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United States Regulation of Antimicrobial Pesticides

Sally HayesScientific and Regulatory Consultants, Inc., Columbia City, IN, USA

14.3

Introduction

The Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) outlines the registration requirements for antimicrobial pesti-cides in the United States. This law, administered by the Environ-mental Protection Agency (EPA), is not the only law governing antimicrobial pesticides. There are numerous variables and issues that an applicant must understand to ensure that the antimicro-bial product is in compliance with all applicable laws, regulations and policies.

The FIFRA provides the overall framework for the federal pes-ticide registration program and requires pesticide products be registered by the EPA before distribution or sale in the United States [1]. The Office of Pesticide Programs (OPP) within the EPA is responsible for registering or licensing pesticide products. The EPA mission is to protect not only the environment, but also public health. Pesticide registration decisions are based on a detailed assessment of the potential effects of a product on human health and the environment, when used according to label direc-tions, and any required efficacy data.

Pesticide history

The primary federal laws that regulate antimicrobial pesticides are FIFRA and the Federal Food, Drug and Cosmetic Act (FFDCA) [2]. FFDCA limits pesticide residues on food. The two most important amendments to FIFRA are the Food Quality Protec-tion Act (FQPA) [3] and the Pesticide Registration Improvement Act (PRIA).

Pesticide laws have been in existence since the early 1900s. The early laws, administered by the US Department of Agriculture (USDA), focused on labeling and consumer protection. In 1947, the first Federal Insecticide, Fungicide, Rodenticide Act was passed. It was not until 1970 that the EPA was formed as a central repository of all laws impacting the environment.

In 1996, substantive changes to FIFRA were enacted with the passage of FQPA. This law formally recognized that antimicro-bial products were uniquely different from other pesticide prod-ucts. A separate definition for antimicrobial pesticides was provided and the Antimicrobial Division (AD) was created within the OPP for regulating antimicrobial pesticides. The

Russell, Hugo & Ayliffe’s: Principles and Practice of Disinfection, Preservation and Sterilization, Fifth Edition. Edited by Adam P. Fraise, Jean-Yves Maillard,

and Syed A. Sattar.

© 2013 Blackwell Publishing Ltd. Published 2013 by Blackwell Publishing Ltd.

Introduction, 269Pesticide history, 269Environmental protection agency structure,

270Antimicrobial pesticides overview, 270Determining whether a product is a

pesticide, 271Obtaining a pesticide registration, 272The registration process, 272Labels, 274

Registrant obligations, 274Antimicrobial testing program, 274State pesticide registration, 274Treated articles, 274Devices, 275Minimum risk pesticides, 275Nanotechnology, 275OECD antimicrobial efficacy methods, 275Conclusions, 275References, 275

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The BPPD is responsible for pesticides derived from natural materials such as animals, plants, bacteria and certain minerals. Biopesticides fall into three major classes:1. Microbial pesticides consist of a microorganism (e.g. bacteria, fungi, virus or protozoa) as the active ingredient.2. Plant-incorporated protectants (PIPs) are pesticidal sub-stances that plants produce from genetic material that has been added to the plant.3. Biochemical pesticides are naturally occurring substances that control pests by non-toxic mechanisms.

The RD handles conventional pesticides that are generally syn-thetic materials which directly kill or inactivate the pest. These include herbicides, rodenticides, molluskides, insecticides, etc.

The EPA also has ten regional offices. Each region is responsible for executing EPA programs within the respective states and ter-ritories assigned to the region. Federal EPA has delegated author-ity to the regions for certain activities including import/export regulations and initiation of enforcement actions.

Antimicrobial pesticides overview

The EPA categorizes antimicrobial pesticides based on the type of efficacy claim(s). Public health products are intended to control microorganisms in any inanimate environment is of public health concern. Examples are disinfectants used in hospitals, swimming pool disinfectants and sanitizers used in food-handling establish-ments. Non-public health products are used against microorgan-isms not considered to be of public health concern. Examples are algae, odor-causing bacteria, bacteria which cause spoilage, dete-rioration or fouling of materials, and microorganisms infectious only to animals.

