There have been a number of changes in the last decade, which have raised questions as to how manufacturers should design cleaning and sterilization validation in order to be in compliance with new standards. This article provides answers to questions posed by manufacturers addressing the challenges of current cleaning processes, the selection of test soils, and the application of current test methods.

This hinged device is a common instrument requiring cleaning.

By John Broad, Dave Albert, and Laurie Nawrocki
At a Glance
  • Published guidelines
  • Issues with design
  • Ensuring proper cleaning
  • Labeling
Reusable medical devices have been used in health care facilities since the turn of the century. Over the years, the devices have become more sophisticated because advances in diagnostic and therapeutic medicine have led to more sophisticated designs. As designs become more complex, the process of adequately cleaning, disinfecting, and sterilizing these instruments has become more complex as well.

Manufacturers of reusable medical devices are responsible for supporting their product claims for reprocessing reusable devices in healthcare facilities. Meeting this responsibility involves developing instructions for preparing the device for reuse and conducting testing that validates these instructions. Proving cleaning, disinfection, and/or sterilization efficacy is not the only consideration involved in device reuse. Other issues related to device function, physical integrity, and biocompatibility must also be addressed.

When choosing a validation process for reusable medical devices, U.S. manufacturers rely on guidance from FDA and validation methods developed by the Association for the Advancements of Medical Instrumentation (AAMI), as well as international standards. AAMI has been working with the International Organization for Standardization (ISO) and the American National Standard Institute (ANSI) on the development of guidance for cleaning and sterilization methods for reusable medical devices. The development of new device designs and cleaning agents may cause a shift in the ability to validate cleaning processes that have been used successfully in the past. The following question and answer presentation will address many of the concerns companies have with regard to the reuse of medical devices.

Q: What scientific guidelines (both domestic and international) should be followed in order to effectively clean reusable medical devices?
A: Scientific guidelines have been developed to provide assistance to device manufacturers in designing, testing, and labeling of devices intended for reuse in health care facilities. These are discussed in the following new and existing standards:

Technical Information Report TIR No. 12 entitled "Designing, Testing, and Labeling Reusable Medical Devices for Reprocessing in Health Care Facilities," published by the AAMI (2004). The updated TIR covers a number of general topics:
  • Design Considerations - Physical, material, total system, and user design
  • Decontamination - Cleaning agents, water quality supplies, equipment, and methods used in health care facilities and cleaning validation programs
  • Disinfection With Liquid Chemicals - Classification of medical devices based on degree of risk, disinfectant selection, toxicity, and material compatibility
  • Sterilization - Available processes, design considerations, efficacy testing methods, sterilant residue, and documentation requirements of hospital information
  • Device/Sterilant/Equipment Compatibility
  • Regulatory Considerations - FDA regulatory classification and requirements
Sterilization of Medical Devices ST 81 2004 - Information provided by the manufacturers for the processing of resterilizable medical devices. Published by AAMI (2004). This standard lists the required information to be provided by medical device manufacturers, so that medical devices can be reprocessed in a safe manner. The standard covers:
  • Preparation at the point of use
  • Cleaning
  • Drying
  • Inspection, maintenance, and testing
  • Packaging
  • Disinfection and sterilization
  • Storage
This standard also provides examples of processes (decontamination and sterilization) for various types of reusable devices.Sterilization of Reusable Devices ISO 17664:2004 - Information provided by the manufacturer for the processing of resterilizable medical devices. Published by AAMI. The standard covers the same topics as mentioned in ST 81.Technical Information (TIR) Report No. 30 - Entitled a compendium of process, materials, test methods, and acceptance criteria for cleaning reusable medical devices. Published by AAMI (2003). This standard provides information regarding test protocols, test soils, and acceptance criteria for manufacturers to validate the cleaning process for reusable medical devices.

The hinge of a grasping forcep requires the use of an effective cleaning system that ensures a satisfactory result.
Q: How is the intended use of the device determined?
A: The Center for Disease Control and Prevention (CDC) recommends disinfection or sterilization based on three end use categories (CDC, 1985):

Critical items - These devices are in direct contact with blood or areas of the body not usually in contact with contaminants. Examples of such devices include surgical instruments, endocavity probes, implants, biopsy forceps/scissors, and ophthalmic irrigation devices. Sterilization is required for these devices.

