21 CFR Part 11 Common Questions and Answers

What is FDA 21 CFR Part 11? (32 Questions and Answers)

by | Jul 12, 2023 | 21 CFR Part 11

FDA 21 CFR Part 11, what is it?

FDA 21 CFR Part 11 specifies the regulatory requirements used in Food and Drug Administration (FDA) regulated industries for electronic records and signatures.

It outlines the requirements that companies must comply with to ensure the integrity, authenticity, and confidentiality of electronic records and signatures.

In response to the common questions and concerns surrounding FDA 21 CFR Part 11, we have compiled a list of the most frequently asked questions about the regulation. This article provides clear and concise answers to help you better understand what 21 CFR Part 11 entails.

Compliance with 21 CFR Part 11 is essential for companies using electronic records and signatures in FDA-regulated industries.

Life Science companies are now widely embracing 21 CFR Part 11 compliant solutions to effectively manage regulated processes and ensure rigorous compliance. One solution these companies utilize is eQMS software.

SimplerQMS provides an eQMS software compliant with 21 CFR Part 11 and designed specifically for Life Science companies. You can talk to our quality experts and book a personalized demo to learn how SimplerQMS can help your company work more efficiently and ensure compliance.

Table of Contents:

What Is FDA 21 CFR Part 11?

21 CFR Part 11 is part of a regulation by the FDA governing electronic records and signatures.

It outlines requirements for ensuring the reliability, authenticity, and integrity of electronic records and signatures used in FDA-regulated industries.

The initial publication of 21 CFR Part 11 occurred on March 20, 1997, and has been in effect since August 20, 1997. The most recent change to the regulation, as of July 2023, was made on March 2, 2023.

What Is the Main Purpose of the FDA 21 CFR Part 11?

The main purpose of 21 CFR Part 11 is to ensure the trustworthiness and reliability of electronic records and electronic signatures equivalent to traditional paper records and handwritten signatures.

The 21 CFR Part 11 establishes requirements to ensure data integrity, security, and reliability in electronic records and signatures to achieve its aim.

What Are the Main Benefits of 21 CFR Part 11?

Implementing 21 CFR Part 11 provides several main benefits, which include:

  • Improved Data Integrity: The regulation ensures the accuracy, completeness, and reliability of electronic records, reducing the risk of errors and data inconsistencies.
  • Regulatory Compliance: Following the requirements of 21 CFR Part 11 helps companies meet FDA regulations, demonstrating their commitment to data integrity, security, and reliability.
  • More Efficient Workflow Processes: Electronic records and signatures enable streamlined and automated processes, reducing the reliance on manual paperwork and improving efficiency.
  • Streamlined Collaboration: Electronic systems facilitate data sharing across teams, departments, and sites, enabling faster decision-making and smoother workflows.
  • Improved Auditability: The requirements for audit trails and electronic signatures improve the auditability of electronic records, making it easier to track and review actions taken.
  • Increased Security: 21 CFR Part 11 outlines the implementation of robust security measures, such as user authentication, access controls, and data encryption, ensuring the confidentiality, integrity, and availability of electronic records.
  • Simplified Recordkeeping: Electronic recordkeeping eliminates the need for physical storage space and reduces administrative burdens associated with manual recordkeeping, allowing for more efficient and organized data management.

Who Needs to Comply With 21 CFR Part 11?

Companies operating in FDA-regulated industries that use electronic records and electronic signatures must comply with 21 CFR Part 11.

In the Life Sciences, this includes but is not limited to pharmaceutical companies, biotechnology firms, medical device manufacturers, clinical laboratories, and others involved in developing, manufacturing, testing, or distributing FDA-regulated products.

When Does 21 CFR Part 11 Apply?

21 CFR Part 11 applies whenever electronic records and signatures are used and managed for activities subject to FDA regulations.

It applies to a range of FDA-regulated activities within the pharmaceutical, biotechnology, medical device, and related industries, including different stages of product development, such as research and development, manufacturing, and distribution.

Would you like to assess whether you need to comply with the regulation? You can use the 21 CFR Part 11 applicability assessment to determine if your system for managing electronic records and signatures needs to comply with the 21 CFR Part 11 requirements.

What Are the FDA Electronic Records Predicate Rules?

