This guidance document is being distributed for comment purposes only.
Document issued on: May 2, 2011
Comments and suggestions regarding this draft document should be submitted within 90 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Alternatively, electronic comments may be submitted to http://www.regulations.gov . All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.
For questions regarding devices regulated by the Center for Devices and Radiological Health, contact Steven Turtil at (301) 796-6305, or by e-mail at firstname.lastname@example.org , or Sheila Murphey, M.D. at (301) 796-6302, or by e-mail at email@example.com. For questions regarding devices regulated by the Center for Biologics Evaluation and Research (CBER), contact the Office of Communication, Outreach and Development at 800-835-4709 or 301-827-1800 or firstname.lastname@example.org.
When final, this document will supersede “Labeling Reusable Medical Devices for Reprocessing in Health Care Facilities: FDA Reviewer Guidance” dated April 1996.
Additional copies are available from the Internet. You may also send an e-mail request to email@example.com to receive an electronic copy of the guidance or send a fax request to 240-276-3151 to receive a hard copy. Please use the document number (1644) to identify the guidance you are requesting.
Office of Communication, Outreach and Development, HFM-40
When final, this guidance will supersede Labeling Reusable Medical Devices for Reprocessing in Health Care Facilities: FDA Reviewer Guidance. This draft guidance document updates and clarifies the recommended content of, and review procedures for, premarket notification submissions [510(k)], premarket approval (PMA) applications, humanitarian device exemption (HDE) applications, and investigational device exemptions applications (IDE), concerning the labeling instructions for reprocessing reusable medical devices. In addition, this draft document provides more detail about FDA’s recommendations for the validation of processes intended to support reprocessing.
FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.
In recent years, there has been a significant advance in knowledge and technology involved in reprocessing reusable medical devices. Additionally, there has been an evolution towards more complex reusable medical device designs that are more difficult to clean and disinfect or sterilize. The revision of this guidance reflects scientific advances in this area. Under FDA labeling regulations, 21 CFR Part 801, a device must have adequate directions for use, which include instructions on preparing a device for use. Instructions on how to reprocess (i.e., clean and disinfect or sterilize) a reusable device are critical to ensuring a reusable device is appropriately prepared for its next use.
This guidance provides recommendations regarding reuse instructions in labeling for reusable medical devices and the validation of the recommended reprocessing process in the instructions. The recommendations are applicable to the three device reprocessing situations below.
Please note that while this guidance addresses all 3 of the above categories, the majority of devices addressed by this guidance are reusable devices. Accordingly, for editorial convenience, this document identifies “reusable devices” as the primary subject.
Some sections of the guidance are not applicable to single use devices initially supplied non-sterile. These sections are the establishment of the use life criteria for reusable devices (Criteria 6.l), as well as those that address cleaning instructions related to the removal of organic soil due to previous patient exposure.
This document is not intended to be an in-depth guidance on device design and testing factors related to infection control. Manufacturers should take infection control recommendations and practices into account during the design of reusable devices to facilitate cleaning and any necessary disinfection or sterilization. Design and testing factors are addressed in device-specific FDA guidance documents, when available for a particular device type.
Under FDA labeling regulations, 21 CFR Part 801, a device must have adequate directions for use, which include instructions on preparing a device for clinical use. Instructions on how to process (i.e., sterilize) a single use device intended to be sterilized prior to usage and provided non-sterile to the end user and reprocess (i.e., clean and disinfect or sterilize) a reusable device are necessary for ensuring that a device is effectively prepared for its clinical use.
B. Ensuring the Safety of Reusable Medical Devices
Both the manufacturer of the reusable medical device and the user of the device have roles to play in ensuring the safe and effective reprocessing of medical devices. Manufacturers of reusable medical devices should provide adequate labeling that includes instructions for reprocessing and reusing devices safely. The labeling should provide sufficient instructions on how to prepare the device for the next patient use. The user should be able to follow these instructions because they should refer to materials and equipment available to device users. The manufacturer should maintain in the Device Master Record and/or design history file as appropriate, documentation of tests that were performed to demonstrate that the instructions are complete and understandable and can reasonably be executed by the user. (The device master record must comply with the requirements of 21 CFR 820.181; the design history file must comply with requirements of 21 CFR 820.30(j).) The users should ensure that they have the facilities, equipment, and easy access to manufacturer-specified sterilization/disinfection agents to execute the instructions, and that the instructions are followed for every patient use of the device.
C. Process Overview
In general, reprocessing reusable medical devices involves three steps.
A more detailed overview of each reprocessing step is provided in Appendix A. In Section VI, this guidance provides FDA’s recommendations for developing reprocessing instructions that help users avoid errors during reprocessing. Instructions that are clear and easy to follow help assure devices are properly reprocessed and safe for reuse. In Sections VII to IX, this guidance describes FDA’s recommendations for testing your reprocessing methods to validate that both the instructions and the method can assure proper reprocessing and safe reuse. A simple process overview is presented below as Figure 1.