Semi-critical items - These devices are non-invasive and normally contact intact mucous membranes. They include devices such as flexible endoscopes, endotracheal tubes, and breathing circuits. High level disinfection is a minimum process requirement for products in this category.

Non-critical items - Devices not in contact with the patient. If contact is made, it is only with intact skin. Examples of such devices include cuffs for measuring blood pressure, beds, crutches, etc. These devices rarely transmit disease. High, intermediate, and/or low level disinfection is recommended. Products can be cleaned with a simple detergent.
Design Considerations
Q: What are some of the device design, testing, and labeling issues associated with reusable medical devices?

A: These issues have been raised by manufacturers considering test programs for new devices or to support changes in product design or disinfection/sterilization processing instructions.

A reusable medical device intended for reprocessing must be designed to function safely and effectively following sterilization in a health care setting. Reusable devices must be designed to withstand multiple cleaning, sterilant, or disinfectant exposures. The number of cleaning and exposure cycles to which a device can be subjected without loss of effective functioning will help determine the useful life of the product.

Most devices composed of cleaning and sterilant-tolerant materials will withstand more than 100 cycles. Testing should be designed to address not only the efficacy of the cleaning and sterilization cycle, but also biocompatibility and functional performance of the device. This can be accomplished by exposing a product to multiple cycles, including any cleaning steps between cycles for the number of cycles equivalent to projected maximum useful life. Following these exposures, there should be a demonstration of functionality, physical integrity, and biocompatibility through adequate testing.

When the device is a single use device and the end user must sterilize the product, the manufacturer should provide the user with sterilization instructions. To provide these instructions, the manufacturer must have validation data to support the sterilization process. A manufacturer should conduct studies in the same manner as recommended in guidance documents, under Sterilization Efficacy Testing, to provide data to demonstrate that the instructions provide the product with an equivalent Sterility Assurance Level (SAL) of 10-6.

Q: What design features pose difficulties in cleaning the device?
A: The following design features may cause challenges in the cleaning procedures:
  • Narrow lumens of flexible endoscopes
  • Crevices, hinges, and rough porous surfaces
  • Luer locks
  • Surfaces between insulating sheaths
  • Dead ended lumens
Q: Is it necessary to thoroughly clean a reusable device even when disinfectants or sterilants are used?
The cleaning process may serve several purposes. It removes blood, protein, fats, carbohydrates, and other potential contaminants from surfaces, crevices, joints, and lumens of a device. Cleaning may also reduce the quantity of particles, microorganisms, and endotoxins. The organic material must be effectively removed to ensure it will not protect the microorganisms from the effects of Ethylene Oxide, steam, and liquid chemical disinfectants/sterilants and risk of transmitting infectious microorganisms from one patient to another. However, prions, the causative agent of transmissible spongiform encephalopathies, have demonstrated an unusually high resistance to germicidal chemicals and heat. For more information on the processing devices exposed to prions, refer to AORN (2004) and the recommendations of the CDC, ASHCSP, and IAHCSMM.

The information provided in AAMI TIR 30 list several soils that have been developed by several countries to test the efficacy of cleaning a variety of reusable medical devices. Furthermore, the TIR provides testing methods for the detection of soil proteins, fats, carbohydrates, endotoxins, and viable microorganisms. These tests provide data that verifies that the manufacturers recommended cleaning procedure, using a specific cleaning agent, is effective for a particular device.

Q: How does one choose the appropriate soil and test method for the cleaning validation studies?
No single test soil is appropriate for all medical devices. The cleaning procedure developed should be based on the type of contamination expected on the device, design features, and potential for the patient to come in contact with pathogens. For example, the organism and bioburden challenge appropriate for devices entering the sterile body cavity will be different than that for a device that contacts the mucosa and intact skin. Intravascular devices that come in contact with sterile body cavities should be soiled with whole blood and serum.

Q: What test methods are commonly used for cleaning validation procedures?
Verification is usually performed in a laboratory setting, selecting an artificial soil mixture that closely simulates the level of contamination expected in clinical use. For example, simulated blood or body fluids may be formulated using a mixture of calf serum, dry milk powder, and a 1:1 rabbit blood/saline mixture (Miles, 1991).

