New Approach Methodologies in
Drug Discovery and Development
Over 90% of drugs that pass animal testing fail in human trials. The FDA's NAMs roadmap is reshaping preclinical discovery. As a leading CRO, Crown Bioscience’s NAMs services leverage in vitro human-relevant testing systems to bridge the translational gap.
What Are New Approach Methodologies (NAMs)?
New Approach Methodologies (NAMs) are the FDA's term for advanced alternatives to traditional animal testing, including in vitro human-based systems, in silico models, and other innovative platforms that improve predictive accuracy. By adopting these methods, sponsors can establish a robust weight-of-evidence (WoE) strategy for IND submissions while drastically reducing reliance on traditional animal testing. They fall into three broad categories:
- Human-relevant in vitro and cell-based assays
- Organ-on-chip and 3D/organoid systems
- In silico and AI-driven predictive models
Human-Relevant 3D Platforms
Human-Relevant 3D Organoid Platform (HUB Technology)
Preclinical oncology drug development has historically been bottlenecked by traditional in vitro cell lines that fail to replicate true human tumor biology. To bridge this translational gap, Crown Bioscience provides an extensive living biobank of patient-derived organoids (PDO) and patient-derived xenograft-derived organoids (PDXO). Developed using IP-protected Hubrecht Organoid Technology (HUB) protocols, these 3D models preserve original cancer stem cells, genomic architecture, and histopathological features.
Advanced Screening and Mechanistic Insights
By establishing standardized, assay-ready organoid batches, we compress timelines without sacrificing biological accuracy. Sponsors can execute large-scale phenotypic screens, multi-drug combination studies, and targeted radiation testing.
- OrganoidXplore™: A high-throughput, panel-based screening service that tests candidate efficacy across up to 247 distinct organoid models spread over 14 indications in under six weeks.
- High-Content Imaging (HCI): Moves beyond single-endpoint viability measurements and offers mechanistic insights to deliver multiplexed, imaging-based morphological readouts that quantify how cells dynamically interact under treatment.
- Multi-omics Database Access: Every model in our searchable organoid database is fully characterized with comprehensive microscopy, IC50 data, and deeply annotated genomic and transcriptomic profiles.
By transitioning from simplistic 2D assays to highly predictive 3D organoids, drug developers can reliably identify responder populations and address potential mechanisms of drug resistance before making in vivo or clinical commitments.
Integrated In Silico Modeling and Translational Continuity
A primary objective of NAMs is to establish a cohesive weight-of-evidence (WoE) framework that streamlines the path to Investigational New Drug (IND) applications. Crown Bioscience uniquely facilitates this by anchoring virtual data structures to real-world biological outcomes, establishing an uninterrupted translational bridge from computational insight to clinical execution.
Connecting AI Prediction with Biological Validation
Through strategic partnerships connecting AI-driven simulation platforms with our empirical biobanks, we help sponsors map complex pharmacokinetic and pharmacodynamic (PK/PD) profiles early in discovery.
- Matched In Vitro/In Vivo Workflows: Because our PDXO models share identical genetic backgrounds with our Patient-Derived Xenograft (PDX) in vivo models, datasets maintain absolute continuity. Sponsors can run massive high-throughput screens in silico or in vitro, pinpoint the exact molecular targets, and transition to tightly focused, highly predictive mouse clinical trials.
- Translational Biomarker Discovery: Advanced bioinformatics and spatial transcriptomics map tissue-slice drug responses directly to clinical databases. This enables accurate human dose-setting simulations and the precise stratification of patient populations based on real genetic data.
This unified dry-lab and wet-lab integration transforms raw screening data into definitive, actionable milestones, actively de-risking the clinical phase and reducing reliance on traditional animal models.
How do NAMs compare with traditional preclinical models?
NAMs are designed to complement or replace certain aspects of traditional animal testing by leveraging human-relevant biology, advanced in vitro systems, computational modeling, and translational biomarkers. The table below highlights key differences between conventional preclinical approaches and modern NAM-based strategies used in drug development.
