Autoclaves, validation

Steam sterilization validation. All autoclave operations conform to the Master Validation Plan employed at ABC Pharmaceutical Industries. The autoclave has undergone installation qualification, operational qualification, and performance qualification. The autoclave is revalidated on an annual basis. The equipment steam sterilization cycle revalidation data for the autoclave are provided in validated archives. 

The following load configurations have been validated on the autoclave ... 

The complexity of the sterile filtration operation and the CGMP regulations require the validation of sterilizing filter systems. The validation of a sterile filtration operation can be complex, with many operational parameters and their interactions needing to be identified, controlled, and predicted for each end product to demonstrate that sterility is adequately achieved by the filtration process. In the commonly used steam sterilization process, the heat parameters are identified and in-process controls specified such that a level of sterility assurance can be reproducibly obtained. In steam sterilization, the important parameter of heat, measured by temperature, can be accurately measured and continuously monitored to ensure the operational integrity of the autoclave however, unlike steam sterilization, filtration sterilization cannot be monitored on a continuous basis throughout the process. 

APPENDIX I EXAMPLE PROTOCOL FOR VALIDATION OF THE STERILIZATION PROCESS IN A STEAM AUTOCLAVE... 

To provide the method to be used for the validation of the sterilizing process using an autoclave containing. ... 

Parenteral Drug Association. Moist Heat Sterilization in Autoclaves Cycle Development, Validation and Routine Operation. PDA technical report 1, revision, draft 11. Bethesda, MD, May 2001. 

Failure to achieve the optimal temperature required for heat induced antigen retrieval. When using a waterbath or steamer, allow sufficient time for the retrieval buffer to equilibrate to a temperature range of 95-99 °C. At high altitude (greater than-4,500 feet), the buffer will boil at less than 95 °C. Utilize a closed heating system such as a pressure cooker, autoclave or Pascal, or utilize a low temperature protocol if standardization of the validated procedure is not affected. 51-65... 

The steam sterilization system (see Figures 5-9) used by S.G.D. Serail is designed with autoclave -type vessel construction to resist sterilization pressure combined with a control system permitting the validation of the sterilization cycles and eventual determination of the experimental FO sterilization value. 

Aseptic Assembly. The first interventions performed are those that prepare the equipment for the aseptic process. This entails the removal of sterilized materials and equipment items from the autoclave and transfer to the location where the aseptic processing activities will be performed. This is ordinarily followed by the assembly/preparation of the equipment for the process. Aseptic assembly in which sterilized parts are removed from protective materials, installed and adjusted in preparation for the aseptic process are perhaps the most potentially invasive of all of the activities which must be performed. The operator must be meticulous in their execution of these tasks to prevent the inadvertent contamination of product contact surfaces. Strict adherence to the principles of aseptic technique described earlier is essential. These interventions are a necessary part of every aseptic activity, and it is common to identify the first containers filled as they may be more indicative of potential problems with the aseptic assembly. For this reason, the validation program should include process simulations that include containers filled immediately after the set-up of the equipment. 

Sterilizer parameters are specific to combinations of product, presentation, and autoclave. They must be established empirically. Heat penetration studies done prior to the performance qualification phase of validation serve the purpose of determining the loading patterns, prevacuums, and temperature and pressure settings, etc.which ensure that the sterilization specification is delivered to the product and that it is delivered uniformly throughout the load. 

The load will be exposed to a defined autoclave treatment (the validation cycle). 

More often than not the number of Bis used is about 20-30. Larger numbers up to 100 may be necessary to address very large autoclaves or in thermal mapping studies, but in validation there is little extra statistical confidence to be gained by doing so. In most microbiology QA laboratories, 20-30 Bis can be handled conveniently. 

Periodically it is wise to repeat bio-validation. Changes do occur in autoclaves and no change control procedure, no matter how rigorously implemented, is infallible. The purpose of requalification is to determine if any unforeseen change has arisen to affect the sterility assurance provided to the items being sterilized. 

Bio-Validation of Laboratory Autoclaves Used for Sterilizing Microbiological Media... 

Steam sterilization in autoclaves has a long and strong scientific basis (see above). The essence of validation of steam sterilization processes is to demonstrate that temperature and time conditions are being achieved uniformly through every item included the autoclave load and that the lethality being achieved in practical situations corresponds to that which would be expected from sterilization theory. 

Each piece of equipment must be validated before it serves another piece of equipment/ system during validation of the latter (e.g. water system before steam generator steam generator before autoclave). 

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