A method proposed by AAMI for evaluating the effectiveness of the cleaning process is to add Geoacillus stearothermophilus spores at approximately 104 to 105 organisms per device (used as a tag). The soiled device is then cleaned according to the manufacturer's instructions and the remaining spores are recovered and enumerated. It is important that the recovery technique be validated prior to determining the efficacy of cleaning. The efficacy of cleaning can then be determined by subtracting the spores recovered from the device after cleaning from the spores recovered from a control sample (soiled without cleaning). The testing should be sufficient to ensure that the cleaning procedure can be duplicated in the health care facilities. A benchmark bioburden reduction level by cleaning should show at least a three log reduction. Published data shows that this is possible for flexible endoscopes (Alfa, et al., 1999). Viable count determination can be useful, but they should not be used as the only marker for cleaning efficacy since loss of viability may demonstrate a reduction of viable organism and cannot detect the removal of residual soil residues.

Q: What other methodologies may be used to evaluate cleaning efficacy?
A: Protein and carbohydrates are markers that can be used to evaluate the effectiveness of cleaning a medical device. Blood cells contain hemoglobin, and with effective cleaning, the blood can be removed. There are methods of testing for residual hemoglobin from extracts of the devices (Alfa, et al., 1999). Endotoxins (gram negative bacterial cell wall molecule) are found in tap water used to clean reusable devices and can cause a systemic pyrogenic reaction if a critical reusable device is contaminated with endotoxins and enters the body cavity. The endotoxin levels extracted from a clean device can be analyzed by various methods (ANSI/AAMI ST72).

The phenol-sulfuric acid assay is a broad spectrum method for carbohydrates, measuring both mono- and polysaccharides. Calibration curves of micrograms sugar vs. 490 nm for mannose, glucose, and galactose are shown to provide reliable determinations (typically ±3%-4%) of corresponding methyl glycosides and linear and branched-chain oligosaccharides containing the corresponding reactive hexose residue.

The bicinchoninic acid (BCA) protein assay is a highly sensitive reagent for the spectrophotometric determination of protein concentration in solution. It is considered to be the most sensitive of the colorimetric protein methods available today. Many of the detergents (Triton X-100, SDS, Brij, Lubrol, Chaps, Tween 20 and 80, etc.), buffers (Sodium Phosphate, Hepes Buffer, Sodium acetate, etc.), and salts (sodium and potassium chloride) commonly used to study and remove proteins are compatible with the reagent.

Q: What acceptance criteria exist for the user verification tests?
One of the most difficult questions to address for manufacturers on the topic of cleaning is how clean is clean? The TIR 30 has provided a number of references that address issues regarding acceptance criteria for cleaning effectiveness. The following limits have been cited published data for various types of reusable devices. One reference (Alfa, et al., 2002) showed average levels of the various markers after cleaning were: • Protein: <6.4 µg/cm2 • Carbohydrate: <1.8 µg/cm2 • Hemoglobin: <2.2 µg/cm2 • Endotoxin: <2.2 EU/cm2 • Bacterial reduction: 3 logs
Regulatory Considerations
Q: What regulatory issues should be considered by manufacturers?
A: The FDA has made recommendations on labeling reusable devices for premarket clearance and compliance with quality systems.

In April of 1996, the FDA's Office of Device Evaluation (ODE) issued a draft guideline entitled "Labeling Reusable Medical Devices for Reprocessing in Health Care Facilities: FDA Reviewer Guidance." This document was intended for use as a checklist to evaluate a reusable device's labeling content for conformance with all applicable requirements to ensure an adequately prepared device for repeated, multi-patient use.

The responsibility for the labeling is dual. The manufacturer of the device is responsible for supporting the reuse claim, providing procedures that can be reasonably executed by the user. The user of the device (health care facility) is responsible for having the proper facilities and equipment to execute and follow the instructions.

