ICCVAM Agency Activities

FDA has announced a plan to replace animal testing in the development of monoclonal antibody therapies and other drugs with more effective, human-relevant methods. The approach is outlined in FDA’s “Roadmap to Reducing Animal Testing in Preclinical Safety Studies.”  An April 10 press release provides an overview of the approach.

FDA will reduce, refine, or potentially replace animal testing using a range of approaches, including artificial intelligence-based computational models of toxicity and cell lines and organoid toxicity testing in a laboratory setting. Implementation of the regimen will begin immediately for investigational new drug applications, where inclusion of new approach methodology (NAM) data is encouraged. To make determinations of efficacy, the agency will begin using pre-existing, real-world safety data from other countries with comparable regulatory standards where the drug has already been studied in humans.

The roadmap describes how FDA will collaborate with ICCVAM to coordinate validation efforts and leverage data and expertise available in other government agencies. The roadmap specifically mentions the Complement Animal Research in Experimentation (Complement-ARIE) project as an avenue through which development of relevant NAMs could be supported. Complement-ARIE is a National Institutes of Health Common Fund project focused on accelerating the development, standardization, validation, and use of human-based NAMs .

Presentation slides are now available from the October 2024 workshop, “Advancing Quantitative Analysis in Human Health Assessments through Probabilistic Methods.” This workshop, organized by the U.S. Environmental Protection Agency (EPA) Office of Research and Development in conjunction with NICEATM, was held to facilitate discussion of probabilistic methods in human health risk assessment. This workshop provided examples of application of probabilistic methods in chemical risk assessments, highlighted ongoing research, and discussed the needs and challenges for the regular use of these methods. Workshop participants gained a greater understanding of probabilistic methods within the context of human health and how these methods may ultimately be implemented. A workshop report is in preparation for publication later this year.

The next webinar in the EPIC series on the use of new approach methodologies (NAMs) in risk assessment will cover “NAM-based strategies for systemic toxicity assessment.” The webinar will be held on Wednesday, March 12 at 11:00 a.m. ET.

The webinar will feature presentations by Katie Paul Friedman, EPA, and Elisabet Berggren, European Commission Joint Research Centre. Paul Friedman will describe PODNAM, a NAMs-based point-of-departure for systemic toxicity, and summarize international activities to characterize the concordance between a PODNAM and a traditional systemic toxicity point-of-departure. Berggen’s presentation will consider challenges and possible ways to progress towards a system of chemical safety assessment not relying on animal testing based on the knowledge and experience of today.

The EPIC series covers timely topics on the use of NAMs for risk assessment within EPA and the California Department of Pesticide Regulation (CDPR). The series began in August 2023 and continues quarterly; links to past webinars are available. The webinar series is co-organized by EPA, PETA Science Consortium International, the Institute for In Vitro Sciences, and the California Department of Pesticide Regulation.

EPA hosted its fourth Conference on the State of Science on Development and Use of NAMs for Chemical Safety Testing on November 5-6, 2024. Slides from the conference are now available.

This hybrid meeting with in-person participation took place on EPA’s campus at Research Triangle Park, North Carolina. At the conference, attendees heard from representatives from EPA, other federal agencies, industry, universities, and international organizations on the state of the science on the development and use of NAMs for chemical safety testing.

The NIH Common Fund, along with the Office of the NIH Director, Office of Strategic Coordination has published a Notice of Funding Opportunity to support the Complement Animal Research in Experimentation (Complement-ARIE) Program. The funding opportunity will be administered by the National Center for Advancing Translational Sciences on behalf of NIH. Complement-ARIE will accelerate the development, standardization, validation, and use of human-based NAMs.

Investigators with expertise and insights into the area of NAMs are encouraged to consider applying for these funding opportunities. Funding will support technology development centers that will stimulate the development of combinatorial NAMs to support scientific areas of need, with emphasis on increased biological complexity and throughput, innovative combinatorial approaches, and data sharing according to findability, accessibility, interoperability, and reusability (FAIR) principles. Developing these NAMs will require multi-disciplinary expertise in disease research, personalized medicine, screening therapeutics for safety and efficacy, and regulatory science. The NIH Common Fund intends to commit approximately $18M per year to fund 4-5 awards. The deadline for applications has been extended to March 18.

Complement-ARIE program goals include:

• To better model and understand human health and disease outcomes across diverse populations.
• To develop NAMs that provide insight into specific biological processes or disease states.
• To validate mature NAMs to support regulatory use and standardization.
• To complement traditional models and make biomedical research more efficient and effective.

Registration is open for upcoming workshops on “Meeting the Requirements of the Animal Welfare Act” offered by the USDA National Agricultural Library’s Animal Welfare Information Center. Live virtual workshops will be offered on Wednesday and Thursday, February 26-27, from 1:00-4:30 p.m. EST each day, and on Wednesday and Thursday, April 8-9, from 1:00-4:30 p.m. EDT each day. There is also a self-paced asynchronous version of the workshop available. Hosted by Oregon State University, this version provides the same content as the live workshop available on a flexible schedule. 

The Animal Welfare Information Center was established to help the regulated community comply with the Animal Welfare Act. The Center provides information on approaches to prevent duplication of animal experimentation and alternative methods that replace, reduce, or refine animal use. More information about the Center, including an introductory video, is available on their website.

