Sterilization Validation Planning

  1. Why Pacific BioLabs Should Conduct Your Dose Audits and Sterility Tests
  2. Prevalidation Checklist
  3. Sterility Assurance Level
  4. Sterilization Process Validation Protocol
  5. How Can I Complete My Validation ASAP?

Why Pacific BioLabs Should Conduct Your Dose Audits and Sterility Tests?

  • Over 30 years of experience providing sterility testing services for medical device and pharmaceutical manufacturers.
  • Pacific BioLabs’ proximity to radiation contract sterilization facilities minimizes sample shipment time and expense.  Pick-up service is available at some sterilization facilities.
  • Pacific BioLabs works closely with contract sterilizers to expedite the processing of your samples.
  • Pacific BioLabs has extensive standard operating procedures covering all aspects of sterility testing operations.
  • Product sterility testing is aseptically performed in a certified cleanroom by experienced technicians.
  • Samples for lot release are put on test within 2 days of sample receipt.
  • Environmental controls are performed for all sterility tests.
  • Samples are monitored daily. Clients are immediately advised by phone should growth occur.
  • Growth occurring in sterility tests is thoroughly investigated using genotypic microbial identification systems.
  • Reports with test results are emailed or mailed the day required incubation ends.

Pacific BioLabs’ facility contains a dedicated cleanroom sterility testing suite. The suite is constantly maintained under positive pressure that cascades from core cleanrooms to a gowning room to a sample disinfection room to an ambient pressure entrance area. Sterility testing is performed in HEPA filtered hoods by fully gowned test technicians. All media used in sterility testing is steam sterilized in validated autoclave cycles. Each batch of media is tested for growth promotion. The temperature in all chambers used to incubate samples is continuously monitored by a Rees Scientific Facilities Monitoring System which provides audible and phone alerts in the event of temperature excursions beyond defined parameters.

Pre-Validation Checklist

    • Evaluate candidate materials, components and packaging compatibility with ethylene oxide gas, gamma or electron beam radiation sterilization processes. Material manufacturers and contract sterilizers can assist with this evaluation.
    • Select method of sterilization.
    • Screen materials for biocompatibility.
    • Pacific BioLabs offers comprehensive biocompatibility testing services in accordance with FDA, ISO and AAMI Guidelines. For more information, please call for a complimentary copy of Pacific BioLabs’ booklet Assessing Biocompatibility.  For assistance in designing an appropriate biocompatibility testing plan for your device, please call client services at 510-964-9000.
    • Manufacture finished devices. (Be sure to manufacture enough for both biocompatibility testing of finished devices and your sterilization validation.)
    • Conduct finished device biocompatibility testing.
    • Select your contract sterilizer and execute a contract sterilization agreement with them.
    • Submit a product sample to Pacific BioLabs for evaluation.
    • Select validation methodology in consultation with contract sterilizer and Pacific BioLabs.
    • Generate sterilization process validation protocols for both physical and microbiological aspects of validation.
    • Send samples for initial phase validation testing to Pacific BioLabs, i.e. bioburden method validation, bioburden, sample item portion preparation (if required), bacteriostasis/fungistasis test.
    • Schedule physical validation (e.g. dose map study or EO chamber qualification).
    • Schedule post-sterilization microbiological testing with Pacific BioLab

    Sterility Assurance Level

    Sterility is defined as the state of being free from viable microorganisms. A sterility assurance level (SAL) is defined as the probability of an item being nonsterile after it has been exposed to a validated sterilization process. Most medical devices are sterilized to achieve a SAL of 10-6, which is the probability of one in a million items being nonsterile. Any sterile medical device that may be sold in Europe must be sterilized at a SAL of 10-6. In the USA, some less critical devices (e.g. specimen cups) are sterilized at a SAL of 10-3. In setting up a validation program, the sterility assurance level that will be required for the medical device must be chosen.

    Sterilization Process Validation Protocol

    For an initial validation of the sterilization process for a medical device, cGMP regulations require a written validation protocol. The validation protocol is an outline of the requirements of a proposed validation effort. The protocol will include a complete identification of the medical device, a statement of purpose, the name of the contract sterilizer, the name of the testing laboratory, a list of the tests that are required, references for the test procedures to be used and criteria that will be used to judge if the validation effort has been successful. Specific test procedures can also be provided to clients who request them.

    Pacific BioLabs will customize a sterilization validation protocol to meet individual client requirements. Once the initial validation is successfully completed, no additional validation protocols are normally required for subsequent revalidation, i.e. quarterly dose audits or subsequent single lot validations for the same product using the same method. Please call Pacific BioLabs to discuss your sterilization validation requirements.

    How Can I Complete My Validation ASAP?

    • Anticipate sample requirements. Some manufacturers do not adequately plan for the sample requirements of a complete sterilization validation.
    • Submit your evaluation sample early, even if it is only a prototype. This is particularly helpful for large and complex products. Pacific BioLabs’ staff will help you anticipate possible validation problems, determine your budget for validation costs and sample requirements, and design your validation protocol.
    • Request your validation protocol early. A well-prepared, detailed protocol is critical for smooth and timely completion of your validation.  It is also required in order to meet FDA/ISO regulations. Early preparation of the validation protocol can save you several weeks in your validation timeline.
    • Submit bioburden test method validation samples early.  Fourteen sterile samples are required for bioburden method validation testing. The bioburden recovery test occasionally fails initially causing the need for additional testing. This can delay your project by several weeks. It is wise to keep it off the critical path of your validation project.
    • Allow extra time if SIP (sample item portion) preparation is required in a radiation dose validation. For some large devices, it may be necessary to use a scaled-down version of the product for bioburden studies and the verification dose resistance experiment. For complex devices, disassembly and/or sectioning may be required prior to irradiation and testing.
    • Submit bacteriostasis/fungistasis(B/F) samples early. The B/F test requires three to six sterile samples —sterilized using the same process you will use on your final product. The B/F test sometimes fails initially causing the need for additional testing. This is a frequent source of delay in validation projects.
    • For AAMI/ISO 11137 Method 1, reserve 100 extra samples from each validation lot. If one lot has more than double the bioburden of either of the other two lots, the 100 samples for the dose audit test should come from the lot with the highest bioburden.
    • For VDmax validations, it is preferable to include 20 samples for verification dosing. 10 samples will be tested for sterility. If growth occurs in less than one sample, the validation is acceptable. If growth occurs in two samples, the other 10 samples can be tested for sterility. If no growth occurs in the second 10 samples, the validation is acceptable. If growth occurs in greater than three of 20 samples, additional testing is required.
    • Submit bacteriostasis/fungistasis(B/F) samples early. The B/F test requires three to six sterile samples —sterilized using the same process you will use on your final product. The B/F test sometimes fails initially causing the need for additional testing. This is a frequent source of delay in validation projects.
    • Let us know when your samples are coming. The more notice you give us, the easier it is for Pacific BioLabs to meet your turnaround time requirements.
    • Include clear and complete Request for Analysis forms with each sample submission. This helps us avoid errors and speeds up your sample login.
    • Respond quickly if something goes wrong. Most validations go smoothly. If a problem does arise, Pacific BioLabs will notify you promptly. Your quick response will help us keep your validation on track, on budget and on time

    PBL’s Sterility Assurance Booklet
    Download the free booklet

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