ALT TEXT -- Flowchart. Figure 1, process overview. Use leads to point-of-use processing (initial treatment to remove and/or prevent drying of soil and contaminants), which leads to thorough cleansing (and return to use, or). That leads to either disinfection (low, intermediate, or high level) or sterilization.
We recommend that you also refer to the following Technical Information Reports (TIR) developed by the Association for the Advancement of Medical Instrumentation (AAMI) when developing labeling instructions for reusable medical devices:
In accordance with 21 CFR Part 801, a device must have adequate directions for use, which for a reusable device should include reprocessing instructions. There are two components to establishing safe and effective reprocessing instructions:
Cleaning, disinfection, and sterilization are understood to be distinctly different processes.
Cleaning is the physical removal of organic soil, and the methods used for cleaning should be designed to remove such contamination effectively. Effective cleaning should:
In comparison, disinfection and sterilization processes are intended to kill microorganisms, and the agents employed for disinfection and sterilization should possess microbicidal properties. Accordingly, cleaning, disinfection, and sterilization steps should be validated separately and independently of each other since the purpose of each process differs.
An overview of reusable medical device processing is found in Appendix A of this document. Appendix C provides additional information on the definitions of common terms used. Appendix E provides additional resources, such as FDA labeling guidance documents, that may be useful when developing user instructions.
B. FDA Review of Reprocessing Instructions
FDA will review the labeling containing reprocessing instructions when we review premarket submissions for reusable medical devices. If the proposed labeling is deficient based on any of the criteria described within this guidance document, then FDA will inform you of the deficiency. In response, you may submit revised labeling, or alternatively, provide your rationale why the labeling is adequate. In the latter case, we recommend you include supporting documentation.
All cleaning, disinfection, and sterilization procedures should be validated, and validations should be completed prior to submission of your pre-market application to ensure that they meet the parameters you have indicated in your labeling. You may use current FDA recognized test methods available from standards organizations. (A searchable data base of FDA recognized consensus standards is available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm ).
When evaluating a 510(k), FDA generally compares the labeling for the legally marketed predicate device to the labeling for the new device. As part of the review process, FDA identifies differences and assesses the impact of the differences on substantial equivalence. However, reprocessing instructions for some older, predicate legally-marketed, reusable devices may not be consistent with state-of-the-art infection control procedures, so a labeling comparison alone will not be sufficient to demonstrate that a device is clean, disinfected, or sterile. If post-market experience indicates potentially unsafe reprocessing due to inadequate instructions, FDA may recommend that instructions be changed to address the need for improved reprocessing procedures to resolve reported adverse events. Reprocessing instructions should be tested to assure user needs and intended uses are met.
C. Resources for Developing Reprocessing Instructions
You should consult the resources listed below before developing reprocessing instructions for reprocessing reusable medical devices.
D. Human Factors in Developing Reprocessing Instructions
Your labeling should address the seven criteria below for clear reprocessing instructions to help ensure users understand and correctly follow the instructions.
Criterion 1. Labeling should reflect the intended use of the device.
Your labeling should include instructions for a reprocessing method that reflects the physical design of the device, its intended use, and the soiling and contamination to which the device is subject during clinical use. Appropriate reprocessing instructions depend on whether the device will:
When likely contamination may include human blood or body fluids capable of transmitting bloodborne pathogens, the requirements of the OSHA Standard 29 CFR 1910.1030 Occupational Exposure to Bloodborne Pathogens must be included in labeling. 6
Criterion 2. All reprocessing instructions for reusable devices should advise users to thoroughly clean the device.
In general, the effectiveness of each step in the reprocessing of a reusable medical device will influence the effectiveness of subsequent steps. The fact that adequate reprocessing depends upon the thoroughness of cleaning emphasizes the importance of ensuring the instructions to the user result in thorough cleaning.
Cleaning is only the first step in reprocessing. Details of the cleaning procedure will vary depending on the complexity of the device. See Section VIII for recommendations about the validation of cleaning processes. Devices with features which may result in soil retention, or have features that make them difficult to clean, will need to be disassembled in order to be completely cleaned. The instructions/diagrams for adequate disassembly should be included in the cleaning instructions.
The cleaning step should be described in the labeling as part of an overall reprocessing regimen. You should evaluate the rigor of the cleaning step in terms of its ability to eliminate organic soil from the device. The effectiveness of the cleaning step in making the device ready for the next patient will influence the effectiveness of subsequent processes, including any terminal processing.
Directions may include the use of protective covers on the device, to try to reduce the extent of cleaning needed before the device can be reused (e.g., bronchoscopes). If you recommend the use of protective covers, your labeling should include the recommendation to use only legally marketed protective covers. However, the cleaning and disinfection instructions for your device should assume the device is used uncovered, because of the potential for loss of cover integrity during use. Unnoticed loss of cover integrity may result in degrees of soiling that are difficult to see but will present a risk to the health of the next patient unless the device is properly reprocessed.
Criterion 3. The instructions should indicate the appropriate microbicidal process for the device.
Your instructions should be consistent with current infection control practice. The microbicidal process recommended should be sterilization, or high, intermediate, or low level disinfection, depending upon the intended use of the device.
