Heat sterilization equipment

The instruments, meters, weighing and measuring equipment of an appropriate range and precision shall be available for production and quality control. Their status shall be clearly labeled and their checking schedule shall be defined. Heat sterilization equipment, equipment for filling aseptic or sterilized products and sterile filters shall be validated after installation and their revaiidation schedule shall be defined. 

Fragile, heat- sensitive equipment Ethylene oxide Chemical Sterilization Disinfection Ethylene oxide under expert supervision ... 

Dry heat is used to sterihze and depyrogenate components and drug products. The definition of dry heat sterilization is 170 °C for at least 2 hours and a depyrogenation cycle at 250 °C for more than 30 minutes. Typical equipment includes tunnel sterilizers (force convection, infrared, fiame) and microwave sterilizers. An important aspect is the need to ensure air supply is filtered through HEPA filters. Biological indicators such as Bacillus subtilis can be used to gauge the performance of sterilization. 

Aseptic BPS machines are subject to steam-in-place sterilization following standard CIP cycles. The SIP cycles are routinely measured by thermocouples located in fixed positions along the product pathway. Validation of SIP cycles should be carried out to demonstrate that consistent sterilization temperatures are achieved throughout the equipment to prove that the system can be effectively sterilized. Validation should also identify suitable positions for routine use, or justify the fixed probe positions already in place. The SIP validation is generally carried out with the help of additional thermocouples and should include the use of biological indicators (appropriate for moist heat sterilization). Test locations should include areas which may be prone to air or condensate entrapment. An accurate engineering line drawing of the system to aid identification of suitable test locations and document test locations selected should be available. 

As with any sterilization process, the first step in dry-heat sterilizer validation involves qualification of all the equipment and instrumentation used. This step includes examination and documentation of all utilities, ductwork, filters, and control valves or switches for the oven or tunnel unit, and the calibration of the instrumentation used in validating and monitoring the process. The instruments used are as follows ... 

In step 5, the qualification stage, the critical issue is that the protocol for IQ/OQ of the equipment and the facility include the established method and acceptance criteria. The IQ/OQ report should include the maintenance program to keep the equipment in good condition for reproducibility of the product. For qualification of the equipment and process for terminal sterilization, the following standards should be referred to ISO 13408-1 [6] and 11138-1 [7] for general issues, ISO 11134 [8] and 11138-3 [9] for moist heat sterilization, ISO 11135 [10] and 11138-2 [11] for ethylene oxide sterilization, and ISO 11137 [12] for radiation sterilization. 

Glass equipment will normally be sterilized by dry-heat sterilization. Smaller equipment, like plastic tubes and rubber stoppers, can be sterilized by autoclaving. 

Dry-heat sterilization is generally a less complicated process than steam sterilization it is, however, relatively slow and requires higher temperatures and/or longer exposure times. This is because of the fact that microbial lethality is lower with dry heat than that for steam at the same temperature. There are various temperatures and periods of treatment for dry heat depending on the pharmacopeia. The U.S. Pharmacopeia (USP) states that the dry-heat sterilization process for containers for sterile pharmaceutical products should be at a temperature of 160-170°C for a period of 2-4 hr. The British Pharmacopeia states that items sterilized by dry heat should be kept at a temperature not less than 160°C for at least 1 hr. For the Pharmacopeia Nordica, the recommendation is 30 min at 180°C. Different materials and sterilization equipment used account for the discrepancies between these pharmacopeias, but there is also a lack of sufficient information concerning dry-heat sterilization. ... 

All pharmacopeias consider moist-heat sterilization as the method of choice, i.e., the method to be preferred, unless, of course, the product to be sterilized is incompatible with the characteristics of steam. The reason for this preference is the fact that moist-heat sterilization provides the best combination of flexibility, reliability, and low equipment and operating costs. 

Ethylene Oxide. Ethylene oxide, C2H4O. is a colorless flammable gas that liquefies at I2°C. It has been used to sterilize temperature-sensitive medical equipment and certain pharmaceuticals that cannot be heat sterilized in an auuxrlavc. Ethylene oxide diffuses readily through porous materials and very effectively de.stroys all forms of microorganisms at ambient temperatures."... 

The basic raw materials required include starting culture E. coli cells), nutrients (glucose and salts), tryptophan, water, ammonia and air. The process equipment includes fermentor, mixing tank, continuous heat sterilizer, centrifugal compressor, air filter and storage tank. 

Each heat sterilization cycle should be recorded by appropriate equipment with suitable accuracy and predsion, e.g., on a time/temperature chart with a suitably large scale. The temperature should be recorded from a probe at the coolest part of the load or loaded chamber, this point having been determined during the validation the temperature should preferably be checked against a second independent temperature probe located at the same position. The chart, or a photocopy of it, should form part of the batch record. Chemical or biological indicators may also be used but should not take the place of physical controls. 

The physical parameters of the process are monitored in normal production runs to obtain additional information on the process and its reliability. Extra temperature-sensitive devices installed in an autoclave or dry-heat sterilizer (in addition to probes used routinely) will permit an in-depth study of the heat distribution for several loads. Heat-penetration measurements are recommended for injectable products of higher viscosity or with volumes larger than 5 ml. A tableting press equipped with pressure-sensitive cells will be helpful in collecting statistical data on the uniformity of die-fill and therefore on mass uniformity. 

Each heat sterilization cycle should be recorded on a time/temperature chart with a suitably large scale or by other appropriate equipment with suitable accuracy and precision. The position of the temperature probes used of controlling and/or recording should have been determined during the validation, and... 

Steam sterilizer or dry heat sterilizer or other suitable equipment... 

Dry heat is suitable for sterilizing equipment, non-aqueous liquids and other materials which can withstand the temperature required. 

Dry heat is suitable for sterilizing equipment, non-aqueous liquids and other materials which can withstand the temperatures required. Various combinations of temperature and time are recommended in-official compendia but other combinations of temperature and time can be used provided they have been validated. 

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