eCTD Submission Checklist: The Complete Module-by-Module Preparation Guide
An eCTD submission checklist is a verification tool ensuring all Electronic Common Technical Document components are complete and compliant before regulatory submission. Approximately 40% of eCTD submissions contain preventable errors that proper checklists catch before gateway rejection.
An eCTD submission checklist is a comprehensive document verification tool that ensures all required components of an Electronic Common Technical Document (eCTD) are complete, properly formatted, and compliant with regulatory authority specifications before submission. A thorough eCTD checklist prevents gateway rejections, reduces 120-day letters, and accelerates drug approval timelines.
Submitting an eCTD without a systematic checklist is like performing surgery without a pre-operative protocol. The consequences of missing a single document or validation step can cascade into months of delays and hundreds of thousands of dollars in rework costs.
Industry estimates suggest that a significant proportion of eCTD submissions contain preventable errors that could have been caught with proper pre-submission verification. The cost of a single gateway rejection can exceed tens of thousands of dollars in direct rework costs, not counting the timeline impact.
In this guide, you'll learn:
- Complete eCTD checklist requirements for all 5 modules
- Module-by-module document checklists with specific file requirements
- Regional submission requirements for FDA, EMA, and Health Canada
- Pre-submission validation checklist to prevent gateway rejections
- How to download our free eCTD submission checklist template
What Is an eCTD Submission Checklist?
eCTD submission checklist - A structured verification document used to confirm every required element of an Electronic Common Technical Document is present, properly formatted, and compliant with regional specifications. Required by regulatory professionals as the final quality gate before transmission to FDA, EMA, Health Canada, and other regulatory authorities.
An eCTD submission checklist is a structured verification document that regulatory professionals use to confirm every required element of an Electronic Common Technical Document submission is present, properly formatted, and compliant with regional specifications. The eCTD checklist serves as the final quality gate before transmission to regulatory authorities.
Key characteristics of an effective eCTD submission checklist:
- Covers all five eCTD modules with document-level specificity
- Includes regional variations for FDA, EMA, Health Canada, and other agencies
- Addresses both technical validation and content completeness requirements
- Provides a traceable audit trail for quality assurance
- Integrates with the eCTD publishing workflow
The ICH M8 eCTD specification requires approximately 150+ distinct document types across the five modules. A comprehensive eCTD submission checklist ensures none are missed.
The eCTD submission checklist differs from basic validation tools in that it verifies not just technical compliance (XML schema, file naming) but also content completeness (required documents present) and regulatory alignment (regional requirements met).
Complete eCTD Module Checklist Overview
Before diving into module-specific requirements, understanding the overall eCTD structure helps ensure nothing is missed. The eCTD checklist must address all five modules, though requirements vary by submission type.
Create a master checklist tracking spreadsheet that references all module-specific checklists. Include columns for section number, document name, target completion date, assigned reviewer, and status. This single-view dashboard prevents overlooked items when coordinating across multiple teams.
eCTD Module Structure Summary
| Module | Name | Content Type | Regional Variation | Typical Document Count |
|---|---|---|---|---|
| Module 1 | Administrative Information | Forms, labeling, cover letters | Region-specific | 15-50 documents |
| Module 2 | CTD Summaries | Overviews and written summaries | Harmonized | 20-40 documents |
| Module 3 | Quality (CMC) | Drug substance and product data | Harmonized | 100-500 documents |
| Module 4 | Nonclinical | Pharmacology and toxicology | Harmonized | 50-200 documents |
| Module 5 | Clinical | Clinical study reports | Harmonized | 200-2,000+ documents |
eCTD Submission Type Requirements
Different submission types require different module completeness:
| Submission Type | Module 1 | Module 2 | Module 3 | Module 4 | Module 5 |
|---|---|---|---|---|---|
| Original NDA/BLA | Full | Full | Full | Full | Full |
| IND (Initial) | Full | Partial | Full | Full | Partial |
| ANDA | Full | Full | Full | Limited | Limited |
| Supplement (CMC) | Full | 2.3 only | Changed sections | N/A | N/A |
| Annual Report | Full | N/A | Changed sections | N/A | N/A |
| Amendment | Full | As needed | As needed | As needed | As needed |
Module 1 Checklist: Administrative Information
Module 1 contains region-specific administrative documents, forms, and labeling. This module varies significantly between regulatory authorities and is often the source of preventable submission errors.