FDA uses the Spaulding Classification 7 scheme described below for critical, semi-critical and non-critical devices to describe the effect of microbicidal processes on the potential risk of infection caused by the device. Because the Spaulding classification does not address all clinical device uses and reprocessing needs in detail, it has been modified as needed.
a. Critical Devices
Critical devices are devices that are introduced directly into the bloodstream or which contact a normally sterile tissue or body space during use. FDA recommends that you instruct end users to thoroughly clean and sterilize critical devices after each use. There is a likelihood of microbial transmission and risk of infection (subclinical or clinical) if the device is not sterile.
Examples of critical devices are surgical instruments and endoscopes used in sterile body cavities (such as laparoscopes, arthroscopes, intravascular endoscopes), and all endoscope biopsy accessories.
b. Semi-Critical Devices
Semi-critical devices are devices that contact intact mucous membranes or non-intact skin. They do not ordinarily penetrate tissues or otherwise enter normally sterile areas of the body. These devices should be reprocessed to be free from all microorganisms. However, intact mucosal surfaces are relatively resistant to small numbers of spores. FDA recommends that you instruct end users to thoroughly clean these devices and then reprocess them by high level disinfection or, if feasible, by sterilization.
Examples of semi-critical devices include endotracheal tubes, laryngoscope blades and other respiratory equipment, esophageal manometry probes, diaphragm fitting rings, etc. Means of high-level disinfection used in health care facilities include liquid chemical sterilants used at high level disinfection conditions and hot water pasteurization (often used for respiratory and anesthesia equipment reprocessing).
Endoscopes which contact intact mucosal surfaces may be used with invasive devices such as biopsy forceps. Therefore, sterilization may be preferable to high level disinfection if feasible. Heat-stable endoscopes (mostly rigid endoscopes) should be processed by steam sterilization. For heat-labile endoscopes, available "low temperature" reprocessing technologies include hydrogen peroxide gas plasma sterilization, ozone sterilization, ethylene oxide (EO) sterilization (the need for device aeration should be considered) and liquid chemical sterilant/high level disinfectant chemical systems used to provide either liquid chemical sterilization or high level disinfection. Note that whichever endoscope reprocessing method(s) is/are recommended, the compatibility of the endoscope with the method(s) and the ability of the method(s) to successfully reprocess the endoscope's lumen length and diameter should be validated and then stated in the Instructions for Use.
c. Non-Critical Devices
Non-critical devices are instruments and other devices whose surfaces contact only intact skin and do not penetrate it. Non-critical devices also include devices that do not directly contact the patient but may become contaminated with microorganisms and organic soil during patient care. FDA recommends thorough cleaning and then intermediate or low level disinfection for non-critical devices depending on the nature and extent of contamination. Items contaminated with blood or body fluids which may contain bloodborne pathogens should receive intermediate level disinfection with a product having an EPA-registered claim for activity against hepatitis B after cleaning. 8 Blood glucose meters are an example of a blood-contaminated device which has been a source of hepatitis B transmission during patient to patient use when not properly cleaned and disinfected and used with strict compliance with glove use and hand washing after glove removal.
Devices in contact with intact patient skin, or devices used in patient care which may become contaminated with patient microorganisms during use but are not visibly contaminated with blood or body fluids can usually be effectively prepared for safe reuse by cleaning and low level disinfection. Note that some disinfectants are also fairly effective cleaning agents while others are not. Consider the worst case microbes to which the device may be exposed during clinical use, the likelihood of significant organic soiling of the device during use and the ability of the device material to repeatedly withstand disinfectant contact when selecting a disinfectant to validate and then recommend for use with your device. Consider the products which are frequently used in health care settings when selecting a disinfectant to study and validate. If a product/product class can damage the materials in your device, your device label should include a warning not to use that product/class of products to reprocess your device. Be aware that in some clinical situations, isolation precautions recommended for use by CDC may include the use of specific disinfectants (i.e., patients with Norovirus infection, patients with Clostridium difficile infection). Always recommend that the user follow the specific EPA label disinfectant contact times when using the disinfectant. If your device has unsealed seams/crevices through which excessive liquid disinfectant could reach the interior of your device and damage it, you should caution users about this potential hazard and provide specific use instructions which can prevent it, such as avoiding the application of excess liquid to your device.
Examples of devices that contact only intact skin are blood pressure cuffs, stethoscopes, and skin electrodes. Examples of devices that have no direct patient contact, yet may become contaminated during patient care are infusion pumps and ventilators.
Other devices may not become contaminated with pathogens during use, may not require disinfection, and therefore may be suitable for use after cleaning only (e.g., room vital signs monitor).
Criterion 4. Reprocessing recommendations should be technically feasible.
Reprocessing recommendations should be technically feasible in the intended location (e.g., health care facility or home use). The equipment and accessories needed to implement the instructions should also be available in the intended location.
