DRY HEAT STERILISATION PHARMACOPOEIAL REQUIREMENTS USP (<1211> Sterilization and Sterility Assurance of Compendial Articles Dry Heat

t Sterilization) A typical acceptable range in temperature is + 15C when the unit is operating at not less than 250C. In addition to the batch process described above, a continuous process is frequently employed to sterilize and depyrogenate glasswareusually requires a much higher temperature and shorter dwell time. In the qualification and validation program, in view of the short dwell time, parameters for uniformity of temperature, and particularly the dwell time, should be established. A microbial survival probability of 10-12 is considered achievable for heat stable articles or components. Synopsis of what follows: Use of B.I. (e.g. Bacillus subtilis) recommended here but see below also <1035> where this is contradicted; use of Endotoxin Challenges (> 1,000 USP Units) recommended for validation that suitable depyrogenation has occurred and have to show > 3 log reduction in endotoxin units in each instance. Mentions that endotoxin challenges may be applied direct to glassware but does not state has to be this way (we do not do this). USP (<1035> Biological Indicators for Sterilization Dry Heat) For dry heat sterilization , spores of Bacillus subtilis spp. are sometimes used to validate the process. During the validation of dry heat sterilization processes, endotoxin depyrogenation studies are frequently conducted in lieu of microbial inactivation studies during the establishment of sterilization cycles because the inactivation rate of endotoxin is slower than the inactivation rate of Bacillus subtilis spores. In practice the reduction of endotoxin titer by three or more logs will result in a process that also achieves a probability of nonsterility substantially lower than 106 . Typical Characteristics: 1.0 x 106 to 5.0 x 106 spores per carrier, average D-value of 1.9 at 160C, has to be a minimum of 1.0 minute and a maximum of 3.0 minutes. Survival Time: minimum of 4.0 minutes, maximum of 14.0 minutes, Kill Time: minimum of 10.0 minutes, maximum of 32.0 minutes. EP (5.1.1 Methods of Preparation of Sterile Products Dry Heat Sterilisation) Minimum of 160C for at least 2 hours. Other combinations of time and temperature can be used once a minimum reliable S.A.L. of 10-6 shown. Dry heat at temperatures greater than 220C is frequently used for sterilisation and depyrogenation of glassware. In this case, demonstration of a 3 log reduction in heat resistant bacterial endotoxin can be used as a replacement of biological indicators. EP (5.1.2 Biological Indicators of Sterilisation Dry Heat Sterilisation) Use spores of Bacillus subtilis (e.g. var. niger ATCC 9372 now called Bacillus atrophaeus ATCC 9372).

The number of viable spores exceeds 1 x 105 per carrier and the D-value at 160C is approximately 1min to 3min. Dry heat at temperatures greater than 220C is frequently used for sterilisation and depyrogenation of glassware. In this case, demonstration of a 3 log reduction in heat resistant bacterial endotoxin can be used as a replacement of biological indicators.