The FDA’s Innovative Science and Technology Approaches for New Drugs (ISTAND) Program is one of the clearest windows into how New Approach Methodologies (NAMs) are moving from promise to regulatory reality.
As of the 21st of January, 2026, 20 ISTAND technologies have now been disclosed in the FDA’s Drug Development Tool (DDT) database. 15 were accepted into the program and 5 rejected. While the sample size is still modest, the dataset is large enough to reveal meaningful patterns about regulatory expectations, timelines, and which technologies are most likely to succeed.
Below is a snapshot of what these 20 ISTAND submissions tell us about the current and future state of NAMs.
1. Review Timelines Are Accelerating Dramatically
One of the most striking trends is how quickly ISTAND is moving.
- Average time to decision for Letters of Intent (LOIs) submitted before 2025:
361 days - Average time for LOIs submitted in 2025:
168 days
That’s a reduction of more than 50%. As more focus is put onto NAMs and reviewers become more experienced, these timelines may accelerate further.
2. ISTAND Is Open to Global Innovation, but America Dominates
The program has accepted technologies from the UK and Europe for review, reinforcing ISTAND’s openness to global science. However, the majority of applicants and acceptances originate from U.S.-based organizations, reflecting:
- Early alignment with FDA regulatory frameworks
- Proximity to FDA engagement and pre-submission interactions
- Strong U.S. academic–industry NAMs ecosystems
This does not mean non-U.S. developers are disadvantaged, but it does mean regulatory fluency matters.
3. Acceptance Cuts Across Organization Types
ISTAND is not favoring a single type of applicant. Accepted technologies span:
- Large Pharma (e.g. AstraZeneca, Johnson & Johnson)
- Mid-Sized Biotech and NAM Developers (e.g. Integral Molecular, Emulate)
- Academic and Non-Profit Institutions (e.g. Texas A&M, The 3Rs Collaborative)
This diversity makes the FDA’s position clear. Credibility comes from the science and its regulatory framing, not organizational size.
4. Microphysiological Systems (MPS) Are (Currently) Favored Over Spheroids
Among the most revealing trends is the current preference for MPS/organ-on-a-chip technologies.
- 6 MPS technologies accepted
- 0 spheroid/organoid technologies accepted
- 2 of the 5 rejected technologies were spheroid-based
This does not imply spheroids lack scientific or even regulatory value. However, within ISTAND, the historical preference for MPS to be used for preclinical applications (instead of early screening and discovery) favors regulatorily-relevant Contexts of Use.
For developers, this underscores the importance of regulatory utility, not just biological sophistication. Spheroid and organoid developers need to catch up.
5. Critical Preclinical Endpoints Are Well Represented
The accepted technologies span a wide range of high-impact regulatory endpoints, including:
- Drug-induced liver injury (DILI)
- Drug-induced kidney injury (DIKI)
- Cardiotoxicity
- Developmental and reproductive toxicity (DART)
- Target specificity
- Dose ranging
This breadth demonstrates that NAMs are no longer confined to narrow use cases. They are increasingly positioned as decision-enabling tools across all questions relevant to regulators.
6. A Clear Divide: In Vitro for Preclinical, In Silico for Clinical
Another consistent pattern emerges when technologies are mapped to development stage:
- 100% of preclinical ISTAND technologies are in vitro
- 100% of clinical-stage ISTAND technologies are in silico or algorithmic
This may change in the future, but despite the preclinical applications of in silico NAMs being widely discussed, they haven’t yet been represented in the FDA’s qualification program.
7. The Dominant Reason for Rejection: Context of Use
Rejection decisions are often multifactorial, but one issue stands out.
- 4 of the 5 rejected technologies list “Context of Use” as the first or sole reason for rejection
This reinforces a critical lesson for ISTAND applicants:
Regulatory success is not about how innovative a technology is. It is about how your technology helps regulators make decisions.
Technologies that fail to clearly articulate what regulatory decision they support, in which setting, and as a replacement or complement to what existing technologies will fail to meet the acceptance criteria of the ISTAND program.
Choose InnovApproach Consulting
At InnovApproach Consulting, we have firsthand experience navigating the full ISTAND qualification process, including developing and refining COUs for complex technologies. InnovApproach consultants were leaders in the first successful ISTAND submissions and helped define the submission process.
If your team is developing a NAM and wants to ensure it is validated, qualified, and positioned for regulatory acceptance, contact InnovApproach Consulting.
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