By Heather F. Collins, M.S. and Barbara A. Christianson
On October 2, 2019, the U.S. Environmental Protection Agency (EPA) published a notice in the Federal Register announcing the availability of, and soliciting public comment on, the draft document entitled “Antimicrobial Performance Evaluation Program (APEP) A (Draft) Risk Based Strategy to Ensure the Effectiveness of Hospital-Level Disinfectants” (draft Strategy). EPA states that “The draft Strategy provides a framework to ensure that registered hospital-level disinfectants and tuberculocide products continue to meet Agency efficacy standards once they are in the marketplace.”
The draft Strategy was developed in response to EPA’s Office of Inspector General’s (OIG) report “EPA Needs a Risk-Based Strategy to Assure Continued Effectiveness of Hospital-Level Disinfectants,” which recommends EPA’s Office of Pesticide Programs (OPP) to develop a risk-based strategy to assure the effectiveness of public health pesticides used in hospital settings once products are in the marketplace. EPA developed the draft Strategy based on OIG’s recommendations.
EPA states that the draft Strategy uses a risk-based approach “to inform the Agency on the prioritization and selection of hospital-level disinfectants and associated label claims for testing,” and states that its order of priority is as follows:
- Product label claims for specific microbes and disease prevalence data;
- Evaluation of uncommon label claims and unique product application processes; and
- Evaluation of products tested using new and/or recently revised methods.
Additional refinement factors may also be considered such as:
- Issues identified during post-registration, product reregistration, and registration review;
- Trends observed under the previous testing program (Antimicrobial Testing Program (ATP)); and
- Products with high production volumes.
EPA states that it will be considering two options individually or in combination for obtaining samples for testing: (1) EPA purchase of products in the marketplace; and (2) product samples provided by the registrant. Several options for allocating efficacy and chemistry testing resources may be utilized individually or in combination; these options include: (1) Office of Pesticide Programs Microbiology Laboratory and the Analytical Chemistry Laboratory; (2) interagency agreements and contracts; (3) third-party verification testing; and (4) registrant testing; and/or Data Call-Ins.
In the Federal Register notice, EPA lists six focus questions on which it is specifically requesting public comment:
- Please comment on the proposed risk factors and refinements, their proposed prioritization, their strengths and limitations, and recommendations for other risk factors not considered.
- Are the options provided for sample collection suitable for the purpose of the testing program, and if not, what approaches would you suggest to optimize sample collection. Please provide advantages and disadvantages to your recommendations as appropriate.
- Should the Agency and/or stakeholders conduct the laboratory evaluation (formulation chemistry and product efficacy) of disinfectant products? Provide examples to support your opinions and itemize situations where one approach would be more favorable versus the other.
- Please comment on the flexibility and feasibility of the example workplan approach (See Appendix A, draft Strategy).
- Please comment on the proposed communication strategy to convey test results to registrants and the general public including the preferred frequency of updates.
- Please provide suggested routes for resolution of efficacy failures. Previously, these were addressed by “regulatory fixes” to include retesting, label amendments, etc.
EPA states that the draft Strategy may be of interest to health care/hospital professionals and all entities who have EPA registered antimicrobial products that are available in the marketplace, particularly those with products that make hospital disinfectant claims (e.g., claims against Staphylococcus aureus and Pseudomonas aeruginosa) and other claims for notable public health pests (e.g., Clostridium difficile, methicillin resistant Staphylococcus aureus, Mycobacterium spp.).
All comments on the draft Strategy document must be received by EPA on or before December 2, 2019. EPA expects to publish the APEP final strategy in 2020 and schedule implementation to begin in 2022.
Documents referenced in the draft Strategy are available at www.regulations.gov in Docket Number EPA-HQ-OPP-2018-0265. More information on the APEP is available on our blog.
By Lisa M. Campbell and Heather F. Collins, M.S.
