[Federal Register Volume 87, Number 125 (Thursday, June 30, 2022)]
[Proposed Rules]
[Pages 39025-39033]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-13954]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 878
[Docket No. FDA-2022-N-0794]
General and Plastic Surgery Devices; Reclassification of Optical
Diagnostic Devices for Melanoma Detection and Electrical Impedance
Spectrometers, To Be Renamed Computer-Aided Devices Which Provide
Adjunctive Diagnostic Information About Lesions Suspicious for Melanoma
AGENCY: Food and Drug Administration, Health and Human Services (HHS).
ACTION: Proposed amendment; proposed order; request for comments.
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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
proposing on its own initiative to reclassify optical diagnostic
devices for melanoma detection and electrical impedance spectrometers,
both of which are postamendments class III devices (product codes OYD
and ONV, respectively), into class II (special controls), subject to
premarket notification. FDA is also proposing a new device
classification regulation with the name ``computer-aided devices which
provide adjunctive diagnostic information about lesions suspicious for
melanoma,'' along with special controls that the Agency believes are
necessary to provide a reasonable assurance of safety and effectiveness
for these devices. If finalized, this order will reclassify these
devices from class III to class II and the submission of a premarket
approval application (PMA) for these devices will no longer be
required, and instead the submission of a premarket notification
(510(k)) will be required.
DATES: Submit either electronic or written comments on the proposed
order by August 29, 2022. 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. The https://www.regulations.gov electronic filing system will accept comments until
midnight Eastern Time at the end of August 29, 2022. 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-2022-N-0794 for ``General and Plastic Surgery Devices;
Reclassification of Optical Diagnostic Devices for Melanoma Detection
and Electrical Impedance Spectrometers, To Be Renamed Computer-Aided
Devices Which Provide Adjunctive Diagnostic Information about Lesions
Suspicious for Melanoma.'' Received comments, those filed in a timely
manner (see ADDRESSES), 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 Eastern Time, 240-402-7500.
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
[[Page 39026]]
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.govinfo.gov/content/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, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Neil Ogden, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 4612, Silver Spring, MD 20993, 301-796-6397,
[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).
Section 513(a)(1) of the FD&C Act defines the three classes of
devices. Class I devices are those devices for which the general
controls of the FD&C Act (controls authorized by or under section 501,
502, 510, 516, 518, 519, or 520 (21 U.S.C. 351, 352, 360, 360f, 360h,
360i, or 360j) or any combination of such sections) are sufficient to
provide reasonable assurance of safety and effectiveness; or those
devices for which insufficient information exists to determine that
general controls are sufficient to provide reasonable assurance of
safety and effectiveness or to establish special controls to provide
such assurance, but because the devices are not purported or
represented to be for a use in supporting or sustaining human life or
for a use which is of substantial importance in preventing impairment
of human health, and do not present a potential unreasonable risk of
illness or injury, are to be regulated by general controls (section
513(a)(1)(A) of the FD&C Act). Class II devices are those devices for
which general controls by themselves are insufficient to provide
reasonable assurance of safety and effectiveness, and for which there
is sufficient information to establish special controls to provide such
assurance, including the issue of performance standards, postmarket
surveillance, patient registries, development and dissemination of
guidelines, recommendations, and other appropriate actions the Agency
deems necessary to provide such assurance (section 513(a)(1)(B) of the
FD&C Act). Class III devices are those devices for which insufficient
information exists to determine that general controls and special
controls would provide a reasonable assurance of safety and
effectiveness, and are purported or represented to be for a use in
supporting or sustaining human life or for a use which is of
substantial importance in preventing impairment of human health, or
present a potential unreasonable risk of illness or injury (section
513(a)(1)(C) of the FD&C Act).
Devices that were not in commercial distribution before 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: (1) FDA
reclassifies the device into class I or II or (2) 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 the
premarket notification procedures in section 510(k) of the FD&C Act (21
U.S.C. 360(k)) and part 807, subpart E, of FDA's regulations (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 class 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 administrative
order, can reclassify the device into class I or class 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
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 Co. v. Finch, 422 F.2d 944, 951 (6th Cir. 1970)).
