Document ID: FDA-2018-N-1553-0001
Agency: fda
Document Type: Proposed Rule
Title: Radiology Devices; Reclassification of Medical Image Analyzers
Posted Date: 2018-06-04T04:00Z

[Federal Register Volume 83, Number 107 (Monday, June 4, 2018)]
[Proposed Rules]
[Pages 25598-25604]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-11880]

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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: Proposed order.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
issuing this proposed order to reclassify medical image analyzers 
applied to mammography breast cancer, ultrasound breast lesions, 
radiograph lung nodules, and radiograph dental caries detection as 
postamendments class III (premarket approval) devices (regulated under 
product code MYN), into class II (special controls), subject to 
premarket notification. FDA is also identifying the proposed special 
controls that the Agency believes are necessary to provide a reasonable 
assurance of safety and effectiveness of the device. These devices are 
intended to direct the clinician's attention to portions of an image 
that may reveal abnormalities during interpretation of patient's 
radiology images by the clinician. If finalized, this order will 
reclassify these types of devices from class III to class II and reduce 
regulatory burdens on industry as these types of devices will no longer 
be required to submit a premarket approval application (PMA) but can 
instead submit a less burdensome premarket notification (510(k)) before 
marketing their device.

[[Page 25599]]

DATES: Submit either electronic or written comments on the proposed 
order by August 3, 2018. Please see section X of this document for the 
proposed effective date when the new requirements apply and for the 
proposed effective date of a final order based on this proposed order.

ADDRESSES: You may submit comments as follows: Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before August 3, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of August 3, 2018. Comments received 
by mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are postmarked or the delivery service 
acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal Rulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2018-N-1553 for ``Radiology Devices; Reclassification of Medical 
Image Analyzers.'' Received comments will be placed in the docket and, 
except for those submitted as ``Confidential Submissions,'' publicly 
viewable at https://www.regulations.gov or at the Dockets Management 
Staff between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Robert Ochs, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 4312, Silver Spring, MD 20993-0002, 301-796-6661, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the 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 categories (classes) of devices, 
reflecting the regulatory controls needed to provide reasonable 
assurance of their safety and effectiveness. The three categories 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 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) of the FD&C Act. 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.
    Reevaluation of the data previously before the Agency is an 
appropriate basis for subsequent action where the reevaluation is made 
in light of newly available regulatory authority (see Bell v. Goddard, 
366 F.2d 177, 181 (7th Cir. 1966); Ethicon, Inc. v. FDA, 762 F. Supp. 
382, 388-391 (D.D.C. 1991)), or in light of changes in ``medical 
science'' (Upjohn v. Finch, 422 F.2d 944, 951 (6th Cir. 1970)). Whether 
data before the Agency are old or new, the ``new information'' to 
support reclassification

[[Page 25600]]

under 513(f)(3) must be ``valid scientific evidence'', as defined in 
section 513(a)(3) of the FD&C Act and 21 CFR 860.7(c)(2). (See, e.g., 
General Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens 
Mfrs. Assoc. v. FDA, 766 F.2d 592 (DC Cir.1985), cert. denied, 474 U.S. 
1062 (1986)). FDA relies upon ``valid scientific evidence'' in the 
classification process to determine the level of regulation for 
devices. To be considered in the reclassification process, the ``valid 
scientific evidence'' upon which the Agency relies must be publicly 
available. Publicly available information excludes trade secret and/or 
confidential commercial information, e.g., the contents of a pending 
PMA (see section 520(c) of the FD&C Act (21 U.S.C. 360j(c)).
    In accordance with section 513(f)(3) of the FD&C Act, the Agency is 
proposing to reclassify medical image analyzers applied to mammography 
breast cancer, ultrasound breast lesions, radiograph lung nodules, and 
radiograph dental caries detection from class III into class II on the 
basis that there is sufficient information to establish special 
controls, in addition to general controls, to provide reasonable 
assurance of the safety and effectiveness of the device.
    Section 510(m) of the FD&C Act provides that a class II device may 
be exempted from the 510(k) premarket notification requirements, if the 
Agency determines that premarket notification is not necessary to 
reasonably assure the safety and effectiveness of the device.