NICEATM has published an addendum to the July 2021 report, “Prospective and Retrospective Evaluation of the Eye Irritation Potential of Agrochemical Formulations.” The new document expands the number of substances identified as moderately or mildly irritating to the eye based on historical rabbit test data. It also includes results from additional in vitro eye irritation methods. 

NICEATM collaborated with the PETA Science Consortium International e.V., EPA, and member companies of the trade association CropLife America to develop an in vitro defined approach for classification of eye irritation potential of agrochemical formulations based on U.S. and international hazard classification systems. The data presented in these documents support ongoing work to develop nonanimal defined approaches for assessing eye irritation potential of agrochemical formulations.

On January 6, FDA issued draft guidance to provide recommendations on the use of artificial intelligence (AI) intended to support a regulatory decision about a drug or biological product’s safety, effectiveness, or quality. This is the first guidance the agency has issued on the use of AI for the development of drug and biological products. The FDA’s human and animal medical product centers, along with the agency’s Office of Inspections and Investigations, Oncology Center of Excellence, and Office of Combination Products worked collaboratively on this draft guidance to ensure consistency across the agency. In developing these recommendations, the FDA incorporated feedback from interested parties including sponsors, manufacturers, technology developers and suppliers, and academics.

FDA is accepting comment on the draft guidance through April 7. A Federal Register notice provides instructions on how to submit comments; an FDA press release provides an overview of the draft guidance.

The NIH Common Fund, along with the Office of the NIH Director, Office of Strategic Coordination has published a Notice of Funding Opportunity to support the Complement Animal Research in Experimentation (Complement-ARIE) Program. The funding opportunity will be administered by the National Institute of Environmental Health Sciences on behalf of NIH.

This funding will support establishment of Complement-ARIE’s New Approach Methodologies (NAMs) Data Hub and Coordinating Center. This center will provide a centralized data hub and searchable repository for NAMs, establish standards for data reporting and model credibility, develop strategies for interoperability, sustainability, and data reuse, and develop tools for data analytics, dissemination, and sharing. It will also serve as the coordinating center for the overall Complement-ARIE program, helping to drive internal program cohesion and fostering community collaborations, including administrative and logistical support while organizing the Complement-ARIE semi-annual investigators meeting. The NIH Common Fund intends to fund one award of approximately $5M per year. Letters of intent are due February 10. Applications will be accepted starting February 10 and will be due March 10.

Complement-ARIE will accelerate the development, standardization, validation, and use of human-based NAMs. Complement-ARIE program goals include:

• To better model and understand human health and disease outcomes across diverse populations.
• To develop NAMs that provide insight into specific biological processes or disease states.
• To validate mature NAMs to support regulatory use and standardization.
• To complement traditional models and make biomedical research more efficient and effective.

The NIH Common Fund, along with the Office of the NIH Director, Office of Strategic Coordination has published a Notice of Funding Opportunity to support the Complement Animal Research in Experimentation (Complement-ARIE) Program. The funding opportunity will be administered by the National Center for Advancing Translational Sciences on behalf of NIH. Complement-ARIE will accelerate the development, standardization, validation, and use of human-based NAMs.

Investigators with expertise and insights into the area of NAMs are encouraged to consider applying for these funding opportunities. Funding will support technology development centers that will stimulate the development of combinatorial NAMs to support scientific areas of need, with emphasis on increased biological complexity and throughput, innovative combinatorial approaches, and data sharing according to findability, accessibility, interoperability, and reusability (FAIR) principles. Developing these NAMs will require multi-disciplinary expertise in disease research, personalized medicine, screening therapeutics for safety and efficacy, and regulatory science. The NIH Common Fund intends to commit approximately $18M per year to fund 4-5 awards. Letters of intent are due January 24, 2025. Applications will be accepted starting January 28 and will be due February 28.

Complement-ARIE program goals include:

• To better model and understand human health and disease outcomes across diverse populations.
• To develop NAMs that provide insight into specific biological processes or disease states.
• To validate mature NAMs to support regulatory use and standardization.
• To complement traditional models and make biomedical research more efficient and effective.

On November 5, EPA released Version 2.5 of the CompTox Chemicals Dashboard. Updated tools include SeqAPASS and ToxCast. Some featured updates are:

• A new default option, “Formula Contains,” for the Advanced Search > Molecular Formula Search.
• Addition of a “Reply” column to the Comments page.
• Updates of Hazard and high-throughput phenotypic profiling (HTPP) data and assay descriptions, respectively, to accordions to be more widely accessible.
• Inclusion of the MS-Ready mass and MS-Ready formulae in the downloaded Batch Search file after MS-Ready SMILES are selected.

FDA and Triangle Centers of Excellence in Regulatory Science and Innovation (CERSI) and the are hosting a hybrid workshop February 27-28, 2025, on “Pediatric Developmental Safety Assessment and Novel Alternative Methods.” The on-site location is FDA White Oak Campus in Silver Spring, MD. In-person attendance is capped at 150. Registration is available until 5 p.m. ET on February 26. Nicole Kleinstreuer, NICEATM Director, will present on “NAMs Across Agencies.”

Workshop objectives include:

• To understand the current programs in federal agencies related to novel alternative methods and pediatric developmental biology.
• To discuss the identification and utilization of secondary targets in pediatric developmental safety assessment.
• To review the use of juvenile animal studies and in vitro tools to assess pediatric developmental safety assessment.
• To explore the use of model-informed drug development techniques such as quantitative systems pharmacology and the use of artificial intelligence and machine learning in pediatric developmental safety assessment.