On August 28, 2019, the U.S. Environmental Protection Agency (EPA) released the Frequently Asked Questions (FAQ) web resource for the Series 810 – Product Performance Test Guidelines: Antimicrobial Efficacy Test Guidelines. As of August 28, 2019, efficacy testing should be in compliance with the following Product Performance Test Guidelines published by EPA in February 2018:
- 810.2000: General Considerations for Testing Public Health Antimicrobial Pesticides, Guide for Efficacy Testing;
- 810.2100: Sterilants, Sporicides, and Decontaminants, Guide for Efficacy Testing; and
- 810.2200: Disinfectants for Use on Environmental Surfaces, Guide for Efficacy Testing.
The guidelines provide recommendations for the design and execution of laboratory studies to evaluate the effectiveness of antimicrobial pesticides against public health microbial pests. 83 Fed. Reg. 8666. EPA states that these FAQs “provide prompt and transparent guidance to all applicants regarding commonly asked questions concerning the 810 guidelines updated in February 2018.”
With the exception of confirmatory testing (as described under OCSPP guideline 810.2000, Section (B)(7)), all studies initiated on or after August 28, 2019, should be in compliance with the 2018 revised guidelines for testing. The study initiation date is defined under 40 CFR Part 160.3 as the date the protocol is signed by the study director. Studies that were initiated prior to the implementation date but submitted to EPA for review after the implementation date may use either the previous 2012 version of the guidelines or the 2018 revised guidelines, as appropriate. EPA states that it “intends to address confirmatory testing through a separate guidance, which will be made available for public comment prior to finalization.”
The FAQs include general testing questions and questions related to each specific guideline. The appendices to the FAQs include examples of label use-directions for dilutable products, repeat testing guidance with example scenarios, and sample virucidal calculations.
There has been some concern in the regulated community regarding the need for clarification on the guidelines before they became effective. EPA’s new FAQs are intended to provide these clarifications, but the timing of their issuance may be of concern to some. Also of interest is whether additional FAQs will be issued in the future.
By Lisa M. Campbell and Heather F. Collins, M.S.
On May 3, 2019, the U.S. Environmental Protection Agency (EPA) announced it was making final a single correction to the data requirements for antimicrobial pesticide products codified in 40 C.F.R. Part 158, subpart W. 84 Fed. Reg. 18993. The correction clarifies that the 200 parts per billion (ppb) level described in the antimicrobial pesticides data requirements regulations (40 C.F.R. § 158.2230(d)) “is based on total estimated daily dietary intake for an individual and not on the amount of residue present on a single food,” as EPA states was incorrectly implied by the previous regulatory text. EPA initially proposed this change on August 18, 2017 (82 Fed. Reg. 39399) because it agreed to do so in a settlement agreement with the American Chemistry Council (ACC) after ACC filed a petition for review of the 2013 final rule titled “Data Requirements for Antimicrobial Pesticides” (78 Fed. Reg. 26936 (May 8, 2013)) in the U.S. Court of Appeals for the District of Columbia Circuit. Specifically, EPA agreed to make this correction to “make the language consistent” with the U.S. Food and Drug Administration’s (FDA) policy set forth in FDA’s “Guidance for Industry, Preparation of Food Contact Notifications for Food Contact Substances: Toxicology Recommendations. Final Guidance. April 2002.” EPA states that the change is intended to “enhance understanding of the data required to support an antimicrobial pesticide registration and does not alter the burden or costs associated with these previously promulgated requirements” and that it is not establishing “any new data requirements or any other revisions (substantive or otherwise) to existing requirements.” The final rule will become effective on July 2, 2019.
By Lisa M. Campbell and Lisa R. Burchi
On November 7, 2018, the U.S. Environmental Protection Agency (EPA) announced that it was ordering Pool Water Products Inc. to stop selling an improperly registered pesticide, ALL CLEAR 3” Jumbo Chlorinating Tablets. The announcement states that even though the ALL CLEAR 3” Jumbo Chlorinating Tablets product was registered with EPA, Pool Water Products was selling and distributing an unregistered version of the product made in China that has not been evaluated by EPA.
