[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,
[email protected].
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