Where Pre-IND Meetings Go Wrong
A former reviewer's field guide to the seven ways sponsors waste a Pre-IND meeting, and what it takes to get concrete answers instead.
PublishedYou'll learn how to:
- Submit when you can still act on FDA feedback: Ask FDA for a meeting when your plans are detailed enough to evaluate but still open to change. Your briefing package should ask narrow questions tied to a specific plan rather than open-ended ones FDA can only answer with boilerplate.
- Construct arguments to minimize assumptions: build a package that ties each plan to your specific product and clinical study, organized the way FDA reads it, and reconcile the cross-functional story so the team speaks in one voice. Don't make FDA assume anything, clearly explain why your approach supports safety and efficacy.
- Treat FDA's Feedback as their IND Position: FDA's Guidance states that Pre-IND feedback isn't binding, but that doesn't mean you can ignore it. If FDA raises concerns or gives feedback, address those seriously because those "non-binding" concerns become binding at IND.
A Pre-IND meeting is one of the few chances to get FDA’s read on your program before you have spent serious money on it. Used well, it tells you whether your nonclinical package will hold, whether your first-in-human design is safe enough to clear the 30-day review, and where the agency sees risk you have not considered yet. Used badly, it produces a document highlighting all the problems in your program that will haunt you for years to come.
The uncomfortable part is that most of what you get out of the meeting is decided before it happens. FDA answers the questions you actually ask, at the level of detail your briefing package supports. Vague questions and a thin package produce vague, boilerplate feedback. A sharp package and sharp questions produce the specific, checkable feedback that makes the slot worth having.
More detail isn’t necessarily going to lead to a better meeting if you’re not aligned with FDA and don’t give any justification for your approach. You need to know what FDA wants to see, show the review team how your approach aligns with what FDA expects, and proactively address any gaps with valid, scientific justification.
This playbook outlines the seven ways sponsors most often waste a Pre-IND meeting, drawn from our experiences on FDA and sponsor side, with what you should be aiming for.
01 · TIMING
Timing, timing, timing
The most common structural mistake is holding the meeting at the wrong point in development with insufficient information to allow FDA to provide good feedback. There’s two ways this can manifest. One is pursuing the wrong meeting type, like being too early for Pre-IND where the subject of your questions are more appropriate for INTERACT. The other way is when you’re too early, and your CMC, nonclinical, and clinical plans are still concepts so your questions come out as “what should we do at all?” rather than “is this specific plan acceptable?” FDA cannot commit to a plan you have not built yet, and their feedback reflects that. Without a proper strategy, you’ve just wasted a scarce opportunity for feedback, and you won’t get endless opportunities to re-submit.
Too late is just as expensive. If you’ve already locked in pivotal nonclinical studies, built out manufacturing suites, or even started an early trial in another country, it’s a much bigger cost to make changes. When FDA then flags a problem, this is going to take a lot of time and money to resolve.
02 · YOUR QUESTIONS
Vague questions get boilerplate answers
The single biggest driver of a useless meeting is a set of questions FDA can only answer with boilerplate. “Is our overall development plan acceptable?” invites FDA’s feedback recommending “the sponsor should ensure the program adequately supports the proposed indication.” You will nod, but have learned nothing or even worse, assume that this feedback means there’s no major issues. “Do you have any additional comments on our CMC approach?” and “Is our clinical trial design reasonable?” fail the same way.
Good Pre-IND questions are narrow and tied to a specific plan you have laid out in the package. They hand FDA a concrete option to endorse or reject and a reason to put on the record. The difference is not politeness. It is whether you leave with something you can build on.
Although they might seem aligned with recommendations for decision-focused questions, asking whether FDA will allow an IND to proceed or approve a BLA asks for input for an answer they cannot give in an INTERACT or Pre-IND. FDA knows you want your IND to be allowed to proceed and your BLA approved; don’t force them. Similarly, don’t ask whether you’re eligible for RMAT, Fast Track, or Breakthrough Therapy designation.
| Weak question | Sharper version |
|---|---|
| Do you have comments on our CMC approach? | Will you accept a potency strategy of assay A plus assay B at IND, with C deferred because it is not yet technically feasible? |
| Is our nonclinical plan sufficient? | Is a 3-month toxicity study in species X adequate based on our rationale for a single species? |
| Are you going to approve our IND? | Is our proposed starting dose and escalation scheme acceptable given the dose-justification analysis in Section 4? |
03 · THE BRIEFING PACKAGE
Plans asserted, not shown
Even sharp questions fail if the package behind them is thin. Across CMC, nonclinical, and clinical, the recurring problem is the same: the plan is asserted rather than shown, and it is not tied to the specific product and trial in front of the reviewer.
For CBER and OTP products, the platform reflex is the most damaging version of this. “Our platform behaves this way” is not evidence that this construct, at this dose, in this population, behaves that way. Reviewers have seen the platform argument used to skip characterization that later turned out to matter. Show why the platform information applies here, or do not lean on it.
| Common gap | What good looks like | |
|---|---|---|
| CMC | Identity, critical quality attributes, and control strategy vaguely described; no potency concept | Product clearly defined; a potency assay concept even if not final; a realistic comparability plan for foreseeable process changes |
| Nonclinical | Species, model, duration, and endpoints not justified against the clinical plan | Each study tied to the intended route, dose range, schedule, and population, with model selection defended |
| Clinical | Vague eligibility, unclear starting dose and escalation, exploratory endpoints with no primary objective | A first-in-human design with key inclusion/exclusion criteria, a clear primary endpoint, and a dose-selection rationale |
04 · STRUCTURE
Correct but scattered still fails
Content that is right but scattered still fails. When key CMC details, the manufacturing process, the release tests, the specifications, are spread across slides and long narratives, the reviewer cannot quickly find them or trace how your nonclinical data support the proposed trial. Organize the package the way FDA reads it, in an eCTD-like structure, so each discipline can go straight to its section.
