This action might not be possible to undo. Are you sure you want to continue?
is it? For what products is it required? How is it accomplished? Who does it? How is it regulated? What standards apply?
What is sterilization?
Free from any living organisms Sterilization: Process of killing or removing microorganisms from a product to insure that it is sterile
Dentists. other health care facilities Some specialty food product manufacturers . Manufacturers of any product that enters the body. except by ingestion: Medical Device Manufacturers Pharmaceutical Manufacturers (both human & veterinary) Hospitals.Who needs to sterilize? Anyone who supplies a product on which the presence of microorganisms could present a health risk.
drain bags. ophthalmic and some topical products In vitro Diagnostics±for heath care related testing Prepared Media ± for microbiology testing . cleanroom garments specimen cups.Some Products Requiring Medical DevicesSterility exam and surgical gloves. surgery supplies Pharmaceuticals injectable and inhalation drugs nasal. syringes. surgical tools. wound care products. IV bags implants. catheters. sutures needles.
Products are filled or assembled using sterile components maintained under sterile conditions. Aseptic processing is used for drug products that are adversely affected by terminal sterilization processes.45 micron or smaller membrane filters. Filtration is often used in aseptic processing.How is sterilization accomplished? Filtration Many liquids can be sterilized by passing through 0. Aseptic processing is performed in cleanrooms or in isolators (closed environments without humans). Aseptic Processing .
Ethylene Oxide Gas Radiation ± gamma and electron beam Steam (moist heat) Dry heat. other technologies Terminal Sterilization Processes: . plasma hydrogen peroxide (Steris Sterrad). pulsed bright light. UV light. chemicals.Terminal Sterilization How is sterilization accomplished? Finished products are exposed to a validated process to kill any living microorganisms.
Selection of a Sterilization Process ± How do you decide? FDA requires terminal sterilization unless the product would be adversely effected. . Steam . particularly those packaged with drugs or any other component not compatible with radiation.the preferred method for many liquid products and reusable medical devices intended for sterilization in hospitals. Ethylene oxide ± a method widely used for medical device kits. The vast majority of medical devices requiring sterility are sterilized by one of the following three methods: Radiation ± a method preferred for many types of single use medical devices.
. Dosimetric release: No product quarantine is required after dose validation. Dose Uniformity: The dose distribution ratio within the product does not typically exceed 1.5:1.Sterilization Process Selection Advantages and Disadvantages Gamma Radiation ± Advantages Simple process: The only parameter to control is exposure time which in turn controls the radiation dose delivered to the product. Excellent penetration: Gamma rays readily penetrate dense or complex products.
. Material degradation: A few materials degrade after terminal sterilization radiation dosing.Sterilization Process Selection Gamma Radiation ± Disadvantages Limited applicability to kits: It cannot be used for kits or complex products containing any component that is incompatible with or not approved for radiation sterilization (such as a drug products).
Less material degradation: Some radiation sensitive materials degrade less with E-beam than if gamma sterilized Dosimetric release: After successful dosimetry studies and microbiological validation of the dose. no product quarantine is required after sterilization.Sterilization Process Selection Electron Beam Radiation ± Advantages Fast process ± can sometimes be done as end of the production process. .
Sterilization Process Selection E-Beam Radiation ± Disadvantages Limited penetration: It is often not appropriate for dense or complex products. Sensitive to product configuration: Various densities in a product can affect dose distribution. Extensive dose mapping is often required. Product configuration changes require new dose mapping studies. Dose Uniformity: There is potential for higher variation within the product. .
Many good contract service providers throughout U. Good for kits: EO does not penetrate ampules of drug products.S. . Parametric Release: Improving EO equipment control technology is facilitating parametric release validation for some products (no end process microbiological testing and product quarantine pending results).Sterilization Process Selection Ethylene Oxide ± Advantages: Well characterized process: Appropriate for a wide variety of materials and products. a common kit component.A.