The EPA requires submission of efficacy data to support each public health claim. Submission of data for non-public health organisms is generally not required but must be on file with the registrant. The EPA retains the right to require submission of non-public health data on a case-by-case basis.

More than 5000 antimicrobial end use pesticide products are currently registered with EPA. There are over 275 active ingredi-ents used in antimicrobial products [6]. The resulting product may be marketed in a variety of forms including wipes, sprays, liquids, powders and gases. Nearly 60% of antimicrobial products are registered to control microorganisms of public health concern in hospitals and other healthcare environments [4].

Public health antimicrobial pesticide categoriesPublic health categories are organized by the degree of effective-ness. The efficacy achieved determines the label claims and use sites allowed for the antimicrobial pesticide.

Sterilants represent the highest or most efficacious level of anti-microbial pesticide. Sterilants destroy or eliminate all forms of bacteria and fungi, including their spores, and viruses. Since spores are the most difficult form of a microorganism to kill, the EPA considers the term “sporicide” synonymous with sterilant.

FQPA also required the EPA take into account the unique nature of antimicrobial pesticides when registering non-food antimi-crobial pesticides.

The FQPA strengthened the health-based safety standard for pesticide residues in all foods. It uses a “reasonable certainty of no harm” as the general safety standard for food uses. The FQPA requires the EPA to consider all non-occupational sources of exposure, including drinking water and residential exposure. It requires evaluation of exposure to other pesticides with a common mechanism of toxicity when setting tolerances [4]. The FQPA also changed how the OPP conducted risk assessments. Emphasis is now placed on the sensitivity of infants and children to pesticides. The OPP can also group chemicals that have common mechanisms of toxicity but must also look at non-pesticide as well as pesticide uses when deter-mining risk.

Pesticides used on food or food contact surfaces must meet the requirements of FIFRA as well as certain portions of FFDCA. Before pesticides are allowed in materials used in manufacturing, packing, packaging, transporting or holding food, the Food and Drug Administration (FDA) must determine that there is a “rea-sonable certainty of no harm” presented. Once known as “indirect food additives”, FDA now refers to these materials as “food contact substances” and evaluates safety through the food contact notifi-cation process. EPA then determines whether a tolerance, that is a maximum permissible pesticide residue on a particular food/feed commodity, is needed, or if the pesticide can be exempted from a tolerance.

Environmental protection agency structure

The OPP at the EPA administers the registration aspects of FIFRA. Within the OPP there are three divisions that handle the registration activities for all pesticides: the Antimicrobial Division (AD), Biopesticides and Pollution Prevention Division (BPPD) and Registration Division (RD).

The AD is responsible for antimicrobial pesticides, such as disinfectants and sanitizers. Antimicrobial pesticides: (i) disin-fect, sanitize, reduce or mitigate growth or development of microbiological organisms; or (ii) protect inanimate objects (e.g. floors, walls), industrial processes or systems, surfaces, water or other chemical substances from contamination, fouling or dete-rioration caused by bacteria, viruses, fungi, protozoa, algae or slime [5]. Antimicrobial pesticides do not include liquid chemical sterilant products (including any sterilant or subordinate disin-fectant claims on such products) for use on critical or semicritical medical device products. These products are regulated by the FDA’s Center for Devices and Radiological Health (CDRH). Anti-microbial pesticides used on non-critical medical device prod-ucts are jointly regulated by the EPA and FDA. The FDA has exempted these general purpose disinfectants from premarket notification but they are still subject to the Quality System Regu-lation, Part 820.

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family with its susceptibility profile. From Klein and DeForest, viral strains are categorized into three clusters based on their structure or inactivation susceptibility [10]. To make a claim for the emerging pathogen, the EPA must have reviewed and accepted a successful study against a virus in the same or higher cluster (i.e. a more difficult to inactivate virus) thus predicting the product’s effectiveness against the emerging pathogen.

Information regarding the emerging pathogen cannot be added to the product’s marketing label. However, the guidance contains provisions that allow effectiveness against the emerging pathogen to be provided on websites, technical literature or through other means. No submission to the EPA is required as long the registrant adheres to the guidance.

