21 CFR Part 11 Basics: Connecting the Dots From Regulation to Compliance in the Life Sciences Industry
Ensure Compliance & Efficiency of Software Solutions
By Jackie Davidson
Regulatory Intelligence and Innovation, Sware
You’ve probably heard of 21 CFR Part 11, the regulation that controls electronic records and electronic signatures. However, maybe you are new to the pharmaceutical industry, life sciences software solutions, or computer system validation in the pharmaceutical industry. If so, you’ll want to know a lot more about a little regulation called 21 CFR Part 11 and how to connect the dots from this regulation to the pharma industry and compliance. What is 21 Part 11 and how does it relate to GxP compliance in the pharmaceutical industry? Why is it important? What are the drivers behind validating GxP systems prior to regulated use? Are there solutions to help with common validation process stumbling blocks? We’ll answer your questions regarding Part 11, and its meaning for the pharma, medical device, and other life science industries in this post.
What is Part 11?
21 Code of Federal Regulations (CFR) Part 11, “Electronic Records; Electronic Signatures,” is an FDA regulation. It is intended to ensure that the electronic records and electronic signatures used in regulated industries – such as the pharmaceutical industry – are the equivalent of paper records and wet signatures. When first published in 1997, 21 CFR Part 11 was pivotal in GxP-regulated life sciences industries because these companies were moving from keeping paper-based records to using automated workflows and record keeping.
At the time, the software industry was young, systems developed for the GxP life sciences were clunky, and often unreliable. The industry was unsure how to test these systems, so most went for a blanket, “test everything” approach. This practice raised concerns about the burden and cost of validation and GxP compliance in the pharmaceutical industry. When GxP certification systems were small and locally hosted, with infrequent updates, it was plausible that a company might keep up with validation demands. With the evolution of Software as a Service (SaaS) systems in the 2000s, and with the rapid pace of today’s technology, it has become almost impossible for companies to meet compliance demands using traditional computer software validation methodology. This situation resulted in the release of the draft FDA Computer Software Assurance guidance in 2022 – the topic of our previous blogs in this series.
21 CFR Part 11 Buzzwords
Let’s review some key definitions around this topic:
- Electronic Record: Any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.
- Handwritten Signature: The scripted name or legal mark of an individual handwritten by that individual and executed or adopted with the present intention to authenticate a writing in a permanent form.
- Electronic Signature: A computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual's handwritten signature.
- Predicate Rule: Any rule, regulation, or requirement that can be found in the 21 CFR Food and Drug Regulations, the Public Health Service (PHS) Act, or any FDA regulation (e.g., GLP, GMP, GCP). Predicate rules are regulations that “came before” 21 CFR Part 11 and required record keeping; they apply to the actual process being performed (e.g., running a lab test and recording the notes in a lab notebook) that would have been required before Part 11 existed (e.g., manual entry of a batch record into a logbook and manual approvals of the batch). If the same process were to be automated, the requirement to keep the record still exists, but the software must be validated to ensure its access controls, suitability for intended use, and data integrity.
What Are the Key Requirements of 21 CFR Part 11 around Computer Systems Validation?
21 CFR Part 11 concerns itself not only with electronic records and electronic signatures, but also with the controls that ensure the integrity of GxP systems, their data, and electronic signatures executed in those systems. The most important controls for GxP compliance in the pharmaceutical industry (and other life sciences industries) include:
1. Validation: Electronic systems that are used to create, modify, maintain, or transmit electronic records must be validated to ensure accuracy, reliability, and consistency of the information stored within – to provide that the system can maintain records as robust as, and equivalent to, paper records. The validation process must prove that GxP systems perform their intended functions correctly and consistently and that the GxP systems are fit for the intended use.
2. Access Controls: Part 11 requires strict access controls to electronic records and systems. Part 11-compliant GxP systems must include unique user credentials (unique IDs and passwords), user authentication, and limitations on GxP system privileges to prevent unauthorized access or modifications. These standards are crucial for reducing risk and are based on best practices that aim to protect systems from unauthorized access.
3. Audit Trails: Part 11 mandates the use of access-controlled, secure, read-only, computer-generated audit trails to provide a chronological history, ensuring traceability and accountability for changes to GxP-compliant systems. Audit trails record and document any changes or modifications to electronic records throughout the lifespan of a life sciences software solution, making them key in ensuring data integrity. These audit trails include critical metadata – the old value that was changed, the new value, identification of the user making the change, the date and time of the change, and the reason for the change.
4. Electronic Signatures: Part 11 defines the requirements for electronic signatures, which serve as the equivalent of handwritten signatures. Electronic signatures executed in computerized systems are the legal equivalent of handwritten (wet) signatures and must be unique, secure, and capable of being verified and authenticated.
What Benefits Do 21 CFR Part 11 and Computer System Validation Provide to the Life Sciences Industry?
1. Data Integrity: 21 CFR Part 11 plays a critical role in ensuring the integrity of electronic data generated within the life sciences industry. It helps prevent data tampering and unauthorized access while maintaining the accuracy and reliability of electronic records, which are essential for compliance and decision-making processes in the pharmaceutical and related industries.