Product release must be delayed until residuals dissipate to acceptable levels.Sterilization Process Selection Ethylene Oxide ± Disadvantages Comparatively complex process: Four factors are required to achieve a successful sterilization cycle: time. foil pouches). EO & ECH Residuals: Some materials retain residuals. . humidity and EO gas concentration/distribution. Penetration Limitations: EO does not easily penetrate some sealed areas of devices or some sealed packages (ie. temperature.
Sterilization Process Selection Steam ± Advantages Simple process: The only two parameters to control are time and temperature. Excellent process for reusable medical devices that are not adversely affected by temperatures >121C (up to 135 C). Highly reliable and easily controlled. . Widespread capability: All hospitals and many other heath care facilities have steam sterilizers. Excellent process for liquids that are not heat sensitive.
. Generally not appropriate for most single use disposable medical devices produced in high volumes and sold as sterile.Sterilization Process Selection Steam ± Disadvantages Comparatively high temperature required: Many products and packaging materials cannot tolerate temperatures of >121C.
. At PBL. steam is also frequently used for client reusable medical device steam sterilization validations. Laboratories ± daily use of steam sterilization to support microbiology testing.Sterilization ± Who performs it? Product Manufacturers ± especially with filtration. aseptic processes. Hospitals ± daily use of steam sterilization for a wide variety of in-house needs.
.Sterilization ± Who performs it? Contract Sterilizers Provide terminal sterilization services to medical device manufacturers. Have extensive capacity in EO and radiation sterilization in many facilities widely distributed throughout the U.S. Sterilize a significant percentage of all single use disposable medical devices manufactured.
biopharmaceuticals) CDRH ± Center for Devices and Radiological Health (medical devices) International Regulatory Agencies .Sterilization ± How is it regulated? FDA CDER ± Center for Drug Evaluation and Research (pharmaceuticals) CBER ± Center for Biologic Evaluation and Research (vaccines.
fda.CGMP Final Rule. Packing or Holding of Drugs. . Quality System Regulation (1996) Available at www. General (1978) Part 211: Current Good Manufacturing Practice for Finished Pharmaceuticals (1996) 210 & 211 available at: www.Sterilization ± How is it regulated? CGMP regulations in 21 CFR Part 210: Current Good Manufacturing Practice in Manufacturing.gov/cdrh/humfac/frqsr. Processing.gov/cder/dmpq/ Parts 808.html A written agreement with contract sterilizer is required. 812 & 820: Medical Device .fda.
gas.What standards apply? USP 25 ± applies to drug products. 3 ± Validation of Dry Heat Processes (1981) No. radiation. 17 ± Current Practices in the Validation of Aseptic Processes (1993) PDA Technical Reports (guidance documents) . dry heat. filtration and aseptic processing) No. 1 ± Validation of Steam Sterilization Cycles (1978) No. Chapter <1211> Sterilization and Sterility Assurance of Compendial Articles (contains brief sections on steam.Sterilization .
Sterilization . AAMI = Association for the Advancement of Medical Instrumentation ISO = International Standards Organization ANSI = American National Standards Institute Most AAMI/ANSI standards are FDA recognized. . AAMI TIRs are cited by FDA as relevant guidance documents.S.What standards apply? ANSI/AAMI/ISO standards apply to sterilization of medical devices ± both in U. but are not recognized standards. and internationally.
ANSI/AAMI/ISO Standards Ethylene Oxide Sterilization Medical Devices ± Validation and routine control of EO sterilization (ANSI/AAMI/ISO 11135: 1994) Contract Sterilization for EO (AAMI TIR 14:1997) Process development and performance qualification for ethylene oxide sterilization microbiological aspects (AAMI TIR 16:2000) Parametric release for EO sterilization (TIR 20) Biological Evaluation of Medical Devices-Part 7: EO sterilization residuals (10993-7) .
