By Lisa R. Burchi, James V. Aidala, and Heather F. Collins, M.S.

On May 31, 2023, the U.S. Environmental Protection Agency (EPA) released a final rule exempting a class of plant-incorporated protectants (PIP) created using genetic engineering, from registration requirements under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and from the food or feed residue tolerance requirements under the Federal Food, Drug, and Cosmetic Act (FFDCA). 88 Fed. Reg. 34756. PIPs are pesticidal substances produced by plants and the genetic material necessary for the plant to produce the substance. According to EPA’s May 25, 2023, press release, this rule will reduce costs for the regulated community and result in increased research and development activities, consistent with Executive Order 14081 on advancing biotechnology. EPA states that the rule also may result in the commercialization of new pest control options and reduced use of conventional pesticides. The final rule will be effective on July 31, 2023.

EPA states the final rule will allow PIPs to be exempt from FIFRA registration and FFDCA tolerance requirements in cases where they both pose no greater risk than PIPs that EPA has already concluded meet safety requirements, and when they could have otherwise been created through conventional breeding. The final rule reflects the biotechnological advances made since 2001, when EPA first exempted PIPs derived through conventional breeding from FIFRA registration and FFDCA tolerance requirements but did not at that time exempt PIPs created through biotechnology.

In the rule, EPA provides criteria and definitions that identify two categories of PIPs that are exempted through this action from FIFRA registration and FFDCA tolerance requirements:

• “PIPs created through genetic engineering from a sexually compatible plant” in which genetic engineering has been used to insert or modify a gene to match a gene found in a sexually compatible plant (to be codified at 40 C.F.R. Section 174.26); and
• “Loss-of-function PIPs” in which the genetically engineered modification reduces or eliminates the activity of a gene, which then helps make the plant resistant to pests (to be codified at 40 C.F.R. Section 174.27).

For the first exempted category, EPA will require a notification process for EPA to confirm that the PIP is eligible for the exemption. For the second exempted category (loss-of-function PIPs), developers of PIPs can submit to EPA a self-determination letter that the exemption applies. EPA also is establishing recordkeeping requirements for these exempted PIPs, clarifying general qualifications for exemption at 40 C.F.R. Section 174.21; clarifying the relationship between the existing exemptions for PIPs from sexually compatible plants (40 C.F.R. Section 174.25) and the newly issued exemption for “PIPs created through genetic engineering from a sexually compatible plant” (40 C.F.R. Section 174.26); and allowing the existing inert ingredient exemption at 40 C.F.R. Section 174.705 to include genetic engineering.

EPA notes that in the future, as biotechnology advances further, it intends to consider exempting additional categories of PIPs from both FIFRA registration and FFDCA tolerance requirements as well as adding categories of exempted PIPs to the list of categories that do not require EPA confirmation of eligibility.

Additional information, including the response to comment document, is available in docket EPA-HQ-OPP-2019-0508.

Commentary

This final rule is the next step for EPA’s Office of Pesticide Programs (OPP) on the path of EPA’s regulation of biotechnology pesticide products. It sets forth how OPP will handle products created by “Clustered Regularly Interspaced Short Palindromic Repeats” (CRISPR). In more general terms, CRISPR refers to manipulating plant genes with a method that was not available at the time the first biotechnology regulations were developed by EPA in the mid-1990s. This is why EPA needs to “update” its regulations, which is the purpose of the final rule.

Proponents of biotechnology methods argue that CRISPR allows the genes of plants to be manipulated more precisely and can be used to “simply” drop out a gene or add one from the same -- sexually compatible -- genome of the target plant. It follows that this is much like “traditional plant breeding” only done more precisely and more rapidly. Critics will likely raise questions about whether any product using this method, and not using traditional methods, might have some kind of unexpected result or unintended eventual effect. One can expect some adverse comments regarding these products even though EPA (among many others) lays out a rationale that this is an extension of its current regulations exempting products of traditional plant breeding from regulation under FIFRA/FFDCA (and not exempting such products from other regulatory authorities).

There also were concerns raised in comments submitted in response to the October 9, 2020, proposed rule. In particular, some in industry remain concerned that the final rule creates differential treatment for products due solely to the methods of development (i.e., biotechnology vs. conventional), thus subjecting products created using biotechnology to additional regulatory and recordkeeping requirements, even in cases when those products could have been created using older research and development approaches.

EPA’s basic requirements for biotechnology products that regulate inter-species gene manipulation would not change. Also worth noting is that the rule also would allow a developer to submit the product for EPA review to affirm that it qualifies for the exemption (i.e., a M009 Pesticide Registration Improvement Act (PRIA) action, which can lead to EPA delays in processing). The EPA docket includes a slide deck with a helpful summary of the final rule and its rationale.

