The INTERACT Meeting Playbook

INTERACT — INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs — is the earliest formal meeting FDA offers. This meeting sets applicants up for a more formal subsequent meeting, a Pre-IND, ahead of an investigational new drug (IND) application to allow you to study your therapy in humans. INTERACT meetings are intended for novel products facing a novel, challenging issue early in development, where getting FDA’s read now could keep the program from stalling later.

Both CDER and CBER have strict limitations on meetings, so INTERACT can be an additional opportunity for FDA feedback even if you’re uncertain whether you meet all the criteria. Carefully framing your submission is critical to ensure FDA accepts your meeting request and product development strategy.

For cell and gene therapies, INTERACT meetings are run by CBER’s Office of Therapeutic Products (OTP), and is the same review team you’ll work with during the Pre-IND, IND, all the way up to the Biologics License Application (BLA). This playbook covers what INTERACT is for, the narrow window in which it makes sense, what belongs in scope, the data you need in hand, and how to get started.

01 · THE PURPOSE

What INTERACT is actually for

INTERACT is intended to facilitate IND-enabling efforts when an applicant is facing a novel, challenging issue that might otherwise delay entry into the clinic. This meeting happens prior to a Pre-IND and the questions typically relate to what it will take to support a future IND, not to the fine detail of a clinical protocol. Topics squarely within scope include:

• Preclinical models and toxicology: choice of appropriate species or models, and the necessary studies for a novel product.
• CMC and manufacturing: testing and comparability strategies aimed at demonstrating product safety adequate to support a first-in-human study.
• Potency assays: although not required until much later in development, potency assays are a challenging part of BLAs and FDA’s feedback early in the process contribute to success.
• Proof-of-concept design: advice on the pilot safety or biodistribution studies needed to support first administration in humans.
• Novel first-in-human populations: general recommendations where the target population is novel and there is no prior precedent or guidance.
• Early data collected outside a U.S. IND: how to approach further development of an early-stage product with limited CMC, pharm/tox, or clinical data.

The common thread is questions for which no existing FDA Guidance gives you a clear answer. However, even if you think you have a plan, don’t rule out an INTERACT. Tthe complexity of biologics means that almost all programs have at least one question without a detailed prescriptive answer in Guidance. If you’re developing a cell and gene therapy, chances are you’re eligible for INTERACT.

02 · THE WINDOW

The Goldilocks timing problem

INTERACT has a narrow window. The right time is when you have identified the investigational product to evaluate in a clinical study and have run some preliminary preclinical proof-of-concept work with that intended product, but have not yet designed and conducted your definitive toxicology studies. Land outside that window on either side, and the request is likely to be denied.

Few development programs fit neatly into such a narrow window, and this is where appropriate framing comes into play. You are not required to submit everything you’ve done, and you can decide what to include in an INTERACT. Your submission should include why the timing is appropriate: make it easy for the reviewers to accept your INTERACT.

Too early (premature)

Just right (INTERACT)

Too advanced (go to pre-IND)

No specific investigational product identified; no preclinical POC or pilot data; no studies yet run with the intended clinical product.

Product (or product-derivation strategy) selected; preliminary POC done; definitive tox not yet designed; a genuinely novel issue is blocking progress.

POC and some safety studies done and you’re designing definitive tox; manufacturing process and preliminary lot-release defined; same platform already submitted to OTP; or clinical data already exist for the same product and indication.

WHY THE WINDOW IS SO TIGHT

INTERACT is a one-time, early conversation that is the precursor, not a substitute, for the pre-IND meeting. If you have already progressed to designing definitive toxicology or have locked your manufacturing process, FDA will tell you the right venue is pre-IND. If you cannot yet name your product or show any proof-of-concept, there is nothing concrete for FDA to advise on. Be strategic when framing your product development in your INTERACT.

03 · SCOPE

Establish a strategic scope for your INTERACT

Some of the most common denials come from asking INTERACT to answer questions it was never meant to address. Three categories belong somewhere else entirely:

• Jurisdiction or regulatory pathway: whether your product is a drug, device, biologic, or combination product, or which Center leads. The pathway is dependent on the specific question, but many jurisdiction and associated pathway questions go to the Office of Combination products via a Pre-Request for Designation (Pre-RFD).
• 361 HCT/P status: whether a product is regulated solely under Section 361 of the PHS Act and 21 CFR Part 1271. That is the Tissue Reference Group’s remit, not OTP’s INTERACT.
• Definitive preclinical safety studies: questions about your definitive toxicology program belong in the pre-IND meeting and should be kept out of the INTERACT package. However, it’s easy enough to continue with INTERACT for input on CMC, just don’t mention your definitive toxicology studies.
• Clinical studies: INTERACT focuses on early product development and FDA will not be ready for a detailed clinical review. They’ll give some feedback, but you’ll get better clinical review in the Pre-IND

Even if your timing is perfect, mixing out-of-scope questions into the package is a fast route to a denial. Similarly, including detailed information about topics that are too mature for INTERACT is an easy way for FDA to refuse the meeting request. Good news is that there is no requirement to include details of your entire program, so you only have to provide information that supports INTERACT eligibility.