Determining whether a product is a pesticide

A pesticide is any substance or mixture of substances intended for preventing, destroying, repelling or mitigating any pest. Pests can be insects, mice and other animals, unwanted plants (weeds), fungi or microorganisms like bacteria and viruses. The term pes-ticide applies to insecticides, antimicrobials, herbicides, fungi-cides and various other substances used to control pests. Under US law, a pesticide is also any substance or mixture of substances intended for use as a plant regulator, defoliant or desiccant. The intended use of a product, expressed or implied, is the main determinate of its pesticide status. If a product is represented in any manner (written or verbal) to have pesticidal properties then it is considered a pesticide by the FPA whether or not it is regis-tered [11].

A product is also classified as a pesticide if it contains an ingre-dient that has no other commercially viable use except as a pes-ticide or the person distributing or selling the product has actual or constructive knowledge that the product will be used as pesti-cide [12]. The definition of pesticides is broad, but certain prod-ucts are excluded from the definition [13]:• Liquid chemical sterilants intended and labeled only for use on critical or semicritical medical devices; these are regulated by the FDA.• Drugs used to control fungi, bacteria, viruses or other micro-organisms in or on living humans or animals; these are regulated by the FDA.• Fertilizers, nutrients and other substances used to promote plant survival and health are not considered plant growth regula-tors and thus are not pesticides.• Biological control agents, except for certain microorganisms, are exempted from regulation by the EPA.• Cleaners, deodorizers and bleaches making no pesticidal claims.Other products are pesticides but have been exempted from FIFRA regulation. These include:• Items containing a pesticide to protect the article itself from deterioration; that is article preservatives commonly known as “treated articles”. Certain conditions must be met for a treated article to be eligible for the FIFRA exemption [14].

Disinfectants destroy or irreversibly inactivate bacteria, fungi and/or viruses but not their spores. There are three levels of dis-infectants [7]:1. Hospital disinfectants: these are capable of killing both Gram-negative and Gram-positive bacteria. The EPA has identified three organisms that a hospital disinfectant must be effective against: Pseudomonas aeruginosa, Staphylococcus aureus and Salmonella enterica. Claims against additional bacteria, viruses or fungi are allowed if supported with data. Products intended for use in patient care areas of healthcare facilities including hospitals, surgery centers, dental suites and nursing homes must achieve this efficacy profile.2. General or broad-spectrum disinfectants: these are capable of killing both Gram-negative (S. enterica) and Gram-positive (S. aureus) bacteria but are not required to be effective against P. aeruginosa. Claims against additional bacteria, viruses or fungi are allowed if supported with data. Label claims for use in patient care areas of healthcare facilities are not allowed.3. Limited disinfectants: these are capable of killing either Gram-negative (S. enterica) or Gram-positive (S. aureus) bacteria. Claims against additional bacteria are allowed, but only in the category in which the product showed effectiveness. Label claims for use in patient care areas of healthcare facilities are not allowed.

Sanitizers reduce, but do not necessarily eliminate, microor-ganisms from the inanimate environment. There are two types of sanitizers [7]:1. Non-food contact sanitizers: these must demonstrate a 99.9% reduction against Gram-positive (S. aureus) and Gram-negative bacteria (Klebsiella pneumoniae or Enterobacter aerogenes) over a parallel untreated control in ≤5 min. EPA policy does not allow virucidal, tuberculocidal or fungicidal sanitizing claims.2. Food contact sanitizers: these must demonstrate a 99.999% reduction against Gram-positive (S. aureus) and Gram-negative bacteria (Escherichia coli) over a parallel control in 30 s. Though the EPA requires effectiveness to be demonstrated in 30 s, existing policy limits the contact time stated on the label to 60 s. EPA policy does not allow virucidal, tuberculocidal or fungicidal sani-tizing claims.

Emerging pathogensThe EPA generally requires the submission of efficacy data to support all public health claims. However, with emerging pathogens this is not always possible due to unavailability of the wild strain, biosafety concerns, incompatibility with disin-fection test methods, etc. An emerging pathogen is a newly appearing infectious organism that is “capable of causing disease in humans under natural transmission conditions” [8]. The EPA has developed a policy to help identify products effec-tive against emerging viral pathogens [9]. Before the guidance can be used by a registrant, the Centers for Disease Control and Prevention (CDC) must identify and publish the emerging virus taxonomy.

