[Federal Register Volume 85, Number 14 (Wednesday, January 22, 2020)]
[Rules and Regulations]
[Pages 3545-3548]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-00494]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 892

[Docket No. FDA-2018-N-1553]


Radiology Devices; Reclassification of Medical Image Analyzers

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
issuing a final order to reclassify medical image analyzers applied to 
mammography breast cancer, ultrasound breast lesions, radiograph lung 
nodules, and radiograph dental caries detection, postamendments class 
III devices (regulated under product code MYN), into class II (special 
controls), subject to premarket notification. These devices are 
intended to direct the clinician's attention to portions of an image 
that may reveal abnormalities during interpretation of patient 
radiology images by the clinician. FDA is also identifying the special 
controls that the Agency believes are necessary to provide a reasonable 
assurance of safety and effectiveness of the device type.

DATES: This order is effective February 21, 2020.

FOR FURTHER INFORMATION CONTACT: Robert Ochs, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3680, Silver Spring, MD 20993-0002, 301-796-6661, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended, 
establishes a comprehensive system for the regulation of medical 
devices intended for human use. Section 513 of the FD&C Act (21 U.S.C. 
360c) established three classes of devices, reflecting the regulatory 
controls needed to provide reasonable assurance of their safety and 
effectiveness. The three classes of devices are class I (general 
controls), class II (special controls), and class III (premarket 
approval).
    Devices that were not in commercial distribution prior to May 28, 
1976 (generally referred to as postamendments devices), are 
automatically classified by section 513(f)(1) of the FD&C Act into 
class III without any FDA rulemaking process. Those devices remain in 
class III and require premarket approval unless, and until, the device 
is reclassified into class I or II, or FDA issues an order finding the 
device to be substantially equivalent, in accordance with section 
513(i) of the FD&C Act, to a predicate device that does not require 
premarket approval. The Agency determines whether new devices are 
substantially equivalent to predicate devices by means of premarket 
notification procedures in section 510(k) of the FD&C Act (21 U.S.C. 
360(k)) and part 807 (21 CFR part 807).
    A postamendments device that has been initially classified in class 
III under section 513(f)(1) of the FD&C Act may be reclassified into 
class I or II under section 513(f)(3). Section 513(f)(3) of the FD&C 
Act provides that FDA acting by order can reclassify the device into 
class I or II on its own initiative, or in response to a petition from 
the manufacturer or importer of the device. To change the 
classification of the device, the proposed new class must have 
sufficient regulatory controls to provide a reasonable assurance of the 
safety and effectiveness of the device for its intended use.
    On June 4, 2018 (83 FR 25598), FDA published in the Federal 
Register a proposed order to reclassify the device type from class III 
to class II, subject to premarket notification. The comment period on 
the proposed order closed on August 3, 2018.

II. Comments on the Proposed Order

    In response to the June 4, 2018, proposed order (83 FR 25598), FDA 
received two comments including from

