OTP IND Milestone (Type B) Meetings
End of Phase (EOP) meetings (e.g., EOP1, EOP2)
The purpose of an End of Phase 1 meeting is to discuss further product development plans.
The purpose of an End of Phase 2 meeting is to determine the safety of proceeding to Phase 3, and to evaluate:
- the Phase 3 plan and protocols
- the adequacy of current studies
- plans to assess pediatric safety and effectiveness
- identify any additional information necessary to support a marketing application for
- the product and indications under investigation
- CMC readiness for Phase 3 (e.g., adequate critical quality attributes (CQAs) and qualified potency assay).
Submission of End of Phase (Type B) meeting requests to OTP
The sponsor should submit the meeting request as an amendment to the existing IND. The meeting request should include a list of the specific objectives of the meeting and a list of questions [grouped by discipline, e.g., Chemistry, Manufacturing, and Controls (CMC), pharmacology / toxicology, clinical, statistical].
Courtesy emails to the Regulatory Project Manager (RPM) for the IND and to OTPRPMS@fda.hhs.gov regarding submission of the meeting request to the file is greatly appreciated.
OTP does not send an acknowledgement email or letter following OTP’s receipt of a meeting request. However, by the timelines described in Table 2, OTP will send the decision to grant or deny the meeting request, along with the meeting date, if granted, or reasons for denial.
Table 2: Timelines for End of Phase (Type B) Meetings
OTP Response to Meeting Request** |
14 days |
|---|---|
|
Meeting Scheduling or WRO issued*** |
70 days |
|
Meeting package due to OTP |
At least 50 days before the scheduled date of the meeting or WRO**** |
|
Meeting Length |
60 minutes |
|
OTP Preliminary Response to questions in the package to Sponsor (for teleconferences or face-to-face meetings) |
NLT* 5 days before the meeting |
|
Sponsor’s Response to FDA preliminary response (for teleconferences or face-to-face meetings) |
NLT 3 days after receipt of Preliminary Responses |
*NLT – No Later Than
Source: Table 2 information from the Formal Meetings Between the FDA & 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.
**** If the scheduled date of a Type B (EOP) meeting is earlier than 70 days after FDA receipt of the meeting request, then the requester’s meeting package will be due no sooner than 6 calendar days after the date of the FDA letter granting the meeting.
When feasible, End of Phase 2 meetings generally should be held before the sponsor makes major commitments of effort and resources to specific Phase 3 trials. Sponsors should plan ahead and consider topics they will want to discuss at milestone meetings such as EOP, because OTP will not be able to honor requests for additional meetings, even if the sponsor considers these additional meetings to be urgent for their business needs. The scheduling of an End of Phase 2 meeting is not intended to delay the transition of an investigation from Phase 2 to Phase 3. It is expected, however, that the product development (CMC) program aligns with clinical development before initiating Phase 3 studies.
Only one meeting will be granted per milestone (e.g., one EOP2 meeting), if, upon evaluation, the stage of development matches the requested milestone. Milestone meetings should be multidisciplinary. OTP will not grant separate “clinical” and “CMC” EOP meetings. Many aspects of product development are interdependent; therefore, attempts to separate meetings into discipline-specific discussions can lead to inadvertent miscommunications and duplication of effort.
OTP will attempt to honor the requested format.
The meeting package for an EOP meeting is due 50 days before the scheduled meeting date. The package should include background information on the sponsor's plan for future Phase 2/ 3 studies as applicable, including summaries of the Phase 1 and 2 investigations, and the specific protocols for the proposed clinical study(ies). Additionally, for EOP2 meetings, the specific protocol for the Phase 3 clinical study(ies) should be accompanied by a detailed statistical considerations section, plans for any additional nonclinical studies if warranted, plans for pediatric studies, including a timeline for protocol finalization, enrollment, completion, and data analysis, or information to support any planned request for waiver or deferral of pediatric studies. In addition, the package should include information necessary to assess CMC readiness for Phase 3 (e.g., adequate Critical Quality Attributes (CQAs) and qualified potency assay).
-
Number of questions
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 12 questions (inclusive of sub-questions) would be considered reasonable. For example, Questions 1a, 1b, 1c, 1d, 2, and 3 would be 6 questions.
Written Response Only (WRO) is considered to be equivalent to 60-minute meetings. Therefore, the maximum of 12 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. OTP will not commit to reviewing packages greater than 250-300 pages or answering questions that require review of this much material.
-
Timing of meeting package submission
Sponsors should follow the timelines for meeting package submission, as described in the Formal Meetings Between the FDA & Sponsors or Applicants of PDUFA Products Guidance for Industry and as indicated above in Table 2. OTP will state the date a meeting package is to be submitted in the meeting confirmation notice when the meeting is granted.
Prior to the sponsor meeting
-
OTP will send the preliminary response according to the timeline indicated above in Table 2.
-
The sponsor is expected to respond to OTP’s preliminary responses according to the timeline indicated above in Table 2.
-
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 follow-up on topics from the preliminary responses or pose new questions, then the sponsor should submit these follow-up or new questions as an IND amendment.
- 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) that were 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 limit the time of 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 Minutes
OTP will issue meeting minutes within 30 calendar days after the meeting. OTP’s version of the meeting minutes is official and the final record of the meeting. OTP minutes 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 minutes 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 minutes.
If sponsors disagree with the content of OTP’s minutes, OTP’s meeting minutes will not be altered except to correct a substantive mistake for the record (on extremely rare occasions).
Request for Clarification
To ensure the sponsor’s understanding of OTP feedback from meeting discussions or a WRO, sponsors may submit clarification questions to the Regulatory Project Manager (RPM) within 20 calendar days following receipt of meeting minutes or a WRO. OTP will consider the request for clarification, and if determined to be limited to a clarifying nature (i.e., to confirm something in minutes or a WRO issued by OTP, rather than raising new issues or new proposals), OTP will issue a response in writing within 20 calendar days after receipt of the clarifying questions. OTP’s response will reference the original meeting minutes or WRO.