VALIDATION OF DRY HEAT STERILIZATION METHODS
Lila dhar*1, Surender Jalandra
1 Seth G. L. Bihani S. D. College Of Technical Education,
Institute Of Pharmaceutical Sciences & Drug Research,
Gaganpath, Sri Ganganagar, Rajasthan 335001
Dry heat is sometimes used for sterilization instead of the much more efficient moist heat because some materials are sensitive to moisture. Dry heat is often used to ensure that glass and other laboratory equipment is free of pyrogenic material. The process of sterilization within a chamber or hot air tunnel is a critical process and there is a regulatory requirement for validation of the process in most countries. Validation is defined as the documented procedure of obtaining, recording and interpreting results to ensure that the dry heat sterilization process has been and will be consistently effective. Dry heat sterilizer validation consists of accurately measuring the temperature at critical points within the sterilization chamber throughout the process. Dry heat process generally employs a temperature between 250°C and 400°C for varying time. The sterilizer is required to heat all parts of its load up to the specified temperature for a specified period long enough to achieve the desired sterility.
Reference Id: PHARMATUTOR-ART-1578
Dry heat is one of the most commonly used methods to sterilize and/or depyrogenate pharmaceutical components and products. Dry heat sterilization is often used for heat-stable oils, ointments and powders. Most often, depyrogenation of parenteral containers is performed utilizing a dry heat oven. The depyrogenation process is also utilized on certain heat-stabile components, glass containers, metal equipment, etc. to render the item and final parenteral product free of pyrogens. The equipment utilized to provide the dry heat medium must be validated to ensure that the system is able to provide sterile and/or depyrogenated components, on a reproducible basis. The validation of a dry heat sterilization and depyrogenation process involves approaches and procedures which parallel those utilized for steam sterilization. The efficiency of any heat treatment is determined by the design and source of the heat. Hot air is substantially less efficient in a thermal transfer medium as compared to steam. The validation effort must include heat distribution, heat penetration, bioburden and pyroburden determination, filter integrity, and microbial/endotoxin challenges. [Agalloco James, Carleton Frederick J,]
TYPES OF DRY HEAT STERILIZERS
The types of dry heat sterilizers commonly employed in the pharmaceutical industry are forced-convection batch sterilizers, infrared tunnel sterilizers, forced-convection tunnel sterilizers, continuous flame sterilizers, microwave, and laser/plasma sterilizers.[Sharma P.P,]
Two types of dry-heat sterilization systems are utilized in the pharmaceutical industry today. They are the conventional hot air oven and the tunnel system. The major difference between the two systems, as far as validation is concerned, is the belt or line speed variable with the tunnel system. The key to validating a dry-heat sterilizer is to prove its repeatability. This means that the unit can consistently perform under a given set of conditions to generate materials that are sterile, pyrogen-free, and particulate-free. Repeatability in dry-heat sterilization obviously involves consistency and reliability in attaining and maintaining a desired temperature. The desired temperature must be reached in all areas of the heating chamber. There will always be an area in the chamber that represents a cold spot; that is, an area that is most difficult to heat up to the desired temperature. This cold spot must be identified so that validation studies involving thermocouple monitoring and microbial challenges can be done at this location. If certain key GMP features of the dry-heat sterilizer are not controlled, with time the cold spot within the sterilizer will change and the key element of validation repeatability cannot be achieved. The GMP features of both the batch oven and tunnel sterilizer that must be controlled before doing any validation studies. Without control of these processes features, validating or even qualifying a dry-heat sterilizer is a total waste of time and money.
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:
1. Temperature recorders and thermocouples
2. Constant-temperature baths
3. Amp meters
5. Dioctylphthalate generators
6. Particle counters
Key Process Features to Control Prior to Validating Dry-Heat Sterilizers
Basic Equipment Performances That Must Be Verified Prior to Calibration-Validation Studies
Validation studies conducted on dry-heat sterilizers can be divided into two basic components. One component envelops all the physical processes, which must be validated, such as temperature control, air particulate levels, and belt speeds. Second component involve the process destroys both microbial and pyrogenic contaminants.
The USP recommends that validation of sterilization cycles for heat stable components include a microbial survival probability of 10K12 of Bacillus subtilis spores. It also recommends that to validate depyrogenation cycles, appropriate items should be charged with a minimum of 1000 EU of purified endotoxin, where the LAL test is used to demonstrate the endotoxin has been inactivated to not more than 1/1000 of the original amount (3-log reduction). The cycles are no longer defined by a minimum time and temperature requirement. Historically, the dry heat sterilization cycles were defined as 1708C for not less than two hours, while depyrogenation cycles were defined at a minimum of 2508C for not less than 30 minutes. A typical cycle might employ temperatures in the range of 1808C to 3008C. The temperatures at the lower end of this range will sterilize, while the higher temperatures in the range are suitable for depyrogenation. The cycle effectiveness will also be dependent on cycle time. The total time for batch cycle completion is often greater than three hours including cooling of the load. [Hugo and Russell’s]
DRY HEAT STERILIZATION
Dry heat is believed to destroy microorganism by causing oxidation.
Two types of dry-heat sterilization systems are utilized.
The conventional hot air oven
The tunnel system.
BATCH OVEN VALIDATION
1. Air balance determination: Air should be balanced so that positive pressure is exerted to the non sterile side when the door is opened
2. Heat distribution of an empty chamber: Thermocouples should be situated according to a specific predetermined pattern. Repeatability of temperature attainment and identification of the cold spot can be achieved if the temperature range is ±15°C at all monitored locations. Heat-distribution studies can also be conducted as a function of variable airflow rates.
3. Heat-penetration studies:These studies should be designed to determine the location of the slowest heating point within a commodity at various locations of a test load in the sterilizer. Thermocouples are placed in the commodities located in the areas likely to present the greatest resistance to reaching the desired temperature. Normally, three replicate cycles are run at Minimum and maximum temperatures. The cold spot must not move during the replicate studies. Other variations in the cycle affecting heat penetration at the cold spot can be studied, and these might include (a) test load variations, (b) temperature set point variations, and (c) variations in the time of exposure.
4. Mechanical repeatability: During all these studies, mechanical repeatability in terms of air velocity, temperature consistency, and reliability and sensitivity of all the oven and instrumental controls must be verified.
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