The guidance, applicable only to viruses, uses a hierarchal approach based on viral structure which imparts a given viral

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not expressly provide for the transfer of registrations but the EPA has historically allowed transfers. Transferring a registration is accomplished by submitting a document, signed by authorized representatives of the companies, stating that the transfer is unconditional and irrevocable. The company owning the regis-tration, that is the “transferor”, also must provide a notarized statement certifying that the person signing the transfer agree-ment is authorized to bind the transferor; that no court order prohibits the transfer; and that the transfer is authorized under federal, state and local laws, and relevant corporation charters, bylaws or partnership agreements.

The registration process

The EPA must determine that a product is safe and efficacious prior to granting market approval. This requires the EPA to evalu-ate both the active ingredient(s) and each non-pesticidal ingredi-ent (referred to as inert ingredients) in the context of the application site and the rate of application.

The EPA evaluates the chemistry, toxicology, environmental and ecological fate profile of the active ingredient to determine there are no undue risks for the intended use site. The data required vary depending upon whether the product is used directly or indirectly on food, or is used indoors, outdoors or in aquatic settings. The EPA uses this information to determine the risk to humans, the environment and non-target species.

A new use of an active ingredient may trigger the need for additional risk assessments. For example, if an active ingredient has been evaluated for indoor, non-food uses and an applicant applies for an indoor, food use, the EPA will consider this a new use requiring an additional risk assessment. This assessment may determine that data gaps exist that must be fulfilled before a registration can be granted.

The EPA performs a similar evaluation for each inert; that is, formulation components that do not have pesticidal activity. For inerts used in non-food settings, the EPA typically does not expect an applicant to conduct new studies. Supporting information can be supplied from publically available literature and summaries of existing data. The EPA will also accept structural activity relation-ship (SAR) data with a scientific rationale explaining the rele-vancy of the surrogate to the proposed inert. New inerts for use in direct or indirect food settings are approved through petition-ing the EPA for the establishment of a tolerance or exemption from tolerance. Along with the information described above for non-food inerts, a discussion of anticipated dietary (from food and drinking water), residential (dermal, inhalation and inciden-tal oral) and occupational exposures from the proposed and exist-ing pesticidal uses of the chemical is required. All filings are published in the Federal Register for 30-day public comment. After the EPA’s review is completed, a Final Rule is published in the Federal Register allowing use of the inert under the appropri-ate use pattern.

• Minimum-risk pesticides containing certain low-risk ingredi-ents, such as garlic and mint oil, meeting certain conditions are exempt from EPA registration [1]. State regulatory requirements may still apply.A device used to “trap, destroy, repel or mitigate” a pest is regu-lated as a pesticide but is exempt from EPA registration. Pesticide devices use only physical or mechanical action to control pests.

Obtaining a pesticide registration

Once a company has determined it wants to market a pesticide product there are three avenues for obtaining a regis-tration: (i) file for a registration; (ii) supplementally register an existing EPA registered product; or (iii) purchase an existing registration.

File a registrationEach applicant for registration must file:• Various administrative forms.• Proposed product labeling.• Statement of formula.• Technical and scientific data that meet the data requirements related to the proposed product.• Statement of whether any data compensation requirements apply.

Supplemental registration processSection 3(e) of FIFRA allows pesticide registrants to distribute or sell a registered pesticide product under a different name instead of or in addition to their own. Such distribution and sale is termed “supplemental distribution” and the product is termed a “distributor product”. The EPA requires the company that owns the EPA registration, that is the “basic registrant”, to submit a Notice of Supplemental Distribution when they enter into an agreement with a second company that will distribute their product under the second company’s name and product name.

The distributor is considered an agent of the basic registrant for all intents and purposes under the Act, and both the registrant and the distributor may be held liable for violations pertaining to the distributor’s product. Therefore, the longest part of the sup-plemental registration process is usually obtaining the basic reg-istrant’s approval of the supplemental label.