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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.

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By Timothy D. Backstrom and Lisa M. Campbell

On June 19, 2018, 16 federal agencies, including the U.S. Environmental Protection Agency (EPA), issued a final rule delaying until January 21, 2019, the general compliance date for 2017 revisions to the policy governing studies with human subjects that are sponsored or utilized for regulatory purposes by the federal government (83 Fed. Reg. 28497).  These revisions to the human testing policy were adopted on January 19, 2017, in a final rule (82 Fed. Reg. 7149) that amended and expanded the “Common Rule” governing human testing originally promulgated in 1991.  The 2017 revisions to the human testing policy were originally scheduled to take effect on January 19, 2018, but the agencies published an interim final rule on January 22, 2018, that delayed the effective date for the new policy until July 19, 2018.  Thereafter, on April 20, 2018, the same 16 agencies published a proposed rule (83 Fed. Reg. 17595) to delay the general compliance date for an additional six-month period, and to allow regulated entities to implement certain burden-reducing provisions during this interim period. 

The rule delaying the effective date of the 2017 revisions for an additional six months takes effect on July 19, 2018.  In the period between July 19, 2018, and January 21, 2019, regulated entities must continue to comply with the requirements of the human testing policy as it was in effect prior to the 2017 revisions.  Notwithstanding this general rule, affected institutions will be permitted (but not required) to implement, for certain research, three burden-reducing provisions.  Those three provisions are:

• The revised definition of “research,” which deems certain activities not to be research covered by the Common Rule;
• The elimination of the requirement for annual continuing review with respect to certain categories of research; and
• The elimination of the requirement that institutional review boards (IRB) review grant applications or other funding proposals related to the research.

The principal purposes of the additional delay in implementation of the 2017 revisions to the human testing Common Rule are to allow more time for affected institutions to prepare for compliance and for the federal agencies that have adopted the new policy to issue further guidance.  The final rule states that the agencies do not expect that any additional delay in the implementation of the policy will be needed.

More information on the federal policy for the protection of human subjects is available in our blog under key phrases human subjects and common rule.

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By Lisa M. Campbell and Margaret R. Graham

On March 20, 2017, the U.S. Environmental Protection Agency (EPA) published in the Federal Register a notice that it was delaying the effective date of five regulations, including the final rule on the certification of pesticide applicators.  The effective date for this final rule is now May 22, 2017 (original effective date was March 6, 2017).  In the notice, EPA states that it is “taking this action to give recently arrived Agency officials the opportunity to learn more about these regulations and to decide whether they would like to conduct a substantive review of any of these regulations.”  The new effective date of May 22, 2017, could be delayed further if EPA officials decide to conduct a substantive review.  More information on the pesticide applicator certification rule is available in our memorandum Final EPA Rule Requires Stronger Standards for Applying Riskiest Pesticides.

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By Lisa M. Campbell and Lisa R. Burchi

The final rule revising the U.S. Environmental Protection Agency (EPA) regulations governing the minimum risk pesticide exemption from pesticide registration requirements was published in the Federal Register on December 28, 2015.  The revisions include codifying the inert ingredients list and adding specific chemical identifiers, where available, for all active and inert ingredients permitted in products eligible for the minimum risk pesticide exemption.  Labeling requirements for minimum risk pesticides are also revised to require manufacturers to list ingredients on product labels with a designated label display name and to provide the producer’s contact information on the products’ labels.  EPA states that the revisions are intended to “clarify the terms of the original exemption and to provide additional clarity and transparency concerning the ingredients that are currently used in exempted products.”  Information regarding the proposed rule that was issued on December 31, 2012, is available in our memorandum entitled EPA Proposes Revisions to Minimum Risk Exemption for Pesticides.

The final rule will become effective on February 26, 2016.  The compliance date for the new label requirements is February 26, 2019. 

Under the revised regulations, the minimum risk exemption requirements are as follows:

• Condition 1:  The product's active ingredients must be only those that are listed in 40 C.F.R. Section 152.25(f)(1).  Previously, the regulations included only the names of the active ingredients.  Under the newly revised reguations, the new Table 1 includes the “Label Display Name,” the “Chemical Name,” any “Specifications,” and the Chemical Abstracts Services Registry Number (CAS No.). 
  • In response to comments, EPA restored two active ingredients inadvertently omitted from the proposed rule (sodium chloride and ground sesame plant) and clarified how “mint and mint oils” are listed.  EPA also has changed the name of one active ingredient from cedar oil to cedarwood oil and clarified its chemical names and CAS Nos.
  • EPA removed United States Pharmacopeia (USP) specifications for 19 active ingredients because such specifications would have removed technical grade active ingredients that are currently eligible but do not meet USP specifications, and EPA states that it did not intend with this rule to add or remove substances from the ingredients list.  The USP specification for castor oil remains since that was part of the original active ingredient list.

