Barrier isolators that enclose aseptic filling equipment are being proposed as a means of: (1) assisting in achieving a 10(-6) sterility assurance level (SAL) in the filling area and (2) minimizing the clean environment required in the manufacturing area. The need for operator and maintenance access to the interior of the barrier isolators presents difficulties in achieving the above goals. Several methods are available for reducing the microbial level inside the isolation barrier. If the objective is the decontamination of all surfaces inside the enclosure, saturated steam at atmospheric pressure can be used. If the objective is to sterilize the inside of the enclosure, saturated steam at atmospheric pressure with added H2O2 can be used. Test data and practical interface considerations relative to various methodologies will be reviewed.

Air Pressure↗

PubMedDate not supplied

Heat resistance of Bacillus coagulans spores suspended in various parenteral solutions.

Bacillus coagulans, ATCC 51232 (formerly referred to as FRR B666), was previously reported to be a potentially excellent biological indicator. The organism was grown on a relatively simple sporulation media and the spores were evaluated for moist heat resistance in various parenteral solutions. Resistance was determined using the survivor curve method. For those solutions which appeared to be inhibitory to the outgrowth of Bacillus coagulans, ATCC 51232, further investigations were performed to evaluate the inhibitory effect. The results obtained demonstrated that the organism had the highest resistance in Calcium Gluconate Injection; USP (100 mg/mL) at 120 degrees C.

Bacillus↗

PubMedDate not supplied

Resistance of Neosartorya fischeri to wet and dry heat.

Dry heat resistance parameters for Neosartorya fischeri ascospores were obtained at 90 degrees C and 95 degrees C under 30%, 40%, 50%, 60%, and 75% relative humidity (RH) conditions. The dry heat treated spores were exposed to saturated water vapor (for 20-24 h at 4 degrees C) prior to recovery in buffer held at two temperatures (0 degrees C and 80 degrees C). Approximately the same level of recovery was obtained at the two buffer temperatures except at the shortest heating times for the heat treatment carried at 30% and 40% RH, where the number of survivors was significantly higher for spores placed in the buffer held at 80 degrees C. The effect of this high temperature was attributed to heat activation of the ascospores that remained dormant during the dry heat treatment conditions mentioned above. The wet heat resistance of N. fischeri ascospores was also determined at temperatures ranging from 82.5 degrees C to 95 degrees C. The results indicate that as the RH decreased, the heat resistance of the ascospores increased. There were about four orders of magnitude difference in the heat resistance between wet heat (100% RH) and the lowest dry heat treatment condition (30% RH).

Ascomycota↗

PubMedDate not supplied

Factors affecting recovery of Neosartorya fischeri ascospores after exposure to dry heat.

Recovery of Neosartorya fischeri ascospores subjected to a dry heat treatment (DHT) at 95 degrees C, 50% relative humidity (RH) for 60 minutes increased exponentially as the initial temperature of the recovery buffer increased. Different diluents were evaluated and the same recovery pattern was obtained when water or dilute buffers were used to recover the DHT spores. However, when glycerol was added to the buffer, the number of spores recovered in solutions held in ice water increased with increasing glycerol concentration. When the DHT spores were exposed to an atmosphere saturated with water vapor (100% RH) before being placed in the buffer, the recovery was independent of the initial temperature of the buffer. This occurred even if the spores were subsequently dried before being introduced into the buffer. It is hypothesized that the temperature-dependent recovery was due to injury of the DHT spores during the sudden rehydration in dilute solutions at low temperatures.

Ascomycota↗

PubMedDate not supplied

Discussion of the Z-value to use in calculating the F0-value for high-temperature sterilization processes.

The appropriate z-value to use in integrating heat process time-temperature data in the temperature range of 120.0-140.0 degrees C (248.0-284.0 degrees F) is discussed. We conclude that for control of Clostridium botulinum there is little risk in extrapolating a public health F0-value for C. botulinum to temperatures in the 132.0-138.0 degrees C (270.0-280.0 degrees F) range using a z-value of 10.0 degrees C (18.0 degrees F). It would seem prudent, at this time, when extrapolating data to conditions in the 132.0-138.0 degrees C (270.0-280.0 degrees F) range, that as a starting point an F0-value of 3.0 minutes be used as the minimum public health process. A design z-value of 10.0 degrees C (18.0 degrees F) is appropriate for Clostridium sporogenes to temperatures of 140.0 degrees C (284.0 degrees F). To control thermophilic microorganisms such as Bacillus stearothermophilus and Bacillus coagulans with processes at temperatures from 120.0-140.0 degrees C (248.0-284.0 degrees F), the effective z-value will be in the range of 7.0-8.0 degrees C (12.6-14.4 degrees F) instead of 10.0 degrees C (18.0 degrees F). This means that when we design and calculate processes at temperatures from 120.0-140.0 degrees C (248.0-284.0 degrees F), using a z-value of 10.0 degrees C (18.0 degrees F), the lethal effect against these organisms will be much larger than indicated by the F0-value of the process.

Clostridium botulinum↗