How NAMs get accepted

Validation and qualification are different

Validation shows a method is reliable and relevant for a purpose. Qualification is a regulator's formal conclusion that a tool can be used for a specific context of use without being re-justified in each submission.

FDA's framework

The March 2026 CDER draft guidance asks sponsors to address four things:

1. Context of use: the question and the decision the data supports.
2. Human biological relevance: how well the system reflects the biology at stake.
3. Technical characterization: reproducibility, performance and limits.
4. Fit for purpose: whether the evidence is enough for the decision.

FDA also reviews NAM data case by case inside INDs without formal qualification. Most use today runs that way.

Routes to acceptance

• Case-by-case use in a submission: fastest, but creates no reusable precedent.
• Drug Development Tool qualification, including ISTAND for novel tools: slow, but reusable.
• EMA qualification opinions, such as Simcyp PBPK (August 2025).
• OECD test guidelines and defined approaches for chemicals.
• Agency lists of accepted methods, such as EPA's TSCA and FIFRA list.

The evidence gap

• FDA's review of NAM submissions found organ-chip and 3D model data less common than conventional in vitro data.
• FDA scientists showed common liver injury biomarker assays can mislead in liver-chip media.
• IQ MPS Affiliate surveys of 20+ pharma companies found adoption limited by reproducibility, cost and unclear regulatory use.

What to watch

• FDA's decision on Emulate's Liver-Chip full qualification package.
• How FDA finalizes the March 2026 draft guidance.
• Outputs of NIH's validation and qualification network.
• Whether C-Path's coalition produces shared performance standards.