Registration is free of charge and required for in-person and virtual attendance. 

EPA will host a webinar, “Computational Toxicology and Exposure Communities of Practice: Updates to the Web-based Interspecies Correlation Estimation (Web-ICE) Application,” on December 12 at 11 a.m. ET. The webinar will present an overview of the Web-ICE application and its use within EPA. Web-ICE is a new approach methodology developed and applied by EPA to predict acute toxicity for diverse species from limited surrogate species data. Web-ICE was developed to address data gaps in species sensitivity and reduce reliance on uncertainty factors in ecological risk assessment. Web-ICE uses least squares regression of species sensitivity to predict acute toxicity to taxa for chemicals with limited measured toxicity data from the known toxicity of a surrogate species. The newly released Web-ICE v4.0 has over 4,700 models representing 478 aquatic animal species, over 100 models representing 69 algae species, and over 850 models for 156 species of terrestrial birds and mammals. A new feature of Web-ICE v4.0 is the Bulk ICE module, which provides predictions from all available surrogates to maximize the taxonomic diversity of modelled output.

The next webinar in the EPIC series on the use of new approach methodologies (NAMs) in risk assessment will cover “Regulatory tools for assessing the skin sensitization potential of chemicals and a case study using the SARA-ICE model.” The webinar will be held on Wednesday, December 11 at 11:00 a.m. EDT.

The webinar will feature presentations by Donna Macmillan, International Collaboration on Cosmetics Safety, and NICEATM scientists Emily Reinke, Inotiv (contractor supporting NICEATM). Macmillan will describe the development of an internationally accepted guideline for defined approaches to skin sensitization, and how to apply the defined approaches published in the guideline. Reinke will discuss the Skin Allergy Risk Assessment – Integrated Chemical Environment (SARA-ICE) Bayesian statistical model for derivation of a point-of-departure for quantitative risk assessment for skin sensitization.

The EPIC series covers timely topics on the use of NAMs for risk assessment within EPA and the California Department of Pesticide Regulation (CDPR). The series began in August 2023 and continues quarterly; links to past webinars are available. The webinar series is co-organized by EPA, PETA Science Consortium International, the Institute for In Vitro Sciences, and CPDR.

Videos are now available from presentations from the 11th Annual 3Rs Symposium held September 4-5. Topics discussed included microphysiological systems, animal/organ sharing, optimizing animal breeding, and research design and statistical strategies. Videos are available on the National Agricultural Library, Animal Welfare Information Center’s website.

The 3Rs Symposium is an annual event organized by:

• Center for Alternatives to Animal Testing, Johns Hopkins University
• Bloomberg School of Public Health Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine
• USDA Animal Welfare Information Center at the National Agricultural Library
• NIH Office of Laboratory Animal Welfare

Materials from previous 3Rs Symposiums are available on the Animal Welfare Information Center’s website.

A colloquium on “Emerging Concepts in Hazard Identification and Exposure Assessment of Per- and Polyfluoroalkyl Substances” will be held Tuesday, December 3 from 9:00-12:45 p.m. Speakers from federal agencies, academia, and testing laboratories will discuss dietary sources of PFAS and methods for assessing and communicating their health risks. The webcast is open to the public at no charge.

This is the latest event in a series organized by the Society of Toxicology and the FDA Human Foods Program (formerly the Center for Food Safety and Applied Nutrition). The colloquia present scientific information that is high-quality, cutting-edge, future-oriented toxicological science to provide a well-grounded foundation to inform the work of FDA employees. 

The National Eye Institute is leading an NIH collaboration to incentivize the creation, development, and validation of a quantitative data sharing index. The Data Sharing Index (S-index) Challenge aims to incentivize and reward effective data sharing practices by assessing how effective a researcher is in sharing their data in a way that has utility for future study. This metric will incorporate factors such as adherence to findable, accessible, interoperable, and reusable (FAIR) standards; data timeliness; completeness of annotation; frequency of utilization in other studies; and related publications and patents. This metric seeks to recognize and incentivize the efforts of individuals and teams in sharing data, rather than just the value of the data itself.

Phase 1 of the Challenge will open in April 2025; the deadline to register to participate is March 3, 2025. In Phase 1, participants will engage in brainstorming and idea generation, culminating in the submission of a proof-of-concept proposal. These proposals will compete in the first round, with up to six finalists selected to receive a $15,000 prize and advance to Phase 2. The Challenge will award up to $1M to support development of winning submissions. 

A webinar on "Microphysiological Systems (MPS) for Chemical Risk Assessment" is scheduled for October 28 from 10:00 a.m.-12:00 p.m. (ET), and is cohosted by the Johns Hopkins Center for Alternatives to Animal Testing, FDA Human Foods Program, and the International MPS Society. The focus of the webinar is on advancing applications of microphysiological systems (MPS) in chemical risk assessment and safety testing. The event will bring together regulators and researchers to explore the role of MPS in various research and regulatory settings, offering attendees the opportunity to engage with practical experiences and technical knowledge that drive innovation in this field. The webinar will be the first in a series aimed at fostering collaboration between leading investigators and regulators, providing a platform for exploring both established and potential applications of in vitro methods in chemical safety.

