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Checklist Plug-and-play starting point Quality Assurance

Checklist: NDA / BLA Filing Readiness (Refuse-to-File Avoidance)

A plug-and-play checklist to confirm an NDA or BLA is complete and filing-ready across all five eCTD modules before submission, reducing Refuse-to-File risk, with inspection-readiness items and a filled specimen.

Document type: Checklist

Read and copy the template below into your own quality system. It is a generic starting point for your own internal use, provided as is, with no warranty; see the Terms and License. Adopting it does not by itself create compliance.

This is a ready-to-use filing-readiness checklist for a marketing application (NDA under FD&C Act 505 / 21 CFR 314, or BLA under PHS Act 351 / 21 CFR 601). The purpose is to cross the 60-day filing review without a Refuse to File and to be ready for the inspections that gate approval. Work each item to Yes, N/A with rationale, or a documented gap. Replace every <<FILL: ...>> placeholder. A filled specimen follows.

Checklist control

FieldEntry
Checklist number<<FILL: CHK-ID>>
Application typeNDA 505(b)(1) / NDA 505(b)(2) / BLA 351(a)
Product / candidate<<FILL>>
Target submission date<<FILL>>
PDUFA goal date (once assigned)<<FILL>>
Completed by<<FILL>>

Module 1: Regional / administrative

#ItemStatus (Y / N / NA)Location
1.1Application form (356h) complete and signed<<FILL>><<FILL>>
1.2Proposed labeling (prescribing information) in required format<<FILL>><<FILL>>
1.3REMS proposal or rationale for none<<FILL>><<FILL>>
1.4Financial disclosure (Part 54) for clinical investigators<<FILL>><<FILL>>
1.5Patent and exclusivity information (NDA)<<FILL>><<FILL>>
1.6Pediatric plan (PREA) / rare-disease considerations addressed<<FILL>><<FILL>>
1.7User fee paid or waiver requested (PDUFA)<<FILL>><<FILL>>

Module 2: Summaries

#ItemStatusLocation
2.1Quality Overall Summary (QOS) complete and consistent with Module 3<<FILL>><<FILL>>
2.2Nonclinical overview and summaries<<FILL>><<FILL>>
2.3Clinical overview and summaries, including integrated summaries of safety and efficacy<<FILL>><<FILL>>

Module 3: Quality (CMC)

#ItemStatusLocation
3.1Drug substance: manufacture, control, characterization, container-closure<<FILL>><<FILL>>
3.2Drug product: composition, manufacture, control, container-closure<<FILL>><<FILL>>
3.3Analytical method validation reports complete<<FILL>><<FILL>>
3.4Process validation (or process performance qualification) summary<<FILL>><<FILL>>
3.5Stability data supporting the proposed shelf life and storage statement<<FILL>><<FILL>>
3.6(BLA) potency assay, comparability, impurity profile, viral safety, cell-bank characterization<<FILL>><<FILL>>
3.7Comparability between clinical and commercial material demonstrated<<FILL>><<FILL>>

Module 4: Nonclinical study reports

#ItemStatusLocation
4.1Pharmacology, PK/ADME, and toxicology study reports complete<<FILL>><<FILL>>
4.2GLP compliance statements present<<FILL>><<FILL>>

Module 5: Clinical study reports

#ItemStatusLocation
5.1Pivotal-trial clinical study reports (ICH E3) complete<<FILL>><<FILL>>
5.2Datasets in required standard (CDISC SDTM/ADaM) and define files<<FILL>><<FILL>>
5.3Database lock and statistical analysis plan finalized before unblinding<<FILL>><<FILL>>
5.4Integrated safety and efficacy summaries reconcile with study reports<<FILL>><<FILL>>
5.5Case report form and source-data traceability intact<<FILL>><<FILL>>

Inspection readiness (gates the approval)

#ItemStatusLocation
6.1Pre-Approval Inspection (PAI) readiness: named site(s), process validated, state of control demonstrable<<FILL>><<FILL>>
6.2BIMO readiness: pivotal-site data verifiable, source documents retrievable, audit trails intact<<FILL>><<FILL>>
6.3Data-integrity self-check across the modules (no unreviewed audit trails, no unreconciled queries)<<FILL>><<FILL>>
6.4Mock inspection completed with findings closed<<FILL>><<FILL>>

Sign-off

RoleNameSignatureDate
Regulatory lead<<FILL>>
CMC / quality lead<<FILL>>
Clinical / biostatistics lead<<FILL>>
QA<<FILL>>

Filled specimen

Illustrative extract for a BLA 351(a).

#ItemStatusLocation
2.1QOS complete, reconciled to m3Ym2/2.3, cross-check log QC-2026-071
3.6Potency relative-bioassay validated; HCP and viral-safety packages completeYm3/3.2.S and 3.2.A
3.7Comparability clinical vs commercial process demonstratedYm3/3.2.S.2.6 comparability report CMP-2026-004
5.3Database locked 30 Apr 2026, SAP final 12 Apr 2026 (pre-unblinding)YDM lock memo DM-2026-019
6.2BIMO readiness: two pivotal sites pre-audited, source retrievableYGCP audit reports AUD-2026-030/031

Items 3.7 and 6.2 are the classic delay points: a comparability gap between clinical and commercial biologic material, or a BIMO data-integrity finding at a pivotal site, can hold an otherwise approvable BLA.

Common Refuse-to-File and delay triggers this checklist prevents

  • Missing or mis-formatted labeling, forms, or integrated summaries (administrative RTF).
  • Module 3 gaps: incomplete method or process validation, stability that does not support the claimed shelf life.
  • For biologics, comparability between clinical and commercial process not demonstrated.
  • Database lock or SAP finalized after unblinding, undermining the statistical evidence.
  • Data-integrity findings surfacing at PAI or BIMO that were never self-identified.

How to adapt this checklist

  1. Set the application type and candidate in the control block.
  2. Trim Module 3 rows to NDA or expand for BLA-specific biologics content.
  3. Point each location cell to the actual eCTD leaf.
  4. Run the inspection-readiness section against a real mock inspection, not on paper.
  5. Confirm the current regulations and ICH references before relying on them; this is educational guidance, not regulatory advice.
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