[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
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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)).
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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
[[Page 25604]]
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