By Lisa M. Campbell, James V. Aidala, Lisa R. Burchi, and Barbara A. Christianson

 On May 6, 2022, the U.S. Environmental Protection Agency (EPA) published a notice in the Federal Register announcing the availability of, and requesting comments on, data related to aquatic toxicity of chitosan salts. 87 Fed. Reg. 27059. Specifically, EPA is seeking comments on the following two aquatic toxicity reports submitted by Tidal Vision Products, LLC (Tidal Vision), the company that submitted a petition to EPA on October 10, 2018, requesting that EPA add chitosan to the list of active ingredients eligible for EPA’s minimum risk pesticide exemption under Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Section 25(b):

1. Tidal Vision USA. (2019). Aquatic Toxicology Report by Eurofins Environmental Testing Test America. Lab I.D. No. B4345. Report Date: June 17, 2019. EPA Master Record Identification (MRID) 51861901.
2. Tidal Vision USA. (2019). Aquatic Toxicology Report by Eurofins Environmental Testing Test America. Lab I.D. No. B4421. Report Date: August 28, 2019. EPA Master Record Identification (MRID) 51861902.

EPA is seeking input on how these reports may be used by EPA in its assessment of aquatic toxicity of chitosan and its salts. EPA states “chitosan may form as a salt (e.g., acetate, lactate, hydrochloride, and salicylate) when it is solubilized in acids for end use product formulation and subsequently applied in the environment” and the new information submitted by Tidal Vision pertains to these salts.  Comments on the aquatic toxicity reports are due on or before June 6, 2022, in Docket EPA-HQ-OPP-2019-0701.

As background, EPA on August 20, 2020, announced that it was seeking to add chitosan to the list of active ingredients allowed in minimum risk pesticides that are exempt from pesticide registration requirements and was providing to the United States Department of Agriculture (USDA) for review a draft regulatory document titled ‘‘Pesticides; Addition of Chitosan to the List of Active Ingredients Allowed in Exempted Minimum Risk Pesticides Products.”  A minimum risk product must meet six specific conditions to be exempt from pesticide registration. One of those conditions is that the active ingredient in the minimum risk pesticide be one that is listed specifically by EPA. If EPA adds chitosan to the list of minimum risk pesticide active ingredients, pesticide products containing chitosan could qualify as minimum risk pesticides provided the other conditions also are satisfied (e.g., using inert ingredients approved by EPA for use in minimum risk pesticides, not making any public health claims).

On November 2, 2020, EPA requested comments on the proposed rule to add chitosan to the list of active ingredients eligible for the exemption. In the May 6, 2022, Notice, EPA states that  comments received on the proposed rule expressed concerns regarding derivatives of chitosan that are likely to be produced when chitosan is mixed with certain acids and on the potential hazard for aquatic organisms exposed to chitosan salts. Because of the concerns raised, EPA now is requesting comments on the two aquatic toxicity reports that pertain to these salts.

Commentary

EPA continues to remain focused on listing this specific substance rather than address other issues related to minimum risk pesticides that have been raised by industry to EPA over many years. There is, for example, a petition filed in 2006 by the Consumer Specialty Products Association (CSPA) requesting that EPA modify the minimum risk pesticide regulations to exclude products claiming to control public health pests from the Section 25(b) exemption. Comments submitted in response to the November 2, 2020, proposed rule raise additional concerns, including but not limited to the fact that the vast majority of states now require registration of minimum risk pesticides, thus shifting the burden away from EPA with costly and potential inconsistent results.

Though this EPA list is called “minimum risk,” it more accurately could be described as -- “so safe no one could, or at least should, have any concern about toxicity.”  There is long-standing reluctance for EPA to call any pesticide whatsoever as “safe” for various reasons, even to the point of an outright prohibition on using the word “safe” on registered labels.  (This is the clever distinction that “minimum risk” pesticides do meet the FIFRA definition of a pesticide, but the Section 25(b) designation allows that the label not be subject to EPA review and registration of the label.) 