The distributor label must be the same as the basic registrant’s EPA-accepted label except for allowances to identify the distribu-tor product and company name, distributor EPA number and place of manufacture. The distributor cannot add claims, addi-tional sites or organisms but can choose to omit claims that are on the EPA-registered label as long as required language – that is precautionary statements, signal words, etc. – remains.

Purchase an existing registrationPurchasing an existing registration allows a prospective registrant to avoid the time and cost of filing for a registration. FIFRA does

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Citing dataApplicants are allowed to cite any data in the EPA’s files to support their proposed registration. The data cited must be from a sub-stantially similar product. If an applicant chooses to provide some or all of the required data in this manner, they must comply with the data compensation obligations provided in FIFRA. Except for exclusive-use data, an applicant is allowed to cite data without the permission of the data holder. In exchange, the applicant must notify the registrant of the data used and offer reasonable com-pensation for use of the data. The applicant must certify to the EPA that compensation offers have been made to all potential data owners.

If the applicant and data holder cannot reach an agreement regarding compensation, FIFRA provides a binding arbitration process. The finding of the arbitrator is final and cannot be overturned except in the case of fraud, misrepresentation or similar actions. Data that is 15 years or older is considered by the EPA to be in the public domain and therefore not compensa-ble. These data can be cited by an applicant without an offer of compensation.

Data submitted to support a new active ingredient, a new com-bination of active ingredients or a new use for an existing active, is extended additional data rights. These data are granted exclusive-use protection for 10 years after the date of initial reg-istration. Any follow-on applicant must have written authoriza-tion to use the data.

Waiver requestsAn applicant can request waivers for data requirements they feel are not applicable to their product; for example a flammability waiver request for products that contain no combustible or flam-mable material. A written scientific justification must be provided for EPA consideration.

EPA review processA separate application is needed for each pesticide product. The EPA also does not allow directions for an end use product to be on the same label as a product used for formulating other prod-ucts such as a manufacturing use product. When the EPA receives an application, it undergoes a “front-end” review to determine that all required elements have been submitted. The EPA has 21 days to complete this review. Any deficiencies identified during this period must be addressed by the applicant or the package will be returned. During this period, if the applicant does not already have an EPA company number, the EPA will assign a number.

During the front-end review, the EPA assigns a file symbol and master record identification number(s) (MRID) for the data sub-mitted. A file symbol consists of the company’s EPA number and a series of letters, for example 123-RE. The letters will be con-verted to numbers when the registration is granted. MRID numbers are a series of eight unique numbers used to identify a specific study.

Under PRIA, each division of the OPP has established timelines and fees for various registration actions. After the 21-day review,

Registration of end use products (EPs) requires the EPA to evaluate chemistry, acute toxicology and, where required, efficacy data. The label is a critical component of the registration as the proposed claims will determine what efficacy data must be gener-ated to support the product. FIFRA and the Code of Federal Regulations (CFR) include specific requirements for label lan-guage and format and, therefore, govern what must (and what cannot) appear on the label [15]. It is often said that “the label is the law” when referring to EPA-registered pesticide products.

Fulfilling data requirementsRegistrants must address all data required to support the use pat-terns and label claims made for a proposed product. This can be done by:• Conducting data studies.• Citing data from the EPA’s existing database.• Requesting a waiver.

Conducting data studiesStudies may be conducted by the applicant or by third party labo-ratories. All studies must be conducted in accordance with 40 CFR paragraph 160 good laboratory practice (GLP) standards. The GLP standards prescribe three possible statements that describe how the study complies with GLP. The GLP compliance statement is required in all final study reports. It is important to note if the EPA audits a study and finds GLP deviations not noted in the final report compliance statement, the applicant, not the laboratory, is responsible for any civil and/or criminal penalties that may result.

Testing of unregistered products or new uses of registered products may require testing under conditions of use, for example swimming pool disinfectants. This testing must be evaluated to determine if an experimental use permit (EUP) is required. In general, EUPs are issued for pesticides containing any active ingredient, or combination of active ingredients, that have not been included in any previously registered pesticide and new uses of active ingredients. Testing performed in laboratories is gener-ally exempt but it is important to note that testing of unregistered disinfectants under actual use conditions is subject to EUPs. The state and local area in which the test is conducted may also require EUPs to be issued.