Users reprocessing reusable devices should have the ability to carry out the reprocessing steps. The type of sterilizer, and the manufacturer-validated sterilization cycle parameters and accessories should be available to the users. For example, radiation sterilization is generally only used in manufacturing facilities. Steam sterilization is the most common method of sterilization used in health care facilities. EO, gas/plasma, and liquid chemical sterilization processes are also available in many health care facilities. Dry heat and chemical vapor sterilization are less common.
FDA recommends that the instructions specify sterilization parameters that are technically feasible for the user. That is, sterilization cycle parameters in the labeling should be consistent with cycle parameters found on commonly available, legally marketed, sterilizers used in health care facilities. For examples of cycle parameters commonly found on health care steam and EO sterilizers at the time of this guidance, please see Appendix B.
FDA also recommends that, where possible, your validation data be generated in FDA-cleared sterilizers and with FDA-cleared accessories. Designing validation protocols in accordance with the conventional parameters represented in Appendix B provides assurance that your device is compatible with essential existing FDA-cleared equipment. Alternatively, you should address issues such as the chamber size and chamber load differences that may exist between "industrial" and "health care facility" sterilizer models, and you should address whether or not health care facility sterilizer cycles can actually replicate the cycle conditions achievable in larger industrial sterilizer models.
The expression “extended cycle” has gained common usage to describe any sterilization cycle that includes specifications that deviate from those found on commonly used, FDA-cleared sterilizers, and for which there are no FDA-cleared sterilization accessories. These extended cycles typically include longer exposure times and/or higher temperatures, but may also otherwise deviate from more conventional sterilization cycles. Implementation of such cycles poses serious technical challenges in health care facilities.
FDA advises against including extended cycle recommendations in product labeling for a number of reasons. Foremost among these reasons is that FDA evaluates physical and microbiological performance validation data and product labeling claims for discrete cycle parameter specifications as part of the clearance process for sterilizers and accessories. While many sterilizers are designed with manual over-ride controls for time and temperature, sterilizers are cleared only for those discrete cycle specifications for which FDA has received adequate validation data. When a sterilizer is cleared for a 10 minute, 135ºC, gravity cycle, there is no assurance that the physical performance of that sterilizer will be the same throughout a 20, 30, or 60 minute cycle. The user of a FDA-cleared sterilization wrap for which the Agency has evaluated physical and microbiological performance data for a 4 minute, 132ºC, pre-vacuum cycle, has no assurance that the performance characteristics of this wrap apply to a 8, 16, or 24 minute cycle, as it may no longer be able to maintain sterility. A similar rationale applies to the use of biological indicators and other process indicators to monitor cycles for which they have not been validated, or received FDA clearance. Therefore, FDA does not consider such extended cycles to be technically feasible for health care facility users.
Recommendations related to the validation of reprocessing and cleaning instructions are presented in Sections VII, VIII, and IX.
Criterion 5. The processing instructions should include only devices and accessories that are legally marketed.
Many products used in reprocessing reusable devices in health care settings are currently subject to FDA premarket notification as class II devices. These include sterilizers and accessories (e.g., sterilization wraps and containers) used in health care facilities, as well as liquid chemical sterilants and disinfectants intended for use in reprocessing medical devices. Many products used in initial cleaning steps are not “medical devices.”
Criterion 6. The instructions should be comprehensive.
Comprehensive instructions enable the user reprocessing the device to understand precisely how to implement the entire reprocessing procedure safely and effectively. There may be several acceptable formats for instructions.
Your reprocessing instructions should include the elements below. If any of the elements are not applicable to your type of device, you should state this in your premarket submission.
a. Special Accessories
The instructions should describe any special cleaning and disinfection or sterilization accessories that are needed for safe reprocessing. The instructions should also identify any special tools, sizes and types of brushes, trays, test kits, specific types of sterilization wraps, containers, or protective covers. Custom brushes should be included. The instructions should also provide sufficient detail so that the user can purchase the correct items or identify a source for the purchase of such items.
b. Special Pre-Processing Handling
As needed, labeling should include any instructions for special pre-processing handling. For example, for devices contaminated with protein material, a special pre-processing handling instruction that helps prevent drying of the device surface prior to cleaning may be appropriate as this will facilitate cleaning.
c. Disassembly and Reassembly
If the device consists of more than one removable part, then disassembly and reassembly instructions should be included to facilitate cleaning by the end user. The equipment needed to perform disassembly and reassembly activities should be included. For ease of use, labeling should include step-by-step instructions for disassembly and reassembly. Diagrams and/or illustrations are recommended. In addition, the instructions should indicate the location where the user performs the step, e.g., at the point of use.
Disassembly and reassembly instructions should be explicit, device specific, and should reflect the validation activities. Expressions such as “disassembly, if applicable” leave the determination of “applicability” to the discretion of the end user and such language should not be included. If a device must be disassembled for cleaning, the instructions should be validated to assure that proper reassembly can be performed, and should provide the end user with a method to verify that reassembly has been properly performed, to assure that the device is in operable condition for the next use. Disassembly and reassembly instructions should include information to inspect the device and components for wear and tear.
d. Method of Cleaning
The labeling should recommend a detailed validated method of cleaning. The method may be manual or mechanical (e.g., washer, washer/disinfector, ultrasonic washer). Cleaning instructions should include a list of the appropriate parameters for any recommended method.
