FDAwasher WorstCase

Stakeholder Validation

Stakeholder ArtificialSoils

Stakeholder DifficultLocations

Stakeholder EndPoints

Stakeholder FluidExtraction

Stakeholder Endotoxin

FDALiquidDisinfectant WorstCase

FDALiquidDisinfectant SimulatedUse

SUDReprocess WorstCase

SUDReprocess CleaningTestMethod

SUDReprocess EndPoints

SUDReprocess Validation

SUDReprocess ProcessValidation

ScopeAdvisory Labeling

ScopeAdvisory AERlabeling

SUDstakeholder CleaningInstructions

SUDstakeholder Validation

SUDstakeholder Endpoints
Class II Special Controls Guidance Document: Medical Washers and Medical Washer-Disinfectors; Guidance for the Medical Device Industry and FDA Review Staff:

Simulated-use testing should evaluate the performance of the medical washer-disinfector under “worst case conditions.” FDA defines “worst case conditions” as testing at the minimum parameters for the process variables in each cycle.


FOOD AND DRUG ADMINISTRATION SECOND ANNUAL CDRH/CBER MDUFMA STAKEHOLDER MEETING Gaithersburg, Maryland Thursday, November 18, 2004

Comments of Steve Turtil, scientific reviewer in the Office of Device Evaluation:

The next thing we wanted to see was validation of those cleaning instructions and that is when these things are used in the worst conceivable way, when they are really, really soiled and when they go through the cleaning in the worst conceivable way, the shortest times, the lowest concentrations of detergents, we want to know that we are still going to be reaching acceptable end points.


Guidance for Industry and FDA Reviewers Content and Format of Premarket Notification [510(k)] Submissions for Liquid Chemical Sterilants/ High Level Disinfectants Document issued on: January 3, 2000:

III.H.4. Simulated-Use and In-Use Tests: d. Simulated-use Testing 2) Incorporate other factors into the test that impede cleaning and germicide activity, e.g., a representative inorganic and organic challenge added to the inoculum. Include an organic challenge representative of the type of worst case organic load to which the device is exposed during actual use, such as serum, blood, and secretions, and may remain associated with the device following cleaning.


Guidance for Industry and FDA Reviewers Content and Format of Premarket Notification [510(k)] Submissions for Liquid Chemical Sterilants/ High Level Disinfectants Document issued on: January 3, 2000:

III.H.3. Potency Tests 2) Worst case conditions for a reused germicide - a germicide from a production run, stored to expiration, stressed to the end of its claimed reuse life, and diluted to its minimum recommended or effective concentration, if necessary. Incorporate into the simulated reuse protocol any factors that may impact the performance of the germicide, such as an organic load, dilution, water quality, temperature variation, and pH changes.


FOOD AND DRUG ADMINISTRATION SECOND ANNUAL CDRH/CBER MDUFMA STAKEHOLDER MEETING Gaithersburg, Maryland Thursday, November 18, 2004

Comments of Steve Turtil, scientific reviewer in the Office of Device Evaluation:

So again we took a real close look at what sort of artificial soils were used and the simulated use protocols, then we took a look at the cleaning validation protocols to make sure that they were really worst case, and we wanted to see finally all the details for the test protocols, cleaning end points, and other information. The cleaning validation protocols should support and confirm the effectiveness of the routine cleaning instructions and should include consideration of -- and again this is very, very abridged, we spent a lot of time with this, it's very elaborate, the details we were looking at, very device specific, but  we'd want to see that the soil that's used, artificially soilees(?), represents intended clinical exposure.


FOOD AND DRUG ADMINISTRATION SECOND ANNUAL CDRH/CBER MDUFMA STAKEHOLDER MEETING Gaithersburg, Maryland Thursday, November 18, 2004

Comments of Steve Turtil, scientific reviewer in the Office of Device Evaluation:

In the test protocols, we want to see all the details, cleaning end points,


FOOD AND DRUG ADMINISTRATION SECOND ANNUAL CDRH/CBER MDUFMA STAKEHOLDER MEETING Gaithersburg, Maryland Thursday, November 18, 2004

Comments of Steve Turtil, scientific reviewer in the Office of Device Evaluation:

In addition when it comes to simulating use, we want to make sure that the most difficult locations on the device are soiled, we want to see that the duration of soiling is equivalent to what we would expect in clinical use, worst case, and when it came to use of the device,


FOOD AND DRUG ADMINISTRATION SECOND ANNUAL CDRH/CBER MDUFMA STAKEHOLDER MEETING Gaithersburg, Maryland Thursday, November 18, 2004

Comments of Steve Turtil, scientific reviewer in the Office of Device Evaluation:

we want to know that after these things are cleaned, the test is performed on them on the extraction fluid is representing really what has been left on the device, and the test methods -- just basic methods validation should be performed for these, you know, proper controls, standards and calibrations.


