On September 30, 2022, the FDA User Fee Reauthorization Act of 2022 (PDUFA VII, 2023-2027) was signed into law by the President of the United States. There have been several changes made under this version of the user fee program, here, we focus on the addition of a new formal PDUFA meeting type: Type D meetings and expansion of Initial Targeted Engagement for Regulatory Advice (INTERACT) meetings, originally developed for CBER products (June 2018) to expand to CDER Products. We provide a discussion of what these additional meetings include, the timeline, and expectations from these initiatives. For more details see the FDA's Commitment Letter.

INTERACT meetings are intended to facilitate early discussions of novel questions and unique challenges in early development (i.e., for sponsors that are not yet ready for a pre-IND meeting). INTERACT meeting discussions may focus on topics such as the design of IND-enabling toxicity studies, complex manufacturing technologies or processes, and the development of innovative devices to be used with drug or biological products. INTERACT meetings can be used to clarify the Agency’s expectations, science-based requirements, regarding product development programs and to help facilitate more efficient product development.

These meetings were first provided to acquire early development input for the complexities of products regulated by the Center for Biologics Evaluation and Research (CBER). The meetings will now also encompass products regulated by the Center for Drugs Evaluation and Research (CDER) under PDUFA VII.

The following questions and topics are appropriate in the scope of the new INTERACT meetings:

• Questions for all CDER and CBER products (i.e., questions where there is no existing guidance or other information in writing from the FDA the company could reference). These meetings are intended to provide FDA feedback on issues that a sponsor needs to address before a pre-IND meeting, including issues such as the choice of appropriate preclinical models or necessary toxicology studies for novel drug platforms or drug candidates.
• CMC issues or testing strategies aimed to demonstrate product safety, adequate to support first-in-human study.
• Overall advice related to the design of proof-of-concept or other pilot safety/biodistribution studies necessary to support the administration of an investigational product in a first-in-human clinical trial.
• General recommendations regarding a future first-in-human trial in a target clinical population where the population is novel and there is no prior precedent or guidance.
• Recommendations on approach for further development of an early-stage product with limited CMC, pharmacology/toxicology, and/or clinical data that were collected outside of a US IND.

Other topics not included in the previously mentioned list must be agreed upon with the FDA on a case-by-case basis.

• Type D meetings were added to the already existing FDA meeting types (A, B, and C). Type D meetings are intended to focus on a narrow set of issues (e.g., often one, but typically not more than two issues and associated questions). The request for a Type D meeting may include:
• A follow-up question that raises a new issue after a formal meeting (i.e., more than just a clarifying question about a FDA response from a prior meeting).
• A narrow issue on which the sponsor is seeking Agency input with only a few
• associated questions.
• A general question about an innovative development approach that does not
• require extensive, detailed advice.

The Type D meetings are not intended to cover more than two topics at a time. If the sponsor has multiple issues or a complex single issue with multiple questions they should request a Type C Meeting, rather than multiple Type D Meetings. Additionally, the issue to be discussed in a Type D meeting should not require input from more than three disciplines or divisions at FDA. If the meeting request is outside the scope of a Type D meeting, FDA will inform the sponsor that the meeting will be converted to the appropriate meeting type (Type B or C). The sponsor may then either withdraw their request or accept FDA's meeting-type conversion without resubmitting a new request. As Type D meetings have a 14-day response time, they are ideal for (relatively) rapid advice.

The Agency may determine that a written response to the sponsor's questions will be the best means of providing feedback and advice for Type D and INTERACT meetings (as with pre-IND and Type C meetings) even though the sponsor has requested a face-to-face meeting. If the FDA determines that a written response is adequate, they will inform the requester of the date to expect the response.

The INTERACT and Type D Meetings are introduced in addition to the pre-existing FDA meeting types: 

• Type A Meetings are used to address major issues for an otherwise stalled development program (i.e., a “critical path” meeting) or to address an important safety issue. Post-action meetings requested within three months after an FDA regulatory action other than approval will also generally be considered Type A meetings.
• Type B Meetings are for development milestones (e.g., pre-IND, pre-NDA, end-of-phase). Meetings regarding REMS or post-marketing requirements that occur outside the context of the review of a marketing application will also generally be considered Type B meetings.
• Type C Meeting is any type of meeting other than Type A, B, B(EOP), D, or INTERACT, and often is seen as an “across-the-board” meeting.

Table 1 below indicates the timeframes for FDA’s response to a meeting request.

Table 1: FDA Meeting Types and Response Times Included in PDUFA VII

*If the scheduled date of a Type B(EOP) or C meeting is earlier than the timeframes specified above, the meeting background package will be due no sooner than six calendar days following the response time for Type B(EOP) meetings and seven calendar days for Type C meetings.
EOP = end of phase.

The FDA anticipates releasing a revised version of its current draft guidance by September 30, 2023, that includes information related to INTERACT, Type D meetings, and follow-up opportunities. Additionally, FDA will update relevant Manual of Policies and Procedures (MAPPs) and Standard Operating Policies and Procedures (SOPPs).

The future expectations regarding the additions are in-line with the needs for these new types of meetings. Therefore, the INTERACT is expected to help streamline activities for companies in early clinical development and need to get early feedback on the CMC, nonclinical and/or clinical development programs where there is otherwise no guidance. 

Type D performance goals will be phased in starting in fiscal year (FY) 2023. By FY 2023, the FDA aims to conduct 50% of Type D meetings or respond to meeting requests within 50 calendar days. A 10% performance increase is expected each year, with a goal of 90% by FY 2027.

The most valuable input you can elicit from Health Authorities (HAs) is based on your questions to them and how you support and explain your position. Questions should be clear and well-defined and data to support your position should be provided in a complete, yet concise manner. If you receive Health Authority (HA) advice during development, it is best to adhere to this advice or discuss unresolved issues at a future meeting.

• Prioritize the points that you need to discuss.
• Be transparent with previous feedback from the FDA or other Agencies.
• Anticipate likely questions and responses for your questions/positions and practice responding with your team prior to meeting with the Agency.

Our unique team placement both in the US and Europe can help you optimize interactions with regulatory authorities, including the preparation and conduct of Health Authority meetings and, specifically, new FDA Type D and INTERACT meetings. Schedule a meeting with us now.