Pre-IND Meetings with the FDA: Everything You Need to Know

The pre-Investigational New Drug (pre-IND) meeting with the FDA is a crucial step in the drug development process. It provides an opportunity for sponsors to seek critical feedback on their development plans and clarify regulatory requirements before submitting an IND application.

This guide will delve deeply into the intricacies of preparing for and approaching a pre-IND meeting, integrating insights from experts to create a robust framework for success.

What is a Pre-IND Meeting?

The pre-IND meeting is a formal engagement, mandated by the Prescription Drug User Fee Act (PDUFA), designed to facilitate dialogue between the FDA and sponsors. It serves as a platform for sponsors to discuss their development programs and seek guidance on scientific and regulatory matters.

The FDA offers several types of meetings, but the pre-IND meeting is categorized as a Type B meeting, which means that once the meeting request is received, the FDA will schedule it within 60 calendar days.

During this meeting, the FDA provides feedback on the proposed strategies, helping to streamline the development process.

The key objectives here include:

Obtaining FDA Feedback: Address significant challenges faced by the sponsor in areas such as quality, non-clinical, clinical, and regulatory strategies.
Clarifying Development Plans: Ensure that the development plans align with FDA expectations to minimize the risk of clinical holds upon IND submission.
Optimizing Resources: Avoid unnecessary studies and focus on essential data that will support the IND application.

Keep in mind that limited data is acceptable for early meetings as long as it is accompanied by a clear regulatory strategy and a well-defined plan for future studies. Sponsors should not shy away from asking for guidance based on the information they currently have, emphasizing their commitment to safety and efficacy.

Determining the Right Time for a Pre-IND Meeting

Timing is critical when considering a pre-IND meeting. The FDA suggests that these meetings are particularly beneficial under the following circumstances:

Targeting Serious or Life-Threatening Diseases: If your product addresses such conditions, early feedback can be invaluable.
New Molecular Entities: Understanding regulatory expectations can shape development strategies for drugs that are novel or innovative.
Absence of Specific Guidance Documents: If there are no existing FDA guidance documents relevant to your product, the pre-IND meeting can clarify regulatory pathways.
Presence of Complex Questions: Whenever significant uncertainties exist regarding the development plan, a pre-IND meeting can provide critical clarity.

Preparing for the Meeting—Inside Our Playbook

We've helped hundreds of teams prepare for pre-IND meetings. Here are a few best practices we've come to include in our strategy.

Crafting the meeting request letter

A well-structured meeting request letter is the first formal step in engaging with the FDA. This document should include:

Objective of the Meeting: Clearly articulate the goals you hope to achieve during the meeting, such as clarifying regulatory pathways or discussing data requirements.
Agenda: Outline the topics to be discussed to guide the meeting’s focus.
Draft List of Questions: Provide specific questions grouped by discipline (clinical, non-clinical, CMC). This helps the FDA understand what expertise is required in the meeting and facilitates a targeted discussion. Also, formulate questions that are specific and direct, avoiding open-ended queries that may lead to vague or non-committal responses.
Proposed Date and Time: Suggest potential dates and times for the meeting, considering the FDA's schedule.
Background Information: Include a brief overview of the product, its intended indication, and any preliminary data that provides context.

Submit the meeting request to the relevant FDA division as early as possible, ideally 2-3 months before your anticipated meeting date, to secure the desired date.

Preparing the briefing package

The briefing package or document is a cornerstone of the pre-IND meeting preparation. It provides the FDA with the necessary background to engage in a meaningful discussion. A well-crafted document can also establish a strong initial impression, showcasing the sponsor's professionalism and thoroughness. A poorly constructed briefing package may negatively impact the FDA's perception of the sponsor's capabilities.

Key components include:

Product Overview: Include detailed information about the drug, such as its mechanism of action, proposed indication, and target population.
Clinical Synopsis: Present a draft protocol for the first clinical study, detailing endpoints, inclusion/exclusion criteria, and safety measures. Providing a draft protocol can facilitate FDA feedback, as they may comment on aspects not directly queried.
Non-Clinical Data: Summarize relevant studies that provide insight into the drug's safety and efficacy, including dose-ranging studies and safety pharmacology data.
CMC Information: Detail the manufacturing process through a flowchart and list testing and specifications planned for the drug product.

All sections of the briefing package should be interconnected and reference one another. A cohesive narrative is essential for helping the FDA reviewers understand the product’s development context and demonstrating that all project aspects are aligned. Disjointed information can lead to confusion and misinterpretation.