FDA Module 1 Document Checklist
The FDA Module 1 checklist covers all administrative requirements for submissions to the U.S. Food and Drug Administration:
| Section | Document | Required For | Checklist Status |
|---|---|---|---|
| 1.1 | Cover Letter | All submissions | [ ] |
| 1.2 | Form FDA 356h (Application Form) | NDA, BLA, ANDA | [ ] |
| 1.2 | Form FDA 1571 (IND Application) | IND | [ ] |
| 1.2 | Form FDA 3674 (Certifications) | NDA, BLA | [ ] |
| 1.3.1 | US Patent Information | NDA, ANDA | [ ] |
| 1.3.2 | Patent Certification | ANDA | [ ] |
| 1.3.3 | Exclusivity Claims | NDA, BLA | [ ] |
| 1.3.4 | Tropical Disease Priority Review | If applicable | [ ] |
| 1.4.1 | US Prescribing Information (USPI) | NDA, BLA, ANDA | [ ] |
| 1.4.2 | Patient Labeling (Medication Guide) | If required | [ ] |
| 1.4.3 | Container/Carton Labels | NDA, BLA, ANDA | [ ] |
| 1.5 | References | If new documents | [ ] |
| 1.6 | Environmental Assessment or Claim | All | [ ] |
| 1.7 | Debarment Certification | NDA, ANDA, BLA | [ ] |
| 1.8 | Financial Disclosure | NDA, BLA | [ ] |
| 1.9 | Field Copy Certification | If applicable | [ ] |
| 1.10 | PDUFA Cover Sheet (Form FDA 3397) | NDA, BLA | [ ] |
| 1.11 | Pediatric Administrative Information | If applicable | [ ] |
| 1.12 | REMS (Risk Evaluation/Mitigation) | If required | [ ] |
| 1.14 | Promotional Materials | If applicable | [ ] |
Verify Form FDA 356h signatures are dated within 30 days of submission. Outdated signatures are a common cause of administrative deficiencies that delay review initiation.
FDA Module 1 Verification Checklist
Form FDA 356h Requirements:
- [ ] Current version of form used
- [ ] All applicable sections completed
- [ ] Authorized signature present
- [ ] Date of signature within 30 days of submission
- [ ] Application type correctly indicated
- [ ] Manufacturing sites listed accurately
USPI Requirements:
- [ ] Follows current FDA labeling guidance
- [ ] Highlights section present (if NDA)
- [ ] Full prescribing information complete
- [ ] Black box warning (if required)
- [ ] PDF bookmarked appropriately
- [ ] Cross-referenced to clinical data
EMA Module 1 Document Checklist
The EMA Module 1 checklist addresses European regulatory requirements:
| Section | Document | Required For | Checklist Status |
|---|---|---|---|
| 1.0 | Cover Letter | All submissions | [ ] |
| 1.2 | Application Form | MAA, Variation | [ ] |
| 1.3.1 | Summary of Product Characteristics (SmPC) | MAA | [ ] |
| 1.3.1 | Annexes (II, IIIA, IIIB) | MAA | [ ] |
| 1.3.1 | Package Leaflet | MAA | [ ] |
| 1.3.2 | Mock-ups | MAA | [ ] |
| 1.3.3 | Product Information - Accelerated | MAA | [ ] |
| 1.4.1 | Expert Statements - Quality | MAA | [ ] |
| 1.4.2 | Expert Statements - Nonclinical | MAA | [ ] |
| 1.4.3 | Expert Statements - Clinical | MAA | [ ] |
| 1.5 | Information on Experts | MAA | [ ] |
| 1.6.1 | Environmental Risk Assessment | All | [ ] |
| 1.7 | Information for Orphan | If applicable | [ ] |
| 1.8 | Information on Pharmacovigilance | MAA | [ ] |
| 1.9 | Information on Clinical Trials | MAA | [ ] |
| 1.10 | Responses to Questions | If applicable | [ ] |
