[Federal Register Volume 87, Number 250 (Friday, December 30, 2022)]
[Rules and Regulations]
[Pages 80444-80446]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-28430]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 882

[Docket No. FDA-2022-N-3188]


Medical Devices; Neurological Devices; Classification of the 
Pediatric Autism Spectrum Disorder Diagnosis Aid

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
classifying the pediatric Autism Spectrum Disorder (ASD) diagnosis aid 
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 the pediatric Autism Spectrum Disorder diagnosis 
aid's classification. We are taking this action because we have 
determined that classifying the device into class II (special controls) 
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.

DATES: This order is effective December 30, 2022. The classification 
was applicable on June 2, 2021.

FOR FURTHER INFORMATION CONTACT: Mohua Choudhury, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. 4102, Silver Spring, MD 20993-0002, 240-
402-3095, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Upon request, FDA has classified the pediatric Autism Spectrum 
Disorder diagnosis aid as class II (special controls), which we have 
determined will provide a reasonable assurance of safety and 
effectiveness. In addition, we believe this action will enhance 
patients' access to beneficial innovation, in part 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 as, and remains 
within, class III and requires premarket approval unless and until FDA 
takes an action to classify or reclassify the device (see 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 (see 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. 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 
application 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 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 classification is considered to be the 
initial classification of the device.
    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 3, 2020, FDA received Cognoa, Inc.'s request for De 
Novo classification of the Cognoa ASD Diagnosis Aid. 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, 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 21 U.S.C. 360c(a)(1)(B)). 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.

[[Page 80445]]

    Therefore, on June 2, 2021, 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 
882.1491.\1\ We have named the generic type of device pediatric Autism 
Spectrum Disorder diagnosis aid, and it is identified as a prescription 
device that is intended for use as an aid in the diagnosis of Autism 
Spectrum Disorder in pediatric patients.
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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 following risks to health associated 
specifically with this type of device and the measures required to 
mitigate these risks in table 1.

   Table 1--Pediatric Autism Spectrum Disorder Diagnosis Aid Risks and
                           Mitigation Measures
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            Identified risks                   Mitigation measures
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Device failure or incorrect analysis     Clinical performance testing;
 leading to:                              Software verification,
                                          validation, and hazard
                                          analysis; and Labeling.
     False positives resulting
     in inappropriate patient treatment
     and potentially delayed diagnosis
     of a non-ASD condition.
     False negatives resulting
     in delayed diagnosis and patient
     treatment.
Use error or misinterpretation of        Usability assessment, and
 results resulting in a, false positive   Labeling.
 or false negative.
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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. 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 order. This device is subject to premarket notification 
requirements under section 510(k) of the FD&C Act.
    At the time of classification, pediatric Autism Spectrum Disorder 
diagnosis aids are 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.

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 individually or cumulatively 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 21 CFR 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 system regulation, have been 
approved under OMB control number 0910-0073; and the collections of 
information in 21 CFR parts 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.  882.1491 to subpart B to read as follows:


Sec.  882.1491  Pediatric Autism Spectrum Disorder diagnosis aid.

    (a) Identification. A pediatric Autism Spectrum Disorder diagnosis 
aid is a prescription device that is intended for use as an aid in the 
diagnosis of Autism Spectrum Disorder in pediatric patients.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Clinical performance testing must demonstrate that the device 
performs as intended under anticipated conditions of use, including an 
evaluation of sensitivity, specificity, positive predictive value, and 
negative predictive value using a reference method of diagnosis and 
assessment of patient behavioral symptomology.
    (2) Software verification, validation, and hazard analysis must be 
provided. Software documentation must include a detailed, technical 
description of the algorithm(s) used to generate device output(s), and 
a cybersecurity assessment of the impact of threats and vulnerabilities 
on device functionality and user(s).
    (3) Usability assessment must demonstrate that the intended user(s) 
can safely and correctly use the device.
    (4) Labeling must include:
    (i) Instructions for use, including a detailed description of the 
device, compatibility information, and information to facilitate 
clinical interpretation of all device outputs; and
    (ii) A summary of any clinical testing conducted to demonstrate how 
the device functions as an interpretation of patient behavioral 
symptomology associated with Autism Spectrum Disorder. The summary must 
include the following:
    (A) A description of each device output and clinical 
interpretation;
    (B) Any performance measures, including sensitivity, specificity,

[[Page 80446]]

positive predictive value (PPV) and negative predictive value (NPV);
    (C) A description of how the cutoff values used for categorical 
classification of diagnoses were determined; and
    (D) Any expected or observed adverse events and complications.
    (iii) A statement that the device is not intended for use as a 
stand-alone diagnostic.

    Dated: December 27, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-28430 Filed 12-29-22; 8:45 am]
BILLING CODE 4164-01-P


