Write pre-IND correspondence and focused requests for FDA advice

How do you write an answerable request for FDA development advice?

State the product, application stage and specific decision, then pair each question with the sponsor’s proposed approach, relevant evidence and limitations. Supply the formulation, exposure, study or assay context needed to interpret the question. Distinguish ordinary advice correspondence from a formal meeting request, and preserve FDA’s actual response without converting advice into authorization or a promise of approval.

Before you begin

Pre-IND correspondence and IND comment/advice requests; formal meeting requests and briefing packages remain distinct 1.6 tasks.

What you will prepare: A concise question-and-evidence package with an explicit requested response.

1.12.1: orient FDA to the development decision

Identify the sponsor, product, proposed indication, development stage and any assigned pre-IND/application reference. Explain what decision is blocked and why the available guidance does not resolve it. Summarize the proposed product, formulation and route sufficiently to make the question meaningful.

For a first-in-human development question, useful inputs may include the proposed study synopsis, relevant pharmacology/toxicology findings, exposure rationale and clinical-material description. Select evidence that addresses the question; do not send an undifferentiated research archive. A correspondence item is not a substitute for a formal meeting request or the background package when that is the chosen procedure.

1.12.4: request a comment on a defined proposal

State the question, the sponsor's proposed approach, the evidence supporting it and the consequences of alternatives. If requesting comments on an information amendment, identify that amendment and the exact section needing feedback. Ask one decision per numbered question where practical.

An editorial format is: “We propose [specific approach] for [defined population/product/stage], based on [referenced evidence]. Does FDA agree that [precise aspect] is appropriate for [next decision]?” Replace every bracket with established facts. Avoid asking whether the entire program is acceptable when only one assay or cohort is described.

Ordinary advice does not itself authorize a clinical investigation or establish that future data will support approval. Preserve the actual response and distinguish advice, a request for information and a formal agency action.

Check what the recipient can answer from the package

Have a reviewer answer each question using only the supplied references. If the reviewer needs the product concentration, study version or proposed exposure to understand the question, add that context or identify it as unresolved. Number attachments and use controlled versions.

Fictional editorial exercise: the letter asks whether a bridging study can be omitted but does not describe the old and new formulations. The useful next step is a comparison and supporting rationale, not a stronger sentence requesting agreement. If the IND is already active, change the identity and purpose accordingly rather than leaving a pre-IND title on the document.

Test whether each question can be answered from the supplied record

Use a question map to expose missing context before sending a letter. The map is a drafting aid; the appropriate meeting or correspondence procedure still determines the actual package.

Bridging exercise: the team asks to omit additional work after changing a formulation. Prepare the old/new formulation comparison, identify which material generated the existing evidence and explain the proposed bridge. If product exposure or comparability remains uncertain, state that uncertainty. A stronger request for agreement cannot compensate for an undefined change.

Keep one decision per numbered question where practical. Separate a question about whether existing evidence supports initiating a study from a question about whether the study design could support a later application. They can require different background and different agency expertise. Preserve the scope of the answer rather than extending advice about one cohort or assay to every future use.

For an information amendment, §312.31 specifically provides for requesting FDA comment. Identify the amendment, evidence location and matter on which comment is requested. Section 312.41(c) describes communications under that section as advisory unless accompanied by a clinical hold order. Read the whole communication before categorizing it; a letter can contain consequential action as well as discussion.

If a formal meeting is the right interaction, use the meeting request and background-package guides. The older pre-IND FAQ remains useful for packet content, but its historical scheduling suggestions should not replace the applicable current meeting framework. Use the meeting follow-up guide to preserve qualifications and resolve ambiguity.

Frequently asked questions

Sources and revisions

Requirements, source recommendations and editorial preparation advice have different roles. Review the scope and revision of the source you use.

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