ICCVAM Biennial Report 2022-2023

In 2015, ICCVAM initiated a series of Communities of Practice webinars to provide opportunities for detailed presentations on a current topic relevant to alternative test method development.

• The 2022 webinar, presented on Jan. 25, was titled New Approach Methodologies to Assess (Developmental) Neurotoxicity. In this webinar, two scientists discussed new approach methodologies (NAMs) that are being considered or developed for assessing potential effects of chemicals on the nervous system. NICEATM scientist Helena Hogberg, Ph.D., discussed use of in vitro assays for developmental neurotoxicity assessment. Jyotshnabala Kanungo, Ph.D., of the FDA National Center for Toxicological Research summarized their studies using zebrafish to assess the effects of dietary supplements on drug safety and drug–drug interactions.
• The Jan. 30, 2023, Communities of Practice webinar focused on Emerging Approaches for Anchoring Biological Relevance of New Approach Methodologies. In this webinar, three scientists from the academic and private sectors discussed approaches to evaluating NAMs that focus on the biological relevance of the NAM to the species of regulatory interest. Lorna Ewart, Ph.D., of Emulate Inc. discussed their work on using MPS to predict liver toxicity. James McKim, Ph.D., IONTOX/LifeNet Health LifeSciences summarized studies using integrated organ models of absorption, distribution, metabolism, and excretion. Finally, Tamara Tal, Ph.D., Helmholtz-Centre for Environmental Research UFZ explained their approach to building confidence in larval zebrafish behavior assays.

ICCVAM’s goals include promotion of national and international partnerships between governmental and nongovernmental groups, including academia, industry, advocacy groups, and other key stakeholders. To foster these partnerships, ICCVAM holds public forums annually to share information and facilitate direct communication of ideas and suggestions from stakeholders.

• View materials from the 2022 Public Forum.
• View materials from the 2023 Public Forum.

ICCVAM public forums started in 2014. The 2022 meeting was held virtually on May 26-27 and expanded to two days to cover the large number of activities ongoing within member agencies. More than 100 individuals attended the meeting virtually each day. The program featured 15 presentations from eight of the 17 ICCVAM member agencies each describing activities both to advance new approaches to safety testing of chemicals and medical products and to reduce the amount of testing required. Updates were also provided on ICCVAM committee and international activities. Commenters at the meeting praised the accomplishments of NICEATM, ICCVAM, and ICCVAM member agencies. They asked that agencies establish specific goals and timelines for acceptance of alternatives to animal testing and stressed the need for education and communication about availability and use of alternatives.

The 2023 public forum was held in person on May 18-19 at NIH in Bethesda, MD, with an option for remote viewing. The event featured 15 presentations from 12 ICCVAM member agencies on activities directed toward reducing and replacing animal use for chemical safety testing, as well as updates on ICCVAM workgroup and international activities. The meeting generated broad public interest with over 200 viewers. Presentations from both agency representatives and stakeholder groups highlighted new approach methodologies (NAMs) with the potential to replace animal testing. Speakers from two test method developers described new technologies that could be used to identify chemicals that can cause neurotoxicity in developing embryos or DNA damage. Several presentations focused on regulatory agencies’ initiatives to reduce animal use requirements. Commenters welcomed ICCVAM’s development of an updated validation guidance document on criteria to establish confidence in new methods for regulatory application.

The Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) is a federally chartered advisory group that advises NICEATM, ICCVAM, and the Director of NIEHS about ICCVAM activities.

Traditionally held in person, the September 21-22, 2022, SACATM meeting was held virtually because of restrictions on gatherings due to COVID-19. About 300 people viewed each day of the webcast; representatives from two International Cooperation on Alternative Test Methods (ICATM) participating organizations presented or attended. ICCVAM asked SACATM members to specifically advise on metrics and measures of success and new approaches to validation. In response, SACATM members urged ICCVAM agencies to expand their efforts to measure progress in adoption of new approach methodologies (NAMs) for chemical testing. They encouraged agencies to work with stakeholders to share data on animal use and provide incentives for reducing animal use. The committee also encouraged ICCVAM agencies to consider relevance to human biology when evaluating a non-animal test method for a specific purpose, rather than relying on a simple comparison to historic animal data.

