ICCVAM Biennial Report 2024-2025

Throughout 2024 and 2025, NIEHS provided funding for small businesses developing technologies of interest to Institute goals. The funding was offered as part of the 2024 and 2025 Omnibus Solicitations of NIH, Centers for Disease Control and Prevention, and FDA for small business grant applications to support the development and commercialization of innovative technologies. Areas of high priority included the development of:

• Informatics tools and platforms to organize, store, retrieve, extract, and integrate information on exposures and health effects data
• 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
• 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 (MPS)
• Approaches to characterize and integrate key molecular and cellular changes related to effects of toxicant exposures in carcinogenicity, developmental neurotoxicity (DNT), 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

In 2024 NIEHS provided funding to small businesses as part of the RFA-ES-23-008: Novel Approaches for Developmental Neurotoxicity Testing funding announcement. The funding aimed to support the development of novel and innovative approaches and new approach methodologies (NAMs) that can be applied in testing strategies to better understand the role of environmental chemicals in the etiology of neurodevelopmental disorders. The overall goal was to develop effective ways to address current challenges and gaps in the assessment of DNT. These screening systems or technologies, when fully developed and validated with appropriate throughput and controls, were expected to provide cost-effective, quicker and/or comprehensive results to understand the underlying role of environmental chemicals in this endpoint.

NIEHS participated in the Applicant Assistance Program conducted by the Small Business Programs of the National Institutes of Health. This free 10-week program assisted small businesses in preparing a Small Business Innovation Research or Small Business Technology Transfer grant application. Participants received services such as application needs assessment, mentoring, application preparation support, and application review to help applicants maximize their chances of success.

In January 2024, the NIH Council of Councils approved the concept for the NIH Common Fund's Complement Animal Research in Experimentation (Complement-ARIE) program. Complement-ARIE will accelerate the development, standardization, validation, and use of human-based NAMs, and significantly advance the 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 screening therapeutics for safety and effectiveness. Complement-ARIE 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.

In 2025, Complement-ARIE issued funding opportunities for researchers interested in supporting development of key resources. Award announcements will be made in early 2026.

• Comprehensive NAMs Technology Development Centers 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. 
• A Data Hub and Coordinating Center will house a searchable repository for various NAMs data types, establish standards for data reporting and model credibility, develop and implement integrated testing strategies, establish strategies for interoperability and sustainability data reuse, and develop tools for data analytics, dissemination, and sharing. 

Complement-ARIE also sponsored a crowdsourcing competition for innovative ideas on NAMs. The Complement-ARIE Challenge prize competition offered $1,000,000 in total prize money to diverse teams with ideas for new ways of using NAMs to conduct basic research, uncover disease mechanisms, and translate knowledge into products and practice. Twenty projects received funding in early 2025 under this challenge.

In September 2025, Complement-ARIE launched the Reduction to Practice Challenge. This collaboration with FDA and EPA invited multidisciplinary teams to submit proposals for innovative human-based combinatorial NAMs with the potential to be implemented within a three-year period. Winning proposals will be funded up to $1,430,000 in cumulative cash prizes and receive validation and/or qualification support by the Complement-ARIE Validation and Qualification Network (VQN). Phase 1 challenge winners will be announced in July 2026.

The Complement-ARIE VQN is a public–private partnership to accelerate the deployment and regulatory implementation of NAMs. The VQN will establish common data elements and standardize reporting for preclinical, clinical, and safety performance. In 2025, the Foundation for the National Institutes of Health, which partners with NIH in administering Complement-ARIE, requested submissions of in vitro, in silico, and in chemico research models developed enough to undergo a detailed evaluation to determine readiness for validation and qualification, including identifying if additional studies and data are needed. Based on the submissions, the Foundation chose four NAM concepts focused on DNT, acute oral toxicity, inhalation toxicity, and preterm birth to serve as the foundation for collaborative, precompetitive pilot projects. 

The National Science Foundation, NIH, and FDA established the Foundations for Digital Twins as Catalyzers of Biomedical Technological Innovation program to accelerate innovations in biomedical technologies through the development of principled mathematical, statistical, and engineering foundations for digital twins and synthetic human models in healthcare applications. Launched in 2024, the program offered awards totaling over $6M to support interdisciplinary research projects. These included projects to develop and use digital twins and synthetic data in biomedical and healthcare applications, with a particular focus on open-source regulatory science tools for in silico models used in the evaluation of medical devices. Topics addressed by the awarded research projects included the development of mathematical models for virtual clinical trials of medical devices; statistical tools for analyzing the verification, validation and uncertainty quantification of digital twin models, including topological methods; and synthetic data and digital twin approaches for cancer, neurodegenerative diseases, and Type 1 diabetes.

To support participation in the Cancer Tissue Engineering Collaborative Research Program, since 2017 NCI has offered grants to support the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. The goals of the program are to (1) catalyze the advancement of innovative, well-characterized in vitro and ex vivo systems available for cancer research, (2) expand the breadth of these systems to several cancer types, and (3) promote the exploration of cancer phenomena with biomimetic tissue-engineered systems. The program awards grants of up to $400,000 to fund projects that can continue for up to five years. Projects ongoing during 2024 and 2025 included the development of a microengineered colon-cancer chip, models for screening chemotherapeutic agents, models to study metastasis development, and an ovarian model that enables the study of how the menstrual cycle affects the development of ovarian cancer.

