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 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.
By Lisa M. Campbell, Lisa R. Burchi, and Timothy D. Backstrom
On September 19, 2016, the U.S. Environmental Protection Agency’s (EPA) Office of Inspector General (OIG) issued a report, EPA Needs a Risk-Based Strategy to Assure Continued Effectiveness of Hospital-Level Disinfectants, the result of OIG’s review of EPA’s Antimicrobial Testing Program (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.” OIG found that the ATP “does not assure that hospital-level disinfectant products continue to be effective after they are registered,” specifically that:
- Once the EPA tests a product and it passes, it is listed as Agency Confirmed Efficacy on the agency’s website and is typically not tested again; the long-term efficacy of the product cannot be assured.
- EPA relies on manufacturers to voluntarily submit product samples for testing. In the last three years, out of the approximately 300 registered hospital disinfectant products that have not been tested, manufacturers submitted only 12 samples to EPA for ATP efficacy testing.
Importantly, however, OIG concludes: “Although the program as currently designed and conducted does not assure that most hospital disinfectant products continue to be effective, at this point it is redundant and unnecessary to make adjustments, since the EPA is concurrently having the products re-registered.”
OIG makes two major recommendations:
- EPA should suspend administering the current Antimicrobial Testing Program until completion of the one-time re-registration process.
- EPA should develop a risk-based antimicrobial testing strategy to assure the effectiveness of public health pesticides used in hospital settings once products are in the marketplace. At a minimum, OIG states, the strategy should:
- Include a framework for periodic testing to assure products continue to be effective after registration.
- Define a program scope that is flexible and responsive to current and relevant public health risks.
- Identify risk factors for selecting products to test.
- Identify the method to be used for obtaining samples for testing.
- Designate a date to commence risk-based post-registration testing.
In its response, EPA agreed with OIG’s recommendations, and stated it will develop a plan to coordinate and implement the discontinuation of the present-day program, with the closure of the ATP program to take place by November 2017. EPA also stated that by December 2018 it plans to develop a risk-based strategy to assure the effectiveness of public health pesticides used in hospital settings once products are in the marketplace.
Registrants of the affected products should monitor closely the development of EPA’s plans both to discontinue the program and to establish this new risk-based strategy for assuring product efficacy.
By Lisa R. Burchi and Margaret R. Graham
On September 2, 2016, the U.S. Environmental Protection Agency (EPA) issued guidance to registrants on the process for making claims against emerging viral pathogens not on EPA-registered disinfectant labels (Guidance). A draft of this guidance was issued in April 2016 and comments were sought at that time. More information concerning the draft guidance is available in our blog item EPA Combats Emerging Pathogens Through Updating Guidance for Antimicrobial Pesticide Products.
The current Guidance document, which EPA states “provides general guidance to registrants that can be used to identify effective disinfectant products for use against emerging viral pathogens and to permit registrants to make limited claims of their product’s efficacy against such pathogens,” includes changes incorporated following EPA’s review of the three public comments received in response to that draft.
The Guidance retains the voluntary two-stage process, but amends the first stage as indicated:
- In the first stage, which may be performed prior to any outbreak, registrants with an eligible disinfectant product may submit a request, via label amendment or during the registration of a new product, to control a specific emerging viral pathogen to add a designated statement to the master label and additional terms to the product registration. If the product meets the eligibility criteria suggested in this Guidance, [EPA] generally will approve the amendment. Approval of the amendment would include additional terms and conditions of registration regarding how the designated statement may be published and communicated.
In its response to comments document, EPA responded to several comments, including:
- Changes were made to EPA’s mandated non-label statements to remove certain language that could be considered redundant.
- EPA is developing a coordinated process with the Centers for Disease Control and Prevention for the purpose of providing a more standardized and consistent approach to emerging viral pathogen outbreaks. Once this process is established, the agency expects to consult with the U.S. Department of Agriculture to develop a similar approach.
- The Guidance document allows for the addition of emerging pathogen claim language to the master label during the new product registration process if the product is eligible. Additional language has been added to multiple locations in the Guidance document to clarify that the process is appropriate for new product registrations.
- EPA “may consider allowing use of additional modes of claim communication under future versions of this Guidance document, however, hangtags and other promotional materials are not authorized at this time. Because the statements authorized under this Guidance are pesticidal claims that do not meet the FIFRA registration criteria, it is essential that these off-label claims are not made outside of an emerging pathogen outbreak as described in the Guidance. Accordingly, the Guidance limits these off-label claims primarily to communications outlets that are wholly within the registrant’s control (800 numbers, social media and websites) from which the off-label claims can be immediately removed. Hangtags and other promotional materials directed towards general consumers are largely out of the registrant’s control once the products enter the chain of commerce, and may persist long after the period during which the off-label claims are authorized.”
EPA also notes that this Guidance document “provides general guidance to EPA, pesticide registrants, applicants for pesticide registrations, and the public. This guidance is not binding on EPA or any outside parties, and EPA may depart from the guidance where circumstances warrant and without prior notice.”