This issue of possible risks from adding chitosan to the Section 25(b) list in light of the studies EPA seeks comment on appears to allow EPA to back away from its intended designation as minimum risk or to have the public comment reaffirm EPA’s assessment that chitosan’s safety profile is sufficiently beyond reproach to align with the other members of this category.  There are many other pesticides considered of very low risk but not so low as to have made the Section 25(b) list until now.  That there is a hint of debate about possible toxicity could signal that future additions to the list are being contemplated to encourage more “minimum risk” product development.  Or more simply, it may signal EPA’s reaction to the comments received has triggered some reconsideration of how “minimum” any minimum risk needs to be to qualify for the Section 25(b) list.

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By Heather F. Collins, M.S. and Barbara A. Christianson

On April 15, 2022, the U.S. Environmental Protection Agency (EPA) announced final product performance data requirements for products claiming efficacy against certain pests. 87 Fed. Reg. 22464. This action officially incorporates EPA’s already existing product performance standards requirements for certain invertebrate pests into the Code of Federal Regulations (CFR).  EPA states this action also increases the efficiency of its approval process and will save registrants time and money.

Product performance standards are intended to make it easier for pesticide registrants to know the efficacy data that EPA requires to demonstrate that a pesticide product works as claimed. By adding these requirements into the CFR, EPA states that it intends to help ensure that submitted data meet EPA’s needs and scientific standards and satisfy a requirement of the 2018 Pesticide Registration Improvement Extension Act (PRIA 4). EPA notes as part of the agreement between pesticide stakeholders and public interest groups reflecting the environmental and farmworker safety communities in the development of PRIA, “PRIA 4 specifically establishes a new maintenance fee set-aside of up to $500,000/year to develop and finalize rulemaking and guidance for product performance data requirements for certain invertebrate pests of significant public health or economic importance. Specific to this rule, PRIA 4 requires EPA to finalize product performance data requirements by September 30, 2021, for certain pesticides intended for preventing, destroying, repelling, or mitigating specified invertebrate pest of significant public health or economic importance.”

This final rule includes product performance data requirements for the categories of invertebrate pests specified in PRIA 4, which EPA states it intends to satisfy the rulemaking requirement. EPA notes that this final rule covers some invertebrate pests in addition to those specified in PRIA 4 due to their public health, economic, or ecological significance (e.g., wood destroying insects).

EPA states that it believes this final rule will save registrants approximately $17,000 per data package submitted to EPA by reducing waste and unnecessary testing, and believes it will reduce burden hours by 4,683 annually, including 4,515 hours from reduced paperwork burden associated with data generation and 168 hours from reduced paperwork with the application process.

This final rule codifies product performance data requirements to support registration of products claiming efficacy against three categories of invertebrate pests: 

• Those identified to be of significant public health importance (e.g., ticks, mosquitoes, cockroaches);
• Wood-destroying insects (e.g., termites); and
• Certain invasive invertebrate species (e.g., Asian long-horned beetle).

EPA states that the latter two categories are pests considered to be of significant economic or ecological importance.

The final rule is effective on June 14, 2022.

Commentary

Codifying the product performance data requirements for invertebrate pests should increase transparency to registrants regarding the efficacy data that they typically would need to generate and submit for products to make labeling claims against these specific pests. Registrants of the products at issue should monitor these requirements closely.

