Guidance for the Efficacy Evaluation of Products for Claims against Drug-Resistant Candida auris
Candida auris (C. auris) is an emerging fungal pathogen that has caused severe illness in healthcare facilities in several countries, including the United States. C. auris is a yeast type of fungus and it is often multidrug-resistant, meaning that it is resistant to multiple antifungal drugs commonly used to treat Candida infections. Some strains are resistant to all three major classes of antifungals. C. auris can spread in healthcare settings through contact with contaminated environmental surfaces or equipment, or from person to person.
The Centers for Disease Control and Prevention (CDC) have recommended thorough daily and post-discharge cleaning of hospital rooms of patients with C. auris infections using an EPA-registered product with a hospital disinfectant claim and claims for C. auris (List P) or Clostridioides difficile (List K). Shared equipment (e.g., ventilators, physical therapy equipment) should also be cleaned and disinfected before being used by another patient. For additional information, refer to the CDC.
EPA recognizes the public health implications of this fungal pathogen in healthcare settings and the importance of having available EPA-registered disinfectants with demonstrated efficacy against drug resistant C. auris. Since antifungals that kill drug-resistant C. auris are also effective against nondrug-resistant C. auris, EPA has developed this guidance to facilitate the testing of products for effectiveness against all C. auris to ensure that they perform as intended. Specifically, this guidance provides recommendations for laboratory methodology on how to: (1) produce and store cultures of drug-resistant C. auris, and (2) evaluate the effectiveness of antimicrobial products intended to treat surfaces contaminated with drug-resistant C. auris.
EPA previously posted guidance and methods for antimicrobial efficacy testing of C. auris in March 2017. After consultation with technical experts at CDC, EPA updated its guidance to further address the prevalence and impact of drug-resistant C. auris isolates in the United States. EPA is now recommending that all studies initiated on or after Oct. 15, 2021, be conducted with C. auris isolate AR Bank #0385, a drug-resistant strain. Products whose efficacy is based on AR Bank #0385 data will be able to make claims of effectiveness against both C. auris and drug-resistant C. auris. Products with C. auris claims supported by AR Bank #0381 data will be able to maintain the claim that they are effective against C. auris. However, in order to include a claim for drug-resistant C. auris, data on the AR Bank #0385 strain must be submitted according to this revised test method.
This guidance document describes:
- Test methodology
- Eligible product types
- Test criteria
- Data submission procedures for efficacy data
- Labeling guidance
- Special label instructions for cleaning prior to disinfection against drug-resistant Candida auris
- Previously initiated GLP study protocols
This guidance is not binding on EPA or any outside parties, and EPA may depart from the guidance within where circumstances warrant and without prior notice. Registrants and applicants may propose and submit modifications to the recommended test methodology to the agency for assessment. Please contact the Product Manager for your product or proposed product to facilitate discussion of modifications to the test methodology. This guidance may be updated in the future.
EPA is responsible for regulating hospital disinfectants and other antimicrobial pesticides used in healthcare and other settings pursuant to the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). This guidance addresses efficacy testing for antimicrobial pesticides intended to be used as disinfectants on hard, non-porous surfaces in a variety of product formulations (water-soluble powders, liquids, sprays, towelettes, etc.) against drug-resistant C. auris. A recommended standard quantitative method for testing C. auris on hard, non-porous surfaces to support hospital disinfectant label claims against drug-resistant C. auris has been developed. This updated method supersedes the previous C. auris test method.
EPA recommends that in order to establish a drug-resistant C. auris claim, the product should meet the testing specifications for a hospital disinfectant. Recommended data collection for a hospital disinfectant claim is described in the most current version of EPA’s Product Performance Test Guidelines, OCSPP 810.2200. View the product performance test guideline.
To obtain a C. auris claim, applicants should use the methodology provided below.
- To evaluate the efficacy of the product against drug-resistant C. auris, follow EPA Microbiology Laboratory Branch (MLB) Standard Operating Procedures (SOPs) and the recommended testing criteria described in this guidance. See the MLB SOPs.
- For product performance, use the latest version of EPA MLB SOP MB-35: Quantitative Method for Evaluating the Efficacy of Antimicrobial Products against C. auris on Hard, Non-Porous Surfaces.
- To verify product neutralization, use the latest version of EPA MLB SOP MB-37: Neutralization of Microbicidal Activity against C. auris using the Quantitative Method.
If approved by EPA, C. auris claims may be added to formulations of hospital disinfectants supported by acceptable efficacy data as outlined in the most current version of EPA’s Product Performance Test Guidelines, 810.2200. See below for specifics for various formulation types that are suitable for testing using the latest version of EPA MLB SOP MB-35.
- Liquid formulations and water soluble powders.
- A liquid applied as a spray using a pump or trigger sprayer may be evaluated as a liquid.
- For all other spray formulation types (aerosols) and other formulations such as mists, foams, and gels, the applicant should submit for agency review and approval prior to testing an efficacy testing protocol consistent with the anticipated application and use pattern of the product.
- Towelettes may be evaluated using liquid directly expressed from the towelette for the efficacy evaluation. In addition, data should be generated to assess the amount of liquid remaining on a hard, non-porous surface treated (wiped) with the towelette per the label instructions, as well as chemical testing for the expressed liquid active ingredient concentration. The agency recommends conducting visual and gravimetric wetness tests in an environmental chamber as described below.
