A WHITE PAPER

REUSABLE MEDICAL DEVICE DISINFECTION AND CLEANING VALIDATION REQUIREMENTS

By Steven G. Richter, Ph.D.

A WHITE PAPER

REUSABLE MEDICAL DEVICE DISINFECTION AND CLEANING VALIDATION REQUIREMENTS

INTRODUCTION Reusable medical devices come in all shapes and sizes from specula to colonoscopes. Generally, these devices have expensive components that require them to be cleaned and disinfected or sterilized. This paper describes the salient points for validating that a medical device can be safely reused. It covers disinfection processes, not sterilization. The cleaning validation information contained within is germane to all reusable medical devices.
Steven G. Richter, Ph.D.

Recently, the U.S. Food and Drug Administration (FDA) began requiring additional information on 510(k) submissions, demanding clarity in the options afforded to practitioners. Microbiologists generally treat all medical devices equally, even though many devices require special treatment. Historically, manufacturers were not required to validate that cleaning and disinfection processes were effective in reducing microbial and protein loads to safe levels. The FDA may have asked manufacturers for data regarding disinfectant use during reprocessing. Frenetically, manufacturers would perform cursory simulated-use tests that may not pass muster with FDA reviewers today. Currently, the FDA requires validation studies for both disinfection and cleaning. These studies are important to the manufacturer because they will validate the safety and efficacy of the disinfection process. It is important to qualify both the cleaning and disinfecting processes prior to validation activities. Microtest has been performing validation studies for many years. This white paper will help the practitioner determine the best practices for performing these pivotal studies.

1.

SYNOPSIS OF STANDARDS On their Web site, the FDA recognizes many consensus standards (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm). These standards can be used to support the study protocols and the FDA data (questions) requirements. Currently, the FDA recognizes the following AAMI/ANSI standards: ST-79 Comprehensive guide to steam sterilization and sterility assurance in health care facilities ST-81 Sterilization of medical devices: Information to be provided by the manufacturer for the processing of resterilizable medical devices ST-58 Chemical sterilization and high-level disinfection in health care facilities The FDA places the primary responsibility for developing and validating methods for effective reprocessing of a reusable medical device on the manufacturer of the device. The manufacturer is expected to validate that the device can be cleaned and disinfected or sterilized adequately to allow the device to be reused. As outlined by the FDA, the manufacturer must test and validate any labeling claims of fitness for reuse that are provided in the instructions for the handling, cleaning, disinfection, packaging, and sterilization of medical devices in a health care facility. To demonstrate compliance with label claims, manufacturers of cleaning agents must validate that their cleaners provide the expected level of soil removal and also must determine their materials compatibility. AAMI TIR30 addresses the issues related to manufacturers validation testing for cleaning medical devices. OTHER APPLICABLE DOCUMENTS: AAMI TIR12: Designing, testing, and labeling reusable medical devices for reprocessing in health care facilities: A guide for medical device manufacturers AAMI TIR30: A compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices AAMI TIR7: Chemical sterilants and high-level disinfectants: A guide to selection and use ASTM E1837-96: Standard test method to determine efficacy of disinfection processes for reusable medical devices (simulated use test) ASTM E-2314-03: Standard test method for determining the effectiveness of cleaning processes for reusable medical instruments using a microbiological method (simulated-use test) There obviously is a degree of confusion regarding these standards in terms of continuity and compliance. So how do you set up a test protocol and make it worst case for validation purposes? This paper is aimed at helping practitioners with the operation portion of cleaning and disinfection validation studies. Each medical device is different in its principle, engineering, and body contact area. The cleaning and disinfection studies can be performed as a single element or a combination of elements (simulated use). Some FDA reviewers are asking for all of these studies. Therefore, it is important to define your parameters prior to 510(k) submissions. First and foremost, the cleaning and disinfection processes should be qualified prior to validation. These notebook studies can be invaluable for setting the procedures for successful validation outcomes. Qualification studies are worked out with the reuse study project manager. The following are important aspects of this process:

2.

CLEANING STUDIES Challenge material: soil choices and bacterial species Cleaner type: enzymatic category (lipase, proteinase) Presoak/soak contact time and water temperature Water quality (pH and hardness) Brushes for manual cleaning Precleaning rinse Post-cleaning rinse Drying time and temperature Pass/fail criteria: log reduction or acceptable levels DISINFECTION STUDIES Disinfectant classification: low/intermediate/high Use dilution and storage Immersion and flushing for disinfectant 100% product contact Time and temperature Water quality (pH and hardness) Rinse method (sterile water) Pass/fail criteria (log reduction) CLEANING STUDIES POINTS TO CONSIDER Technical Information Report (TIR) 30 is the penultimate cleaning document used in the medical device industry. This report contains a compendium of test methods and acceptance criteria for the cleaning of reusable medical devices. Some pertinent information is indicated below. Enzyme cleaners work best within narrow pH and temperature ranges. Various enzyme cleaners are used for medical devices. Proteinase/lipase dual-enzyme lichen-based enzyme cleaners are the general choice of most manufacturers. Manual cleaning elements are broken down into the following categories: Hydration Friction Digestion Solubilization Fluidics

3.