Health Canada Module 1 Document Checklist
| Section | Document | Required For | Checklist Status |
|---|---|---|---|
| 1.2.1 | HC Application Form | NDS, ANDS | [ ] |
| 1.2.2 | HC Administrative Application Form | NDS, ANDS | [ ] |
| 1.3.1 | Canadian Product Monograph | NDS, ANDS | [ ] |
| 1.3.2 | Draft Labels | NDS, ANDS | [ ] |
| 1.4.1 | Declaration - Regulations | All | [ ] |
| 1.4.2 | Declaration - Clinical Trials | If applicable | [ ] |
| 1.5 | References | If applicable | [ ] |
Module 2 Checklist: CTD Summaries
Module 2 contains the high-level summaries that regulatory reviewers evaluate first. The eCTD document checklist for Module 2 must ensure consistency with detailed data in Modules 3, 4, and 5.
Module 2 Document Requirements Checklist
Schedule a "Module 2 to Module 3/4/5 alignment audit" one week before final submission. Have a senior regulatory person read the Module 2 summaries while simultaneously spot-checking the corresponding detailed sections in Modules 3-5. This catches summary-to-body inconsistencies that reviewers will definitely notice.
| Section | Document | Word Limit/Length | Required For | Checklist Status |
|---|---|---|---|---|
| 2.1 | Table of Contents | Complete eCTD | All | [ ] |
| 2.2 | Introduction | 1-2 pages | NDA, BLA | [ ] |
| 2.3 | Quality Overall Summary (QOS) | ~40 pages typical | NDA, BLA, ANDA | [ ] |
| 2.4 | Nonclinical Overview | ~30 pages typical | NDA, BLA | [ ] |
| 2.5 | Clinical Overview | ~30 pages typical | NDA, BLA | [ ] |
| 2.6 | Nonclinical Written/Tabulated Summaries | Variable | NDA, BLA | [ ] |
| 2.7 | Clinical Summary | ~400 pages typical | NDA, BLA | [ ] |
Module 2.3 Quality Overall Summary Checklist
The QOS is critical for CMC review. Verify the following eCTD submission requirements:
Drug Substance (2.3.S) Verification:
- [ ] General information matches Module 3.2.S.1
- [ ] Manufacturer information accurate
- [ ] Manufacturing process summary consistent with 3.2.S.2
- [ ] Characterization data summarized from 3.2.S.3
- [ ] Specification table matches 3.2.S.4.1
- [ ] Analytical procedure references correct
- [ ] Stability summary consistent with 3.2.S.7
Drug Product (2.3.P) Verification:
- [ ] Description matches 3.2.P.1
- [ ] Composition table accurate
- [ ] Pharmaceutical development summary complete
- [ ] Manufacturing process summary from 3.2.P.3
- [ ] Specification table matches 3.2.P.5.1
- [ ] Stability summary consistent with 3.2.P.8
Module 2.7 Clinical Summary Checklist
| Section | Content | Cross-Reference To | Checklist Status |
|---|---|---|---|
| 2.7.1 | Biopharmaceutics Summary | Module 5.3.1 | [ ] |
| 2.7.2 | Clinical Pharmacology Summary | Module 5.3.3, 5.3.4 | [ ] |
| 2.7.3 | Clinical Efficacy Summary | Module 5.3.5 | [ ] |
| 2.7.4 | Clinical Safety Summary | Module 5.3.5, 5.3.6 | [ ] |
| 2.7.5 | Literature References | Module 5.4 | [ ] |
| 2.7.6 | Synopses of Individual Studies | Module 5.3 | [ ] |
Module 3 Checklist: Quality (CMC)
Module 3 is typically the largest module and requires the most detailed eCTD document checklist. CMC documentation errors are a leading cause of 120-day letters.
