[Federal Register Volume 85, Number 14 (Wednesday, January 22, 2020)]
[Rules and Regulations]
[Pages 3540-3543]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-00497]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 892

[Docket No. FDA-2019-N-5610]


Medical Devices; Radiology Devices; Classification of the 
Radiological Computer-Assisted Diagnostic Software for Lesions 
Suspicious for Cancer

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA or we) is classifying 
the radiological computer-assisted diagnostic (CADx) software for 
lesions suspicious for cancer 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 radiological 
CADx software for lesions suspicious for cancer'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, in part by reducing regulatory burdens.

DATES: This order is effective January 22, 2020. The classification was 
applicable on July 19, 2017.

FOR FURTHER INFORMATION CONTACT: Ryan Lubert, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3574, Silver Spring, MD, 20993-0002, 240-402-6357, 
ryan.lubert@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the CADx software for lesions 
suspicious for cancer 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 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

[[Page 3541]]

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 to a predicate device that does not require 
premarket approval (see 21 U.S.C. 360c(i)). We determine whether a new 
device is substantially equivalent to a predicate 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 established the first procedure for De Novo classification 
(Pub. L. 105-115). Section 607 of the Food and Drug Administration 
Safety and Innovation Act modified the De Novo application process by 
adding a second procedure (Pub. L. 112-144). 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 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 21 U.S.C. 360c(f)(2)(B)(i)). As a 
result, other device sponsors do not have to submit a De Novo request 
or premarket approval application in order to market a substantially 
equivalent device (see 21 U.S.C. 360c(i), defining ``substantial 
equivalence''). Instead, sponsors can use the 510(k) process, when 
necessary, to market their device.

II. De Novo Classification

    On April 7, 2017, Quantitative Insights Inc. submitted a request 
for De Novo classification of the QuantX. 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.
    Therefore, on July 19, 2017, 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 
892.2060.\1\ We have named the generic type of device radiological 
computer-assisted diagnostic (CADx) software for lesions suspicious for 
cancer, and it is identified as an image processing device intended to 
aid in the characterization of lesions as suspicious for cancer 
identified on acquired medical images such as magnetic resonance, 
mammography, radiography, or computed tomography. The device 
characterizes lesions based on features or information extracted from 
the images and provides information about the lesion(s) to the user. 
Diagnostic and patient management decisions are made by the clinical 
user.
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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--Radiological CADx Software for Lesions Suspicious for Cancer
                      Risks and Mitigation Measures
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            Identified risk                    Mitigation measures
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Incorrect lesion(s) characterization     Certain design verification and
 leading to false positive results may    validation activities
 result in incorrect patient management   identified in special control
 with possible adverse effects such as    (1) and Certain labeling
 unnecessary treatment, unnecessary       information identified in
 additional medical imaging and/or        special control (2).
 unnecessary additional diagnostic
 workup such as biopsy.
Incorrect lesion(s) characterization     Certain design verification and
 leading to false negative results may    validation activities
 lead to complications, including         identified in special control
 incorrect diagnosis and delay in         (1) and Certain labeling
 disease management.                      information identified in
                                          special control (2).
The device could be misused to analyze   Certain design verification and
 images from an unintended patient        validation activities
 population or on images acquired with    identified in special control
 incompatible imaging hardware or         (1) and Certain labeling
 incompatible image acquisition           information identified in
 parameters, leading to inappropriate     special control (2).
 diagnostic information being displayed
 to the user.

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Device failure could lead to the         Certain design verification and
 absence of results, delay of results     validation activities
 or incorrect results, which could        identified in special control
 likewise lead to inaccurate patient      (1) and Certain labeling
 assessment.                              information identified in
                                          special control (2).
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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. In order 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, radiological CADx software for 
lesions suspicious for cancer 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 the guidance document ``De Novo Classification 
Process (Evaluation of Automatic Class III Designation)'' have been 
approved under OMB control number 0910-0844; the collections of 
information in 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 part 820, regarding the 
quality system regulation, have been approved under OMB control number 
0910-0073; and the collections of information in parts 801 and 809, 
regarding labeling, have been approved under OMB control number 0910-
0485.

List of Subjects in 21 CFR Part 892

    Medical devices, Radiation protection, X-rays.

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

PART 892--RADIOLOGY DEVICES

0
1. The authority citation for part 892 continues to read as follows:

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


0
2. Add Sec.  892.2060 to subpart B to read as follows:


Sec.  892.2060  Radiological computer-assisted diagnostic software for 
lesions suspicious of cancer.

    (a) Identification. A radiological computer-assisted diagnostic 
software for lesions suspicious of cancer is an image processing 
prescription device intended to aid in the characterization of lesions 
as suspicious for cancer identified on acquired medical images such as 
magnetic resonance, mammography, radiography, or computed tomography. 
The device characterizes lesions based on features or information 
extracted from the images and provides information about the lesion(s) 
to the user. Diagnostic and patient management decisions are made by 
the clinical user.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Design verification and validation must include:
    (i) A detailed description of the image analysis algorithms 
including, but not limited to, a detailed description of the algorithm 
inputs and outputs, each major component or block, and algorithm 
limitations.
    (ii) A detailed description of pre-specified performance testing 
protocols and dataset(s) used to assess whether the device will improve 
reader performance as intended.
    (iii) Results from performance testing protocols that demonstrate 
that the device improves reader performance in the intended use 
population when used in accordance with the instructions for use. The 
performance assessment must be based on appropriate diagnostic accuracy 
measures (e.g., receiver operator characteristic plot, sensitivity, 
specificity, predictive value, and diagnostic likelihood ratio). The 
test dataset must contain sufficient numbers of cases from important 
cohorts (e.g., subsets defined by clinically relevant confounders, 
effect modifiers, concomitant diseases, and subsets defined by image 
acquisition characteristics) such that the performance estimates and 
confidence intervals of the device for these individual subsets can be 
characterized for the intended use population and imaging equipment.
    (iv) Standalone performance testing protocols and results of the 
device.
    (v) Appropriate software documentation (e.g., device hazard 
analysis; software requirements specification document; software design 
specification document; traceability analysis; and description of 
verification and validation activities including system level test 
protocol, pass/fail criteria, results, and cybersecurity).
    (2) Labeling must include:
    (i) A detailed description of the patient population for which the 
device is indicated for use.
    (ii) A detailed description of the intended reading protocol.
    (iii) A detailed description of the intended user and recommended 
user training.
    (iv) A detailed description of the device inputs and outputs.
    (v) A detailed description of compatible imaging hardware and 
imaging protocols.
    (vi) Warnings, precautions, and limitations, including situations 
in which the device may fail or may not operate at its expected 
performance level (e.g., poor image quality or for certain 
subpopulations), as applicable.

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    (vii) Detailed instructions for use.
    (viii) A detailed summary of the performance testing, including: 
Test methods, dataset characteristics, results, and a summary of sub-
analyses on case distributions stratified by relevant confounders 
(e.g., lesion and organ characteristics, disease stages, and imaging 
equipment).

    Dated: January 9, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-00497 Filed 1-21-20; 8:45 am]
 BILLING CODE 4164-01-P


