Introduction: In the life sciences sector, aligning with 21 CFR Part 11 isn’t just good practice—it’s crucial. This regulation, part of the Code of Federal Regulations, ensures the reliability of electronic records and signatures for FDA-regulated entities like pharmaceuticals, medical device manufacturers, and biotech firms. Let’s simplify what this means and how to stay compliant.
It’s all about making electronic records and signatures as trustworthy as their paper counterparts. Think of it as the FDA’s seal of approval on your digital data.
The Aim is to guarantee the authenticity, integrity, and security of electronic records, streamlining processes in GxP (Good [Clinical/Laboratory/Manufacturing] Practices) environments. It is important to maintain data integrity is non-negotiable for product safety and quality.
What is 21 CFR Part 11 ?
CFR Title 21 focuses on “Food and Drugs“, and Part 11 is devoted to “Electronic Records” and “Electronic Signatures“
FDA 21 CFR Part 11 was established to ensure the reliability, authenticity and integrity of e-records and e-signatures, and was introduced to address the rising use of electronic systems (in place of traditional paper-based systems) for documenting and maintaining records related to Good Manufacturing Practice and other regulated quality management activity.
FDA 21 CFR Part 11 compliance is the state of organizational adherence with a key regulation issued from the FDA electronic compliance guidelines.” to map out requirements for electronic records and signatures.
Key Requirements of 21 CFR Part 11:
Firms must validate computer systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records.
Systems must generate accurate and secure audit trails to document significant actions taken with electronic records.
Electronic signatures must be unique to the individual, securely managed, and contain appropriate controls to prevent unauthorized use.
Systems must have controls in place to ensure only authorized individuals have access to electronic records and electronic signatures.
Measures must be implemented to ensure the integrity and accuracy of electronic records throughout their lifecycle.
Implementing 21 CFR Part 11 compliance strategies
Compliance is crucial for companies in regulated Gxp industries to maintain data integrity, and therefore to ensure the safety, efficacy and quality of their manufactured products.
- Conduct Thorough System Validation: Regularly validate your systems to ensure they accurately and consistently produce the desired outcomes.
- Implement Robust Security Measures: Use encryption, access controls, and audit trails to safeguard electronic records and signatures.
- Train Your Team: Ensure that all relevant personnel are trained on the importance of 21 CFR Part 11 and the specific procedures related to electronic records and signatures.
Let’s divide this complaince checklist into 4 parts as below, as per FDA electronic compliance guidelines
Part 1: Validation
- Ensure systems are validated to maintain product quality and comply with regulations.
- Check for system features that allow identification of altered records, ensure records are retrievable, limit access to authorized users, and enforce the correct sequence of operations.
- Verify that system inputs are from validated devices, provide documented training to users and IT staff, and ensure a policy holds individuals accountable for actions under their electronic signatures.
- Control access to system documentation and use encryption and digital signatures for security.
Part 2: Audit Trails
- Establish secure, time-stamped audit trails that log changes to electronic records, ensuring previous information remains accessible
- Audit trails should be retrievable, reviewable during Audits, and include detailed logs of user actions, change logs, and revision controls.
- Ensure electronic signatures are unique, cannot be reused or reassigned, and are verified for the individual’s identity. Biometric and non-biometric signatures must be secure and unique to the user.
- Compliance requires formal change control procedures and a collaborative effort to falsify signatures, highlighting the importance of audit trail integrity.
Part 3: Copies of Records
- Systems must be capable of producing accurate and complete copies of electronic records in both paper and electronic forms for FDA inspection.
- Use automated methods for record conversion or export, ensuring records are traceable and accessible for regulatory review.
Part 4: Record Retention
- Secure storage of records and signatures is essential, with controls in place to maintain the uniqueness and periodic validation of user IDs and passwords.
- Implement procedures for password management, unauthorized use detection, loss management, and electronic device security to protect against unauthorized access and ensure document safety.
Maintaining 21 CFR Part 11 compliance
- Mastering 21 CFR Part 11 compliance ensures maintaining 21 CFR Part 11 compliance throughout its lifecycle,
- Long-Term Strategy: Compliance is an ongoing journey requiring constant oversight of your electronic records system.
- Internal Audits: Use them to find and fix compliance gaps, ensuring your data management is up to scratch
21 CFR Part 11 Noncompliance
Like any mandatory FDA regulation, failure to comply with the requirements of 21 CFR Part 11 can have negative consequences for your business. If an FDA auditor finds a Part 11 infraction, you’ll receive a Form 483 inspectional observation outlining the problem.
Repeated failure to comply will bring a warning letter, and persistent non-compliance could even result in recall of connected products or shutdown of your organization.
So Always, stay vigilant with regular FDA inspection audits and a compliance checklist covering system validation, audit trails, record copies, and secure storage.
Real-World Example: In Lifescience Industry
Let’s consider a pharmaceutical/helthcare company engaged in activities. Compliance with 21 CFR Part 11 is essential throughout the manufacturing process. Here are some examples of electronic records and signatures that might fall under the scope of Part 11:
Electronic Records:
- Electronic batch records for pharmaceutical manufacturing
- Electronic medical records in healthcare facilities
- Electronic laboratory notebooks for research and development
- Electronic reports generated by analytical instruments
- Electronic quality control documents and reports
Electronic Signatures:
- Digital signatures used to sign electronic records and documents
- Biometric signatures, such as fingerprints or facial recognition
- Typed usernames and passwords used to authenticate electronic signatures
- Smart card signatures using a card reader and PIN number
- Passwords used to approve electronic transactions
Software platforms and solutions that helps with 21 CFR Part 11 requirements
These are just a few examples of the many software platforms and solutions available that comply with Part 11. When selecting a solution, it’s important to carefully evaluate its features and capabilities to ensure it meets your specific compliance needs.
- DocuSign – DocuSign is a widely-used electronic signature platform that offers a range of features to ensure compliance with Part 11. These include document encryption, user authentication, and detailed audit trails.
- Adobe Sign – Adobe Sign is another popular electronic signature solution that complies with Part 11. It offers a variety of security features, including multi-factor authentication, digital certificates, and audit trails.
- Veeva Systems – Veeva Systems offers a suite of software solutions for the life sciences industry that are designed to comply with Part 11 requirements. Their solutions include electronic data capture, document management, and clinical trial management tools.
- MasterControl – MasterControl is a quality management system (QMS) that includes features for electronic records and signatures that comply with Part 11. It includes digital signature capabilities, audit trails, and user authentication controls.
Useful links
- https://www.fda.gov/regulatory-information/search-fda-guidance-documents/part-11-electronic-records-electronic-signatures-scope-and-application
- https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-11
- https://health.ec.europa.eu/system/files/2016-11/annex11_01-2011_en_0.pdf
- https://ispe.org/publications/guidance-documents
Sagar Pawar
Computer System Validation Specialist
