Meetings for Regenerative Medicine Advanced Therapy (RMAT) and Breakthrough Therapy (BT) Designated Products
Breakthrough Therapy (BT) Designation and Regenerative Medical Advanced Therapy (RMAT) Designation are two of the expedited programs that may apply to cellular and gene therapy products that are intended to treat, modify, reverse, or cure a serious condition. Refer to Guidance for industry Expedited Programs for Serious Conditions - Drugs and Biologics , Expedited Programs for Regenerative Medicine Therapies for Serious Conditions Guidance for Industry, and SOPP 8212: Management of Breakthrough Therapy-Designated Products: Sponsor Interactions and Status Assessment Including Rescinding for more information on BT and RMAT designation criteria and other expedited programs.
OTAT recommends that sponsors of regenerative medicine therapies engage in discussions with OTAT review staff early during product development. In particular, the Type B meetings described, including the pre-IND, end-of-phase and pre-BLA meetings, represent critical points in product development.
With regard to the number of meetings associated with RMAT or BT designation, products that receive both designations are treated as having a single designation. For example, a product that receives both RMAT and BT designation will be granted only one Initial Comprehensive Meeting.
RMAT/BT –Initial Comprehensive Meeting (Type B)
After a product receives BT or RMAT designation, sponsors are encouraged to request an “Initial Comprehensive Meeting”, which is a multidisciplinary comprehensive discussion of the drug development program, including planned clinical trials and plans for expediting the manufacturing development strategy. OTAT will attempt to honor the requested format. If another milestone meeting is pending at the time that a product receives BT or RMAT designation, OTAT may suggest combining the Initial Comprehensive Meeting with the milestone meeting. If a product receives BT or RMAT designation late in product development, particularly after a pre-BLA meeting has been held, an Initial Comprehensive Meeting is not necessary. Refer to SOPP 8212: Management of Breakthrough Therapy-Designated Products: Sponsor Interactions and Status Assessment Including Rescinding Appendix A on Initial Comprehensive Meeting.
Submission of Initial Comprehensive Meeting (Type B) 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 [email protected] 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.
Table: Timelines for Type B Meetings
|
OTAT Response to Meeting Request** |
21 days |
|
Meeting Scheduling or WRO issued*** |
60 days |
|
Meeting package due to OTAT |
At least 30 days before the scheduled date of the meeting or WRO |
|
Meeting Length |
60 minutes |
|
OTAT Preliminary Response to questions in the package to Sponsor (for teleconferences and face-to-face meetings) |
NLT* 2 days before the meeting |
|
Sponsor’s Response to FDA preliminary response (for teleconferences and face-to-face meetings) |
NLT than 24 hours before the meeting |
*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.
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.
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. Meeting packages are typically 50 – 100 pages. 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 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 forgo 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.
Meeting Minutes
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
The teleconference/face-to-face 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 tcon, 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.
RMAT/BT – End of Phase and Pre-BLA (Type B) Meetings
OTAT will grant these milestone meetings if, upon evaluation, the stage of development matches the requested milestone. Please refer to the specific milestone meetings, e.g., EOP, pre-BLA, described elsewhere on the website. Only one meeting will be granted per milestone (e.g., one EOP2). Milestone meetings should be multidisciplinary. OTAT will not grant separate “clinical” and “CMC” EOP mtgs. Refer to the milestone meeting section above.
OTAT will attempt to honor the requested format.
RMAT/BT – Non-Milestone Meetings
Milestone and non-milestone meetings for products with RMAT or BT designation, are scheduled as Type B (see Table above). If the sponsor proposes several discipline-specific meetings within one year, OTAT recommends that the sponsor consolidate the number of these meetings by combining topics and also consider if some of the information can be submitted as an amendment to the IND for informal feedback, as opposed to a formal meeting request.