Whether data before the Agency are old or new, the information to
support reclassification 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 (D.C. Cir.1985)).
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))). Section
520(h)(4) of the FD&C Act provides that FDA may use, for
reclassification of a device, certain information in a PMA 6 years
after the application has been approved.
In accordance with section 513(f)(3) of the FD&C Act, FDA is
issuing this proposed order to reclassify optical diagnostic devices
for melanoma detection and electrical impedance spectrometers, both of
which are postamendments class III devices, into class II (special
controls) subject to premarket notification, under a new device
classification regulation with the name ``computer-aided devices which
provide adjunctive diagnostic information about lesions suspicious for
melanoma.'' FDA believes the standard in section 513(a)(1)(B) of the
FD&C Act is met as there is sufficient information to establish special
controls, which, in addition to general controls, would provide
reasonable assurance of the safety and effectiveness of these
devices.\1\
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\1\ FDA notes that the ACTION caption for this final order is
styled as ``Proposed amendment; proposed order,'' rather than
``Proposed 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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[[Page 39027]]
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 a reasonable assurance of the
safety and effectiveness of computer-aided devices which provide
adjunctive diagnostic information about lesions suspicious for melanoma
and, therefore, the Agency does not intend to exempt this proposed
class II device from the requirement for premarket notification
(510(k)) submission as provided under section 510(m) of the FD&C Act.
II. Regulatory History of the Devices
Under section 513(f)(1) of the FD&C Act, optical diagnostic devices
for melanoma detection and electrical impedance spectrometers are
automatically classified into class III because they were not
introduced or delivered for introduction into interstate commerce for
commercial distribution before May 28, 1976, and have not been found
substantially equivalent to a device placed in commercial distribution
after May 28, 1976, which was subsequently classified or reclassified
into class II or class I. Therefore, they are subject to PMA
requirements under section 515 of the FD&C Act (21 U.S.C. 360e).
On November 1, 2011, FDA approved a PMA for MELAFIND, the first
optical diagnostic device for melanoma detection to obtain FDA
premarket authorization (Refs. 1-5). MELAFIND is intended for use on
clinically atypical cutaneous pigmented lesions with one or more
clinical or historical characteristics of melanoma, excluding those
with a clinical diagnosis of melanoma or likely melanoma. FDA filed the
PMA for MELAFIND (P090012) from MELA Sciences, Inc. on June 9, 2009. At
a meeting on November 18, 2010, the FDA General and Plastic Surgery
Devices Panel (the ``Panel'') reviewed the MELAFIND PMA (Ref. 6). Among
other things, the Panel raised concerns regarding the potential use of
MELAFIND by non-dermatologists and untrained operators, and regarding
the risk that negative MELAFIND readings could lead to false negative
diagnoses (e.g., where no referral forward or biopsy is done based on a
negative MELAFIND finding) (Ref. 7). By a vote of eight to seven (with
one Panel member abstaining), the Panel voted that the benefits of the
device for the proposed indications outweighed its risks for the
proposed indications.
FDA subsequently approved the device for use by dermatologists
choosing to obtain additional information for a decision to biopsy (and
not for confirming a clinical diagnosis of melanoma), and for use only
on certain types of lesions--for example, lesions with a diameter
between 2 mm and 22 mm, that are accessible by the MELAFIND imager, and
that are sufficiently pigmented, among other things (Ref. 8). FDA also
imposed certain labeling requirements on the device, including a
requirement that the labeling specify that device is for use only by
physicians trained in the clinical diagnosis and management of skin
cancer (i.e., dermatologists) who have also successfully completed a
training program in the appropriate use of the device. FDA required
that the sponsor conduct a post-approval study. The study was
terminated in 2016 when additional data were provided in support of the
safety and effectiveness of the device.
On June 28, 2017, FDA approved a PMA for NEVISENSE, the first
electrical impedance spectrometer to obtain FDA premarket
authorization. NEVISENSE is indicated for use on cutaneous lesions with
one or more clinical or historical characteristics of melanoma, when a
dermatologist chooses to obtain additional information when considering
biopsy. It is not for use on clinically obvious melanoma and is to be
used as one element of the overall clinical assessment.
