Computer Systems Validation: Dollars and Sense

Abstract

The Food and Drug Administration's (FDA) concern about the use and validation of computer systems in support of preclinical toxicology studies has caused a tremendous flurry of activity in the pharmaceutical industry. The FDA, in 1963, published the Guide to Inspection of Computerized Systems in Drug Processing, fondly referred to as the “Blue Book.” This guide addressed processes controlled by the computer in the production setting, governed by the Good Manufacturing Practices. A similar agency document applying to preclinical toxicology does not exist. FDA representatives have presented verbal guidelines ranging from the reasonable to the outrageous.

Therefore, the industry has had to define the preclinical validation process for itself. Committees, both internal and external to individual firms, have been established to define validation and to determine how to perform validation testing to meet internal company standards and external federal regulations. In search of the true meaning of validation and the perfect validation plan, people in the industry have flocked to validation meetings, workshops seminars, and courses. It soon became obvious that a magic elixir did not exist, but the activity stimulated a lot of thought and formal positions on the validation process. Most individual firms have developed and implemented a validation policy and plan. Committees within the Pharmaceutical Manufacturer's Association (PMA) have prepared articles for journal publication and discussion with the FDA. The current status seems to indicate that we have completed a phase in this validation project and are looking to review, gain approval (internal management, industry, and external agency), and move onward.

During this review time, a question to ask is, “What is the price tag on validation?” (How much is the firm willing to pay to perform this function while guaranteeing compliance with internal standards and agency regulations?) Preclinical toxicology must operate within a specific budget, and therefore the validation process must also be performed within budgetary limits. A validation objective must include a qualitative subject and a quantitative predicate. By formulating the validation objective in this manner, the firm is forced to determine the essential functions that must be performed to meet internal quality standards and agency regulations and to determine how to perform those functions in a cost-effective manner.

The body of this article will discuss costs incurred in development and implementation, and operational phases of the validation process will be discussed. A recommended use of the term will be proposed and incorporated into a validation objective. Strategies for reducing validation costs will be discussed.