II. Regulatory History of the Devices

    This proposed order covers 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 that are assigned product code MYN. 
These postamendments devices are currently regulated as class III 
devices under section 513(f)(1) of the FD&C Act. FDA has experience 
reviewing and analyzing data and information for medical image 
analyzers since premarket approval of the first device for these uses 
in 1998. On June 26, 1998, the Center for Devices and Radiological 
Health (CDRH) approved the first CADe device included in this 
reclassification order. In the December 30, 1998, Federal Register 
notice (63 FR 71930), FDA announced a PMA approval order for R2 
Technology, Inc. M 1000 Image Checker and the availability of the 
summary of safety and effectiveness data for the device. Since 1998, 11 
devices have received premarket approval for the analysis of several 
modalities, including mammography, ultrasound, as well as chest and 
dental radiographs. Based upon our review experience and consistent 
with the FD&C Act and FDA's regulations, FDA believes that these 
devices should be reclassified from class III into class II because 
there is sufficient information to establish special controls that can 
provide reasonable assurance of the device's safety and effectiveness.
    This proposed order does not apply to medical image analyzers/CADe 
devices currently classified under Sec.  892.2050 (21 CFR 892.2050), 
Picture archiving and communication system. FDA has regulated other 
CADe devices intended to aid lung nodule and colon polyp detection from 
computed tomography images as class II devices under Sec.  892.2050, 
Picture archiving and communication system and assigned the following 
product codes:
     NWE (Colon Computed Tomography System, Computer-Aided 
Detection);
     OEB (Lung Computed Tomography System, Computer-Aided 
Detection);
     OMJ (Chest X-Ray Computer Aided Detection).
    There have been no recalls for class II CADe devices. As of the 
date of this proposal, FDA has received three recalls for class III 
devices and one Medical Device Report (MDR), however, in the past 10 
years only one recall for the class III devices has been received due 
to distribution of the CADe device without PMA approval. None of these 
recalls were classified as a Class I recall. There were also no MDRs 
related to either the class III medical image analyzers or class II 
CADe devices in the past 10 years. This evidence suggests that the 
safety profiles for existing class III CADe devices are similar to the 
class II CADe, and consequently that our regulatory controls applied 
should be similar.

III. Device Description

    This proposed order applies to medical image analyzers including 
CADe devices for mammography breast cancer, ultrasound breast lesions, 
radiograph lung nodules, and radiograph dental caries detection that 
are currently regulated as class III devices as postamendment devices. 
These devices are 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. These devices incorporate 
pattern recognition and data analysis capabilities and operate on 
previously acquired radiology images, including mammography, 
radiograph, and ultrasound. These devices are not intended to replace 
the review by a qualified radiologist or to be used for triage. 
Furthermore, these devices are not intended to recommend diagnosis of 
any diseases.

IV. Proposed Reclassification

    The Radiological Devices Panel (the Panel) convened on March 4-5, 
2008 (Ref. 1) and discussed issues relating to how medical image 
analyzers including CADe devices are used in clinical decisionmaking, 
how the performance of the devices should be evaluated, and the 
information needed to determine whether the device provides a 
reasonable assurance of its safety and effectiveness. Additional 
discussions were held regarding medical image analyzers for mammography 
and radiograph applications. Following the 2008 Panel Meeting, FDA 
convened a second meeting of the Panel on November 18, 2009. The 2009 
Panel Meeting was asked to discuss two proposed draft guidances for the 
evaluation of medical image analyzers and the Agency's regulatory 
strategy for these devices (Ref. 2). Subsequently, the two draft 
guidance documents were finalized by FDA and were made public on July 
3, 2012 (Refs. 3 and 4). The guidance document entitled ``Clinical 
Performance Assessment: Considerations for Computer-Assisted Detection 
Devices Applied to Radiology Images and Radiology Device Data--
Premarket Approval (PMA) and Premarket Notification [510(k)] 
Submissions'' provides guidance regarding clinical performance 
assessment studies for CADe applied to radiology images and radiology 
device data. The guidance document entitled ``Computer-Assisted 
Detection Devices Applied to Radiology Images and Radiology Device 
Data--Premarket Notification [510(k)] Submissions'' provides guidance 
regarding premarket notification (510(k)) submissions for CADe applied 
to radiology images and radiology device data. These guidance documents 
describe clinical and non-clinical methods to evaluate the safety and 
effectiveness of CADe devices, including medical image analyzers 
covered by this proposed order. In addition to the two guidance 
documents, the Panel's discussion regarding the benefits and risks of 
medical image analyzers that were discussed at the 2008 and 2009 Panel 
meetings have been taken into consideration by the Agency when 
developing the proposed special