NIEHS and NICEATM have entered into a public-private partnership with the International Collaboration on Cosmetics Safety (ICCS) to conduct a landscape analysis on the current state of non-animal, human-relevant methods and approaches for assessing systemic toxicity. The analysis will focus on describing existing efforts, and will highlight gaps, challenges, and opportunities associated with human-relevant models of systemic toxicity. The intent is to provide sufficient coverage of the landscape both to address pragmatic near-term needs and to shape the future of how safety assessments are performed. This work will use a generative artificial intelligence approach to drastically decrease the time and improve efficiency of completing the analysis, which is expected to be completed in Spring 2025. 

The NIH Common Fund, along with its partner NIH Institutes, Centers, and Offices, has published two Notices of Funding Opportunity (NOFOs) to support the Complement Animal Research in Experimentation (Complement-ARIE) Program. Complement-ARIE will accelerate the development, standardization, validation, and use of human-based New Approach Methodologies (NAMs).

Investigators with expertise and insights into the area of NAMs are encouraged to consider applying for these funding opportunities, which will support Technology Development Centers and a Data Hub and Coordinating Center. NIH also encourages collaborative investigations combining expertise in in vitro, in silico, and in chemico NAMs. NIH expects to offer four or five awards with funding of approximately $18M per year.

• First estimated application due date for the Technology Development Centers (UM1 Clinical Trial Option) is February 28, 2025.
• First estimated application due date for the Data Hub and Coordinating Center (U24 Clinical Trial Option) is March 10, 2025.

Complement-ARIE program goals include:

• To better model and understand human health and disease outcomes across diverse populations.
• To develop NAMs that provide insight into specific biological processes or disease states.
• To validate mature NAMs to support regulatory use and standardization.
• To complement traditional models and make biomedical research more efficient and effective.

EPA released a detailed review of major environmental statutes that summarizes which EPA laws or regulations require vertebrate animal testing, such as laboratory testing done on rats, mice, or rabbits. The report concludes that many statutes and regulations guiding EPA’s authority are broadly written and do not preclude the use of scientific information from NAMs, which are defined as any technology, methodology, approach, or combination that can provide information on chemical hazard and risk assessment to avoid the use of animal testing.

This report is a deliverable in EPA’s NAMs Work Plan, which was originally released in June 2020 and updated in November 2021. The Work Plan outlines the Agency’s strategies and objectives for increasing the rigor and sophistication of Agency assessments while reducing the reliance on vertebrate animals to test chemicals in regulatory, compliance, enforcement, and research activities through the use of NAMs. The assessments will remain fully protective of human health and the environment. The first objective in the Work Plan was to evaluate regulatory flexibility for accommodating NAMs, and the report accomplishes that objective.

• EPA’s next Computational Toxicology and Exposure Communities of Practice webinar will focus on “Using Environmental RNA to Understand the Effects of Pollution on Aquatic Ecosystems.” The webinar is on Thursday, September 26, at 11:00 a.m. EDT. Marissa Geroux of the Center for Environmental Measurement and Modeling will explain what environmental RNA (eRNA) is and how is it used in environmental science, and discuss use of eRNA metabarcoding to assess the impacts of emerging contaminants on aquatic communities. Information about the Communities of Practice webinar series and a link to register for this webinar are available.
• EPA is hosting its fourth “Conference on the State of Science on Development and Use of NAMs for Chemical Safety Testing” on November 5-6. This will be a hybrid meeting with in-person participation on EPA’s campus at Research Triangle Park, NC. Registration to attend in person is open until October 22 or until the venue capacity is reached. Information and a link to register are available.
• EPA has released updates of the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) and Generalized Read-Across (GenRA) tools. These and other EPA CompTox tools are available on the EPA CompTox website.

The U.S. Environmental Protection Agency (EPA) Office of Research and Development, in conjunction with NICEATM, is convening a workshop to facilitate discussion of probabilistic methods in human health risk assessment. This workshop will provide examples of the application of probabilistic methods in chemical risk assessments, highlight ongoing research, and discuss the needs and challenges for the regular use of these methods. The workshop will be held in person at EPA in Research Triangle Park, NC and also webcast. In-person attendees should register by Tuesday, September 24.

Those planning to attend in person are invited to submit abstracts for a poster session. Abstracts should describe projects or activities relevant to workshop agenda topics. Abstracts will be accepted until Friday, September 13 or until 40 abstracts are received. Organizers will contact submitters to confirm poster acceptance and provide logistical details about the presentation.

The National Academies of Sciences, Engineering, and Medicine recently recommended consideration of how and when traditional deterministic approaches for human health risk assessment (i.e., toxicity value point estimates) can be transitioned towards probabilistic methods for deriving risk-specific doses. This workshop will highlight past examples where probabilistic methods were implemented to derive chemical-specific toxicity values, provide insight into the current state of the research surrounding probabilistic methods in chemical risk assessments, and discuss the future directions for implementing these probabilistic methods in human health assessments. The agenda will feature sessions on four subtopics:

• Probabilistic exposure
• Toxicokinetics
• Benchmark dose modeling
• Toxicity value determination

Throughout these sessions interdisciplinary panels comprising subject matter experts from government, industry, academia, and nongovernmental organizations will conduct panel discussions to evaluate the proposed methods and provide suggestions for how the transition might be implemented. Workshop participants should gain a greater understanding of probabilistic methods within the context of human health assessments and learn how these methods may ultimately be implemented.