EPA’s action, which it states applies to nationwide distribution, transport and sales of the product, follows a statewide stop-sale order issued earlier this month by the Arizona Department of Agriculture when state inspectors discovered the unregistered pesticide, which is used to disinfect pools, during an August 30 inspection of the company’s Phoenix warehouse.
This case exemplifies the need for companies to understand Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) registration and amendment requirements, and the importance that a product’s label, formula, and manufacturing process match exactly with the information submitted to EPA and upon which EPA relied in approving the registration. Many composition and processing changes require an amendment to be approved by EPA; failure to do so could result in an enforcement action such as this one.
More information on pesticide registration issues is available on our blog.
By Heather F. Collins, M.S., and Sheryl Lindros Dolan
On June 21, 2018, during the U.S. Environmental Protection Agency’s (EPA) Office of Pesticide Programs (OPP) webinar, EPA discussed the new draft risk-based strategy for ensuring the performance of public health antimicrobial products and announced the intended replacement of the former Antimicrobial Testing Program (ATP) with the new Antimicrobial Product Evaluation Program (APEP). Comments on the draft risk-based strategy may be submitted to EPA until July 16, 2018.
Public health antimicrobial products are those products that bear a claim to control microorganisms that pose a threat to human health, and whose presence cannot readily be observed by the user, including microorganisms infectious to people in any area of the inanimate environment. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) requires product performance (i.e., efficacy) data to support registration of antimicrobial products bearing a public health claim.
EPA began the webinar with an overview of the Office of Inspector General (OIG) Report entitled “EPA Needs a Risk-Based Strategy to Assure Continued Effectiveness of Hospital-Level Disinfectants.” Report #16-P-0316 (Sept. 19, 2016). OIG conducted a review of EPA’s ATP to “determine whether the program ensures the efficacy of EPA-registered hospital sterilants, disinfectants, and tuberculocides (“hospital-level disinfectants”); and to evaluate options for improving the ATP.” See Bergeson & Campbell, P.C.’s article dated September 21, 2016, “Results of EPA OIG’s Review of EPA’s Antimicrobial Testing Program” for a full summary of the OIG report. In the 2016 report, OIG recommends OPP suspend administering the current ATP and develop a risk-based strategy to assure the effectiveness of public health pesticides used in hospital settings once products are in the marketplace. EPA agreed with OIG’s recommendations.
EPA provided that “[t]he intent of the [APEP] is to ensure continued effectiveness of antimicrobial products with public health claims (hospital disinfectants, tuberculocides, and other health care claims) in the marketplace. The maintenance and development of technically-sound test methods, quality improvement tools (e.g., peer review of new protocols), and outreach and stewardship activities will further support the program.”
The risk-based testing strategy will ensure the effectiveness of public health pesticides used in hospital settings by:
- Establishing a framework for periodic testing after registration;
- Defining a program that is responsive to current public health risks;
- Identifying risk factors for selecting products to test;
- Establishing a process to be used for obtaining samples for testing; and
- Setting a date to begin risk-based post-registration testing.
Risk-based factors under consideration by EPA include:
- Use of healthcare-associated infection data reports;
- Claims against microorganisms of greatest concern to healthcare-associated infections (e.g., Clostridium difficile, MRSA,VRE);
- Emerging pathogens and homeland security considerations;
- Trends in previous ATP compliance history (e.g., claims against Mycobacterium bovis BCG);
- Atypical label claims (e.g., very short contact times, use sites and surfaces, new product delivery and application procedures);
- Claims not evaluated under the previous ATP;
- New and unusual active ingredients;
- Formulation chemistry-related issues (e.g., shelf-life/stability once prepared, lack of expiration dates);
- Use of new or procedurally-revised test methods;
- Tips and complaints;
- Issues identified during reregistration (e.g., frequency of repeat testing, acceptance criteria not met); and
- Link to other federal initiatives.
