EPA Provides Expedited Pathway for Companies to Claim “Long-Lasting” Efficacy for Antiviral Products

On October 14, 2020, the U.S. Environmental Protection Agency (EPA) released a much-anticipated draft guidance that is intended to help companies demonstrate to EPA that their products have “long-lasting” or “residual” effectiveness on surfaces against viruses like SARS-CoV-2, the coronavirus that causes COVID-19. EPA has not before now provided guidance on how stakeholders can demonstrate to EPA’s satisfaction that their product remains efficacious for periods of time given the broad diversity of contact opportunities and scenarios, which is why this guidance is so significant. Pursuant to Title VII of the Coronavirus Aid, Relief, and Economic Security (CARES) Act, EPA intends to expedite reviews for addition of residual (i.e., extended or long-lasting) efficacy claims for currently registered products or new product registrations that are listed on EPA’s Disinfectant List N, that would qualify for List N, or products that can be used as a residual supplement to disinfectants on List N.

Under the Pesticide Registration Improvement Act (PRIA), typical decision review timeframes for these types of registration actions range from four months for amendments and new registrations for products similar to existing products, to 24 months for new active ingredient submissions (Antimicrobials Division (AD) PRIA Action Code Tables). EPA states that for antimicrobial products that may be of use against SARS-CoV-2, it is “currently making every effort to expedite the review and make regulatory decisions for the submissions discussed in this document by at least one to two months faster than the normal PRIA timeframe, depending on the submission, provided the procedures described in this interim guidance are followed.” EPA notes that as it gains more experience with expedited procedures, it may revise the expected completion timeframes for these actions.

EPA will expedite review of the applications for amended registrations and new registrations that do not include a new active ingredient for the residual effect claims listed in the summary table. EPA cautions that applicants need to be aware, however, that to expedite these submissions, it is necessary for EPA to receive all of the information specified. To the extent that EPA does not receive the identified information, EPA states that it may not be able to process these submissions in an expedited fashion. In any such cases, EPA may default to the PRIA timeframe otherwise associated with the submission after consultation with the registrant.

Products with residual effect claims that qualify for this expedited review fall into two major categories: (1) disinfectants that also provide residual efficacy; and (2) supplemental residual antimicrobial products (e.g., coatings, paints, solid surfaces) that do not meet EPA’s standards for disinfectants but are intended to be used as a supplement to standard List N disinfectants.

EPA notes that depending on their intended use, some antimicrobial products may be subject to both EPA and U.S. Food and Drug Administration (FDA) jurisdiction (e.g., liquid chemical disinfectants and devices used to disinfect health care facilities and non-critical medical devices), and therefore may require FDA review. Other products may be subject to FDA’s exclusive jurisdiction (e.g., liquid chemical disinfectants and devices used against microorganisms in or on humans or other animals, liquid chemical sterilants for use on a critical or semi-critical medical devices) and are outside the scope of the guidance.

In addition to releasing the draft residual efficacy protocols, EPA has also released an updated draft testing protocol for evaluating a copper surface’s ability to kill bacteria and a draft protocol for evaluating the efficacy of antimicrobial surface coatings. According to EPA, “[t]hese laboratory testing methods act as a foundation for EPA’s interim guidance to registrants regarding residual effectiveness.

While EPA does not have an approved standard method to support virus claims for these types of products, EPA states that the following information is intended to provide interim guidance on the study design elements necessary to support these types of claims. EPA states that it may consider other methods or studies to support residual efficacy claims, provided they are scientifically sound. Applicants are highly encouraged to consult with EPA prior to submitting. Of significant interest, EPA states that products may make both types of residual claims provided that they are supported by the appropriate data.

Due to lab capacity concerns, EPA plans to consider non-GLP (Good Laboratory Practice) data to support residual claims provided that the study submission accurately represents how the study differs from the GLP standards in the 40 C.F.R. Section 160.12 statement of non-compliance. Additional details provided in the EPA guidance on how to qualify products for residual disinfectants or supplemental residual antimicrobial products are outlined below.