Electronic records predicate rules are requirements outlined in the Federal Food, Drug, and Cosmetic Act (the Act), Public Health Service Act (the PHS Act), and FDA regulations, other than 21 CFR Part 11, regarding electronic records, electronic signatures, and computer systems.

Companies using electronic records, signatures, or systems as per one of the predicate rules, such as 21 CFR Part 210, 211, and 820, must also comply with the requirements of FDA 21 CFR Part 11.

What Is FDA 21 CFR Part 11 Compliance?

FDA 21 CFR Part 11 compliance refers to acting following the requirements outlined in 21 CFR Part 11.

Compliance involves implementing the necessary controls and procedures to ensure the integrity, authenticity, and reliability of electronic records and signatures, as well as meeting security and data management requirements.

A compliant system helps avoid common noncompliances with 21 CFR Part 11 and potential regulatory and administrative actions from the FDA and US court, such as monetary penalties and product seizure.

Interested in learning the key steps to achieve compliance?

Find everything you need to know about 21 CFR Part 11 compliance in our article.

How To Be 21 CFR Part 11 Compliant?

To be compliant with 21 CFR Part 11, companies must fulfill the requirements outlined in the part of a regulation.

One effective approach is implementing compliant software eQMS solutions designed to streamline quality management processes and help ensure compliance with the FDA 21 CFR Part 11.

To assess the implementation of the 21 CFR Part 11, you can use a 21 CFR Part 11 compliance checklist.

What Makes a Computer System 21 CFR Part 11 Compliant?

A 21 CFR Part 11 compliant system should be able to ensure data integrity, security, and confidentiality of electronic records and signatures, while also providing compliance with the requirements outlined in 21 CFR Part 11.

Compliant system capabilities include, but are not limited to:

  • Detecting any invalid or altered records.
  • Generating accurate and complete copies of records in both human-readable and electronic formats.
  • Enabling accurate retrieval of records throughout the retention period.
  • Limiting system access to only authorized individuals.
  • Implementing secure and time-stamped audit trails.
  • Linking signatures to electronic records.
  • Issuing unique identification codes and passwords.
  • Enabling backup and recovery of data in the event of a system failure.

There is also confusion between 21 CFR Part 11 “compliant” and 21 CFR Part 11 “ready” systems, which are distinct states.

21 CFR Part 11 ready refers to a system with features aligning with 21 CFR Part 11 but may need configuration or validation for full compliance.

On the other hand, a 21 CFR Part 11 compliant system means the system has undergone validation and meets the regulation’s requirements. This makes it suitable for FDA-regulated environments without additional modifications.

What Are the Three Primary Areas of 21 CFR Part 11?

The three primary areas of 21 CFR Part 11 are categorized into subparts A, B, and C, which are as follows:

Subpart A – General Provisions: Define 21 CFR Part 11’s scope and applicability and provide key definitions for terms used throughout the regulation.

Subpart B – Electronic Records: Specify requirements for creating, modifying, and maintaining electronic records. It includes controls and procedures for ensuring data security, implementing audit trails, and limiting system access.

Subpart C – Electronic Signatures: Specifically addresses the use of electronic signatures. It outlines the requirements for their proper use, including controls for identification codes and passwords.

What Are 21 CFR Part 11 Requirements?

21 CFR Part 11 requirements include the controls and procedures to ensure the authenticity, integrity, and confidentiality of electronic records and prevent the signer from easily denying the legitimacy of the signed record.

In a brief overview, the 21 CFR Part 11 requirements are the following:

  • 21 CFR 11.1: Scope of regulation
  • 21 CFR 11.2: Implementation
  • 21 CFR 11.3: Definitions of terms
  • 21 CFR 11.10: Controls for closed systems
  • 21 CFR 11.30: Controls for open systems
  • 21 CFR 11.50: Signature manifestations
  • 21 CFR 11.70: Signature and record linking
  • 21 CFR 11.100: General electronic signatures requirements
  • 21 CFR 11.200: Electronic signature components and controls
  • 21 CFR 11.300: Controls for identification codes and passwords

You can learn more about the requirements outlined in the regulation in our dedicated article about the 21 CFR Part 11 requirements.

What Is an Electronic Record Under 21 CFR Part 11?

An electronic record under 21 CFR Part 11 is any digital information managed and processed electronically within the scope of 21 CFR Part 11.