For manual cleaning, the labeling should specify the duration of each processing step, temperatures, water quality, and other conditions. Similarly, for automated cleaning, the labeling should specify all processing conditions. The instructions should recommend equipment settings such as time, temperature, and maximum device load size.
Whether the cleaning method is manual or automated, the labeling should contain comprehensive directions for each cleaning, rinsing, and drying step, so that users can accurately follow the steps or program them into the device washer or washer/disinfector.
Labeling for medical devices that are at risk for becoming contaminated with patient materials through routine handling by health care workers should include instructions for surface cleaning. Even when only simple surface cleaning is recommended, the label should identify the suggested method, any cautions for specific locations or materials, any disassembly needed and any subsequent steps.
When surface cleaning is recommended for a device whose internal components, which are not contaminated during normal use, could be damaged by contact with liquids such as disinfectants, instructions should describe how to adequately clean the device without damaging it. Where appropriate, surface cleaning instructions should provide users with information on how to prevent disinfectant contact with internal device components that are not designed for contact with liquids.
e. Cleaning Agents
The instructions should recommend only cleaning agents or classes of agents (e.g., anionic detergents, surface-active detergent/disinfectants such as quarternary ammonium compounds, and enzymatic detergents) that were used during the cleaning validation studies and that have been demonstrated to be compatible with the device and are effective cleaning agents. Labeling should include instructions for the preparation and use of those agents, or refer to the cleaning agent labeling for preparation and use instructions (e.g., according to the detergent manufacturer’s instructions). Labeling should identify the recommended detergents, whether conventional and/or enzymatic, and include mixing instructions for the detergents if needed. Mixing instructions may be specific (e.g., mix 1 ounce of detergent per gallon of water), or may refer to the product instructions for the user (e.g., mix according to the detergent manufacturer’s instructions). Labeling for use on specific medical devices should be consistent with the EPA or FDA-cleared labeling for the product recommended for use.
Note: Instructions should be clear regarding the difference between cleaning (removal of soil) and disinfection (reduction of microbes), and labeling recommendations should reflect the distinction between the use of a cleaning agent versus a disinfecting agent.
f. Lubricating Agents
Use of lubricating agents is an effective way of extending the use-life of some medical devices. Lubricants may reduce the friction commonly associated with metal-on-metal movements, and thereby reduce device wear and corrosion, and extend the use-life of some medical devices.
Lubricants may be water-based or oil-based. If applicable, labeling for the reusable device should refer to the lubricating agent labeling for preparation and use instructions of those agents.
The instructions should recommend lubricating agents, or a class of lubricating agents (e.g., water soluble lubricants) that are compatible with the medical device, its intended use, and with any subsequent processing steps such as sterilization.
If your instructions specify the use of lubricating agents, then you should validate the device reprocessing methods based on the use of the agents under the conditions of use.
The labeling should recommend specific directions for rinsing after cleaning if appropriate and after use of liquid chemical sterilants / high level disinfectants to remove the processing chemical residues. These directions should include the type and quality of rinse water, volume, temperature, and duration of rinse. Rinsing may be manual or mechanical. If the rinsing instructions in the cleaning and disinfecting/sterilizing product's labeling are sufficient, then reusable device labeling may refer to those instructions.
Rinsing instructions should be validated to show that residual cleaning agents are reduced to a level that will not interfere with subsequent reprocessing steps, and that liquid chemical germicides are reduced to a level that is nontoxic.
FDA generally does not recommend saline solutions as the final rinse because saline solutions, when applied or after drying on the device, may interfere with subsequent disinfection or sterilization steps. Saline rinses may also lead to corrosion on certain devices, as well as to the build-up of inorganic residues.
h. Visual Inspection
All routine cleaning instructions should include instructions for visual inspection. The instructions should advise the user that if the device is determined to not be visually clean at the end of processing, the user should repeat the relevant, previous cleaning steps or alternatively, safely dispose of the device. Additionally, labeling should recommend visual inspection along with acceptance or failure criteria related to device performance (e.g., unacceptable deterioration, such as corrosion, discoloration, pitting, cracked seals), as well as instructions to properly dispose of devices that fail.
i. Method of Disinfection or Sterilization
For reusable devices intended to be disinfected or sterilized, labeling should specify at least one validated method for disinfection or sterilization.
Manufacturers of reusable devices should ensure that sterilization processes listed in labeling are compatible with the reusable device. Different microbicidal processes may be effective for different types of devices. Each type of process has its advantages and limitations. For example, heat-labile devices should be sterilized by a non-thermal process (e.g., chemical vapor, gas/plasma, or liquid chemical sterilant).
Specifications for sterilization equipment vary with manufacturers and models. Labeling should identify the particular sterilization method and type, and list the cycle parameters which you have validated.