Module 3.2.S Drug Substance Checklist
| Section | Document | Required Content | Checklist Status |
|---|---|---|---|
| 3.2.S.1.1 | Nomenclature | INN, USAN, CAS, codes | [ ] |
| 3.2.S.1.2 | Structure | Molecular formula, weight, stereochemistry | [ ] |
| 3.2.S.1.3 | General Properties | Physical/chemical properties | [ ] |
| 3.2.S.2.1 | Manufacturer(s) | Name, address, responsibilities | [ ] |
| 3.2.S.2.2 | Description of Manufacturing Process | Flow diagram, narrative | [ ] |
| 3.2.S.2.3 | Control of Materials | Specifications, suppliers | [ ] |
| 3.2.S.2.4 | Controls of Critical Steps | In-process controls | [ ] |
| 3.2.S.2.5 | Process Validation | Validation protocol/report | [ ] |
| 3.2.S.2.6 | Manufacturing Process Development | History, changes | [ ] |
| 3.2.S.3.1 | Elucidation of Structure | Spectral data, interpretation | [ ] |
| 3.2.S.3.2 | Impurities | Identification, qualification | [ ] |
| 3.2.S.4.1 | Specification | Release and shelf-life specs | [ ] |
| 3.2.S.4.2 | Analytical Procedures | Method descriptions | [ ] |
| 3.2.S.4.3 | Validation of Analytical Procedures | Validation reports | [ ] |
| 3.2.S.4.4 | Batch Analyses | COAs for batches | [ ] |
| 3.2.S.4.5 | Justification of Specification | Scientific rationale | [ ] |
| 3.2.S.5 | Reference Standards | Primary and secondary | [ ] |
| 3.2.S.6 | Container Closure System | Description, suitability | [ ] |
| 3.2.S.7.1 | Stability Summary | Tabulated data | [ ] |
| 3.2.S.7.2 | Post-Approval Stability Protocol | Protocol and commitments | [ ] |
| 3.2.S.7.3 | Stability Data | Study reports | [ ] |
Module 3.2.P Drug Product Checklist
| Section | Document | Required Content | Checklist Status |
|---|---|---|---|
| 3.2.P.1 | Description and Composition | Dosage form, composition table | [ ] |
| 3.2.P.2.1 | Components of Drug Product | Compatibility, function | [ ] |
| 3.2.P.2.2 | Drug Product | Formulation development | [ ] |
| 3.2.P.2.3 | Manufacturing Process Development | Process selection rationale | [ ] |
| 3.2.P.2.4 | Container Closure System | Selection rationale | [ ] |
| 3.2.P.2.5 | Microbiological Attributes | Preservative effectiveness | [ ] |
| 3.2.P.2.6 | Compatibility | Reconstitution, administration | [ ] |
| 3.2.P.3.1 | Manufacturer(s) | Name, address, responsibilities | [ ] |
| 3.2.P.3.2 | Batch Formula | Batch size, formula | [ ] |
| 3.2.P.3.3 | Description of Manufacturing Process | Flow diagram, narrative | [ ] |
| 3.2.P.3.4 | Controls of Critical Steps | In-process controls | [ ] |
| 3.2.P.3.5 | Process Validation | Validation reports | [ ] |
| 3.2.P.4.1-6 | Control of Excipients | Specifications for each | [ ] |
| 3.2.P.5.1 | Specification(s) | Release and shelf-life | [ ] |
| 3.2.P.5.2 | Analytical Procedures | Method descriptions | [ ] |
| 3.2.P.5.3 | Validation of Analytical Procedures | Validation reports | [ ] |
| 3.2.P.5.4 | Batch Analyses | COAs for batches | [ ] |
| 3.2.P.5.5 | Characterization of Impurities | Identification, qualification | [ ] |
| 3.2.P.5.6 | Justification of Specification | Scientific rationale | [ ] |
| 3.2.P.6 | Reference Standards | Primary and secondary | [ ] |
| 3.2.P.7 | Container Closure System | Description, suitability | [ ] |
| 3.2.P.8.1 | Stability Summary | Tabulated data | [ ] |
| 3.2.P.8.2 | Post-Approval Stability Protocol | Protocol and commitments | [ ] |
| 3.2.P.8.3 | Stability Data | Study reports | [ ] |
Create a batch number reconciliation spreadsheet before compiling Module 3. Track every batch number across stability data (3.2.S.7, 3.2.P.8), batch analyses (3.2.S.4.4, 3.2.P.5.4), and process validation sections to prevent cross-reference errors.