The National Institutes of Health (NIH) has published its landscape analysis for the Complement Animal Research in Experimentation (Complement-ARIE) program.

Complement-ARIE will accelerate the development, standardization, validation, and use of human-based NAMs that more accurately model human biology, and complement, or in some cases, replace traditional research models. To ensure the Complement-ARIE program focused on the best opportunities and areas of greatest need for human-based model development, a comprehensive landscape analysis was conducted to collect information on ongoing efforts in the NAMs space. The analysis described existing efforts, and highlighted gaps, challenges, and opportunities in the areas of human-based models of health and disease including:

• In vitro models
• In silico models
• In chemico cell-free models
• FAIRness of data needed to train, interpret, and use NAMs (FAIR = findable, accessible, interoperable, reusable)

NICEATM scientists were key contributors to the landscape analysis. In addition to NICEATM Director Nicole Kleinstreuer, seven members of the Inotiv contract support team are acknowledged as authors of the landscape analysis report.

The National Institutes of Health (NIH) Common Fund has announced a Notice of Intent to Publish a Funding Opportunity for the Complement Animal Research in Experimentation (Complement-ARIE) program. Complement-ARIE will accelerate the development, standardization, validation, and use of human-based new approach methodologies (NAMs) that more accurately model human biology, and complement, or in some cases, replace traditional research models.

Complement-ARIE program goals include:

• To better model and understand human health and disease outcomes across diverse populations.
• To develop NAMs that provide insight into specific biological processes or disease states.
• To validate mature NAMs to support regulatory use and standardization.
• To complement traditional models and make biomedical research more efficient and effective.

The Complement-ARIE program plans to issue a Notice of Funding Opportunity to support the Complement-ARIE Comprehensive NAMs Technology Development Centers. The goal/intent of these Centers is to stimulate the development of combinatorial NAMs in the areas of greatest need.

Publication of the funding opportunity is anticipated on October 18. The Notice of Intent to Publish a Funding Opportunity is available now. More information about the Complement-ARIE Program is also available and interested persons can keep up to date with future announcements by signing up for the Complement-ARIE listserv.

The National Institutes of Health (NIH) National Institute on Aging 3-D In Vitro Tissue Systems Workshop will be held July 29, 9:00 a.m. – 5:00 p.m., and July 30, 9:00 a.m. – 3:00 p.m. (EDT). The workshop aims to examine how complex mammalian 3-D in vitro tissue platforms can be developed, validated, and leveraged to study aging. The goals are to assess the status of the field and critical needs, to define future directions, and to outline opportunities and priorities to better support the development of novel in vitro platforms for research on aging.Researchers at all career stages interested in modeling aging in vitro are invited to attend.

An agenda with a list of presentations, speakers, and times, and registration are now available. Contact Tiziana Cogliati with any questions about the workshop.

The National Institutes of Health (NIH) Office of Strategic Coordination (OSC) Community Engagement Workshop will be held July 24-25 from 9:00 a.m. – 4:30 p.m. Day 1, and 9:00 a.m. – 12:30 p.m. Day 2. This workshop brings together differing perspectives from an array of individuals that represent their communities to gather their thoughts and opinions about challenges and opportunities regarding NIH Common Fund data science resources.

The NIH Common Fund cultivates large publicly available biomedical and behavioral datasets. This data may be used by the research and medical community to make new discoveries or generate new hypotheses. During this workshop, NIH would like to identify barriers that currently exist to using data and learn what outreach, training, and support can be provided to the biomedical community.

Douglas Sheeley, Acting Director of OSC will give the welcome and introduction. Krystal Tsosie, Assistant Professor in the School of Life Sciences and Associate Director of Biodiversity Knowledge Integration at Arizona State University is the keynote speaker. More information regarding speakers, a full agenda and workshop registration are now available.

The National Center for Advancing Translational Sciences (NCATS) Assay Guidance Manual (AGM) program is hosting a two-day workshop, Wednesday, October 23, 11:00 a.m. – Thursday, October 24, 5:15 p.m. (EDT) covering a broad range of critical concepts. This workshop is offered virtual and free to attend, and is jointly organized by NCATS, Biomedical Advanced Research and Development Authority (BARDA), University of California San Diego (UCSD), and The University of North Carolina at Chapel Hill (UNC). More information including a full agenda and registration are now available.

The workshop goal is to provide scientists with best practices and standards for rigor in the field of computational drug discovery to enable accurate and reproducible results. This workshop will also cover case studies for AI-driven drug discovery campaigns as well as an overview of new trends and gaps in the field.

Specific goals and objectives:

• Provide participants with data sources and best practices in building and maintaining databases used for developing robust and rigorous AI-based drug discovery models/methods.
• Introduce participants to the available computational methodologies utilized in drug discovery and discuss their utility and limitations.
• Provide case studies for digital drug discovery and an overview of new trends in the field.
• Provide guidelines and considerations for developing robust and reproducible in silico models.
• Discuss challenges in data quality and data sharing as well as affordability, accessibility, transferability, accuracy, and reproducibility of AI-driven computational techniques.
• Identify gaps in translation of these in silico models to therapies and seed discussions around best practices to help bridge the gaps in the field.

