FDA Proposes Reclassifying Mycobacterium Tuberculosis Immunity Tests to Class II Devices

The Food and Drug Administration proposed reclassifying Mycobacterium tuberculosis cell-mediated immunity tests from Class III to Class II devices on March 30, 2026, according to the Federal Register. The agency said the change, based on recommendations from the Microbiology Devices Panel, aims to establish special controls that support the safe and effective diagnosis of tuberculosis infection through immune response assays.

The proposed reclassification affects Mycobacterium tuberculosis cell-mediated immunity tests, including immune response enzyme-linked immunospot assays, which detect in vitro responses to peptide antigens associated with tuberculosis infection, according to the Federal Register notice published March 30, 2026. The Food and Drug Administration (FDA) said the move would shift these tests from Class III to Class II medical devices, subject to special controls alongside general controls, thereby establishing a regulatory framework intended to ensure safety and effectiveness.

The FDA also requires limit of detection testing with both susceptible and resistant MTB strains and analytical reactivity evaluations to ensure assay inclusivity.

This initiative follows unanimous recommendations from the FDA’s Microbiology Devices Panel, which met on September 7, 2023, to review tuberculosis interferon gamma release assays (IGRA) under product codes NCD and OJN. The panel affirmed the FDA’s identification of health risks associated with these assays as complete and accurate, agreeing that the available data supported reclassification to Class II. Panel members also recommended that new submissions comply with the same clinical and analytical validation standards as currently approved tests, officials said.

The proposed special controls outlined by the FDA include requirements for external positive assay controls using Mycobacterium tuberculosis complex isolates, internal controls, and validation of pre-analytical specimen preparation procedures. Labeling must include warnings about the risk of false-negative results, which could contribute to disease progression and transmission, according to agency documents.

Under the current classification, these qualitative immune response assays are designated as Class III devices, necessitating premarket approval. The reclassification would allow manufacturers to pursue market authorization through the less burdensome premarket notification process, commonly known as 510(k), providing a legal pathway for marketing these devices under Class II controls, the FDA said.

The Microbiology Devices Panel’s September 2023 meeting also included discussions of assays for hepatitis B virus and parvovirus, but the unanimous vote to initiate reclassification specifically targeted the Mycobacterium tuberculosis cell-mediated immunity tests, sources confirmed. The panel’s recommendations reflect a broader regulatory approach consistent with prior FDA actions on tuberculosis diagnostic devices.

This proposal builds on historical precedents, including the reclassification of nucleic acid-based Mycobacterium tuberculosis detection devices from Class III to Class II on May 30, 2014, as documented in the Federal Register (79 FR 31023). That earlier action followed a 2012 FDA proposal (77 FR 16126) to reclassify nucleic acid systems intended as aids in diagnosing pulmonary tuberculosis. Subsequent to that reclassification, the FDA issued a guideline on October 22, 2014, establishing special controls for those nucleic acid devices.

The FDA’s docket for this current proposal remains pending public inspection, with the agency inviting comments and data submissions to inform the final rulemaking process. The docket number and related materials are available in the Federal Register notice dated March 30, 2026. Public input and further panel discussions may influence the final classification and associated regulatory requirements.

The agency emphasized that the special controls and validation standards are designed to mitigate risks identified by the panel, particularly the risk of false-negative results that could lead to untreated tuberculosis cases and ongoing transmission. The FDA’s guidance documents for industry and staff provide detailed instructions on the analytical, clinical, and pre-analytical validation necessary to meet these standards.

If finalized, the reclassification would align tuberculosis cell-mediated immunity tests with the FDA’s current regulatory framework for in vitro diagnostic devices, facilitating broader availability while maintaining rigorous safety and effectiveness criteria. The agency’s action reflects an evolving understanding of tuberculosis diagnostics and regulatory science, officials said.