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a healthcare professional in the medical device industry and a 
professional society by the close of the comment period, each 
containing one or more comments on one or more issues. We describe and 
respond to the comments in this section of the document. The order of 
response to the commenters is purely for organizational purposes and 
does not signify the comment's value or importance nor the order in 
which comments were received.
    (Comment 1) One commenter supported the proposed reclassification 
and requested that the Agency provide examples to further clarify what 
devices may fall within the scope of the proposed reclassification 
action. The commenter offered three use cases as examples: (1) A 
concurrent-read software device that shows computer assisted or aided 
detection (CADe) marks (on the regions of interest) intended to draw 
the clinicians' attention during their standard review workflow, (2) a 
software device that provides quantitative measures of disease risk, 
and (3) a software device that suggests prioritization of the cases in 
a review list/worklist for a clinician's reading session.
    (Response 1) FDA agrees that providing examples as part of the 
preamble would provide further clarity in the scope of the 
reclassification order. FDA stated in Section II of the proposed order 
(83 FR 25598) that, if finalized, the reclassification would cover 
medical image analyzers including CADe devices for mammography breast 
cancer, ultrasound breast lesions, radiograph lung nodules, and 
radiograph dental caries detection that are assigned product code MYN. 
Therefore, if example number 1 from the commenter above provided is a 
CADe device intended for use in the clinical applications noted above, 
it likely falls within the scope of this reclassification order. FDA 
believes that examples number 2 and number 3 identified in Comment 1 
would not be appropriately classified as medical image analyzers or 
CADe devices. Therefore, these two examples are device types not 
covered by this reclassification. Specifically, FDA believes that 
example number 2 is likely a computer-aided diagnosis device, which FDA 
has classified separately under 21 CFR 892.2060 Radiological computer-
assisted diagnostic (CADx) software for lesions suspicious for cancer, 
and example number 3 is likely a computer-aided triage device, which 
FDA has classified separately under 21 CFR 892.2080, Radiological 
Computer Aided Triage and Notification Software.
    FDA believes that the identification language in Sec.  892.2070(a) 
(21 CFR 892.2070) of the classification regulation as described in the 
proposed order adequately identifies the types of devices that would be 
affected by this reclassification action and declines to further modify 
the identification language for medical image analyzers.
    (Comment 2) The commenter generally supported the proposed 
reclassification and proposed special controls but recommended the 
following additional special controls to ensure the safety and 
effectiveness of the devices:
     Collect postmarket data: The commenter recommends that FDA 
consider adding special controls that require the collection of 
postmarket data when necessary to ensure that the device performance is 
acceptable in clinical use and to allow for a comparison to premarket 
data submitted for 510(k) clearance.
     Employ periodic retraining: The commenter recommends that 
FDA consider adding special controls for periodic retraining of 
clinicians to ensure that they understand the use of the device 
according to device labeling and the appropriate reading protocol to 
follow.
     Implement quality assurance requirements: The commenter 
notes that there are no quality assurance requirements in the proposed 
special controls to assure the medical image analyzer does not fail or 
to ensure that it operates at its expected performance level. 
Accordingly, the commenter asks FDA to consider adding special controls 
for a well-defined device-specific quality assurance process.
    (Response 2) FDA disagrees with this comment. The Agency believes 
that the special controls, as identified in the proposed order, 
together with general controls, are sufficient to provide reasonable 
assurance of safety and effectiveness of medical image analyzers. FDA 
does not believe that a requirement for collecting postmarket data as a 
special control is necessary to provide reasonable assurance of the 
safety and effectiveness for medical image analyzers devices. FDA has 
nearly 20 years of experience regulating medical image analyzers as 
class III devices considered within the scope of this reclassification, 
and postmarket studies have not been required during this period. 
Additionally, there have not been signals observed during this time 
that would suggest postmarket studies were necessary. As stated in the 
proposed order, in the past 10 years, there have been no medical device 
reports related to these CADe devices. FDA has only classified one 
recall for these CADe devices due to distribution of the CADe device 
without prior premarket application approval. Further, FDA still 
maintains the authority to require manufacturers to conduct postmarket 
surveillance of class II devices under section 522 of the FD&C Act (21 
U.S.C. 360l) when certain conditions are met.
    FDA does not believe that an additional special control regarding 
user retraining is necessary to provide reasonable assurance of the 
safety and effectiveness of medical image analyzers. The Agency 
believes that it has identified the risk of misuse by a physician and 
that the measures described in this final order will be effective in 
mitigating this probable risk to health, mainly Sec.  892.2070(b)(2) 
that requires the labeling of these devices to include a detailed 
description of the intended user and user training that addresses 
appropriate reading protocols for the device.
    While FDA agrees that appropriate quality assurance (QA) approaches 
are helpful in ensuring that a medical image analyzer consistently 
operates at its expected performance level, FDA disagrees with the need 
to write specific QA requirements for the end-users into the special 
controls. FDA believes specifying end-user QA requirements may be 
redundant with the special controls already identified in this final 
order (see specifically Sec.  892.2070(b)(1) and (2)), in combination 
with general controls, including especially the Quality System (QS) 
Regulations under part 820 (21 CFR part 820). In addition, because many 
different approaches to address QA exist, coupled with the general and 
special controls requirements that are already applicable to this 
device type, FDA does not believe that defining specific QA 
requirements in the special controls is necessary to reasonably assure 
safety, and FDA believes manufacturers should consider the need for, 
and most appropriate methods, to evaluate potential changes in CADe 
performance over time. This information should address the general 
controls as well as special controls (see specifically Sec.  
892.2070(b)(2)), including providing user training, identifying 
compatible hardware, identifying limitations, and providing operating 
instructions.

III. The Final Order

    Based on the information discussed in the preamble to the proposed 
order (83 FR 25598, June 4, 2018), the comments received for the 
proposed order, prior panel discussions, and FDA's experiences over the 
years in reviewing