The 11th Annual 3Rs Symposium: Practical Approaches to Each of the 3Rs, a virtual webinar, will be held September 4-5 and 11-12, 10:00 a.m. – 1:30 p.m. (ET). The symposium is jointly organized by Center for Alternatives to Animal Testing, Johns Hopkins University Bloomberg School of Public Health, the Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, the USDA’s Animal Welfare Information Center (AWIC) at the National Agricultural Library, and the Office of Laboratory Animal Welfare, National Institutes of Health.

The goal of the symposium is to bring together experts and practitioners to share information and discuss new and practical approaches to the 3Rs. Sessions are designed for investigators, laboratory animal veterinarians, care staff, and IACUC members and staff. Residents, students, and postdocs are also welcome. There will be opportunities built into the program for attendees to ask questions, comment, or offer suggestions. More information, including a full agenda, and ticket information are now available.

The U.S. Environmental Protection Agency (EPA) conducted a value of information (VOI) analysis to weigh the public health and economic trade-offs associated with the timeliness, uncertainty, and costs of conducting the EPA Transcriptomics Assessment Product compared to traditional human health assessment processes. EPA’s VOI framework and a report on a case study applying the framework are now available.

Fewer than a quarter of the tens of thousands of chemicals in commerce--as well as those found in the environment, various waste streams, and the human body--have traditional toxicity or epidemiological data that can inform human health risk assessments. VOI analysis is a systematic approach to determine the “value of information” in economic terms. It allows comparison of “what we already know” and “what we will know” to determine which data generation methodologies are most valuable for decision-making. While the potential application of value-of-information analysis for toxicology has been discussed for a number of years, practical applications of such an analysis in toxicology to real-world problems are lacking.

A novel feature of the EPA framework was the inclusion of a time dimension that permits incorporation of the cost of delay in incorporating additional information. The case study described in the report applied this framework to compare a short-term in vivo transcriptomic assay approach to developing protective reference doses with the traditional chronic rodent bioassay and human health assessment process. A panel of the EPA Board of Scientific Counselors was convened to assess the scientific rigor of this case study and the resulting conclusions.

The Department of Health and Human Services has released the 2024-25 Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Omnibus Grant Solicitations. This funding is available for small business grant applications to support development and commercialization of innovative technologies. 

Projects being funded by NIEHS under these solicitations include development of toxicity screening, testing, and modeling approaches that support Tox21 and other NTP goals. Areas of high priority include development of:

• Informatics tools and platforms to organize, store, retrieve, extract, and integrate information on exposures and health effects data.
• Application of machine learning methods and natural language processing for extracting and integrating diverse data types and for generating causal networks from experimental data and public knowledgebases.
• Adapting or developing new methods and tools for automating environmental health-related literature and systematic reviews, including article selection and prioritization, data extraction, study quality evaluation, and summarization of environmental health impacts.
• Mid- to high-throughput and high-content assays using in vitro or tissue chip technologies to screen and rank toxicity of emerging engineered nanomaterials for cytotoxicity, genotoxicity, and metabolic toxicity.
• Human and rodent organotypic culture models and microphysiological systems.
• Approaches to characterize and integrate key molecular and cellular changes related to effects of toxicant exposures in carcinogenicity, developmental neurotoxicity, or cardiotoxicity.
• Screening systems that incorporate genetic diversity into toxicology testing.
• Short-term tests, assays, or systems designed specifically to reduce or replace existing regulatory animal studies for acute toxicity (oral or inhalation), reproductive or developmental toxicity, carcinogenicity, or ocular toxicity.

The first deadline for applications under this announcement is September 5. Complete information about eligibility, applying, and deadlines is available at:

• PA-24-245, SBIR opportunities, clinical trial not allowed.
• PA-24-246, SBIR opportunities, clinical trial required.
• PA-24-247, STTR opportunities, clinical trial not allowed.
• PA-24-248, STTR opportunities, clinical trial required.

More information about the program is available on the NIEHS SBIR/STTR webpage.

EPA is hosting its fourth “Conference on the State of Science on Development and Use of NAMs for Chemical Safety Testing” on November 5-6. This will be a hybrid meeting with in-person participation on EPA’s campus at Research Triangle Park, NC. Registration to attend in person is open until October 22 or until the venue capacity is reached. Register to attend either in person or virtually.

At the conference, attendees will hear from representatives from EPA, other federal agencies, industry, universities, and international organizations on the state of the science on the development and use of NAMs for chemical safety testing. General information about the conference is already accessible; an agenda will be posted when available.

The next webinar in the EPIC series on the use of new approach methodologies (NAMs) in risk assessment will cover “The CATMoS model for acute oral toxicity and evaluation of its potential use in a regulatory context for pesticide hazard and risk assessment.” The webinar will be held on Wednesday, August 28 at 11:00 a.m. EDT. Registration and more information are now available.

The webinar will feature presentations by NICEATM scientist Kamel Mansouri, National Institute of Environmental Health Sciences (NIEHS), and Michael Lowit, U.S. Environmental Protection Agency (EPA) Office of Pesticide Programs. Mansouri will discuss the Collaborative Acute Toxicity Modeling Suite (CATMoS), a global project to develop predictive in silico models for assessing chemical safety. These models cover five endpoints relevant to regulatory frameworks and are now being evaluated for use by the EPA. Lowit will describe a collaboration between EPA, NICEATM, and the Humane Society of the United States to apply CATMoS to predicting acute toxicity of technical grade active ingredients for pesticides registered by the EPA.

