OTP INTERACT Meetings

INTERACT or an INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs is a meeting at a specific time early in product development. The appropriate timing for an INTERACT is when a sponsor has identified the investigational product to be evaluated in a clinical study and conducted some preliminary preclinical proof-of-concept studies with the intended investigational product but has not yet designed and conducted definitive toxicology studies. Considerations for whether the status of product development is premature or too advanced for an INTERACT Meeting are discussed later in this webpage. For additional details on a development program’s qualification for INTERACT, how to request and where to send the meeting request for products regulated in OTP/CBER, please see SOPP 8101.1: Regulatory Meetings with Sponsors and Applicants for Drugs and Biological Products. Additionally, sponsors may now email meeting requests to cberdcc_emailsub@fda.hhs.gov, if the product is regulated in CBER. 

*Note: If you are submitting a meeting request for a CDER-regulated product, contact druginfo@fda.hhs.gov for instructions on how to submit it to CDER.

Table 1: Timelines for INTERACT Meetings

OTP Response to Meeting Request**	21 days
Meeting Scheduling or WRO issued***	75 days
Meeting Package Due to OTP	With meeting request
Meeting Length	60 minutes
OTP Preliminary Response to Questions in the Package to Sponsor	NLT* 5 days before the meeting
Sponsor’s Response to FDA Preliminary Response	Sponsor’s Response to FDA preliminary response

*NLT – No Later Than
Source: Information from the Formal Meetings Between the FDA & Sponsors or Applicants of PDUFA Products Guidance for Industry
**Calendar days from FDA receipt of the meeting request to the date that OTP will respond with the decision to grant or deny the meeting, as well as specifying the format and date of the meeting, if granted.
*** Calendar days from FDA receipt of the meeting request to date the meeting will be held, or the WRO will be issued.

OTP Procedures Following an INTERACT Meeting Request

• OTP does not send an acknowledgement email or letter following OTP’s receipt of the request. However, OTP will send the decision to grant or deny the meeting request, along with the meeting date, if granted, or reasons for denial by Day 21.  
• SOPP 8101.1: Regulatory Meetings with Sponsors and Applicants for Drugs and Biological Products states that INTERACT Meetings will be held within 75 calendar days of receipt of the meeting request.
• OTP will try to provide a tentative list of meeting attendees with the meeting confirmation.

Considerations for a Complete and Informative INTERACT Meeting Package

Meeting Package and Number of Questions

The meeting package should be submitted with the meeting request. The sponsor’s meeting package should include clearly worded and targeted questions that directly address concerns about the product development programs. The number of questions in a meeting package should not exceed what can be reasonably discussed within the duration of the allotted meeting time. For a 60-minute meeting, a maximum of 10 questions (inclusive of sub-questions) would be considered reasonable. For example, Questions 1a, 1b, 1c, 1d, 2, and 3 would be equivalent to 6 questions.
Written Response Only (WRO) is considered to be equivalent to 60-minute meetings. Therefore, the maximum of 10 questions (inclusive of sub-questions) is applicable.

Size of Meeting Package

It is important to include background information sufficient to support the questions in the package. OTP may cancel a meeting if the meeting package is grossly inadequate and does not contain sufficient information to enable FDA to address the questions. However, voluminous meeting packages are discouraged. Meeting packages should be succinct and not to exceed 50 pages. OTP will evaluate the meeting request and package for completeness and appropriateness for an INTERACT Meeting based upon the meeting criteria described in SOPP 8101.1: Regulatory Meetings with Sponsors and Applicants for Drugs and Biological Products.

Below are best practices for Chemistry, Manufacturing, and Controls (CMC), pharmacology/toxicology (P/T), and clinical content of an INTERACT Meeting package.

Chemistry, Manufacturing, and Controls (CMC)

The CMC section of the INTERACT briefing package should provide:

1. A summary or high-level description of the product, its manufacturing process and the proposed characterization and lot release tests.
2. The sponsor’s position and justification for all of the sponsor’s questions.
3. References to published information related to the product, along with copies of the publications.

OTP recommends that sponsors refer to:

• Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)
• Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs)

Pharmacology / Toxicology

The pharmacology/toxicology section of the INTERACT briefing package should provide:

1. A comprehensive summary of all preclinical (in vitro and in vivo) studies conducted thus far using the intended clinical product, and the results obtained. Contributions from publications that the sponsor considers relevant to their program should be integrated into this summary, and copies of each publication should also be provided.
2. A detailed discussion, with protocol outlines, regarding the additional preclinical proof-of-concept studies the sponsor thinks they need to conduct to adequately support administration of the intended clinical product in the target patient population.
3. The sponsor’s position and justification for all questions the sponsor poses.
4. Questions regarding definitive preclinical safety studies are discussed in the Pre-IND meeting and should not be included in the INTERACT package.

OTP recommends that sponsors refer to the FDA guidance “Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products.”

Clinical

In the context of an INTERACT, clinical comments are generally high-level recommendations regarding the overall clinical development program, and do not focus on details of a specific clinical protocol.

The INTERACT briefing package should describe:

1. the disease of interest
2. target study population
3. available natural history information/data on the condition
4. available treatment options for condition and
5. brief outline of first-in-human study

OTP recommends that sponsors refer to the FDA guidance “Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Guidance for Industry.”

