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 OTAT
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 OTATRPMS@fda.hhs.gov regarding submission of the meeting request to the file is greatly appreciated.
OTAT does not send an acknowledgement email or letter following OTAT’s receipt of a meeting request. However, by the timelines described in the Table, OTAT will send the decision to grant or deny the meeting request, along with the meeting date, if granted, or reasons for denial.
OTAT Response to Meeting Request**
Meeting Scheduling or WRO issued***
Meeting package due to OTAT
At least 50 days before the scheduled date of the meeting or WRO****
OTAT 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 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 OTAT 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 OTAT 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. OTAT 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.
OTAT 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. OTAT 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. OTAT 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 the Table. OTAT 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
OTAT will send the preliminary response according to the timeline indicated above in the Table.
The sponsor is expected to respond to OTAT’s preliminary responses according to the timeline indicated above in the Table.
If the sponsor finds that OTAT’s preliminary responses and advice are sufficiently clear and complete to obviate the need for further discussion, the sponsor should inform OTAT in writing as soon as possible so that OTAT may cancel the meeting. These responses would then become the official OTAT 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 OTAT’s preliminary responses document numbering format.
- After receiving OTAT’s preliminary response, the sponsor should not submit new questions and new information (e.g., alternative approaches or new proposals to address OTAT comments) that were not previously submitted in the original briefing package. OTAT preliminary responses are prepared after deliberative review, and usually include cross‑discipline internal discussion, of the original meeting package and questions. OTAT 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 OTAT’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 OTAT preliminary responses. As stated above, during the meeting the OTAT team will not be able to provide feedback on new information (e.g., new question, alternative approaches or new proposals to address OTAT 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 OTAT staff will be familiar with the meeting package content and questions, OTAT recommends that sponsors limit the time of a presentation and use the allotted meeting time to obtain clarifications to OTAT’s preliminary responses to the sponsor’s questions.
OTAT recommends that time be reserved at the end of the meeting for the sponsor to summarize the major discussion points and action items.
OTAT will issue meeting minutes within 30 calendar days after the meeting. OTAT’s version of the meeting minutes is official and the final record of the meeting. OTAT 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, OTAT may not review such submissions; therefore, the absence of an OTAT response to such submissions does not imply OTAT concurrence with the sponsor’s version of the minutes.
If sponsors disagree with the content of OTAT’s minutes, OTAT’s meeting minutes will not be altered except to correct a substantive mistake for the record (on extremely rare occasions).
Post-meeting follow-up (teleconference/face-to-face vs. WRO)
For meetings scheduled as teleconference or face-to-face (F2F)
The teleconference/F2F meeting is the sponsor’s opportunity to obtain clarification on OTAT’s preliminary response. Due to workload, OTAT will not be able to address follow-ups or additional questions, via email or teleconference, after the meeting is held. If additional questions arise, the sponsor may submit the questions/alternative approaches or new data to the existing IND as an amendment for OTAT feedback.
- For Written Reponses Only
Simple requests for clarification of OTAT WRO may be sent to the Regulatory Project Manager (RPM) within 20 days after receipt of the WRO. The sponsor should include their request for clarifications for all disciplines in a single follow-up request. Generally, only questions of a clarifying nature will be considered, i.e., to confirm something in the WRO issued by OTAT, rather than raising new issues or new proposals.
Examples of such simple requests for clarification include:
- Typos and misstatements by OTAT
- The OTAT responses can be interpreted ambiguously and are unclear to the sponsor (e.g., “Did you mean A or B?”)
Examples of follow-up requests that are beyond clarification and therefore not appropriate:
- Questions related to new information not included in the briefing package
- Questions related to the adequacy of new proposals to address OTAT comments [(e.g., new clinical trial designs, study endpoints, new patient population, new/modified assays, new preclinical study design, new materials (i.e., raw materials, source materials )]
If such questions arise, the sponsor may submit these questions, alternative approaches, or new data to their existing IND as an amendment for OTAT consideration.
OTAT will consider the follow-up request, and if determined to be limited to clarification, OTAT will issue a response in writing within 20 calendar days after receipt of the clarifying questions. If OTAT determines that a short teleconference would be the best format for follow-up, then OTAT will attempt to hold this informal teleconference within 20 days after receipt of the request for clarification. OTAT will not provide the sponsor with minutes for such informal teleconference.