US FDA Regulatory Meetings

Understanding the various types of regulatory meetings available with the US FDA is crucial for successful drug development.

These meetings provide essential opportunities for pharmaceutical companies and sponsors to receive FDA guidance, discuss development strategies, and address specific challenges throughout the drug development process. Each meeting type serves a distinct purpose and follows specific protocols designed to maximize their effectiveness and efficiency.

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Types of Meetings with the FDA

The FDA offers several types of regulatory meetings:

• Type A
• Type B
• Type B End of Phase (EOP)
• Type C
• Type D
• INitial Targeted Engagement for Regulatory Advice on CDER and CBER ProducTs (INTERACT)

While Type B and Type B End-of-Phase meetings are the most commonly known, Type A meetings primarily address specific issues like clinical holds. Type C meetings cover development-related discussions that don't fall under other meeting categories, while Type D meetings focus on narrow sets of issues.

The newest category, INTERACT, is designed specifically for discussing novel product development even before reaching the pre-IND stage.

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Meeting Formats and Scheduling

The FDA offers four different formats for regulatory meetings:

• Face to face: Core attendees from both FDA and Sponsor meet in person
• Virtual face-to-face: Core attendees from both FDA and Sponsor meet via Zoom, MS Teams, etc.
• Teleconference: Audio only via Zoom, MS Teams, etc.
• Written Response Only: The FDA provides written answers to questions submitted in the meeting request and briefing book.

Among these options, face-to-face meetings are generally recommended, when possible, as they allow for more comprehensive discussions. It’s worth noting that written responses can sometimes be interpreted differently than intended, whereas in-person discussions allow for immediate clarification and broader conversation about overall development plans.

When scheduling a regulatory meeting with the FDA, sponsors must submit their meeting requests through official channels, either the electronic gateway (ESG), CDER NextGen Portal, or email. These submission requirements apply to all six types of FDA meetings.

The timing of briefing book submissions varies by meeting type. For Type A, Type D, and INTERACT meetings, briefing books should be submitted alongside the initial meeting request. Other meeting types allow for a time gap between the request and briefing book submission.

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Meeting Request Content

Meeting requests should typically include no more than ten questions. While exceeding this number won't automatically result in denial, it's important to consider that meetings usually last only one hour, making it difficult to address more than ten questions effectively.

The meeting request should contain enough information for the FDA to evaluate whether to grant the meeting and determine the most appropriate meeting format. While detailed data can be reserved for the briefing book, the request should clearly outline the current development status, drug product information, and context for the questions being asked.

Though the FDA doesn't provide specific templates for meeting requests, they do require certain key information:

• Application number
• Product name
• Proposed regulatory pathway
• Proposed indication
• The meeting type being requested
• Pediatric study plans (if applicable)
• Human factors engineering plan (if applicable)
• Combination product information (if applicable)
• Suggested dates and times
• List of questions by discipline

Questions should be worded in a way that encourages yes or no responses from the FDA. A common and effective approach is to begin questions with "Does the agency agree..." This structure typically prompts the FDA to provide a definitive answer along with any additional feedback, particularly if they disagree with the proposed plans or data. Each question should include relevant background information to help the FDA understand the reasoning behind the inquiry.

For the purposes of this blog, we will be focusing on Type B, INTERACT and Type D meetings.

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Type B Meeting?

Type B meetings include several other important meeting types:

• Pre-IND meetings are the most well known Type B meetings.
• Pre-EUA meetings are designed to discuss emergency authorizations.
• Pre-NDA and Pre-BLA meetings allow discussion before submitting these applications.
• Post-action meetings are typically requested three or more months after receiving FDA responses that aren't approvals, such as complete response letters or refuse-to-file letters following NDA or BLA submissions.

Type B meetings also include discussions about overall development programs for products that have received special designations, specifically Breakthrough Therapy Designation or Regenerative Medicine Advanced Therapy designation.[VH2]?

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Type B Meeting: Pre-IND Meeting?

Pre-IND meetings typically represent a sponsor's first formal interaction with the FDA unless their product qualifies for an INTERACT meeting. These meetings allow sponsors to discuss early development plans with the FDA before submitting an IND application, covering CMC, nonclinical studies, and clinical trials.

While many pre-IND meetings focus on products that haven't yet been tested in humans, they're also commonly held for products that have undergone Phase 1 studies abroad and are preparing for their first US clinical trial. The ideal timing for these meetings is 6 to 12 months before the planned IND submission.

