For life sciences companies subject to U.S. Food and Drug Administration (FDA) regulations, 21 CFR Part 11 governs how electronic records and electronic signatures are created, modified, maintained, archived, retrieved, and transmitted. A compliant quality management system (QMS) must not only enforce the technical controls required by the regulation but also maintain thorough documentation to demonstrate adherence.
This documentation is critical for validation, audit readiness, and avoiding FDA enforcement actions such as Form 483s or warning letters.
Below is a detailed overview of the documentation your QMS needs to comply with FDA 21 CFR Part 11.
1. System Validation Documentation
The FDA requires companies to validate systems used to manage electronic records and signatures. Validation ensures the system performs as intended and maintains data integrity over time.
Required documentation includes:
- Validation Plan (VP): Outlines the scope, responsibilities, deliverables, and testing approach.
- User Requirements Specification (URS): Details what the system must do from a business perspective.
- Functional Requirements Specification (FRS): Describes system functions and how they meet user needs.
- Risk Assessment: Evaluates potential risks to record integrity and defines mitigation measures.
- Validation Protocols (IQ/OQ/PQ): Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) protocols and results.
- Traceability Matrix: Maps requirements to test cases and results.
- Validation Summary Report (VSR): Confirms that all validation activities were completed and requirements met.
This documentation must be reviewed, approved, and retained in a controlled environment.
2. Standard Operating Procedures (SOPs)
SOPs are essential for governing how systems are used and how compliance is maintained.
Key SOPs for 21 CFR Part 11 compliance include:
- Electronic Records Management: Procedures for creating, modifying, and archiving records.
- Electronic Signature Usage: How electronic signatures are applied, their meaning, and authentication requirements.
- System Access and Security: Defines access levels, password requirements, account creation, and termination.
- Audit Trail Review: Procedures for reviewing and managing system audit trails.
- System Backup and Recovery: Defines data backup frequency, storage, and disaster recovery plans.
- Change Control: Steps to follow for system changes, updates, or patches, including revalidation when required.
- Training Records Management: Ensures users are trained and qualified to use the system in a compliant manner.
All SOPs must be version-controlled, approved, and accessible to users.
3. Audit Trails and Electronic Logs
Part 11 requires secure, computer-generated audit trails for any action that creates, modifies, or deletes a record. The system must log:
- Who performed the action
- What the action was
- When the action occurred (timestamp)
- Why (if applicable, such as for changes or deletions)
Documentation needed includes:
- Audit trail configuration documentation
- Audit trail review procedures and logs
- Evidence that audit trails are tamper-evident and cannot be disabled
Audit logs should be retained as long as the corresponding records and made readily available for review during inspections.
4. Access Control and Security Documentation
Part 11 mandates strict control over who can access electronic records and what they can do. The system must support individual user identification and prevent unauthorized access.
Required documentation includes:
- Access control policies and procedures
- User account management logs (creation, modification, deactivation)
- Password management rules (length, expiration, complexity)
- Role-based access configurations and approval documentation
- Periodic access reviews and audit logs
This documentation ensures only authorized users access the system and that access rights align with job responsibilities.
5. Electronic Signature Documentation
Electronic signatures must be uniquely linked to the individual, clearly indicate their intent (e.g., approval, authorship), and include date and time stamps.
Required documentation includes:
- Signature manifestation setup (visible to users and reviewers)
- Signature linking to specific records
- Signature meaning definitions (e.g., “approved by,” “reviewed by”)
- User agreements to use electronic signatures (can be a training record or signed form)
- Signature log or certificate repository
These elements ensure that electronic signatures are legally equivalent to handwritten signatures and are protected from forgery.
6. Training and Qualification Records
The FDA expects evidence that users are trained and qualified to use the QMS and follow SOPs that support compliance.
Required records include:
- Training curricula and materials related to 21 CFR Part 11 and system use
- User training completion logs with dates, names, and course content
- Role-based training matrices
- Qualification records for key personnel (system administrators, QA reviewers)
Training documentation must be available for review and should be kept up to date as roles or systems change.
7. Record Retention and Archiving Documentation
Records subject to FDA regulations must be retained for the required duration and remain accessible and readable.
Documentation includes:
- Record retention policies for each record type
- Record storage location mapping (e.g., cloud server, archive database)
- Long-term accessibility plans
- Format migration procedures (to prevent obsolescence)
This helps prove your organization can provide complete, accurate, and accessible records throughout their retention period.
8. Vendor Qualification
If your QMS is provided by a vendor (especially cloud-based), the FDA expects you to demonstrate vendor reliability and system suitability.
You may need:
- Vendor qualification questionnaire or audit report
- Service level agreements (SLAs) and responsibilities
- System documentation from the vendor (e.g., validation packages, certifications)
- Third-party penetration test results or security certifications (SOC 2, ISO 27001)
Vendor documentation helps you meet your responsibility for system performance, even if you don’t host it.
Ensure Audit Readiness Through Documentation
21 CFR Part 11 compliance isn’t just about system features. It’s about documenting how those features work, how they’re maintained, and how users interact with them.
A modern QMS purpose-built for regulated industries should provide much of this documentation out of the box. But it’s still up to your organization to maintain SOPs, validate usage, and ensure users are trained and accountable.
By keeping thorough, up-to-date documentation in each of these areas, you’ll be ready for inspections, reduce compliance risk, and strengthen the integrity of your electronic quality processes.
We’ve put together a checklist that can help. Download the 21 CFR Part 11 checklist to help guide you through the process.
