ABSTRACT

The validation of sterilizing filtrations, and of the sterilizing filters involved is critical to

the production of a sterile drug product, or of a sterile active pharmaceutical ingredient

(API). The sterility of the drug preparation cannot be ascertained by analysis of its

samples. It is impossible to test every drug container to assess its sterility. Similarly, a

statistical determination of sterility would require so large a sampling as to be

impractical. Validation of a process provides the assurance that its product is sterile. Such

validation is a regulatory requirement (FDA, 1985). Validation of the filters used to

achieve a sterile API is also necessary. It serves to assure that they perform in the manner

intended; this may also be a regulatory requirement if there are no further sterilizing steps

for the ingredient after its being formulated into the final product. Validation of a

sterilizing filtration process used for pharmaceutical liquids essentially involves three

things: determining the effect of the liquid on the filter, determining he effect of the filter

on the liquid, and demonstrating that the filter removes all microorganisms from the

liquid under actual processing conditions, resulting in a sterile filtrate (Madsen, 2006).