is needed. Thus, no more than ~30 minutes should be planned for discussion time. The clear advantage of the real-time meeting minutes pilot is that the final meeting summary is sent much earlier than 30 days after meeting. Based on our experience this could be expected ~8 days after the meeting.
As Biopharma Excellence regularly prepares and conducts numerous FDA meetings, EMA scientific advices or protocol assistance meetings and national scientific advice procedures, we have substantial experience on all points relevant for a successful meeting: How to present the topics of interest well to the different agencies, how to identify the right questions, how to prepare a briefing book that allows the agency to understand the case very well and how to receive a positive feedback on your questions. We at Biopharma Excellence are happy to support you in the preparation of an agency meeting and ultimately make it a successful interaction. To learn more about our services in this area, please contact us.