In 1987, when the US Food and Drug Administration issued its Guideline on General Principles of Process Validation, a young FDA reviewer asked her supervisors, "What does this term validation really mean?"

"We don't know," they responded.

Much has changed in the past 18 years. So much has changed, in fact, that the current concept of process validation, once a fresh idea in quality control, and which later became accepted dogma, may now be ready for the trash bin. With companies achieving new levels of process understanding, what does it mean to validate a manufacturing process? Industry leaders and FDA are now examining that question and looking at new models to follow.

Although the 1987 guideline did not introduce the concept of validation, it did plant the notion firmly in industry. It defined validation as:

establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes (1).

The continuous quality verification model

Validating without understanding

Fernando Muzzio, PhD, a professor in the Department of Biochemical Engineering at Rutgers University (Piscataway, NJ, http://www.rutgers.edu/) says the main problem underlying the traditional approach to validation is that that we don't understand our manufacturing processes very well. And if we don't, our validation activities are essentially meaningless. "How can we agree to validate a process we don't understand?" he asks. "You know the old tale about the emperor's new clothes? Well, that's validation. Validation is, and always was, a fantasy."