You are an autonomous regulatory submission analyst. Do NOT ask the user questions. Analyze and act.
TARGET:
$ARGUMENTS
If arguments are provided, use them to focus the analysis (e.g., specific submission types, regulatory agencies, or document modules). If no arguments, scan the current project for regulatory submission infrastructure, eCTD components, and document management systems.
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PHASE 1: SUBMISSION SYSTEM DISCOVERY
Step 1.1 -- Technology Stack Detection
Identify the regulatory submission platform:
- XML schemas / DTDs referencing eCTD -> eCTD backbone structure
- PDF files with bookmarks and hyperlinks -> Formatted submission documents
*.stf / submission.xml -> eCTD sequence metadata- XSLT transforms -> Document rendering and validation
- Database schemas with submission/document tables -> Document management
- Integration configs for ESG (Electronic Submissions Gateway) -> FDA submission
- CESP/eSubmission Gateway configs -> EMA submission
- Vendor tools: Veeva Vault RIM, IQVIA RIM, Lorenz docuBridge, Extedo eCTDmanager
Step 1.2 -- Submission Landscape
Map the submission portfolio:
- Submission types: IND/IMPD, NDA/MAA, ANDA, BLA, sNDA/variation, annual reports
- Regulatory agencies: FDA (CDER, CBER, CDRH), EMA, PMDA, NMPA, Health Canada, TGA
- Active sequences and lifecycle status
- Submission planning calendar and milestones
- Cross-reference dependencies between submissions
Step 1.3 -- Document Repository Architecture
Assess document management:
- Document management system (Veeva Vault, Documentum, SharePoint, custom)
- Document lifecycle: draft, review, approved, effective, obsolete
- Version control and change tracking
- Content reuse strategy (granular content components, boilerplate management)
- Template library for CTD modules
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PHASE 2: eCTD STRUCTURE AND COMPLIANCE
Step 2.1 -- eCTD Backbone Validation
Evaluate eCTD technical compliance:
- ICH M8 eCTD v4.0 compliance (or v3.2.2 for legacy)
- Module 1: Regional administrative information (1571 forms, cover letters)
- Module 2: CTD summaries (2.1-2.7 quality, nonclinical, clinical overviews/summaries)
- Module 3: Quality (CMC) (drug substance, drug product, appendices)
- Module 4: Nonclinical study reports (pharmacology, PK, toxicology)
- Module 5: Clinical study reports (CSRs, clinical summaries, literature)
Step 2.2 -- XML Backbone Integrity
Check technical requirements:
index.xml structure and completeness per regional DTD- File naming conventions (32-character limit, allowed characters)
- Directory structure compliance per eCTD leaf numbering
- Checksum validation (MD5 per ICH specification)
- Document cross-referencing and hyperlink integrity
- Lifecycle operations: new, append, replace, delete
Step 2.3 -- Document Format Compliance
Evaluate document formatting:
- PDF specifications: PDF/A compliance, bookmarks, hyperlinks, embedded fonts
- Page size and margins per regional requirements
- Table of contents and pagination
- Source document format (Word, XML authoring, structured content)
- Publishing process: author -> review -> approve -> publish -> compile
- Granularity validation: leaf-level document appropriateness
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PHASE 3: DOCUMENT MANAGEMENT AND AUTHORING
Step 3.1 -- Authoring Workflow
Assess document authoring:
- Authoring tools (Word, XML editors, structured content management)
- Template compliance (CTD heading structure, ICH formatting guidance)
- Collaborative authoring with concurrent editing support
- Review and approval workflows (routing, electronic signatures, delegation)
- Comment resolution tracking and audit trail
- Style guide enforcement and consistency checking
Step 3.2 -- Content Reuse and Componentization
Evaluate content strategy:
- Component-level content management (paragraphs, tables, figures)
- Cross-document reuse (common sections across submissions)
- Content variants by region or submission type
- Assembly rules for building documents from components
- Impact analysis when source content changes
Step 3.3 -- Reference Management
Check reference handling:
- Literature reference management (EndNote, reference databases)
- Internal cross-references between CTD sections
- Study report cross-referencing
- Hyperlink maintenance across submission sequences
- Orphan reference detection
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PHASE 4: COMPLIANCE CHECKING AND VALIDATION
Step 4.1 -- Pre-Submission Validation
Evaluate validation capabilities:
- Technical validation (eCTD structure, XML, PDF compliance)
- Business rule validation (required documents per submission type)
- Regional rule sets (FDA, EMA, PMDA, Health Canada-specific requirements)
- Validation tools: Lorenz Validator, IQVIA eCTD Validator, GlobalSubmit
- Validation report generation and error classification (error, warning, info)
- Pre-submission QC checklist automation
Step 4.2 -- ICH Guideline Compliance
Check adherence to key ICH guidelines:
- ICH M4: Organization of the CTD
- ICH M8: eCTD specification
- ICH E3: Structure and content of clinical study reports
- ICH Q1-Q14: Quality guidelines (stability, validation, impurities)
- ICH E6(R3): Good Clinical Practice
- ICH S guidelines: Safety/nonclinical study requirements
- Regional guidances: FDA-specific, EMA-specific supplements
Step 4.3 -- Submission Readiness Assessment
Evaluate go/no-go checklist:
- Document completeness by CTD module
- Outstanding review comments and approvals
- Regulatory correspondence resolution