Traditional Preclinical Models vs. NAMs
| Research Need | Traditional Approach | NAMs and Potential Benefits | Related Crown Bioscience Solution |
|---|---|---|---|
| Drug Efficacy Screening | 2D cancer cell lines or rodent xenograft models | Patient-derived organoids (PDOs/PDXOs) more accurately capture human tumor biology and heterogeneity than traditional 2D or xenograft models. | Patient-Derived Organoids (PDO/PDXO), OrganoidXplore™, extensive living organoid biobank |
| Safety Assessment | Animal toxicology studies | Human-relevant in vitro assays and ex vivo systems support earlier identification of human-specific toxicities. | Off-target binding assays, GI toxicity assays, Hemato-toxicity assays, cytokine release assays, multiplex immunoassays |
| Immuno-Oncology Evaluation | Murine immune models | Humanized models, ex vivo patient tissues, and immune cell co-cultures enable more clinically relevant assessment of immune responses and immunotherapies. | Organoid & immune cell co-culture platforms, EVPT |
| Biomarker Discovery | Limited animal tissue analysis | Multi-omics profiling and translational biomarker assays improve biomarker identification and support more precise patient stratification. | Clinical Biomarker Services, spatial biology, flow cytometry, multiplex IHC/IF, ctDNA analysis, proteomics |
| Mechanism of Action Studies | Single-endpoint viability assays | High-content imaging and multiplex functional assays provide deeper insight into drug response mechanisms. | High-Content Imaging (HCI), multiplex biomarker analysis, image-based phenotyping, gene engineered models |
| Patient Population Selection | Generalized animal responses | Molecularly characterized patient-derived models support precision medicine and help identify likely responders. | Annotated PDO/PDXO biobank with genomic, transcriptomic, and drug response datasets, Organoid Xplore |
| PK/PD Prediction | Species-based extrapolation | In silico modeling integrated with human biological data improves prediction of human drug behavior. | Bioinformatics and translational data integration, AI-enabled partner workflows, PK/PD support |
| IND-Enabling Decision Making | Separate in vitro and in vivo workflows | An integrated, weight-of-evidence approach combining NAMs builds greater confidence in advancing candidates into clinical development. | Integrated discovery platform linking organoids, PDX models, biomarker analysis, and bioinformatics |
| Regulatory Alignment | Traditional animal-focused studies | FDA-supported human-relevant approaches align with evolving regulatory expectations. | Human-relevant preclinical models, translational assays, IND-supporting study design |
| Development Timeline | Sequential testing across multiple models | High-throughput screening and integrated NAM workflows enable faster, more efficient preclinical development. | OrganoidXplore™, large-scale organoid screening, standardized assay-ready platforms |
Integrated Solutions:
One Partner, Bench to Bedside and Back
NAMs are most powerful not as isolated technologies, but as part of a continuous translational cycle. Crown Bioscience is uniquely positioned to support that full cycle - from early discovery, through IND-enabling packages, into clinical development, and back again - because we operate as a single, integrated partner across each stage rather than a series of disconnected vendors.
This continuity is what allows sponsors to build genuine scientific confidence in their NAMs data, rather than confidence in any one platform alone.
- Bench: Discovery and IND-enabling data generation. Our organoid, PDX, and ex vivo platforms generate efficacy, mechanism-of-action, and safety data selected to be Fit-for-Purpose for a defined Context of Use, whether that's early candidate triage, immunotoxicity risk assessment, or patient stratification ahead of clinical trial design.
- Bedside: Clinical translation. Because our preclinical models are built from clinically annotated patient material, the biomarkers and stratification strategies developed at the bench carry forward into clinical biomarker services - supporting patient selection, companion diagnostic strategy, and trial design with a shared genetic and molecular foundation.
- Back to bench: Closing the loop. Clinical response and biomarker data flow back into our model systems, refining patient-derived organoid and PDX selection, sharpening Context of Use definitions, and improving predictive accuracy for the next program. Each cycle strengthens the weight-of-evidence case for future candidates.
Let us know your specific questions for NAMs and properly setting up your drug research program for success.
