Every pharmaceutical, biotechnology, and medical device product moves through a regulated lifecycle. From the first preclinical study to post-market surveillance decades later, regulatory requirements govern what documentation must exist, what standards it must meet, and how compliance is demonstrated to regulatory authorities.
This guide maps the regulatory landscape across all five lifecycle domains — the frameworks, the documentation requirements, and where compliance gaps most commonly occur.
Phase 1: Discovery & Preclinical
Regulatory framework: 21 CFR Part 58 (GLP), 21 CFR Part 11, ICH M3(R2), ICH S guidelines
The preclinical phase establishes the safety foundation for human testing. GLP regulations (21 CFR Part 58) govern nonclinical laboratory studies intended to support FDA submissions. Key documentation requirements include study protocols, raw data with complete audit trails, quality assurance statements, and final study reports.
Common compliance gaps: Incomplete study protocol documentation, inadequate data integrity controls under Part 11, GLP study reports missing required QA statements, and nonclinical study designs that don't align with ICH M3(R2) timing requirements for the intended clinical phase.
IND-enabling studies must demonstrate that the drug can be safely administered to human subjects. The documentation standard is specific: preclinical pharmacology, toxicology data, and ADME studies must satisfy both the scientific and regulatory requirements for an IND application under 21 CFR Part 312.
Phase 2: Clinical Development
Regulatory framework: ICH E6(R2) (GCP), 21 CFR Part 312 (IND), 21 CFR Part 50/56, ICH E2–E9 guidelines
Clinical trials are the most complex regulatory environment in drug development. GCP requirements under ICH E6(R2) govern trial conduct, site monitoring, data management, safety reporting, and documentation across every trial phase.
Key documentation: Clinical protocols, informed consent forms, investigator brochures, clinical study reports, DSMB charters and meeting minutes, monitoring reports, and IND safety reports.
Common compliance gaps: Protocols missing required safety monitoring procedures, informed consent documents that don't satisfy 21 CFR Part 50 requirements, inadequate source data verification documentation, investigator brochure content gaps against ICH E7, and clinical study reports that don't follow ICH E3 structure requirements.
The IND submission itself (21 CFR Part 312) requires specific content sections — nonclinical data, clinical protocols, investigator information, and manufacturing information for the investigational product. Each section has defined content requirements that are frequently incomplete in initial submissions.
Phase 3: Manufacturing & Quality
Regulatory framework: 21 CFR Parts 210/211 (drug GMP), 21 CFR Part 820 (device QSR), ICH Q7–Q12, EU GMP Annexes
Manufacturing quality is the most inspected regulatory domain. FDA conducts thousands of GMP inspections annually, and the top 483 observations have remained consistent for over a decade — inadequate investigation procedures (§211.192), failures to follow written procedures (§211.100), and inadequate laboratory controls (§211.160).
Key documentation: Standard Operating Procedures (SOPs), batch records, deviation reports, CAPA records, process validation protocols and reports, environmental monitoring data, cleaning validation, and equipment qualification records.
Common compliance gaps: Deviation investigations that lack documented scientific rationale for root cause determination, CAPA records that track closure but don't evaluate root cause rigor, SOPs that don't map to current regulatory requirements, and process validation documentation that doesn't satisfy FDA's lifecycle approach.
For medical devices, 21 CFR Part 820 Quality System Regulation (transitioning to ISO 13485 harmonization) adds design control requirements, design history file documentation, and design review records.
Phase 4: Regulatory Submissions
Regulatory framework: ICH M4 (CTD), eCTD specifications, 21 CFR Part 314 (NDA), 21 CFR Part 601 (BLA), regional requirements
The regulatory submission is the culmination of all lifecycle documentation. The eCTD format (ICH M4) structures submissions into five modules, each with specific content requirements:
Module 1: Regional administrative information. Module 2: Quality Overall Summary (2.3), Nonclinical Overview (2.4), Clinical Overview (2.5), Nonclinical Summaries (2.6), Clinical Summaries (2.7). Module 3: Quality (CMC) — drug substance, drug product, manufacturing. Module 4: Nonclinical study reports. Module 5: Clinical study reports.
Common compliance gaps: Incomplete Module 2 summaries that don't satisfy ICH M4E/M4S content requirements, Module 3 CMC sections with manufacturing data inconsistencies, cross-module reference errors, missing benefit-risk analyses in Module 2.5, and eCTD technical format errors.
Complete Response Letters — FDA's formal notification that a submission cannot be approved as filed — most frequently cite CMC deficiencies, clinical data gaps, and labeling issues. Most CRL-triggering deficiencies existed in the documentation long before the submission was assembled.
Phase 5: Post-Market & Pharmacovigilance
Regulatory framework: 21 CFR 314.80 (US reporting), ICH E2A–E2F, EU GVP Modules, REMS guidance
Post-market surveillance is an indefinite regulatory obligation. As long as a product is on the market, the manufacturer must maintain pharmacovigilance systems, submit periodic safety update reports, manage risk, and report adverse events within defined timelines.
Key documentation: Individual Case Safety Reports (ICSRs), Periodic Safety Update Reports (PSURs/PBRERs), Risk Management Plans (RMPs), Development Safety Update Reports (DSURs), REMS assessments, and signal evaluation reports.
Common compliance gaps: PSUR/PBRER content that doesn't satisfy ICH E2C(R2) requirements for integrated benefit-risk analysis, risk management plans that don't adequately address identified risks per EU GVP Module V, delayed aggregate safety reporting, and adverse event narratives with inadequate causality assessment methodology.
The cross-domain reality: These five phases don't operate independently. Preclinical data becomes submission Module 4. Clinical data becomes Module 5. Manufacturing quality becomes Module 3. Post-market safety data can require changes to labeling, clinical protocols, and manufacturing processes simultaneously. Regulatory intelligence that spans the full lifecycle — connecting signals across GLP, GCP, GMP, submissions, and pharmacovigilance — is the only way to detect the systemic patterns that siloed tools miss.
Full Lifecycle Regulatory Intelligence
Clinplex AI provides regulatory intelligence across all five lifecycle domains. Upload documents from any phase — GLP protocols, clinical study reports, SOPs, eCTD modules, PV reports — or integrate with your existing enterprise systems (Veeva Vault, MasterControl, TrackWise, CTMS, RIM, safety databases) for continuous monitoring.
Every document analyzed against applicable regulatory frameworks with severity scoring, exact citations, and remediation roadmaps. Cross-domain pattern detection connects signals across domains that no single-domain tool can see.
Same AI-powered analysis whether you're a pre-IND biotech managing documents in file folders or a global pharma company running enterprise systems across 50 sites.
Start with One Document. From Any Stage.
Upload a regulatory document for a free gap analysis — or schedule a demo to see the full lifecycle platform.
Try Free Analysis →