This document provides information on the background, scope, and meeting scheduling for the CBER INitial Targeted Engagement for Regulatory Advice on CBER producTs (INTERACT) program. An INTERACT meeting enables sponsors to obtain preliminary informal consultation with the Agency at an early stage of development prior to a pre-IND meeting, subject to Agency resource constraints.
Development of innovative investigational products can introduce unique challenges due to unknown safety profiles, complex manufacturing technologies and issues, incorporation of innovative devices, and the use of cutting-edge testing methodologies.
Through an INTERACT meeting, sponsors can obtain initial, nonbinding advice from FDA regarding chemistry, manufacturing and controls, pharmacology/toxicology, and/or clinical aspects of the development program. This informal meeting can: 1) assist sponsors conducting early product characterization and preclinical proof-of-concept studies; 2) initiate discussion for new delivery devices; 3) inform sponsors about overall early-phase clinical trial design elements; and 4) identify critical issues or deficiencies for sponsors to address in the development of innovative products.
An INTERACT meeting is not intended to take the place of a pre-IND meeting, which occurs prior to the submission of an IND to discuss the scope and design of planned initial studies, design of animal studies needed to support human clinical testing, and the format for the IND.1 Conversely, an INTERACT meeting also is not a venue to provide advice to sponsors who have yet to initiate any product development activities. Prior to requesting an INTERACT meeting, a sponsor needs to have selected a specific investigational product or a product-derivation strategy to evaluate in a clinical study.
Products that are further along the development pathway should be discussed in the context of a pre-IND meeting. Pre-IND submissions typically include a description of product manufacturing and testing; summaries of completed and planned preclinical studies; and a Phase 1 clinical study design or protocol. Each of these elements may be further refined after the pre-IND meeting, to support an IND. Information about pre-IND and IND submissions is available in the FDA guidance document, “Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products.”
The INTERACT program generally consists of one consultation on issues that a sponsor needs to address, often this is prior to moving forward with the submission of a pre-IND meeting request, such as choice of appropriate preclinical models or necessary toxicology studies. The INTERACT program is also intended for such occasions when development of innovative investigational products introduces new safety concerns due to the unknown safety profiles resulting from the use of complex manufacturing technologies, innovative devices, or cutting-edge testing methodologies.
4. Examples Within the Scope of INTERACT
The following are examples of questions and topics within the scope of an INTERACT meeting, grouped by discipline:
Chemistry, Manufacturing and Controls (CMC)
- Discussion of CMC issues and testing strategies aimed at demonstrating product safety, adequate to support a first-in-human study. For example:
- Innovative technologies for the qualification of new cell substrates.
- Product-manufacturing (e.g., cell sources, donor eligibility determination for allogenic cellular products and qualification of international donors).
- Product dependent and manufacturing process dependent reagents, starting materials and critical product components.
- Qualification of a novel delivery device related to a specific investigational product.
- Discussion of complex software issues and strategies to support device use in clinical studies.
- Overall advice related to the design of proof-of-concept or other pilot safety/biodistribution studies necessary to support administration of an investigational product in a first-in-human clinical trial.
- Specific questions on: 1) the adequacy of the selected animal models; 2) study design (e.g., endpoints, dose levels, route of administration, dosing regimen); and 3) acceptability of innovative preclinical testing strategies, products and/or delivery modalities.
- Advice on modification of a preclinical program or study design, as applicable, to ensure judicious use of animals.
- General recommendations regarding a future first-in-human trial in a target clinical population. These recommendations may vary based on scientific knowledge about the disease and regulatory experience with the disease.
- Provide recommendations regarding the approach for further development of an early stage product for which limited CMC, pharmacology/toxicology and/or clinical data were collected outside of a U.S. IND.
5. Examples Outside the Scope of INTERACT
The following are examples of questions and topics that are generally outside the scope of an INTERACT meeting, grouped by discipline:
Chemistry, Manufacturing and Controls
- Questions about candidate product selection for further development (including circumstances where the sponsor has not decided between multiple product options or the investigational product has not been identified).
- Situations in which the sponsor previously has received formal regulatory advice about a similar product and indication.
- Questions regarding the adequacy and design of definitive toxicology studies. Agency input on the design of definitive preclinical toxicology studies occurs in the context of pre-IND meetings.
- Pre-review of completed proof-of-concept or toxicology studies. Reviews of the final study reports for the completed studies occurs in the setting of IND submissions.
- Questions regarding a preclinical testing plan where no preliminary data from pilot studies are provided.
- Routine questions regarding specific aspects of clinical study protocol design, such as inclusion and exclusion criteria. (Review of clinical study designs or protocols occurs in the context of pre-IND submissions.)
6. BLA Device Considerations
An INTERACT consultation may be requested by developers of innovative blood screening devices regulated as BLAs by CBER to discuss issues that a sponsor needs to address prior to moving forward with the submission of a pre-IND meeting request for these devices (e.g., complex software issues, analytical performance requirements). Contact CBER at INTERACT-CBER@fda.hhs.gov to discuss your specific situation.
7. Meeting Scheduling
Requests for INTERACT meetings should be forwarded to INTERACT-CBER@fda.hhs.gov. In order to assess the request, please provide:1) a summary of the product and disease being treated, 2) information about the product development to date and future development plans, if appropriate and 3) questions the sponsor wishes to have addressed. Sponsors will receive a response regarding the scheduling of their requested meeting from the responsible office within 21 calendar days of receipt. Although CBER will do its best to hold INTERACT meetings within 90 calendar days of receiving requests, resource constraints may limit scheduling within this timeframe.
For a productive meeting, we recommend that sponsors review the following procedure: SOPP 8214, INTERACT Meetings with Sponsors for Drugs and Biological Products, which describes CBER’s expectations for meeting requests and subsequent meeting packages. INTERACT meetings will generally be conducted via teleconference.