Common Reasons for INTERACT Meeting Denials

Not all product development programs qualify for an INTERACT Meeting. Listed below are examples of reasons for denying an INTERACT Meeting request:

• A meeting was previously held for this product.
• A meeting package does not accompany the INTERACT Meeting request.
• The meeting package is substantially deficient, significantly limiting the ability to provide constructive feedback.
• The questions are focused on jurisdiction or regulatory pathway. OTP does not use INTERACT Meetings to answer questions about:
  • Whether a product is appropriately regulated as a drug, device, and/or biological product or combination product, or what Center or Office should be the lead in review. For such questions, the sponsor may contact OTP Policy Group at OTP_ADP@fda.hhs.gov.
  • Or whether it is appropriately regulated solely under Section 361 of the PHS Act and regulations in 21 CFR Part 1271. For such questions, the sponsor may visit the Tissue Reference Group website at https://www.fda.gov/vaccines-blood-biologics/tissue-tissue-products/tissue-reference-group or contact the Tissue Reference Group in OTP at TissueReferenceGroup@fda.hhs.gov.
• The stage of the product development program is premature or too advanced for an INTERACT Meeting. For example:
  • A request may be premature if:
    • The sponsor does not specify the investigational clinical product.
    • The sponsor does not provide preclinical proof-of-concept (POC) or other pilot data.
    • The sponsor has not conducted any preclinical studies (e.g., proof-of-concept studies) with their intended clinical product.
  • A request may be too advanced for an INTERACT Meeting and more appropriate for a pre-IND meeting if:
    • The sponsor has completed proof-of-concept (POC) and some safety studies and is at the point of design and conduct of definitive toxicology studies
    • The sponsor has defined the manufacturing process to be used for the clinical studies and has developed assays and preliminary lot release criteria.
    • The preclinical testing and manufacturing process for the product uses the same or a similar platform as for other product(s) submitted to OTP by the same sponsor.
    • Clinical data exist from previous studies for the same product and clinical indication.

Best Practices for Managing INTERACT Meetings with OTP

Prior to the INTERACT Meeting

For INTERACT Meetings, as indicated in the table above, OTP will send the preliminary response no later than 5 days before the scheduled meeting.  The sponsor is expected to respond to OTP’s preliminary responses not later than 3 days prior to the scheduled teleconference (see Table above).

• If the sponsor finds that OTP’s preliminary responses and advice are sufficiently clear and complete to obviate the need for further discussion, the sponsor should inform OTP in writing as soon as possible so that OTP may cancel the meeting. These responses would then become the official OTP responses to the sponsor’s questions.
  • If, after cancellation of the INTERACT Meeting, the sponsor subsequently wishes to follow-up on topics from the preliminary responses or pose new questions, then the sponsor should submit these follow-up or new questions in their Pre-IND meeting. 
• If the sponsor wishes to continue with the meeting, the sponsor should identify which of the original questions in the briefing package they wish to discuss and list the questions in the proposed order of discussion. As a rule, the meeting discussion follows the prioritized order of importance set by the sponsor, with the understanding that all questions may not be addressed due to time constraints.   When referencing questions, the sponsor should use OTP’s preliminary responses document numbering format.
• After receiving OTP’s preliminary response, the sponsor should not submit new questions and new information (e.g., alternative approaches or new proposals to address OTP comments) that were not previously submitted in the original briefing package. OTP preliminary responses are prepared after deliberative review, and usually include cross discipline internal discussion of the original meeting package and questions.  OTP will not have adequate time to review new material and have sufficient inter-discipline internal discussion necessary to prepare answers to new questions.  Therefore, sponsors should thoughtfully prepare their meeting package and questions.
  • In some situations, a sponsor may want to develop new questions/alternative approaches in response to OTP’s preliminary responses or discussion at the meeting.  Such new questions/alternative approaches should be submitted as part of the Pre-IND meeting package.

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During the INTERACT Meeting

The meeting is the sponsor’s opportunity to obtain clarifications on OTP preliminary responses. As stated above, during the meeting the OTP team will not be able to provide feedback on new information (e.g., new questions, alternative approaches or new proposals to address OTP comments) that was not previously submitted in the original briefing package.

Sponsors may choose to make a presentation at the beginning of the meeting.  However, because OTP staff will be familiar with the meeting package content and questions, OTP recommends that sponsors forgo a presentation and use the allotted meeting time to obtain clarifications to OTP’s preliminary responses to the sponsor’s questions. 

OTP recommends that time be reserved at the end of the meeting for the sponsor to summarize the major discussion points and action items.

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After the INTERACT Meeting

OTP will NOT issue a meeting summary after the meeting.  For INTERACT Meetings, preliminary responses will be annotated and resent within 30 days if advice provided changes as a result of the meeting. 

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Requests for Clarification

A request for clarification may be sought after an INTERACT Meeting, to ensure the requestor’s understanding of FDA feedback provided in a preliminary response (if the formal meeting was canceled), meeting summary, or written response only (WRO) issued by OTP.

Find out more about Requests for Clarification