The pre-IND meeting process follows a specific timeline:

• Sponsors should first request a pre-IND number from either CBER or CDER (depending on which center regulates their drug) 30 days before submitting their meeting request.
• The FDA then has 21 days to respond with their decision to grant the meeting and specify the meeting format.
• If granted, sponsors should submit their briefing book at least 30 days before the scheduled meeting.
• When the FDA determines a face-to-face meeting isn't necessary, they typically provide written responses within 60 days of the initial request.

Though not mandatory, pre-IND meetings have become standard practice as they help prevent potential clinical holds. During these meetings, the FDA can identify any missing elements required for clinical studies and share specific knowledge about particular products or indications that might not be readily available to sponsors. The FDA may also provide guidance on additional testing requirements or important considerations for drug development. These meetings ultimately help sponsors receive FDA recommendations for future development work and ensure they're on the right track before submitting their IND application.

Common topics discussed in pre-IND meetings vary by discipline. For CMC, discussions often focus on manufacturing processes, process controls, and specifications for drug substances and products. Complex products may require additional discussion about product characterization. When significant manufacturing changes occur between toxicology and clinical batches, sponsors often seek FDA agreement on process comparability.

For nonclinical aspects, sponsors typically discuss the design of definitive toxicology studies or seek confirmation that their completed studies adequately support proposed clinical work. Clinical discussions commonly center on study design and inclusion/exclusion criteria.

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INTERACT Meeting

INTERACT meetings are a relatively new meeting type designed specifically for novel products facing unique development challenges where little or no regulatory guidance exists and are in early development. Originally limited to CBER-regulated products, these meetings are now available for CDER-regulated products as well.

The FDA maintains strict eligibility criteria for these meetings. Sponsors should have identified a specific investigational product they intend to test clinically and completed preliminary preclinical proof-of-concept studies. However, they should not have conducted definitive toxicology studies or advanced further in nonclinical development.

The INTERACT meeting process follows specific timelines:

• Sponsors should submit their meeting request and briefing book simultaneously.
• The FDA schedules the meeting within 20 days of receiving these materials and provides preliminary responses no later than five days before the meeting.
• Sponsors are expected to respond to these preliminary comments within three days.
• If granted, the meeting occurs approximately 75 days after the initial request.
• While formal minutes aren't issued, the FDA provides an updated preliminary response document with meeting discussions within 30 days.

Type D Meeting

Type D meetings are a relatively new category designed to address narrow, specific issues at key development points where timely feedback is crucial. Unlike INTERACT meetings, Type D meetings have no specific requirements regarding the product development stage. However, they are limited to no more than five questions and should focus on only one or two topics. If a meeting request covers more than two topics or requires reviewers from three or more FDA disciplines, it will be denied and redirected to a Type B or Type C meeting.

The Type D meeting process follows an expedited timeline:

• Sponsors have to submit their meeting request and briefing book simultaneously.
• The FDA schedules the meeting within 14 days and provides preliminary responses no later than five days before the meeting.
• Sponsors are expected to respond to these preliminary comments within three days.
• If granted, the meeting occurs approximately 50 days after the initial request, making it about 25 days shorter than a Type C meeting.

Type D meetings are particularly useful in specific scenarios, such as:

• Following up on questions from previous formal meetings (beyond simple clarifications)
• Discussing innovative development approaches or clinical trial designs
• Addressing data presentation methods
• Reviewing efficacy endpoints for clinical trials
• Discussing specific analytical methods like potency testing

The key benefits of Type D meetings include efficient drug development, focused feedback on specific issues, and quick turnaround time (50 days from request submission). This prevents development delays and allows sponsors to proceed with FDA guidance rather than taking risks on uncertain decisions.

For comparison, the different meeting types follow distinct timelines:

• INTERACT meetings: within 75-day timeline, with meeting package required at request.
• Type B meetings: within 60-day timeline, with briefing materials due 30 days before the meeting.
• Type D meetings: within 50-day timeline, with meeting package required at request.?

HiRO's Regulatory Support

At HiRO, we leverage years of experience in partnering with biotech companies across the US, Europe, and the Asia-Pacific region.

We offer comprehensive support that includes managing submissions and guiding sponsors in crafting effective regulatory strategies, particularly tailored for early-stage products that may benefit from expedited pathways. Through our strategic regulatory support, we assist sponsors in optimizing the value of their FDA meetings and guidance, ensuring a clear pathway to successful submissions. By fostering open communication and collaboration with regulatory agencies, we help our clients address potential challenges proactively, ultimately advancing their development programs more efficiently.

With HiRO as your regulatory partner, you can navigate the complexities of the regulatory landscape with confidence, accelerating your journey from innovation to market and ensuring that groundbreaking therapies reach those who need them most.