- Gravimetric and Physical Wetness Determination.
For each batch, use three pre-cleaned 12-inch × 12-inch glass or stainless steel carriers or 150 × 20 mm glass Petri plates to represent the surface to be treated.
Pre-clean each carrier surface with 70% ethanol rinse in deionized water and air dry.
Record the weight (weight #1: dry and untreated).
Distribute the liquid in the canister or package; remove and discard the first 3-5 towelettes.
For each carrier, remove one towelette from the container, unfold, and wipe the carrier surface in a circular fashion without lifting the towelette. Treat up to the edge of the carrier.
Re-weigh; record the results (weight #2: wet and treated).
Allow carriers to sit horizontally with the lid off for the contact time in an environmental chamber set at 35±5% relative humidity and 20-25°C.
Record the final weight (weight #3: post contact time).
Document the residual wetness by photograph or video.
Use a single dry sheet of Kim Wipe (e.g., 11 cm × 21 cm) in the visualization of wetness, record observations.
The data must show the presence of free-liquid on the treated surface by weight and physical observations (presence of wetness).
- Gravimetric and Physical Wetness Determination.
Applicants should consult with the agency for other formulation types prior to developing data in support of registration to determine whether protocols should be submitted for review and approval prior to commencement of testing.
Culture Production: The use of drug-resistant C. auris isolate AR Bank #0385 is recommended for testing. Stock cultures and test cultures should be produced following the latest version of EPA MLB SOP MB-35. See FDA-CDC Antimicrobial Resistance Isolate Bank to obtain information about the microbe. The drug resistance should conform to the drug-resistance profile located on the FDA-CDC Antimicrobial Resistance Isolate Bank; refer to the latest version of EPA MLB SOP MB-35 for the recommended assays.
Number of Batches and Test Coupons per Batch: Test two batches of the product, one batch per day, using separate test cultures, at the lower certified limit(s) (LCL) listed on the confidential statement of formula of the product. For each batch, evaluate five carriers against the product and three untreated control carriers.
Neutralizer Confirmation: Conduct neutralization testing to confirm and document the effectiveness of the product neutralizer. Refer to the latest version of EPA MLB SOP MB-37.
Contact Time: The contact time for the product should not exceed 10 minutes.
Product Diluent: Ready-to-use products should be tested as formulated. For products that require dilution, the diluent should be consistent with that used for the hospital disinfectant claim, or use 375 ppm hard water as specified in the latest version of EPA MLB SOP MB-35.
Soil Load: Include the three-part soil load specified in the latest version of EPA MLB SOP MB-35 in the test inoculum.
Control Carrier Counts: Each of the three control carriers should exhibit C. auris counts of a minimum of 1.0 × 105 to a maximum of 1.0 × 106 colony forming units (CFUs) per carrier.
Evaluation of Success: Attain a minimum mean 5.0 log reduction (LR) in viable C. auris cells in each of the two tests.
Modifications to the Test Procedures: When recommended methods are modified by the applicant to support specific claims for a product, the applicant should submit the complete testing protocol, identifying and describing each modification to the agency for review and evaluation prior to the initiation of the tests. All materials and procedures employed in the testing should be fully described.
To assist in the proper review and evaluation of product performance, complete descriptions of the test employed and the results obtained should be submitted to the agency. All test reports should include, at the least, the information cited in the agency’s Product Performance Test Guidelines, OCSPP 810.2000 - General Considerations for Testing Antimicrobial Agents (refer to the section on data submission and reporting). The Good Laboratory Practice Standards (GLPs) regulations at 40 CFR 160 apply to studies to support registration of all antimicrobial products. View the GLP regulations.
Kills and/or inactivates C. auris on hard, non-porous surfaces.
Kills a minimum of 99.999% of drug-resistant C. auris on hard, non-porous surfaces.
- Personal Protection: Wear appropriate barrier protection such as gloves, gowns, masks, or eye covering.
- Cleaning Procedure: Fecal matter/waste must be thoroughly cleaned from surfaces/objects before disinfection by application with a clean cloth, mop, and/or sponge saturated with the product. Pre-cleaning is to include vigorous wiping and/or scrubbing and all visible soil is removed. Surfaces in patient rooms are to be cleaned in an appropriate manner, such as from right to left or left to right, on horizontal surfaces, and top to bottom, on vertical surfaces, to minimize spreading the organism. Restrooms are to be cleaned last. Do not reuse soiled cloths.
- Infectious Waste Disposal: Materials used in the cleaning process that may contain feces/wastes are to be disposed of immediately in accordance with local regulations for infectious materials disposal.
This section provides guidance for registrants with study initiation dates between Oct. 15, 2020, and Oct. 15, 2021.
- EPA will accept studies conducted with isolate AR Bank #0381 for products whose active ingredients are either sodium hypochlorite or hydrogen peroxide plus acetic acid. For products with other active ingredients, it will be necessary to retest using isolate AR Bank #0385.
- Control carrier populations that were direct plated and not filtered are acceptable.
- If blood serum (e.g., horse serum, fetal bovine serum, etc.) was used as the soil load, the data are acceptable.
- If raw data were not included in the final report, registrants should amend the report to add the raw data and report no recovery outcomes for treated carriers as a log density of 0.