Validation of Sterilization

Hevi Milda Lestari 0811013158

All sterilization processes require validation of the efficacy and reproducibility of the process. Depending on the type of sterilization, this may be accomplished by partial, sub-lethal, or repetitive processing, using representative product and/or biological challenges. WuXi AppTec offers a full range of services in this area, from testing alone to full management of the validation.

Early Sterilization
In 1979, the principal medical device sterilization modalities in use were ethylene oxide (EtO) and radiation primarily gamma as well as some saturated steam. This was mainly due to the proliferation of disposable medical devices. For the most part, they were constructed of heat-labile plastics and required a low-temperature (below 121.1 C) sterilization process. This trend continues today with the development of new and improved medical-grade materials for construction and packaging films. These materials have provided unique properties for packaging novel medical devices. While contract sterilizers now sterilize an increased percentage of medical devices, the principal modes of sterilization remain the same: EtO and radiation.

 The basic principles of these sterilization processes have not changed significantly.Steam and EtO processes still involve exposing a device in a pressurized chamber to a predetermined set of conditions for a specific time. Radiation still involves exposing a device to a specific dose of radiation in a carrier tote (gamma) or conveyor system (E-beam). Early literature references (for example, Kaye and Phillips , Bruch, Tallentire, Pflug, Perkins, Davis, Stumbo, Masefield, Christensen, Whitby, and Block) remain valid and pertinent today.

EtO Validation
AAMI has been an active participant in generating the industrial validation standards for all major sterilization processes used to process medical devices since the 1970s. For example, in 1981, the Industrial Ethylene Oxide Sterilization Working Group authored AAMI Recommended Practice OPEO: 1981

 This document, titled Guideline for Industrial Ethylene Oxide Sterilization of Medical Devices, was subsequently revised several times. In 1988, it was issued as ANSI/AAMI ST27:1988. As part of the review of the document in 1992, the working group examined ISO document 11135. It should be noted that the ISO document was based on a draft standard prepared by the European Standardization Committee (CEN), and thus reflected a global perspective on the subject. It is part of AAMIs practice to harmonize its work with international standards wherever possible.

 At that time, AAMI decided to adopt ISO 11135 verbatim as the ANSI/ AAMI revision to ST27. The document was subsequently published in 1994 as ANSI/AAMI/ISO 11135:1994. This international document mainly addressed requirements, though ANSI/ AAMI documents historically provided additional guidance to industrial users also. Consequently, the working group decided to develop TIRs to supplement the information contained in 11135. To date, there have been a series of TIRs published for EtO

 AAMI TIR 14:1997, Contract Sterilization for Ethylene Oxide. AAMI TIR 15:1997, Ethylene Oxide Sterilization Equipment, Process Considerations, and Pertinent Calculations. AAMI TIR 16:2000, Process Development and Performance Qualification for Ethylene Oxide Sterilization. AAMI TIR 20:2001, Parametric Release for Ethylene Oxide Sterilization. AAMI TIR 28:2001, Product Adoption and Process Equivalency for Ethylene Oxide Sterilization.

 One of the important advancements over the last decade has been the acceptance of parametric release of EtO-processed product lots. This practice is now offered by most contract sterilizers. Parametric release of EtO product lots allows a product turnaround time of days, rather than the weeks traditionally required with EtO sterilization.

Radiation Validation
On an analogous path and parallel timeframe, AAMI was also developing radiation-sterilization standards. The Radiation Sterilization Working Group developed two American National Standards in the 1980s. One was the Guideline for Electron Beam Radiation Sterilization of Medical Devices, ANSI/AAMI ST31:1990, and the other was the Guideline for Gamma Radiation Sterilization, ANSI/AAMI ST32:1991.

As part of the required review of these documents, the AAMI working group reviewed the corresponding ISO 11137 document, Sterilization of Health Care Products Requirements for Validation and Routine Control Radiation Sterilization.

 he group tried to ascertain whether the documents could be harmonized. The working group decided to adopt ISO 11137 verbatim as the ANSI/AAMI revisions to ST31 and ST32. The document was subsequently published as ANSI/AAMI/ISO 11137:1994. As with the EtO document, AAMI also generated TIRs to provide additional guidance for U.S. users of 11137:

 AAMI/ISO TIR 13409:1996,Sterilization of Health Care Products Radiation Sterilization Substantiation of 25 kGy as a Sterilization Dose for Small or Infrequently Produced Batches. AAMI TIR 17:1997, Radiation Sterilization Material Characterization. AAMI/ISO TIR 15844:1998, Sterilization of Health Care Products Radiation Sterilization Selection of a Sterilization Dose for a Single Product Batch. AAMI/ISO TIR 13409/A1:2000, Sterilization of Health Care Products Radiation Sterilization Substantiation of 25 kGy as a Sterilization Dose for Small or Infrequently Produced Batches, Amendment. ANSI/AAMI/ISO TIR 15843: 2000, Sterilization of Health Care Products Radiation Sterilization Product Families and Sampling Plans for Verification Dose Experiments and Sterilization Dose Audits, and Frequency of Sterilization Dose Audits. AAMI TIR 27:2001,Sterilization of Medical Products Radiation Sterilization Substantiation of 25 kGy as a Sterilization Dose Method VDmax.

Steam Validation
Concurrently with the activities in the EtO and radiation arenas, the Industrial Moist Heat Sterilization Working Group was also developing standards. ANSI/AAMI ST25,Guideline for Industrial Sterilization of Medical Products,was published in the 1980s. The last revision of this document was published in 1987.

 As a part of the required review of this document, the group decided to adopt ISO 11134, Sterilization of Health Care Products Requirements for Validation and Routine Control Industrial Moist Heat Sterilization, verbatim as the ANSI/AAMI revision. The document was subsequently published as ANSI/AAMI/ISO 11134:1993. AAMI TIR 13:1997, Principles of Industrial Moist Heat Sterilization,was written to provide additional guidance on 11134.

Conclusion
The subject of sterilization validation is dynamic. Discussions continue on a worldwide basis with the ultimate goal of achieving global harmonization. ANSI/AAMI/ISO 14937, Sterilization of Health Care Products: General Requirements for Characterization of a Sterilizing Agent and the Development, Validation, and Routine Control of a Sterilization Process for Medical Devices, was published in 2000. It provides a standardized procedure for validating new sterilization technologies

The current revisions of ISO and CEN documents are proceeding. The desired results are single harmonized standards for all sterilization processes. We are therefore getting closer to the objective. Unfortunately, the progress of the standards-generation process at times appears glacial in speed. However, it is a process that is worth the effort and ultimate reward. Watch the pages of MD&DI for developments in the process.