Traditional sterilization processes, such as steam and EO, are sufficiently well-standardized among sterilizer manufacturers that sterilizer cycle identification may be limited to the critical cycle parameters. (Accessories for these sterilization processes also may be identified using only the critical cycle parameters.) Refer to Appendix B for typical parameters of sterilization cycles currently used in health care facilities.
Sterilization processes using newer low temperature chemical sterilization methods vary in proprietary characteristics from one device manufacturer to another. Therefore, for these sterilization processes (e.g., hydrogen peroxide (H2O2), and ozone (O3)), the manufacturer of the device, the sterilizer model, and the specific cycle identification (name or cycle parameters) should be specifically identified in labeling. (Accessories for these sterilization processes should be labeled by the accessory manufacturer to specify sterilizer manufacturer, sterilizer model, and sterilizer cycle name and/or cycle parameters.)
For all methods, complete cycle specifications should include all critical cycle parameters and other pertinent information that identifies the cycle. For example:
j. Special Post-Process Handling
Instructions should include special post-processing procedures, as needed, in order to reduce or eliminate recontamination before use or reuse.
For example, labeling should include instructions for reducing sterilant residuals (e.g., by aeration) during post-process handling after a process that may leave sterilant residuals on the device such as sterilization by EO or vaporized hydrogen peroxide. Labeling should recommend a post-processing aeration time that is consistent with the maximum acceptable levels of residuals.
In the case of EO sterilization, CDRH has accepted EO residuals information based on the recognized standard, ANSI/AAMI/ISO 10993-7:2008 “Biological Evaluation of Medical Devices – Part 7: Ethylene Oxide Sterilization Residuals.”
Active device drying is another post-processing procedure which may reduce or eliminate recontamination of unwrapped devices after high level disinfection/liquid chemical sterilization reprocessing of devices because they will be wet at the end of reprocessing. Labeling should recommend that the user thoroughly dry the device, after processing and before storage, to inhibit any subsequent growth of waterborne microbes.
Labeling should also recommend a validated drying time specification for terminal sterilization methods for wrapped/contained devices. Moisture remaining on wrapped/contained product after sterilization could compromise the package integrity and performance by impairing the sterile barrier properties of the packaging materials and the effectiveness of the seals.
The reprocessing procedure should minimize or eliminate delays between steps. Delays should be avoided because delays may create conditions favorable to microbial growth or colonization, which may increase the challenge to subsequent steps such as cleaning and disinfection/sterilization. For example, delays between point-of-use pre-processing and cleaning may create conditions that promote biofilm formation. Organic contamination, such as biofilms, may increase the challenge to cleaning, and may also inactivate or prevent full penetration of a disinfectant or sterilant. Such time delays should therefore be kept to a minimum.
The time interval between cleaning and sterilization, i.e., complete processing, is also important. If complete processing is delayed, labeling should recommend an intermediate and effective drying step before any delayed sterilization.
l. Reuse Life
The labeling should inform the user how many times, based on testing, the device can be reused; or provide the user with a mechanism or method to ascertain whether the device has exceeded its use-life.
This may be done by validating the number of times the product can be reprocessed and reused, and providing this specification in the labeling. For example, the labeling for a reusable device may state the maximum number of reuses and provide a specific tracking method.
Alternatively, labeling should provide the user with a method to establish that the device is still within performance specifications and instructions to dispose of devices that fail. Examples include:
m. Special Label Designations, Warnings, and Precautions
Single use devices that are initially supplied non-sterile to the end user and require the end user to sterilize the device before use, and reusable devices that are initially supplied non-sterile to the end user and require the end user to sterilize the initial packaged device and to subsequently reprocess the device after initial use (i.e., cleaning and sterilization), should be prominently labeled "Non-sterile" in large type directly on the manufacturer’s original device package in a manner which precludes separation of "Non-sterile" from the device.
Labeling should include any special warnings or precautions about the reprocessing procedure, when warranted. These may be related to user safety or emphasize conditions that could significantly alter the safety or effectiveness of reprocessing or the performance of the device.
n. Patient or Lay Use
Devices that are intended to be maintained by a patient or lay care provider (e.g., family member or other) should have reprocessing instructions which are understandable to a lay person, and which can be performed at home. The equipment and accessories needed to implement the instructions should also be readily available in the intended location of use.
See also FDA’s “Guidance on Medical Device Patient Labeling.” 10
o. Reference to Guidelines or Accessory Labeling
The labeling of the reusable device, in addition to all of the recommendations set forth in this guidance, may also refer the user to professional organization’s clinical practice guidelines, the clinical guidelines of the CDC, or the OSHA Standard 29 CFR 1910.1030 Occupational Exposure to Bloodborne Pathogens 6 for the additional education of users. Please note that such clinical practice guidelines may not always accurately reflect regulatory considerations for medical devices and should not be used in place of the recommendations of this guidance. The regulatory label of a medical device or a disinfectant cleared by EPA or FDA should always be followed when recommending product use.