The September 21-22, 2023, SACATM meeting was held in person at NIEHS in Research Triangle Park, NC. About 70 people attended in person and over 100 people viewed each day of the webcast; representatives from four participating organizations of the ICATM presented or attended. This event focused on detailed discussion of the status of replacement of animal testing for required acute toxicity testing and approaches to validation for new methods. Participants also considered how NAMs could be used to improve environmental health protection. SACATM members and commenters praised ICCVAM agencies on their accomplishments in reducing animal use for determining whether chemicals might cause acute effects such as oral toxicity and skin sensitization. They advised agencies on how they might address remaining challenges, such as predicting whether chemicals might cause complex effects such as developmental neurotoxicity, or characterizing effects of PFAS and other emerging contaminants. They also emphasized the need for clear communication from agencies to stakeholders.

ICCVAM agencies convened workshops and webinars during 2022 and 2023, summarized in the table below, to foster collaboration and provide information about alternative testing methods. 

During 2022 and 2023, several ICCVAM agencies published new webpages summarizing activities to advance alternative methods.

• In June 2023, CPSC updated its Policy on Animal Testing web page. It has been redesigned to be more user-friendly and have direct access to necessary information and documents. One of the resources available on this page is CPSC’s “Guidance for Industry and Test Method Developers: CPSC Staff Evaluation of Alternative Test Methods and Integrated Testing Approaches and Data Generated from Such Methods to Support FHSA Labeling Requirements.”
• In 2020, FDA launched “Advancing Alternative Methods at FDA,” which highlights activities of its Alternative Methods Working Group. A 2023 update expanded this site from a single page to a site with pages providing information on:
  • FDA partnerships to advance alternatives.
  • FDA implementation of alternative methods.
  • The FDA alternatives webinar series.
  • Relevant publications and events.
• EPA maintains a number of webpages describing efforts to replace and reduce animal use for chemical safety testing. The Office of Research and Development’s “New Approach Methods Research” site links to the EPA’s 2021 New Approach Methods Work Plan, which describes objectives and strategies to implementing new approach methodologies (NAMs). Other links from this page lead to EPA’s Catalog of NAMs Training Materials and materials from EPA NAMs Conferences. The EPA Office of Pesticide Programs provides a webpage describing its “Strategic Vision for New Approach Methodologies – Metrics.” This page includes data compiled by the Hazard and Science Policy Council, the Chemistry and Acute Toxicology Science Advisory Council, and other groups about how EPA activities and guidance documents have reduced the number of animals used in testing and saved EPA and stakeholder resources. The Office of Pollution Prevention and Toxics “Predictive Models and Tools for Assessing Chemicals” site links to models and tools that can be used to assess hazards, exposure, and environmental fate of new chemicals.
• DOI’s USGS is preparing a public webpage titled “Reducing Animal Use in Ecotoxicity Testing and Biomonitoring.” It briefly describes the types of ecotoxicological work conducted by the DOI, the 6R Principles, and ongoing efforts to reduce animal use and increase use of non-animal alternatives. It also provides some animal alternative reports and training opportunities.
• A major update of the USDA National Agricultural Library’s Animal Welfare Information Center (AWIC) website in 2022 improved user experience and streamlined information discovery; a new introductory video gives an overview of AWIC resources.

EPA created its New Approach Methods (NAMs) Work Plan to prioritize agency efforts and resources toward activities that aim to reduce the use of vertebrate animal testing while continuing to protect human health and the environment. The Work Plan was first released in June 2020 and updated in December 2021.

To implement the Work Plan’s objective of “Engage and Communicate with Stakeholders,” EPA developed and implemented a NAMs training program in 2021-2023. This program provides users courses and workshop with the appropriate level of oversight to enable them to use EPA NAMs tools and approaches in their own work. During 2022-2023, EPA hosted five trainings on ECOTOX Knowledgebase, CompTox Chemicals Dashboard, ECOTOX, GenRA, and httk. EPA also posted six tool tips videos for the CompTox Chemicals Dashboard, and created a one-stop-shop website for all available training materials. In all, 321 participants attended the ECOTOX NAMs training in May 2022, 554 attended the CompTox Chemicals Dashboard training in October 2022, and 575 attended the February 2023 ECOTOX training.