In 2006, the EPA enacted a rule that extended the Federal Policy for the Protection of Human Subjects of Research (the Common Rule) to cover all third-party intentional dosing studies submitted to the OPP in support of a pesticide registra-tion. Pregnant or nursing women and children are not allowed to participate in any pesticide studies that involve intentional dosing. The EPA has established a Human Studies Review Board (HSRB) to review all protocols and human studies for pending pesticide actions. These human studies are also posted for public comment. Once this process is completed, EPA will then decide whether the human study can be used to support a proposed registration. Swimming pool and spa studies are exempt from this requirement.

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comparative and safety claims [18]. The EPA has issued addi-tional guidance in the Label Review Manual, PRN 93-6 and the EPA’s label consistency website [15, 19, 20]. It is unlawful to dis-tribute or sell a misbranded pesticide [21].

Registrant obligations

The registrant is the company that owns the EPA-registered pes-ticides. A registrant must produce the product at an establishment listed with the EPA using product containers with EPA-accepted labeling. The product must contain the declared amount of active “up to the expiration time indicated on the label” [22] or to the “date of use” [23] if there is no expiration date. A registrant must also report adverse effects, including efficacy failures, associated with the pesticide, maintain production, disposal and import/export records, file yearly pesticide producer’s reports and register each product name in the state or US territory it will be offered for sale.

Antimicrobial testing program

The Antimicrobial Testing Program (ATP) began in 1991 with hospital sterilants. The program continues today with testing of hospital disinfectants and tuberculocides. The EPA collects samples from manufacturers or from the marketplace for testing. The purpose of the testing is to ensure that products in the mar-ketplace meet the registered efficacy claims. If a product fails testing, it is subject to enforcement and possible stop to sales or recall. If the failure cannot be refuted through additional testing or test method issues, the registrant may need to modify label claims, remove claims, reformulate or cancel the registration in response to an ATP failure.

State pesticide registration

Following federal EPA approval, pesticide products must be reg-istered in each state where the product will be sold, manufactured, distributed or transported. State laws, state fees and the state agencies regulating pesticides differ from state to state. After initial state approval, the product registration must be main-tained through annual renewals.

Treated articles

Treated articles are articles or products that are treated with a pesticide to protect the article or product themselves. For example, paints often contain a fungicide that protects the dried paint film from degradation from algae. These articles are exempted from all aspects of FIFRA if certain conditions are met. To meet the treated articles exemption, the treatment must be intended to

the PRIA review clock begins. If it is determined during the review period that additional data or other information must be supplied, a PRIA extension can be requested to allow the appli-cant to gather the requested information and for the EPA to review the new data.

Once the EPA determines a product does not present an unrea-sonable risk, a registration is granted with the condition that the registrant submit any additional information that may be requested by the EPA in the future. Thus, EPA registrations are termed “conditional”. This condition is placed on each registra-tion, except pesticides with human dietary exposure undergoing Special Review or certain pesticides used on food or feed crops.

Changes to registrationsAfter a registration has been granted by the EPA, amendments to the label, formula, packaging or manufacture of the product can be made through an amendment or notification process. The EPA has outlined minor changes that may be filed as notifications or non-notifications in Pesticide Registration Notice (PRN) 98-10. All other modifications must be made through the amendment process with any required supporting information or data.

Labels

FIFRA defines labels as “the written, printed, or graphic matter on, or attached to, the pesticide or device or any of its containers or wrappers”, and labeling as “all labels and all other written, printed, or graphic matter (a) accompanying the pesticide or device at any time; or (b) to which reference is made on the label” [16]. The information on pesticide labels provides information to the consumer on how to safely use the pesticide product. In addition, the label content is critical to the EPA’s determination of data requirements and risk assessments needed to support the intended use of the pesticide. The following information is required on EPA pesticide labels: the brand name, the name and amount of the pesticide (active) ingredient, EPA registration and establishment number, child hazard statement, signal word, net contents, precautionary and first aid statements, physical and environmental hazards, directions for use, and storage and dis-posal instructions.

