Rule2026-07860
Medical Devices; Immunology and Microbiology Devices; Classification of the Alzheimer's Disease Pathology Assessment Test
Primary source
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Published
April 22, 2026
Effective
April 22, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, the Agency, or we) is classifying the Alzheimer's disease pathology assessment test into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for classification of the Alzheimer's disease pathology assessment test. We are taking this action because we have determined that classifying the device into class II will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.
Full Text
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<title>Federal Register, Volume 91 Issue 77 (Wednesday, April 22, 2026)</title>
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[Federal Register Volume 91, Number 77 (Wednesday, April 22, 2026)]
[Rules and Regulations]
[Pages 21379-21381]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-07860]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2026-N-3930]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Alzheimer's Disease Pathology Assessment Test
AGENCY: Food and Drug Administration, HHS.
ACTION: Final amendment; final order.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
classifying the Alzheimer's disease pathology assessment test into
class II (special controls). The special controls that apply to the
device type are identified in this order and will be part of the
codified language for classification of the Alzheimer's disease
pathology assessment test. We are taking this action because we have
determined that classifying the device into class II will provide a
reasonable assurance of safety and effectiveness of the device. We
believe this action will also enhance patients' access to beneficial
innovative devices, in part by reducing regulatory burdens.
DATES: This order is effective April 22, 2026. The classification was
applicable on May 4, 2022.
FOR FURTHER INFORMATION CONTACT: Woosung (David) Cho, Center for
Devices and Radiological Health, Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 66, Rm. 3461, Silver Spring, MD 20993-0002,
301-796-5998, <a href="/cdn-cgi/l/email-protection#95c2fafae6e0fbf2bbd6fdfad5f3f1f4bbfdfde6bbf2fae3"><span class="__cf_email__" data-cfemail="e8bf87879b9d868fc6ab8087a88e8c89c680809bc68f879e">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA (the Agency or we) has classified the Alzheimer's
disease pathology assessment test into class II (special controls),
which we have determined will provide a reasonable assurance of safety
and effectiveness of the device. In addition, we believe this action
will enhance patients' access to beneficial innovation, in part by
reducing regulatory burdens by placing the device into a lower device
class than the automatic class III assignment.
The automatic assignment of class III occurs by operation of law
and without any action by FDA, regardless of the level of risk posed by
the new device. Any device that was not in commercial distribution
before May 28, 1976, is automatically classified into, and remains
within, class III and requires premarket approval unless and until FDA
takes an action to classify or reclassify the device (21 U.S.C.
360c(f)(1)). We refer to these devices as ``postamendments devices''
because they were not in commercial distribution prior to the date of
enactment of the Medical Device Amendments of 1976, which amended the
Federal Food, Drug, and Cosmetic Act (FD&C Act).
FDA may take a variety of actions in appropriate circumstances to
classify or reclassify a device into class I or II. We may issue an
order finding a new device to be substantially equivalent under section
513(i) of the FD&C Act (21 U.S.C. 360c(i)) to a predicate device that
does not require premarket approval. We determine whether a new device
is substantially equivalent to a predicate device by means of the
procedures for premarket notification under section 510(k) of the FD&C
Act (21 U.S.C. 360(k)) and part 807 (21 CFR part 807).
FDA may also classify a device through ``De Novo'' classification,
a common name for the process authorized under section 513(f)(2) of the
FD&C Act (see also part 860, subpart D (21 CFR part 860, subpart D)).
Section 207 of the Food and Drug Administration Modernization Act of
1997 (Pub. L. 105-115) established the first procedure for De Novo
classification. Section 607 of the Food and Drug Administration Safety
and Innovation Act (Pub. L. 112-144) modified the De Novo
classification process by adding a second procedure. A device sponsor
may utilize either procedure for De Novo classification.
Under the first procedure, the person submits a premarket
notification (510(k)) for a device that has not previously been
classified. After receiving an order from FDA classifying the device
into class III under section 513(f)(1) of the FD&C Act, the person then
requests a classification under section 513(f)(2).
Under the second procedure, rather than first submitting a 510(k)
and then a request for classification, if the person determines that
there is no legally marketed device upon which to base a determination
of substantial equivalence, that person requests a classification under
section 513(f)(2) of the FD&C Act.
Under either procedure for De Novo classification, FDA is required
to classify the device by written order within 120 days. The
classification will be according to the criteria under section
513(a)(1) of the FD&C Act. Although the device was automatically placed
within class III, the De Novo
[[Page 21380]]
classification is considered to be the initial classification of the
device.
We believe this De Novo classification will enhance patients'
access to beneficial innovation, in part by reducing regulatory
burdens. When FDA classifies a device into class I or II via the De
Novo process, the device can serve as a predicate for future devices of
that type, including for 510(k)s (see section 513(f)(2)(B)(i) of the
FD&C Act). As a result, other device sponsors do not have to submit a
De Novo request or premarket approval application to market a
substantially equivalent device (see section 513(i) of the FD&C Act,
defining ``substantial equivalence''). Instead, sponsors can use the
less burdensome 510(k) process, when necessary, to market their device.