[[Page 25601]]

controls provided in this proposed order below.
    Since publication of these guidance documents, the Agency has 
gained considerable experience in reviewing medical image analyzers 
using the methods described in the aforementioned guidance documents. 
Further, as part CDRH's 2014-2015 strategic priority ``Strike the Right 
Balance Between Premarket and Postmarket Data Collection,'' a 
retrospective review of class III devices subject to a PMA was 
completed to determine whether or not, based on our current 
understanding of the technology, reclassification may be appropriate. 
During this retrospective review, FDA determined that sufficient 
information exists such that the risks of false positive and false 
negative results, misuse, and device failure can be mitigated, to 
establish special controls that, together with general controls, can 
provide a reasonable assurance of the safety and effectiveness of 
medical image analyzers and therefore proposes these devices be 
reclassified from class III to class II. On April 29, 2015, FDA 
published a notice in the Federal Register entitled ``Retrospective 
Review of Premarket Approval Application Devices; Striking the Balance 
Between Premarket and Postmarket Data Collection'' in which FDA 
announced plans to consider reclassifying medical image analyzers 
identified with the MYN product code from class III to class II (80 FR 
23798). No adverse comments were received regarding our proposed intent 
for MYN.
    In accordance with section 513(f)(3) of the FD&C Act and 21 CFR 
part 860, subpart C, FDA is proposing to reclassify postamendments 
medical image analyzers, including CADe devices for mammography breast 
cancer, ultrasound breast lesions, radiograph lung nodules, and 
radiograph dental caries detection, from class III into class II. FDA 
believes that there is sufficient information to establish special 
controls, in addition to general controls, that would effectively 
mitigate the risks to health identified in section V and provide 
reasonable assurance of the safety and effectiveness of these devices. 
Absent the special controls identified in this proposed order, general 
controls applicable to the device are insufficient to provide 
reasonable assurance of the safety and effectiveness of the device.
    FDA is proposing to create a separate classification regulation for 
medical image analyzer devices that will be reclassified from class III 
to II. Under this proposed order, if finalized, the medical image 
analyzer devices will be identified as a prescription device. As such, 
the prescription device must satisfy prescription labeling requirements 
(see Sec.  801.109 (21 CFR 801.109), Prescription devices). 
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) and Sec.  801.5 (21 CFR 801.5), as long as the 
conditions of Sec.  801.109 are met. In this proposed order, if 
finalized, the Agency has identified the special controls under section 
513(a)(1)(B) of the FD&C Act that, together with general controls, will 
provide a reasonable assurance of the safety and effectiveness for 
medical image analyzer devices.
    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. For this type of device, FDA has 
determined that premarket notification is necessary to provide 
reasonable assurance of safety and effectiveness and, therefore, does 
not intend to exempt these proposed class II devices from the premarket 
notification requirements. Persons who intend to market this type of 
device must submit to FDA a 510(k) and receive clearance prior to 
marketing the device.
    This proposal, if finalized, will decrease regulatory burden on the 
medical device industry and will reduce private costs and expenditures 
required to comply with Federal Regulations. Specifically, regulated 
industry will no longer have to submit a PMA but can instead submit a 
510(k) to the Agency for review prior to marketing their device. A 
510(k) is a less-burdensome pathway to market a device which typically 
results in a more timely premarket review compared to a PMA and reduces 
the regulatory burden on industry in addition to providing more timely 
access of these types of devices to patients.

V. Risks to Health

    From the Panel discussions on March 4-5, 2008, and November 18, 
2009, along with the peer-reviewed literature (Refs. 5-8) and FDA's 
experiences over the years in reviewing submissions for these devices 
and similar devices, FDA determined the probable risks to health 
associated with medical image analyzers including CADe devices for 
mammography breast cancer, ultrasound breast lesions, radiograph lung 
nodules, and radiograph dental caries detection are as follows: (1) 
False positive results may result in complications, such as incorrect 
management of the patient with possible adverse effects, and 
unnecessary additional radiology imaging and/or invasive procedures, 
such as biopsy; (2) false negative results could result in 
complications, including incorrect diagnosis and delay in disease 
management; (3) the device could be misused to analyze images from an 
unintended patient population or on images acquired with incompatible 
imaging hardware or incompatible image acquisition parameters, 
resulting in possibly lower device performance; (4) the device could be 
misused by not following the appropriate reading protocol, which may 
lead to lower sensitivity; and (5) device failure could result in the 
absence or delay of device output, or incorrect device output, which 
could likewise lead to inaccurate patient assessment.