The EPA has authority to review all language, both pesticidal and non-pesticidal, on a label. When the EPA grants registra-tion of a product, a label with an accepted stamp is provided. The EPA stamped label contains all accepted uses and claims. No product marketing label is allowed to make claims that are not on the master label. Any non-mandatory language, either pesticidal or non-pesticidal, is not required to be on the mar-keting label. Any marketing literature or advertisements must be consistent with the terms of the registration; that is the master label.

Labeling that bears any statement, design or graphic that is false or misleading is “misbranded” [17]. The EPA’s regulations detail specific examples that constitute misbranding including

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protect the article or product itself and only non-public health claims may be made. In addition, the pesticide used to treat the article must be registered with the EPA for this use.

Devices

A pesticidal device is any instrument or contrivance (other than a firearm) intended for trapping, destroying, repelling or mitigat-ing any pest. The regulations exempt “ultraviolet light systems, certain water and air filters, or ultrasonic devices that make claims that the device kills, inactivates, entraps, or suppresses growth of fungi, bacteria, or viruses in various sites” [24]. The premise of a device is that it works by a mechanical or physical means to control pests. If a chemical substance is included and the “device” does not produce its intended effect without it, then it is classified as a pesticide and not a pesticide device. For example, a filter that uses pore size only to trap microorganisms is a pesticide device; however, a filter that is treated with a chemical to capture or kill microorganisms is a pesticide.

Pesticide devices are exempt from EPA registration but are still subject to labeling requirements. Pesticide device labels cannot have false or misleading statements and must list the pesticide establishment number. While pesticide devices are exempt from EPA registration, several states require registration. These states have varying requirements for registration.

Minimum risk pesticides

The EPA has determined that pesticides containing certain active and inert ingredients have a sufficiently safe profile that allow exemption from EPA registration. These are classified as minimum risk pesticides. They are often called 25(b) products since this is the FIFRA section addressing these products.

To qualify as a minimum risk pesticide, specific conditions must be met. The product can contain only actives that are identi-fied in the regulations, only inerts identified as “inert ingredients of minimal concern”, all ingredients must be listed on the label, and public health claims are not allowed [25]. While minimum risk pesticides are exempt from EPA registration, several states require registration. These states have varying requirements for registration.

Nanotechnology

Nanotechnology has been in existence for quite some time. There is not a uniformly standard definition but generally the particles are classified as nanoparticles if they are 1–100 nm in size. The OPP defines nanomaterial as “An ingredient that contains parti-cles that have been intentionally produced to have at least one dimension that measures between approximately 1 and 100 nanometers” [26]. Nanomaterials may exhibit different physical

properties than larger-sized materials. Thus, it is believed that nanomaterials may present different health and environmental hazards. The EPA is in the process of determining whether additional or new data requirements will be required for nanomaterials.

OECD antimicrobial efficacy methods

The EPA efficacy requirements currently rely upon methods that are largely unique to the USA. The EPA is actively participating in an Organization for Economic Cooperation and Development (OECD) process of developing internationally harmonized anti-microbial efficacy methods. The goal is to create validated, repro-ducible, quantitative methods that will be accepted in all OECD member countries. While each country may be able to establish its own performance criteria, label claims, test conditions, replica-tion, etc., the development of harmonized methods should facili-tate the sharing of data and review across OECD regulatory agencies.

Conclusions

Antimicrobial pesticides are primarily regulated by the EPA under FIFRA. The laws are complex and the interpretations are evolving as new technologies and emerging health issues arise. The EPA must constantly balance its mission of protecting the public health and the environment with evolving science and public policy. Registrants must remain aware of these changes to ensure that their products are efficacious and in compliance with current regulations and policy.

References

1 Federal Insecticide, Fungicide, and Rodenticide Act, amended (7 U.S.C., 136 et.

seq.) Section 3(a), http://agriculture.senate.gov/Legislation/Compilations/Fifra/

FIFRA.pdf (accessed June 18, 2012).