In 2021, FDA published “Advancing New Alternative Methodologies at FDA,” which provided updates on activities to advance development of alternatives to animal use and their application to regulatory decision-making. The report was developed by the FDA Alternative Methods Working Group to highlight the progress made by FDA scientists in laying the groundwork to integrate alternatives to animal testing into FDA regulatory programs. Two reports issued in 2022 expanded on topics discussed in the report:

• The 2022 “Update to the Focus Areas of Regulatory Science (FARS) Report” outlines topics FDA has identified as needing continued targeted investment. FDA reviewed each of the focus areas from the 2021 report, and this document provides important updates to the examples highlighted in the report.
• A November 2022 report on “Successes and Opportunities in Modeling & Simulation for FDA” was prepared by the FDA Modeling and Simulation Working Group. The report:
  • Elucidates how and where modeling and simulation is used across FDA, and the type and purpose of modeling and simulation used.
  • Presents a selection of modeling and simulation case studies from across nearly all FDA centers, which demonstrate how modeling and simulation is playing a tangible role in FDA fulfilling its mission.
  • Identifies opportunities for FDA to better harness modeling and simulation in upcoming years by embracing computational advances and new (and big) data streams to develop improved public health solutions.

FDA scientists also gave presentations on activities to advance alternatives at several public meetings during 2022 and 2023. Details of these presentations and presentation slides are available on the FDA website.

As part of FDA’s commitment to promote novel technologies for potential regulatory use, FDA gives developers and others the opportunity to present their new methods and methodologies directly to FDA scientists. Educational opportunities to hear more about new predictive in vitro, in vivo, and in silico methods is vital to ensuring that FDA regulators and researchers have a broad skill set and remain current with cutting-edge science and technology. Developers presented 29 webinars during 2022 and 2023; presentations described in silico models and in vitro platforms such as MPS, organoids, and engineered tissues relevant to contexts including drug-induced liver injury, neurotoxicity, inhalation toxicity, and veterinary medicine. Information for prospective presenters is available on the FDA website.

The 1985 amendments to the Animal Welfare Act established the Animal Welfare Information Center (AWIC), an information service at the USDA National Agricultural Library. AWIC’s mission is to provide information pertinent to employee training that could prevent unintended duplication of animal experimentation and on improved research methods that could reduce or replace animal use and minimize pain and distress to animals.

Within the National Agricultural Library website, AWIC provides information to the toxicology community related to the development and use of alternatives to toxicity testing, as well as information and guidelines on mandatory and regulatory testing set by various agencies. These web pages highlight peer-reviewed publications and other online resources that discuss ways to replace, reduce, and refine animal use in toxicity testing. A major update of the website in 2022 improved user experience and streamlined information discovery; a new introductory video gives an overview of AWIC resources.

During 2022 and 2023, 340,587 people visited the AWIC website. These visits generated a total of 580,863 page views. AWIC also provides information on animal use alternatives through outlets such as presentations and posters, workshops, webinars, and conference exhibits. Through these outlets, AWIC presented to over 4,348 participants at 78 different outreach events in 2022 and 2023, collectively. At these outreach events, AWIC described best practices for searching and finding current literature on methods to reduce, refine, or replace animal use in testing and experimentation.

AWIC offers workshops on meeting the requirements of the Animal Welfare Act. These workshops provide guidance on where to find 3Rs literature and resources, instruction on database literature searching techniques (e.g., search syntax), and demonstration of alternatives literature searches. They are free and open to the public. During 2022 and 2023 AWIC presented six of these workshops to a total of 789 attendees. Information about upcoming workshops is available on the AWIC website. This page also provides a link to online on-demand self-paced training for users unable to participate in a live workshop.

The National Library of Medicine developed ALTBIB to provide users with a predeveloped strategy to search PubMed citations information on alternatives to animal testing. In early 2021, responsibility for hosting and maintenance of ALTBIB transitioned to NICEATM, and ALTBIB now resides on the NTP website. In addition to the basic search strategy, the National Library of Medicine’s ALTBIB contained a page with a list of topics focused on non-animal testing platforms or endpoints for which users might be interested in searching for alternatives to animal testing. This page was not included in the NICEATM ALTBIB launch because the topics and search strategies provided were out of date, and resources were not immediately available to update them.

Over the past couple of years, USDA's Animal Welfare Information Center (AWIC) has been developing search strategies, known as “hedges”, for topics specific to alternatives. The focus of AWIC’s activity has been refinement of animal use, and their hedges tend to be focused on animal species. In 2023, NICEATM and AWIC collaborated to develop hedges on topics focused on replacement of animal use. Topics under development include MPS, QSAR models for hazard identification, non-animal tests for developmental neurotoxicity and acute inhalation toxicity, and in vitro to in vivo extrapolation (IVIVE). The hedges are currently being refined by an AWIC-sponsored working group with input from NICEATM subject matter experts and will be made available on a new webpage on the ALTBIB site in spring 2024.