OTP Type C Meetings to Discuss New Surrogate Endpoint(s)
Submission of Type C Meeting Requests to OTP, to Discuss New Surrogate Endpoint(s)
Type C Meetings to Discuss New Surrogate Endpoint(s) are a type of formal meeting with FDA for development programs where the sponsor intends to use a biomarker as a surrogate endpoint that has not been used previously as the primary basis for product approval in the proposed context of use. This meeting will apply to new surrogate endpoints in support of either accelerated or traditional approval. The purpose of this meeting is to discuss the feasibility of the surrogate as a primary endpoint and identify any gaps in knowledge and discuss how they might be addressed. The outcome of this meeting may require further investigation by the sponsor and discussion and agreement with OTP before the surrogate endpoint could be used as the primary basis for product approval. This meeting is expected to occur when the sponsor has preliminary clinical study results that show that the proposed biomarker responds to the candidate product at doses that appear to be generally tolerable.
The sponsor should submit the meeting request as an amendment to the existing IND or as a pre-submission if the sponsor does not have an IND or BLA with OTP. The meeting request should include a list of the specific objectives of the meeting and a list of questions.
OTP does not send an acknowledgement email or letter following OTP’s receipt of a meeting request. However, by the timelines described in Table 8, OTP will send the decision to grant or deny the meeting request, along with the meeting date, if granted, or reasons for denial.
Table 8: Timelines for Type C Meetings to Discuss New Surrogate Endpoint(s)
|
OTP Response to Meeting Request** |
21 days |
|---|---|
|
Meeting Scheduling or WRO issued*** |
75 days |
|
Meeting Package Due to OTP |
With the Meeting Request |
|
Meeting Length |
60 minutes |
|
OTP Preliminary Response to Questions in the Package to Sponsor |
NLT* 5 days before the meeting |
|
Sponsor’s Response to FDA Preliminary Response |
NLT 3 days after receipt of Preliminary Responses |
*NLT – No Later Than
Source: Table 8 information from the Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products Guidance for Industry
**Calendar days from FDA receipt of the meeting request to the date that OTP will respond with the decision to grant or deny the meeting, as well as specifying the format and date of the meeting, if granted.
*** Calendar days from FDA receipt of the meeting request to date the meeting will be held, or the WRO will be issued.
Meeting Package and Number of Questions
Unlike other Type C Meeting requests, for Type C Meetings to Discuss New Surrogate Endpoint(s), the meeting package should be submitted with the meeting request, which includes preliminary human data indicating impact of the product on the biomarker at a dose that appears to be generally tolerable.
Please refer to Considerations for Discussion of a New Surrogate Endpoint(s) at a Type C PDUFA Meeting Request document and "Early Engagement with FDA to Discuss Novel Surrogate Endpoints" November 27, 2018 Issue | FDA to prepare the meeting package.
The sponsor’s meeting package should include a limited number of clearly worded and targeted questions that directly address concerns about the drug development programs. The number of questions in a meeting package should not exceed what can be reasonably discussed within the duration of the allotted meeting time. For a 60-minute meeting, a maximum of 10 questions (inclusive of sub-questions) would be considered reasonable. For example, Questions 1a, 1b, 1c, 1d, 2, and 3 would be six questions. Written Response Only (WRO) is considered to be equivalent to 60-minute meetings. Therefore, the maximum of 10 questions (inclusive of sub-questions) is applicable.
Size of Meeting Package
It is important to include background information sufficient to support the questions in the package. OTP may cancel a meeting if the meeting package is grossly inadequate and does not contain sufficient information to enable FDA to address the questions. However, voluminous meeting packages are discouraged. Meeting packages are typically 50 – 100 pages. OTP will not commit to reviewing packages greater than 250-300 pages or answering questions that require review of this much material.
Prior to the Sponsor Meeting
- OTP will send the preliminary response according to the timeline indicated above in Table 8.
- The sponsor is expected to respond to OTP’s preliminary responses according to the timeline indicated above in Table 8.
- If the sponsor finds that OTP’s preliminary responses and advice are sufficiently clear and complete to obviate the need for further discussion, the sponsor should inform OTP in writing as soon as possible so that OTP may cancel the meeting. These responses would then become the official OTP responses to the sponsor’s questions.
- If, after cancellation of the meeting, the sponsor subsequently wishes to seek clarification from the preliminary responses, then the sponsor may submit a request for clarification. Find out more about Requests for Clarification
- If the sponsor wishes to continue with the meeting, the sponsor should identify which of the original questions in the briefing package they wish to discuss and list the questions in the proposed order of discussion. As a general rule, the order of discussion is usually the order of importance to the sponsor. When referencing questions, the sponsor should use OTP’s preliminary responses document numbering format.
- After receiving OTP’s preliminary response, the sponsor should not submit new questions and new information (e.g., alternative approaches or new proposals to address OTP comments) not previously submitted in the original briefing package. OTP preliminary responses are prepared after deliberative review, and usually include cross-discipline internal discussion, of the original meeting package and questions. OTP will not have adequate time to review new material and have sufficient inter-discipline internal discussion necessary to prepare answers to new questions. Therefore, sponsors should thoughtfully prepare their meeting package and questions.
- In some situations, a sponsor may want to develop new questions/alternative approaches in response to OTP’s preliminary responses or discussion at the meeting. Such new questions/alternative approaches should be submitted as an amendment to the sponsor’s existing IND.
During the Meeting
The meeting is the sponsor’s opportunity to obtain clarifications on OTP preliminary responses. As stated above, during the meeting the OTP team will not be able to provide feedback on new information (e.g., new question, alternative approaches or new proposals to address OTP comments) that was not previously submitted in the original briefing package.
Sponsors may choose to make a presentation at the beginning of the meeting. However, because OTP staff will be familiar with the meeting package content and questions, OTP recommends that sponsors forgo a presentation and use the allotted meeting time to obtain clarifications to OTP’s preliminary responses to the sponsor’s questions.
OTP recommends that time be reserved at the end of the meeting for the sponsor to summarize the major discussion points and action items.
Meeting Summary
OTP will issue a meeting summary within 30 calendar days after the meeting. OTP’s version of the meeting summary is official and the final record of the meeting. OTP summaries are not a meeting transcript, but focus on any clarifications (e.g., of unclear preliminary responses), agreements and disagreements, and action items as discussed during the meeting.
The sponsor may submit their version of the meeting summary to the file to summarize their understanding of issues discussed at the meeting. However, OTP may not review such submissions; therefore, the absence of an OTP response to such submissions does not imply OTP concurrence with the sponsor’s version of the summary.
If sponsors disagree with the content of OTP’s meeting summary, OTP’s meeting summary will not be altered except to correct a substantive mistake for the record (on extremely rare occasions).
Requests for Clarification
A request for clarification may be sought after a Type C Meeting, to ensure the requestor’s understanding of OTP's feedback provided in a preliminary response (if the formal meeting was canceled), meeting summary or written response issued by OTP.
Find out more about Requests for Clarification
Resources:
- Considerations for Discussion of a New Surrogate Endpoint(s) at a Type C PDUFA Meeting Request
- Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products
- Surrogate Endpoint Resources for Drug and Biologic Development | FDA
- "Early Engagement with FDA to Discuss Novel Surrogate Endpoints" November 27, 2018 Issue | FDA