ANSI/AAMI/ISO Standards Radiation Sterilization Sterilization of health care products Requirements for validation & routine control ± Radiation sterilization (ISO 11137:1995) Method 1 (for large & frequent production batches) Method 2 (for radiation sensitive & problematic bioburden products) Selection of a sterilization dose for single production batch (AAMI/ISO TIR 15844:1998) Substantiation of 25 kGy as a sterilization dose ± Method VD-max (AAMI TIR 27:2001) .
ANSI/AAMI/ISO Standards Radiation Sterilization Radiation sterilization material qualification (AAMI TIR 17:1997) 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 (ANSI/ AAMI/ISO TIR 15843:2000) .
.ANSI/AAMI/ISO Standards Industrial Steam Sterilization Principles of moist heat sterilization (AAMI TIR 13:1997) Sterilization of health care products ± Requirements for validation and routine control ± Industrial moist heat sterilization (ANSI/AAMI/ISO 11134:1993) An industrial dry heat sterilization proposed standard is in the development process.
AAMI/ISO/ANSI Standards Sterilization in Health Care Facilities Designing. testing and labeling reusable medical devices for reprocessing in health care facilities: A guide for device manufacturers (AAMI TIR 12:1994) Good hospital practice: Steam sterilization and sterility assurance in health care facilities (ANSI/AAMI ST46:2002) Guidelines for the selection and use of reusable rigid container systems for EO and steam sterilization in health care facilities (ANSI/AAMI ST33:1996) .
dry heat & EO table top sterilizers Safe handling & biological decontamination of reusable medical devices (ANSI/AAMI ST35) Chemical sterilants & disinfectants Flash sterilization (steam at 132C) Processing of reusable surgical textiles .ANSI/AAMI/ISO Standards Additional standards on: Sterilization in Health Care Facilities Steam.
ANSI/AAMI/ISO Standards Laboratory Testing ± Microbiology Sterilization of medical devices ± Microbiological methods ± Part 1: Estimation of the population of microorganisms on a product (ANSI/AAMI/ISO 11737-1:1998) Sterilization of medical devices ± Microbiological methods ± Part 2: Tests of sterility performed in the validation of a sterilization process (ANSI/AAMI/ISO 117372:1998) .
PQ of manufacturing environment control equipment ± cleanrooms. OQ.Sterilization: How is it validated? Aseptic Processing IQ. isolators. hepa filters. Media fills ± run microbiological growth medium in place of product through entire production process Filtration Microbial challenge studies Filter integrity testing .
EO concentration measurement devices. subtilis spore strips. (Usually performed by contract by sterilizers.I.I.s are tested for sterility.) Exposed products & B. PQ Do chamber studies with thermocouples. OQ. humidity sensors. EO residuals .Sterilization: How is it validated? Ethylene Oxide Equipment IQ. B-F test.s are most commonly B. Half & full cycles with biological indicators Validation support testing Product bioburden.) Fractional cycles with products and biological indicators (B.
Determination of product bioburden Verification dose resistance experiment . do bioburden test method validation Dose is determined based on product bioburden. First. Irradiate products at ³sublethal´ verification dose level. Before sterility test. Test the verification dosed samples for sterility. do B-F testing to validate test method.Sterilization: How is it validated? Radiation Dose mapping study Dosimeters are placed in products at contract sterilizer.
stearothermophilus) Then sterility testing of product & B. PQ of steam sterilizer Temperature profiles of product during sterilization cycles (using thermocouples) Fractional and/or half cycles with product & B.I.s . OQ.I.s (G.Sterilization: How is it validated? Steam IQ.
. Cleaning validations for reusable devices Product/Packaging validation and expiration dating. Microbial environmental monitoring of the manufacturing environment.Other Considerations for Sterile Products Biocompatibility of finished products and manufacturing materials. Bacterial endotoxin testing for blood contact products.
org PBL Compliance Guides Sterility Assurance Compliance Assessing Biocompatibility Online at www.aami.Some Useful References ANSI/AAMI/ISO standards and TIRs available at www.com .usp.org USP 25 ± order from www.pacificbiolabs.
Thanks Comments? Questions? .