Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling Part5

Validation of Cleaning Process

This section describes FDA’s recommendations on how to comply with the QS requirements

discussed in the previous section regarding the validation of processes designed to clean reusable medical devices. Although many FDA-recognized consensus standards related to medical device sterilization are available, limited standards or guidances are currently available regarding
cleaning of medical devices.

You should conduct validation activities to demonstrate: 1) that your methods (manual or

mechanical) are adequate to allow the device to undergo further processing and to eventually be reused safely; and 2) that your reprocessing instructions are effective in conveying the proper reprocessing methods to the user.

A.     Validation of the Cleaning Process Using Worst-Case Testing

You should validate the cleaning process you provide in your labeling. Your validation
activities should be based on comprehensive validation protocols that use soils that are
relevant to the clinical use conditions of the device. These should include the worst-case
(least rigorous) implementation of the cleaning process, medical devices that represent
the worst-case (most challenging to reprocess and most contaminated), and at least two
quantitative test methods that are related to the clinically relevant soil. The cleaning

process validation protocols should 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 justifiable number of replicate samples to support the validity of any instructions based on the tests being performed.

1.  Artificial Soil, Inoculation Sites, and Simulated Use

Implementation of a well-established, simulated use test protocol should be an integral part of reprocessing validation.

a.  Artificial Soil

The manufacturer should select an artificial test soil, the composition of which
accurately represents materials that the device would likely be exposed to during

an actual clinical use, and would create the greatest (worst-case) challenge to the
cleaning process. For example, a laryngoscope is intended to provide visualization
of the larynx as part of a medical procedure, including facilitation of tracheal
intubation, cardiopulmonary resuscitation, and surgery in this anatomical location.
A laryngoscope would likely be exposed to both blood and mucus. Therefore, to
simulate a worst case cleaning challenge, the artificial test soil should be a multi-
component soil that includes substances that simulate both blood and mucus. Note
that conducting separate cleaning validations for blood and mucus individually
would not be representative of a worst case challenge, because the mixture of
blood and mucus is more difficult to clean.

The artificial test soil chosen should allow at least two clinically relevant soil
components to be quantified for validation testing (e.g., total organic carbon,
protein).

FDA does not recommend the use of spore (or any other microbial marker) log
reduction testing as a method to determine the effectiveness of the cleaning
method. Currently, there is lack of adequate scientific evidence regarding whether
or not the removal of bacterial spores directly correlates to the removal of clinical
organic soil from the devices. Such testing only indicates how well a process
reduces spore count and provides no information on any other component of
organic soil.

b.  Inoculation Sites

Soil inoculations should mimic worst-case clinical use conditions. We

recommend you use the artificial soil to inoculate the device in all locations likely to contact patient materials, including all locations that are difficult to clean.

c.  Simulated Use Conditions

Simulated use conditions for the validation studies should be considered,

especially for devices with features at risk for the accumulation of soil with

repeated use. In such cases, your validation studies should use devices that have
undergone some simulated use. Your validation studies should incorporate
multiple full use cycles and should be designed to assess the accumulation of soil
over time. The number of simulated use cycles that you use should be
scientifically justified.

If the device is powered or becomes hot during clinical use, these situations should be replicated during simulated use testing. Examples of such devices include powered hand-pieces and electrosurgical instruments.

Simulated use conditions should account for real-world use conditions to mimic
worst-case clinical use (e.g., the worst-case duration of clinical exposure). You
should also conduct all functional procedures (repeated articulations, flexures,

manipulations) for which the device is intended in order to soil the device sufficiently to represent worst-case conditions.

If the device is likely to be repeatedly subjected to “pushing” soil into a hard to
reach area during use, validation soiling should include repeated soiling to
adequately reproduce such a “worst-case” use situation. If after clinical use of the
device, drying of soil might occur and cleaning might not be performed
immediately after use (such as with loaner devices that will be shipped without
adequate reprocessing), the validation methods should allow soils to dry for a
length of time that simulates worst-case (longest duration). The control devices
should be prepared and processed in exactly the same manner as the test devices;
positive control devices should be soiled and negative control devices should not
be soiled.

2.   Validation Protocols: Documentation of Methods Designed to Test the

Cleaning Process

Validation protocols should support the cleaning instructions provided in your device labeling; they should be detailed and specific with respect to the parameters such as time, temperature and concentrations.

The cleaning validation protocols should use the shortest times, lowest temperatures,
weakest dilutions, etc., for each step of the cleaning instructions. You should perform
a detailed, side-by-side comparison of the text of the cleaning instructions and the text
of the validation protocols, to identify and account for all worst-case processing
conditions.

Examples of worst-case processing conditions:

§     If the cleaning instructions recommend a 10 to 20 minute pre-soak, the

validation protocols should specify 10 minutes.

§     If the cleaning instructions advise the user to manually clean at 45ºC ± 5ºC,

the validation protocols should specify cleaning at 40ºC.

