Many sponsors of CBER-regulated products are familiar with pre-IND meetings, but there’s a new program called INTERACT, which stands for Initial Targeted Engagement for Regulatory Advice on CBER products. FDA’s goal for INTERACT is to provide advice to sponsors even earlier during development than what’s allowed under the pre-IND program. INTERACT provides an opportunity to obtain informal and non-binding FDA feedback on specific CMC, preclinical, and clinical issues that are raised by the sponsor in the briefing package.
In my opinion, all sponsors should consider scheduling an INTERACT meeting, since FDA’s feedback at this critical stage in development can lead to tremendous time and cost savings.
The optimal timing for INTERACT is after preliminary preclinical proof-of-concept (POC) and safety data have been generated but prior to initiation of definitive preclinical studies. Only one INTERACT meeting is granted per development program, and a teleconference is the only option for the type of meeting. Although there are no PDUFA-mandated timelines for INTERACT, CBER tries to schedule the teleconference as soon as feasible.
Some key elements to include in the briefing package are:
- A detailed scientific rationale for studying the product in the proposed study population
- CMC Information
- Description of the investigational product and manufacturing procedures
- Preclinical Information
- Detailed summary of completed in vitro and in vivo preclinical studies
- Results of POC and pilot safety studies
- Summary of the overall preclinical development plan, including discussion of future preclinical studies that are intended to provide safety justification for the clinical study
- Clinical Information
- Brief synopsis of the initial clinical study and overall clinical development plan
- Rationale for the target patient population
- Intended dosing regimen for the clinical study
- Safety and feasibility justification for the study procedures -- e.g., choice of the route of administration and dedicated delivery device(s)
Here’s some advice for an effective INTERACT meeting:
- Be sure not to schedule the meeting too early or too late in development
- Ensure that the content of the briefing package is sufficiently detailed
- Ask pointed questions in the briefing package regarding important CMC, preclinical, and clinical issues
- Avoid giving an extensive introductory summary, which reduces the time for substantive discussion during the teleconference
- Plan out the agenda to maximize time spent discussing key issues
- Understand that FDA generally will not agree to new proposals during the INTERACT meeting
- Request clarification if FDA’s rationale is unclear
- Ask the FDA Review Team about the possibility of additional interactions – e.g., if you’d like to receive feedback on a future preclinical protocol
Further information about INTERACT can be found on the FDA website: https://www.fda.gov/vaccines-blood-biologics/industry-biologics/interact-meetings-initial-targeted-engagement-regulatory-advice-cber-products.
Steve Winitsky, M.D., Vice President Technical brings over 11 years of former FDA experience as a Medical Officer, Team Leader, and Acting Branch Chief in the Office of Tissues and Advanced Therapies (OTAT, formerly known as OCTGT) in the Center for Biologics Evaluation and Research (CBER). Dr. Winitsky gained extensive experience with review and supervision of cell and gene therapy files -- INTERACTs (previously known in OTAT/OCTGT as pre-preINDs), INDs, and BLAs; plasma protein files -- INDs and BLAs; device files -- 510(k)s, IDEs, PMAs; and combination biologic and device files.
Dr. Winitsky served as the primary clinical reviewer for approximately 90% of the cardiovascular files regulated by OTAT/OCTGT, along with oversight of numerous files covering over 50 clinical indications (e.g., inborn errors of metabolism, infectious disease, solid organ transplant, orthopedics, endocrinology, immunology, rheumatology, in utero repair) as Team Leader and Branch Chief. He worked closely with the Center for Devices and Radiological Health (CDRH) in reviewing combination biologic and device files. During his time in OTAT/OCTGT, he was involved in Working Groups that were responsible for drafting and finalizing FDA and CBER Guidances and implementing PDUFA and 21st Century Cures initiatives. He also reviewed or supervised the review of numerous Fast Track, Regenerative Medicine Advanced Therapy (RMAT), and Breakthrough Designation request applications.
Dr. Winitsky earned a B.A. in Chemistry from Columbia University in New York in 1992. He then went on to earn his M.D. from the University of Miami School of Medicine in Florida in 1996. He was an internal medicine resident at Emory University and completed his residency in the NHLBI/NIH Clinical Associate Program in 1999, continuing as a Clinical and Research Fellow in the NHLBI Cardiology Branch, Laboratory of Molecular Cardiology, Molecular Physiology Section. Dr. Winitsky has received several Recognition Awards from the Food and Drug Administration, the most recent being an FDA Outstanding Service Award and a CBER Director’s Distinguished Service Award.