The FDA had cleared more than 700 AI-enabled medical devices through three distinct pathways as of 2025. The regulatory mechanism determines not only whether a device can be sold but what clinical claims its manufacturer can make and how much post-market surveillance is required. Understanding the difference between 510(k), De Novo, and PMA matters for anyone evaluating AI medical devices for clinical deployment.
The 510(k) Pathway
The 510(k) pathway requires a manufacturer to demonstrate substantial equivalence to a legally marketed predicate device. Most AI medical device clearances in the United States come through 510(k). The pathway does not require clinical trials. It requires a comparison to an existing device and evidence that the new device performs at least as well as the predicate on specified performance metrics. For AI radiology tools, the predicate is often an earlier version of the same tool or a non-AI decision-support system.
The De Novo Pathway
When no suitable predicate exists, manufacturers can request De Novo classification. The FDA evaluates the novel device against a risk-based standard and, if granted, the De Novo decision itself becomes a predicate for future 510(k) submissions. The first AI device cleared through De Novo for a given indication creates the template for subsequent clearances in that category.
The PMA Pathway
Premarket Approval applies to the highest-risk devices and requires valid scientific evidence, typically clinical trials, demonstrating reasonable assurance of safety and effectiveness. PMA is rare for AI medical devices. The clinical trial requirement is expensive and slow relative to 510(k). Most AI device manufacturers structure their submissions to qualify for 510(k) rather than PMA.
The EU AI Act Comparison
The EU AI Act classifies most medical AI as high-risk and requires conformity assessment, registration in an EU database, and post-market monitoring plans. The March 2026 European Radiology review documented convergence between FDA, EU, and China NMPA frameworks on core requirements including performance testing, bias evaluation, and transparency, with meaningful differences in stringency and enforcement.
Limitations
FDA clearance establishes safety and effectiveness relative to a predicate, not superiority over current standard of care. A cleared AI device may be no better than existing tools; clearance does not mean clinically beneficial. Post-market surveillance requirements for cleared AI devices are less rigorous than those applied to high-risk drugs.
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Primary sources: FDA AI/ML medical device database; March 2026 European Radiology review of international AI medical device frameworks.