n the early years, trying to champion and implement computer validation was quite challenging. The industry faced the unfamiliar installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ) concepts. The common reaction to computer validation back then was quite similar to the Kübler–Ross "Five Phases of Grief" cycle (1). Some readers may have similar recollections and probably have heard some of the following responses:
- Phase 1, Denial: "Our mission is to implement systems, not to write documents and fill out forms," or "Who says we have to do it, show me the regulations."
- Phase 2, Anger: "We have years of experience in developing and implementing systems, we don't need !@#$*** validation," or "You are joking, you want me to do what?"
- Phase 3, Bargaining: "Do we have to do all of those things?" or "Can we do this instead...?"
- Phase 4, Depression: "This feels similar to paying a luxury tax," or "This is stressing me out, I don't have the time and resources to do all this work."
- Phase 5, Acceptance: "Oh well, fine, if you really want me to do it, I'll do it."
We have transitioned from the "common sense" and "it depends" environment to a risk-based and risk-management environment, especially since the US Food and Drug Administration is on board with risk management (2). We hope that a risk-management approach will level off the inconsistencies inherent to the "it depends" approach. Only time will tell whether it will be successful. By this transition, however, it seems that along the way we have inadvertently proved Darwin's theory of evolution: we have evolved and transitioned from a less-structured environment to a more technically structured and scientifically minded methodology to computer validation.
Origins of the computer-validation concept and approach
Although the concept of good manufacturing practices (GMPs) dates back to the early 1900s, current GMP regulations are mostly based on the practices that were revised in the mid-1970s, when the medical-device regulation amendments were introduced. It was during this time period that the manufacturing-validation concept (now known as process validation) was first discussed by FDA officials Bud Loftus and Ted Byers (3). In the late 1980s, the manufacturing-validation concept and approach of conducting IQ, OQ, and PQ were applied to computer validation. This approach was selected in part for the benefit of the relationship between industry and FDA. It was hoped that FDA would accept the computer-validation approach because it was already familiar with and accepting of the IO, OQ, PQ concept. Within the industry, applying IQ, OQ, PQ to computer validation was challenging at first. This was at a time when validation concepts such as unit testing, module testing, and integration testing in information technology and software engineering already were being practiced. Interestingly, this IQ, OQ, PQ concept has withstood the test of time and is still prominent today, although some may have substituted and intertwined other types of testing into the fold, including unit and integration testing, as well as other variations of testing (e.g., site-acceptance testing and factory-acceptance testing).
Perspective on regulations and regulatory guidance