What Does an End of Phase 1 (EOP1) FDA Meeting Involve?

 An End of Phase 1 (EOP1) meeting with the U.S. Food and Drug Administration (FDA) is a crucial milestone in the drug development process. This meeting provides an opportunity for sponsors to discuss the results of Phase 1 clinical trials and obtain FDA feedback before proceeding to Phase 2. In this article, I discuss some of the key components of an EOP1 meeting:

1. Meeting Request and Background Information:

   • Sponsors initiate the process by requesting an EOP1 meeting with the FDA. This request should include a comprehensive background on the investigational drug, its mechanism of action, and the Phase 1 trial design.
   • 
     
   • An EOP1 meeting is considered a Type B meeting, which has a 14 day response time for the FDA to respond to the request on whether it is granted or not. The FDA guidance is that the meeting should take place within 60 days of the request.

According to FDA guidance, the meeting request must include the following information:

• The proposed meeting format (i.e., face to face, teleconference/videoconference, or WRO).
• The date the meeting background package will be sent by the requester.
• A brief statement of the purpose of the meeting. This statement should include a brief background of the issues underlying the agenda. It also can include a brief summary of completed or planned studies and clinical trials or data that the requester intends to discuss at the meeting, the general nature of the critical questions to be asked, and where the meeting fits in overall development plans. Although the statement should not provide the details of trial designs or completed studies and clinical trials, it should provide enough information to facilitate understanding of the issues, such as a small table that summarizes major results.
• A list of the specific objectives or outcomes the requester expects from the meeting.
• A proposed agenda, including estimated times needed for discussion of each agenda item.
• A list of requested FDA attendees and/or discipline representative(s). Note that requests for attendance by FDA staff who are not otherwise essential to the application’s review may affect the ability to hold the meeting within the specified time frame of the meeting type being requested. Therefore, when attendance by nonessential FDA staff is requested, the meeting request should provide a justification for such attendees and state whether or not a later meeting date is acceptable to the requester to accommodate the nonessential FDA attendees.

The meeting request should include the following information:

• The application number (if previously assigned).
• The product name.
• The chemical name, established name, and/or structure.
• The proposed regulatory pathway (e.g., 505(b)(1), 505(b)(2)).
• The proposed indication(s) or context of product development.
• Pediatric study plans, if applicable.
• Human factors engineering plan, if applicable.
• The meeting type being requested (i.e., Type A, Type B, Type B (EOP), or Type C).
• Combination product information (e.g., constituent parts, including details of the device constituent part, intended packaging, planned human factors studies), if applicable.
• Suggested dates and times (e.g., morning or afternoon) for the meeting that are consistent with the appropriate scheduling time frame for the meeting type being requested (see Table 2 in section VI.B., Meeting Granted). Dates and times when the requester is not available should also be included.
• A list of proposed questions, grouped by FDA discipline. For each question there should be a brief explanation of the context and purpose of the question

1. Meeting Package Preparation:

   • Prior to the meeting, sponsors compile a meeting package that includes detailed information on the Phase 1 trial, such as protocols, patient demographics, safety data, and preliminary efficacy data. The package is often referred to as a "Briefing Book" or "Briefing Package".
   • 
     
   • According to FDA guidance, the meeting package is submitted to the FDA no later than 30 days before the scheduled date of the meeting and should be organized according to the proposed agenda. The meeting package should be a sequentially paginated document with a table of contents, appropriate indices, appendices, and cross references. It should be tabbed or bookmarked to enhance reviewers’ navigation across different sections within the package, both in preparation for and during the meeting
   • 
     
   • Meeting packages generally should include the following information, preferably in the order listed below:

• The application number (if previously assigned).
• The product name.
• The chemical name, established name, and/or structure
• The proposed regulatory pathway (e.g., 505(b)(1), 505(b)(2)).
• The proposed indication(s) or context of product development.
• The dosage form, route of administration, and dosing regimen (frequency and duration).
• Pediatric study plans, if applicable.
• Human factors engineering plan, if applicable.
• Combination product information (e.g., constituent parts, including details of the device constituent part, intended packaging, planned human factors studies), if applicable.
• A list of all individuals, with their titles and affiliations, who will attend the requested meeting from the requester’s organization, including consultants and interpreters.
• A background section that includes the following:
• A brief history of the development program and relevant communications with the FDA before the meeting
• Substantive changes in product development plans (e.g., new indication, population, basis for a combination), when applicable
• The current status of product development
• A brief statement summarizing the purpose of the meeting and identifying the type of milestone meeting, if applicable.
• A proposed agenda, including estimated times needed for discussion of each agenda item.
• A list of the final questions for discussion grouped by FDA discipline and with a brief summary for each question to explain the need or context for the question. Questions regarding combination products should be grouped together.
• Data to support discussion organized by FDA discipline and question. Protocols, full study reports, or detailed data generally are not appropriate for meeting packages; the summarized material should describe the results of relevant studies and clinical trials with some degree of quantification, and any conclusion about clinical trials that resulted. The trial endpoints should be stated, as should whether endpoints were altered or analyses changed during the course of the trial.

1. Agenda Setting:

   • The sponsor and the FDA collaborate to set the meeting agenda. This includes outlining specific topics for discussion, such as safety and efficacy findings, plans for Phase 2, and any questions or concerns.
   • 
     

2. Meeting Presentation:

   • During the EOP1 meeting, sponsors provide a structured presentation summarizing Phase 1 trial data. This includes a detailed analysis of safety profiles, dose-response relationships, pharmacokinetics, and pharmacodynamics.
   • 
     

3. Safety Assessment:

   • A significant portion of the meeting is dedicated to safety. Sponsors must address any adverse events observed during the Phase 1 trial and propose strategies for managing them in future studies.
   • 
     

4. Efficacy Discussion:

   • Sponsors present any preliminary efficacy data, if available. The FDA evaluates the clinical relevance and potential impact on future trial design.
   • 
     

5. Regulatory Strategy:

   • Sponsors should outline their proposed Phase 2 trial design and endpoints. The FDA provides input on the acceptability of these plans and may suggest modifications to enhance the trial's success.
   • 
     

6. Questions and Clarifications:

   • Both parties engage in a dialogue to address questions, concerns, and recommendations. The FDA may offer guidance on specific issues, such as patient populations, trial duration, or endpoints.
   • 
     

7. Next Steps:

   • The EOP1 meeting concludes with a discussion of the next steps. Sponsors should leave with a clear understanding of the FDA's feedback and any requested actions or additional data.
   • 
     

8. Meeting Minutes:

   • Detailed meeting minutes are crucial. Sponsors are responsible for preparing these minutes, which should accurately capture all discussions and agreements reached during the meeting.
   • 
     

9. Follow-up Actions:

   • Sponsors should promptly address any action items identified during the meeting and incorporate FDA feedback into their development plan for Phase 2.

In summary, an End of Phase 1 meeting with the FDA is a pivotal point in drug development. It requires careful preparation, a thorough presentation of Phase 1 data, and a collaborative discussion with the FDA to ensure alignment on the path forward for Phase 2. Accurate documentation and timely follow-up are essential for a successful transition to the next stage of clinical development.