ICCVAM Agency Activities
News Published Since Last Biennial Report
This page contains ICCVAM agency activities announced in NICEATM News, an email list that distributes announcements of interest to those developing alternatives to animal use for chemical safety testing. Subscribe to NICEATM News
ICCVAM agency activities occurring since the last ICCVAM Biennial Report are listed below. Activities that occurred before January 2020 will be described in ICCVAM Biennial Reports.
FDA Partnership to Apply Lung Chips to Safety Evaluation of COVID-19 Vaccines and Therapies
FDA has entered into a Cooperative Research and Development Agreement (CRADA) with Emulate, Inc. to enable multiple studies using Emulate’s Organ-Chips across FDA offices in priority research areas. Organ-Chips are in vitro systems that recreate the natural physiology of specific human tissues and organs. Some projects will evaluate COVID-19 vaccines or investigate human immune response against SARS-CoV-2, the virus that causes COVID-19. Under the CRADA, FDA will use a range of Organ-Chips to study the safety, efficacy, and mechanisms of action of drugs regulated by the FDA. This new CRADA agreement follows the successful completion of the first Emulate CRADA with the FDA initiated in 2017 that focused on toxicity studies using Emulate’s Liver-Chip. Details on the CRADA are provided in Emulate’s October 29 press release.
Presentations and Video Available from EPA NAMs Conference
EPA hosted the Second Annual “Conference on the State of the Science on Development and Use of New Approach Methods (NAMs) for Chemical Safety Testing” virtually on October 19-20. The virtual conference was presented in response to the September 2019 directive by EPA Administrator Andrew Wheeler to reduce the EPA’s use of mammalian studies. Conference topics included:
To view the conference presentations and recordings, visit the conference website. If you attended the conference and would like to submit feedback on the EPA New Approach Methods Work Plan, email NAM@epa.gov.
OSHA, PHMSA Request Public Input in Advance of International Meetings
OSHA and DOT Pipeline and Hazardous Materials Safety Administration (PHMSA) will hold virtual public meetings on Thursday, November 19. The purpose of the November 19 meetings is to consider public comments and gather information in advance of:
The PHMSA public meeting will be held on November 19 from 9:00 a.m. to 12:00 p.m. EST. The OSHA public meeting will be held November 19 from 1:00 p.m. to 4:00 p.m. EST. General information about the OSHA meeting was published in an October 22 Federal Register notice. Specific information regarding each meeting will be available on the OSHA website as it becomes available.
These meetings will be open to the public on a first-come, first served basis. Attendees must pre-register for all meetings.
EPA Announces Guidance to Waive Toxicity Tests on Animal Skin, New Webpages on Metrics and NAMs
On October 7, EPA requested public comment on draft guidance that would allow researchers to forego testing chemicals on animal skin in certain circumstances. Based on a retrospective analysis conducted by EPA, which concluded that such studies provide little to no added value in regulatory decision-making, the proposed guidance would allow waivers for studies on single active ingredients used in pesticides. This guidance, when finalized, is expected to save up to 750 test animals annually from unnecessary testing, as well as EPA, industry, and laboratory resources.
EPA has published a webpage summarizing its strategic vision for adopting NAMs. Three webpages linked from this page have details of EPA activities in this area.
NIH Hosting Seminar on Grants Process October 27-30
NIH will present a “Virtual Seminar on Program Funding and Grants Administration” on October 27-30, beginning at 1:00 p.m. EDT each day. This seminar will provide attendees an opportunity to learn about the NIH grants processes, programs, and policies, and will include information specific to small business programs. It is primarily aimed at persons new to the NIH grants process but also includes sessions focused on more in-depth polices and processes for more advanced participants. The event is free.
FDA and Global Partners to Study Coronaviruses Using In Vitro Models
FDA has awarded over $5 million to a global collaboration to inform the development of treatments and vaccines for coronavirus infections. The collaboration, led by the University of Liverpool, will sequence and analyze samples from humans and animals to create profiles of various coronaviruses, including SARS-CoV-2, which causes COVID-19.