The EPIC series covers timely topics on the use of NAMs for risk assessment within EPA and the California Department of Pesticide Regulation (CDPR). The series began in August 2023 and continues quarterly; links to past webinars are available. The webinar series is co-organized by EPA, PETA Science Consortium International, the Institute for In Vitro Sciences, and CPDR.

A new report, “In Silico Technologies: A Strategic Imperative for Accelerating Breakthroughs and Market Leadership for FDA-regulated Products,” has been published by the Reagan-Udall Foundation for the FDA.

The report urges the adoption of in silico technologies such as artificial intelligence and machine learning for development and safety evaluation of products that influence human health. This report strives to bridge the gap between technical and business teams in the ecosystem of products regulated by the U.S. Food and Drug Administration (FDA) and the nation’s food supply by building the business case for industry investment in in silico technologies as a strategic imperative for accelerating breakthroughs and market leadership in FDA-regulated products. NICEATM Director Nicole Kleinstreuer was a contributor to the report.

A new NTP webpage will allow users to easily search PubMed for information on specific topics related to alternatives to animal testing. NICEATM and the U.S. Department of Agriculture (USDA) National Agricultural Library’s Animal Welfare Information Center (AWIC) collaborated to develop search strategies, known as “hedges,” for topics specific to alternatives. Hedges are now available for the following topics:

• Alternatives to animal use for assessing acute inhalation toxicity.
• Alternatives to animal use for assessing developmental neurotoxicity.
• In vitro to in vivo extrapolation.
• Microphysiological systems.

Additional hedges are under development; please contact Catherine Sprankle with suggestions of additional topics.

AWIC has developed search hedges for a number of animal welfare topics, and offers guidance and assistance for literature searches on animal use alternatives. For more information and to access these resources, visit the USDA website.

The Occupational and Inhalation Exposures Research Program within the NIEHS Division of Translational Toxicology recently released a “Request for Information (RFI) on the Use of In Vitro Lung Models in Inhalation Toxicology Research with Potential Application to Regulatory Decision-Making.” Responses to this RFI will guide the Division’s research in this area and align it with the needs of the broader research and regulatory communities. Respondents are specifically asked to respond by June 7 and provide information about:

• Applications for which in vitro lung models have been used.
• The most important scientific knowledge gaps underlying the assessment of the effects of inhaled substances on human health.
• Current technical challenges and limitations related to using in vitro lung models in research.
• Ongoing concerted efforts by individuals or groups to utilize in vitro lung models in routine hazard or risk assessment.

The fourth webinar in the EPIC series on the use of new approach methodologies (NAMs) in risk assessment will cover “Advancing eye irritation assessment with non-animal methods for industrial chemicals and agrochemicals: progress at the U.S. EPA.” The webinar will be held Wednesday, May 29 from 11:00 a.m.–12:30 p.m. EDT. The speakers include Lindsay O’Dell, EPA Office of Pesticide Programs, and Renee Beardslee, EPA Office of Pollution Prevention and Toxics.

The EPIC series covers timely topics on the use of NAMs for risk assessment within EPA and the California Department of Pesticide Regulation (CDPR). The series began in August 2023 and continues quarterly. Links to past webinars are available at the link above. The webinar series is co-organized by EPA, PETA Science Consortium International (PSCI), the Institute for In Vitro Sciences, and CPDR. 

The National Institute of Environmental Health Sciences (NIEHS) is convening a two-day virtual workshop on horizon scanning to proactively identify and improve responses to emerging contaminants, emergencies, and issues of concern. Horizon scanning activities engage experts in conversations to predict responses or capabilities that may be needed. This workshop will establish a network or community of practice for sharing information about horizon scanning in the context of environmental health. Participants will produce one or more publications summarizing existing tools, research gaps, guidance, or strategies for proactively identifying emerging contaminants or issues of concern and best practices for communicating hazard information to affected communities. The workshop will be held in two sessions on Tuesday, April 30 and Tuesday, May 7.

The NIEHS Small Business Program is accepting applications for its Applicant Assistance Program (AAP). This free, 10-week program is designed to assist small businesses in preparing a Small Business Innovation Research or Small Business Technology Transfer grant application in time for the September 5, 2024, deadline. AAP provides participants with services such as application needs assessment, mentoring, application preparation support, and application review. AAP aims to increase the number of applications from underrepresented small businesses, especially women-owned and socially and economically disadvantaged companies, and offers support and resources to help those applicants maximize their chances of success. Two webinars are being presented on April 25 and May 14 to provide information about the program and answer questions from potential participants.

The application portal opens April 25. Submit applications by May 21, 5:00 pm ET.

EPA is hosting a free New Approach Methods (NAMs) Tools Training Workshop on April 24–25 from 9:00 a.m.–5:30 p.m. (EDT) both days. The workshop will be presented in-person only at EPA’s Research Triangle Park campus in Durham, NC. Space is limited. Preference will be given to registrants who are able to attend both days of the workshop.