It includes a combination of text, graphics, data, audio, pictorial, or other information created, modified, maintained, archived, retrieved, or distributed by a computer system as per 21 CFR 11.3(b)(6).

In addition to text documents, the following information assets are also included:

  • Images
  • Sound files
  • Videos
  • Test records
  • Source code
  • Spreadsheets

What Are 21 CFR Part 11 Requirements for Electronic Records?

21 CFR Part 11 requirements for electronic records are the procedures and controls Life Science companies must employ to ensure the authenticity and integrity of records.

All the requirements for electronic records are outlined in Subpart B of 21 CFR Part 11.

Subpart B includes requirements such as system validation, record generation, system access control, audit trails, operational checks, device checks, system user training, system documentation, signatures and records linking, signatures information, and more.

Want to dive deeper into the specific requirements? Read more about it in our article about 21 CFR Part 11 compliant electronic records.

What Is the Difference Between Open and Closed Systems in 21 CFR Part 11?

The difference between open and closed systems in 21 CFR Part 11 is the level of control over system access.

A closed system refers to an environment where access to the system is controlled by individuals responsible for its electronic records.

An open system refers to an environment where system access is not controlled by individuals who are responsible for the content of electronic records. In such systems, there may be less control over who can access the system and change the electronic records.

The difference between open and closed systems is important as it defines additional security measures to ensure compliance with 21 CFR Part 11 requirements.

What Is Computer System Validation According to 21 CFR Part 11?

Computer system validation is a process used to ensure that a computer system meets its intended use and complies with all applicable regulations.

It ensures the authenticity, integrity, and, when appropriate, confidentiality of electronic records, according to 21 CFR 11.10(a). Ensuring the ability to detect invalid or altered records is also essential.

21 CFR Part 11 outlines that computer system validation is necessary every time such systems are implemented or modified. It is required for computerized systems that are used to create, modify, maintain, or transmit electronic records or signatures subject to FDA regulations.

What Approach Is Recommended for Validating Electronic Systems?

The recommended approach for validating electronic systems is risk-based as outlined by industry guidelines such as ISPE GAMP5.

This means that the validation activities are prioritized based on the system’s risk and impact on product quality, data integrity, and patient safety. By conducting a thorough risk assessment, companies can identify critical functionalities and potential vulnerabilities.

What Does Accurate Record Generation Mean?

Accurate record generation refers to the 21 CFR 11.10(b) requirement that electronic records are created in a manner that ensures their accuracy and reliability, ensuring data integrity.

It means that the generated records should faithfully represent the information they are intended to capture without any intentional or unintentional alterations or discrepancies.

What Does Limited System Access Mean?

Limited system access means that access to computer systems used for electronic recordkeeping should be restricted to authorized individuals only.

Appropriate controls and procedures should be in place to prevent unauthorized access, ensuring that only authorized personnel can create, modify, or access electronic records as per 21 CFR 11.10(d).

Enforcing limited access for users involves implementing various measures to ensure that only authorized individuals can access computer systems used for electronic recordkeeping.

You can enforce limited access for users according to 21 CFR Part 11 by implementing the following methods:

  • Unique identification codes and passwords
  • Role-based access control
  • Multifactor authorization
  • Transaction safeguards to prevent unauthorized use of codes and passwords
  • Verify the identity of the users

What Is an Audit Trail Under 21 CFR Part 11?

An audit trail under 21 CFR Part 11 is a secure, computer-generated, time-stamped record that captures and documents all user actions and system activities related to creating, modifying, or deleting electronic records.

It serves as a reliable source of information for tracking and verifying the integrity and authenticity of electronic records throughout their lifecycle.

What Are 21 CFR Part 11 Requirements for Audit Trails?

The requirements for audit trails are as follows according to 21 CFR 11.10(e):

  • Secure and protected from unauthorized access.
  • Computer-generated.
  • Time-stamped.
  • Contain information about who made changes to the electronic records, what changes were made, and when.
  • Retained for at least as long as required for the corresponding electronic records.
  • Readily available for FDA review and copying.
  • Not obscure previously recorded information.

Looking for more information on audit trails? Check out our dedicated article about the audit trail requirements in 21 CFR Part 11.

What Are Operational System Checks According to 21 CFR Part 11?

Operational system checks refer to measures implemented within electronic systems to enforce the proper sequencing of steps and events according to 21 CFR 11.10(f).

