What is 21 CFR Part 11?

21 CFR Part 11 is a regulation established by the U.S. Food and Drug Administration (FDA) that sets the criteria for electronic records and electronic signatures (ERES) to be considered trustworthy, reliable, and equivalent to paper records and handwritten signatures. It applies to all FDA-regulated industries, including pharmaceuticals, biotechnology, medical devices, and other life sciences companies.

The purpose of 21 CFR Part 11 is to facilitate the use of technology in regulated environments while ensuring that data integrity, security, and traceability are preserved. It covers the systems and processes used to manage FDA electronic records and electronic signatures the FDA requires.

This regulation is especially crucial for organizations submitting documentation electronically to the FDA. It ensures that these records are secure, traceable, and cannot be altered without proper controls.

Validating Systems for Part 11 Compliance

Validation is a cornerstone of Part 11 compliance, ensuring that systems used to manage electronic records perform as intended. The FDA expects companies to validate systems using a risk-based approach, prioritizing systems that impact product quality, safety, or data integrity. A risk-based approach allows organizations to allocate resources efficiently, focusing validation efforts on critical systems while maintaining compliance.

Key considerations for validation include:

• Documented evidence that software systems meet user requirements and function consistently.
• Validation plans, test protocols, traceability matrices, and reports.
• Ongoing maintenance and periodic revalidation when changes are made.

When considering a vendor for your controlled documents and signatures, ask what is required of you to maintain validation. You may need re-validate each time they release a software update, and update your SOPs to match. Depending on the level of difficulty, this can be a resource and time-intensive process.

Kivo is unique in its approach to validation. We handle all validation - on our side AND the client’s - for every release, and our SOPs are updated as well. We call this “lifetime validation” - you can set it and forget it! Learn more in our trust center. 

Audit Trail Requirements

21 CFR Part 11 mandates that any changes to FDA electronic records be tracked through secure, computer-generated audit trails. Audit trails must be retained for up to 25 years, depending on the country, and must remain secure and tamper-proof. Systems must enforce access controls to ensure that only authorized users can view or modify the audit trail.

Audit trails must record:

• The date and time of actions that create, modify, or delete records.
• The identity of individuals performing actions.
• The reason for changes, when appropriate.

An unbroken audit trail is an essential component of federal review and approval. However, it is common to move documents in and out of multiple systems in the course of clinical trials. You may move a document from one site to another, from one CRO to another, and so forth. Each of these audit trails must be maintained and accessible. Make sure to discuss how your partners, such as your CRO are maintaining these records.

Kivo’s data migration tool goes one step further than most. When data is input into our system, we recompile any preexisting audit trails into a single, unbroken record - regardless of the number of systems your document has passed through. This simplifies inspector, auditor, or investor review!

User Access and Security Control Requirements

Effective security is essential for Part 11 compliance. The regulation requires strict controls over user access to systems containing FDA-regulated data. These controls help ensure that only verified users can access and interact with FDA electronic records.

Best practices include:

• Role-based access, ensuring users only have permissions necessary for their job.
• Least-privilege principle to reduce risk of unauthorized access.
• Unique user IDs to support traceability and accountability.
• Secure login mechanisms with password management and account lockout controls.

As you consider solutions, ask your vendors how access is granted and revoked. If this can only be done at the vendor side, how often will you have to make those requests, and what is their response time? If you can manage it yourself, how many options are there for role-based access? Is it customizable to your needs?

Kivo’s access permissions are fully customizable, down to the individual level. We use both role-based and team-based structures, so you can easily grant or revoke a entire group at a time, or just an individual. We also provide inspector-specific roles, designed to streamline their experience of the platform and allow you to better control the study narrative.

Electronic Signature Requirements

Electronic signatures must be legally binding and equivalent to handwritten signatures under 21 CFR Part 11. Each electronic signature must be linked to its corresponding record to prevent repudiation. Additionally, systems must ensure signatures cannot be copied or reused without proper authorization.

The regulation outlines requirements for:

• The printed name of the signer.
• The date and time of the signature
• The purpose of the signature (e.g., approval, review, authorship)

Record Retention and Retrieval Guidelines

Electronic record retention is critical to demonstrate compliance over time. Organizations should ensure systems support data integrity during long-term storage, accounting for file format obsolescence and necessary migrations. Retrieval systems must allow for prompt access by authorized users and regulators alike.