This workshop builds on EPA’s ongoing NAMs virtual trainings and will give participants the opportunity to advance their knowledge on EPA NAMs tools through overview sessions, in-depth learning, interactions with tool and data owners, and tool-specific case studies. EPA NAMs tools featured in the workshop include:

• Adverse Outcome Pathway (AOP) Wiki
• Chemical Exposure (ChemExpo) Knowledgebase
• Cheminformatics Modules
• CompTox Chemicals Dashboard
• Ecotoxicology (ECOTOX) Knowledgebase
• Generalized Read-Across (GenRA) tool
• High-Throughput Toxicokinetics (httk) R package
• Sequence Alignment to Predict Across-Species Susceptibility (SeqAPASS) tool
• Toxicity Estimation Software Tool (TEST)
• Toxicity Forecasting (ToxCast)

Attendees will have an opportunity to get a sneak peek at a new Non-Targeted Analysis (NTA) Web Application and RapidTox, a new suite of workflows to address targeted human health data needs in support of decision-making.

The next webinar in the EPIC series on the use of NAMs in risk assessment, co-organized by the U.S. Environmental Protection Agency (EPA), PETA Science Consortium International, Institute for In Vitro Sciences, and the California Department of Pesticide Regulation (CPDR), will cover “Establishing confidence in new approach methodologies.” The webinar will be held on Wednesday, February 21 from 11:00 a.m.–12:30 p.m. EST. ICCVAM member Elijah Petersen, National Institute of Standards and Technology, will discuss the forthcoming ICCVAM document, “Validation, Qualification, and Regulatory Acceptance of New Approach Methods.” Corrie Ellison, Procter & Gamble, will present a case study discussing the process of gaining confidence in alternative approaches for assessing the toxicity of branched carboxylic acids. 

The EPIC series covers timely topics on the use of NAMs for risk assessment within EPA and CDPR. The series began in August 2023 and will continue quarterly. 

A February 1 statement from NIH Director Monica Bertagnolli announced NIH acceptance of a working group’s recommendations on NAMs activities.

A working group of the Advisory Committee to the Director was charged with identifying areas in which the development and use of novel alternative methods would provide maximal value to biomedical research. The working group’s activities culminated in a December 2023 report to the Advisory Committee with seven specific recommendations on how NIH should work with the scientific community to support development and use of NAMs. In her statement, Bertagnolli noted how the recommendations build on an existing foundation of NIH investment in NAMs projects as NIH continues to advance the validation and regulatory implementation of NAMs in partnership with other federal agencies via ICCVAM.

On January 25, the NIH Council of Councils approved the concept for the new NIH Common Fund's Complement Animal Research In Experimentation (Complement-ARIE) program. Complement-ARIE will speed the development, standardization, validation, and use of human-based new approach methodologies (NAMs), and significantly advance understanding of human health and disease by providing a range of ready and standardized biomedical research models. Developing these models will require expertise in disease research, personalized medicine, and in screening therapeutics for safety and effectiveness. The Complement-ARIE program will bring together experts in these areas via efforts such as technology development projects and centers, resource coordinating centers, validation networks, community engagement and training, and strategic key-partner engagement.

Registration is open for upcoming workshops on “Meeting the Requirements of the Animal Welfare Act” offered by the USDA Animal Welfare Information Center. Live virtual workshops will be offered on Wednesday and Thursday, March 6-7, from 1:00-4:00 p.m. EST each day, and on Wednesday and Thursday, May 8-9, from 1:00-4:00 p.m. EDT each day. There is also a self-paced asynchronous version of the workshop available.

The Animal Welfare Information Center was established to help the regulated community comply with the Animal Welfare Act. The Center provides information on approaches to prevent duplication of animal experimentation and alternative methods that replace, reduce, or refine animal use. More information about the Center, including an introductory video, is available on the Center’s website.

The National Center for Biotechnology Information (NCBI) is hosting a codeathon on “Building Transparent ML/AI Solutions to Advance Biological Research.” The event will address the growing need for collaboration, knowledge sharing, and exploration of the transparent deployment of machine learning (ML) and artificial intelligence (AI) in research. The codeathon will be held virtually from February 26 to March 1; those interested in participating should register by Monday, January 15. 

This event will bring together developers, data scientists, and tech enthusiasts to build equitable and transparent ML/AI solutions that tackle various problems in healthcare, research, education, and more. During the week-long codeathon, teams of 5-10 people will collaborate virtually to design and build innovative solutions that promote fairness, transparency, and accountability in AI/ML algorithms and models. Teams that want to leverage NCBI databases or publicly available scientific data for deep learning are encouraged to apply. Priority will be given to projects that make use of NCBI data and tools. At the end of the event, teams will present their work to each other, representatives from the National Institutes of Health (NIH), and the public. Team products will be made publicly available, and participants will be encouraged to co-author a joint manuscript and share their work online and at conferences.

In a January 2024 Federal Register notice, EPA announced a new framework for identifying eye irritation and corrosion hazards for new chemicals reviewed under the Toxic Substances Control Act (TSCA).

With this new framework, EPA will place increased weight on data from non-animal test methods that are more reproducible and provide results more relevant to humans. This will streamline the decision-making process and increase efficiency through a standard process for EPA to use each time it evaluates eye irritation or corrosion hazards test data. The new framework supports EPA’s mandate under TSCA to promote the development and implementation of alternative test methods and strategies that can provide information on chemical hazards without animal testing. This framework also supports EPA’s ongoing efforts to reduce the use of animal testing and make the Agency’s review of new chemicals more efficient, helping to bring new chemicals to market more quickly while protecting human health.