MaRS Library Sterilization: Healthcare products
According to the US Centers for Disease Control and Prevention, sterilization means “the use of physical or chemical procedure to destroy all microbial life, including highly resistant bacterial endospores.”1
The objective of sterilization is to completely destroy or remove all microorganisms (including spore-forming and non-spore-forming bacteria, viruses, fungi and protozoa) that could contaminate a healthcare product (for example, those introduced in the manufacturing process via raw materials, process, equipment, facilities or personnel).
Although Good Manufacturing Practices (GMP) are applied throughout the manufacture of healthcare products to minimize preventable microbial contamination, products that are labelled “sterile” and can be sterilized in their final containers normally undergo a sterilization process. For products that cannot be sterilized in their final containers, aseptic processing is needed.2
The sterilization method used and the efficacy of the process depends on factors such as the costs, the characteristics of product and packaging materials, the extent and type of contamination(s), and the conditions under which the final product has been prepared. Traditional sterilization methods are described below.2,3
Dry heat sterilization
Dry heat sterilization achieves sterilization via the oxidation of cell constituents. It requires a higher temperature than moist heat and a longer exposure time. It is most suitable for heat-stable, non-aqueous materials that cannot be sterilized by steam due to its deleterious effects (for example, the product is moisture-sensitive) or its failure to penetrate (for example the product is packaged in glassware container).
Moist heat sterilization
Moist heat sterilization exposes microorganisms to saturated steam under pressure which achieves the irreversible denaturation of enzymes and structural proteins. It is commonly used in aqueous preparations, surgical dressings and medical devices. A steam autoclave, for example, uses this method.
Ethylene oxide―in a fixed chamber
Ethylene oxide (EO) is used to sterilize items that are heat- or moisture-sensitive. The disadvantages are that the EO gas can leave toxic residues on sterilized items, and it presents several physical and health hazards to personnel and patients. Thus, the maximum levels of EO residual gas and ethylene chlorohydrin that remain on the product should be evaluated as required by ISO 10993-7. Biological Evaluation of Medical Devices – Part 7: Ethylene Oxide sterilization residuals.
Radiation (gamma and electron beam)
Radiation affects the ionization of molecules in organisms. Mutations are thus formed in the DNA and these reactions alter replication of the microbes. This method can be used for certain active ingredients, drug products and medical devices.
Liquid chemical sterilants
Liquid chemical sterilants are used to sterilize single-use medical devices that contain material(s) of animal originwhich are not compatible with commonly applied sterilization methods. Examples of such devices include biological heart valvesand tissue patches.4
Regulatory submissions and sterilization data
In regulatory submissions, information on the sterilization method used and its validation as well as a description of the packaging to maintain product sterility are normally included.* This is to ensure that the proper sterility assurance level (that is, 10-6 for all medical devices, except 10-3 for devices that only contact intact skin) can be consistently achieved before a healthcare product can be labelled as “sterile.”3
If the characteristics, quality, safety and effectiveness of the healthcare product after sterilization may be affected, consider doing testing (for example, biocompatibility, bench, animal and clinical studies) on the finished sterilized healthcare product for inclusion in the regulatory submission.
When conducting sterilization activies, follow the applicable, recognized standards (such as ISO 11137, ISO 11737, ISO 11135). For medical devices that are shipped non-sterile and are intended to be sterilized by users, or those that are reusable and meant to be re-sterilized by users, the product labelling should provide adequate information regarding at least one suitable method of sterilization and any needed precautions or safeguards that need to be followed. The labelling should also include information such as special cleaning methods, any changes in the physical characteristics of the device that may result from reprocessing which can affect its safety, effectiveness or performance, and any limit on the number of times for resterilization and reuse.5
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In the US, if a company decides to use a sterilization method that is considered non-traditional, an inspection of the sterilization facility may be considered a priority in the post-market period. Such non-traditional methods could include EO not being used in a fixed chamber, or the use of high-intensity light, chlorine dioxide, ultraviolet light, combined vapour and gas plasma, filtration methods, a vapour system such as peroxide or peracetic acid, or a limited use of liquid peracetic acid system in endoscopy with a metal instrument.3
*For drugs that are sterilized via aseptic processing, information on the aseptic fill manufacturing processes should also be submitted.6
The information presented in these articles is intended to outline the general processes, principles and concepts of the healthcare product development lifecycle. Since regulatory requirements are ever-changing, it is current only as of the date of publication and not intended to provide detailed instructions for product development. Every healthcare product is unique and therefore so is its associated product development lifecycle. Specific advice should be sought from a qualified healthcare or other appropriate professional.
Published: October 17, 2012
- Centers for Disease Control and Prevention. (2011, January). Healthcare-associated infections (HAIs): Sterilization or disinfection of medical devices. Retrieved June 5, 2012, from http://www.cdc.gov/HAI/prevent/sd_medicalDevices.html.
- World Health Organization. (2011). The International Pharmacopoeia Methods of analysis: 5. Pharmaceutical technical procedures: 5.8 Methods of sterilization. Retrieved June 7, 2012, from http://apps.who.int/phint/en/p/docf/
- U.S. Food and Drug Administration. (2002). Updated 510(k) sterility review guidance K90-1; Final guidance for industry and FDA. Retrieved August 14, 2012, from http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm072783.htm.
- ISO 14160. (2011). Sterilization of health care products – Liquid chemical sterilizing agents for single-use medical devices utilizing animal tissues and their derivatives – Requirements for characterization, development, validation and routine control of a sterilization process for medical devices.
- U.S. Food and Drug Administration. (1989). Labeling: Regulatory Requirements for Medical Devices. Retrieved June 5, 2012, from http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm095308.pdf.
- U.S. Food and Drug Administration. (1994, November). Guidance for Industry for the Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products. Retrieved October 3, 2012, from http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072171.pdf.
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