2 Federal Food, Drug, and Cosmetic Act, as amended through December 31, 2004,

http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugand

cosmeticactfdcact/default.htm (accessed June 18, 2012).

3 The Food Quality Protection Act, 1996, http://www.epa.gov/endo/pubs/

fqpa.pdf (accessed June 18, 2012).

4 Environmental Protection Agency (n.d.) Pesticides Frequent Questions, http://

pesticides.supportportal.com/ics/support/default.asp?deptID=23008 (accessed

June 18, 2012).

5 Federal Insecticide, Fungicide, and Rodenticide Act, amended (7 U.S.C., 136 et.

seq.) Section 2 (mm), http://agriculture.senate.gov/Legislation/Compilations/

Fifra/FIFRA.pdf (accessed June 18, 2012).

6 Environmental Protection Agency (n.d.) Pesticides: Topical and Chemical Fact

Sheets, http://www.epa.gov/pesticides/factsheets/antimic.htm (accessed June 18,

2012).

7 Environmental Protection Agency (n.d.) What are Antimicrobial Pesticides?,

http://www.epa.gov/oppad001/ad_info.htm (accessed June 18, 2012).

8 Woolhouse, M.E.J. and Gowtage-Sequeria, S. (2005) Host range and emerging

and reemerging pathogens. Emerging Infectious Diseases, 11 (12), 1842–1847.

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9 Environmental Protection Agency (n.d.) Antimicrobial Policy and Guidance

Documents: Disinfection Hierarchy and Emerging Pathogens Guidance, http://

www.epa.gov/oppad001/regpolicy.htm (accessed June 18, 2012).

10 Klein, M. and DeForest, A. (1983) Principles of viral inactivation, in Dis -

infection, Sterilization, and Preservation, 3rd edn (ed. S. Block), Lea & Febiger,

Philadelphia, pp. 422–434.

11 Environmental Protection Agency (revised as of July 1, 2011) 40 CFR §162.4(a),

EPA.

12 Environmental Protection Agency (revised as of July 1, 2011) 40 CFR §152.15,

EPA.


EPA.

14 Environmental Protection Agency (revised as of July 1, 2011) 40 CFR §152.25(a),

EPA.

15 Environmental Protection Agency (n.d.) Label Review Manual, http://

www.epa.gov/oppfead1/labeling/lrm/ (accessed June 18, 2012).

16 Federal Insecticide, Fungicide, and Rodenticide Act, amended (7 U.S.C., 136

et. seq.) Section 2 (p), http://agriculture.senate.gov/Legislation/Compilations/

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17 Federal Insecticide, Fungicide, and Rodenticide Act, amended (7 U.S.C.,

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18 Environmental Protection Agency (revised as of July 1, 2011) 40 CFR §156.10(a)

(5), EPA.

19 Environmental Protection Agency (1993) Pesticide Registration Notice 93-6:

False or Misleading Statements Related to Efficacy; Revision of PR Notice 91-7,

http://www.epa.gov/PR_Notices/#1993 (accessed June 18, 2012).

20 Environmental Protection Agency (n.d.) Pesticide Labeling Consistency, http://

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21 Federal Insecticide, Fungicide, and Rodenticide Act, amended (7 U.S.C.,

136 et. seq.) Section 12(a)(1)(E), http://agriculture.senate.gov/Legislation/

Compilations/Fifra/FIFRA.pdf (accessed June 18, 2012).

22 Environmental Protection Agency (revised as of July 1, 2011) 40 CFR §156.10(g)

(6)(ii)), EPA.


EPA.

24 Federal Government (1976) Federal Register, 51065–51066, http://www.epa.gov/

compliance/resources/policies/monitoring/devicepolicy.pdf (accessed June 18,

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25 Environmental Protection Agency (revised as of July 1, 2011) 40 CFR §152.25(f),

EPA.

26 Jordan, W. (2010) Nanotechnology and Pesticides, Pesticide Program Dialogue

Committee, Environmental Protection Agency, http://www.epa.gov/pesticides/

ppdc/2010/april2010/session1-nanotec.pdf (accessed June 18, 2012).