How to Have a Successful Pre-IND Meeting

Introduction

The path to developing an approved biopharmaceutical drug is a long and expensive journey that begins with basic research, then through preclinical?development, followed by early and late phase clinical trials, and finally, regulatory approval. By the time a biopharmaceutical product goes through this process and is FDA approved, it can take up to ten years and cost up to a billion dollars.?

Before a company invests significant amounts of time and money in developing a product, it is prudent to seek input from the regulatory agency that will eventually approve the drug as early in the development process as possible. Because biologics are challenging to manufacture and very expensive to produce, seeking agreement with the regulatory authorities on a new product’s CMC development and manufacturing strategy as early in the development process as possible can avoid unnecessary delays and expenses.?

The pre-IND meeting is the first formal opportunity for feedback from the FDA. The goal of this meeting is to get the FDA's agreement on?the product's proposed early phase development plan for moving a product into early-stage human clinical trials. This whitepaper describes how sponsors can benefit from actively engaging the FDA during this process. If handled properly, this meeting will significantly increase the probability of getting the IND approved and moving the product into early phase clinical trials.?In addition, a valuable opportunity is presented to build a strong and positive working relationship with the FDA.?This paper is focused on the CMC sections of the IND but other areas outside CMC can also benefit from reading this paper.

Requesting the Meeting

Once requested, the FDA will try to grant the pre-IND meeting within sixty days; however, with recent backlogs, the FDA may find it challenging to meet this timeframe. To accommodate demand, the FDA will often provide written?responses to the sponsor instead of holding a formal meeting. A pre-IND meeting based on written FDA responses can still be valuable in de-risking the IND process when following the advice in this whitepaper.

The meeting request should specify the objectives of the meeting and?the types of questions the sponsor plans to ask. The sponsor must describe the questions they intend to ask so the FDA can schedule the right reviewers for the meeting. Questions to the FDA should be phrased so the agency can either agree or disagree. Speculative and open-ended questions are difficult for the FDA to address and will significantly diminish the value of the meeting. Pre-IND meetings are most productive when the questions focus on specific issues.?

The meeting request should also include a list of individuals from the sponsoring company, their titles, and those of any affiliates, such as consultants who will attend the meeting on behalf of the sponsor. Although many meetings are currently written responses only, always include a preferred meeting format in the meeting request, such as face-to-face, teleconference, or videoconference.?

The Briefing Package

To prepare for the meeting, the sponsor must send a pre-IND meeting briefing package to the FDA at least thirty days before the meeting. In addition to any questions the sponsor has for the FDA, the CMC portion of the briefing package should list the proposed manufacturing sites and an?overview of the planned drug substance and drug product manufacturing processes. If possible, also try to include a list of the analytical assays that will be used to release the drug substance and drug product and for stability studies.?

Including the sponsor’s plan for characterizing the reference standard is also helpful since the FDA requires the product to be well characterized in the IND. Having the FDA review the characterization plan as part of the pre-IND meeting will reduce the risk of potential issues during the IND review. If there will be differences in the manufacturing process between the pre-clinical and clinical batches, they need to be discussed, especially if the pre-clinical batch will be used for IND enabling toxicology studies or to create a reference standard that will later be used for product release and stability testing of the clinical batches.

The briefing package should include the batch analysis data for any batches already produced. If sufficient data are available, the pre-IND meeting is a good time to propose initial product specifications to get FDA feedback. Usually, this meeting happens before clinical materials have been produced, so these will likely be based on pilot batches and available development data.

If a bioassay is available, the briefing package is an excellent place to introduce it to the FDA. If a bioassay is not yet available, it is essential to ask the FDA if a surrogate assay such as an ELISA is sufficient to open the IND. It is better to get an initial read on whether the agency feels the bioassay or use of a surrogate such as ELISA is appropriate for opening the IND than to spend time, money, and energy developing an assay that the agency later feels is inappropriate and potentially delaying the opening of the IND.

Preparing for the Meeting

Before the meeting, the sponsor team should regularly meet to prepare. During these meetings, the team should define potential issues and questions from the FDA. The team should develop responses for each question and determine who will respond to each point during the pre-IND meeting.

To track these potential FDA issues, the sponsor should create a question and answers document that is updated and refined throughout meeting preparations. This document should also include fallback positions endorsed by the team in case the FDA rejects the proposal.

Before the meeting, the FDA will review the briefing package and provide written comments. They will also provide written answers to any questions included in the briefing package.?These preliminary responses are generally received 1-5 days before the meeting. Based on this feedback, the sponsor needs to decide their overall position on each response and prepare questions for any items that need further clarification from the FDA.?If the FDA has significant concerns, the sponsor must draft a plan to address each to get constructive feedback during the meeting. The sponsor then needs to prepare opening remarks for the meeting. Once the questions and opening remarks are created, the sponsor team should perform a final run-through of the opening remarks, questions, and responses to the FDA’s written comments.

During The Meeting

If a teleconference or face-to-face meeting is scheduled, the sponsor team must take detailed notes. Since the meeting time is limited, the sponsor team must be organized and succinct. Generally, only an hour is given, with approximately 5 minutes for introductions and another 5 minutes for a wrap-up. This leaves about fifty minutes to cover everything related to the IND, including CMC, toxicology, pharmacology, and the proposed clinical protocol.

After the Meeting

If the pre-IND meeting was a teleconference or a face-to-face meeting, the sponsor team should meet as soon as possible to review the notes taken during the meeting and align on each point discussed with the FDA. Usually, within four weeks of the meeting,?the FDA will issue the final meeting minutes. When the FDA sends its official meeting minutes, they will include their written response to the briefing package, a summary of each point discussed during the meeting, and their thoughts on how each issue needs to be addressed. If, upon reviewing the final FDA minutes, the sponsor has any notable comments or disagreements, these need to be communicated in writing to the FDA as soon as possible with the request for the meeting minutes to be amended to address the sponsor's comments.

Conclusion

After actively engaging the FDA during the pre-IND meeting process, the sponsor and the FDA should have worked through any potential issues and established a documented path on how the sponsor plans to move the product through the IND process and into early phase clinical trials. By actively engaging the FDA during the pre-IND meeting, the sponsor significantly decreases the risk of clinical hold issues and creates the framework for a positive future relationship with the FDA. Feel free to get in touch with the author with any questions.