Comparison of Sterilizers and Sterilization Processes
| Moist Heat Sterilization of Aqueous Liquidsa | Steam Sterilization by Direct Contactb | ||
|---|---|---|---|
| 1 | Load Items | Containers filled with aqueous liquids (products, intermediates, laboratory media, and waste materials) are sterilized while sealed. | Items requiring direct exposure to saturated steam consist of elastomeric closures, equipment, utensils, and other heat-stable items of stainless steel, glass, fabrics, plastic, and other materials. The items comprise what are known variously as porous, hard goods, parts, or equipment loads. |
| 2 | Steam Usage | Steam (and/or superheated water) is used to heat the exterior of the sealed container, which in turn heats the aqueous contents. The heating medium never comes in contact with the liquid within the container. | Clean (or pure) steam is introduced and must come into direct contact with the surfaces of the load items. Plant steam can be used in the jacket to reduce the amount of clean steam required. |
| 3 | Steam Quality | No predefined requirement as steam is not in product contact. Clean (pure) steam is not required.c | Evaluated against ISO 17665 for non-condensable gases, moisture fraction, and super heat.d Condensate from the chamber steam meets the chemical test requirements for water for injection. |
| 4 | Item Description | The water-filled containers can be made of glass or plastic ranging in size from <1 mL to >20 L. The sealed containers can be vials, ampoules, prefilled syringes, flexible plastic bags, or other containers. | Items made of stainless steel, elastomeric, glass, and other heat-stable materials. Single items or assemblies of items in complex geometries for formulation, filtration, filling, or other use. |
| 5 | Item Geometry | In terminal sterilization of finished products all containers are identical in size and fill volume. In other uses multiple container sizes and varying volumes can be sterilized together. | With the exception of container components, i.e., elastomeric closures, where all items are identical, the items in the load vary in dimension, weight, and configuration. |
| 6 | Heat Sensitivity of Load Items | Varies with the fluid and container with an established upper limit of time–temperature or F0. With the exception of containers with biowaste materials, most liquid-filled containers can tolerate only a single sterilization cycle. | These items are considered to be heat stable through at least one or more sterilization cycles. A few elastomeric items can only be sterilized once without adverse impact to their properties. |
| 7 | Wrapping of Items | Aside from terminal sterilization products for which an overwrap is needed to protect the product from air and/or light during their shelf life, the liquid containers are not wrapped. Individual containers incorporate hermetic seals. | With a few exceptions (primarily very large and complex items) the items are completely wrapped with a permeable protective layer. Large items have all openings covered. The number of layers should be minimized to facilitate air/condensate and steam transmission. Wrapping of items is not always hermetic. |
| 8 | Load Size Adaptations | Sterilizer design and cycle control approach must consider the effect of load size on process lethality and material/product quality attributes. | Provided the means for air removal is fixed, the maximum load can typically be established as “worst case”. |
| 9 | Use of Vacuum/Air Removal | This is typically not required, as additional air may be necessary to maintain container integrity throughout the sterilization process. | Multiple alternating pulses of vacuum and steam are used to facilitate the removal of air from inside the wrapping and the items themselves. Gravity displacement cycles are considered unacceptable because they fail to meet equilibration time expectations. |
| 10 | Equilibration Time | Not applicable. | Must meet ISO 17665 requirements of 15 s (small sterilizers) and 30 s (sterilizers >600 L).d |
| 11 | Condensate Removal | This is optional depending upon the specific sterilizer design being used. Unusual in many terminal sterilization (steam-water-air and superheated water) sterilizer designs. | This is addressed throughout the process. The bulk of condensate occurs at the beginning; however, removal of condensate must continue throughout the cycle. |
| 12 | Temperature Setpoint | This can vary in order to best preserve the chemical/physical quality attributes of the liquid being sterilized. | Typically, all processes are executed slightly in excess of 121°C. In hospital settings, higher temperatures/shorter dwell times may be used. |
| 13 | Sterilizer Temperature Setpoint Location | Varies with the sterilizer design, including locations in the drain, heat source, chamber wall, etc. | Typically, in the sterilizer drain, which assures temperatures above the setpoint throughout the chamber. |
| 14 | Sterilization Cycle Dwell Period | This varies with temperature to preserve the chemical/physical quality attributes of the liquid. F0 target varies according to the process/product requirement. | Typically, not less than 15 min at the setpoint temperature. A fixed time period is established during validation. |
