Regulatory guidelines allow for formal meetings between the FDA and sponsors or applicants to discuss the development and review of an investigational new drug (IND) application for drugs or biologic products. This meeting, known as a pre-IND meeting, is intended to address specific questions related to the initial US clinical study (also known as a first-in-human [FIH] study for new drugs and biologics) and other questions that could affect the IND application, including those related to the nonclinical program, manufacturing and product quality for the investigational product, and regulatory considerations.
The pre-IND meeting typically includes a discussion of scientific and regulatory aspects of the drug as they relate to safety and/or potential clinical hold issues. Sponsors are strongly encouraged to take advantage of the pre-IND meeting for the following reasons:
- The information gained from the meeting can help ensure a complete IND application is submitted and potentially help avoid clinical holds
- The meeting presents a formal opportunity to gather the FDA’s perspectives, recommendations, and preliminary agreement (or disagreement) on critical aspects of your development program
- The meeting is an opportunity to build a constructive relationship with the FDA
- No fees are required for this meeting
Requesting a Pre-IND Meeting & Timelines
The request for a pre-IND meeting should be submitted to the FDA review division that will be overseeing your eventual IND application and should include the following information:
- Product name, application number (if applicable), and chemical name and structure
- Proposed indication(s) or context of product development
- Type of meeting being requested (i.e., Type A, Type B, or Type C). If a Type A meeting is requested, the rationale should be included
- A brief statement of the purpose and objectives of the meeting
- A proposed agenda
- A list of proposed questions grouped by discipline. For each question there should be a brief explanation of the context and purpose of the question
- A list of all individuals with their titles and affiliations who will attend the requested meeting from the sponsor’s or applicant’s organization as well as any consultants
- A list of FDA staff, if known, or disciplines asked to participate in the requested meeting
- Suggested dates and times (e.g., morning or afternoon) for the meeting that are within the appropriate time frame of the meeting type being requested
- The desired format of the meeting (i.e., face to face, teleconference, or videoconference)
When stating the purpose and objectives of the meeting, the sponsor should not provide detailed documentation of trial designs or of completed nonclinical and clinical studies but should provide just enough information to facilitate understanding of the issues, such as a small table that summarizes major results. This statement should include:
- A brief background of the issues underlying the agenda
- A brief summary of completed or planned clinical, nonclinical, or both types of studies
- Clinical trials or data that the sponsor or applicant intends to discuss at the meeting
- The general nature of the critical questions to be asked
- Where the meeting fits in overall development plans
Once the meeting request has been submitted, it is up to the FDA to decide whether to grant or deny the request and to determine the appropriate format for an approved meeting. For pre-IND meeting requests (and requests for other “Type B” meetings), the FDA will typically respond within 21 days of receiving the request, and meetings are generally scheduled within 60 days of the request. Sponsors should therefore submit their request approximately two months before they would like to have the pre-IND meeting.
Preparing for a Pre-IND Meeting
Because the pre-IND meeting represents a critical milestone in the regulatory process, it is important that sponsors maximize the value of the meeting. There is typically only one pre-IND meeting allotted per investigational product, so sponsors must prepare well for this meeting to ensure they get all the feedback they need to progress their development program. Below is a high-level checklist for sponsors planning for and immediately following a pre-IND meeting:
- Submit a pre-IND meeting request, including critical questions for which you would like the FDA’s input
- Submit a pre-IND briefing package that adequately supports the questions in the request and any sponsor positions
- Assign roles and responsibilities for team members both during the preparatory stage and at the meeting
- Outline and rehearse contingency plans
- Consider the need for a formal presentation
- Critically evaluate preliminary feedback from the FDA and the implications for your program
- Prepare follow-up discussion points, questions, and “fallback positions” on key questions at the meeting
The meeting’s briefing package content will vary depending on the product, indication, phase of product development, and issues to be discussed. The briefing package should ultimately be focused on providing information relevant to the discussion topics in order to enable the FDA to adequately prepare for the meeting.
The briefing package should also provide a summary of information relevant to the product and any supplementary information needed to develop thoughtful responses to questions raised by the sponsor or applicant. Hence, full study reports or detailed data sets are generally not appropriate for pre-IND meeting packages; rather concise data summaries should be included that reasonably describe the decisions and results of relevant studies.