Each element has a beneficial effect on the removal of body fluids, tissues, or excrement, such as saliva, blood, stool, urine, mucus, protein, and fat. The challenge soil should approximate the exposure level of bacteria and body fluids and tissues. A device will require a thorough analysis of potential cleaning based on worst-case scenarios in order to achieve a robust and comprehensive study outcome. BACTERIAL CHALLENGES POINTS TO CONSIDER The choice of bacterial species depends on where the device is being used. For example, endoscopes are used in the gastric area and normally encounter gram-positive and gram-negative bacteria, along with yeasts and molds. Endoscopes would also encounter blood, mucus, saliva, and tissue. Typical bacterial challenges are 1 x 104 CFU per device. Three log reductions may be required by FDA reviewers. A robust study would utilize gram-positive and gram-negative bacteria as tags. The selected soil marker would be inoculated with these bacteria. The device would be dried for 1 hour and then cleaned. After cleaning, rinsing, and drying, the device would be extracted to determine residue levels of soil (protein, CHO, endotoxin, or hemoglobin). One must pay attention to cleaning crevices, lumens, and joints (nooks and crannies). I would like to mention that no single test soil is appropriate for all medical devices. For instance, bacteria would not be appropriate for devices that enter sterile body cavities. Devices used in the GI tract would require an endotoxin challenge in the test soil. Log reduction numbers with endotoxin challenges are not typical due to the stickiness of the lipopolysaccharide molecule. Other devices that are not subjected to endotoxins and are not used in blood path direct, should not be tested with an endotoxin test soil. ARTIFICIAL SOIL TYPES: SELECTION CRITERIA AAMI TIR30 (Table 6) lists 12 soil types for the practitioner to use in cleaning studies. Historically, Huckers soil was the choice. However, Huckers soil was concocted for washer-disinfection units used for anesthesia equipment and bed pans (TIR30). Data indicate that Huckers soil is beyond the worst-case scenarios seen in soiled devices used on patients. AAMI TIR12 also references Huckers soil. Yet, other soils are becoming more appropriate due to medical device design characteristics and use. ATS-B soil contains bacteria, protein, CHO, endotoxin, and hemoglobin. This test soil type is recommended for flexible endoscopes, which are one of the most frequently reused devices in the United States. Other devices may require a spore tag or bacteria coupled with soil emulsions. Again, it is important to review device applications and the potential for body fluid or tissue contact. The TIR30 acceptance criteria are based on published data primarily from endoscopes. Endoscopes were the first devices that were suspected (in the 1980s) of causing nosocomal infections due to inadequate cleaning and disinfection. Acceptance criteria listed in the TIR recommends a three log reduction of bacterial challenges as a reasonable expectation. With regards to other markers, limited published data dating back to 2002 indicate that the average levels of markers after cleaning are as follows: Endotoxin < 2.2 EU/mL Protein < 6.4 ug/cm2 Carbohydrate < 1.8 ug/cm2 Hemoglobin < 2.2 ug/cm2

4.

Whether or not we can use these levels as acceptance criteria is questionable. For example, endotoxin molecules or LPS (lipid polysaccharide) are sticky molecules, which means they are difficult to remove from plastics, metals, and other polymeric components. To reduce them to 2.2 EU/mL would be challenging. If the product is not being used in blood contact direct applications then endotoxin challenges may have little value. AAMI TIR12: Designing, testing, and labeling reusable medical devices for reprocessing in health care facilities: A guide for medical device manufacturers This TIR has value in that it explains obligations that U.S. manufacturers have under the FDA labeling regulations (21 CFR 801). Additional FDA guidance is available at its Web site (http://www.fda.gov/cdrh/ode/198.pdf).