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By Lynn L. Bergeson and Carla N. Hutton

The U.S. Environmental Protection Agency (EPA) announced on April 18, 2022, that it will hold a webinar on May 11, 2022, entitled “Data-Driven Solutions to Reducing Animal Use in Ecotoxicity.” Speakers will include:

• Carlie LaLone, Ph.D., EPA Office of Research and Development (ORD), on “The Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool: Extrapolating Knowledge Computationally.” EPA states that regulatory decision-making for chemical safety relies upon toxicity data generated from laboratory test species for the protection of wildlife in the environment. Typically, ecological risk assessments integrate safety factors to account for interspecies variability. According to EPA, the SeqAPASS tool is a more informed way to extrapolate knowledge from model species to other species that does not require the use of animals in toxicity testing and instead uses existing protein sequence knowledge. LaLone will describe EPA’s SeqAPASS tool and its applications for cross-species extrapolation relative to understanding conservation of biology and predicting chemical susceptibility.
• Michael Lowit, Ph.D., EPA Office of Pesticide Programs (OPP), on “Exploring Potential Reductions in Fish Testing in a Regulatory Context.” According to EPA, as part of its commitment to reducing animal testing, OPP is conducting retrospective analyses of existing data to evaluate critically which EPA guideline studies form the basis of regulatory decisions. EPA states that the results from these analyses can inform if reductions can be made to the number of animals used without reducing the quality of ecological risk assessments. EPA is currently conducting a retrospective analysis for fish acute toxicity tests, which are used by OPP to assess potential risk to fish species from pesticides. For each pesticide, EPA typically requires in vivo testing of three different fish species. Lowit will focus on the relative sensitivity among species subjected to in vivo fish acute toxicity studies. The results of this analysis will inform whether there is a basis for reducing the number of species while providing sufficient information to support pesticide registration decisions.

The webinar is co-organized by the People for the Ethical Treatment of Animals (PETA) Science Consortium International, EPA, and the Physicians Committee for Responsible Medicine (PCRM). EPA notes that it does not necessarily endorse the views of the speakers. Registration is now open.

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By Heather F. Collins, M.S. and Barbara A. Christianson

On October 15, 2021, the U.S. Environmental Protection Agency (EPA) announced that it has revised its guidance for evaluating the efficacy of antimicrobial pesticides against Candida auris (C. auris). EPA states that pesticide manufacturers seeking to register their products with a C. auris claim should use this updated guidance to test the effectiveness of the products against a drug-resistant strain of C. auris.

EPA states that C. auris is an emerging, multidrug-resistant yeast (a type of fungus). It can cause serious infections and spreads easily among hospitalized patients and nursing home residents. C. auris can spread in healthcare settings through contact with contaminated environmental surfaces or equipment, or from person to person. According to the Centers for Disease Control and Prevention (CDC), more than one in three patients with an invasive (e.g., affecting the blood, heart, or brain) C. auris infection die.

In 2017, in consultation with the CDC, EPA issued interim guidance for testing the effectiveness of hospital disinfectants against C. auris. Subsequently, based on input from the CDC on its tracking of clinical cases of multi-drug resistant C. auris isolates in the United States, the laboratory data were generated to ensure antimicrobial efficacy against a more relevant strain of the pathogen.

Working closely with experts from the CDC, EPA conducted a comparative evaluation of isolates and found that the drug-resistant isolates were more tolerant to some disinfectant treatments. Since a drug-resistant isolate (AR Bank #0385) is highly relevant to current outbreaks in the United States, it is considered a suitable test microbe for regulatory purposes.

The 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.

Under the updated guidance, all new products seeking registration with claims against C. auris should test for efficacy using the more relevant strain (AR Bank #0385). Efficacy testing using AR Bank #0381 is acceptable in some cases where the study initiation date is between October 15, 2020, and October 15, 2021. For study initiation dates between October 15, 2020, and October 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.

Existing antimicrobial products with C. auris claims based on the previous strain (AR Bank #0381) will be allowed to retain their claim of effectiveness against C. auris. To claim effectiveness against drug-resistant C. auris, EPA requires retesting with the more relevant strain (AR Bank #0385) identified in the updated guidance and according to the revised test method.

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By Lisa M. Campbell and Lisa R. Burchi

On September 29, 2021, the U.S. Environmental Protection Agency (EPA) announced developments in its efforts to address per- and polyfluoroalkyl substances (PFAS) in the environment. In particular, EPA provided an update on its progress in testing pesticide products and containers for PFAS.