Part 11 requires that records:

• Be retained for up to 25 years based on applicable regulations.
• Remain accessible, readable, and usable throughout their lifecycle.

Many teams do not plan far enough ahead for their record retention, and may assume that their vendors (CROs, etc) will store their data indefinitely. However many CROs do not cover such long storage periods in their contracts. If they do continue to store your data, it may be at a much higher cost than you were anticipating! So make sure you…

• Understand how your data is being stored across vendors
• Have a transfer plan in place to migrate that data at study closure
• Know where you are going to put it and what it will cost long-term!
• Make sure that storage solution provides regular data integrity checks

System Controls and Change Management

Robust change management procedures are required to maintain Part 11 compliance as systems evolve. Kivo provides tools for SOP and quality document control, making it easier to manage the documentation and training processes required for compliant operations.

For systems control and change management, companies must implement:

• Change control protocols that document the rationale, impact, and testing of changes.
• Configuration management to track system settings and updates.
• Standard operating procedures (SOPs) and user training to ensure proper usage.

Again, check with your vendors on how often they update their SOPs, and the level of work you will need to do to update yours to match. And don’t overengineer your processes! Keep it right-sized for the scale of your operations so they are easier to update, especially for smaller sponsors.

Vendor and Supplier Management

Compliance doesn't end at your organization’s walls. Vendor qualification is essential for any third-party systems or services in electronic record management. Shared compliance scenarios should be documented to avoid gaps in accountability.

For vendor and supplier management, organizations must:

• Assess vendor systems and security controls.
• Define shared responsibilities in contracts.
• Ensure vendors understand and support 21 CFR Part 11 requirements.

You can keep track of vendors in spreadsheets, but depending on the number of vendors you are managing, you may want to have them stored within your quality system, and ideally, linked directly to the related documentation, such as licenses, audit results, etc.

To dive deeper into how to get started with SOPs and quality processes in your organization, check out this recent webinar with Quality Expert Angella Hamilton on how to keep Quality simple!

FDA Inspection Readiness

Getting to inspection isn’t just another to-do—it’s a huge deal. If your team is preparing for an FDA inspection, take a moment to appreciate what that really means: you’ve made it through the heavy lifting. The countless hours spent building quality systems, writing and reviewing SOPs, validating tools, and running mock inspections have all been leading up to this. Reaching this point means your team is doing something right. It means you’re ready.

At Kivo, we know how much work goes into getting here, and we’re in your corner the whole way. Our tools are designed to make inspection readiness feel a little less intimidating—and a lot more manageable. From organizing your validation docs and audit trails to giving inspectors a streamlined view of your records, we help make the inspection process smoother for everyone involved.

Recommended steps to ensure FDA inspection readiness include:

• Keep all your SOPs, training records, and validation documents in one easy-to-navigate place (yes, we can help with that).
• Run mock inspections—not just once, but a few times. They’re great for spotting any last-minute gaps.
• Get familiar with what inspectors tend to flag, such as missing audit trails or inadequate validation.

Whether it’s your first inspection or your tenth, you deserve to walk into it feeling confident. You’ve put in the work—and with a little prep (and a partner like Kivo), you’re more than ready to show it off.

Alignment with Other Standards and Regulations

Understanding 21 CFR Part 11 also means considering its relationship to other global compliance standards. Integrated frameworks reduce duplication and help harmonize processes across markets.

Aligning with global standards improves efficiency and broadens compliance with:

• EU Annex 11: Similar to Part 11 but includes additional expectations for risk management and personnel responsibilities.
• ISO 13485: Quality management for medical devices.
• GAMP 5:Guidance for validating automated systems in a regulated environment.

Kivo and Part 11 Compliance

Kivo already supports full Part 11 compliance, providing a validated platform that meets the requirements of 21 CFR Part 11, EU Annex 11, and aligns with ISO 13485 and ISO 9001 standards. Today, life sciences organizations use Kivo to confidently manage secure, compliant electronic records and workflows across regulated processes. As part of your Kivo subscription, DocuSign is included at no additional cost, a benefit that can lower costs for your organization while ensuring legally binding, FDA-compliant electronic signatures.

With Kivo, you can:

• Ensure compliance from the ground up using a system purpose-built for FDA-regulated industries.
• Seamlessly manage SOPs, training records, and validation documentation.
• Simplify your FDA electronic records and electronic signatures FDA requirements with confidence.