This week, the FDA published four new LOI (Letter of Intent) determinations for the ISTAND Program; two acceptances and two rejections. There are now 11 technologies formally accepted into the ISTAND Program including 7 in vitro systems for preclinical testing.
Of the 7 accepted in vitro NAMs:
- 4 are microphysiological systems (MPS) or organ-on-a-chip technologies
- 3 use standard 2D cell culture techniques
- 0 are 3D organoids or spheroids
MPS and organoid systems often pursue similar applications for predicting tissue toxicity. These numbers tell an important story.
MPS technologies are currently being favored over organoids in the race toward regulatory acceptance.
An updated summary of all technologies accepted into the FDA ISTAND Program, as of 18 November 2025.
Why MPS Technologies Are Pulling Ahead
The FDA has not made any statement as to why MPS seems to be outcompeting organoids or spheroids. It may have to do with how the technologies are designed and deployed. Microphysiological Systems are highly complex and relatively low throughput. They are expensive but closely recapitulate a specific tissue type. This naturally lends to their use later in developmental pipelines for use in IND. Organoids and spheroids are often grown in 96-well format and can be adapted for high-throughput use. This may drive their application more towards early drug discovery. The consequence of this may be that organoid and spheroid Context of Use (COU) statements are less refined and less relevant for regulatory use.
But the explanation may be simpler. Perhaps MPS companies have simply been more aggressive in pursuing regulatory acceptance.
What This Means for NAM Developers
The first wave of ISTAND-accepted technologies will shape the regulatory landscape for years. MPS is setting the pace, and organoid developers may need to adapt quickly if they want a seat at the regulatory table. If they fail to enter regulatory qualification soon, organoids and spheroids may permanently be a generation behind similar technologies.
For now, MPS is winning the NAMs race.
Partner with InnovApproach Consulting
Are you an organoid developer looking to be the first accepted into the ISTAND program? Are you an MPS developer wanting to catch the competition? Contact us! InnovApproach specializes in the validation and qualification of NAMs and has hands-on experience with every step of the ISTAND Program. Learn more about InnovApproach here.
An updated timeline of all accepted and rejected submissions to the FDA ISTAND Program including latest submission milestone, as of 18 November 2025.
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