As part of this three-year project, investigators will evaluate how in vitro models of coronavirus infection, including human organs-on-chips, compare to in vivo responses in animal models and humans. Ultimately, these in vitro models may be employed in the development of biologics, drugs, or devices to treat COVID-19.
For more information about the project, visit:
September 24 Webinar to Discuss EPA Phenotypic Profiling Approach
A webinar organized by ASCCT and the European Society for Toxicology In Vitro will describe “Phenotypic Profiling for High-throughput Chemical Screening at the U.S. EPA”. The webinar will be presented Thursday, September 24, from 10:00-11:00 a.m. EDT.
The Center for Computational Toxicology & Exposure at EPA has been an integral part of developing new approach methodologies in computational toxicology. The tiered in vitro approach to toxicity testing relies on high-throughput assays to derive a potency estimate for chemical bioactivity and to gain information about putative mechanisms of action. In this webinar, Johanna Nyffeler, EPA, will outline how image-based high-throughput phenotypic profiling (HTPP) assays can provide both types of data required for tiered in vitro testing. She will describe a study that demonstrated that the HTPP assay can be used to derive potency estimates and some mechanistic features that can be used for the prioritization of chemicals.
Previously recorded ASCCT webinars are available on their website.
EPA Seeks Nominees for TSCA Scientific Advisory Committee on Chemicals
EPA is seeking nominations of scientific experts to be considered for appointment to the TSCA Science Advisory Committee on Chemicals. The committee provides independent advice and expert consultation on the scientific and technical aspects of implementing TSCA.
Nominations should be received by September 1. This announcement was originally issued in March 2020 with an April deadline, but subsequent legal decisions have affected the criteria used to evaluate nominees. All nominations and comments submitted in response to the March notice will be considered by EPA and do not need to be resubmitted.
Nominees should have expertise in one or more of the following subject areas: human health and ecological risk assessment, biostatistics, epidemiology, pediatrics, physiologically based pharmacokinetics, toxicology and pathology, and chemical exposures of sensitive populations. An August 17 Federal Register notice [85 FR 50020] has details on the call for nominations, including instructions for submitting nominations.
FIFRA SAP to Meet in September; Pre-meeting August 25 Open to Public
EPA will convene a public peer review meeting of the FIFRA Scientific Advisory Panel (SAP) on September 15-18. Panelists will consider and review the use of new approach methodologies (NAMs) to derive extrapolation factors and evaluate developmental neurotoxicity for human health risk assessment.
On Tuesday, August 25, there will be a virtual public preparatory meeting to consider the scope and clarity of the draft charge questions for this peer review. More information about both meetings is available in a June 17 Federal Register notice.
The FIFRA SAP provides independent scientific advice, information and recommendations to the EPA Administrator on pesticides and pesticide-related issues as to the impact of regulatory actions on human health and the environment. At this meeting, EPA is seeking advice and recommendations from the FIFRA SAP on scientific issues associated with:
FDA Accepting Proposals for Alternative Methods Webinar Series
The FDA Office of the Chief Scientist is launching a webinar series on alternative methods. The webinar series supports FDA’s commitment to promote novel technologies and potentially incorporate them into its regulatory review, as applicable.
Test method developers who participate in this webinar series will have the opportunity to introduce their new technology to FDA and give individual FDA programs the option to contact them for further information. Please note, however, that participation in FDA’s webinar series does not constitute FDA’s endorsement of a new method or oblige FDA to assist the developer in qualifying a new method for regulatory use.
To be considered for the webinar series, please submit the following information to firstname.lastname@example.org:
FDA will respond within 60 days to your webinar submission. For more information, visit the FDA website.
Webinar Will Describe a Literature Informatics Tool for Chemical Research
A webinar organized by ASCCT and ESTIV will describe “PubMed Abstract Sifter: A Literature Informatics Tool for Chemical Research.” The webinar will be presented Thursday, August 20, from 10:00-11:00 a.m. EDT.