II. De Novo Classification
On November 20, 2020, FDA received Fujirebio Diagnostics, Inc.'s
request for De Novo classification of the Lumipulse G [beta]-Amyloid
Ratio (1-42/1-40) device. FDA reviewed the request in order to classify
the device under the criteria for classification set forth in section
513(a)(1) of the FD&C Act.
We classify devices into class II if general controls by themselves
are insufficient to provide reasonable assurance of safety and
effectiveness of the device, but there is sufficient information to
establish special controls that, in combination with the general
controls, provide reasonable assurance of the safety and effectiveness
of the device for its intended use (see section 513(a)(1)(B) of the
FD&C Act). After review of the information submitted in the request, we
determined that the device can be classified into class II with the
establishment of special controls. FDA has determined that these
special controls, in addition to the general controls, will provide
reasonable assurance of the safety and effectiveness of the device.
Therefore, on May 4, 2022, FDA issued an order to the requester
classifying the device into class II. In this final order, FDA is
codifying the classification of the device by adding 21 CFR
866.5840.\1\ We have named the generic type of device ``Alzheimer's
disease (AD) pathology assessment test,'' and it is identified as 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 imaging agents. The device is
intended to assess the underlying AD-associated pathology in
conjunction with clinical assessment to increase diagnostic certainty.
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\1\ FDA notes that the ``ACTION'' caption for this final order
is styled as ``Final amendment; final order,'' rather than ``Final
order.'' Beginning in December 2019, this editorial change was made
to indicate that the document ``amends'' the Code of Federal
Regulations. The change was made in accordance with the Office of
Federal Register's (OFR) interpretations of the Federal Register Act
(44 U.S.C. chapter 15), its implementing regulations (1 CFR 5.9 and
parts 21 and 22), and the Document Drafting Handbook.
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FDA has identified the risks to health associated with this type of
device and the measures required to mitigate these risks in table 1.
Table 1--Risks to Health and Mitigation Measures for Alzheimer's Disease
Pathology Assessment Test
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Identified risks to health Mitigation measures
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Failure to correctly interpret test Special controls (1) and (2).
results can lead to false positive
results (leading to workup and anxiety
regarding a serious diagnosis that is
incorrect) or false negative results
(leading to delays in getting treatment
and delays planning early in the course
of this progressive disease).
Incorrect test results that provide Special controls (1) and (2).
false positive results (leading to
workup and anxiety regarding a serious
diagnosis that is incorrect) or false
negative results (leading to delays in
getting treatment and delays planning
early in the course of this progressive
disease).
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FDA has determined that special controls, in combination with the
general controls, address these risks to health and provide reasonable
assurance of safety and effectiveness of the device. For a device to
fall within this classification, and thus avoid automatic
classification in class III, it would have to comply with the special
controls named in this final order. The necessary special controls
appear in the regulation codified by this final order.
Under the FD&C Act, submission of a premarket notification under
section 510(k) (21 U.S.C. 360(k)) is required to reasonably assure the
safety and effectiveness of class II devices unless FDA determines that
the device type should be exempt under section 510(m) of the FD&C Act.
At this time FDA has not made this determination for Alzheimer's
disease pathology assessment tests. This device is therefore subject to
premarket notification requirements under section 510(k) of the FD&C
Act.
III. Analysis of Environmental Impact
The Agency has determined under 21 CFR 25.34(b) that this action is
of a type that does not normally have a significant effect on the human
environment. Therefore, neither an environmental assessment nor an
environmental impact statement is required.
IV. Paperwork Reduction Act of 1995
This final order establishes special controls that refer to
previously approved collections of information found in other FDA
regulations and guidance. These collections of information are subject
to review by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). The collections
of information in part 860, subpart D, regarding De Novo classification
have been approved under OMB control number 0910-0844; the collections
of information in 21 CFR part 814, subparts A through E, regarding
premarket approval have been approved under OMB control number 0910-
0231; the collections of information in part 807, subpart E, regarding
premarket notification submissions have been approved under OMB control
number 0910-0120; the collections of information in 21 CFR part 820
regarding quality management system regulation have been approved under
OMB control number 0910-0073; and the collections of information in 21
CFR parts 801 and 809, regarding labeling have been approved under OMB
control number 0910-0485.
List of Subjects in 21 CFR Part 866
Biologics, Laboratories, Medical devices.
[[Page 21381]]
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
866 is amended as follows:
PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES
0
1. The authority citation for part 866 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 866.5840 to subpart F to read as follows:
Sec. 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 Sec. 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.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-07860 Filed 4-21-26; 8:45 am]
BILLING CODE 4164-01-P
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