EPA states that as part of its ongoing efforts, it is releasing an internally validated method for the detection of 28 PFAS compounds in oily matrices, such as pesticide products formulated in oil, petroleum distillates, or mineral oils. According to EPA, the oily matrix method is modified from EPA Method 537.1, a method that is mainly used for drinking water and was previously used in analyzing PFAS in fluorinated high-density polyethylene (HDPE) containers.

The new method is intended to assist pesticide manufacturers, state regulators, and other interested stakeholders in testing oily matrix products for PFAS and joining efforts to detect any possible contamination. In the announcement, EPA states: “In a shared interest to remove PFAS from the environment, if companies find PFAS in their product, EPA is requesting that they engage in good product stewardship and notify the Agency.”

In developing this method, EPA collaborated with the Maryland Department of Agriculture. As part of this collaboration, the method was used to analyze three stored samples of mosquito control pesticide products as well as samples obtained directly from the product line from the pesticide manufacturer. EPA determined that none of the tested samples contained PFAS at or above EPA’s method limit of detection.

EPA states that its investigation continues to determine the scope of this issue and its potential impact on human health and the environment. EPA acknowledges that “[t]o date, the only PFAS contamination in mosquito control pesticide products that the Agency has identified originated from fluorinated HDPE containers used to store and transport a different mosquito control pesticide product.” EPA will continue to test additional fluorinated containers to determine whether they contain and/or leach PFAS and will present those results when the studies are complete. EPA further states it is working with other federal agencies and trade organizations to raise awareness of this issue and discuss expectations of product stewardship. EPA also is encouraging the pesticide industry to explore alternative packaging options, such as steel drums or non-fluorinated HDPE.

Additional information on EPA’s oily matrix method report and information on PFAS in pesticide packaging is available here.

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By Lara A. Hall, MS, RQAP-GLP and Heather F. Collins, M.S.

On March 17, 2021, the U.S. Environmental Protection Agency (EPA) announced the issuance of the final guidance document entitled "Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Technical Chemicals & Supporting Retrospective Analysis" (EPA 705-G-2020-3722; Docket ID: EPA-HQ-OPP-2016-0093) that expands the potential for data waivers for acute dermal studies to single technical active ingredients (AI) used to formulate end-use products. This new guidance builds upon the final guidance for waiving acute dermal toxicity tests for pesticide formulations published by EPA on November 9, 2016, and is an example of EPA’s continued efforts to reduce animal testing and achieve its goal of eliminating all EPA requests for studies and EPA funding of studies on mammals by 2035.  EPA states that this guidance is expected to reduce the number of test animals used annually by approximately 750, as well as save EPA, industry, and laboratory resources.

The new final guidance document also allows EPA to harmonize with the Pest Management Regulatory Agency (PMRA) of Canada, which published guidance on acute dermal toxicity waivers for both end-use product formulations and technical chemicals in 2017. 

In developing the new guidance, EPA states that the Office of Pesticide Programs (OPP) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) conducted a retrospective analysis of rat acute oral and acute dermal LD50 studies for 249 AIs across numerous chemical classes and toxicity categories in the EPA pesticide categorization scheme.  The overall purpose of this analysis was to address the utility of the acute dermal toxicity study for single AIs in pesticide labeling, such as the signal word and precautionary statements. Fumigants and rodenticides were excluded from this retrospective analysis based on their physical state and/or anticipated exposures to them. EPA concluded that:

• For 67 percent of the 249 technical chemicals, the results of both oral and dermal acute toxicity studies fall within the same Toxicity Category; 
• For 32 percent of the chemicals, the oral study falls within a lower (i.e., more protective) Toxicity Category;
• Thus, for 99 percent of the chemicals in the analysis, if the dermal study had not been available and labeling had been based only on the Toxicity Category for the oral acute toxicity study, the labeling requirements would have been equally or more protective; 
• For the two remaining chemicals (less than 1 percent), factors other than the dermal acute toxicity may influence labeling requirements; and
• The acute dermal toxicity studies provide little to no added value in regulatory decision making. 