Module 3 Cross-Reference Verification Checklist
Critical Module 3 consistency checks:
| Data Element | Module 3 Location | Must Match | Checklist Status |
|---|---|---|---|
| Batch numbers | 3.2.S.4.4, 3.2.P.5.4 | 3.2.S.7.3, 3.2.P.8.3 | [ ] |
| Specifications | 3.2.S.4.1, 3.2.P.5.1 | 2.3 QOS tables | [ ] |
| Manufacturer addresses | 3.2.S.2.1, 3.2.P.3.1 | Module 1 forms | [ ] |
| Manufacturing process | 3.2.S.2.2, 3.2.P.3.3 | 2.3 QOS description | [ ] |
| Stability conditions | 3.2.S.7.3, 3.2.P.8.3 | ICH Q1A requirements | [ ] |
| Impurity limits | 3.2.S.3.2, 3.2.P.5.5 | ICH Q3A/Q3B thresholds | [ ] |
Module 4 Checklist: Nonclinical Studies
Module 4 contains nonclinical pharmacology and toxicology data. The eCTD publishing checklist for Module 4 must address Study Tagging File (STF) requirements.
Module 4 Document Requirements Checklist
| Section | Study Type | Required Documents | Checklist Status |
|---|---|---|---|
| 4.2.1.1 | Primary Pharmacodynamics | Study reports | [ ] |
| 4.2.1.2 | Secondary Pharmacodynamics | Study reports | [ ] |
| 4.2.1.3 | Safety Pharmacology | Core battery studies | [ ] |
| 4.2.1.4 | Pharmacodynamic Drug Interactions | If applicable | [ ] |
| 4.2.2.1 | Analytical Methods (ADME) | Method validation | [ ] |
| 4.2.2.2 | Absorption | PK study reports | [ ] |
| 4.2.2.3 | Distribution | Tissue distribution | [ ] |
| 4.2.2.4 | Metabolism | In vitro/in vivo metabolism | [ ] |
| 4.2.2.5 | Excretion | Mass balance | [ ] |
| 4.2.2.6 | PK Drug Interactions | DDI studies | [ ] |
| 4.2.2.7 | Other PK Studies | As applicable | [ ] |
| 4.2.3.1 | Single-Dose Toxicity | Acute toxicity | [ ] |
| 4.2.3.2 | Repeat-Dose Toxicity | Subacute, subchronic, chronic | [ ] |
| 4.2.3.3.1 | In Vitro Genotoxicity | Ames, chromosomal aberration | [ ] |
| 4.2.3.3.2 | In Vivo Genotoxicity | Micronucleus | [ ] |
| 4.2.3.4.1 | Carcinogenicity (Long-term) | If required | [ ] |
| 4.2.3.4.2 | Carcinogenicity (Short/medium-term) | If applicable | [ ] |
| 4.2.3.5.1 | Fertility and Early Embryonic Development | Segment I | [ ] |
| 4.2.3.5.2 | Embryo-Fetal Development | Segment II | [ ] |
| 4.2.3.5.3 | Pre- and Postnatal Development | Segment III | [ ] |
| 4.2.3.6 | Local Tolerance | As applicable | [ ] |
| 4.2.3.7.1 | Antigenicity | If applicable | [ ] |
| 4.2.3.7.2 | Immunotoxicity | ICH S8 studies | [ ] |
| 4.2.3.7.3 | Mechanistic Studies | If applicable | [ ] |
| 4.2.3.7.4 | Dependence | If applicable | [ ] |
| 4.2.3.7.5 | Metabolites | If applicable | [ ] |
| 4.2.3.7.6 | Impurities | Qualification studies | [ ] |
| 4.2.3.7.7 | Other | Phototoxicity, etc. | [ ] |
Module 4 STF (Study Tagging File) Checklist
Standardize your nonclinical Study ID nomenclature early in the project planning phase. Use a consistent format (e.g., TOX-001, TOX-002) and maintain a master Study ID registry. This prevents the common error of having different Study ID variations across Module 2 references versus the actual Module 4 study reports.
