Sterilization of biological materials

UNSTEADY-STATE THERMAL PROCESSING AND STERILIZATION OF BIOLOGICAL MATERIALS... 

Sec. 9.12 Unsteady-State Thermal Processing and Sterilization of Biological Materials 569... 

Where sterilization of starting materials is required, it should be carried out, where possible, by heat. Where necessary, other appropriate methods may also be used for inactivation of biological materials (e.g. irradiation). 

The tests for microbial limits and recommendations for microbial quality criteria of raw materials, excipients, drug substances, and pharmaceutical products have been established in pharmacopoeial compendia for over 30 years. These tests are listed in the USP 24 Chapter (61) Microbial Limits Tests and in the Ph. Eur. 3rd ed.. Biological Tests 2.6.12 and 2.6.13, Microbial Contamination of Products Not Required to Comply with the Test for Sterility (total viable count, tests for specified microorganisms) and the JP XIII 30 Microbial Limit Test. 

The predominant method for terminal sterilization is moist heat, and a substantial percentage of sterile products are processed in this manner. (Estimates range from 5 to 15% of all sterile products are terminally sterilized.) The sterilization often requires the attainment of a balance between sterility assurance and degradation of the material s essential properties [42],The overkill sterilization method is preferred for heat-resistant materials, and may be usable for terminal sterilization where the formulation can tolerate substantial heat input. The bioburden/biological indicator approach uses less heat input but requires increased control over the titer and resistance of the bioburden organisms present. 

Manual on radiation sterilization of medical and biological materials (1973) Technical Reports Series No. 149. International Atomic Energy Agency, Vienna Hygiene Recommendations (1972) Drug manufacturers association, Stockholm (Dec. 1972)... 

Sterilization by exposure to ethylene oxide is bounded by at least four variables gas concemratton, time of exposure, temperature, and humidity. It is also affected by product design, packaging design, and the composition of packaging materials. The shape, size, and materials of construction of individual sterilizers, the location of gas entry ports, and the presence or absence of forced circulation may all influence sterility assurance. There is no theory to describe these interactions. Validation and routine control of ethylene oxide sterilization processes boils down finally to the integration of all of these variables by reference to biological monitors. 

Consideration of packaging materials should be specific to particular sterilization cycles and should extend beyond primary packaging materials to include the potential effects of secondary packaging (shelf packs or shippers) and pallets on sterility assurance. In some instances these latter factors may need to be addressed on a sterilizer specific basis, where variations have been suspected of being the cause of erratic and unpredictable biological test failures. The important packaging factors to consider are... 

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