As of the date of issuance of this proposed order, fewer than 6
years have transpired since FDA's approval of PMA Supplement 11 for
MELAFIND (P090012 S11) and the PMA and PMA supplements for NEVISENSE
(PMA P150046 and P150046 S1-S4). Therefore, no information from these
documents has been used in support of this proposed order to reclassify
optical diagnostic devices for melanoma detection and electrical
impedance spectrometers into class II (see section 520(h)(4) of the
FD&C Act (21 U.S.C. 360j(h)(4))).
As of the date of issuance of this proposed order, there has been a
single recall involving the MELAFIND device, and no recalls involving
the NEVISENSE device. The MELAFIND recall was initiated by the firm in
April 2015 due to the display of probability and histogram data on the
device's user interface that was not covered by the device's approval.
This recall was classified as class II and was terminated in May 2016.
FDA has received no Medical Device Reports (MDRs) associated with
optical diagnostic devices for melanoma detection or electrical
impedance spectrometers.
As of the date of issuance of this proposed order, no other optical
diagnostic devices for melanoma detection or electrical impedance
spectrometers have been approved by FDA.
III. Device Description
Optical diagnostic devices for melanoma detection and electrical
impedance spectrometers are postamendments devices classified into
class III under section 513(f)(1) of the FD&C Act. An optical
diagnostic device for melanoma detection is a prescription device for
use in the detection of melanoma and high-grade lesions among atypical
lesions in order to rule out melanoma, through the use of visible and
infrared optical radiation to generate images of targeted atypical
lesions. The device is a multispectral, non-invasive, and automated
(objective) computer-vision system that classifies the image of a
pigmented skin lesion based upon the degree of 3-dimensional
morphological disorganization. It is intended for use on clinically
atypical cutaneous pigmented lesions with one or more clinical or
historical characteristics of melanoma, excluding those with a clinical
diagnosis of melanoma or likely melanoma.
An electrical impedance spectrometer is a prescription device used
on cutaneous lesions with one or more clinical or historical
characteristics of melanoma, when a dermatologist chooses to obtain
additional information when considering biopsy. The device consists of
a control unit and a disposable electrode, which is used to measure
electrical impedance of skin lesions and provide an output called the
electrical impedance spectroscopy score. An electrical impedance
spectrometer is not for use on clinically obvious melanoma, and is to
be used as one element of the overall clinical assessment. The output
given by the device is to be used in combination with clinical and
historical signs of melanoma to obtain additional information prior to
a decision to biopsy.
FDA proposes to revise 21 CFR part 878 to create a new device
classification regulation with the name ``computer-
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aided devices which provide adjunctive diagnostic information about
lesions suspicious for melanoma.'' A computer-aided device which
provides adjunctive diagnostic information about lesions suspicious for
melanoma is a device that is used to aid in the decision-making process
for melanoma detection. The device is intended for prescription use by
a physician trained in the clinical diagnosis and management of skin
cancer (e.g., a dermatologist) on skin lesions with one or more
clinical or historical characteristics of melanoma, and is based on a
computer algorithm to analyze optical or other physical properties of a
skin lesion. The algorithm returns a classification of the skin lesion
regarding melanoma when a physician trained in the clinical diagnosis
and management of skin cancer chooses to obtain additional information
when considering biopsy. The device is not for use as a stand-alone
diagnostic. Optical diagnostic devices for melanoma detection and
electrical impedance spectrometers are both examples of computer-aided
devices which provide adjunctive diagnostic information about lesions
suspicious for melanoma. FDA believes that computer-aided devices which
provide adjunctive diagnostic information about lesions suspicious for
melanoma can facilitate more accurate triaging and management of those
lesions. The devices can provide physicians trained in the clinical
diagnosis and management of skin cancer an additional source of
adjunctive information when triaging patient care for melanoma.