Assessing and understanding chemical effects requires assembling information from a wide variety of sources, including millions of articles in the biomedical literature. Literature informatics approaches can help researchers make use of this information in more effective ways. In the webinar, Nancy Baker, Leidos, Inc., will describe the PubMed Abstract Sifter, a freely available literature tool from the U.S. Environmental Protection Agency (EPA). With the Abstract Sifter, researchers can easily retrieve and triage citations from PubMed and visualize the literature landscape for a set of chemicals. The tool is supplied with template queries that facilitate the exploration of mechanistic information by using the language of adverse outcome pathways and key characteristics of carcinogens.
Small Business Grants Available for Test Method Development
The Department of Health and Human Services (HHS) has released the 2020 SBIR and STTR Omnibus Grant Solicitations. These solicitations will be used by the National Institutes of Health and other offices within HHS to fund researcher-initiated projects in health, medicine, and life sciences. Projects being funded by the NIEHS under this solicitation include development of toxicity screening, testing, and modeling approaches that support Tox21 and other NTP goals. Areas of high priority include development of:
The first deadline for applications under this announcement is September 8. More information is available on the NICEATM website.
NIEHS has also reissued the Funding Opportunity Announcement for its Commercialization Readiness Pilot program. These grants support commercialization of previously funded SBIR and STTR Phase II and Phase IIB projects by funding activities not typically supported through Phase II or Phase IIB grants or contracts. Small businesses that have had an active National Institutes of Health SBIR or STTR Phase II or Phase IIB award within the last 36 months are eligible to apply. Awardees will receive up to $300,000. Standard SBIR/STTR application deadlines apply for these grants; the next deadline is September 8..
Article Describes Updates to ICE
A new article in Toxicology In Vitro provides an overview of and summarizes recent updates to the NICEATM Integrated Chemical Environment (ICE). ICE provides tools and curated data centered around chemical safety assessment. This article describes updates to ICE, including improved accessibility and interpretability of in vitro data via mechanistic target mapping and enhanced interactive tools for in vitro to in vivo extrapolation (IVIVE).
Bell et al. 2020. An integrated chemical environment with tools for chemical safety testing. Toxicology In Vitro. https://doi.org/10.1016/j.tiv.2020.104916.
EPA Releases New Approach Methods Work Plan
On June 23, EPA released its New Approach Methods Work Plan, which was created in response to the EPA Administrator’s 2019 directive to prioritize activities that will reduce the use of animal testing while continuing to protect human health and the environment. The work plan was developed by experts across the agency to set the objectives and strategies for using new approach methods to meet the ambitious goals set out in the Administrator's directive.
EPA Paper Examines Variability of In Vivo Data
A new publication in the journal Computational Toxicology describes EPA’s studies to quantify the variance in data from systemic in vivo toxicology studies. Data from these studies are often used as a reference for evaluating new approach methodologies (NAMs). However, variability in animal study data limits NAM accuracy. The findings from this study suggest quantitative considerations for building scientific confidence in NAM-based systemic toxicity predictions.
Pham et al. 2020. Variability in in vivo studies: defining the upper limit of performance for predictions of systemic effect levels. Computational Toxicology. https://doi.org/10.1016/j.comtox.2020.100126.
NTP Postdoc Opportunity
Recruitment is underway for a postdoctoral fellow with training and experience in statistics and/or bioinformatics to join the newly formed, interdisciplinary Spatiotemporal Health Analytics Group in the Division of the NTP at NIEHS. This group is also affiliated with the National Institute on Minority Health and Health Disparities of NIH. The successful candidate will gain research training and experience in spatiotemporal methods and applications that bridge human health exposure science, epidemiology, and toxicology. Fellows will have the opportunity to propose related research for internal or external funding. The initial appointment is for two years.
Candidates should have doctoral degrees in statistics, bioinformatics, toxicology, or epidemiology. Other relevant experience includes scientific writing and oral communication, spatial analysis, big data, data visualization, analyzing toxicity assays and -omic data sets, and using software such as R, MATLAB, GitHub, and LaTeX. For more information or to apply, contact Dr. Kyle Messier at email@example.com.
New Tool Maps Chemical Effects on the Human Body
Acting NICEATM Director Nicole Kleinstreuer is coauthor of a new publication in the journal Nucleic Acids Research that describes the Tox21BodyMap tool. Tox21BodyMap is an intuitive webtool allowing a user to identify target organs in the human body where a substance is estimated to be more likely to produce effects.