These checks help ensure that operations are performed in the intended order and that any deviations or unauthorized actions are detected and addressed promptly.

What Are Device Checks According to 21 CFR Part 11?

Device checks are procedures implemented to verify the validity and reliability of data input sources or operational instruction in electronic systems, as defined by 21 CFR 11.10(h).

These checks assess the integrity of the devices, such as terminals, used to interact with the system. By conducting device checks, companies can ensure that the data entered, or instructions provided through the devices are accurate and appropriate for the intended operations.

What Training Requirements Are Required for 21 CFR Part 11 Compliance?

Training requirements required for 21 CFR Part 11 compliance specify that individuals who use electronic record and signature systems have the appropriate education, training, and experience to perform their assigned tasks according to 21 CFR 11.10(i).

Training records are documented proof of the training conducted in a company. These records are subject to the same requirements as any electronic record within the scope of 21 CFR Part 11 and are subject to the same controls.

You can learn more about the requirements for training records according to 21 CFR Part 11 by reading our article.

What Is a Policy of Responsibility for Using Electronic Signatures?

A policy of responsibility for using electronic signatures refers to a written document outlining the rules and guidelines regarding using electronic signatures within a company as per 21 CFR 11.10(j).

It holds individuals accountable and responsible for their actions initiated under their electronic signatures, preventing record and signature falsification.

The written document can be an Electronic Signature Agreement, signed by all users, indicating their acceptance and acknowledgment that their electronic signature carries the same legal weight as a handwritten signature.

What Documentation Requirements Apply to 21 CFR Part 11 Compliant Systems?

21 CFR Part 11 compliant systems should follow documentation requirements according to 21 CFR 11.10(k).

Documentation system requirements involve controlling the distribution, access, and use of system documentation for operation and maintenance purposes.

It also includes implementing revision and change control procedures that maintain an audit trail documenting the chronological development and modification of the system documentation.

What Is an Electronic Signature Under 21 CFR Part 11?

An electronic signature under 21 CFR Part 11 refers to a computer data collection of symbols executed and authorized by an individual.

The electronic signature is considered legally binding and is equivalent to the individual’s handwritten signature, according to 21 CFR 11.3(b)(7).

Electronic signatures are different from digital signatures.

Digital signatures are a type of electronic signature based on cryptographic methods to improve security as per 21 CFR 11.3(b)(5).

To learn more about key requirements, benefits, and best practices for 21 CFR Part 11 compliant electronic signatures see our comprehensive article on this topic.

If I Have Electronic Signatures, Do I Need To Comply With Electronic Record Requirements?

Yes, if you have electronic signatures being used to sign electronic records within an FDA-regulated industry, you must comply with the electronic record requirements outlined in 21 CFR Part 11.

Compliance with electronic records and signature requirements is necessary to ensure records’ integrity, authenticity, and reliability.

What Are 21 CFR Part 11 Requirements for Passwords and Identification Codes?

The requirements for passwords and identification codes outline controls to ensure electronic signatures’ security and integrity as per 21 CFR 11.300.

The requirements for passwords and identification codes include the following:

  • Implement unique password and identification code combinations for each individual.
  • Periodically check and revise password and identification codes to prevent password aging.
  • Follow loss management procedures to deauthorize lost or stolen devices with password and identification codes. Issue replacements using suitable and rigorous controls.
  • Use transaction safeguards to prevent unauthorized use of passwords and identification codes. Detect and report unauthorized use attempts to the system security unit and organizational management.
  • Periodically test devices that use or generate passwords and identification codes to ensure they function as intended.

You can see our dedicated article about 21 CFR Part 11 password requirements to explore the requirements in greater detail.

How Can I Identify if a System Is Compliant With 21 CFR Part 11?

To identify if a system complies with 21 CFR Part 11, you can request the software vendor provide proof of compliance. The vendor should be able to provide you with documentation that their system has been tested and is compliant with 21 CFR Part 11 requirements.

A vendor should undertake several actions and provide evidence to support their claim. Here are some proof of compliance you can ask the vendor to provide:

  • Documentation that the system has been validated, including test procedures and the results of the tests.
  • Information on the system access and security controls to protect the integrity and confidentiality of electronic records and signatures.
  • Security procedures for responding to incidents, including procedures for reporting incidents, investigating them, and taking corrective action.
  • Records of audits or inspections conducted to ensure compliance with 21 CFR Part 11.