EPA states that it believes the retrospective analysis fully supports the conclusion that waivers may be granted for acute dermal toxicity studies for pesticide technical chemicals, except for fumigants and rodenticides.  Waivers may be accepted for fumigants and rodenticides on a case-by-case basis with appropriate scientific rationale. EPA maintains the ability to request acute dermal toxicity data on a case-by-case basis, but states that it anticipates granting the waiver in most cases.

Additional information on EPA’s efforts to reduce animal testing is available here.

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By Barbara A. Christianson

On October 26, 2020, the U.S. Environmental Protection Agency (EPA) announced that it is soliciting public comment on the interim guidance on registering products that claim to have “residual” or “long-lasting” effectiveness against viruses.  This announcement follows up on EPA’s October 14, 2020, announcement that it would begin expediting its review of products with residual efficacy intended for use against SARS-CoV-2, the coronavirus that causes COVID-19.  While traditional disinfectants only kill viruses and bacteria that are on the surface at the time they are used, surfaces treated with residual antimicrobial products kill pathogens that come into contact with the surface days, weeks, or years after the product is applied.

EPA announced in an October 26, 2020, memorandum that it is seeking feedback from the public on the expedited process, design elements for evaluating residual product claims, and the test methods associated with this initiative. 

All comments on the interim guidance must be submitted to Docket Number EPA-HQ-OPP-2020-0529 on or before January 4, 2021. 

The interim guidance documents -- Interim Method for Evaluating the Efficacy of Antimicrobial Surface Coatings, Interim Guidance - Expedited Review for Products Adding Residual Efficacy Claims, and Interim Method for the Evaluation of Bacterial Activity of Hard, Non-Porous Copper-Containing Surface Products -- are available in Docket Number EPA-HQ-OPP-2020-0529.  More information on the interim guidance is available on our blog.

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By Lisa M. Campbell, Heather F. Collins, M.S. and Barbara A. Christianson

On October 14, 2020, the U.S. Environmental Protection Agency (EPA) released a much-anticipated draft guidance that will allow companies to demonstrate that their products have “long-lasting” or “residual” effectiveness on surfaces against viruses like SARS-CoV-2, the coronavirus that causes COVID-19.  EPA’s guidance specifies scientific testing requirements for two different types of products:  (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.

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.  These 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 briefly 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.

1. 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.

2. 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.

1. 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.

2. 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.”

3. 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.

4. 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.”

5. 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 “if 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.

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By Lynn L. Bergeson, Lisa M. Campbell, and Carla N. Hutton

On October 14, 2020, the U.S. Environmental Protection Agency (EPA) released much-anticipated draft guidance that will allow companies to demonstrate that their products have “long-lasting” or “residual” effectiveness on surfaces against viruses like SARS-CoV-2, the coronavirus that causes COVID-19.  As most know, 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.  Importantly, EPA states that pursuant to Title VII of the Coronavirus Aid, Relief, and Economic Security (CARES) Act, it is providing notice of its intention to expedite reviews for addition of residual (i.e., extended or long-lasting) efficacy claims for currently registered or new product registrations that are 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.  The guidance specifies scientific testing requirements for two different types of products, supplemental residual antimicrobial products and residual disinfectants.  According to EPA, 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.  EPA notes that these products can supplement, but do 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 EPA will add them to a separate List N appendix.

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.”

More information will be available in a forthcoming memorandum that will be available on our website.

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By Lisa M. Campbell, Lara A. Hall, MS, RQAP-GLP, and Heather F. Collins, M.S.

On October 7, 2020, the U.S. Environmental Protection Agency (EPA) announced that it is requesting comments on its draft guidance that would allow registrants, in certain circumstances, to forgo testing chemicals on animal skin to determine whether a pesticide would lead to adverse effects.  This new draft guidance is part of EPA’s continued efforts to reduce animal testing and achieve its goal of eliminating all EPA requests for studies and EPA funding of studies on mammals by 2035.