The National Eye Institute is leading an NIH-wide collaboration to incentivize the creation, development, and validation of a quantitative author-level metric known as the Data Sharing Index (S-index). The S-Index Challenge aims to incentivize and reward effective data sharing practices by assessing how well researchers share data in ways that enable meaningful reuse in future studies.

The S-index metric will incorporate factors including adherence to findable, accessible, interoperable, and reusable (FAIR) principles; data timeliness; completeness of annotation; frequency of reuse in other studies; and related publications and patents. Rather than focusing solely on the intrinsic value of datasets, this metric emphasizes and recognizes the contributions of individuals and teams who enable impactful data sharing. 

The two-phase application and evaluation process began in April 2025 and will conclude in February 2026, with up to a total of $1M in awards to be announced in July 2026. 

This Challenge is intended to serve as a catalyst for advancing data sharing practices and to foster collaboration across the research ecosystem. While it represents an important step forward, the culmination of the Challenge is not the endpoint as substantial work will still be needed to support implementation, drive community adoption, and integrate data sharing metrics into existing research and incentive structures.

Organoids are small, lab-grown models that mimic the structure and function of human organs and are transforming how researchers study disease and evaluate treatments. To date, most organoid models have been created through trial and error, making them difficult to reproduce across laboratories and slowing their adoption in both research and industry.

In 2025, NIH announced the establishment of the Standardized Organoid Modeling (SOM) Center, an integrated platform dedicated to developing standardized organoid-based NAMs. The initiative was launched by the NIH Division of Program Coordination, Planning, and Strategic Initiatives, in collaboration with other NIH institutes, centers, and offices including NCI and NCATS. The center will initially focus on organoid models of the liver, lung, heart, and intestine, with plans to expand to the brain, thymus, and other disease-specific models. The SOM Center will serve scientists and researchers, regulatory agencies, and clinicians and precision medicine experts. 

To ensure consistency, transparency, and broad scientific benefit, the following policies will guide SOM Center access and use:

• Open Science Policy: All protocols, data, and models will be openly shared via FAIR principles to maximize community benefit and reuse.
• Affordable Access: Physical organoids and digital resources will be made available at minimal cost to NIH-funded and other qualified investigators.
• Regulatory Alignment: All models and data will be developed in alignment with standards recognized by agencies such as FDA, OECD, and ICCVAM to facilitate potential use in regulatory contexts.
• Performance Qualification Framework: All organoid systems will undergo predefined benchmarking against structural, molecular, and functional criteria to establish reproducibility and comparability across sites.
• Ethical and Inclusive Use: The SOM Center prioritizes heterogeneity in human cell lines (age, sex, ancestry), community engagement, and bioethical oversight to ensure models are representative and equitable.
• Training and Use Compliance: Users must complete relevant training modules and adhere to standard operating procedures to ensure reproducibility and ethical use.
• Data Contribution Encouraged: Collaborating researchers are encouraged to contribute their results (including negative data) to enhance collective learning and protocol refinement.

The NCI mission is to lead, conduct, and support cancer research across the nation to advance scientific knowledge and help all people live longer, healthier lives. NCI accomplishes its research goals in part by providing grants to researchers and method developers whose work is relevant to NCI’s interest areas, including cancer biology, cancer screening and early detection, and cancer treatment. Information about grant opportunities and applying for grants is available on the NCI website.

In 2024 and 2025, NCI grants supported a large number of projects relevant to NAMs development and application. Details about extramural grants to NCI and other NIH institutes can be found via the NIH RePORTER database. Examples of NCI-funded projects relevant to NAMs include:

• Organoid models to support drug discovery for glioblastoma and epigenetics research in colorectal cancer
• Patient-derived organoids for use in personalized treatment and drug discovery for breast, ovarian, pancreatic, and other tumor types
• Application of bioprinter technology and hydrogel supports to improve development efficiency and reproducibility of organoid models
• Microfluidic platforms using stem cells to study and reprogram neutrophils used for cancer therapy
• Deep learning models to predict drug sensitivity and genetic dependency of adult and pediatric cancers
• A user-friendly web tool that allows researchers to explore and predict cancer dependencies, genes essential for the survival and proliferation of cancer cells
• Application of Bayesian regression models to improve design of clinical trials

NIH announced in July 2025 that moving forward, funding opportunities should incorporate language regarding the consideration of NAMs, and it will no longer issue Notice of Funding Opportunities exclusively supporting animal models. This followed a statement by NIH Acting Deputy Director for Program Coordination, Planning, and Strategic Initiatives, Nicole Kleinstreuer, Ph.D., at a July 7 FDA-NIH “Workshop on Reducing Animal Testing.” A video in which Dr. Kleinstreuer discusses the new direction with NIH Director Jay Bhattacharya is available on YouTube.

In April 2025, NIH announced an initiative to expand innovative, human-based science to improve health and disease research and medical product development while reducing animal use. The initiative seeks to provide more predictive models of human disease by leveraging human-derived data and advanced technologies such as MPS (“organs-on-chips”), 3D organoids, and AI-driven digital twins. By prioritizing research that better reflects human biology, the NIH aims to bridge the translational gap where animal models fail to predict human outcomes, particularly in complex areas such as neurodevelopment and chronic disease, while simultaneously reducing the scientific community's reliance on animal models. In August 2025, the NIH released a unified strategy that reiterated the agency’s commitment to develop and apply human-based NAMs and reduce animal use. To lead this initiative, NIH is establishing an Office of Research Innovation, Validation, and Application to coordinate efforts to develop, validate, and scale the use of NAMs across the agency’s biomedical research portfolio and serve as a hub for interagency coordination and regulatory translation for public health protection.