The cost of disorganization is specific and predictable. Instead of substantive feedback, you get clarification questions, and FDA defers detailed CMC comment to the IND. That deferral is usually the opposite of what you wanted: you came for an early read on CMC and left with a promise to look later (as a review issue).
05 · TEAM ALIGNMENT
Internal disagreement shows up live
Pre-IND packages are built by clinical, CMC, nonclinical, and regulatory teams, often on different assumptions that never get reconciled before submission. On the call, that shows up as conflicting answers to FDA’s questions.
FDA reads that as a signal about the program, not just the meeting. A company team that cannot answer basic design questions consistently looks unready, and reviewers respond by deferring feedback they might otherwise have given or taking a more conservative approach. Some questions they could have answered get pushed simply because the plan underneath them is still moving. FDA interactions are most successful when all parts of a company speak with a single voice and when a company comes to FDA with a position.
06 · PRECEDENT AND PRIOR FEEDBACK
Leaning on precedent the wrong way
Two opposite errors show up around precedent. The over-reliance version is “you allowed X for a similar product, so we assume you will allow it here,” without rationale for why this same situation applies to your product, nor do you address any difference in risk profile, mechanism, or population. FDA does not owe an explanation for decisions they made on other products, and the burden is on you to draw the comparison.
The under-use version is failing to bring your own history into the room. If you had an INTERACT meeting or informal advice, summarize it and show how you incorporated it, rather than making the review team reconstruct the story from separate submissions. A brief, tabular history of prior FDA feedback and your response to each point is one of the cheapest ways to build reviewer confidence.
07 · WHAT THE FEEDBACK MEANS
Influential, but not binding
Sponsors routinely misjudge what Pre-IND feedback is. It is highly influential but not binding, and it is based on the data and plans you showed at the time. Both extreme readings get programs into trouble.
The lock-in error treats early agreement as permanent: “FDA said this was fine at Pre-IND, so we do not need to revisit it,” even after the program has changed enough that the original answer no longer applies. The dismissal error treats the feedback as mere opinion to be ignored, which is how sponsors walk into an avoidable clinical hold or a rough IND review. Neither reading is correct.
| The mistaken belief | The result | |
|---|---|---|
| Lock-in | "FDA already blessed this, so it is settled." | You carry forward advice that no longer fits a program that has since changed. |
| Dismissal | "It was only informal advice; we will do what we want." | You surface the disagreement at IND, when it can trigger a hold. |
08 · FAQ
Frequently asked questions
Why do Pre-IND meetings fail to deliver useful feedback? FDA is ready and eager to give specific and actionable feedback because it leads to higher quality INDs that are easier to review. However, FDA can only work with the Pre-IND package they’re given: vague questions supported by insufficient information produce vague answers with boilerplate feedback. Sharp questions and a complete briefing package with well-reasoned arguments produce the specific, actionable feedback that makes the interaction worthwhile.
When is the right time to hold a Pre-IND meeting? When your plans are detailed enough to evaluate but still open to change. If your only questions are open-ended, you are too early and your strategy is not sufficiently established; if the answer can no longer alter what you have already built, it’s too late to act on FDA’s feedback.
What makes a good Pre-IND question? A good Pre-IND question is narrow and tied to a specific plan you have laid out in the package, and presents FDA a concrete option to endorse or reject. Avoid asking whether your IND will be allowed to proceed, whether you are eligible for RMAT, Fast Track, or Breakthrough Therapy designation, or whether your BLA will be approved because FDA cannot give those answers at a Pre-IND.
Is FDA’s Pre-IND feedback binding? FDA’s feedback at Pre-IND (and INTERACT) is not technically binding, but know that it is usually reflective of their position and is unlikely to change unless new information is provided. Since the next FDA interaction is IND, use the Pre-IND feedback to understand what you need to provide for a successful IND.
What should a Pre-IND briefing package show? Plans that are tied to your specific product and trial, and organized in an eCTD-like structure so each discipline can go straight to its section. Data should be in summary form and include information on CMC, Pharm/Tox, and clinical. For platform-based products, show why the platform information applies to this construct.
FDA sources & references
- Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products — Guidance for Industry; the framework, package content, and timelines for Pre-IND (Type B) meetings. fda.gov ↗
- 21 CFR Part 312 — Investigational New Drug Application; the regulations governing INDs and the 30-day review. fda.gov ↗
- 21 CFR 312.47 — Meetings; the regulatory basis for Pre-IND and other sponsor–FDA meetings. fda.gov ↗
- INTERACT Meetings (Initial Targeted Engagement for Regulatory Advice on CBER/CDER Products) — Guidance for Industry; the earlier interaction for novel, blocking questions ahead of the Pre-IND. fda.gov ↗
- Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs) — Guidance for Industry; CMC expectations for gene therapy INDs. fda.gov ↗
- Preclinical Assessment of Investigational Cellular and Gene Therapy Products — Guidance for Industry; nonclinical program design for cell and gene therapies. fda.gov ↗
- Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs — Guidance for Industry; the expected content of a Phase 1 IND. fda.gov ↗
This document is general educational information about FDA Pre-IND meetings and IND-enabling development for biologics and advanced therapies. 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 or the applicable regulations. Pre-IND strategy is highly product- and indication-specific, and FDA’s views are informal and non-binding. Confirm current FDA procedures and consider professional review of your specific program before acting.