Residual Disinfectant Claims

Residual disinfectants must clear a higher standard of efficacy than supplemental residual antimicrobial products. Residual disinfectant products must be effective within 10 minutes of a virus or bacteria contacting a treated surface and must remain effective for up to 24 hours. Surfaces treated with residual disinfectants must not require additional cleaning or disinfection during this window. EPA-approved residual disinfectant products are eligible to be added to List N. In addition, long-lasting coating products must satisfy all requirements for standard disinfectant claims (non-residual) to be eligible for residual disinfectant claims and must have undergone testing to support standard disinfectant claims.

To support a claim as a residual bactericidal disinfectant, applicants should use EPA’s Residual Self-Sanitization Protocol with the following modifications:

• Base Bacteria — Consistent with EPA Guideline 810.2200, Staphylococcus aureus (ATCC No. 6538) and Pseudomonas aeruginosa (ATCC No. 15442) should be used to support the case residual disinfectant claim.
   
• Conduct testing on three product lots at the lower certified limit (LCL) for each bacterium. In accordance with the OCSPP 810.2000 Test Guideline, certificates of analysis should be submitted to substantiate the tested concentration.
   
• Residual testing to support additional vegetative bacteria is not needed. Claims can be bridged from the standard disinfectant (non-residual data) for additional bacteria. For example, if a product has data to support a base disinfectant claim (Staphylococcus aureus and Pseudomonas aeruginosa) and data to support disinfectant claims for additional vegetative bacteria (e.g., Escherichia coli or MRSA), residual data are only needed for the base bacteria, and not additional bacteria, to support residual claims for those vegetative bacteria for which base disinfectant claims are supported.
   
• According to the Residual Self-Sanitization Method, durability testing should include 12 wear cycles, consisting of abrasions (alternating wet and dry) and re-inoculations to support a 24-hour residual disinfectant claim. Each wear cycle consists of four passes (two back and forth) of the abrasion material over the surface followed by re-inoculation. Additional details can be found in the method.
   
• Products should achieve a = 5-log reduction in = 10 minutes ± 5 seconds for qualifying bacteria when compared to the parallel abrasion and re-inoculation controls to support residual disinfectant claims.
   
• According to the OCSPP 810.2200 Test Guideline, the performance standard and time to meet the performance standard are consistent with the standards for non-residual disinfectants.
   
• At this time, expedited review is limited to residual disinfection claims of 24 hours or less based on data generated in accordance with the re-inoculation and abrasion cycles specified in the referenced protocol.
   

A. Residual Virucidal Claims

EPA’s Residual Self-Sanitization Protocol with the modifications below should be used to support residual virucidal claims. Virucidal efficacy should be assessed consistent with the principles of ASTM E1053 (e.g., recovery, cytotoxicity, neutralization, and calculations), the standard virucidal method detailed in OCSPP 810.2200 Product Performance Test Guideline.

• To support residual virucidal claims, acceptable non-residual virucidal efficacy (3-log reduction) should be demonstrated for the product at = 10-minute contact time consistent with the OCSPP 810.2200 Product Performance Test Guideline.
   
• Residual virucidal data should be generated for the most difficult to kill virus that that the product claims to kill. Claims for residual effect against the other viruses can be bridged from the non-residual virucidal data supporting the product. For additional information on selecting the most difficult to kill virus, see EPA’s Emerging Viral Pathogens Guidance.
  
  • To be considered for List N, virus testing should include a non-enveloped virus or a human coronavirus (SARS-CoV-2 or human coronavirus 229E).
     
• Testing on two product lots should be conducted at the LCL.
   
• According to the Residual Self-Sanitization Method, durability testing should include 12 wear cycles consisting of abrasions (alternating wet and dry) and re-inoculations to support a 24-hour residual disinfectant claim. Each wear cycle consists of four passes of the abrasion material over the surface followed by re-inoculation. Additional details can be found in the method.
   
• Products should achieve = 3-log reduction in = 10 minutes ± 5 seconds for the hardest to kill virus when compared to the parallel abrasion and re-inoculation controls to support residual virucidal claims.
  
