From 21CFR Part 11 to Computer Software Assurance

It has been over a quarter century since the FDA introduced the regulatory requirements for electronic records and electronic signatures. In the same year, Pathfinder reached Mars, Netflix shipped its first DVD, and Titanic premiered at the Tokyo International Film Festival. DVDs, the initial WIFI standard, and the PNG image format were created. Amazon and eBay had just launched a couple years before, and Google was still a figment of the imagination. Suffice to say in 1997, we were at the dawn of the internet as we know it.

A lot has changed since 21 CFR Part 11 was introduced. Blackberries came and went. Bluetooth hit the market. And the 21 CFR regulations themselves evolved over time, adapting to better align with the ever-advancing technological landscape. As we reflect on the time when these regulations were first introduced, let’s look at why those regulations were introduced, the progression of the regulations over the years, and the guidance on meeting CSA today.

Initially, the FDA was requested by the pharmaceutical industry to be able to use electronic signatures and records for all regulated activities that were currently being done on paper. Working groups started in 1992 to address this issue and bring Part 11 to the industry. After numerous comments on the Advance Notice of Proposed Rule Making (ANPRM), the FDA publishes the final rule in March of 1997, with Part 11 going into effect in August of 1999.

21 CFR Part 11, titled "Electronic Records; Electronic Signatures," established the regulatory framework for the use of electronic records and electronic signatures in the pharmaceutical and medical device industries. Enacting this regulation reflects the FDA's commitment to allowing for the latest technologies while ensuring that the electronic systems maintain the same level of trustworthiness, reliability, and authenticity as traditional paper-based systems.

Part 11 compliance covers a wide range of aspects, including system validation, audit trails, electronic signatures, and data security. The validation of computer systems used in regulated processes is a cornerstone of Part 11, ensuring that these systems consistently produce accurate and reliable results. Audit trails, which provide a chronological record of system activities, are essential for tracking changes and ensuring accountability. Electronic signatures, equivalent to handwritten signatures, ensure the authenticity and integrity of electronic records.

The General Principles of Software Validation (GPSV) and Computer Systems Validation (CSV) are critical processes in the healthcare and life sciences industry that are used in various aspects of production, quality control, and regulatory compliance. This systematic and documented approach involves validating and verifying the performance of both software and hardware components to ensure they meet predetermined requirements. The validation process typically includes activities such as risk assessment, installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ). These steps aim to confirm that the computer systems consistently produce accurate and reliable results while adhering to regulatory standards.

In recent years, the landscape of computer software assurance has been evolving with advancements in technology and has placed a growing emphasis on agility and innovation. Traditional CSV approaches often involved extensive documentation and testing, which could be time-consuming and resource intensive. The shift towards more dynamic and iterative software development methodologies, such as Agile and DevOps, has prompted a reevaluation of CSV practices. Organizations are exploring ways to integrate validation activities seamlessly into the software development life cycle, ensuring that validation is an ongoing and integral part of the process rather than a separate and time-consuming activity. This change in approach allows for faster and more adaptive responses to changes in software, ultimately enhancing the efficiency and effectiveness of computer software assurance in regulated industries.

To integrate into the SDLC more seamlessly, in September of 2022, the FDA provided recommendations on CSA in medical device production and quality systems, detailing methods, and testing activities to establish confidence and fulfill regulatory requirements. CSA is nothing new to the FDA; these draft recommendations just repackage the existing risk-based approach to provide better guidance and firm suggestion in moving towards a more automated testing approach.

Computer Software Assurance (CSA), while different from Computer Systems Validation (CSV), is a holistic approach to managing the risks associated with software systems throughout their lifecycle. It allows companies to use common sense, previous experience, and data-based analysis to focus on more risk laden activities. CSA encompasses activities such as software validation, testing, and ongoing monitoring to ensure that software functions as intended and continues to meet regulatory requirements. In the context of the life sciences industry, CSA becomes a critical component in maintaining the reliability and integrity of computerized systems.

The integration of CSA involves proactive measures such as rigorous software validation and testing protocols, the ability to use exploratory and ad-hoc testing, adherence to industry-recognized standards, and continuous monitoring of software performance. By implementing CSA practices, organizations can identify and address potential software vulnerabilities earlier, reducing the risk of data corruption, loss, or unauthorized access.

The integration of 21 CFR Part 11 compliance and CSA is a natural progression in the pursuit of comprehensive data integrity and reliability in the life sciences sector. Both frameworks share common goals of ensuring the accuracy, consistency, and security of electronic records and software systems.

To successfully integrate Part 11 compliance and CSA, organizations must adopt a risk-based approach. This involves conducting thorough risk assessments, implementing appropriate security measures, and establishing robust processes for software validation and ongoing assurance. Collaboration between quality assurance teams, IT professionals, and regulatory affairs experts is crucial to achieving a harmonized and effective approach.

In the ever-evolving landscape of the life sciences industry, where technology plays an increasingly prominent role, synergy between 21 CFR Part 11 compliance and Computer Software Assurance is essential. This integration not only addresses current regulatory requirements but also positions organizations to adapt to future technological advancements. By prioritizing data integrity and reliability through these frameworks, the industry can uphold the highest standards of quality, safety, and efficacy in the development and manufacturing of pharmaceuticals and medical devices.

TTC Global brings hands-on experience within the Health and Life Sciences Industry and supports clients in overcoming software quality problems related to the software development lifecycle, regulatory compliance, and legacy IT software. Our expertise in Quality Engineering and software testing solutions for the Health and Life Sciences industry improves software quality, customer satisfaction, speed to market, and eliminates production defects in the field, while using the CSA guidance.