The labeling practice instructing users to "follow routine hospital reprocessing procedures for this device" is considered unacceptable, as there are many devices for which these procedures do not exist. The FDA guidance document identifies seven criteria for reprocessing which must be addressed in the instructions.
  1. "The instructions must include initial processing (nonsterile, single use device) or reprocessing (reusable device) instructions."
  2. A statement is required indicating that the device "must be thoroughly cleaned before reuse." Note that the cleaning process for the device is critical for assuring success in the microbicidal processes.
  3. "The instructions must indicate the appropriate microbicidal process for the device." This relates to the sterilization or level of disinfection appropriate for the device based on the device's patient contact category.
  4. "The processes must be feasible considering the intended location of reprocessing." The processes and instructions must adequately reflect the equipment and knowledge needed to carry out the reprocessing steps.
  5. "The instructions must be understandable."
  6. "The instructions must be comprehensive." This is the section of the labeling that needs to specifically describe the procedures necessary "to execute the processing regimen safely and effectively." There are many components to this section and the intent is to be as comprehensive as possible regarding special tools, accessories, maintenance procedures, cleaning agents, and methods for disinfection or sterilization (based on experimental data). Without these instructions, the label may be declared deficient and returned to the manufacturer for further clarification.
  7. "The instructions must include only devices and accessories that are legally marketed." Items such as sterilizers used in health care facilities and liquid chemical disinfectants/sterilants are subject to separate FDA clearance and approval.These seven criteria combine to form a user-friendly, validated, and informative instruction packet intended to deliver a safe, anti-infective reusable device.
It is apparent that there are a number of issues a manufacturer of a reusable device must address before a device can be safely used in the health care facility. As reusable device design becomes more sophisticated, the combined efforts of manufacturers, health care practitioners, and regulatory agencies will be needed in order to develop safe and effective instructions for use in reprocessing reusable medical devices in healthcare facilities.
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AAMI TIR No. 12: 2004 - Designing, Testing, and Labeling Reusable Medical Devices for Reprocessing in Healthcare Facilities: A Guide for Device Manufacturers.

AAMI TIR No. 30: 2003 - A compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices.

Biological Evaluation of Medical Devices - Part 7: Ethylene Oxide Sterilization Residual: Draft International Standard ISO/DIS 10993-7.

Center for Disease Control Guidelines for Hand washing and Hospital Environmental Control, Section 2: Cleaning, Disinfecting, and Sterilizing Patient Care Equipment, Atlanta, CDC, 1985.

Draft on Kinetic-Chromogenic LAL Technique; FDA; Department of Health and Human Services; reviewed by members of Centers for Drugs. Veterinary Medicine, Biologics and Medical Devices and reviewer responsible for Kinetic-Chromogenic Technique; Letter dated August 7, 1990, sent to Ronald N. Berzofsky, Director or Research and Development for Whittaker Bioproducts, Inc.

Dubois, M., Gilles, K.A., Hamilton, J.K., Rebers, P.A. and Smith, F. 1956. Colorimetric method for determination of sugars and related substances. Anal. Chem. 28: p. 350.

Food and Drug Administration (FDA). National Center for Drugs and Biologics, Office of Drugs, December 1987. Guideline for Validation of the Limulus Amebocyte Lysate Test as an End Product Endotoxin Test for Human and Animal Parenteral Drugs, Biological Products, and Medical Devices.

ISO 17664: 2004 - Sterilization of medical devices - Information to be provided by the manufacturer for the reprocessing of resterilizable devices.

Miles, R.S. What standards should we use for the disinfection of large equipment? J. Hosp. Infec., 1991, Vol. 18 Suppl. A, pp. 264-272.

Saha, S.K. and Brewer, C.F. 1994. Determination of the concentration of oligosaccharides, complex type carbohydrates, and glycoproteins using the phenol-sulfuric acid method. Carbohydrate Res., 254, pp. 157-167.

Sapan, C.V., Lundblad, R.L. and Price, N.C. 1999. A Review: Colorimetric Protein Assay Techniques. Biotechnol. Appl. Biochm. 29, pp. 99-108.

Smith, P.K, Krohn, R.I., Hermanson, G.T. et al., 1985. Measurement of Protein Using Bicinchoninic Acid. Anal. Biochem. 150, pp. 76-85.
For additional information on the technologies and products discussed in this article, visit NAMSA online at
John Broad is a senior consultant at North American Science Associates Inc. (NAMSA) at the Irvine, CA division. Dave Albert is a senior scientist for the company out of the same division. Laurie Nawrocki is a microbiologist II with NAMSA at the Ohio division. They can be reached at,, and respectively.