  • The performance standard and contact times are consistent with the standard non-residual disinfectants.
     
• At this time, expedited review is limited to residual disinfection claims of 24 hours or less based on data generated in accordance with the re-inoculation and abrasion cycles specified in the referenced protocol.
   

B. Labeling and additional information (both bactericidal and virucidal)

• Products are eligible for inclusion on List N following adherence to the Emerging Viral Pathogens guidance or appropriate testing for a qualifying virus (e.g., SARS-CoV-2 or human coronavirus 229E).
   
• These products may be used as stand-alone disinfectants and do not need a label disclaimer that they are a “supplement to standard disinfection” since they meet the general criteria for disinfectants (effective in = 10 minutes with appropriate log reductions for bacteria and virus).
   

Supplemental Residual Antimicrobial Products

Supplemental residual antimicrobial products work within two hours of a virus or bacteria coming into contact with a surface and can remain effective for weeks to years. These products can supplement, but not replace, routine cleaning and disinfection using products from EPA’s List N: Disinfectants for Use Against SARS-CoV-2 (COVID-19). Approved supplemental residual antimicrobial products are not eligible for inclusion on List N, but will be added to a separate List N appendix.

Qualifying antimicrobial surface coatings, films, fixed/solid, and paint products should demonstrate efficacy against vegetative bacteria first before virus claims can be supported. These products are not required to meet the efficacy standards for disinfectants and can only be approved for use as supplements to standard disinfection. The duration of residual effectiveness claims that EPA will consider for expedited review depends on the type of product, as outlined below.

A. Antimicrobial Surface Coatings and Films

For these products, EPA states that EPA’s draft Performance of Antimicrobial Surface Coatings on Hard Non-porous Surfaces for qualifying bacteria should be used. EPA provides the following additional information for products on which virus claims would be added:

• Test Organisms
  
  • Bacteria — Staphylococcus aureus (ATCC No. 6538) and Pseudomonas aeruginosa (ATCC No. 15442) are the qualifying bacteria required to support supplemental residual antimicrobial surface claims for the proposed claim duration (e.g., one week, two weeks).
    
    • Testing should be conducted on three product lots per bacterium at the LCL.
       
  • To support claims for additional bacteria, testing should be conducted according to the method but with a reduced number of product lots.
    
    • Two lots of product for each bacterium at the nominal concentration.
       
  • Viruses — All viruses for which claims are desired should be tested. The most difficult to kill virus should be subjected to the durability assessment using coating carriers followed by the efficacy assessment to support the proposed duration (e.g., one week, two weeks). All other viruses should be tested using coated carriers that were not subjected to the durability procedure.
    
    • Assessment of virucidal efficacy on the coated carriers should be conducted consistent with ASTM E1053, the standard method specified in EPA’s 810.2200 Efficacy Test Guideline.
       
    • Two lots of product at the LCL should be tested for the most difficult to kill virus. Two lots of product at the nominal concentration should be tested for additional viruses.
      
      • To be considered as a supplement to List N, virus testing should include a non-enveloped virus or a human coronavirus (SARS-CoV-2 or human coronavirus 229E)
         
• Stainless steel carriers will be used to support claims for coatings on hard, nonporous surfaces. Use sites should be limited to hard, non-porous surfaces. Additional material types (e.g., porous materials or textiles) may be proposed by the registrant upon consultation with EPA prior to submission.
   
• The recommended number of abrasions (touches) and cycles of exposure to cleaning or disinfecting chemicals are provided in the method to substantiate durability claims. The method also specifies the chemical disinfecting solutions to simulate cycles of in-service disinfection and cleaning. Additional details can be found in the method.
  
  • Ten cycles of abrasion and/or chemical exposure is equivalent to one week of durability. The number of cycles can be increased in one-week increments to support claims up to four weeks.
     
  • If a product is incompatible with one or more of the test chemistries, this should be discussed with EPA in advance and may limit use sites and surfaces depending on the nature of the incompatibility. EPA does not have a standard method for determining incompatibility. This may be based on research and development data or known incompatibilities with the coating material, for example.
     