VI. Summary of the Reasons for Reclassification

    After considering the information above, FDA has determined that 
all class III medical image analyzers currently approved by FDA should 
be reclassified into class II on the basis that special controls, in 
addition to general controls, can be established to provide reasonable 
assurance of the safety and effectiveness of the device. FDA believes 
that the risks to health associated with medical image analyzers 
applied to mammography breast cancer, ultrasound breast lesions, 
radiograph lung nodules, and radiograph dental caries detection can be 
mitigated with special controls and that these mitigations will provide 
a reasonable assurance of its safety and effectiveness. FDA's reasons 
for reclassification of these devices are as follows:
     The risk of false positive results and false negative 
results can be mitigated by demonstrating, through clinical performance 
assessment (e.g., reader studies), that reader performance improves 
when using the medical image analyzer. In instances where a medical 
image analyzer has the same intended use but has different 
technological characteristics compared to the legally marketed device 
(predicate), a performance comparison of the predicate and new device 
evaluating with the same assessment process on the same dataset that is 
representative of the intended population may be sufficient to 
demonstrate device safety and effectiveness. The risk of false positive 
results and false negative results can be further mitigated by special 
controls that require sufficient information in labeling to provide

[[Page 25602]]

detailed instructions for use to the user and inform the user of the 
expected device performance on a dataset representative of the intended 
population.
     The risk associated with misuse of the medical image 
analyzers on an unintended population can be mitigated by specifying in 
the labeling and indications for use of the device the intended patient 
population for which the device has been demonstrated to be effective. 
This risk can be further mitigated by special controls that require 
informing intended users in the labeling of foreseeable situations in 
which the device is likely to fail or not to operate at its expected 
performance level.
     The risk associated with misuse of the medical image 
analyzer on images acquired from unintended image acquisition hardware 
or image acquisition parameters can be mitigated by special controls 
that require including in the device labeling specifications for 
compatible imaging hardware and imaging protocols.
     The risk resulting from not following the intended reading 
protocol can be mitigated by including in the labeling the indications 
for use of the device, by providing adequate instructions for use 
including a description of the intended reading protocol, and by 
special controls requiring that the device labeling provide a detailed 
description of user training that addresses appropriate reading 
protocols for the device.
     The risk of device failure can be mitigated by requiring 
design verification and validation testing, and special controls that 
require device operating instructions. This risk can be further 
mitigated by special controls that require informing users in the 
labeling of foreseeable situations in which the device is likely to 
fail or not to operate at its expected performance level.

VII. Proposed Special Controls

    FDA believes that the following special controls, in addition to 
general controls, are sufficient to mitigate the risks to health 
described in section V and provide a reasonable assurance of safety and 
effectiveness for these medical image analyzers:
     Design verification and validation must include detailed 
descriptions of image analysis algorithms, detailed descriptions of 
study protocols and datasets, results from performance testing 
demonstrating the device improves reader performance in the intended 
use population, standalone performance testing protocols and results, 
and appropriate software documentation. Performance testing ensures 
that the risk of false positive and false negative results is reduced.
     Labeling for the device must include detailed descriptions 
of the following: patient population, the intended reading protocol, 
the intended user and user training, device inputs and outputs, 
compatible imaging hardware and imaging protocols. In addition, the 
labeling for the device must also include applicable warnings, 
limitations, precautions, device operating instructions, and a detailed 
summary of the performance testing. Detailed instructions for use and 
expected device performance on a dataset representative of the intended 
population in labeling helps minimize the risk of false positive and 
false negative results. Labeling ensures proper use of the device, 
including warnings to inform users of foreseeable situations in which 
the device is likely to fail or not to operate at its expected 
performance level.
    Table 1 shows how FDA believes the special controls set forth in 
the proposed order will mitigate each of the risks to health described 
in section V.

   Table 1--Risks to Health and Mitigation Measures for Medical Image
                                Analyzers
------------------------------------------------------------------------
                                             Mitigation measures/21 CFR
         Identified risk to health                     section
------------------------------------------------------------------------
False positive results....................  Special controls 1 (21 CFR
                                             892.2070(b)(1)) and 2 (21
                                             CFR 892.2070(b)(2)).
False negative results....................  Special controls 1 (21 CFR
                                             892.2070(b)(1)) and 2 (21
                                             CFR 892.2070(b)(2)).
Device misuse (analyzing images from an     Special control 2 (21 CFR
 unintended patient population, images       892.2070(b)(2)).
 acquired with incompatible imaging
 hardware, or incompatible image
 acquisition parameters) resulting in
 possibly lower device performance.
Device misuse (not following the            Special control 2 (21 CFR
 appropriate reading protocol) which may     892.2070(b)(2)).
 lead to lower sensitivity.
Device failure............................  Special control 2 (21 CFR
                                             892.2070(b)(2)).
------------------------------------------------------------------------

