IND-Readiness Checklist

Strategy & timing — before you write a word

FDA pre-IND guidance

Pre-IND meeting held (or consciously skipped with a written rationale)The single highest-ROI step in IND preparation. FDA feedback here prevents rewrites later.Meeting minutes reconciled against the briefing packageWhat FDA agreed to is what the minutes say — not what you hoped they said.Indication and target product profile lockedScope drives every module. A drifting indication invalidates the tox plan.The 30-day clock understood: FDA has 30 days to object; silence means you may proceed21 CFR 312.40. Plan to be dose-ready on day 31.Clinical-hold risk areas reviewed against your program21 CFR 312.42 lists the hold grounds. Read them before FDA does.

Module 1 — Administrative information

21 CFR 312.23(a)

Form FDA 1571 complete, signed, every field addressedThe most common refuse-to-file item. Check the phase boxes twice.Table of contents — navigable and paginatedReviewers navigate by it. A broken TOC slows everything.Introductory statement and general investigational planThe 30-second story of the program: what, why, and what comes next.Draft labeling, including the Investigator's BrochureRisk language here must match the protocol — inconsistencies draw holds.Environmental assessment or claim of categorical exclusion21 CFR Part 25. Usually a categorical exclusion with justification.Debarment certificationFD&C Act 306(k). A missing cert is an automatic RTF.Financial disclosure — Forms 3454/3455 for covered clinical studies21 CFR Part 54. Collect investigator disclosures before the study starts, not after.US agent designated (for foreign sponsors)21 CFR 312.23(a)(1). A foreign sponsor needs a US agent who can act on its behalf.

Module 2 — CTD summaries

ICH M4

CTD table of contents (2.1)Skeleton of the whole submission.Introduction (2.2) — drug class, rationale, intended useSets the frame every reviewer reads first.Quality Overall Summary (2.3) mirrors Module 3Anything in Module 3 not summarized here looks hidden.Nonclinical Overview (2.4) — integrated risk assessment, not a data dumpThe overview must argue, not list. What do the tox data mean for humans?Clinical Overview (2.5) — benefit-risk framing for first-in-humanWhy is it acceptable to give this to people? Answer directly.Nonclinical written and tabulated summaries (2.6)Tables carry the weight here — design them for scanning.Clinical summary (2.7) if any prior human data existsForeign marketing experience, investigator-initiated studies — all of it.

Module 3 — Quality / CMC

21 CFR 312.23(a)(7); ICH M4Q

Drug substance: manufacturer, process description, controls, characterizationFDA must be able to trace every batch back to a controlled process.Specifications, analytical procedures, and validation statusSpecs must be justified; methods must be validated or validation must be in flight with a date.Drug product: composition, manufacturing process, in-process controlsSame traceability standard as drug substance.Container closure system describedCompatibility and integrity data for the clinical presentation.Stability data supporting the proposed trial duration and storage conditionsThe stability package must cover the longest patient exposure you propose.Facilities listed with registration status; inspection readiness assessedA facility FDA can't inspect is a facility that delays you.Adventitious agent safety addressed where applicableBiologics and cell therapies: viral clearance / TSE risk, explicitly.Comparability plan if process changes are anticipated during developmentEarly-phase processes change. Say now how you'll prove comparability later.

Module 4 — Nonclinical

ICH M3(R2), S6, S7A, S2(R1), S5

GLP toxicology: species justified, duration supports proposed clinical exposureICH M3(R2) duration tables. The tox package must cover the clinical plan you actually propose.Safety pharmacology core battery completeICH S7A — cardiovascular, CNS, respiratory. Usually expected before first-in-human.Genotoxicity battery complete or explicitly justified as deferredICH S2(R1). Single-dose healthy-volunteer studies have a defined minimum.Reproductive toxicology plan is phase-appropriateICH S5. Know what's required before women of childbearing potential enroll.Exposure margins calculated — animal-to-human multiples stated plainlyReviewers look for the multiple first. Bury it and you invite questions.All pivotal studies GLP with signed QA statementsA pivotal tox study without a GLP compliance statement is a non-pivotal study.

Module 5 — Clinical

21 CFR 312.23(a)(6)

Protocol: objectives, design, population, dose rationale, stopping rules, safety monitoringDose rationale is the most-scrutinized paragraph in a first-in-human protocol.Investigator's Brochure is current and consistent with the protocolIB risk language and protocol risk language must say the same thing.Prior clinical experience summarized, wherever it occurredForeign studies count. Investigator-initiated studies count.Informed consent template consistent with protocol risksConsent must reflect the actual risks in the IB — not a generic template.Pediatric study plan considered (initial PSP timing assessed)FDASIA requires an iPSP for certain applications. Know whether yours is one of them.

Submission mechanics — the unglamorous part that kills timelines

FDA eCTD guidance

eCTD format validated — no paperFDA requires eCTD. Validate the build before submission day, not on it.ESG gateway account tested end-to-endA gateway failure on day 30 is a self-inflicted delay.Cover letter states exactly what is submitted and what is requestedOriginal IND, new protocol, new investigator — say which.Site readiness: could you dose on day 31?The 30-day clock is real. IRB, contracts, and drug supply should be parallel-tracked.Clinical-hold response plan drafted in advanceDecide now who writes the response and who makes the call — not during the 30 days.Prior FDA correspondence cross-referenced (pre-IND minutes, INTERACT)Show the reviewer you listened. Reference the meeting dates and what you changed.

The IND-Readiness Checklist

Get the full checklist

Start here — strategy before paperwork

Strategy & timing — before you write a word

Strategy & timing — before you write a word

Module 1 — Administrative information

Module 2 — CTD summaries

Module 3 — Quality / CMC

Module 4 — Nonclinical

Module 5 — Clinical

Submission mechanics — the unglamorous part that kills timelines