SELECTIVE INCLUSION

Don’t feel pressured to include everything in your INTERACT. Even if you already have a draft clinical protocol, you might still have non-clinical or CMC questions. Keep your clinical protocol to yourself, and your submission can still be INTERACT-eligible for helpful feedback on definitive pharm/tox studies and potency assay development.

04 · THE EVIDENCE

What you need in hand

INTERACT is not a brainstorming session over a blank page. To be granted and to be useful, the meeting needs something concrete to react to. At minimum you should have a specific investigational product (or a defined product-derivation strategy) and preliminary non-clinical proof-of-concept or pilot data generated with that intended product. Discipline by discipline, expect to bring:

Chemistry, Manufacturing & Controls (CMC)

A high-level description of the product, the manufacturing process, and the proposed characterization and lot-release tests — plus your position and justification for each CMC question, with copies of any relevant publications.

Pharmacology / Toxicology

A comprehensive summary of all in vitro and in vivo studies run so far with the intended clinical product and their results; protocol outlines for the additional POC studies you think you need; and your position on each question. Keep definitive-tox questions out — those are for pre-IND.

Clinical

At a high level: the disease, the target population, available natural-history information, existing treatment options, and a brief outline of the first-in-human study. INTERACT clinical feedback is general, not a protocol review.

05 · ELIGIBILITY

Why requests get denied

CBER’s workload is high, and a poorly constructed INTERACT with uncertain eligibility is easy for the review team to deny. OTP lists specific, recurring reasons it denies INTERACT requests. Most of them are avoidable with planning and scrutiny on what should be included in your submission. If you are concerned about falling into one of these categories, proactively addressing why you are eligible in your submission can help convince the review team.

Reason for denial

How to avoid it

A meeting was already held for this product.

INTERACT is one-time per product; plan the single early conversation carefully.

No meeting package accompanied the request.

The package must be submitted with the request, not after.

The package is substantially deficient.

Include enough information to support every question; a thin package limits the feedback FDA can give.

Questions focus on jurisdiction or pathway.

Route jurisdiction to OTP Policy Group or OCP and 361 status to TRG.

The program is premature or too advanced.

Confirm you are inside the INTERACT window before requesting. If you’re worried about being too advanced, there’s no need to include everything, so be strategic with what you submit.

06 · GETTING STARTED

How to request an INTERACT

The mechanics are specific. INTERACT submission contains both the meeting package together with the meeting request. For a CBER-regulated product, requests may be emailed to OTP’s coordination address or submitted through the electronic gateway. OTP does not send an acknowledgement, but it will respond with a grant or denial by Day 21.

Step

Timeline

OTP responds to the meeting request (grant or deny)

Within 21 calendar days

Meeting held, or Written Response Only (WRO) issued

Within 75 calendar days of receipt

Meeting package due

With the meeting request

Meeting length

60 minutes

OTP preliminary responses sent to applicant

No later than 5 days before the meeting

Applicant responds to preliminary responses

No later than 3 days before the meeting

Keep the package succinct — 50 pages maximum — and the questions targeted, no more than 10 including sub-questions (so 1a, 1b, 1c, 1d, 2, 3 counts as six). A Written Response Only is treated as equivalent to a 60-minute meeting, so the same limits apply.

INTERACT VS. PRE-IND

INTERACT serves as a precursor to Pre-IND, and mapping out what you intend to address in each submission optimizes your FDA feedback. INTERACT is earlier and narrower fairly early in development. The Pre-IND meeting is more comprehensive and opportunity for feedback before you devote resources to the IND and initiation of your human clinical study.

FDA sources & references

• OTP INTERACT Meetings — Timing, package content, denials, and best practices for CGT products. fda.gov ↗
• Formal Meetings Guidance — INTERACT scope and topics within Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products. fda.gov ↗
• SOPP 8101.1 — CBER procedures for INTERACT and other regulatory meetings. fda.gov ↗
• Referenced guidances — Preclinical Assessment of Investigational Cellular and Gene Therapy Products; Considerations for the Design of Early-Phase Clinical Trials of CGT Products; CMC for Human Gene Therapy INDs.

Wondering if you’re ready for INTERACT?

Deffai helps you confirm you’re inside the window, frame in-scope questions, and build a package that earns a meeting — not a denial.

Johnny Lam, PhD — Head of Regulatory Strategy · Laura Rose, PhD — Cofounder & Chief Regulatory Officer

This document is general educational information about FDA’s INTERACT meeting program. It is not legal or regulatory advice and does not create an attorney–client or consulting relationship, nor does it substitute for FDA’s guidance documents, the OTP INTERACT webpage, or SOPP 8101.1. INTERACT eligibility and outcomes are highly product- and program-specific, and FDA advice is informal and non-binding. Confirm current FDA procedures and timelines before acting.