Performance qualifications of sterilization cycle in isolator: Are the qualifications carried out by the manufacturer indisputable?
Institut Curie, Paris, France
Any new equipment used for drug preparation should be qualified in accordance to expected specifications. In the case of sterile preparations, these qualification steps are very often subcontracted to the manufacturer. We report here the pharmaceutical control of the performance qualification with a sterilization process by a hydrogen peroxide (H2O2) 6 log reduction in isolator initially carried out by its own manufacturer.
The sterilizer was tested for 3 days in a row, empty and loaded, placing biological indicators (BI) (Geobacillus stearothermophilus) and chemical indicators (CI) at strategic locations: in the sterilizer and on the load at the same places as the manufacturer: Sterilizer door; paper sides of gauze box and drapes; plastic side of IV administration sets; low and room temperature vial; under the central rail. BIs were incubated for 7 days at 55°C and read daily. We also used negative control, and positive control like control count and spore viability control. The positive cultures were retested via a new qualification process in triplicate and by swabbing the surfaces at the end of sterilization under each BI (swab culture temperature 30°C). Temperature, humidity and H2O2 concentrations were monitored.
All qualification tests performed by the isolator supplier were compliant. Regarding the tests carried out by the pharmaceutical team, the CIs attest 6 log reduction but 5 BIs (24%) were non-compliant (associated with a positive culture). These non-conformities concerned the paper sides of the pack of compresses and drapes (n=4) and a cold vial. Subsequent qualification showed a positive culture again on a cold vial. The surfaces of the swabbed devices were not positive.
The paper sides cannot undergo pre-decontamination and are therefore difficult surfaces to sterilize. Cold vials probably modify the temperature of the load and could thus generate condensation on the surface of the vial which could explain a failed in sterilization. Nevertheless, in the case of the surface of the positive IB swab, the culture was ultimately found to be negative attesting to the complexity of this process. The stages of qualification of a new isolator are fundamental and must be subject to close pharmaceutical monitoring in order to follow the recommendations.