• Condition 2:  Prior to these revisions, EPA’s regulations stated that a product's inert ingredients may be only those that have been classified by EPA as:  (1) List 4A “Inert Ingredients of Minimal Concern”; (2) commonly consumed food commodities, animal feed items, and edible fats and oils as described in 40 C.F.R. Sections 180.950(a), (b), and (c); and (3) certain chemical substances listed under 40 C.F.R. Section 180.950(e).  The final rule codifies, at 40 C.F.R. Section 152.25(f)(2)(iv), a list of inert ingredients permitted in minimum risk pesticide products.  The codified list at Table 2 includes the “Label Display Name,” the “Chemical Name,” and the Chemical Abstract Services Registry Number (CAS No.). 
  • In response to comments, EPA removed from the “Label Display Name” certain bracketed language intended to provide clarifying language, for example, “safety limitations on certain inert ingredients such as vinegar (maximum 8% acetic acid in solutions) to chemical formulas for inert ingredients such as calcite (Ca(CO3)).”  This bracketed language remains in the Chemical Name column to assist manufacturers in correctly identifying inert ingredients eligible for the exemption.
  • As it did with respect to active ingredients, EPA states that this rule is not intended to add or remove any inert ingredients.  EPA states that it is considering developing guidance to describe the petition process and types of information EPA would need to add or delete an inert ingredient from this list.

• Condition 3:  Previously, EPA required that all of the ingredients (both active and inert) be listed on the label, with active ingredient(s) listed by name and percentage by weight and each inert ingredient listed by name only.  Under the provisions of the newly promulgated rule, the label must include the following:  (1) the “Label Display Name” for each active ingredient with its percentage by weight; (2) the “Label Display Name” for each inert ingredient; (3) “prominent” display of the name of the producer or the company for whom the product was produced; and (4) “prominent” display of contact information (i.e., street address including zip code and telephone number) for the producer/company listed.

• Condition 4:  The label cannot include any false or misleading statements.  The final rule does not propose any explicit changes to this condition, but some new changes may affect the requirements necessary to meet this condition.  For example, under the newly promulgated revisions, while all active and inert ingredients may be used in non-food use products, “food and animal feed in commerce can bear pesticide residues only for those ingredients that have tolerances or tolerance exemptions in part 180 of this chapter.”  Regarding requirement, EPA states:
  • EPA is not attempting to enforce adherence to the labels of minimum risk pesticides, which as noted cannot be done for pesticides subject to 40 CFR 152.25(f).  Rather, the Agency is assisting minimum risk pesticide producers in ensuring that the use directions on the product do not cause the label to be false or misleading.  An exemption from FIFRA requirements under section 25(b) of the statute, including the minimum risk exemption at 40 CFR 152.25(f), cannot exempt pesticides from the requirements of a tolerance or tolerance exemption under FFDCA.  Under FFDCA, any pesticide chemical residue to be used in or on foods in commerce in the United States must have either an established tolerance or tolerance exemption.  When a minimum risk product explicitly states on its label that it can be used in or on food or food-use sites in commerce, but one or more of the ingredients does not have an established tolerance or tolerance exemption, the label is indicating that the product may be used in a way that would violate Federal law.  Such a label is therefore false or misleading.

• Condition 5:  The product must not bear claims either to control or mitigate organisms that pose a threat to human health, or to control insects or rodents carrying specific diseases.  The final rule does not change this condition.

EPA states that it intends the newly promulgated revisions to assist manufacturers, the public, and federal, state, and tribal inspectors in determining whether a chemical substance can be used in a minimum risk product (i.e., is eligible for the exemption) as well as to provide improved clarity and transparency for consumers who want more information about the ingredients used in a product.  EPA also hopes that requiring company contact information on labels will provide further transparency and accountability should an adverse event occur during the use of a minimum risk pesticide product.

EPA has determined that the total cost for industry to comply with the labeling requirements of this rulemaking is approximately $800,000, under a three-year implementation period.  The three-year implementation period was extended from the two-year proposed implementation plan in response to comments that “[s]ince most companies update their labels every three years…a rule implementation period of three years will allow most companies to meet the labeling requirements of the rule as part of their normal labeling practices and will therefore keep industry costs to a minimum.” 

EPA’s recently updated minimum risk pesticides webpage includes guidance on pesticide tolerances for minimum risk ingredients and provides alternative formats of the active and inert ingredient lists that may be more suitable for some users.  EPA states that it intends to include additional guidance, as needed, such as labeling guidance for minimum risk pesticides and how to request additional ingredients to be added or removed from the minimum risk exemption shortly after the final rule becomes effective.  

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