Interim Guidance for the Efficacy Evaluation of Products for Claims against Candida auris
EPA has developed two new test methods and associated testing guidance for evaluating the effectiveness of antimicrobial pesticides against Candida auris (C. auris). Specifically, this guidance provides recommendations for laboratory methodology on how to:
- produce and store cultures of C. auris; and
- evaluate the effectiveness of antimicrobial products intended to treat surfaces contaminated with C. 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 some strains are resistant to all three major classes of antifungal drugs. 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 EPA-registered hospital disinfectants with a Clostridium difficile claim. View information from CDC on C. auris.
- Test methodology
- Products potentially eligible for C. auris claims
- Test criteria
- Data submission procedures for efficacy data
- Labeling guidance
This document 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 (carrier type, diluent etc.) to the recommended test methodology to the agency for assessment. 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). There are currently no EPA-registered hospital disinfectants with specific claims for treating environmental surfaces contaminated with C. auris. Thus, EPA is issuing interim regulatory guidance and recommended methodology for evaluating the effectiveness of hospital disinfectants against C. auris.
EPA recommends that in order to establish a 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 C. auris, follow EPA Microbiology Laboratory Branch (MLB) Standard Operating Procedures (SOP) and the recommended testing criteria described in this guidance.
- For product performance, use EPA MLB SOP MB-35: OECD Quantitative Method for Evaluating the Efficacy of Liquid Antimicrobials against Candida auris on Hard, Non-Porous Surfaces.
- To verify product neutralization, use EPA MLB SOP MB-37: Neutralization Confirmation for Evaluating the Efficacy of Liquid Antimicrobials using the OECD Quantitative Method against Candida auris on Hard, Non-Porous Surfaces.
If approved by the agency, 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, OCSPP 810.2100 and 810.2200. See below for specifics for various formulation types that are suitable for testing using 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 an efficacy testing protocol consistent with the anticipated application and use pattern of the product for agency review and approval prior to testing.
- 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 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: CDC has recommended the use of C. auris (isolate AR-0381) for testing. Stock cultures and test cultures should be produced following EPA MLB SOP MB-35. The FDA-CDC Antimicrobial Resistance Isolate Bank website includes information about obtaining the microbe.
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 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 which require dilution, the diluent should be consistent with that used for the hospital disinfectant claim or use the OECD hard water specified in EPA MLB SOP MB-35.
Soil Load: A soil load (e.g., 5% fetal bovine serum) should be included in the test inoculum or use the OECD three-part soil load specified in EPA MLB SOP MB-35.
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. Individual control counts should be within one log of each other.
Evaluation of Success: Attain a minimum mean 5 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 Candida auris on hard, non-porous surfaces.
Kills a minimum of 99.999% or five logs of Candida auris on hard, non-porous surfaces.
Special Label Instructions for Cleaning Prior to Disinfection against Candida auris
- 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.