Referencing the labeling of devices used in reprocessing, for example, an endoscope washer-disinfector, may be acceptable, as long as the referenced labeling is relevant and consistent with the reusable device’s labeling. For instance, labeling for an endoscope may refer, in part, to endoscope washer-disinfector labeling for certain details on scope reprocessing (e.g., placement in chamber).
p. Telephone Number to Request Information
The manufacturer of the reusable device is the appropriate contact for user questions about the reprocessing procedures. The instructions for reusable devices should include a telephone number and email address to obtain additional information about reprocessing the device, including questions on infection control procedures for the device. You may also provide your internet address.
Criterion 7. The instructions should be understandable.
Instructions should be clear, grammatically correct, legible, and in logical order from the initial processing step through the terminal processing step (e.g., pre-processing, disassembly, cleaning, rinsing, reassembly, disinfection or sterilization, final rinsing after disinfection or liquid chemical sterilization, and post-process handling). The instructions should be written in simple language to the greatest extent possible, although they should also be sufficiently detailed to explain the correct procedures for all steps.
Instructions should be in grammatically correct English. 11 Where applicable, instructions may include technique diagrams or other graphic representations designed to communicate recommended practices. However, any graphics should be accompanied by clarifying text. The instructions should be validated as described in Section V.D. of this guidance to ensure that users will be able to understand and follow them.
Manufacturers must validate the design (including reprocessing instructions) of reusable devices and reprocessing procedures associated with reuse in accordance with the Quality System regulation (21 CFR Part 820) to make certain the device can be effectively reprocessed over its use life.
For devices that are subject to design controls under 21 CFR 820.30, labeling (e.g. reprocessing instructions) must be considered during design validation to assure user needs and intended uses are met. The human factors methods used should ensure that the characteristics of the user population and operating environment are considered. (21 CFR 820.30(g)) See Section V.D. of this guidance for more information about human factors in developing reprocessing instructions.
Cleaning and sterilization processes require process validation which provides a high degree of assurance that a device will consistently meet predetermined specifications. (21 CFR 820.75)
This section describes FDA’s recommendations on the validation of processes designed to clean reusable medical devices. Although many FDA-recognized consensus standards related to medical device sterilization are currently available, no standards and no dedicated guidance is currently available related to medical device cleaning.
FDA recommends that the establishment of cleaning methods include two steps.
First, you should develop the cleaning process and instructions, including disassembly if needed. Second, you should conduct validation activities to demonstrate that your methods are adequate to allow the device to undergo further processing and to eventually be reused; and that your reprocessing instructions are effective in conveying the proper reprocessing methods.
Labeling of reusable devices should provide detailed, validated cleaning specifications for routine device processing. This labeling should indicate all parameter specifications for each step of the process, including, for example, time and temperature. Where applicable, this may include specific set points and tolerances or ranges.
Time, temperature, concentration, and other specifications for each step of the process should be specific. Ambiguous or incomplete instructions such as “rinse at room temperature,” or “allow device to dry under ambient conditions” are generally inadequate.
B. Validation of the Cleaning Process Using Worst Case Testing
FDA recommends you validate your recommended cleaning process. Your validation activities should be based on comprehensive validation protocols that use soils that are clinically relevant to the type of device. These should include the worst case (least rigorous) implementation of the cleaning process, medical devices that represent worst case (most contaminated) test devices, and chosen test methods that are related to the clinically relevant soil. Specify predetermined cleaning test endpoints. These protocols should be designed to establish that the most inaccessible locations on your devices can be adequately cleaned during routine processing.
For all testing, you should choose a statistically significant number of replicate samples to support the validity of any instructions based on the tests being performed.
C. Resources for Establishing Simulated Use Protocols
FDA recommends the use of worst case simulated use protocols throughout the validation of the cleaning process. Where applicable, clinicians should be consulted to determine the physical extent of “real world” worst case device contamination. Also, practicality and human factors issues should be considered when establishing your simulation protocols. In addition, the AAMI publication TIR 30:2003, “A compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices” provides a summary of soils and soil recipes that is available in the literature.
D. Documentation of Validation of Reprocessing Methods in Submissions
The nature of the documentation to be submitted to FDA for the validation of your reprocessing process and instructions will depend upon the nature of your application or submission. While all cleaning, disinfection, and sterilization procedures should be validated, the documentation recommended for each type of submission or application is described below.
1. Documentation in Premarket Submissions
A PMA or HDE should include a complete report of the validation of the reprocessing instructions in the manufacturing and design section.
FDA intends to review the reprocessing validation in the same manner as the other manufacturing and design data.
A 510(k) should include validated labeling instructions for reprocessing, based on this guidance. The validation of the reprocessing instructions is part of the QS regulation requirements, 21 CFR Part 820, and may be evaluated during FDA inspections.
A complete report of the validation of the cleaning and reprocessing instructions need not necessarily be included in a 510(k) submission. However, FDA staff may request this data, which the manufacturer should have on file according to 21 CFR Part 820, if submission of validation data is recommended in a specific guidance or on a for cause basis.
2. Documentation in IDEs
An IDE should include a summary of the validation of the reprocessing instructions, when completed.