• This protocol may be modified for films upon consultation with EPA in advance of submission.
   
• If an applicant intends to claim supplemental residual effects longer than four weeks, it should consult with EPA in advance of submission. EPA states that because the ongoing antimicrobial integrity of coatings and films will not be readily visible, it is important that end users have a reasonable expectation of durability.
   
• Products should achieve a 99.9% reduction (3-log) for both bacteria and viruses in comparison to untreated controls within a maximum of two hours but not less than one hour, as EPA is concerned that observations taken before the inoculum has dried (e.g., less than one hour) on the surface may not provide an accurate assessment of the product.
  
  • The time to achieve performance begins at the time of inoculation.

B. Antimicrobial Surface Coatings and Films — Labeling and Additional Information

EPA states that this new category of antimicrobial products should be labeled as supplemental residual antimicrobial surfaces. EPA provides the following additional information:

• As these products do not meet the criteria for a disinfectant due to the longer contact time and lower performance standard, claims for residual disinfectant are not acceptable. As above, contact times for disinfectants are = 10 minutes and with a higher performance standard for bacteria.
   
• Products should carry the following prominent label qualifier that they are a supplement to standard disinfection and cleaning:
  
  • “Although this product DOES NOT meet EPA’s standards for disinfectants, EPA has determined that, when used with an EPA-registered disinfectant, this product can provide some additional protection against [microorganism(s)] for up to X days. This product DOES NOT achieve the same level of efficacy as an EPA-registered disinfectant; it is only intended to provide supplemental protection between routine applications of EPA-registered disinfectants.”
     
• For products eligible only for supplemental residual antimicrobial claims, EPA intends to require as a term of registration that the label and labeling state, “This product does not meet EPA’s efficacy standards to qualify as a stand-alone disinfectant.”
   
• Although these products will not be eligible for List N, they will be eligible as a supplement to List N (N.1) to reflect that they are supplemental treatments (i.e., not stand-alone disinfectants) and intended for use in combination with List N disinfectants.
   
• The following are example acceptable product label claims:
  
  • “Kills 99.9% of [insert microorganism/s] within two hours of exposure when used as part of a comprehensive infection control program/protocol for up to X days.”
     
  • “Continuously reduces [insert microorganism/s] within two hours of exposure when used as part of a comprehensive infection control program for up to X days.”
     

C. Fixed/Solid Surfaces Including Solid Copper and Other Metals and Solid Impregnated Materials and Paints — Method Recommendation

EPA states that these products should use EPA’s Draft Copper Surface Protocol for qualifying bacteria. EPA provides the following additional information for products that wish to have virus claims added.

• Test Organisms
  
  • Bacteria — Staphylococcus aureus (ATCC No. 6538) and Pseudomonas aeruginosa (ATCC No. 15442) are the qualifying bacteria used to support supplemental residual surface claims.
    ​
    • Testing should be conducted on three product lots per bacterium at the LCL.
       
  • To support claims for additional bacteria, testing should be conducted according to the method but with a reduced number of product lots.
    
    • Two lots of product for each bacterium at the nominal concentration.
       
  • Viruses — All viruses for which claims are desired should be tested. The most difficult to kill virus should be subjected to the durability assessment in the copper method, followed by the efficacy assessment. All other viruses should be tested using test carriers that were not subjected to the durability procedure.
    ​
    • Assessment of virucidal efficacy on the coated carriers should be conducted consistent with ASTM E1053, the standard method specified in EPA’s 810.2200 Efficacy Test Guideline.
       
    • Two lots of product at the LCL should be tested for the most difficult to kill virus. Two lots of product at the nominal concentration should be tested for additional viruses.
       
• The recommended number of abrasions (touches) and cycles of exposure to cleaning or disinfecting chemicals are provided in the method in order to substantiate durability claims. The method also specifies the chemical solutions to simulate cycles of disinfection and cleaning.
  
  • As the durability of these types of products can be readily observed, duration claims are not necessary. This is consistent with currently registered copper-containing surface products and paints.
     
