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Medical Sterilization |
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Validating Electron Beam Processing The following protocol details the significant points which must be addressed during the validation of electron beam sterilization, as outlined in ANSI/AAMI/ISO 11137. The requirements of ISO 11137 fall into three major categories:
Minimum Dose Determination Definition - Minimum dose determination is the establishment of the minimum level of radiation which will effectively and consistently eradicate inherent bioburden levels within a specific product or product family. Procedure -- Minimum doses are established using Method 1 and/or Method 2 as defined in the ANSI/AAMI/ISO guideline for irradiation sterilization of medical devices. The most common approach for the establishment of a minimum dose is to use Method 1, otherwise known as a bioburden method. Bioburden analysis is performed by taking ten product samples from each of three separate production lots to a testing laboratory. The average bioburden for each lot and the grand average of all three lots are calculated. If a single lot is more than two times the grand average, that specific single lot average must be used. Based upon this bioburden analysis, the verification dose is determined by means of Table B.1 contained in the ISO guideline. If the specific average bioburden is not listed in the table, the next highest bioburden is utilized. One-hundred samples of either a fourth production lot or one of the three original production lots are then subjected by the sterilizer to the verification dose necessary to achieve a 10-2 sterility assurance level. These 100 samples are then sent to the testing laboratory and incubated for a period of 14 days in TSB at 28 - 32°C. Acceptable results after this 14-day incubation are 0, 1, or 2 positives out of the 100 samples tested. If 0, 1, or 2 positives are obtained, the verification test has been successfully completed and a sterilization dose can be determined again based upon Table B.1 in the ISO document. A sterilization processing dose is normally based upon a 10-3 sterility assurance level for those devices that are non-invasive and do not contact blood or tissue, or 10-6 sterility assurance level for those devices which are invasive and/or have contact with blood or tissue. If the results of the verification exceed two positives (i.e., 3 or more positives), and the positives cannot be attributed to sterility testing techniques, then Method 2 must be selected. Details on Method 2 can be found in the ISO guidelines. Grouping of Products -- The grouping of products can be used to minimize the amount of testing required to establish the minimum dose for each product and/or group of products. Factors to be considered for grouping of products for minimum dose establishment are typically based upon the manufacturing process itself, which includes handling of the product by employees, machine-made parts versus hand-assembled parts, materials of construction, and raw materials suppliers if a purchased sub-assembly is included in the manufacturing process. Maximum Dose Determination Definition -- Maximum dose determination is the establishment of a maximum level of radiation to which the product is to be exposed and which will not effect the form, fit, or function of the product. Typically, the maximum dose is at least two times the minimum sterilization dose. This provides an adequate processing window for electron beam sterilization. The maximum dose is established by the irradiation of representative samples of the product at various dose levels to determine the dose level at which form, fit, or function is compromised. The testing which the product should undergo to determine the impact of irradiation at various dose levels typically falls into the following categories: Form - Can the device still be marketed if there is a color change or change in the device itself? Will such a change inhibit the capability to market and sell the device? Fit - Is the presentation of the product in either the clinical and/or hospital setting compromised with regard to sterility? Is the packaging able to maintain a sterile barrier? Function - Is product performance compromised relative to strength, embrittlement, discoloration and other physical or cosmetic properties? Procedure -- Obtain representative samples of each type or category of device and expose them to a radiation dose equal to, or in excess of, two times the minimum sterilization dose. Typically, Titan Scan customers choose three doses in increments of 5 or 10 kilogray above the doubled minimum dose. Several individual product units are exposed to each dose level. Upon receipt from the irradiator, perform the identified tests and/or evaluations to determine whether or not form, fit or function has been changed within the device. Once completed, and the maximum dose established, any changes to the materials and/or manufacturing process should be evaluated with regard to their potential impact on the established maximum dose. It should be noted that, in most cases, if a material has been qualified for gamma sterilization, the same dose applied by electron beam can be used as a starting point, since electron beam causes significantly less oxidative degradation than gamma rays. This qualification approach is both quick and very cost-effective. Grouping of Products-- Grouping of products for maximum dose establishment is typically done based upon the types of materials used in manufacturing, the manufacturing process itself, and those specific components which may undergo certain stresses during their end use. The rationale for the grouping of products should be documented and maintained. Process Qualification (Dose Mapping) Definition - Process qualification entails dose mapping a particular product and/or group of products. Dose mapping is the determination of the loading configuration which will be used during routine sterilization. Procedure - In dose mapping, dosimeters are placed throughout products at strategic locations to determine the zones of minimum and maximum dose. Three test repetitions need to be performed during dose mapping in order to establish statistical reliability. Dose mapping yields the following results: A max to min ratio which is the ratio of the maximum dose to minimum dose contained within the product The establishment of a carrier loading pattern to be used during routine processing The establishment of the Standard Monitoring Position, which will be used during routine production to monitor processing without opening the boxes. Validation Maintenance As long as there are no changes made relative to the processing method, packaging method or configuration, or raw materials utilized for a product, only the minimum dose needs to be re-validated on a regular basis. Methodology for quarterly dose audits is discussed in detail in AAMI/ANSI/ISO 11137, with Method 1 dose auditing covered in section B.3.5.2. Briefly, the Method 1 audit involves delivery of 10 units of product to the testing lab for bioburden analysis and 100 units of product to the sterilizer for processing at the verification dose established during the initial validation process. The 100 units are then delivered to the testing lab for bioburden analysis. If two or fewer positives are obtained, the original sterilization dose is acceptable and no further action is required. The maximum dose determined by original testing should not need re-evaluation unless product raw materials change. Product does not need to be re-mapped unless there is a change in packaging method, packaging configuration, and/or raw materials used in normal production. Conversion to Electron Beam from Gamma Conversion to e-beam processing from gamma processing is relatively easy since much of the preliminary material compatibility study has already been done in order to qualify gamma. There are essentially four steps necessary in order to change processes:
Conversion to Electron Beam from EtO Because EtO processing qualification differs radically from irradiation processing, it would behoove the manufacturer to validate a change from EO to electron beam by utilizing the procedures established above in Validating Electron Beam Processing, beginning with a simple materials feasibility study and including Minimum and Maximum Dose Establishment and Process Qualification. |