The Paradox of Computer System Validation in the Pharmaceutical Industry

Finding Balance Between Adaptability and Compliance

By Bob Beliveau

Introduction:
Computer System Validation (CSV) is a crucial process in the pharmaceutical industry, ensuring that computer systems supporting regulated activities meet performance requirements and maintain regulatory compliance. While it’s a necessary part of the industry, it presents challenges and paradoxes, particularly when it comes to the adaptability of computer systems. In this blog post, we’ll explore these challenges and discuss how companies can strike a balance between compliance and adaptability.

The Paradox of Standardized vs. Adaptable Systems:
Pharmaceutical companies who use computer systems to support regulated activities must perform CSV. Although CSV is valuable as it evaluates system performance against requirements and ensures regulatory fitness, the process is far from easy. It involves listing requirements, performing risk assessments, and generating and executing test scripts to demonstrate compliance.

There is a well-known inverse relationship between system adaptability and CSV difficulty. In other words, standardized, turnkey systems are easier to validate than customized systems. This is embodied in the Good Automated Manufacturing Process (GAMP) and its tiered categories; Category 1 (Infrastructure S/W) being the most standard and Category 5 (Custom/Bespoke) being the most adaptive. GAMP recommends a much higher degree of testing and validation for the higher category applications.

This leads to the first paradox. Companies often choose standardized products for their ease of validation, instead of their fitness for purpose. This compromise forces users to adjust their business practices to fit the product’s limitations. In turn, this introduces operational drag, driving up staffing costs, increasing the opportunity for error, and causing the emergence of “gapware” to plug the operational hole between the standard product’s functions and business needs.

Figure 1 – Operating Costs of Standardized vs. Adaptable Products

Figure 1 – Operating Costs of Standardized vs. Adaptable Products

The Impact of Rigid CSV Approaches:
Figure 1 shows how this decision plays out over an extended time horizon. If we consider validation as part of operational cost, we see that initially, the standardized product decision is less expensive. But as time goes by, the adaptable product can pivot to meet evolving needs, which is reflected in a shallower operating cost slope. The pace of change continues to increase in the pharmaceutical industry, and this is depicted by an upward-bending operational curve for the standardized product. The organizational costs of working around an inflexible solution increase over time, impacting efficiency and quality.

Finding the Right Balance – Adaptable Systems and Responsive Change Management:
Adaptable computer systems can pivot in response to shifting needs. However, CSV tends to calcify systems in their initial configuration due to the difficulty of re-validation and change control. This leads to the second paradox: an adaptive software system by itself is insufficient unless coupled with a responsive change management approach.

The FDA has recently issued updated Computer Software Assurance guidance (link), recognizing the burden of rigid CSV approaches and the perverse effect of continued use of outdated systems. Many companies have delayed or abandoned software-aided process improvements because of the perceived overhead of CSV, contributing to longer drug development times and increased expense. The new guidance provides an opportunity to reevaluate CSV approaches and to “rightsize” them with respect to risk. Software providers can and should incorporate this thinking and streamline CSV packages accordingly.

Conclusion:
In conclusion, pharmaceutical companies need to strike a balance between adaptability and compliance when implementing computer systems. By considering both the software’s adaptability and the provider’s approach to maintaining a validated state, businesses can achieve a more efficient and responsive system. With the FDA’s updated guidance, it’s time for companies to reevaluate their CSV approaches and adopt more flexible solutions that benefit both their operations and regulatory compliance.