Medical Devices; Neurological Devices; Classification of the Prognostic Assessment Software of Mild Cognitive Impairment

Issuing agencies

Abstract

The Food and Drug Administration (FDA) is classifying the prognostic assessment software of mild cognitive impairment 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 prognostic assessment software of mild cognitive impairment. We are taking this action because we have determined that classifying the device into class II will provide a reasonable assurance of the 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 213 (Thursday, November 5, 2026)</title>
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[Federal Register Volume 91, Number 213 (Thursday, November 5, 2026)]
[Rules and Regulations]
[Pages 69690-69692]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-22590]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 882

[Docket No. FDA-2026-N-12212]


Medical Devices; Neurological Devices; Classification of the 
Prognostic Assessment Software of Mild Cognitive Impairment

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA) is classifying the 
prognostic assessment software of mild cognitive impairment 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 prognostic assessment software of 
mild cognitive impairment. We are taking this action because we have 
determined that classifying the device into class II will provide a 
reasonable assurance of the 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 November 5, 2026. The classification was 
applicable on January 11, 2024.

FOR FURTHER INFORMATION CONTACT: Patrick Antkowiak, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. 4254, Silver Spring, MD 20993-0002, 240-
402-3705, <a href="/cdn-cgi/l/email-protection#500031242239333b7e113e243b3f2739313b103634317e3838237e373f26"><span class="__cf_email__" data-cfemail="f5a59481879c969edbb49b819e9a829c949eb5939194db9d9d86db929a83">[email&#160;protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA (the Agency or we) has classified the prognostic 
assessment software of mild cognitive impairment into class II (special 
controls), which we have determined will provide a reasonable assurance 
of the 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

[[Page 69691]]

placed within class III, the De Novo 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 September 29, 2022, FDA received Darmiyan, Inc.'s request for De 
Novo classification of the BrainSee 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 the 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 January 11, 2024, 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 
882.1454.\1\ We have named the generic type of device ``prognostic 
assessment software of mild cognitive impairment,'' and it is 
identified as a prescription-only device that combines information from 
multiple clinical data sources to produce an output indicative of the 
likelihood that a patient diagnosed with mild cognitive impairment will 
progress to more severe forms of cognitive impairment, or will develop 
dementia, such as Alzheimer's disease dementia, within a specified 
period of time. This device is intended for adjunctive use and not 
intended as a stand-alone diagnostic or prognostic tool.
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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 Prognostic
            Assessment Software of Mild Cognitive Impairment
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       Identified risks to health              Mitigation measures
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Device failure or incorrect analysis     Clinical performance testing;
 leading to                               Postmarket surveillance;
<bullet> False positives or falsely       Software verification,
 high prognostic outputs resulting in     validation, and hazard
 inappropriate patient treatment and      analysis; and Labeling.
 delayed diagnosis of non-Alzheimer's
 disease conditions..
<bullet> False negatives or falsely low
 prognostic outputs resulting in
 delayed diagnosis and/or patient
 treatment..
Use error or misinterpretation of        Human factors/usability
 results leading to.                      assessment; and Labeling.
    <bullet> A false positive or
     falsely high prognostic outputs.
    <bullet> A false negative or
     falsely low prognostic outputs.
    <bullet> Overreliance on device
     output for follow-up.
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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 the 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.
    At the time of classification, prognostic assessment software of 
mild cognitive impairment is for prescription use only. Prescription 
devices are exempt from the requirement for adequate directions for use 
for the layperson under section 502(f)(1) of the FD&C Act (21 U.S.C. 
352(f)(1)) and 21 CFR 801.5, as long as the conditions of 21 CFR 
801.109 are met.
    Under the FD&C Act, submission of a premarket notification under 
section 510(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 prognostic assessment 
software of mild cognitive impairment. This device is therefore subject 
to premarket notification requirements under section 510(k) of the FD&C 
Act.

III. Analysis of Environmental Impact

    We have 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

[[Page 69692]]

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 part 801 
regarding labeling have been approved under OMB control number 0910-
0485.

List of Subjects in 21 CFR Part 882

    Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
882 is amended as follows:

PART 882--NEUROLOGICAL DEVICES

0
1. The authority citation for part 882 continues to read as follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.

0
2. Add Sec.  882.1454 to subpart B to read as follows:


Sec.  882.1454  Prognostic assessment software of mild cognitive 
impairment.

    (a) Identification. Prognostic assessment software of mild 
cognitive impairment is a prescription-only device that combines 
information from multiple clinical data sources to produce an output 
indicative of the likelihood that a patient diagnosed with mild 
cognitive impairment will progress to more severe forms of cognitive 
impairment, or will develop dementia, such as Alzheimer's disease 
dementia, within a specified period of time. This device is intended 
for adjunctive use and not intended as a stand-alone diagnostic or 
prognostic tool.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Data obtained from premarket clinical performance validation 
testing and postmarket surveillance acquired under anticipated 
conditions of use must demonstrate that the device performs as intended 
when used to analyze data from the intended patient population, unless 
FDA determines, based on the totality of the information provided for 
premarket review, that data from postmarket surveillance is not 
required.
    (i) Data provided from paragraph (b)(1) of this section must 
demonstrate the accuracy, precision, and reproducibility of the device 
for predicting progression of patients with mild cognitive impairment 
to more severe forms of cognitive impairment or to dementia, such as 
Alzheimer's disease dementia, based on a clinically relevant reference 
standard for the diagnosis of such disease states or conditions. The 
test data set must include data acquired from a patient population that 
is representative of the intended patient population normally seen in 
clinical practice. The test data set must be independent from data used 
in training/development of the device.
    (ii) Objective performance measures (e.g., sensitivity, 
specificity, positive predictive value, negative predictive value) must 
be reported with relevant descriptive or developmental performance 
measures.
    (2) Software verification, validation, and hazard analysis must be 
provided. Software documentation must include a detailed, technical 
description of the model/algorithm(s) and algorithm inputs and outputs.
    (3) Human factors/usability assessment must demonstrate that the 
intended user(s) in the intended use environment can correctly use the 
device and interpret the device output(s).
    (4) Physician labeling must include:
    (i) A detailed summary of the clinical performance testing methods, 
including results of the performance testing for tested performance 
measures/metrics, selection criteria, and the patient demographics;
    (ii) A description of the patient population that was used in 
development or training of the device algorithm/model;
    (iii) Device limitations or subpopulations for which the device may 
not perform as expected or for whom the device has not been validated;
    (iv) A statement that the device is not a stand-alone diagnostic or 
prognostic tool and that the device output should only be interpreted 
in the context of all available clinical information, including patient 
history, medications, and comorbidities; and
    (v) Information for interpretation of the device outputs detailing 
the risks associated with misinterpretation of the device outputs.
    (5) Patient labeling must include information explaining the device 
output(s) and the associated risks if the device output is incorrect.

Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-22590 Filed 11-4-26; 8:45 am]
BILLING CODE 4164-01-P


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