Borrel et al. 2020. Tox21BodyMap: a webtool to map chemical effects on the human body. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa433.
OSHA and DOT Request Public Input in Advance of International Meetings
OSHA and the DOT Pipeline and Hazardous Materials Safety Administration plan to hold public meetings on Wednesday, June 24, in advance of July meetings of:
The purpose of the June 24 public meetings is to discuss proposals and receive input for the July meetings. Both June 24 meetings will be convened virtually and are open to the public. Interested parties may submit comments by June 11.
EPA Requests Public Comment on Draft Risk Assessment for Antimicrobial Chemicals
In a May 14 Federal Register notice, EPA requested comment on draft human health and ecological risk assessments for registration review of a group of antimicrobial chemicals known as isothiazolinones. EPA specifically requests comment on the use of an in vitro and artificial neural network-based defined approach to determine points of departure used in the isothiazolinone draft risk assessments instead of using laboratory animal data to evaluate risks for dermal sensitization. Comments are due by July 13. The Federal Register notice includes instructions on how to submit comments.
The draft risk assessments rely heavily on work done by NTP, NICEATM, and ICCVAM. The in vitro testing was conducted by the NTP Toxicology Branch. NICEATM analyzed the in vitro data and ran the artificial neural network-based defined approach to provide quantitative potency predictions used to determine points of departure. The ICCVAM Skin Sensitization Expert Group reviewed the NTP testing report and the NICEATM analyses before data were provided to EPA for development of the risk assessments. The use of in vitro and in chemico assays and neural network-based defined approaches is the first use of such information in regulatory risk assessment.
Presentations Available from Webinar on Small Business Funding
Presentations are now available from the April 17 town hall webinar on “Development of New Approach Methodologies to Reduce Animal Use in Toxicity Testing.” The webinar was presented by NIEHS SBIR and STTR program in coordination with NICEATM. The presentations are available on the NTP website. A video of the webinar is available on the NIEHS website.
A key component of the Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States is early interaction between developers of NAMs and end-users, to ensure that the proposed NAMs will meet testing requirements for agency and industry stakeholders. The goal of this webinar was to facilitate improved communication between method developers, including SBIR/STTR applicants, and end-users. The webinar provided an opportunity for assay developers to hear from ICCVAM stakeholders on the desired characteristics and requirements for NAMs. Presenters included representatives from NICEATM, the U.S. Environmental Protection Agency, the U.S. Food and Drug Administration, the U.S. Department of Defense, 3M Corporation, and Novartis.
FDA Webinar to Discuss Artificial Intelligence in Regulatory Science
A webinar on “Artificial Intelligence for Regulatory Science Research” will be presented on Thursday, May 14, at 12 noon EDT. Weida Tong of the FDA National Center for Toxicological Research will review the center’s current thinking and ongoing efforts in the area of artificial intelligence. The webinar is free and open to the public.Artificial intelligence (AI) is a broad concept of training machines to think and behave like humans. It consists of a wide range of statistical and machine learning approaches to learn from existing data/information to predict future outcomes. This webinar will present examples of AI implementation in drug and food safety, natural language processing of regulatory documents, and biomarker discovery and development. The guiding principles and best practice of applying AI in regulatory science research will also be discussed with respect to the context of use and fit-for-purpose application.
Webinar to Discuss Use of Non-animal Skin Sensitization Test Methods
A webinar on “Use of Non-animal Skin Sensitization Test Methods” will be presented on Wednesday, May 27, at 10:00 a.m. EDT. Louis Scarano of the EPA Office of Pollution Prevention and Toxics will discuss their recent review of non-animal skin sensitization tests. Hans Raabe, Institute for In Vitro Sciences, will discuss the use of non-animal skin sensitization test methods for EPA hazard classification and will provide an overview of three currently accepted regulatory test methods. The webinar is being presented by the PETA-ISC, EPA, and PCRM. It is free and open to the public.