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these device types, FDA concludes that special controls, in conjunction 
with general controls, will provide reasonable assurance of the safety 
and effectiveness of medical image analyzers. FDA is adopting its 
findings under section 513(f)(3) of the FD&C Act, as published in the 
preamble to the proposed order (83 FR 25598). FDA is issuing this final 
order to reclassify medical image analyzers, including CADe devices, 
for mammography breast cancer, ultrasound breast lesions, radiograph 
lung nodules, and radiograph dental caries detection from class III to 
class II, and establishing special controls by revising 21 CFR part 
892.\1\ In this final order, the Agency has identified the special 
controls under section 513(a)(1)(B) of the FD&C Act that, together with 
general controls, provide reasonable assurance of the safety and 
effectiveness of these devices.
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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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    Section 510(m) of the FD&C Act provides that FDA may exempt a class 
II device from the premarket notification requirements under section 
510(k) of the FD&C Act, if FDA determines that premarket notification 
is not necessary to provide reasonable assurance of the safety and 
effectiveness of the device. FDA has determined that premarket 
notification is necessary to provide reasonable assurance of safety and 
effectiveness of medical image analyzers, and therefore, this device 
type is not exempt from premarket notification requirements. Persons 
who intend to market a new CADe device must obtain clearance of a 
premarket notification and demonstrate compliance with the special 
controls included in this final order, prior to marketing the device.
    The device is assigned the generic name medical image analyzer, and 
identified as a medical image analyzers, including CADe devices, for 
mammography breast cancer, ultrasound breast lesions, radiograph lung 
nodules, and radiograph dental caries detection, is a prescription 
device that is intended to identify, mark, highlight, or in any other 
manner direct the clinicians' attention to portions of a radiology 
image that may reveal abnormalities during interpretation of patient 
radiology images by the clinicians. This device incorporates pattern 
recognition and data analysis capabilities and operates on previously 
acquired medical images. This device is not intended to replace the 
review by a qualified radiologist and is not intended to be used for 
triage or to recommend diagnosis.
    Under this final order, the medical image analyzer is a 
prescription use only device under Sec.  801.109 (21 CFR 801.109). 
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 Sec.  801.109 are met (referring to 21 U.S.C. 352(f)(1)). 
Under 21 CFR 807.81, the device continues to be subject to 510(k) 
requirements.

IV. Codification of Orders

    Prior to the amendments in the Food and Drug Administration Safety 
and Innovation Act (FDASIA), section 513(e) of the FD&C Act provided 
for FDA to issue regulations to reclassify devices. Although section 
513(e) as amended requires FDA to issue final orders rather than 
regulations, it also provides for FDA to revoke previously issued 
regulations by order. FDA will continue to codify classifications and 
reclassifications in the Code of Federal Regulations (CFR). Changes 
resulting from final orders will appear in the CFR as changes to 
codified classification determinations or as newly codified orders. 
Therefore, under section 513(e)(1)(A)(i), as amended by FDASIA, in this 
final order, we are proposing to codify the classification of medical 
image analyzers, applied to CADe devices for mammography breast cancer, 
ultrasound breast lesions, radiograph lung nodules, and radiograph 
dental caries detection in the new Sec.  892.2070, under which medical 
image analyzers would be reclassified into class II.

V. 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.

VI. Paperwork Reduction Act of 1995

    This final order establishes special controls that refer to 
previously approved FDA collections. 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 807, subpart E have been approved 
under OMB control number 0910-0120; the collections of information in 
21 CFR part 801 have been approved under OMB control number 0910-0485; 
and the collections of information in part 820 have been approved under 
OMB control number 0910-0073.

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.


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0
2. Add Sec.  892.2070 to subpart B to read as follows:


Sec.  892.2070  Medical image analyzer.

    (a) Identification. Medical image analyzers, including computer-
assisted/aided detection (CADe) devices for mammography breast cancer, 
ultrasound breast lesions, radiograph lung nodules, and radiograph 
dental caries detection, is a prescription device that is intended to 
identify, mark, highlight, or in any other manner direct the 
clinicians' attention to portions of a radiology image that may reveal 
abnormalities during interpretation of patient radiology images by the 
clinicians. This device incorporates pattern recognition and data 
analysis capabilities and operates on previously acquired medical 
images. This device is not intended to replace the review by a 
qualified radiologist, and is not intended to be used for triage, or to 
recommend diagnosis.
    (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 a description of the algorithm inputs and outputs, each major 
component or block, and algorithm limitations.
    (ii) A detailed description of pre-specified performance testing 
methods and dataset(s) used to assess whether the device will improve 
reader performance as intended and to characterize the standalone 
device performance. Performance testing includes one or more standalone 
tests, side-by-side comparisons, or a reader study, as applicable.
    (iii) Results from performance testing 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 a sufficient number 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) Appropriate software documentation (e.g., device hazard 
analysis; software requirements specification document; software design 
specification document; traceability analysis; description of 
verification and validation activities including system level test 
protocol, pass/fail criteria, and results; and cybersecurity).
    (2) Labeling must include the following:
    (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 user training 
that addresses appropriate reading protocols for the device.
    (iv) A detailed description of the device inputs and outputs.
    (v) A detailed description of compatible imaging hardware and 
imaging protocols.
    (vi) Discussion of warnings, precautions, and limitations must 
include 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.
    (vii) Device operating instructions.
    (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, such 
as lesion and organ characteristics, disease stages, and imaging 
equipment.

    Dated: January 9, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-00494 Filed 1-21-20; 8:45 am]
 BILLING CODE 4164-01-P