STF validation requirements:
- [ ] Study ID matches across all documents
- [ ] Study type correctly classified per ICH M8
- [ ] Species correctly identified
- [ ] Route of administration accurate
- [ ] Duration of treatment correct
- [ ] GLP compliance statement present (where required)
- [ ] Test article properly identified
- [ ] Study dates accurate
Module 5 Checklist: Clinical Studies
Module 5 typically contains the most documents and requires comprehensive STF tagging. The eCTD checklist for Module 5 must ensure ICH E3 compliance.
Module 5 Document Structure Checklist
| Section | Content | Required Documents | Checklist Status |
|---|---|---|---|
| 5.2 | Tabular Listing | All clinical studies | [ ] |
| 5.3.1.1 | BA Studies | Bioavailability reports | [ ] |
| 5.3.1.2 | Comparative BA/BE Studies | BE study reports | [ ] |
| 5.3.1.3 | In Vitro-In Vivo Correlation | IVIVC reports | [ ] |
| 5.3.1.4 | Bioanalytical Methods | Method validation | [ ] |
| 5.3.2.1 | Plasma PK and Initial Tolerability | PK study reports | [ ] |
| 5.3.2.2 | Intrinsic Factor PK | Renal/hepatic impairment | [ ] |
| 5.3.2.3 | Extrinsic Factor PK | Drug interactions | [ ] |
| 5.3.2.4 | PopPK | Population PK analyses | [ ] |
| 5.3.3.1 | Healthy Subject PD | PD study reports | [ ] |
| 5.3.3.2 | Patient PD and PK/PD | PK/PD modeling | [ ] |
| 5.3.4.1 | Efficacy and Safety by Indication | Controlled studies | [ ] |
| 5.3.4.2 | Uncontrolled Studies | If applicable | [ ] |
| 5.3.5.1 | Controlled Studies | Efficacy trials | [ ] |
| 5.3.5.2 | Uncontrolled Studies | Supportive trials | [ ] |
| 5.3.5.3 | Reports from Multiple Studies | Integrated analyses | [ ] |
| 5.3.5.4 | Other Efficacy Studies | Registry data, etc. | [ ] |
| 5.3.6 | Post-Marketing Experience | If applicable | [ ] |
| 5.3.7 | Case Report Forms | Individual patient data | [ ] |
| 5.4 | Literature References | Published literature | [ ] |
Clinical Study Report (ICH E3) Checklist
Each clinical study report must contain:
| Section | E3 Requirement | Checklist Status |
|---|---|---|
| Title Page | Study ID, title, sponsor, dates | [ ] |
| Synopsis | 3-page summary | [ ] |
| Table of Contents | Complete with page numbers | [ ] |
| List of Abbreviations | All abbreviations defined | [ ] |
| Ethics | IRB/IEC approvals, informed consent | [ ] |
| Investigators | Investigator list and qualifications | [ ] |
| Introduction | Background and rationale | [ ] |
| Study Objectives | Primary and secondary | [ ] |
| Investigational Plan | Design, endpoints, statistics | [ ] |
| Study Patients | Disposition, demographics | [ ] |
| Efficacy Evaluation | Results, analyses | [ ] |
| Safety Evaluation | AEs, labs, vital signs | [ ] |
| Discussion and Conclusions | Interpretation | [ ] |
| Appendices | Protocol, SAP, CRFs | [ ] |
Regional eCTD Submission Requirements Comparison
Understanding regional differences is essential for global submissions. This eCTD checklist comparison highlights key variations.