Publication Discusses FDA Perspective on Use of NAMs in Drug Development
A paper coauthored by Paul Brown, ICCVAM representative from the FDA Center for Drug Evaluation and Research, discusses the center’s view on the opportunities and challenges of using NAMs in drug development, especially for regulatory purposes. The paper includes examples where NAMs are currently being used in nonclinical safety assessments and where they may supplement and/or enhance current testing methods.
Avila et al. 2020. An FDA/CDER perspective on nonclinical testing strategies: Classical toxicology approaches and new approach methodologies (NAMs). Regulatory Toxicology and Pharmacology. https://doi.org/10.1016/j.yrtph.2020.104662.
SOT FDA Colloquium to Discuss Integrated Approaches to Testing and Assessment
SOT and FDA will hold a colloquium on “Integrated Approaches to Testing and Assessment: The Future of Regulatory Toxicology Assessment” on Thursday, May 28, from 8:30 a.m.-12:35 p.m. This event is the latest in the series, “SOT FDA Colloquia on Emerging Toxicological Science: Challenges in Food and Ingredient Safety.” Suzanne Fitzpatrick, FDA principal representative to ICCVAM, is event co-chair. The colloquium will be webcast and is open to the public.
Integrated approaches to testing and assessment (IATAs) are pragmatic, science-based frameworks for chemical hazard or risk characterization. IATAs follow an iterative, integrative approach to answer a defined question with a pre-determined level of certainty in a specific regulatory context. This colloquium will introduce the concept, process, and components that comprise an IATA and present several case studies demonstrating different applications of this decision tool. Issues, challenges, and prospects of adopting IATAs in regulatory risk assessment will be discussed.
New FDA Webpage Highlights Alternative Methods Working Group
FDA has a long-standing commitment to promote the development and use of new technologies to better predict human and animal responses to substances relevant to its regulatory mission. To strengthen that commitment, FDA launched its Alternative Methods Working Group. This group facilitates interactions with global regulatory bodies interested in implementing alternative methods in toxicology. Additionally, the group examines opportunities and viable ways by which emerging methods and new technologies can support regulatory review of risk, safety, and efficacy of FDA-regulated products.
The Alternative Methods Working Group recently launched its webpage, which will highlight FDA’s work in this area. A link to this page and to other ICCVAM agency webpages focused on alternative methods is available on the NICEATM website.
NCATS Funding Use of Tissue Chips to Support COVID-19 Research
NCATS has issued two Notices of Special Interest to support research in collecting and examining data on the risks and outcomes for COVID-19 infections using MPS or tissue chips. Such work is expected to advance the translation of research findings into diagnostics, therapeutics, and vaccines. Applications for both opportunities will be accepted on a rolling basis from May 15, 2020, through January 25, 2022.
FDA Guidance on Immunotoxicity Testing Supports Use of Alternatives
In February, FDA issued draft guidance on “Nonclinical Safety Evaluation of the Immunotoxic Potential of Drugs and Biologics.” This guidance supplements previously issued recommendations on nonclinical evaluations of immunotoxic potential and is intended to assist sponsors in such evaluations. The guidance includes several specific recommendations on assessing potential for dermal sensitization:
In Vitro Methods Support EPA Prioritization for TSCA Testing
In February, EPA announced the designation of 20 chemical substances as low priority under the Toxic Substances Control Act (TSCA). The designation is the third and final step in the prioritization process for reviewing chemical substances under the Frank R. Lautenberg Chemical Safety for the 21st Century Act amendments to TSCA. A low-priority designation means that risk evaluation for these substances is not warranted at this time.
For each chemical substance designated as low priority, EPA published a document describing the information, analysis, and basis for the designation. Information used to support the designation for each chemical included 3Rs approaches:
NICEATM has compiled a summary of 3Rs approaches used to designate these substances as low priority. In addition to the reduction of animal use realized by the approaches described above, designation of each substance as low priority reduces the likelihood that animals will be required for future testing of these substances.
NIEHS to Present Webinar on Grant Opportunities for NAM Development
The NIEHS SBIR/STTR program, in coordination with NICEATM, will host a webinar-based town hall meeting on “Development of New Approach Methodologies to Reduce Animal Use in Toxicity Testing.” The webinar will be held on Friday, April 17 from 1:00-3:00 p.m. EDT.
