The FDA ISTAND (Innovative Science and Technology Approaches for New Drugs) Program is transforming how powerful new tools are evaluated and qualified for use in drug development. From toxicity screening to AI-driven clinical endpoints the FDA is actively reviewing New Approach Methodologies (NAMs) across the preclinical and clinical spectrum.
The figure below highlights a snapshot of current technologies in the ISTAND pipeline as of September 2025. These represent a diverse and growing portfolio of tools that aim to modernize the drug development process and reduce reliance on animal testing. Access to the FDA’s database on NAMs under ISTAND qualification and other DDTs can be found here.
A Look Inside the FDA ISTAND Pipeline
The FDA has accepted multiple technologies into the ISTAND program, spanning in vitro, in silico, and statistical approaches. All are currently in the Letter of Intent (LOI) accepted phase except for Integral Molecular and Emulate, which have advanced to the Qualification Plan (QP) accepted stage.
Preclinical Innovations:
- Integral Molecular: The Membrane Proteome Array (MPA) for flow cytometry-based off-target specificity assessment in vitro. (QP accepted)
- Charles River: The Retrogenix platform for slide-based off-target specificity assessment in vitro.
- Fresenius Kabi: Evaluating local tolerance of leachables through in vitro assays.
- Emulate: The Human Liver-Chip predicts drug-induced liver injury, a critical step toward replacing animal toxicology models. (QP accepted)
- Organ Pathobiology and Therapeutics Institute (OPTIn): A liver acinus microphysiological system designed to refine dosing predictions for candidate drugs.
Clinical-Stage NAMs:
- AstraZeneca: AI/ML-based adjudication of clinical events to improve consistency and speed in endpoint evaluation.
- Brigham and Women’s Hospital: The HF-NLP model applies natural language processing to identify cardiovascular deaths in clinical data.
- Deliberate Solutions: The AI-COA™ platform automates the scoring of depression and anxiety severity.
- Independent Statistical Approach: Weighted Kernel Estimator (WKE) to improve survival analysis in time-to-event endpoints.
The Bigger Picture: Modern Tools for Modern Drug Development
Each of these projects reflects the FDA’s broader vision of modernizing regulatory science. Together they demonstrate how AI, organ-on-a-chip models, and advanced statistical methods are driving a shift away from traditional, animal-based testing.
This aligns closely with the FDA’s roadmap to reduce animal testing, which encourages the adoption of human-relevant, predictive technologies wherever scientifically appropriate. As these tools progress through qualification, they will set new precedents for how NAMs can support INDs, NDAs, and BLAs across the pharmaceutical and biotech industries.
What This Means for Innovators
The current FDA ISTAND portfolio represents only a small fraction of the technologies capable of transforming drug development. Many promising innovations remain untapped, including:
- Computational and AI-driven toxicology models predicting safety outcomes without animal data
- Advanced organoid and microphysiological systems for disease-specific testing
- Machine learning–based endpoint evaluation systems
- Digital biomarkers and wearable-derived measures for modern clinical trials
- Large Language Models (LLMs) with specific use-cases in preclinical and clinical data review
For companies developing these technologies, timing is critical. Once a comparable tool is qualified by the FDA, it becomes a regulatory benchmark. Competitors who delay qualification risk being left behind, their platforms seen as redundant or less innovative.
Achieving ISTAND qualification provides scientific validation and strategic market positioning. Qualified Drug Development Tools often become the reference standards that sponsors and regulators look to, shaping both regulatory expectations and commercial adoption.
Innovators who move early to qualify their NAMs will lead this new era of regulatory science. Those who wait may find themselves competing against technologies that have already defined the standard.
InnovApproach: Experience that Leads the Way
At InnovApproach Consulting, we bring unmatched insight into the ISTAND process. Our founder, Michael Phelan, PhD, led the first technology ever accepted into the program, helping to shape its structure and expectations. We help clients:
- Prepare and submit ISTAND qualification packages
- Integrate NAMs data into FDA submissions
- Align with the FDA’s roadmap to reduce animal testing
If you are developing a novel technology that could accelerate or improve drug development, now is the time to explore ISTAND qualification.
👉 Contact InnovApproach Consulting to learn how we can help you navigate the FDA qualification pathway and bring your innovations to the forefront of regulatory science.
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