FDA vs. EMA vs. Health Canada Requirements
| Requirement | FDA (US) | EMA (EU) | Health Canada |
|---|---|---|---|
| eCTD Version | 3.2.2 or 4.0 | 3.2.2 | 3.2.2 |
| Gateway | ESG | CESP | CESR |
| Module 1 Language | English | English (+ national) | English/French |
| Application Form | FDA 356h | EMA Application Form | HC Forms |
| Labeling Format | USPI/PLR | SmPC | Canadian PM |
| Financial Disclosure | Required | Not required | Not required |
| Environmental Assessment | Required | Required | Not required |
| Expert Declarations | Not required | Required | Not required |
| Manufacturing Authorization | Not in M1 | Required reference | Not required |
| Orphan Documentation | Separate process | Module 1.7 | Separate process |
| Pediatric Information | Module 1.11 | Separate PIP | Separate |
| PDUFA Fee | Required | N/A | N/A |
Regional Module 1 Structure Comparison
| FDA Section | EMA Equivalent | HC Equivalent |
|---|---|---|
| 1.1 Forms | 1.2 Application Form | 1.2.1, 1.2.2 Forms |
| 1.2 Cover Letter | 1.0 Cover Letter | 1.0 Cover Letter |
| 1.3 Patent Info | N/A | N/A |
| 1.4 Labeling | 1.3.1 SmPC | 1.3.1 Product Monograph |
| 1.6 Environmental | 1.6.1 ERA | N/A |
| 1.7 Debarment | N/A | N/A |
| 1.8 Financial | N/A | N/A |
| 1.12 REMS | 1.8.1 RMP | Risk Management |
Pre-Submission Validation Checklist
Technical validation before submission prevents gateway rejections. Use this eCTD publishing checklist as your final quality gate.
Technical Validation Checklist
| Validation Category | Check | Tool/Method | Status |
|---|---|---|---|
| XML Backbone | Schema validation | DTD/XSD validator | [ ] |
| Well-formed XML | XML parser | [ ] | |
| Namespace declarations | Manual review | [ ] | |
| Leaf ID uniqueness | Publishing tool | [ ] | |
| File Naming | 64-character limit | Automated check | [ ] |
| No special characters | Automated check | [ ] | |
| Lowercase extensions | Automated check | [ ] | |
| No spaces | Automated check | [ ] | |
| PDF Documents | Version 1.4-1.7 | PDF validator | [ ] |
| Fonts embedded | PDF validator | [ ] | |
| Bookmarks present | Manual review | [ ] | |
| No encryption | PDF validator | [ ] | |
| Hyperlinks functional | Link checker | [ ] | |
| Checksums | MD5 calculated correctly | Publishing tool | [ ] |
| Files not modified | Checksum verification | [ ] | |
| Folder Structure | ICH M8 compliant | Automated check | [ ] |
| Sequence numbering correct | Manual review | [ ] | |
| STF (Modules 4-5) | Study tagging complete | STF validator | [ ] |
| Study types correct | Manual review | [ ] |
Pre-Submission Quality Checklist
| Quality Check | Description | Status |
|---|---|---|
| Module 1 Complete | All required forms present and signed | [ ] |
| Module 2/3 Consistency | QOS matches CMC data | [ ] |
| Module 2/4 Consistency | Nonclinical overview matches study reports | [ ] |
| Module 2/5 Consistency | Clinical summary matches study reports | [ ] |
| Cross-References Valid | All hyperlinks resolve | [ ] |
| Batch Numbers Match | Consistent across modules | [ ] |
| Specifications Align | 2.3 tables match 3.2.S/P specifications | [ ] |
| Study IDs Consistent | Same IDs in Module 2 and Modules 4/5 | [ ] |
Run your complete eCTD through the agency's test gateway at least 5 business days before planned submission. This buffer allows time to address any unexpected technical issues without impacting your submission deadline.
