Premier Consulting’s regulatory strategists specializing in the US FDA’s 505(b)(2) approval pathway are often asked how a sponsor can recover from a pre-IND meeting that doesn’t go as planned. While we firmly believe that setbacks can be turned into opportunities for growth and success, conducting an optimal pre-IND meeting at the outset is always preferred. In this blog post, we will share valuable strategies and insights for conducting an optimal meeting and navigating the recovery process to get your drug development program back on track if needed.

Preparation

To ensure a successful outcome for your 505(b)(2) pre-IND meeting, thorough preparation is key. Unlike, a 505(b)(2) development program is typically more abbreviated than a traditional IND program, so it’s essential to approach the pre-IND meeting with a strategic mindset, focusing on the regulatory requirements and the path towards a new drug application (NDA).

Start by conducting a comprehensive strategic assessment of your proposed product. This assessment should consider critical issues from multiple perspectives and define the regulatory strategy. This includes identifying the necessary information to streamline the development program, outlining the bridging strategy, and determining the most appropriate listed drug, if applicable. The goal is to minimize regulatory and execution risks through a well-defined clinical, clinical pharmacology, nonclinical, and CMC (chemistry, manufacturing, and controls) development plan and a time and cost analysis for market entry. This robust plan will form the foundation of your pre-IND meeting preparation and discussion.

During the preparation phase, carefully craft your questions in a way that is most likely to elicit valuable FDA feedback for trial design and clarification of next steps. Open-ended questions rarely produce specific feedback. Additionally, assembling the right development and regulatory team is critical for success. A multidisciplinary team encompassing expertise in 505(b)(2) programs, CMC, regulatory affairs, nonclinical, clinical, and clinical pharmacology will ensure comprehensive coverage of all aspects affecting your development program.

Examples of inadequate pre-IND meetings

Unsatisfactory pre-IND meetings can hinder progress and increase regulatory risks. Let’s explore a few examples to understand the common pitfalls and challenges that companies face.

Lack of regulatory knowledge

In one case, the proposed product had no approved drug as a reference but had been marketed unapproved for many years. The sponsor was unaware that the application could still be approved through the 505(b)(2) pathway and qualify as a new chemical entity eligible for marketing exclusivity.

Misunderstanding of pediatric requirements

In this example, a company did not understand the Pediatric Research Equity Act (PREA) and its associated pediatric assessment requirements. This lack of knowledge led to uncertainties regarding submitting a pediatric plan and the required studies, as well as delays in meeting NDA timelines.

Insufficient toxicology studies

Companies sometimes fail to anticipate the nonclinical toxicology and bridging studies that are necessary for a different route of administration from the listed drug. This lack of understanding can lead to inadequate preparation and an inability to provide a strategic and scientific rationale to the FDA during the pre-IND meeting.

Lack of bridging strategy

Inadequate appreciation of the requirements and strategies for bridging in a 505(b)(2) program can create uncertainties as to which studies are required for approval. Such misunderstandings can result in inappropriate clinical pharmacology study designs, insufficient justification of the proposed bridging strategy, and subsequent delays to (or failure to gain) NDA approval.

Recovery Plan

Recovering from an unsatisfactory pre-IND meeting requires a proactive approach.

Start by analyzing the feedback received during the meeting and thoroughly reviewing the FDA’s recommendations and suggestions. Although the feedback may be less than optimal, there are always pearls of wisdom that can be gleaned from it.

Identify the gaps, concerns, and areas that need improvement in your development program. Determine if the filling gaps will require a subsequent FDA meeting.

Engage your multidisciplinary team to address these issues, and develop a robust recovery plan. Ensure clear communication and collaboration among team members, focusing on implementing changes to meet the FDA’s expectations.

It may be necessary to conduct additional studies, refine your clinical trial design, update your nonclinical data, and/or enhance your regulatory strategy based on the feedback received. Therefore, demonstrating a proactive and responsive approach can significantly improve your chances of success.

In the worst cases, another FDA meeting (Type B or C) may be required to obtain the necessary feedback to get the program back on track. But, again, staying focused on the overall strategy is important.

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In summary, an unsatisfactory pre-IND meeting does not spell the end of your drug development journey. By focusing on the strategy and assembling multidisciplinary subject matter experts to discuss the issues, you can develop a recovery plan that sets you on the path to success. Embrace the feedback received, make the necessary adjustments, and leverage your team’s expertise to optimize your development program. With careful planning and proactive measures, you can overcome setbacks and steer your drug development program towards a successful outcome.