According to EPA, the draft dermal toxicity guidance would allow applicants to request waivers for acute dermal toxicity studies on single-active ingredients used to develop end-use products.  The new draft guidance also allows EPA to harmonize with the Pest Management Regulatory Agency (PMRA) of Canada, which published guidance on acute dermal toxicity waivers for both formulations and technical chemicals in 2017.  The draft guidance is in addition to the final guidance for waiving acute dermal toxicity tests published by EPA in November 2016 for pesticide formulations.

In developing the guidance, EPA states that it conducted a retrospective analysis of rat acute oral and acute dermal LD50 studies for 249 active ingredients across numerous chemical classes and toxicity categories.  Fumigants and rodenticides were excluded from this analysis, based on their physical state and/or anticipated exposures to them.  EPA concluded that for 67 percent of the 249 technical chemicals, the results of both oral and dermal acute toxicity studies fall within the same Toxicity Category.  For 32 percent of the chemicals, the oral study falls within a lower (i.e., more protective) Toxicity Category; thus, for 99 percent of the chemicals in the analysis, if the dermal study had not been available and labeling had been based only on the Toxicity Category for the oral acute toxicity study, the labeling requirements would have been equally or more protective.  For the two remaining chemicals (less than 1 percent), factors other than the dermal acute toxicity may influence labeling requirements.  EPA concluded that its requirements for such acute dermal toxicity studies provide little to no added value in regulatory decision making.  EPA states that this guidance, when finalized, is expected to reduce the number of test animals used annually by approximately 750, as well as save EPA, industry, and laboratory resources.

EPA states that it believes the retrospective analysis fully supports the conclusion that waivers may be granted for acute dermal toxicity studies for pesticide technical chemicals, except for fumigants and rodenticides.  Waivers may be accepted for fumigants and rodenticides on a case-by-case basis with appropriate scientific rationale.  Once the guidance is issued in final form, EPA states that applicants who wish to pursue waivers for these studies would submit formal waiver requests as part of the registration application through existing processes and cite the guidance as support for the requests.  EPA maintains the ability to request acute dermal toxicity data on a case-by-case basis, but states that it anticipates granting the waiver in most cases.

Comments on the draft guidance are due on or before November 9, 2020, and can be submitted at http://www.regulations.gov under Docket ID No. EPA-HQ-OPP-2016-0093.

EPA also announced the launch of its new webpage that provides metrics and strategies for reducing and replacing animal testing, including links and resources to all pertinent guidance and work plans tied to the larger Toxicology in the 21st Century Initiative across the federal government.  The directive, issued by EPA Administrator Andrew Wheeler in September 2019, calls for EPA to reduce animal testing and to reduce funding 30 percent by 2025 and eliminate it by 2035.  EPA states that its actions to date to support these efforts include:

• In September 2019, EPA announced $4.25 million in funding for five universities to research and develop alternative test methods for evaluating chemical safety.
• In December 2019, EPA convened a conference for achieving reduced animal testing in chemical safety research and updated its list of New Approach Methodologies (NAM) that could be used in EPA’s work under the amended Toxic Substances Control Act, including adding 21 new test guidelines related to health and ecological effects and six additional EPA policies that reduce the use of animal testing.
• In June 2020, EPA released a NAMs work plan that details how EPA plans to develop, test, and apply chemical safety testing approaches without the use of animals.
• In February 2020, EPA issued final guidance waiving the subacute dietary testing of pesticides on birds when the additional information is unnecessary to support a pesticide registration decision, which is expected to save 720 test animals annually.
• In July 2020, EPA announced new guidance to reduce unnecessary testing on fish, which is expected to save 240 test animals annually.

EPA will host its Second Annual Conference on the State of the Science on Development and Use of NAMs for Chemical Safety Testing virtually on October 19 and 20, 2020.  Additional information on EPA’s efforts to reduce animal testing is available here.

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