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21 CFR Part 11 Compliance Checklist For FDA-Regulated Industries

Written by Jianna Lieberman | May 8, 2025 11:47:25 PM

Meeting 21 CFR Part 11 requirements is a critical concern for teams managing electronic records and signatures in FDA-regulated environments.

If you're searching for a 21 CFR Part 11 compliance checklist, you're likely looking for a clear, practical guide to help ensure your systems, processes, and documentation align with FDA expectations. This article breaks down the regulation into plain language and offers a step-by-step checklist you can actually use.

In this article, you will learn:

  • What 21 CFR Part 11 requires for electronic systems and signatures
  • A detailed checklist that maps directly to compliance requirements
  • Where teams often go wrong and how to avoid common pitfalls

Let’s start by understanding what the regulation actually covers and who it applies to.

What Is 21 CFR Part 11 and Who Needs to Comply?

21 CFR Part 11 is a regulation issued by the U.S. Food and Drug Administration (FDA) that governs the use of electronic records and electronic signatures.

Its primary goal is to ensure that digital systems used in FDA-regulated activities are trustworthy, reliable, and equivalent to paper-based systems.

The regulation applies to any organization that uses electronic systems to create, modify, maintain, archive, retrieve, or transmit records required by FDA regulations. This includes companies involved in pharmaceuticals, biotechnology, medical devices, clinical research, food and beverage manufacturing, and more.

If your organization submits data to the FDA or is subject to FDA inspections, 21 CFR Part 11 likely applies to you.

Kivo is a unified RegOps management system built specifically to serve the life sciences industry. We provide systems for document management, regulatory information management, quality management, and eTMF, which means that 21 CFR Part 11 compliance is a critical part of everything we do.

We use our expertise to help our users stay compliant automatically when they use our software, and we want to use that expertise to provide you with the helpful 21 CFR Part 11 checklist you're looking for.

Key Requirements of 21 CFR Part 11

21 CFR Part 11 sets out specific criteria that electronic records and electronic signatures must meet to be considered trustworthy and equivalent to paper records with handwritten signatures.

These requirements are grouped into several core areas that focus on system integrity, user accountability, and data security:

  • System Validation: Any software used to manage regulated records must be validated to ensure it does what it's intended to do consistently and reliably.
  • Audit Trails: The system must automatically generate secure, computer-generated, time-stamped audit trails to record who did what, when — and preserve those records.
  • User Authentication and Access Controls: Each user must have a unique ID and password, with role-based access to prevent unauthorized data entry or changes.
  • Electronic Signatures: Signatures must be securely linked to their corresponding records and include the signer’s name, date, and meaning of the signature (e.g., approval, review).
  • Record Retention and Retrieval: Records must be stored in a way that allows for accurate, complete, and timely retrieval throughout their retention period.
  • Operational and Procedural Controls: Organizations must establish written policies that govern the use of electronic systems and signatures, including training procedures and documented SOPs.

These controls blend IT, quality assurance, and operational accountability into a single framework designed to protect public health and ensure data credibility.

For life sciences organizations, clinical, quality, and regulatory systems are subject to heightened scrutiny, and failure to meet audit trail, signature, or validation requirements can jeopardize inspections or delay submissions, which is Kivo offers features like pre-validated environments and built-in audit trails designed specifically for these high-stakes workflows.

The Risks of Non-Compliance

Failing to comply with 21 CFR Part 11 can result in costly enforcement actions, delayed approvals, and long-term reputational damage. The FDA actively inspects electronic systems during audits and has issued numerous warning letters to organizations for inadequate audit trails, missing validations, and improperly implemented electronic signatures.

Non-compliance can lead to:

  • FDA warning letters or Form 483 observations
  • Suspended or delayed clinical trials or product approvals
  • Loss of trust from partners, regulators, and investors
  • Costly remediation efforts, system overhauls, or revalidation work

And these aren’t hypothetical outcomes. Real-world cases have shown how simple missteps like lacking documented procedures for electronic records can cascade into major business disruptions.

In life sciences, every regulatory delay has financial and scientific consequences, and staying audit-ready at all times is a competitive advantage. A clean compliance record can accelerate approvals, attract partners, and give regulatory teams more confidence in system integrity.

Kivo helps life sciences teams stay ahead by embedding compliance into the way documents, signatures, and audits are managed, so you're never caught off guard during inspections.

The 21 CFR Part 11 Compliance Checklist

Use the following checklist as a practical tool to evaluate whether your systems and processes align with 21 CFR Part 11.

Each item maps directly to a requirement in the regulation, helping you stay prepared for audits and ensure your electronic records and signatures meet FDA expectations.

✅ System Validation

  • Is the system validated for its intended use?
  • Are validation protocols, reports, and documentation available for review?
  • Is re-validation performed after system updates or configuration changes?

