EPA Extends the Comment Period on the Proposed Framework to Assess the Risk to the Effectiveness of Human and Animal Drugs Posed by Certain Antibacterial or Antifungal Pesticides

On September 26, 2023, the U.S. Environmental Protection Agency (EPA) requested comment on a proposed framework to strengthen the assessment of antimicrobial-resistance risks associated with pesticide use. EPA, the U.S. Department of Health and Human Services (HHS), and the U.S. Department of Agriculture (USDA), under the oversight of the White House Executive Office of the President, have published a concept note. EPA states that the concept note is the first step in creating the framework to improve assessments of potential risks to human and animal health where the use of certain pesticides could potentially result in antimicrobial resistance (AMR) that compromises the effectiveness of medically important antibacterial and antifungal drugs. EPA states that the proposed framework described in the concept note will expand EPA’s current process for assessing the risk that antibacterial or antifungal pesticides may pose to the effectiveness of human and animal antibacterial and antifungal drugs when EPA evaluates pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).

On November 1, 2023, EPA extended the comment period by 30 days; thus, comments are due by December 13, 2023, and can be submitted by searching docket ID EPA-HQ-OPP-2023-0445 at www.regulations.gov

Concept Note

The concept note structures the framework into the following components:

• Resistance Characterization: EPA would evaluate whether a proposed pesticide use could compromise the effectiveness of a medically important human or animal drug. If the resistance characterization identifies such a concern, EPA would conduct a qualitative risk assessment.

• Risk Assessment: EPA would estimate the probability that the proposed use of the antibacterial or antifungal pesticide may result in resistant bacteria or fungi. EPA also would estimate the likelihood of humans or animals being exposed to the newly resistant bacteria or fungi. This assessment would determine the overall risk for resistance associated with the proposed pesticide’s use.

• Risk Management: If the risk assessment identifies areas of concern, the results of the risk assessment are evaluated along with other considerations to decide whether risk reduction measures are needed and, if so, which ones.

The concept note solicits stakeholder input on the proposed structure for the framework and on potential solutions, research, or mitigation approaches to reduce the spread of resistance. EPA and the federal partners are specifically soliciting comment on:

• The clarity of the proposed structure for the framework;

• The types of pesticides that should be evaluated under the framework, either by class or function;

• The factors that should be considered in determining if a proposed pesticide use constitutes a potential risk to human or animal health due to AMR;

• The process for determining which human and animal antibacterial and antifungal drugs should be considered “medically important” and how this term should be defined;

• The mitigation strategies that are currently available to address any potential risk of AMR developing due to pesticide use; and

• A list of knowledge gaps provided in the concept note, that include the following:
  
  
  • How do organisms that might have developed resistance by exposure to these pesticides come into contact with and cause illness in humans or animals (e.g., through direct contact, inhalation, ingestion, healthcare-associated transmission, contamination of water supply, etc.), and which human or animal populations are most affected (e.g., agricultural workers, persons handling compost, persons with immunocompromising conditions, persons living near treated fields, animals for food production, companion animals)?
    
    
  • What are effective strategies to reduce the potential for these pesticides to select for antimicrobial-resistant bacteria and fungi? For example, which agricultural practices (with cost estimates) are effective in reducing the potential for these pesticides to select for AMR, including strategies to reduce the need for pesticide use and practices that reduce the likelihood that pesticide use will result in resistance emergence (e.g., crop rotations, specific pesticide formulations, methods to prevent off-site migration, biological control)?
    
    
  • By which mechanisms do human or animal pathogenic bacteria and fungi spread through populations after becoming resistant through selection by these pesticides?
    
    
  • What are the best approaches to determine the potential for pesticides to select for antimicrobial-resistant pathogens, and do chemical criteria exist that could help determine whether pesticides are more or less likely to pose health risks to humans or animals?
    

The proposed framework would apply to antibacterial and antifungal pesticides with plant agricultural uses (e.g., crops, turf, or ornamentals) or non-agricultural uses (e.g., wood and paint preservation), that could promote AMR and adversely impact the effectiveness of medically important antimicrobials used as human or animal drugs. Pesticides that could compromise the effectiveness of an important human or animal drug might include those pesticides that share a drug class or mechanism of action, and therefore, may be rendered ineffective by a similar mechanism of resistance.