By Lisa M. Campbell and Lisa R. Burchi
In response to the increasing concerns regarding emerging viral pathogens that are not on U.S. Environmental Protection Agency (EPA)-registered disinfectant labels, EPA announced on April 7, 2016, that it was updating its Guidance regarding emerging viral pathogens. Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), EPA is authorized to evaluate the efficacy of antimicrobial products intended to control pathogens that can be detrimental to public health. Many believe that the process under which registrants can identify “effective disinfectant products for use against emerging pathogens,” and the process for EPA to “permit registrants to make limited claims of their product’s efficacy against such pathogens,” have not been clear and efficient. EPA notes, for example, that “[emerging] pathogens are often unavailable commercially, and standard methods for laboratory testing may not have been developed,” such that it “can be difficult to assess the efficacy of EPA-registered disinfectants against such pathogens in a timely manner and to add these viruses to existing product registrations.”
EPA hopes that its Guidance will “expedite the process for registrants to provide useful information to the public” regarding products that may be effective against emerging viral pathogens associated with certain human or animal disease outbreaks.
EPA’s new draft Guidance document, Draft Guidance to Registrants: Process for Making Claims Against Emerging Viral Pathogens Not on EPA-Registered Disinfectant Labels, describes “a voluntary two-stage process to enable the use of certain EPA-registered disinfectant products against these emerging viral pathogens, uses not previously identified on the product label”:
- First Stage: This stage may be performed prior to any outbreak. EPA summarizes the first stage as follows: “registrants with an eligible disinfectant product may submit a request, via label amendment, to add a designated statement to the master label and additional terms to the product registration. If the product meets the eligibility criteria suggested in this Guidance, [EPA] generally will approve the amendment. Approval of the amendment would include additional terms and conditions of registration regarding how the designated statement may be published and communicated.”
- Second Stage: This stage would occur only during a human or animal disease outbreak caused by an emerging virus. EPA summarizes this stage as follows: “In this stage, registrants of products with the previously mentioned label amendment and terms of registration would be allowed to use the designated statement in off-label communications intended to inform the user community/public that the disinfectant product(s) may be used against the specific emerging viral pathogen. These off-label statements can inform the public about the utility of these products against the emerging pathogen in the most expeditious manner and can be more easily removed once the outbreak has ended than statements on a label.”
Comments related to clarity of this Guidance will be accepted until May 6, 2016. For more information, please see our memorandum EPA Announces Updated Guidance for Antimicrobial Pesticide Products Intended to Combat Emerging Pathogens.
By Lisa M. Campbell and Margaret R. Graham
On January 28, 2016, in docket EPA–HQ–OPP–2015–0302, the U.S. Environmental Protection Agency (EPA) posted its revised Antimicrobial Pesticides Use Site Index (USI). In the USI, EPA states that it “has developed [the USI] to provide guidance about the antimicrobial pesticide use sites associated with these antimicrobial pesticide use patterns,” and it “is a guidance document to assist applicants in identifying the data that are necessary to support registration of products and to determine if labeled uses necessitate establishment of a tolerance or exemption from the requirement of a tolerance.” EPA also posted a Response to Public Comments which stated that there have been a number of changes based on comments received, specifically from the American Chemistry Council’s Biocides Panel (ACC or Panel) and the Consumer Specialty Products Association (CSPA). These changes include:
- Clarifying that the USI is a guidance document and that the sites in the USI are not intended for use in labeling;
- Simplifying the USI by organizing example use sites into broader groups;
- Using a tabular format to provide examples of use sites organized by food use description (i.e., direct food use, indirect food use, and nonfood use) within each major use pattern category to make it easier to follow;
- Clarifying that “food” is defined under the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. Section 321(f), and that definition applies, as appropriate, to all food use descriptions;
- Revising the description of “nonfood use” to provide better clarity;
- Deleting from the USI some example use sites that were ambiguous, too vague, too specific, or incorrectly categorized regarding major use pattern category or food use description; and
- Incorporating many of ACC’s suggestions of specific use sites to include in the materials preservatives and wood preservatives general use pattern categories.
More information regarding the draft USI is available in our blog post EPA Releases Guidance Document: Antimicrobial Pesticides Use Site Index.
By Lisa M. Campbell and Sheryl L. Dolan
On September 8, 2015, the Environmental Protection Agency (EPA) announced that it will host a Disinfection Hierarchy Stakeholder Workshop and corresponding webinar on October 7, 2015, from 8:30 a.m. - 5:00 p.m. (EDT). The “disinfection hierarchy” describes the descending order of susceptibility of classes of microorganisms to antimicrobial chemicals. Demonstrated efficacy against a representative organism would support a manufacturer’s claims against more susceptible (easier to kill) organisms, potentially eliminating the need to test against, or alternatively, to submit data for each individual organism. EPA has relied on the disinfection hierarchy concept historically. For example, EPA relied on the disinfection hierarchy concept to take timely action to address the H1N1 virus in 2009, by allowing reliance on Influenza A data. More recently, EPA states that it agreed that use of a registered hospital disinfectant with a label claim for use against a non-enveloped virus was appropriate for disinfection of surfaces contaminated with the ebola virus.