Again, questions posed to the FDA should be strategically designed to elicit desired responses. Instead of simply asking whether a particular study design is acceptable, sponsors should frame their questions to imply a preferred outcome. For instance, rephrasing a question to highlight the rationale behind a proposed approach can guide the FDA toward a more favorable response.

The briefing document must be submitted at least 30 days before the scheduled meeting. If this timeline is not met, the FDA may cancel the meeting, necessitating a reschedule.

A few best practices for creating briefing packages

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Here are some of our best practices for crafting effective briefing packages, whether it's for a Pre-IND, Pre-NDA, or Pre-BLA meeting.

Establish a Clear Purpose and Structure: Ensure the briefing package serves as a comprehensive document that communicates essential information clearly. Include an introduction that outlines the purpose of the meeting, the product being discussed, and the key topics to provide the FDA with a foundational understanding of the meeting’s objectives.
Write Well and Keep Content Concise: Craft content that is clear and succinct, avoiding unnecessary detail that may detract from the main points. Focus each section directly on the questions posed to the FDA to ensure effective communication and engagement, facilitating a productive meeting environment.
Facilitate Engagement and Dialogue: Design your briefing materials to spark meaningful dialogue between the sponsor and the FDA. Structure the content to encourage discussion, helping both parties address critical issues and achieve mutual understanding.
Provide a Thorough Product Overview: Present a comprehensive overview of the product that is accessible and easy to understand, particularly for those not deeply familiar with it. Include essential details such as composition, formulation, mechanism of action, intended indications, and clinical benefits to ensure the FDA can quickly grasp the significance of the product.
Focus on Non-Clinical Data Presentation: Tailor the presentation of non-clinical data based on the meeting type. For pre-IND meetings, emphasize the planned animal studies and their relevance to demonstrating safety and efficacy, ensuring that the information supports the objective of proceeding to clinical trials.
Summarize Comprehensive Clinical Data: Adapt the presentation of clinical data in the briefing book based on the development stage. For pre-NDA and pre-BLA meetings, focus on summarizing key findings from completed trials, including demographics and outcomes, while directly connecting this data to the specific questions posed to the FDA.
Integrate Regulatory Strategy Throughout: Weave the regulatory strategy throughout the briefing book by linking the product overview, non-clinical data, and clinical data to the overall development plan. This coherence helps the FDA understand the context and direction of the product’s development.
Provide Clear Position Statements: For each question posed to the FDA, include a clear position statement that outlines the rationale behind your inquiry and references supporting data in the briefing book. This approach contextualizes your questions and strengthens the argument for your proposed actions.
Frame Questions Carefully: Frame your questions in a way that encourages specific responses from the FDA rather than leaving them open-ended. This precision helps guide the FDA toward providing the information you need to advance your development program effectively.
Conclude with a Summary and Conclusion: End the briefing book with a summary that highlights the main points discussed, reinforcing critical data and the importance of the product’s development. This final recap solidifies the key messages and expresses gratitude for the FDA’s consideration.

Conducting the Meeting

Pre-IND meetings can be conducted via teleconference or video conference, especially in the context of ongoing adaptations due to COVID-19. Face-to-face meetings may also be possible but are less common.

Meetings are typically scheduled for one hour and follow a structured approach:

Introductions (5 minutes): Introduce all attendees from both the sponsor and FDA sides.
Question Discussion (50 minutes): Address questions in the order of priority. It is crucial to focus on the most pressing issues first to ensure they receive adequate time for discussion. Before the meeting, we always identify the most critical questions that need to be addressed first, ensuring that they receive adequate attention within the meeting's time constraints.
Summary and Closing (5 minutes): Reiterate key takeaways and agreements from the meeting, confirming mutual understanding of the discussion points.

We encourage an open dialogue with FDA representatives, ensuring that questions are specific and targeted. This engagement fosters a collaborative environment where both parties can address pressing issues effectively. Also, be ready to receive feedback that may challenge your assumptions or plans. Understanding that the FDA’s guidance is based on extensive experience with similar products can help contextualize their input.

Consider enlisting regulatory consultants who can assist in refining questions and improving the quality of the briefing document. Their experience can provide insights that enhance the effectiveness of your approach.

Post-Meeting Follow-Up

Within 24 to 72 hours following the meeting, the FDA will typically provide preliminary responses to the questions raised. These responses should be carefully reviewed to ensure clarity and comprehensiveness.

If certain questions remain unresolved or require further discussion, communicate this with the regulatory project manager at the FDA. Specify which questions need additional clarification so that the meeting can remain focused on those critical areas.