Because Crown Bioscience manages this cycle under one roof - rather than sponsors coordinating separate vendors for discovery, translational biomarker work, and clinical support - data stay traceable and Fit-for-Purpose determinations stay consistent from first screen to clinical decision-making. That continuity is the foundation of a defensible, evolving weight-of-evidence strategy, and it's what distinguishes Crown Bioscience's NAMs offering from single-platform providers.
Why NAMs Matter for IND-Enabling Programs
Human-relevant models improve translational confidence, can shorten preclinical timelines, and align with FDA’s regulatory direction , reducing risk of late-stage clinical failure driven by species-specific biology.
FDA's Roadmap for Reducing Animal Testing
FDA's roadmap begins with monoclonal antibodies and is expanding to other biologic classes. Key reference documents include the Roadmap to Reducing Animal Testing in Preclinical Safety Studies, the CDER/OND streamlined nonclinical studies inventory, and the April 2025 Year One Progress report.
Crown Bioscience Partnerships
Crown Bioscience is at the forefront of NAMs adoption, collaborating with leading organizations to validate and advance human-relevant research methods across drug discovery and development.
In July 2026, Crown Bioscience joined Critical Path Institute's (C-Path) New Approach Methodologies Developer Coalition (NAMs-DC). This collaborative initiative is dedicated to advancing the validation, qualification and regulatory adoption of innovative human-relevant research methods. Through this partnership, Crown Bioscience contributes its expertise in patient-derived xenograft (PDX) models, patient-derived tumor organoids, ex vivo patient tissue platforms, and translational biomarker analysis to help bridge the gap between NAM development and regulatory implementation.
Crown Bioscience continues to build strategic alliances that advance these methodologies:
Contact us today to learn how to collaborate with Crown Bioscience on advancing New Approach Methodologies.
Frequently Asked Questions
NAMs are non-animal and human-relevant approaches, including in vitro assays, organ-on-chip systems, and in silico modeling, used to predict human drug response more accurately than traditional animal models.
Our in vitro human-relevant testing systems and predictive modeling directly align with the FDA Modernization Act 2.0 framework, allowing sponsors to substitute or supplement animal data with human-relevant metrics to satisfy safety and efficacy milestones.
NAMs can improve the translational relevance of preclinical research by using models that better reflect human biology. These approaches help researchers evaluate drug efficacy, identify biomarkers, understand mechanisms of action, and detect potential toxicities earlier in development, potentially reducing late-stage clinical failures.
No. The FDA is encouraging the use of scientifically appropriate NAMs to reduce reliance on animal testing where possible. Current initiatives focus on integrating human-relevant methods into preclinical development, beginning with certain biologics such as monoclonal antibodies, while continuing to evaluate broader applications.
In some applications, NAMs can reduce or replace certain animal studies. However, many drug development programs currently use NAMs alongside traditional in vivo studies to create a comprehensive weight-of-evidence package that supports regulatory submissions and informed decision-making.
Although NAMs are increasingly used across many therapeutic areas, they are particularly valuable in oncology, immuno-oncology, inflammation, rare diseases, and cell and gene therapy, where human biology and patient heterogeneity are critical for evaluating treatment response.
NAMs enable researchers to generate data from models that more closely resemble human biology, helping bridge the gap between laboratory studies and clinical trials. Combining human-derived models with biomarker analysis and computational approaches can improve confidence in target validation, patient stratification, and therapeutic decision-making.
Patient-derived organoid (PDXO) models, humanized mouse models, and translational biomarker assays supporting IND-enabling and biomarker-driven programs.
PDX and PDXO models retain the parent tumor's genomic architecture and heterogeneity. Utilizing patient-derived organoids (PDXO) for drug screening delivers a highly predictable, human-relevant efficacy readout that functions as a cornerstone of an IND weight-of-evidence (WoE) strategy.
References
Marshall, L. J., Bailey, J., Cassotta, M., Herrmann, K., & Pistollato, F. (2023). Poor Translatability of Biomedical Research Using Animals — A Narrative Review. Alternatives to Laboratory Animals, 51(2), 102–135. https://doi.org/10.1177/02611929231157756
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