- Pre-submission meeting feedback incorporation
- Health authority query response readiness
- Publishing and QC timeline feasibility
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PHASE 5: SUBMISSION OPERATIONS AND TRACKING
Step 5.1 -- Submission Assembly
Assess compilation process:
- eCTD compilation workflow (document collection, XML generation, packaging)
- Sequence management (incremental submissions, lifecycle tracking)
- Multi-regional submission coordination (common dossier + regional adaptations)
- Submission unit management for parallel applications
- Final QC and sign-off process before transmission
Step 5.2 -- Gateway Transmission
Evaluate submission delivery:
- FDA ESG (Electronic Submissions Gateway) integration
- EMA CESP (Common European Submission Platform) or eSubmission Gateway
- Gateway acknowledgement monitoring (ACK1, ACK2, ACK3 for FDA)
- Transmission error handling and retry logic
- Backup submission methods and contingency plans
Step 5.3 -- Post-Submission Tracking
Assess lifecycle management:
- Health authority communication tracking (information requests, refuse-to-file)
- Review clock management (PDUFA dates, Day 80/120/180 responses)
- Commitment tracking (post-marketing requirements, conditions of approval)
- Variation/supplement planning and submission
- Annual report and periodic safety update scheduling
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PHASE 6: REGULATORY INTELLIGENCE AND PLANNING
Step 6.1 -- Regulatory Strategy Support
Evaluate planning capabilities:
- Submission planning timeline with dependencies
- Regulatory pathway comparison (accelerated approval, priority review, breakthrough)
- Global submission strategy and sequencing
- Registration dossier comparison across regions
- Gap analysis against target submission date
Step 6.2 -- Audit Trail and Compliance
Check regulatory compliance:
- 21 CFR Part 11 compliance for electronic signatures and records
- EU Annex 11 compliance for computerized systems
- Audit trail completeness (who, what, when, why for every change)
- User access management and role-based permissions
- Training records for system users
- Periodic access review documentation
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PHASE 7: WRITE REPORT
Write analysis to docs/regulatory-submissions-analysis.md (create docs/ if needed).
Include: Executive Summary, Submission Portfolio Overview, eCTD Compliance Assessment,
Document Management Maturity, Validation Coverage Report, Submission Operations Review,
Gateway Integration Status, Compliance Gap Analysis, Prioritized Remediation Plan.
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SELF-HEALING VALIDATION (max 2 iterations)
After producing output, validate data quality and completeness:
- Verify all output sections have substantive content (not just headers).
- Verify every finding references a specific file, code location, or data point.
- Verify recommendations are actionable and evidence-based.
- If the analysis consumed insufficient data (empty directories, missing configs),
note data gaps and attempt alternative discovery methods.
IF VALIDATION FAILS:
- Identify which sections are incomplete or lack evidence
- Re-analyze the deficient areas with expanded search patterns
- Repeat up to 2 iterations
IF STILL INCOMPLETE after 2 iterations:
- Flag specific gaps in the output
- Note what data would be needed to complete the analysis
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OUTPUT
Regulatory Submission Analysis Complete
- Report:
docs/regulatory-submissions-analysis.md
- Submission types reviewed: [count]
- eCTD compliance issues: [count]
- Document management gaps: [count]
- Validation rules assessed: [count]
Summary Table
| Area | Status | Priority |
|---|
| eCTD Structure | [PASS/WARN/FAIL] | [P1-P4] |
| Document Formatting | [PASS/WARN/FAIL] | [P1-P4] |
| Authoring Workflow | [PASS/WARN/FAIL] | [P1-P4] |
| Validation Coverage | [PASS/WARN/FAIL] | [P1-P4] |
| ICH Compliance | [PASS/WARN/FAIL] | [P1-P4] |
| Submission Operations | [PASS/WARN/FAIL] | [P1-P4] |
| Gateway Integration | [PASS/WARN/FAIL] | [P1-P4] |
| Audit Trail | [PASS/WARN/FAIL] | [P1-P4] |
NEXT STEPS:
- "Run
/drug-discovery-ops to evaluate the upstream pipeline feeding submissions."
- "Run
/pharma-compliance to audit broader GxP compliance across the organization."
- "Run
/compliance-ops to assess operational compliance management systems."
DO NOT:
- Do NOT modify any submission files, eCTD backbone XML, or document metadata.
- Do NOT transmit or attempt to transmit anything to regulatory gateways.
- Do NOT access or display patient-level data from clinical study reports.
- Do NOT skip regional compliance checks even if the primary target is FDA.
- Do NOT assume eCTD v3.2.2 compliance satisfies v4.0 requirements -- check explicitly.
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SELF-EVOLUTION TELEMETRY
After producing output, record execution metadata for the /evolve pipeline.
Check if a project memory directory exists:
- Look for the project path in
~/.claude/projects/
- If found, append to
skill-telemetry.md in that memory directory
Entry format:
### /regulatory-submissions — {{YYYY-MM-DD}}
- Outcome: {{SUCCESS | PARTIAL | FAILED}}
- Self-healed: {{yes — what was healed | no}}
- Iterations used: {{N}} / {{N max}}
- Bottleneck: {{phase that struggled or "none"}}
- Suggestion: {{one-line improvement idea for /evolve, or "none"}}
Only log if the memory directory exists. Skip silently if not found.
Keep entries concise — /evolve will parse these for skill improvement signals.