A key component of the Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States is early interaction between developers of new approach methodologies (NAMs) and end-users, to ensure that the proposed NAMs will meet testing requirements for agency and industry stakeholders. This webinar will facilitate improved communication between method developers, including small business (SBIR/STTR) applicants, and end-users, providing an opportunity for assay developers to hear from ICCVAM stakeholders on the desired characteristics and requirements for NAMs. The agenda will include short presentations from experts from U.S. federal agencies and industries, including pharmaceutical developers, with time allowed for questions from method developers. Presenters include representatives from NICEATM, the U.S. Environmental Protection Agency, the U.S. Food and Drug Administration, the U.S. Department of Defense, 3M Corporation, and Novartis
EPA Issues Challenge to Develop Ecotoxicity Gene Expression Assay
EPA and government and industry partners are sponsoring the EcoTox TARGET innovation challenge. A prize of $300,000 will be awarded to the applicant who successfully develops a low-cost high-throughput technology for measuring global gene expression in samples from four common aquatic toxicity test organisms. Participants must register by March 16.
Paper Describes Predictive Model for Androgenic Activity
A paper now available online from Environmental Health Perspectives describes a worldwide consortium led by EPA to develop models to virtually screen chemicals for their potential androgenic activity. The paper was coauthored by Acting NICEATM Director Nicole Kleinstreuer; the first author is Kamel Mansouri, ILS (contractor supporting NICEATM). Predictions generated by the consensus model developed for the project are available in the NICEATM Integrated Chemical Environment.
Mansouri et al. 2020. CoMPARA: Collaborative Modeling Project for Androgen Receptor Activity. Environ Health Perspect. https://doi.org/10.1289/EHP5580.
New FDA Guidance Available for In Vitro Drug Interaction Studies
FDA published “In Vitro Drug Interaction Studies – Cytochrome P450 Enzyme- and Transporter-mediated Drug Interactions Guidance for Industry” in January. This guidance is intended to help drug developers plan and evaluate studies to determine the drug-drug interaction (DDI) potential of an investigational drug product. It focuses on in vitro approaches to evaluate the interaction potential between investigational drugs with cytochrome P450 enzymes and transporters, as well as how in vitro results can inform future clinical DDI studies. The appendices of this guidance include factors to consider when choosing in vitro experimental systems, key issues regarding in vitro experimental conditions, and more detailed explanations regarding model-based DDI prediction strategies.
FDA Colloquium on Route-to-route Extrapolation February 19
SOT and the FDA Center for Food Safety and Applied Nutrition announce the latest colloquium in their series, “Emerging Toxicological Science: Challenges in Food and Ingredient Safety.” “Route-to-route Extrapolation in the 21st Century” will be held Wednesday, February 19, at the FDA Wiley Auditorium in College Park, Maryland. The colloquium is free and open to the public, but in-person attendees who are not federal employees must register by February 11. The meeting will also be webcast.
The toxicity and pharmacokinetic profiles of substances may vary with the exposure route. If adequate data based on the relevant route of exposure are not available, a route-to-route extrapolation methodology may be employed to predict toxicity and estimate point-of-departure for risk assessment. Route-to-route extrapolation-based approaches use physiologically based pharmacokinetic models to estimate equivalent internal dose for predicting effects. This colloquium will present considerations for conducting route-to-route extrapolations and discuss the possibility of developing consistent methods for utilizing such extrapolations for risk assessment.
Presentations Available from EPA Conference on NAMs
Presentation slides are available from the First Annual Conference on the State of the Science on Development and Use of New Approach Methods (NAMs) for Chemical Safety Testing, presented by EPA on December 17. This conference was one of EPA’s commitments in the "Directive to Prioritize Efforts to Reduce Animal Testing" signed by Administrator Andrew Wheeler on September 10, 2019, calling for EPA to reduce use of mammalian studies. Presentations discuss both animal and non-animal tests used to satisfy testing requirements and establishing baselines for animal use. Presenters included Acting NTP Biomolecular Screening Branch Chief Warren Casey, Acting NICEATM Director Nicole Kleinstreuer, and ICCVAM Co-chair Anna Lowit, EPA.