§     Enzymatic Detergents: In general, “worst-case” implies shortest times, lowest

temperatures, etc. An exception to validation at lowest temperature would be
enzymatic detergents, which typically have “optimally effective” temperature
ranges. Validation protocols should adequately address the temperature range

specified in the cleaning instructions for enzymatic detergents.

§     Medical Washers/Disinfectors: If your process validation uses automated

medical washers/washer disinfectors or ultrasonic cleaners, your worst-case should include the extremes of the intended cycle parameters for the available washer/washer disinfector cycles or ultrasonic cleaners.

§     If a device consists of lumens, ports, or channels that must be flushed during

cleaning, the validation protocol should include minimal flushing

specifications, such as time, flush volume or flow rate, and number of repetitions (e.g., 10 mL flush, performed 3 times).

3.   Testing: Test Types and Protocols

a.  Choice of Test Types

FDA recommends that you use at least two quantitative test methods capable of

directly measuring clinically meaningful levels of clinically relevant soil to meet a relevant, predetermined cleaning endpoint. Many potential test methods exist for the evaluation of soil and contamination, and the effectiveness of cleaning
processes. The AAMI TIR 30 “A compendium of processes, materials, test
methods, and acceptance criteria for cleaning reusable medical devices” provides a summary of test methods available in the published literature.

When choosing a test method, consideration should be given to a number of

factors. These should include, but may not be limited to, the contaminants that the device is expected to come in contact with during actual clinical use (which
should be adequately represented in the artificial soil), the test specificity for
direct measurement of those constituents, and the sensitivity of the test methods in relation to the proposed cleaning endpoints.

Regardless of the test type you choose, visual inspection of both external and internal surfaces should be performed during validation.

You should provide a justification for the test types chosen, including any

relevant documentation (e.g., FDA-recognized standard, published literature,
instructions for use for a commercially-available assay). If your chosen test
method deviates in any way from what is described in the provided
documentation, then you should identify and justify each deviation.

b.  Methods Validation

You should validate the test methods you choose to measure residual soil. Your
documentation of the method should include analytical sensitivity and specificity
information, as well as predetermined cleaning endpoints, and should describe
appropriate controls.

The Agency recommends that your test method include the following controls:

§   Negative device control - The device should be unsoiled and undergo the
      same cleaning and extraction as test devices. The amount of residual soil

should be at or slightly above the negative sample control.

§   Positive device control - The device should be soiled with a known

amount of soil, but not cleaned, and residual soil extracted. The amount of residual soil should be equivalent to or slightly lower than the amount of soil placed.  Soil recovery efficiencies should be calculated and used
during the calculations.

§   Negative sample control - “Extraction” is conducted with no device. This
      sample is used as a blank.

§   Positive sample control - A known amount of soil (at or slightly above the
      limit of quantitation) is added to an “extraction” with no device. This

control addresses interference of the extraction fluid and extraction method with soil detection.

c.  Extraction Method

Devices should be subjected to a validated method of extraction for recovery of
residual soil. The extraction method should be completely described for each
device and its recovery efficiency should be determined as part of its validation.

Exhaustive extraction and extraction using a known quantity of soil are

commonly used methods for determining recovery efficiency. Extraction should
sample all surfaces, including internal surfaces (such as lumens) and mated
surfaces. The worst case challenge (most difficult to remove) components of the
soil should be addressed in the determination of recovery efficiency testing. You
should ensure that the extraction volume used to remove test soil from the device
is not so large that the test marker is diluted below the level of detection for the
assay.

Some device designs include more complex internal structures (e.g., lumens,

internal moving parts) that may become soiled during use, but are difficult to

access during cleaning and extraction. Hence, cleaning methods, including

disassembly, should be designed to access these surfaces. For such geometrically
complex devices, all relevant internal surface areas should be sampled during both
the extraction method validation and device cleaning validation. Thus, for
validation studies, additional disassembly processes may be required in order to
adequately extract residual soil from these difficult to access areas. This
additional disassembly should rarely require disassembly beyond the basic
elemental component units, or require their actual physical destruction.

For devices with internal compartments that are not intended to come in contact
with clinical soil and fluids, you should demonstrate that cleaning solutions, rinse
water and/or patient materials will not penetrate into the internal aspects of the
devices via incomplete seals, seams, or other internal-external contiguous air
spaces.

If you determine that there is a risk of clinical soil or cleaning fluid ingress, you
should demonstrate that the cleaning methods meet the cleaning endpoints for all
internal surfaces that become contaminated at any time during the device’s use
life.

B.      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 extent and nature of real-world, worst-case device contamination. Also, practicality and human factors issues should be considered when establishing your
reprocessing protocols.

In addition, it may be helpful to refer to the AAMI TIR 30 “A compendium of processes,
materials, test methods, and acceptance criteria for cleaning reusable medical devices,”
for additional information specifically regarding soils and soil recipes described in the
published literature.