Asking the appropriate questions during a Pre-IND meeting with the FDA is a critical step in planning a development program.
A Pre-Investigational New Drug Application (Pre-IND) meeting can be a valuable component in planning a development program. For companies that have not previously interacted with the FDA in the early stages of a product’s development, a Pre-IND meeting is an opportunity to receive the Agency’s feedback and guidance. While FDA guidance documents can provide helpful information, they are broadly applicable to several types of products. Through a Pre-IND meeting, a Sponsor can get the Agency’s unique advice for a specific product.
Interacting with the Agency early in a development program can reduce time to market in several ways:
- Identifying and avoiding unnecessary studies
- Ensuring that necessary studies are designed to provide useful information
- Gaining FDA support for a proposed strategy
- Minimizing the potential for a clinical hold
- Providing an opportunity for the creative exchange of ideas
- Obtaining regulatory insight
- Minimizing costs
- Clearly defining the endpoints and goals of the development program
Given these advantages, it’s always advisable to seek the FDA’s guidance early in a drug’s development. The first step is to submit a Pre-IND meeting request letter with the questions for the FDA to answer. Asking the appropriate questions is critical because the FDA uses information in the request letter to determine (a) if a face-to-face or teleconference meeting or written responses should be granted (or denied) and (b) which reviewers will be at the meeting to facilitate a productive discussion.
The key to a successful Pre-IND meeting is getting clarity from FDA reviewers on what development activities are necessary to work toward NDA approval. This clarity allows the Sponsor to estimate the cost, duration, and potential risks of the program and is especially important when developing a 505(b)(2) product. To gain this understanding, Sponsors must ask the right questions in the right way.
Be Clear and Specific
When questions are clear and specific, FDA reviewers will be more likely to provide meaningful and helpful recommendations.
Questions should be direct, clearly stated, and posed in a such a way that FDA reviewers can either agree or disagree with a proposed plan. A brief explanation of the planned study or strategy should be included (typically prior to asking the question). For example, a Sponsor might explain its proposed comparative bioavailability study for a 505(b)(2) development program and then ask the following question:
Does the Agency agree that the proposed approach, if successful, will establish a clinical safety bridge to Listed Drug Z?
This question would likely receive a clear answer from the FDA if the Sponsor also presents a detailed plan or proposal. Conversely, if the proposal is too general or ambiguous, or if the question is open-ended, FDA reviewers may not be able to agree with the study design or to provide useful recommendations for the plan. We recommend not asking questions like these:
What Sponsor-conducted nonclinical studies does the Agency recommend to support opening an IND?
The Sponsor would like to support the safety of Product A by referencing safety information available from the labeling of an approved drug product. What listed drug does the Agency recommend for the Sponsor’s development program?
Do the Research
Ensure that the questions are credible from a scientific and regulatory perspective.
It is important to review all relevant reference information—from FDA websites, guidance documents, and precedents set by recent product approvals—prior to deciding on a drug development plan. This way, a Sponsor can ensure that the questions are well-informed and in line with FDA regulations and guidelines. Where possible, a Sponsor should support the rationale of proposed plans or studies with data from its own studies or strong evidence from published studies. Providing FDA reviewers with supportive scientific evidence increases the chance of obtaining agreement or helpful feedback.
Choosing not to take the time to understand regulatory guidelines before proposing a plan may backfire. Here’s an example:
A Sponsor is planning to develop ABC-101, a topical ointment with Drug X as the active pharmaceutical ingredient, to treat a chronic skin condition. Drug X has been approved as an ointment and the Sponsor learns about Listed Drug Z, a topical ointment indicated for use during ophthalmic surgical procedures. The Sponsor decides to rely on the safety information available from Listed Drug Z to support the safety of its product, based on information presented in the LD’s approved labeling. The Sponsor decides to ask the FDA the following questions:
Does the Agency agree that the proposed 505(b)(2) approach, including reliance on Listed Drug Z (ophthalmic ointment), is appropriate for review of the ABC-101 NDA?
The Sponsor is planning to rely, in part, on the Agency’s previous findings of safety for Drug X, as referenced in the approved labeling of Listed Drug Z. Does the Agency agree with this approach?
While these questions are clear and targeted, the Agency would likely not agree to this approach because the LD is not appropriate for the proposed product. Unlike Listed Drug Z, which is intended for acute use during ophthalmic surgery, ABC-101 is intended for chronic use. Thus, the safety information from the LD would not be sufficient to support the safety of the product.
This example illustrates the importance of doing the research to ensure that the strategies and plans proposed are scientifically and regulatorily sound.
Consider All Aspects of Drug Development
Do not limit questions to the early stages of a program.
The Pre-IND meeting is an opportunity to discuss development plans from the Pre-IND stage up until submission of an NDA. This includes gaining agreement or advice on a program’s integral CMC components and pivotal nonclinical and clinical studies to avoid unnecessary delays and costs.
Here are some examples of the types of questions to consider asking:
Does the Agency agree that the Sponsor-conducted nonclinical studies are sufficient to enable the proposed clinical development program?
Does the Agency agree that the clinical pharmacology information in the LD labeling, in conjunction with the PK data for the Sponsor’s product, is sufficient to fulfill the clinical pharmacology requirements for the NDA?
Does the Agency agree that a control strategy based on the outlined drug substance and drug product quality attributes will be sufficient to support the identity, potency, purity, quality, and stability review of the drug substance and the Sponsor’s drug product?
Giving FDA reviewers a chance to understand the overall plans for developing a product will ensure that the necessary studies are designed to provide the most useful information, an approach which could minimize the costs and potential risks of a development program.
For additional details on how to have a successful Pre-IND meeting, check out Camargo’s previous blog post titled Pre-IND Meetings: How to Achieve Success for 505(b)(2).
If you are in the early stages of your product’s development and considering a Pre-IND meeting, contact us to learn how Camargo can help you map out a strategic development plan to enable a successful and productive interaction with the FDA.