  • If a product is incompatible with one or more of the test chemistries, this should be discussed with EPA in advance and may limit use sites and surfaces, depending on the nature of the incompatibility. EPA states that it does not have a standard method for determining incompatibility. This may be based on research and development data or known incompatibilities with the coating material, for example.
     
• This protocol can be modified for other metals or solid impregnated surfaces or paints upon consultation with EPA.
   
• Products should achieve a 99.9% reduction (3-log) for both bacteria and viruses in comparison to untreated controls within two hours.
  
  • The time to achieve performance begins at the time of inoculation
     

D. Fixed/Solid Surfaces Including Solid Copper and Other Metals and Solid Impregnated Materials and Paints — Labeling and Additional Information

EPA states that these products should be labeled as supplemental residual antimicrobial surfaces. EPA states the following with regard to these products:

• As these products do not meet the criteria for a disinfectant due to the longer contact time and lower performance standard, claims for residual disinfectant are not acceptable.
   
• Products should carry the following prominent label qualifier that they are a supplement to standard disinfection and cleaning:
  
  • “Although this product DOES NOT meet EPA’s standards for disinfectants, EPA has determined that, when used with an EPA-registered disinfectant, this product can provide some additional protection against [microorganism(s)] for up to X days. This product DOES NOT achieve the same level of efficacy as an EPA-registered disinfectant; it is only intended to provide supplemental protection between routine applications of EPA-registered disinfectants.”
     
• For products eligible only for supplemental residual antimicrobial claims, EPA intends to require as a term of registration that the label and labeling should state, “This product does not meet EPA’s efficacy standards to qualify as a stand-alone disinfectant.”
   
• Although these products will not be eligible for List N, they will be eligible as a supplement to List N (N.1) to reflect that they are supplemental treatments (i.e., not stand-alone disinfectants) and intended for use in combination with List N disinfectants. The following are example acceptable product label claims:
  
  • “Kills 99.9% of [insert microorganism/s] within two hours of exposure when used as part of a comprehensive infection control program/protocol.”
     
  • “Continuously reduces [insert microorganism/s] within two hours of exposure when used as part of a comprehensive infection control program.”

E. Supplemental Residual Antimicrobial Products — Stewardship Program

EPA intends to require, as a term of registration, that registrants of all supplemental residual antimicrobial products prepare and implement a written stewardship plan designed to support the responsible use of supplemental residual coatings and antimicrobial surface products. Unlike conventional antimicrobial products, EPA believes that these products represent unique challenges that require timely feedback to ensure proper use and compatibility in combination with current infection control practices. EPA expects that plans would be submitted for EPA review and approval during the registration process, or shortly thereafter (e.g., within two months after the registration date). An approvable plan would address the proper sale (including advertising and promotional materials), distribution, and responsible use of the supplemental residual coatings and antimicrobial surface products. EPA states that plans should include, at a minimum, the following elements:

• Advertising and promotional materials that clearly and consistently include a disclaimer that the product does not meet EPA’s standards for disinfectants and is intended to supplement the use of EPA-registered disinfectants.
   
• Outreach to the infection control community;
   
• Customer feedback consisting of product issues/concerns, adverse events, compliance challenges/observations, and contraindications/adverse events gathered through quarterly registrant-initiated surveys, customer complaints, and suggestion boards; and
   
• Development of a stewardship website.
   

EPA states further that “[i‌]f EPA determines at any time following registration that the Plan is not being adequately or timely implemented or does not effectively ensure the product’s safe and effective use, the registration may be cancelled by the Agency.” It is not clear from the statement whether EPA intends such a cancellation to be a term of the registration or whether it would be undertaken pursuant to the standard FIFRA cancellation procedures.

Commentary

The need for EPA guidance on this topic is crucial, as the societal imperative for effective tools to combat COVID-19 has not diminished with the passage of time. The guidance is especially useful as it is quite granular and seeks to anticipate and address a wide variety of applications, surfaces, residual time periods, and claims. EPA is to be commended for preparing this useful document, and for all the work it has undertaken since the beginning of the pandemic to make available useful tools to combat the virus.