OIG recommends a functional program begin after registration review is completed in 2022. According to OIG, the development of a solid, acceptable testing strategy is key -- the strategy must be finalized and communicated to regulated and public health communities. OIG specified other EPA outreach activities for the testing program that must be considered, e.g., setting and clearly communicating goals and establishing the baseline reporting mechanisms.
EPA expects to release this final strategy in November 2018 and seeks public input prior to implementation. Please submit your comments on this topic by July 16, 2018, to the Office of Pesticide Programs Docket, EPA-HQ-OPP-2018-0265 at https://www.regulations.gov.
For additional information, please visit https://www.epa.gov/pesticide-registration/antimicrobial-testing-program or https://www.epa.gov/pesticide-registration/webinar-risk-based-strategy-ensure-continued-effectiveness-hospital.
By Heather F. Collins, M.S. and Margaret R. Graham
On February 28, 2018, the U.S. Environmental Protection Agency (EPA) announced the availability of three Group B -- Antimicrobial Efficacy Test Guidelines, under Series 810, Product Performance Test Guidelines. The guidelines provide recommendations for the design and execution of laboratory studies to evaluate the effectiveness of antimicrobial pesticides against public health microbial pests. 83 Fed. Reg. 8666. The three final guidelines are:
EPA states these “test guidelines are part of a series of test guidelines established by the Office of Chemical Safety and Pollution Prevention (OCSPP) for use in testing pesticides and chemical substances. The test guidelines serve as a compendium of accepted scientific methodologies and protocols for testing that is intended to provide data to inform regulatory decisions.”
EPA issued draft guidelines in June 2015 and solicited comments. EPA states that some comments received on those draft guidelines have been incorporated into the final versions. EPA states that the revision “is more user friendly and clarifies topics such as confirmatory data, repeat testing, hard water formulation, wetness determination testing for towelettes, and internal toilet testing … [and] also includes information on supplemental testing policies such as lower certified limits, revision of the AOAC Use Dilution Method performance standards and clarified technical details for efficacy testing.”
Documents pertaining to the revision of the product performance guidelines, including public comment submissions, and the agency’s response to comments are available at www.regulations.gov, in Docket No. EPA-HQ-OPP-2015-0276. More information on test guidelines is available on our blog.
By Sheryl Lindros Dolan and Heather F. Collins, M.S.
On September 29, 2017, the U.S. Environmental Protection Agency (EPA) announced the availability of two final test method Standard Operating Procedures (SOP) for evaluating the efficacy of antimicrobials against spores of Clostridium difficile (C. diff):
EPA also released regulatory guidance for test criteria and pesticide claims for these products, specifically “Methods and Guidance for Testing the Efficacy of Antimicrobial Products Against Spores of Clostridium difficile on Hard Non-Porous Surfaces.” EPA states that these test methods and guidance “provide a framework for registrants who seek to make a claim for antimicrobial pesticide products to control C. difficile spores on hard, non-porous surfaces.”
C. diff is an anaerobic, spore-forming bacterium and a frequent cause of hospital-acquired infections. The spores survive on hard surfaces such as glass, metals, and plastics that are commonly found in health-care settings. Hospitals and other health care facilities often use antimicrobial pesticides to reduce the number of spores on environmental surfaces. Registrants seeking antimicrobial product registrations with claims to control C. diff will need to carefully review these documents as they consider the efficacy data that EPA will likely require to support these claims, as well as the claims that can be made and supported for these products.
EPA MLB SOP MB-28 describes the test methodology for producing and storing standardized spore suspensions of C. diff based on ASTM E2839, Standard Test Method for Production of C. difficile Spores for Use in Efficacy Evaluation of Antimicrobial Agents (ASTM International). A spore suspension should be developed and qualified according to EPA MLB SOP MB-28 before an efficacy evaluation can be performed using method EPA MLB SOP MB-31. EPA MLB SOP MB-31 describes a quantitative method intended for evaluating the sporicidal efficacy of liquid disinfectants against spores of C. diff on inanimate, hard, non-porous surfaces.