PRODUCT FAMILIES If a manufacturer supplies a number of different medical devices that share common features and attributes, these devices may be grouped for validation exercises into a product family. This should make it possible to select a product family member or master product that represents worst-case scenarios. The selection criteria should be documented in the validation documents. Master products are selected based on product-related variables that can affect the cleanability of the product families. You must demonstrate that you can bracket the product group with a challenge that is defined as being equally harsh to all devices. For example, all endoscopes have essentially the same features except for length. Therefore, the master product should be selected based on the worst-case cleanability assumption of length. However, materials and matted surfaces may allow you to choose something smaller if design warrants the selection. In any case, it would be a simple exercise to qualify the master product using a cleanability study protocol. This protocol would enable you to select the master product based on data collected during this notebook study. Once this master product is determined, adding products to the validation (by equivalency) can become a quick notebook study. Changes in materials can cause issues with wet ability and cleaning. Notebook studies can also be used for these material changes. THE LAST WORD ABOUT TIR12 The salient points of TIR12 are important to your facilitys technical staff. They cover items such as water quality for cleaning, cleaning implements, rinsing and precleaning, and labeling requirements for manufacturers that recommend manual cleaning. Manufacturers should develop test procedures (wipe tests) that can ascertain whether or not a device is clean. AAMI TIR12 references the ASTM E2314 Standard Test Method for determining the effectiveness of cleaning processes for reusable medical instruments using a microbiological method (simulated-use test). This test method, which is used in the lab setting, is useful to determine particulate or foreign material cleaning efficacy based on a nonpathogenic bacterial endospore suspended in artificial soil. This standard test has value regarding simulated use and cleaning efficacy. Bacterial endospores are used because they are more resistant to any microbiocidal effects of the cleaning process and solutions. Microtests cleaning studies procedure (MTL 1034) complies with this standard.

5.

DISINFECTION: ST-58 AND TIR7 Without cleaning and rinsing the medical device after patient use, it is impossible to achieve disinfection or sterilization of the device. Appropriate cleaning and rinsing removes all extraneous body fluids and tissues, as well as the majority of microorganisms and other residuals that may affect disinfectant chemical action. Disinfectants are categorized by Spaulding into the following scheme: HLD: High-level disinfectant used to treat critical to semicritical devices Example: 2.5% activated glutaraldehyde solutions and peracetic acidhydrogen peroxide mixtures Intermediate-level disinfectant used to treat noncritical medical devices Example: Phenolic compounds Low-level disinfectant used to treat noncritical and medical equipment surfaces Example: Benzalkonium chloride solutions

ILD:

LLD:

TIR7 is a guide to high-level disinfectant selection and use. It also defines which disinfectant classification to use with your device. The FDA uses the Spaulding classification to determine whether a medical device is a critical, semicritical, or noncritical device. Spaulding divided medical instruments and equipment into these three categories based on the risk of infection from contamination on the device. Critical devices are introduced directly into the human body, either into or in contact with the bloodstream or other normally sterile areas of the body. Critical devices present a high degree of risk of transmission of infection if contaminated and, therefore, must be sterile. Semicritical devices contact intact mucus membranes or nonintact skin during use, but do not usually penetrate the blood barrier or other normally sterile areas. If a semicritical device cannot be sterilized, it must be subjected to a high-level disinfection process in which a sterilant is used, though for a shorter exposure time than required to achieve sterilization. Noncritical devices or instruments, which pose the lowest risk of transmission of infection, usually contact only intact skin; these devices must be thoroughly cleaned and might require intermediate or low-level disinfection. Therefore, it is important to set selection criteria for a disinfectant. Each medical device is different and requires review prior to selection. TIR7s disinfectant selection criteria table describes general considerations, health and safety, effectiveness, material compatibility, and cost effectiveness. Material compatibility should be tested according to TIRs recommendations. Worst-case disinfection cycle times and conditions should be used for material compatibility studies. Once a disinfectant has been selected, it is highly recommended that you perform qualification studies prior to validation activities. You must select a disinfectant that is listed on the FDA Web site as cleared via the 510(k) process. The FDA has recently requested data on disinfectant log reduction without using a cleaning process. Although we disagree with this approach, we can offer it to our clients (MTL test #1035H). We believe that a simulateduse test that takes into account the combination of elements (cleaning, then disinfecting) is the appropriate approach.

6.