EPA is considering expanding its use of disinfection hierarchy concepts for the registration of public health antimicrobial pesticides. EPA states that its goals for expanding the use of these concepts are:
- To provide guidance to health care officials and the public on the most effective type of registered antimicrobial products on the market to combat an emerging pathogen; and
- To increase the efficiency of, and lower the costs associated with, registering antimicrobial pesticides, while maintaining a high level of public health protection.
According to the announcement, the workshop will focus on the scientific merits of the hierarchy, and will provide a forum for stakeholders to discuss:
- The current science on which disinfection hierarchy concepts are based;
- Scientific issues that may present challenges for use of the disinfection hierarchy in registering antimicrobial pesticide products; and
- Ideas on how to address these issues.
A panel of approximately 15 stakeholders from the public sector, academia, and industry will address a series of charge questions, followed by the opportunity for audience questions or comments. The current list of panel members is available here.
EPA’s Office of Pesticide Programs has developed a draft white paper on disinfection hierarchy concepts that will serve as the basis for discussion during the workshop. The draft white paper includes questions on which EPA states it is seeking input. The agenda for the workshop is available here.
More information on disinfection hierarchy is available in Bergeson & Campbell, P.C.’s (B&C®) memorandum Summary of Ninth Antimicrobial Workshop.
By Lisa M. Campbell and Lisa R. Burchi
On July 24, 2015, the U.S. Environmental Protection Agency (EPA) issued a Federal Register notice extending the public comment period regarding its proposed Antimicrobial Pesticides Use Site Index (USI) from July 31, 2015 to August 31, 2015. The initial Federal Register notice announcing the availability of EPA’s guidance on the USI was issued on July 1, 2015.
By way of background, in 2014, EPA issued a final rule on Data Requirements for Antimicrobial Pesticides amending the regulations setting forth the data requirements that support an application to register a pesticide product. The final rule contains the data requirements specifically applicable to antimicrobial pesticides that were codified in 40 C.F.R. Part 158, subpart W. The final rule lists 12 antimicrobial use patterns in 40 C.F.R. § 158.2201. The data requirements applicable to a pesticide product depend in part on the product’s use pattern. The general use patterns are broad designations, and are used as columns in the antimicrobial data requirements tables to identify which data requirements might be pertinent to the particular pesticide use site.
EPA has developed the USI to assist antimicrobial pesticide applicants and registrants and to assist EPA staff to identify the use pattern that applies to a pesticide product, and thus the data requirements that must be met to register the product. EPA states that the USI serves as a compilation of the specific use sites that are commonly listed on antimicrobial labels and links these commonly listed use sites with the twelve general use patterns.
The posting of this proposed guidance document for public comment is intended to satisfy a condition of the March 2, 2015, settlement agreement between EPA and the American Chemistry Council (ACC) that followed ACC’s July 2013 initiation of a legal challenge to the data requirements regulation in the U.S. Court of Appeals for the District of Columbia Circuit.
In addition to extending the comments, EPA also published in the docket a Question and Answer document on the USI Webinar for questions submitted to EPA prior to the July 14, 2015, webinar. Additional information regarding the USI is available in EPA Docket EPA-HQ-OPP-2015-0302.
By Lisa M. Campbell
On July 01, 2015, the U.S. Environmental Protection Agency (EPA) issued a notice announcing the availability of and requesting public comment on a proposed guidance document called the Antimicrobial Pesticide Use Site Index (USI).
In 2014, EPA issued a final rule amending the regulations setting forth the data requirements that support an application to register a pesticide product. The final rule contains the data requirements specifically applicable to antimicrobial pesticides, which were codified in 40 C.F.R. Part 158, subpart W. The final rule lists 12 antimicrobial use patterns in 40 C.F.R. § 158.2201. The data requirements applicable to a pesticide product depend in part on the product’s use pattern. The general use patterns are broad designations and are used as columns in the antimicrobial data requirements tables to identify which data requirements might be pertinent to the particular pesticide use site.
EPA has developed the USI to assist antimicrobial pesticide applicants and registrants and EPA staff to identify the use pattern that applies to a pesticide product, and thus the data requirements that must be met to register the product. EPA states that the USI serves as a compilation of the specific use sites that are commonly listed on antimicrobial labels and links these commonly listed use sites with the twelve general use patterns.
The posting of this proposed guidance document for public comment is intended to satisfy a condition of the March 2, 2015, settlement agreement between EPA and the American Chemistry Council (ACC) that followed ACC’s July 2013 initiation of a legal challenge to the data requirements regulation in the U.S. Court of Appeals for the District of Columbia Circuit. Comments are due by July 31, 2015.