EPA solicited comments on the clarity of the test method SOPs and the regulatory guidance in December 2016. EPA received comments from 12 entities. The primary areas of comment included the following:
- Test carrier interaction;
- Additional method validation;
- Verification testing;
- Soil load;
- Use of a standard setting organization to publish test methods;
- Proposed revisions to the guidance document; and
- Proposed revisions to the standard operating procedures.
EPA revised the drafts to incorporate suggested changes. EPA posted its response to those comments in Docket No. EPA-HQ-OPP-2016-0753-0026.
Some of the changes to the guidance document based on submitted comments include clarifying:
- Three batches of test product should be tested on independent test days;
- The inclusion of the three-part soil load is used for all test, control, and test system control carriers; and
- The current document supersedes the previous 2014 guidance document.
The new guidance proposes updated standard label claims and special instructions that are intended to provide greater clarity to the user community.
EPA’s response to comments and other documents associated with this action are available in Docket No. EPA-HQ-OPP-2016-0753 at www.regulations.gov. The methods and guidance also are found on EPA’s Antimicrobial Testing Methods & Procedures Developed by EPA's Microbiology Laboratory webpage, at the Methods tab as Method IDs MB-28 and MB-31, and at the Guidance tab as Sporicidal Claims Against Clostridium difficile.
C. diff is widely recognized as one of the most common causes of healthcare-acquired infection. C. diff infections, spread by transmission of bacterial spores, have proven difficult to prevent. EPA’s new guidance and test methods are intended to clarify the efficacy standards that pesticide products claiming to reduce C. diff spores must meet, as well as the associated claims that can be made. This guidance should bring more clarity to pesticide registrants seeking to register such products and to healthcare facilities in their identification of registered pesticide products that may help them to reduce C. diff spores and thus help with prevention efforts.
By Sheryl L. Dolan and Margaret R. Graham
On August 1, 2017, the U.S. Environmental Protection Agency (EPA) announced the availability of two final test method Standard Operating Procedures (SOP) for evaluating the efficacy of antimicrobial pesticides against two biofilm bacteria, Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus):
EPA also released regulatory guidance for test criteria and pesticide claims for these products, specifically Guidance for Testing the Efficacy of Antimicrobial Products Against Biofilms on Hard, Non-Porous Surfaces. Drafts of the SOPs and the guidance were initially released in October 2016 for comment. EPA received comments from nine entities and revised the drafts to incorporate suggested changes. EPA posted its response to those comments in Docket EPA-HQ-OPP-2016-0357.
EPA states that the two methods are adapted from ASTM International (ASTM) standard methods. EPA MLB SOP MB-19 is used to generate the P. aeruginosa or S. aureus biofilm on coupons. EPA MLB SOP MB-20, the Single Tube Method, then is used to determine the effectiveness of an antimicrobial product in reducing bacteria in biofilm on the coupons.
Notable aspects of the test criteria and claims guidelines include:
- The mean log density for the test organisms of 8.0 to 9.5 for P. aeruginosa and 7.5 to 9.0 for S. aureus; and
- Product performance criterion of a minimum 6-log reduction.
The guidance lists several examples of claims for efficacy against public health biofilm that EPA states are acceptable.
EPA MLB SOP MB-20 is designed to evaluate the efficacy of antimicrobial products that are water soluble powders or liquid formulations. If a company wishes to test a different type of product formulation, or test different target microorganisms, or make any other proposed modifications, it would be well advised to submit proposed alternatives to EPA for review and approval. EPA specifically cautions that the current methodologies are intended for data development to support claims for products registered for use on hard, non-porous surfaces and are not suitable for use sites associated with water systems.
The EPA’s Office of Pesticide Programs’ (OPP) regulation of biofilms has been the subject of increasingly intense commercial interest for years and the availability of this testing guidance is welcome news. While not all will agree with the approach, the new guidance is a helpful addition to OPP’s testing guidance portfolio.
