Understanding and Achieving 21 CFR Part11 and EU Annex 11 Compliance

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Understanding and Achieving 21 CFR Part11 and EU Annex 11 Compliance

By Nataraj Subramani | March 16, 2024 | California, USA

The U.S. Food and Drug Administration’s (FDA) and European Union’s (EU) regulations for Life Sciences are mostly interrelated. Organizations utilizing digital tools, automated processes, or transitioning to electronic systems need to comprehend the regulations in the U.S. FDA’s 21 CFR Part 11 and the EU’s guidelines, Annex 11.

Both guidelines are intended to facilitate Good Manufacturing Practice (GMP) and have been designed to ensure compliance and uphold the quality of computerized data systems in the life science industry. While there are many similarities between Annex 11 and Part 11, the two guidance are comparatively different.

To understand it even simpler, below is a comparison table highlighting key differences between CFR Part 11 and EU Annex 11:

Table 1: High-Level Comparison of Annex 11 and Part 11

Highlights21 CFR Part11EU Annexure11
ScopeElectronic records and signatures employed in FDA-regulated activities by Life Sciences and other entities.Relevant to and based on validation according to GMP, GDP, GLP, GCP, and medical devices.
FocusThe use of electronic signatures and records in open or closed computer systems.Quality management of computerized systems from a risk-based standpoint.
ObjectiveThe stored electronic records and signatures must be equally reliable and trustworthy as paper documents and wet signatures.Quality management of computerized systems from a risk-based standpoint.
Relevance and ValidationRelevant to and based on validation according to GMP, GDP, GLP, GCP, and medical devices.Relevant to GMP but referenced in other areas as well.

Table 2: Similarities and Difference between Annex 11 vs Part-11 Section

Principle11.2(b)- Implementation
11.10(a)- Validation
1. Risk ManagementNot Covered
2. Personnel11.10(i)- Personnel
3. Suppliers and Service ProvidersNot Covered
3.1 Formal AgreementsNot Covered
3.2  Audit SupplierNot Covered
3.3 Review Documentation for COTSNot Covered
3.4 Supplier Audit Available on RequestNot Covered
4. Validation11.10(a)- Validation
4.1 Cover Life CycleNot Covered
4.2 Change Control and Deviations11.10(k)- Documentation Control
4.3 Systems InventoryNot Covered
4.4 User Requirement SpecificationsNot Covered
4.5 Quality Management SystemNot Covered
4.6 Process for Customized SystemsNot Covered
4.7  Evidence of Appropriate Test MethodsNot Covered
4.8 Data Transfer Validation11.10(h)- Device Checks
5. Data11.10(f)- Operational System Checks
11.30- Controls for Open Systems
6. Accuracy Checks11.10(f)- Operational System Checks
7. Data Storage11.10(c)- Protection of Records
7.1 Secured and Accessible11.10(d) Limiting System Access
11.10(e) – Secure Records
11.10(g) – Authority Checks
7.2 Back-UpNot Covered
8.1 Clear Printed Copies11.10(b)- Generate Accurate and Complete Copies
8.2 Batch Release/Changed Since OriginalNot Covered
9. Audit Trails11.10(e) – Electronic Audit Trail
  11.10(k)(2)- Documentation Control
10. Change and Configuration Management11.10(d)- Limiting System Access
11.10(e)- Electronic Audit Trail
11. Periodic Evaluation11.300(b) and (e)- Periodically Checked
11.10(k)- Documentation Control
12. Security11.10(c) – Protection of Records
12.1 Physical/Logical11.10(d) – Limiting System Access
11.10(g) – Authority Checks
11.200 (a) and (b) Biometrics
11.300(a) Unique
11.300(d) – Prevent Unauthorized Use
12.2 CriticalityNot Covered
12.3 Security – Record Events11.300(b)and (c)-Controls for Identification Codes/Passwords
12.4 Data Management/Operators Entries11.10(e)-Controls for Closed Systems
13 Incident ManagementNot Covered
14 Electronic Signature11.50 – Signature Manifestations
14(a) Same as Hand-Written11.1(a) Scope
11.3(b)(7) Definitions
11.100(c) Certify Equivalent to Handwritten
14(b) Permanent Link11.70- Signature/Record Linking
14(c) Time and Date11.10(e)- Electronic Audit Trail
15 Batch ReleaseNot Covered
16 Business ContinuityNot Covered
17 Archiving11.10(c)- Protection of Records for Accurate Retrieval

Table 3: Similarities and Difference between Part-11 vs Annex 11 Section

(Subpart B – Electronic Records and Subpart C – Electronic Signatures) 

11.10 Controls for Closed Systems
11.10(a) Validation4-Validation
11.10(b) Generate Accurate and Complete Copies8.1-Printouts
11.10(c) Protection of Records for Accurate Retrieval17-Archiving, 12-Security, 7-Data Storage
11.10(d) Limiting System Access to Authorized Individuals7.1- Secured and Accessible
10- Change and Configuration Management
12.1-Security, Physical/Logical
11.10(e) Record of Operator Entries (Audit Trail)7.1- Secured and Accessible
9-Audit Trails
10-Change and Configuration Management
12.4- Data Management/Operators Entries
14(c)-Electronic Signature
11.10(f) Operational System Checks5-Data, 6- Accuracy Checks
11.10(g) Authority Checks7.1- Secured and Accessible
12.1-Security, Physical/Logical
11.10(h) Device Checks4.8-Validation
11.10(i) Personnel (who develop, users and maintain systems)2-Personnel
11.10(j) User Accountability for Actions Initiated under e-signaturesNot Covered
11.10(k) Documentation Control9-Audit Trails
4.2- change Control and Deviations
10-Change and Configuration Management
11- Periodic Evaluation
11.30 Controls for open systemsPrinciple (all systems) 5. Data
11.50 Signature Manifestations14-Electronic Signature
11.70 Signature/Record Linking14(b)-Electronic Signature
11.100 General requirements
11.100(a) Unique/Not ReusedNot Covered
11.100(b) Verify IdentityNot Covered
11.100(c) Certify Equivalent to Handwritten14(a) same as hand-written
11.200 Electronic signature components and controls
11.200(a) Not Based on Biometrics12.1-Security, Physical/Logical
11.200(b) Based on Biometrics12.1-Security, Physical/Logical
11.300(a) Unique 12.1-Security, Physical/Logical
11.300(b) Periodically Checked11. Periodic Evaluation
12.3-Security- Record Events
11.300(c) Procedures to deauthorize12.3-Security, Record Events
11.300(d) Prevent Unauthorized Use12.1-Security
11.300(e) Proper Function11-Periodic Evaluation


Part 11 primarily pertains to the utilization of electronic records and signatures within computer systems, whereas Annex 11 concentrates on the quality management of computerized systems. Part 11 mandates that electronic records and signatures maintain the same level of trustworthiness and reliability as paper records and handwritten signatures. Conversely, Annex 11 mandates that computerized systems guarantee equivalent product quality and quality assurance as manual systems.

Annex 11 applies to the  export or manufacture of products in the EU. However, Part 11 applies to e-submissions to the FDA. Part 11 and Annex 11 share similarities, yet diverge in aspects like authenticating the identity and accountability of authorized individuals and reporting to authorities. Annex 11 adopts a risk management perspective concerning criticality and ensures a system approach to periodic evaluations. Each guidance provides detail information to the life science companies to achieve regulatory compliance.

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