✅ Audit Trails

  • Does the system automatically generate secure, time-stamped audit trails?
  • Are changes to records (who, what, when) clearly tracked and unalterable?
  • Are audit trails reviewed regularly and available for inspection?

✅ Access Controls and User Authentication

  • Does each user have a unique ID and password?
  • Are permissions role-based, limiting access based on job function?
  • Is there a process for disabling accounts when users leave the organization?

✅ Electronic Signatures

  • Are e-signatures uniquely tied to specific users?
  • Do signed records include the name, date/time, and purpose of the signature?
  • Is the meaning of each signature clearly defined (e.g., review, approval)?

✅ Record Retention and Retrieval

  • Are electronic records stored securely for the required retention period?
  • Can authorized personnel retrieve records in a human-readable format?
  • Are backup and disaster recovery processes documented?

✅ Standard Operating Procedures (SOPs) and Training

  • Do you have written procedures covering the use of electronic systems and signatures?
  • Are users trained and qualified before being granted system access?
  • Is training documented and repeatable?

Kivo’s platform supports these requirements out of the box: pre-validated environments, complete audit trails, permission-based access, and built-in electronic signature workflows. Our customers can walk into audits with confidence knowing their system was built specifically for 21 CFR Part 11 compliance.

Common Compliance Pitfalls and How to Avoid Them

Even well-intentioned teams can fall short of 21 CFR Part 11 compliance due to misunderstandings, outdated systems, or inconsistent processes. The most common compliance issues tend to arise in areas that require both technical controls and procedural discipline.

Here are the most common pitfalls we see and more importantly, how to avoid them.

1. Incomplete or Missing System Validation

Many teams assume that commercial software is automatically compliant. It’s not. The burden of validation falls on the user, and failing to validate for your intended use can lead to serious findings during an audit.

✅ Tip: Implement a documented validation protocol (IQ/OQ/PQ), and revalidate after significant updates.

2. Lack of Reliable Audit Trails

Systems that either don't track user activity or allow audit trails to be edited are non-compliant. Auditors often flag this as a major deficiency.

✅ Tip: Choose systems with automatic, tamper-evident audit trails that can’t be turned off or altered.

3. Weak Access Controls and Shared Credentials

When multiple people share login credentials or access is not role-based, it breaks the chain of accountability.

✅ Tip: Require unique logins for every user and review access regularly.

4. Improper or Incomplete Electronic Signature Configuration

Signatures that don’t capture the intent (approval, review, etc.) or don’t link clearly to the record may be rejected during inspections.

✅ Tip: Make sure signatures are time-stamped, traceable, and tied to specific actions.

5. Missing or Outdated SOPs and Training

Compliance is about both tools AND behavior. Without written procedures and user training, even the best systems can be misused.

✅ Tip: Maintain SOPs that cover system use, security, and signature responsibilities, and keep training logs up to date.

In life sciences, these “small” issues can derail inspections, delay INDs or NDAs, and trigger costly CAPAs. Kivo helps reduce these risks by combining purpose-built software with embedded compliance best practices.

How Kivo Makes 21 CFR Part 11 Compliance Easy

While we hope this 21 CFR Part 11 compliance checklist has been helpful, the reality is that you shouldn't need to do any of these things manually today.

Modern software capabilities are more than adequate to handle 21 CFR Part 11 compliance, and Kivo's platform makes compliance incredibly easy for life sciences teams by providing:

🔒 Pre-Validated Environment

Kivo provides a validated system environment that meets FDA expectations for software used in GxP workflows. We handle the validation work up front, reducing internal burden and shortening your path to compliance.

🕵️‍♂️ Automatic Audit Trails

Every action in Kivo is tracked in a tamper-evident, time-stamped audit trail. No extra configuration needed, no risk of missing critical data when an inspection is looming.

👥 Role-Based Access Controls

Kivo uses permission-based access that ties directly to user roles. Whether you’re managing study documents, SOPs, or submission content, access is limited to the right people and tracked by user ID.

✍️ Compliant Electronic Signatures

Electronic signatures in Kivo are fully Part 11–compliant: they’re securely linked to records, clearly identify the signer, and log the date, time, and intent (e.g., approval, review, submission).

📄 SOP & Training Alignment

Kivo supports the procedural side of compliance as well, providing tools to manage SOPs, training documents, and records in a unified environment that’s purpose-built for regulated teams.

Whether you're preparing for your first FDA audit or scaling a compliant operation globally, Kivo is designed to make 21 CFR Part 11 compliance easy and straightforward.

If you'd like to see how Kivo can help your team stay compliant across RIMS, QMS, and eTMF, click below to book a demo and learn why hundreds of life sciences teams are switching over to our modern, seamless, RegOps platform.