Although we commonly talk about "disinfectant validation," the US Food and Drug Administration validates only processes (1). Disinfectants themselves are qualified—that is, found to be effective in the context of a given process, just as we qualify the clean steam supply for an autoclave and then validate the steam sterilization process. The approach to disinfection should be similar, so that a working definition for disinfection process validation would be "establishing documented evidence that a disinfection process will consistently remove or inactivate known or possible pathogens from inanimate objects."

The working definition becomes critical as process operators attempt to comply with the current good manufacturing practice (CGMP) requirements of 21 CFR 211.56 (Sanitation) and 21 CFR 211.67 (Equipment cleaning and maintenance). The Sanitation clauses require that "any building used in the manufacture, processing, packing, or holding of a drug product shall be maintained in a clean and sanitary condition." And, the Cleaning and Maintenance provisions stipulate that "Equipment and utensils shall be cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements."

Even though the regulators have never formally defined "disinfectant validation," FDA Form 483 observations and Warning Letters frequently cite failures to ensure proper disinfection.

In 2002 the United States Pharmacopoeia (USP) published the draft General Chapter ‹1072›, "Disinfectants and Antiseptics" (2). This chapter addressed several key factors: selecting chemical disinfectants and antiseptics; demonstrating the effectiveness of disinfectants and antiseptics as bactericidal, fungicidal, and sporicidal agents; and applying disinfectants in manufacturing areas—along with the relevant regulations and safety considerations. The draft did not, however, clearly address disinfectant validation, per se, focusing instead on disinfectant effectiveness, which is a necessary prerequisite of disinfectant validation, but not sufficient in itself to ensure a valid disinfection process.

Draft chapter ‹1072› does say that demonstrating a disinfectant's effectiveness within a pharmaceutical manufacturing environment may require a battery of tests. Two of the tests listed are the "use-dilution test" and the "surface challenge test." As is so often the case, these tests may seem trivial at first glance, but they are not. In practice, they can be complicated and variable, which can make industry process validation personnel apprehensive every time they attempt a disinfection process validation.

Disinfectant effectiveness tests

Table I: Association of Official Analytical Chemists (AOAC ) test methods.

The AOAC's disinfectant effectiveness tests are not the only means of gathering antimicrobial performance data. The United Kingdom accepts the Kelsey-Sykes Capacity test. In most parts of Europe the recognized DET standards come from the systematic approach of the European Committee for Normalization (CEN) and Technical Committee (TC) 216 work program, "Chemical Disinfectants and Antiseptics."