Pre-BLA (Type B) meetings for Original Submissions and Efficacy Supplements
The primary purpose of a pre-BLA meeting is to discuss the planned content of the marketing application. This meeting is an opportunity to:
- identify any major unresolved issues from the development program,
- familiarize the review team with the studies the applicant is planning to rely on to provide evidence of the product’s effectiveness,
- identify the status of ongoing or needed studies adequate to assess pediatric safety and effectiveness,
- acquaint FDA reviewers with the general information to be submitted in the marketing application,
- discuss appropriate methods for statistical analysis of the data, and
- discuss the best approach to the presentation and formatting of data in the marketing application.
- discuss CMC readiness for a BLA, e.g., commercial manufacturing process, and product comparability (if applicable)
Submission of Pre-BLA (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 3, OTP will send the decision to grant or deny the meeting request, along with the meeting date, if granted, or reasons for denial.
OTP Response to Meeting Request**
Meeting Scheduling ***
Meeting package due to OTP
At least 30 days before the scheduled date of the meeting
90 minutes for original BLA submissions, 60 minutes for Efficacy supplemental BLA
OTP Preliminary Response to questions in the package to Sponsor
NLT* 2 days before the meeting
Sponsor’s Response to FDA preliminary response
NLT than 24 hours before the meeting
*NLT – No Later Than
Source: Table 3 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.
The pre-BLA meeting should be requested in advance of the planned submission of the marketing application and should generally occur not less than two (2) months prior to the planned submission of the original BLA or efficacy supplement. Thus, the meeting request should be submitted at least four (4) months prior to the anticipated BLA submission. If a product is eligible for consideration of a rolling review (i.e., by virtue of Breakthrough Therapy, Regenerative Medicine Advanced Therapy, or Fast Track designation), then the applicant should not submit portions of their BLA prior to a pre-BLA meeting. Please see Appendix 2 of Guidance for industry Expedited Programs for Serious Conditions - Drugs and Biologics for information on the Rolling Review process.
OTP attempts to honor the requested format. OTP schedules pre-BLA meetings for 90 minutes.
Only one pre-BLA meeting will be granted for a specific product or indication. Pre-BLA mtgs should be multidisciplinary. OTP will not grant separate “clinical” and “CMC” pre-BLA meetings.
Based on the purpose of the meeting identified above, the sponsor should plan to include adequate information to allow sufficient discussion at the pre-BLA meeting to support a complete BLA application. For example, the sponsor should provide topline results from the clinical studies that are intended to provide the primary evidence of effectiveness and an overview of the safety database (e.g., total number of subjects exposed to the proposed recommended dose/regimen; most common adverse events; serious adverse events; adverse events of special interest). However, some issues, which would be addressed during the review of the BLA, are not appropriate to discuss in a pre-BLA meeting, e.g., acceptance of the proposed commercial specifications.
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 proposed license application submission. 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 a 90-minutes meeting, a maximum of 15 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. 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 indicated above in Table 3. 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 3.
- The sponsor is expected to respond to OTP’s preliminary responses according to the timeline indicated above in Table 3.
- 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 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.
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.