FOOD AND DRUG ADMINISTRATION SECOND ANNUAL CDRH/CBER MDUFMA STAKEHOLDER MEETING Gaithersburg, Maryland Thursday, November 18, 2004

Comments of Steve Turtil, scientific reviewer in the Office of Device Evaluation:

So we are looking for data for that and also for those devices that are labeled non-pyrogenic, we want to make sure that all the proper endotoxin levels are reached.


Guidance for Industry and FDA Staff - Medical Device User Fee and Modernization Act of 2002, Validation Data in Premarket Notification Submissions (510(k)s) for Reprocessed Single-Use Medical Devices: Document issued on: September 25, 2006: III. Specific Validation Data Recommendations 

Document all potential worst case degrees and type of contamination, as applicable, such as blood and other body fluids, fecal material, tissues, lubricants, and residual cleaning agents. The methods and results should document effectiveness of the agents on the specific device under the worst case contamination conditions.


Guidance for Industry and FDA Staff - Medical Device User Fee and Modernization Act of 2002, Validation Data in Premarket Notification Submissions (510(k)s) for Reprocessed Single-Use Medical Devices: Document issued on: September 25, 2006: III. Specific Validation Data Recommendations

Describe the cleaning endpoint used in the tests and the rationale for the endpoint. Describe the sensitivity, specificity, reproducibility, accuracy, and precision (as applicable) of the analytical test methods for determining that the endpoint is achieved, (i.e., the device is clean).

Note: Tests demonstrating a reduction in contamination levels alone are insufficient as an endpoint. Although the common definition of a clean device is one that is visually free of contamination, this condition should be translated by the reprocessor into an objective and measurable endpoint specification. The endpoint should have a visual component but should be supplemented with chemical, microbiological, and/or other physical parameters with tolerances. Devices should not have an endpoint based on visual examination alone. Tests should demonstrate that the cleaning endpoint is achieved independently of subsequent process steps. Test methods may utilize simulations of contamination under controlled lab conditions; however, actual contamination should be used to complete validation testing.


Guidance for Industry and FDA Staff - Medical Device User Fee and Modernization Act of 2002, Validation Data in Premarket Notification Submissions (510(k)s) for Reprocessed Single-Use Medical Devices: Document issued on: September 25, 2006: III. Specific Validation Data Recommendations

Document the cleaning test methods, acceptance criteria, analysis and test results. The results should demonstrate the effectiveness of the cleaning agents when used as labeled or as intended by the reprocessor.


Guidance for Industry and FDA Staff - Medical Device User Fee and Modernization Act of 2002, Validation Data in Premarket Notification Submissions (510(k)s) for Reprocessed Single-Use Medical Devices: Document issued on: September 25, 2006

12. How does FDA interpret the scope of validation data required under MDUFMA? FDA interprets validation data as broad in scope, including information about processing at the point of use to the completion of packaging and sterilization, and other post-process considerations. This guidance provides more discussion on validation data in Section III. Cleaning, sterilization, and functional performance validation of reprocessed SUDs include aspects of both design validation and process validation. Design validation, in this case, should incorporate both the design of the product and the design of the processes to be used in reprocessing the device. FDA interprets the cleaning process to include all steps to remove, inactivate, or contain contamination, beginning immediately after clinical use of the device, and all subsequent steps to decontaminate and clean a device up to packaging and prior to the first step of the sterilization process. This includes all quality control tests. A clean device, as specified by the reprocessor, should be the input for the sterilization process. FDA interprets the sterilization process as beginning after packaging and any preconditioning other than cleaning (e.g., prehumidification for ethylene oxide (EO)) to the end of any post-process conditioning. Manufacturers should assess functional performance after the cleaning and sterilization process validations. Successful process validations then support the overall design validation. The results of the cleaning and sterilization validations provide objective evidence that the particular requirements for a specific intended use can be consistently fulfilled and are equivalent to those of the predicate device.