| 15 | Dwell Period Control Point | Temperature probes positioned either internal or external to the load correlated to attain the required lethality across the entire load. | Typically confirmed by conditions in the sterilizer drain. Load probes are minimally useful for this purpose. |
| 16 | Air Overpressure During Process | Required in the sterilization of flexible containers and pre-filled syringes. May be necessary with other container configurations as well. | Not applicable, as the presence of air during the exposure period is considered detrimental to process lethality. |
| 17 | Cooling of the Load | Integrated cooling of the sterilized containers to a safe temperature for handling. Helps to maintain the liquid's essential quality attributes. In laboratory and biowaste sterilization post dwell cooling may not be provided. | Not required. Loads are removed from the sterilizer and cooled while exposed under ISO 5 unidirectional air. |
| 18 | Drying of the Load | Drying in the chamber is typically not required. Residual heat within the liquid-filled containers may provide some drying after unloading. Steam-air sterilizers result in drier loads. | Drying post-sterilization may be required. Items requiring particularly low moisture may require alternating pulses of vacuum and air (heated air in some applications). |
| 19 | Equipment Variations | Complex and varying designs specific for the requirements of the sterilization process. Continuous sterilizers have been utilized in the highest volume applications. | Standard designs differing primarily only in the size of the chamber. |
| 20 | Empty Chamber Temperature Distribution Studiese | Tight requirements to minimize temperature variation across the loaded chamber. The objective is to provide consistency of heat exposure across the entire load. | Requirement less restrictive as item differences introduce considerably more temperature variation than the location of items. Reliable delivery of the required minimum lethality to the “most difficult to heat” load items is more important than minimizing variation of heat across the entire load. |
| 21 | Loaded Chamber Heat Distribution Studiesf | Tight requirements to minimize temperature variation and thus lethality/product impact variation across the chamber. | Largely irrelevant to effective sterilization of loads with a variety of different items. |
| 22 | Load Cold Spot Determination | Determined during cycle development and correlated to conditions at cycle dwell point sensor to ensure that the essential product quality attributes are not adversely impacted. | Not applicable. Differences in mass, configuration, orientations, etc. among the load items define the “most difficult to heat” item, whose exact position is irrelevant. Cold spot is item dependent, not location independent.g |
| 23 | Load Hot Spot Determination | Determined during cycle development and correlated to conditions at cycle dwell point sensor to ensure that the essential product quality attributes are not adversely impacted. | Not applicable. All items are considered heat stable for at least one sterilization cycle. |
| 24 | Air/Vent Filter Sterilization | Optional. Air overpressure ensures container protection from ingress. | Typically performed in situ at a defined frequency. |
| 25 | Jacket Presence | A jacket is typically present only when the sterilizer is also used for direct contact sterilization and is in use only with those sterilization processes. Sterilizers dedicated to terminal sterilization usually do not require a jacket. | A jacket fed with plant steam at a pressure less than that with the chamber can reduce clean steam usage, reduce condensate formation, and shorten drying times. |
| 26 | Cooling Water Quality Attributes | When water is present in the chamber for sterilization/cooling its microbial properties must be controlled.h | Not applicable, however a fixed temperature/volume is recommended for consistency of vacuum system performance. |
| 27 | Cycle Development/Validation Approachi | Cycles are developed and validated using bioburden-biological indicator (product specific) or bioburden approaches.j Overkill approach use may be possible for heat-stable materials and biowaste. | Overkill approach used for virtually all applications.k |
| 28 | Bioburden Information | Population and resistance of bioburden microorganisms are monitored. | Bioburden information is not a consideration. |
| 29 | Biological Indicator | Varies according to the specific sterilization process utilized. Geobacillus stearothermophilus is used for processes where the product is heat stable or for biowaste treatment. | Geobacillus stearothermophilus is utilized almost exclusively. |
| 30 | Cycle Approval | Each cycle reviewed for conformance to validation requirements. Parametric release requires regulatory pre-approval. | Each cycle reviewed for conformance to validation requirements. |
| 31 | Origin of Requirements | Many of the expectations can be traced to 1976 FDA Proposed LVP regulations.h | Expectations evolved from DHSS, HTM-10 and HTM-2010.l,m |