    In addition, FDA is proposing to limit these devices to 
prescription use under Sec.  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 and Sec.  801.5, as long as the 
conditions of Sec.  801.109 are met (referring to 21 U.S.C. 352(f)(1)). 
Under Sec.  807.81, the device would continue to be subject to 510(k) 
notification requirements.
    If this proposed order is finalized, medical image analyzers 
including CADe devices for mammography breast cancer, ultrasound breast 
lesions, radiograph lung nodules, and radiograph dental caries 
detection will be reclassified into class II. The reclassification will 
be codified in Sec.  892.2070. FDA believes that adherence to the 
proposed special controls, in addition to the general controls, is 
necessary to provide a reasonable assurance of the safety and 
effectiveness of the devices. FDA intends to update the guidance 
document entitled ``Clinical Performance Assessment: Considerations for 
Computer-Assisted Detection Devices Applied to Radiology Images and 
Radiology Device Data--Premarket Approval (PMA) and Premarket 
Notification [510(k)] Submissions'' to make it consistent with this 
reclassification upon finalization of this proposed reclassification 
order.

VIII. 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.

IX. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed order contains no new 
collections of information. Therefore, clearance by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(PRA) (44 U.S.C. 3501-3520) is not required. This

[[Page 25603]]

proposed order refers to previously approved collections of information 
found in other FDA regulations. These collections of information are 
subject to review by OMB under the PRA. The collections of information 
in 21 CFR part 807, subpart E have been approved under OMB control 
number 0910-0120 and the collections of information in 21 CFR part 801 
have been approved under OMB control number 0910-0485.

X. Proposed Effective Date

    FDA proposes that any final order based on this proposed order 
become effective 30 days after its date of publication in the Federal 
Register.

XI. References

    The following references are on display in the Dockets Management 
Staff (see ADDRESSES) and are available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also 
available electronically at https://www.regulations.gov. FDA has 
verified the website addresses, as of the date this document publishes 
in the Federal Register, but websites are subject to change over time.

1. Transcript of the FDA Radiological Devices Panel Meeting, March 
4-5, 2008 (available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfAdvisory/results.cfm?panel=24&searchtype=1&month=0&year=&maxrows=10).
2. Transcript of the FDA Radiological Devices Panel Meeting, 
November 18, 2009 (available at: https://wayback.archive-it.org/7993/20170404002254/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/RadiologicalDevicesPanel/UCM197419.pdf).
3. ``Guidance for Industry and Food and Drug Administration Staff--
Computer-Assisted Detection Devices Applied to Radiology Images and 
Radiology Device Data--Premarket Notification [510(k)] 
Submissions,'' issued July 3, 2012 (https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/cm187294.pdf).
4. ``Guidance for Industry and FDA Staff--Clinical Performance 
Assessment: Considerations for Computer-Assisted Detection Devices 
Applied to Radiology Images and Radiology Device Data--Premarket 
Approval (PMA) and Premarket Notification [510(k)] Submissions,'' 
issued July 3, 2012 (https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm187315.pdf).
5. Dromain, C., B. Boyer, R. Ferr[eacute], et al., ``Computed-Aided 
Diagnosis (CAD) in the Detection of Breast Cancer,'' European 
Journal of Radiology, 82(3): 417-423 (2013).
6. Fenton, J.J., G. Xing, J.G. Elmore, et al., ``Short-Term Outcomes 
of Screening Mammography Using Computer-Aided Detection: A 
Population-Based Study of Medicare Enrollees,'' Annals of Internal 
Medicine, 158: 580-587 (2013).
7. Gur, D., J.H. Sumkin, H.E. Rockette, et al., ``Changes in Breast 
Cancer Detection and Mammography Recall Rates After the Introduction 
of a Computer-Aided Detection System,'' Journal of the National 
Cancer Institute, 96: 185-190 (2004).
8. Noble M., W. Bruening, S. Uhl, and K. Schoelles, ``Computer-Aided 
Detection Mammography for Breast Cancer Screening: Systematic Review 
and Meta-Analysis,'' Archives of Gynecology and Obstetrics, 279(6): 
881-90 (2009).

List of Subjects in 21 CFR Part 892

    Radiology devices.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 892 be 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.  892.2070 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

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confounders, such as lesion and organ characteristics, disease stages, 
and imaging equipment.

    Dated: May 29, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-11880 Filed 6-1-18; 8:45 am]
 BILLING CODE 4164-01-P