It can be beneficial to begin writing the briefing package prior to submitting a pre-IND meeting request, as questions and company positions that are discussed and documented prior to submitting the meeting request generally do not change and additional questions are rarely added. This early planning can help sponsors be better prepared for the meeting and prevent setbacks immediately prior to submitting the package.
The importance of having contingency plans cannot be overstated, especially for complex development programs and unique or nuanced issues. If the FDA disagrees with one or more company positions, the sponsor may be able to provide alternative solutions to which the FDA will agree. This requires adequate preparation and evaluation well in advance of the meeting and is not something you want to do “off the cuff” during the meeting. Role rehearsal and brainstorming sessions among sponsor-side team members are essential for a smooth meeting experience and will help promote successful outcomes.
Phrasing and Structure of Questions
When preparing questions for the pre-IND meeting, it is important not only to consider the content of the questions but also how each question is phrased and structured. It is essential that the questions are presented in a way that ensures clear, unambiguous, and decisive feedback from the Agency. The goal is to receive a clear “yes” or “no” answer, along with additional feedback as the FDA deems appropriate. For this reason, questions should not be open-ended. The following is an example of a common question employed by sponsors asked in two different ways:
- Incorrect: What does the Agency think about the proposed study design?
- Correct: Does the Agency agree that the proposed study design is acceptable?
10 Tips to Prepare for the Pre-IND Meeting
- Consider the scope of the meeting and whether certain disciplines (e.g., CMC, pharmacology/toxicology, clinical pharmacology) should be included in the pre-IND meeting or whether a separate meeting would be more appropriate
- Ensure that the necessary FDA Review disciplines are adequately represented
- Have a “game plan” ready ahead of the meeting, including contingency measures in the event the FDA does not agree with one or more company positions
- Assign roles and responsibilities among the attendees to avert role redundancy and potential miscommunication
- Rehearse internally to ensure you have clarity on the roles and responsibilities of various sponsor attendees and to help ensure a smooth meeting flow
- Designate a moderator who is familiar with the expertise of each sponsor employee to ensure that questions are directed to the correct person, eliminating the need for multiple speakers to address the same question
- Designate a timekeeper at the meeting who will be mindful of the meeting time and ensure that the discussion does not get “bogged down” on one issue. This will help ensure the key meeting objectives are met
- Focus the discussion on critical questions that are pivotal for advancing the program
- Listen carefully to Agency feedback to understand their level of concern about particular issues and recap any feedback at the end of the meeting to ensure the feedback is accurately captured in the meeting minutes
- Seize the opportunity to connect and establish rapport with the review division staff by using open and transparent communication
Benefits of Using a Consultant for a Pre-IND Meeting
Many pharmaceutical companies that request a pre-IND meeting are often embarking on this regulatory activity for the first time. Whether this is a sponsor’s first FDA meeting or another in a long list of FDA interactions over the years, meeting preparation is vital. This is where having an expert consultant involved throughout the process (including attendance at the meeting) can pay great dividends. Some of the benefits of using an expert consultant include:
- Bringing objective expert perspectives rooted in years of experience with this type of regulatory interaction and often with similar programs
- Sharing past experiences and best practices which may help maximize the chances of success and achieve the desired meeting outcome
- Ensuring the sponsor is properly prepared for the meeting with the FDA and that sponsor positions are adequately supported
- Identifying questions that the FDA may ask and creating potential contingency plans should the sponsor’s position be rejected by the FDA
The pre-IND meeting is a unique opportunity to meet with the FDA to discuss questions about your program and to help ensure a complete IND application is submitted. The pre-IND meeting is free of cost and can help avoid clinical holds and costly missteps. It is imperative that sponsors present questions and supporting information clearly and in a way that promotes unambiguous feedback from the FDA and constructive dialogue during the meeting. Finally, adequate preparation is the key to a successful outcome at these meetings.
Nuventra has a team of regulatory affairs experts with many years of experience helping our clients achieve successful IND submissions, including expert guidance for the pre-IND meeting. Contact us today for help preparing for your pre-IND meeting.