After the meeting, we strongly suggest sending a summary of the meeting notes to the FDA. This documentation helps to confirm the understanding of what was discussed and any agreements made during the meeting.

A Few Best Practices for Pre-IND Meetings

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Below are a few more best practices we've found to be critical to incorporate when planning and conducting pre-IND meetings with the FDA.

1. Draft your questions early.

Develop a draft of your pre-IND briefing document when preparing your meeting request letter. This process helps clarify your objectives and identify the most pressing questions. The act of drafting forces your team to think critically about the issues and data at hand, refining the questions you plan to ask.

2. Group your questions by discipline.

When formulating your questions, categorize them by discipline (clinical, non-clinical, and CMC). This organization helps the FDA bring the appropriate experts to the meeting and ensures that discussions are focused and productive.

During the preparation phase, for example, a sponsor might group its questions into three categories:

Clinical: “What endpoints does the FDA recommend for our Phase I trial?”
Non-Clinical: “What additional toxicology studies might be necessary?”
CMC: “Are our proposed manufacturing controls adequate for initial IND submission?”

3. Use visual aids when appropriate.

Include flowcharts and tables in your briefing document. These visual aids can simplify complex data, making it easier for the FDA to review and understand the information presented. Concise summaries and visuals can expedite their review process.

4. Be precise with your draft protocols.

When providing a draft protocol for your first clinical study, ensure it includes specific elements like route of administration, inclusion/exclusion criteria, and blinding methods. Providing detailed drafts can elicit valuable feedback, even on sections not explicitly questioned.

5. Leverage the target product profile.

Although not mandatory, including a target product profile in your briefing document can help direct the FDA’s understanding of your product’s goals. Clearly articulate your vision for the product, including potential endpoints and clinical considerations.

6. Use regulatory consultants effectively.

Almost every sponsor engages at least one regulatory consultant throughout this process. Involve them early in the process; their insights can help refine your approach to the meeting, and they can assist in drafting questions and preparing the briefing document.

A small biotech firm recently engaged us to assist in drafting their briefing document and liaising with the FDA. We not only helped refine their questions but also shareed insights from previous experiences, such as common pitfalls that sponsors encounter during pre-IND meetings.

Final Thoughts and Next Steps

Navigating the IND submission process is complex, time-consuming, and fraught with potential pitfalls. As we've explored in this guide, success requires a strategic approach to pre-IND meetings, rigorous data review processes, robust translational strategies, flexible CMC approaches, and compelling narrative construction.

Pre-IND Package Preparation Services

The FDA Group facilitates the preparation of the Pre-IND package, which is essential for a successful meeting with the FDA. Their services include:

Review of Preclinical Package: We assess the completeness and adequacy of preclinical data, offering insights and recommendations based on regulatory standards. This includes a one-hour teleconference to discuss findings.
Preparation of the Pre-IND Package: We help compile the Pre-IND package, which includes all necessary documentation and ensures it aligns with FDA expectations.
Meeting Request and Questions: We assist in drafting the meeting request, including a well-structured list of questions you want to address during the Pre-IND meeting. This process involves multiple conference calls to refine the questions and responses.
Rehearsal for Pre-IND Meeting: Prior to the actual meeting with the FDA, we conduct rehearsals and training sessions to ensure that client representatives are well-prepared to present their case effectively.

IND Preparation and Submission

Not all scientists are adept writers. Engaging a skilled writer or regulatory expert to craft the briefing book can significantly improve clarity and effectiveness. A good writer can help translate complex scientific information into a narrative that is easy to understand and compelling.

We assist in preparing the IND application using the electronic Common Technical Document (eCTD) format, ensuring compliance with regulatory standards. This includes preparing various modules such as:

Introductory statements and general investigation plans.
Quality Overall Summary (QOS) and Chemistry, Manufacturing, and Controls (CMC) information.
Clinical protocols and summaries.
Providing comprehensive overviews of nonclinical data and any prior human experience.

This preparation involves significant collaboration to ensure all documentation is accurate and complete. After submitting the Pre-IND package, the FDA Group reviews any preliminary feedback from the FDA and prepares the client to address any concerns raised. We also support the preparation of amendments to the IND, which may be required as new data or study designs emerge during the drug development.

We employ a team of over 2,500 consultants, including more than 250 former FDA officials. Our consultants bring firsthand experience in regulatory processes, enhancing the quality of guidance provided to clients. We have direct insight into how FDA reviewers think and operate, helping you align their submissions with agency priorities.