§ 866.5840 — Alzheimer's disease pathology assessment test.

§ 866.5840 Alzheimer's disease pathology assessment test.

(a) Identification. An Alzheimer's disease (AD) pathology assessment test is an in vitro diagnostic device intended to measure one or more analytes in human specimens to assess whether a patient presenting with cognitive impairment and being evaluated for AD and other causes of cognitive decline would test positive or negative for amyloid plaques or neurofibrillary tangles at the time of testing, as measured by FDA-approved positron emission tomography (PET) imaging agents. The device is intended to assess the underlying AD-associated pathology in conjunction with clinical assessment to increase diagnostic certainty.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) Design verification and validation must include:

(i) Detailed documentation of studies demonstrating analytical performance, including precision, linearity, assay interference, cross-reactivity, detection capability, specimen and reagent stability, and hook effect, as applicable. For devices measuring multiple analytes, the detailed documentation must include studies demonstrating the analytical performance of the device in regard to each individual analyte, including precision, linearity, assay interference, cross-reactivity, detection capability, specimen and reagent stability, and hook effect, as applicable.

(ii) Detailed documentation of studies demonstrating clinical performance in the intended use patient population. All eligible subjects must meet the appropriate study inclusion and exclusion criteria that define the intended use population. Relevant demographic and patient characteristics must be documented, including the time from specimen collection for testing with the subject device to PET imaging acquisition; patient cognitive, neurological, and psychiatric assessments; Apolipoprotein E (APOE) carrier status; and patient education level. All specimens must be tested with the users of the subject device blinded to the disease status and PET scan results of the subject from whom the specimen was obtained. Each PET scan must use an FDA-approved PET tracer and must be independently evaluated in a blinded manner and interpreted according to the FDA-required labeling for the PET tracer. For banked specimens, details on storage conditions and storage period must be documented. In addition, documentation must include evidence to support the stability of the archived specimens for the duration of storage.

(iii) Detailed documentation of studies, which are performed using specimens from persons established to be cognitively normal, that establish the upper and lower limits of reference intervals for the output provided by the device. For banked specimens, the detailed documentation must include details on storage conditions and storage period. In addition, the detailed documentation must include evidence to support the stability of the archived specimens for the duration of storage.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) An intended use that provides a description of the measurand(s) (i.e., AD pathology biomarker(s)) the device measures in the specified human specimens, the results provided to the user (including information to facilitate clinical interpretation of all device outputs), the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.

(ii) Limiting statements indicating that:

(A) This device is not intended to be used as a stand-alone test and the test results must be interpreted in conjunction with other diagnostic tools and clinical information.

(B) The safety and effectiveness of the device have not been established for predicting development of dementia or other neurologic conditions or for monitoring the effect of any therapeutic product.

(C) A positive result is associated with the presence of amyloid plaques or neurofibrillary tangles in the brain but does not establish a diagnosis of AD as would be established by neuropathological examination.

(iii) A detailed summary of the performance testing, including results, required under paragraph (b)(1) of this section.

[91 FR 21381, Apr. 22, 2026]