Gateway Submission Checklist
Final checks before transmission:
| Pre-Submission Step | Action | Status |
|---|---|---|
| Gateway Account | Verify ESG/CESP credentials active | [ ] |
| Test Submission | Run through test gateway (if available) | [ ] |
| File Size Check | Total submission under limit | [ ] |
| Antivirus Scan | Scan completed, no modifications | [ ] |
| Final Checksum | Regenerate and verify all MD5s | [ ] |
| Archive Copy | Create validated archive before send | [ ] |
| Acknowledgment Monitor | Set up to track gateway response | [ ] |
FDA's Electronic Submissions Gateway (ESG) provides technical acknowledgment within 1 business day. A successful acknowledgment does not guarantee acceptance-content review follows.
eCTD Submission Timeline Checklist
Planning your submission timeline ensures adequate time for validation and correction cycles.
Recommended Pre-Submission Timeline
| Weeks Before Submission | Activity | Checklist Focus |
|---|---|---|
| 12 weeks | Begin Module 3 assembly | CMC document finalization |
| 10 weeks | Begin Modules 4-5 assembly | Study report formatting |
| 8 weeks | Complete Module 2 drafts | Summary/body consistency |
| 6 weeks | Module 1 preparation | Regional forms, labeling |
| 4 weeks | First full validation | Technical compliance |
| 3 weeks | Cross-module validation | Content consistency |
| 2 weeks | Final corrections | Error remediation |
| 1 week | Gateway simulation | Submission readiness |
| 3 days | Final QC review | Last verification |
| Submission day | Transmit and monitor | Gateway acknowledgment |
Key Takeaways
An eCTD submission checklist is a comprehensive verification document that ensures all required components of an Electronic Common Technical Document are complete, properly formatted, and compliant with regulatory specifications before submission to agencies like FDA, EMA, or Health Canada. The checklist covers all 5 eCTD modules, technical validation requirements, and regional-specific administrative documents.
Key Takeaways
- A comprehensive eCTD submission checklist covers all 5 modules: Module 1 administrative documents are region-specific, while Modules 2-5 follow harmonized ICH requirements but require careful cross-referencing.
- Module 2 to Module 3 consistency is critical: Cross-reference errors between QOS summaries and CMC body data are the leading cause of 120-day letters and indicate potential data integrity issues.
- Regional requirements vary significantly in Module 1: FDA requires financial disclosure and PDUFA fees; EMA requires expert declarations; Health Canada requires bilingual documentation for certain markets.
- Pre-submission validation prevents 40% of common errors: Implementing a five-stage validation protocol (document, module, cross-module, full submission, gateway simulation) catches errors before they cause costly rejections.
- Start eCTD preparation 12 weeks before submission: Adequate timeline allows for proper validation cycles and correction without compromising submission quality.
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Next Steps
A comprehensive eCTD submission checklist is your best defense against preventable errors, but manually tracking hundreds of requirements across modules is error-prone and time-consuming.
Download our free eCTD Submission Checklist to ensure your next submission is complete and compliant. The downloadable checklist covers all 5 modules, regional requirements for FDA/EMA/Health Canada, and pre-submission validation steps.
Want automated eCTD validation? Assyro's AI-powered platform validates your eCTD submission against 10,000+ regulatory rules simultaneously, checking not just technical compliance but cross-module consistency and regional requirements. Catch errors before FDA does.
Organizations managing regulatory submissions benefit from automated validation tools that catch errors before gateway rejection. Assyro's AI-powered platform validates eCTD submissions against FDA, EMA, and Health Canada requirements, providing detailed error reports and remediation guidance before submission.