What Is the Difference Between the FDA 21 CFR Part 11 and EU Annex 11?

The difference between FDA 21 CFR Part 11 and EU Annex 11 are the jurisdiction they apply to and their regulatory status.

FDA 21 CFR Part 11 is specific to the United States and applies to all FDA-regulated industries, including pharmaceuticals, medical devices, and biotechnology. It provides detailed requirements for electronic records and signatures. Compliance with 21 CFR Part 11 is mandatory for companies performing FDA-regulated activities.

On the other hand, EU Annex 11, is part of the European Union’s Good Manufacturing Practice (GMP) guidelines and applies to manufacturers of medicinal products within the EU member states. It focuses specifically on computerized systems used in GMP-regulated environments. Since EU Annex 11 is a guideline, compliance is optional.

You can learn more about the specific differences between FDA 21 CFR Part 11 and EU Annex 11 by reading our dedicated article on the topic.

What Is the Difference Between the FDA 21 CFR Part 11 and ISPE GAMP5?

The difference between FDA 21 CFR Part 11 and ISPE GAMP5 is their regulatory status and purpose.

FDA 21 CFR Part 11 is a part of regulation specific to the United States that outlines requirements for electronic records and signatures in FDA-regulated industries.

ISPE GAMP5 is an international guidance document that provides a risk-based approach for the validation of computerized systems.

How Does SimplerQMS Help Comply With 21 CFR Part 11?

SimplerQMS helps Life Science companies to achieve 21 CFR Part 11 compliance by providing a comprehensive eQMS software solution that facilitates the management of electronic records, signatures, and quality documentation.

Here are some key features and functionalities of SimplerQMS that align with 21 CFR Part 11 requirements:

  • Validated System: SimplerQMS is fully validated according to ISPE GAMP5 and undergoes revalidation when new versions or updates are released, eliminating the need for additional validation resources from our clients.
  • Secure Data Storage and Retrieval: We offer secure cloud storage for records, ensuring documents are protected and readily available during audits. A search feature allows for easy record retrieval based on keywords in titles and content.
  • Limited System Access: SimplerQMS connects with Microsoft Entra ID (previously known as Microsoft Azure Active Directory), enabling secure authentication and authorization and limiting system access to verified and authorized personnel.
  • Time-Stamped Audit Trail: The software provides a comprehensive and accurate audit trail that tracks all system activity, including record access, modifications, and approvals, as well as enabling easy comparison of changes and rollback to previous versions if needed.
  • Employee Training: We provide personalized training sessions support to ensure all system users know how to do their assigned tasks in SimplerQMS.
  • Electronic Signatures: The software offers out-of-the-box 21 CFR Part 11 compliant electronic signatures. Signatures are automatically linked to their respective records, ensuring authenticity and integrity.

Our platform supports compliance with various Life Science requirements, including ISO 9001:2015, ISO 13485:2016, FDA 21 CFR Part 11, 210, 211, and 820, EU GMP Annex 11, EU GMP, and more. With our extensive QMS process support, SimplerQMS software helps companies comply with the necessary standards and regulations.

Some of the QMS process support that the SimplerQMS solution offers includes document management, employee training, change control, CAPA management, complaint management, audit management, supplier management, and more.

If you are interested in identifying the value of an eQMS for your company, download our eQMS Business Case template.

The template allows you to assess the benefits of an eQMS tailored to your needs and present a well-rounded analysis to management.

By using this resource, you can ensure that all critical factors are considered and effectively demonstrate the advantages of implementing an eQMS.

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Final Thoughts

FDA-regulated industries must comply with 21 CFR Part 11, a part of the regulation governing electronic records and signatures. Many companies have questions regarding compliance and understanding the intricacies of the regulation.

In this article, we addressed frequently asked questions to help you gain a better understanding of 21 CFR Part 11, providing insights and guidance to clarify any doubts you may have.

SimplerQMS provides an eQMS solution fully compliant with 21 CFR Part 11 and validated according to ISPE GAMP5. Our system is designed to assist Life Science companies in meeting various compliance requirements.

To discover how SimplerQMS can improve your quality management and compliance efforts, schedule a demo, and talk with our quality experts today.

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