ABSTRACT
There has been from the inception of aseptic processing an understanding among knowledgeable experts that a low level of contamination was to one degree or another inevitable. One needs only to consider relevant international regulatory standards and guidance to confirm this expectation of contamination. For example, neither EU Annex 1 nor the FDA’s Guideline on Sterile Drugs Produced by Aseptic Processing (1,2) suggests that the recovery of viable contamination in monitoring should be an unexpected result. EU Annex 1 stated that in what is defined in that document as a Grade A environment, microbial content of air in environmental monitoring should average <1 CFU, this reflects that the expectation levels of residual contamination must be low, but it neither states nor implies that a zero recovery results are expected or required. Certainly regulations and guidance implies that the target for contamination recovery in process simulation tests and environmental monitoring is zero, but these documents make room for a rare low level contamination event because rationally, where conventional clean room aseptic processing is concerned, it is impractical to do otherwise. Similarly, the United States Pharmacopoeia (USP) chapter <1116>, which is undergoing revision (3), recommends a low, less than 1%, contamination incident rate for ISO 5 environments.
