The sterility test / verification of the performance of hydrogen peroxide decontamination is a vital process – yet the gold standard of Biological Indicators is incredibly flawed. With the introduction of Enzyme Indicators, a better option is finally available.
One of several concerns with BIs, especially when high-value products are handled, is the risk of false positives that can lead to expensive and lengthy failure investigations – which can often lead to batch rejection.
Sterility tests conducted within a conventional clean-room carry a greater risk of cross-contamination than test conducted within an isolator. The advent of isolation technology for sterility testing, since the 1990s, has, in theory, lowered the incidence of false positives. The introduction of EIs will make false positives a thing of the past and offer continual cycle after cycle monitoring of the sterilised area.
The BI verification process is cumbersome in many ways… Two duplicates indicate no-growth, equating to a test pass. Two duplicates indicate growth, signifying a test failure. Cycle parameters are reviewed. One duplicate indicating growth and one no-growth result in an ‘out-of-specification investigation’. This process is then repeated in triplicate. All replicates must indicate no-growth for cycle acceptance.
Once established, the load patterns became the standardised load patterns for sterility testing. No significant changes are permissible without undertaking a new load qualification.
As important a consideration is the frequency of isolator load requalification and, when undertaken, the types of load patterns required. Requalification is to verify that the isolator system and gassing port continue to operate as expected; that is to demonstrate that the gassing system continues to kill a known population of resistant spores (a ‘kill’ or ‘no-kill’ test).
Isolators are most commonly sanitised using hydrogen peroxide vapor (a surface disinfectant) or peracetic acid. Isolators are said to ‘disinfect’ or to ‘sanitise’ rather than ‘sterilise’.
Sanitisation, in this context, describes the reduction of a number of microorganisms within the clean environment as demonstrated through the use of biological indicators (BIs) in validation studies for different isolator cycles.
Up until now only BIs could be used effectively with their associated limitations. EIs provide immediate quantifiable data so that every cycle is validated before batch release. This is just one of EIs’ many advantages.
Everything associated with the use of biological indicators is cumbersome, from the initial verification that the BI appropriate for use, through to the collection, incubation and uncertainty of the process. Yes we do not dispute that BI’s can be made to work however it has and will always be a work around a fallible technology and product.