CONCLUSION I have summarized these standards and TIR documents to be helpful to the reader. The FDA is the driving force for requirements and approvals of 510(k) submissions. We have experienced an increase in cleaning and disinfection validation studies. As we see more published papers on devices, we gain more experience with acceptance criteria for soil challenges. Once we witness what the FDA does regarding reusable medical devices, we anticipate writing another white paper to augment this information. REFERENCES
ST-79: Comprehensive guide to steam sterilization and sterility assurance in health care facilities ST-81: Sterilization of medical devices: Information to be provided for the reprocessing of resterilizable medical devices ST-58: Chemical sterilization and high-level disinfection in health care facilities TIR7: Chemical sterilants and high-level disinfectants: A guide to selection and use TIR12: Design, testing, and labeling reusable medical devices for reprocessing in health care facilities: A guide to medical device manufacturers TIR30: A compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices ASTM E1837-96: Standard test method determining the efficacy of disinfection processes for reusable medical devices (simulated-use test) 6th Edition ASTM E2314-03: Standard test method for determination of effectiveness of cleaning processes for reusable medical instruments using a microbiological method (simulated-use test) Spaulding scheme in Seymour Block, Disinfection, Sterilization, and Preservation (5th Edition), published in 2000 by Lippincott Williams & Wilkins

POST SCRIPT
The FDA released a medical device reuse guidance document on May 2, 2011, following the publication of this paper. This preliminary document (Draft Guidance for Industry and FDA Staff Processing/Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling is available on the web site at (http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm252999.htm). It has been distributed for comment purposes only. The document raises some interesting conflictions between the AAMI TIR and the ASTM simulated use tests. First and foremost is the change from microbial challenges utilized for cleaning studies according to TIR-30. The guidance document recommends the use of a quantitative test method capable of measuring levels of clinically relevant soil (reference TIR 30:2003for recommended soils). Tests such has protein, hemoglobin, carbohydrate, and TOC challenges are recommended because they provide an absolute level of cleanliness compared to microbial challenges used in the past. The FDA does not recommend the use of spore log reduction testing as a method to determine effectiveness of the cleaning methodology. The FDA recommends 510 (k) biological indicators for all validation studies. The guidance document speaks to using worst-case conditions during all validation activities. Cleaning, disinfectant, and sterilization validation activities should be performed separately, since the purpose of each process differs. The processing overview is patient use, then point-of-use processing, then thorough cleaning followed by disinfection or sterilization.

7.

Human factors are covered under the guidance document. In essence you should validate your reprocessing instructions to ensure that the end users will be able to successfully understand and follow them. In the document are seven criteria to follow for reprocessing instructions: 1. 2. 3. 4. 5. Labeling should reflect the intended use of the device. All reprocessing instructions for reusable devices should advise users to thoroughly clean the device. The instructions should indicate the appropriate microbiocidal process for the device. Reprocessing recommendations should be technically feasible. The processing instructions should include only devices and accessories that are legally marketed (i.e., sterilizers with approved 510(k) applications or equivalent sterilizers). 6. The instructions should be comprehensive (time, temperature, concentrations, and other specifications should clearly defined). 7. The instructions should be understandable. Microtest has published a second pertinent reusable medical device paper, Five Steps to Validating the Cleaning Process of Medical Devices, that addresses item # 6, part f and g of the guidance document. This papers main subject covers the determination of safe levels of residual cutting and lubrication oils left on the product prior to implantation. Once promulgated, Microtest will publish a new white paper addressing the new FDA reusable medical devices guidance document. The paper will cover the industry trend for reusable device cleaning, which is transitioning from a microbialbased approach to analytical testing. We plan to address why the scope is changing, what guidance is on the horizon, and how Microtest has already implemented many of these changes.

8.

About Microtest
Microtest Laboratories is a leader in testing services and contract manufacturing for medical devices, pharmaceuticals, and biotechnology. Founded in 1984, the companys expertise and flexible processes enhance product safety and security, speed time to market, and minimize supply chain disruption. Mictrotests unique single-source capability to provide testing and manufacturing solutions allows the company to support a full pharmaceutical or medical device product release. Our facilities in Agawam, Massachusetts, include state-of-the-art aseptic manufacturing areas; analytical chemistry, microbiological, and virological laboratories; Class 100 clean rooms; onsite steam and ethylene oxide sterilization, plus depyrogenation capabilities; purified water systems; and voice/data systems.

About the Author

Steven Richter, Ph.D., is President and Chief Scientific Officer of Microtest Laboratories, Inc. Dr. Richter founded Microtest in 1984 after a distinguished career at the U.S. Food & Drug Administration. Under his leadership, Microtest has provided the medical device, pharmaceutical, and biotechnology industries with premier testing and manufacturing support.

For more information contact:

info@microtestlabs.com (800) 631-1680 www.microtestlabs.com

1-800-631-1680 1-413-786-1680 fax: 1-413-789-4334 Microtest Laboratories, Inc. 104 Gold St P.O. Box 848 Agawam, MA 01001 Microtest is a trademark of Microtest Laboratories, Inc. All other brands may be trademarks of their respective holders. 2011 Microtest Laboratories, Inc. All rights reserved. Printed in U.S.A. 1050026 1/11

9.