More information on antimicrobial pesticides is available on our blog under key phrase Antimicrobial Pesticide. More information on the methods and guidance is available on EPA’s website and in Docket No. EPA-HQ-OPP-2016-0357.
By Lynn L. Bergeson, Sheryl Lindros Dolan, and Margaret R. Graham
On February 17, 2017, the U.S. Environmental Protection Agency (EPA) announced that the Centers for Disease Control and Prevention (CDC) issued guidance revising its recommendation regarding controlling Candida auris (C. auris) infections in U.S. healthcare facilities. The CDC guidance now recommends a “thorough daily and terminal cleaning and disinfection” of patient rooms in which C. auris infection or colonization was present … with the use of an [EPA]-registered hospital-grade disinfectant effective against Clostridium difficile [(C. difficile)] spores.” The new guidance updates the CDC’s clinical alert on C. auris issued in June 2016 after receiving reports from international healthcare facilities that C. auris, “an emerging multidrug-resistant (MDR) yeast, [was] causing invasive healthcare-associated infections with high mortality.” Previously, CDC recommended use of an EPA-registered disinfectant with a fungal efficacy claim.
As EPA is responsible for regulating hospital disinfectants and other antimicrobial pesticides used in healthcare facilities, this updated guidance has particular interest and significance for registrants of hospital disinfectant products. EPA maintains a list of registered antimicrobial products effective against C. difficile (List K) and states that “Guidance to the companies that register antimicrobial products and seek label claims against C. auris is under development.”
By Lisa M. Campbell, Lisa R. Burchi, and Margaret R. Graham
The U.S. Environmental Protection Agency (EPA) has recently announced the availability of two proposed test methods and associated testing guidance for evaluating antimicrobial pesticides against two biofilm bacteria, Pseudomonas aeruginosa and Staphylococcus aureus, for comments. EPA states that registrants of antimicrobial products with public health claims are “required to submit efficacy data to EPA in support of the product’s registration” under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). EPA is soliciting comments on the clarity of the standard operating procedures and the regulatory guidance. The two test methods are:
The Draft Guidance to Assess the Efficacy of Antimicrobial Pesticide Products Intended to Control Public Health Biofilms on Hard, Non-Porous Surfaces describes biofilms and their public health significance; the two test procedures for developing efficacy data supporting biofilm claims; products that may be eligible for biofilm claims; test criteria; data submission procedures for efficacy data; and labeling guidance.
The draft guidance states that the term biofilm “is reserved for claims against biofilm that contain specific bacteria that are directly or indirectly infectious or pathogenic to humans,” and “biofilm claims are considered to be public health claims for which the agency must review and approve appropriate efficacy data.” EPA states: “Examples of use sites that may be supported by the biofilm test methodologies herein, and found acceptable, include restrooms, shower stalls, sink basins or drains (excluding the drain pipe) and nearby hard, non-porous surfaces of walls, countertops, and instrument trays in patient care areas of hospitals. In contrast, claims against non-public health slimicides must also be supported by appropriate efficacy data, however, submission of the data is only required when requested by the EPA.”
The Draft Guidance also sets forth examples of acceptable label claims against public health biofilms and acceptable non-public health claims. The examples of acceptable label claims against public health biofilms are:
- Kills 99.9999% of bacteria* in biofilm on a hard, non-porous surface;
- Kills a minimum of 99.9999% of bacteria* in biofilm;
- Reduces at least 99.9999% of bacteria* growing in biofilm;
- Formulated to kill 99.9999% of bacteria* in biofilm;
- Other related claims:
- Kills biofilm bacteria*; and
- Penetrates biofilm, killing the bacteria* living there.
*[List of bacteria “tested as a biofilm”; at a minimum, Pseudomonas aeruginosa and Staphylococcus aureus].
Examples of acceptable non-public health claims supported by appropriate efficacy data include:
- Cleans away microorganism slime/grunge;
- Maintains control of slime; and
- Controls slime-forming microorganisms.
Comments will be accepted until December 5, 2016.