FDA Codifies 21 CFR 864.3900 for AI Pap-Test Imaging on 5 November 2026: Class II Controls and a Measured Daily Workload for Cytologists

What FDA published in the Federal Register on 5 November 2026

FDA's final order in Docket FDA-2026-N-12384 (91 FR 69687) adds 21 CFR 864.3900, a new device type called the digital cervical cytology slide imaging system with artificial intelligence algorithm. The device scans Pap test slides, and its machine-learning software selects areas of interest and presents them in a gallery for a cytologist to interpret. FDA placed it in class II with special controls. The request came from Hologic for its Genius Digital Diagnostics System with the Genius Cervical AI algorithm, filed on 27 August 2021 and granted on 31 January 2024; the order is effective 5 November 2026.

Which special controls a second AI cytology system must meet

Since the De Novo grant of January 2024, Hologic's device has served as a predicate, so later systems of this type can seek 510(k) clearance instead of a De Novo request. They must still meet the special controls: training and validation data described in detail, results stratified by patient demographics, sites and scanners, a security architecture diagram, and a reader study against the optical microscope.

Why the daily workload clause matters to laboratories

The order also requires clinical data to set a recommended daily maximum workload for readers using the device. Federal laboratory rules cap manual cytology screening at 100 slides in a workday of at least eight hours. For Hologic's device, FDA's decision summary counts each AI-assisted case review as half a slide against that cap.