FDA intends to use judgment when considering the extent of the data needed prior to the initiation of clinical studies to document the safety of the recommended reprocessing process for the device. Validation of all reprocessing methods should be completed prior to approval.
FDA recommends that you follow the recommendations in product specific FDA Guidance documents, as well as those found in standards that are recognized by the FDA consensus standards program, which can be found in FDA’s consensus standards database. 12
FDA recommends that you follow the guidance entitled “Updated 510(k) Sterility Review Guidance K90-1” 1 and any applicable FDA recognized standards.
As stated previously, FDA recommends that, where possible, your validation data be generated in FDA-cleared sterilizers and with FDA-cleared accessories. Alternatively, you should adequately address issues such as the chamber size and chamber load differences that may exist between "industrial" and "health care facility" sterilizer models. In addition, you should address whether or not health care facility sterilizers have been validated by their manufacturers for the sterilizer cycle parameters which are recommended and whether FDA-cleared sterilization monitoring accessories such as biological indicators and other process indicators, sterilization wrap, etc. have been labeled for use with the sterilizer cycle parameters and are available to health care facility users.
FDA recommends that that you propose and validate sterilization cycle specifications that are in accordance with the conventional parameters represented in Appendix B to provide assurance that your device is compatible with necessary FDA-cleared equipment, and may be validly implemented by end users.
As it is difficult for the health care workers responsible for reprocessing reusable devices to assess the amount and resistance of microbial contamination on the devices to be reprocessed, product labeling, professional practices, and institutional infection control procedures help guide the persons who are responsible for reprocessing devices.
Proper handling and reprocessing of reusable medical devices for the next patient is done by carefully adhering to general reprocessing steps described in the following detailed overview, presented as Figure 2.
We recommend that all reusable medical devices be designed and constructed to allow adequate cleaning, because if a device can not be adequately cleaned, any subsequent disinfection or sterilization process may not be effective.
Additional information on reprocessing for some specific devices, such as endoscopes and ultrasound transducers, is available from FDA in our database of guidance documents and by consulting specific review divisions.
STEAM STERILIZATION CYCLES
Table 1. Cycle Times for Gravity-Displacement Steam Sterilization Cycles
Table 2. Cycle Times for Dynamic-Air-Removal Steam Sterilization Cycles
Table 1 and 2 modified and reprinted with permission from ANSI/AAMI ST79:2010 & A1:2010 Comprehensive guide to steam sterilization and sterility assurance in health care facilities. Published by the Association for the Advancement of Medical Instrumentation (AAMI). (C) 2010 AAMI www.aami.org.
EO STERILIZATION CYCLES
Table 3. EO Parameter Specification Ranges
Burgess DJ, Reich RR, Ethylene Oxide Sterilization: Scientific Principles. In Reichert M, Young JH (eds.), Sterilization Technology for the Health Care Facility. 2nd ed. Aspen Publishers, Inc. Gaithersburg, MD. 1997
The following are common microbiological terms that may be used in reprocessing instructions in device labeling derived from referenced literature.,,,,,, The list is not exhaustive. Additional definitions of terms can be found in the referenced literature.
Listed from Most Resistant to Least Resistant.
Modified from Favero, M.S. and Bond, W.W., Chemical Disinfection of Medical and Surgical Materials. In: Disinfection, Sterilization, and Preservation, 5th Ed Phila: Lippincott Williams & Wilkins 2001: 881-917.
The following additional references may be useful resources:
1 Updated 510(k) Sterility Review Guidance K90-1; Final Guidance for Industry and FDA issued August 30, 2002
3 Association for the Advancement of Medical Instrumentation, Designing, testing, and labeling reusable medical devices for reprocessing in health care facilities: A guide for medical device manufacturers, AAMI TIR12:2004, Arlington, VA: AAMI, 2004. Technical Information Report.
4 Association for the Advancement of Medical Instrumentation, A compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices, AAMI TIR30:2003, Arlington, VA: AAMI, 2003. Technical Information Report.
5 Medical Device Use-Safety: Incorporating Human Factors Engineering into Risk Management ucm094461 issued July 18, 2000.
7 Spaulding, EH The role of chemical disinfection in the prevention of nosocomial infections. In: Brachman PS, Eickoff TC, eds Proceedings of the International Conference on Nosocomial Infections, 1970. Chicago: American Hospital Association, 1971:254-274
8 Center for Disease Control and Prevention (CDC), “Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008.
11 21 CFR 801.15(c)(1)
13 Pflug, I.J., Microbiology and Engineering of sterilization Processes, 7th ed. Minneapolis, Environmental sterilization Laboratory. 1990, Chapters 1-3.
14 Sehulster LM, Chinn RYW, Arduino MJ et al Guidelines for environmental infection control in health care facilities, 2003.
16 Association for the Advancement of Medical Instrumentation (AAMI). Sterilization of health care products-Vocabulary. ANSI/AAMI/ISO TIR11139:2006.
17 Block SS, Definition of Terms In: Block SS, ed. Disinfection, Sterilization and Preservation, 5th ed. Phila: Lippincott Williams & Wilkins 2001:19-28.