Guidance for Industry and FDA Staff - Medical Device User Fee and Modernization Act of 2002, Validation Data in Premarket Notification Submissions (510(k)s) for Reprocessed Single-Use Medical Devices: Document issued on: September 25, 2006: III. Specific Validation Data Recommendations

Process Validation: The purpose of process validation is explained above. There are three steps used in process validation that can be adapted to a cleaning process, including both equipment and manual procedures. These steps are installation qualification, operational qualification, and performance qualification. The submission should provide a summary of each of the process validation steps as they apply to the reprocessing of the specific device: The installation qualification can be briefly summarized. For purposes of a 510(k), FDA is primarily interested in a summary of the operational and performance qualification where test and actual loads or sample runs are evaluated. The operational qualification summary data should demonstrate that the cleaning equipment is capable of delivering the specified process within defined tolerances. The performance qualification summary should demonstrate that multiple consecutive runs of the cleaning process with the specific type of device achieve the specified outcome. Explain any failures of the process and means to correct the process. The qualification should demonstrate effective and safe reprocessing after the defined number of iterations specified by the reprocessor.


CDRH/CBER MDUFMA STAKEHOLDER MEETING PRESENTATION SLIDES, November 18, 2004, Washingtonian Marriott, Gaithersburg, Maryland: Reuse of Single Use Devices CDRH/CBER MDUFMA Stakeholder Meeting Presented by: Barbara Zimmerman

Cleaning Process:

Cleaning Instructions should specify: Point-of-Use Decontamination Disassembly, if possible Automated or Manual cleaning, or a combination – time, temperature, brushing duration, etc. Ultrasound – time, temperature, setting (high, medium, low) Detergents, Enzyme Detergents – time, temp., concentration, cycle limit (replenishing) Intermediate Rinse Steps – time, temp., particular water quality specifications.


FDA and CDC PUBLIC HEALTH ADVISORY: Infections from Endoscopes Inadequately Reprocessed by an Automated Endoscope Reprocessing System, September 10, 1999

FDA has also requested that the labeling of the AER include instructions for reprocessing specific models of endoscopes. The instructions should be based on the results of validation studies with the specific endoscope models. The 1993 FDA guidance for AER manufacturers recommended that the AER labeling: list all brands and models of endoscopes that are compatible with the AER; identify the AER’s limitation to process certain brands and models of endoscopes and accessories, or identify the endoscopes and accessories that cannot be reliably reprocessed in the AER; and be compatible with the endoscope manufacturer’s cleaning and disinfection instructions.


FDA and CDC PUBLIC HEALTH ADVISORY: Infections from Endoscopes Inadequately Reprocessed by an Automated Endoscope Reprocessing System, September 10, 1999

Manufacturer Labeling for Endoscopes and AERs Endoscope users should be aware that FDA requires certain information in the labeling of these devices. Since 1996, the Agency has requested manufacturers of reusable medical devices to recommend at least one reprocessing method in their device labeling. The level of reprocessing should be based on the device’s contact with the patient and the risk for disease transmission. Generally, endoscope manufacturers provide manual reprocessing instructions for each endoscope model. Following these instructions should result in endoscopes that are patient-ready.


CDRH/CBER MDUFMA STAKEHOLDER MEETING PRESENTATION SLIDES, November 18, 2004, Washingtonian Marriott, Gaithersburg, Maryland: Reuse of Single Use Devices CDRH/CBER MDUFMA Stakeholder Meeting Presented by: Barbara Zimmerman

Cleaning Validation Protocols

Should Include WORST CASE consideration of: Automated, Manual or a combination – time, temperature, brushing duration Ultrasound – time, temperature, setting (high, medium, low) Detergents, Enzyme Detergents – time, temp., concentration, cycle limit (replenishing). Intermediate Rinse Steps – time, temp., particular water quality specifications.


CDRH/CBER MDUFMA STAKEHOLDER MEETING PRESENTATION SLIDES, November 18, 2004, Washingtonian Marriott, Gaithersburg, Maryland: Reuse of Single Use Devices CDRH/CBER MDUFMA Stakeholder Meeting Presented by: Barbara Zimmerman

Test Protocols and Cleaning Endpoints:

Specify the endpoints of cleaning, and data should meet them – at the end of its use-life. Visual Inspection should be part of both the routine cleaning and the cleaning validation (yet realize the limitations: e.g., lumens). Extraction method should be validated. Test methods should be validated.