The framework is expected to include resistance characterization, qualitative risk assessment, and risk mitigation steps. The goal of the effort is to reduce risks to human and animal health from antimicrobial-resistant pathogens due to pesticide use.

EPA states that after receiving and reviewing public input, feedback will be incorporated as appropriate, and a draft framework will be shared. The public also will have the opportunity to comment on the draft framework before the final framework is published.

Background

AMR is a common phenomenon, occurring in response to threats to a microorganism. In human and agricultural contexts, AMR develops when pathogens such as bacteria or fungi acquire the ability to defeat the drugs designed to kill them. AMR is a growing global public health threat, and the World Health Organization has identified AMR as a top health priority. Preserving the effectiveness of antibacterial and antifungal drugs is essential for protecting the health of humans, animals, and plants. The use of antibacterial or antifungal compounds across settings such as hospitals, at veterinary clinics, or farms can contribute to the emergence of antimicrobial-resistant organisms, and possibly increase the difficulty of treating future infections in humans, animals, and plants.

While antibacterial and antifungal pesticides can be effective at managing these diseases on crops, there is emerging evidence that in rare cases, the use of these pesticides can reduce the effectiveness of some human and animal antibacterial and antifungal drugs. This is because some antibacterial and antifungal pesticides share characteristics with antibacterial and antifungal drugs. If a strain of bacteria or fungi becomes “resistant” to a pesticide, that strain will also be resistant to human or animal drugs that share similar characteristics with the pesticide. As a result, a drug that would normally be used to treat a bacterial or fungal infection may not work well against those resistant bacteria or fungi.

EPA provides the following examples:

• According to USDA, a bacterial disease known as “citrus greening” has spread across Florida since 2005. It has devastated the Florida citrus industry by reducing citrus production by 75 percent and more than doubling the cost of production.

• Farmers sometimes apply antifungal pesticides to protect their crops from fungal diseases. These antifungal pesticides, however, can make strains of a specific fungi (known as Aspergillus fumigatus) resistant. When a human breathes in this resistant strain of fungi, they can develop a fungal infection known as aspergillosis. Because the infection is caused by a strain of Aspergillus fumigatus that is resistant to antifungal pesticides, the infection will also be resistant to antifungal drugs that share characteristics with those antifungal pesticides. As a result, the antifungal drug that doctors would normally prescribe to treat aspergillosis may no longer be effective. Alternative treatments, if they are even available, may not be as effective or may have worse adverse side effects.

Commentary

Of note, the Food and Agriculture Organization of the United Nations (FAO) will release on November 28, 2023, its toolkit, Quadripartite Legislative Assessment Tool for Antimicrobial Resistance, for addressing AMR globally. AMR was the subject of a recent International Bar Association (IBA) session at the IBA Annual Conference in Paris that the Agriculture and Food Section of the IBA, which Lynn L. Bergeson chairs, organized. Panelists included Carmen Bullon, FAO Legal Advisor, and an internationally recognized AMR expert; Philippe Becquet, Independent Expert Consultant, International Feed Industry Federation, an agronomist specializing in animal nutrition; and Gilles Boin, Partner, Qolumn, with a specialization in French and European Products Law. Bullon emphasized the criticality of AMR and the role agricultural, pharma, government, and private stakeholders play in addressing this issue. Anderson Ribeiro, Partner, Souto Correa Advogados, chaired the session with Bergeson. The session explored the legal and policy challenges of preventing the increase of AMR while feeding a growing world population and meeting global food security concerns. Panelists discussed the viable solutions to addressing AMR, and the consequences if action is not taken.

Stakeholders, especially registrants of antibacterial and antifungal pesticides that could promote AMR, are urged to review the concept note made available by EPA and consider providing feedback on the proposed framework structure, knowledge gaps, potential solutions, research, and mitigation approaches to reduce the spread of AMR.

This is an opportunity for industry to submit feedback to the agencies to be considered for possible incorporation into the draft framework that will be shared for public comment in the future. More information about the IBA Agriculture and Food Section is available on its website.