2. Regulatory Compliance: Compliance with 21 CFR Part 11 is mandatory for life sciences organizations using software that directly or indirectly impacts FDA-regulated products, including pharmaceuticals, medical devices, biotechnology, and clinical research. Adhering to the regulation helps companies avoid penalties, maintain regulatory approvals, and build trust with regulatory authorities.
3. Improved Efficiency and Cost Savings: Electronic records and signatures facilitate streamlined processes, reduced paperwork, and faster access to critical information. By embracing electronic systems that comply with 21 CFR Part 11, life sciences companies can enhance operational efficiency, reduce errors, and realize cost savings from accurate documentation and record-keeping practices.
4. Data Security: Part 11’s emphasis on user access controls, authentication, and audit trails helps ensure the security of sensitive information. Protection against data breaches and unauthorized modifications safeguards corporate intellectual property, patient privacy, and overall business reputation.
How Can Sware’s Res_Q™ Platform Help Meet Part 11 Life Sciences Software Compliance Needs?
If the idea of validating your company’s GxP software solutions and understanding computer systems validation in the pharma industry seems overwhelming, let Sware come to your rescue with Res_Q™!
Our Res_Q paperless validation platform provides a purpose-built, workflow-driven solution to many common issues as companies interpret the regulation and work to resolve their validation needs. Res_Q is a GxP-compliant paperless validation software system, tailored for the pharmaceutical/life sciences industries and aligned with the FDA’s latest thinking on computer software assurance (CSA).
You are not alone when you validate with Res_Q: Your subscription includes the Res_Q platform and white-glove support from our on-staff computer systems validation experts. Res_Q also offers compliance modules that provide pre-packaged validations for many popular SaaS platforms, including Veeva, MasterControl, and DocuSign. These modules are continually updated to ensure that periodic releases of SaaS GxP systems remain validated and compliant.
Res_Q compliance modules help you keep your systems in a state of control while cutting your hands-on validation time by up to 80%.
To give you an idea of how Res_Q can simplify your work in life sciences computer systems validation, the table below shows three common Part 11 requirements, the stumbling blocks, and how Res_Q solves the problem:
The Part 11 Requirement
The Res_Q Solution
“Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records,”
– 21 CFR Part 11 Subpart B, Section 11.10(a)
You must ensure that all GxP systems you are using are the latest version, appropriately validated prior to use, and kept in a validated state. You have multiple cloud-based systems that have updates throughout the year. How can you keep up with validation needs to ensure that your systems remain in a state of control?
Res_Q’s built-in functionality and compliance modules make the validation process simple and consistent – with no guesswork required.
“Use of appropriate controls over systems documentation including:
(1) Adequate controls over the distribution of, access to, and use of documentation for system operation and maintenance.
(2) Revision and change control procedures to maintain an audit trail that documents time-sequenced development and modification of systems documentation,”
– 21 CFR Part 11 Subpart B, Section 11.10(K)(1) & (2)
You must establish and follow software change control procedures. What if your organization doesn’t have these procedures in place? What if your organization needs a change control software solution?
Res_Q has a built-in change control module, making it easy to comply – with no extra work needed. SOPs are also available to help you reach compliance.
“The ability to generate accurate and complete copies of records in both human-readable and electronic form suitable for inspection, review, and copying by the agency”
“Protection of records to enable their accurate and ready retrieval throughout the records retention period”
“Limiting system access to authorized individuals”
“Use of secure, computer-generated, time-stamped audit trails to independently record the date and time of operator entries and actions that create, modify, or delete electronic records. Record changes shall not obscure previously recorded information. Such audit trail documentation shall be retained for a period at least as long as that required for the subject electronic records and shall be available for agency review and copying.”
– 21 CFR Part 11 Subpart B, Section 11.10(b), (c), (d) & (e)
You must ensure proof of validation and change management for GxP systems is readily available and inspection ready. You must make sure that your data is secure and available, and that there is an audit trail that captures any changes.
Res_Q secures all your validation collateral in one access-controlled source and provides a Part 11-compliant audit trail.
A Few Final Words
To recap, 21 CFR Part 11 is a pivotal regulation governing the use of electronic records and signatures in the life sciences industry. Its requirements for data integrity, security, and authenticity are crucial for compliance and regulatory approval. Adhering to 21 CFR Part 11 helps foster a culture of quality and reliability in the industry, ultimately benefiting patient safety and the advancement of scientific innovation. By embracing paperless validation platforms and tools that help them meet these requirements, you can enhance efficiency, reduce risks, increase agility and responsiveness to regulatory requests, and build trust with regulatory authorities and stakeholders.
Are you ready to connect the dots between 21 CFR Part 11 and GxP compliance for your operation? We aim to ensure you can effectively implement the best practices to assure optimal GxP compliance – whether in the pharmaceutical industry, or the broader spectrum of life sciences industries. We will guide you through its technical aspects and provide effective guidelines for incorporating current best practices into your workflow.
Talk to the Sware team to start your successful journey today.