STERILE PROCESS VALIDATIDN BY MEDIA FILLS SHOULD SIMULATE ACTUAL CONDITIONS

STERILE PROCESS VALIDATIDN BY MEDIA FILLS SHOULD SIMULATE ACTUAL CONDITIONS of production rather than "worst case" conditions proposed as quality limits by FDA, the Parenteral Drug Association (PDA) maintained in recent comments on the agency's aseptic processing draft guidelines. "It is not possible to guarantee that all environmental factors are operating at their action limits during the performance of a media fill," PDA maintained, and "furthermore, requiring such extreme conditions is not necessary given the high sensitivity of media challenge procedures and close control of operating parameters during normal filling operations." PDA noted that media fills already involve more "worst case" conditions than are normally present during aseptic processing of drug products because "(1) additional manipulative steps often have to be added to the process in order to perform a media fill, (2) there are not preservatives present to counteract the accidental introduction of stray microorganisms during processing as there is during product processing, and (3) the product being produced is a microbiological growth medium." Media fills should simulate normal production situations as closely as possible, PDA said, as requiring "worst case" situations for all possible variables, such as slower than normal filling rates, is "unrealistic." Worst case conditions "could complicate interpretation of data to the extent that it is possible to discredit an otherwise acceptable aseptic processing operation." PDA maintained that the guideline "appears to equate media fills with validation" and does not sufficiently recognize alternatives. "Media fills are only one component, not even a necessary component, of validation of an aseptic filling process," PDA said. PDA also questioned the statement in the guidelines that "a generally acceptable frequency" for revalidation with the media fills "is at least twice each year for each personnel shift applied to each filling/sealing line." PDA argued instead that such frequent media fills are impractical for processes that are performed infrequently, and unnecessary if no significant changes have been made to the manufacturing equipment and procedures, and historical media fill and environmental control data consistently meet specifications." Like the Pharmaceutical Manufacturers Assn. ("The Pink Sheet" May 20, T&G-9), PDA also had several comments on the draft guideline advice concerning the environmental monitoring of air quality. Instead of applying fixed standards for the air in the immediate proximity of the aseptic filling area, PDA recommended that "manufacturers should have the option of establishing their own airborne microbiological contamination alert-action levels based upon the historical data generated with their quantitative sampling devices and incubation conditions."