IV. Proposed Reclassification and Summary of Reasons for
Reclassification
In accordance with section 513(f)(3) of the FD&C Act and 21 CFR
part 860, subpart C, FDA is proposing to reclassify optical diagnostic
devices for melanoma detection and electrical impedance spectrometers
from class III into class II, subject to premarket notification
(510(k)) requirements. FDA believes that there is sufficient
information to establish special controls, and that these special
controls, together with general controls, are necessary to provide a
reasonable assurance of the safety and effectiveness of optical
diagnostic devices for melanoma detection and electrical impedance
spectrometers, to be renamed computer-aided devices which provide
adjunctive diagnostic information about lesions suspicious for
melanoma. Optical diagnostic devices for melanoma detection and
electrical impedance spectrometers are prescription devices, and under
this proposed order, if finalized, computer-aided devices which provide
adjunctive diagnostic information about lesions suspicious for melanoma
will be prescription devices. As such, the devices 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(f)(1)) and 21 CFR
801.5, as long as the conditions of Sec. 801.109 are met.
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 computer-aided devices which provide
adjunctive diagnostic information about lesions suspicious for
melanoma, FDA has determined that premarket notification is necessary
to provide a reasonable assurance of the safety and effectiveness of
these devices. Therefore, the Agency does not intend to exempt these
proposed class II devices from 510(k) requirements. If this proposed
order is finalized, persons who intend to market a computer-aided
device which provides adjunctive diagnostic information about lesions
suspicious for melanoma will need to submit to FDA a 510(k) and receive
clearance prior to marketing the device.
FDA believes that there is sufficient information available to FDA
through the MELAFIND PMA and associated Panel considerations of that
PMA,\2\ published peer-reviewed literature, and FDA's publicly
available MDR database, Manufacturer and User Facility Device
Experience (MAUDE) database, and Medical Device Recall database to
establish special controls that effectively mitigate the risks to
health identified in section V. 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.
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\2\ In accordance with section 520(h)(4) of the FD&C Act, FDA
has not relied on information in PMAs and PMA supplements approved
within the last 6 years to develop proposed special controls or to
otherwise inform the proposed reclassification.
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V. Public Health Benefits and Risks to Health
FDA is providing a substantive summary of the valid scientific
evidence concerning the public health benefits of the use of computer-
aided devices which provide adjunctive diagnostic information about
lesions suspicious for melanoma, and the nature (and if known, the
incidence) of the risks of the devices (see further discussion of the
special controls being proposed to mitigate these risks in section VII
of this proposed order). FDA reviewed data in the PMA for MELAFIND
(P090012) available to FDA under section 520(h)(4) of the FD&C Act,
input from the 2010 Panel on P090012, published peer-reviewed
literature, and postmarket information regarding computer-aided devices
which provide adjunctive diagnostic information about lesions
suspicious for melanoma.
Computer-aided devices which provide adjunctive diagnostic
information about lesions suspicious for melanoma provide a benefit to
the public health by facilitating more accurate triaging and management
of those lesions. The devices can provide physicians trained in the
clinical diagnosis and management of skin cancer an additional source
of adjunctive information when triaging patient care for melanoma.
FDA has identified the following risks to health associated with
the use of computer-aided devices which provide adjunctive diagnostic
information about lesions suspicious for melanoma:
False negative or false positive results--False negative
results could result in complications such as incorrect or delayed
diagnoses and delays in biopsy decisions and melanoma treatment, which
may allow an undetected condition to worsen and potentially increase
morbidity and mortality. False positive results may result in
complications such as incorrect management of the patient, including
unnecessary additional invasive biopsy procedures and more frequent
screenings, as well as the potential administration of inappropriate
treatments and/or the withholding of appropriate treatments, with
possible adverse effects.
Use error/improper device use--The device could be misused
to analyze images from an unintended patient population, an unintended
anatomical site, or lesions having an unintended attribute, or to
analyze images acquired with incompatible imaging hardware or
incompatible image acquisition parameters, potentially resulting in the
device not operating at its expected performance level. The device
could also be misused if the user does not follow the appropriate
reading protocol for using the device to assess lesions of interest,
which may lead to lower accuracy. Inaccurate results may result in the
same complications associated
[[Page 39029]]
with false negative or false positive results as discussed above.
Device failure/malfunction--Device failure or malfunction
could result in the absence or delay of device output, or incorrect
device output, which could lead to inaccurate patient assessment.
Inaccurate results may result in the same complications associated with
false negative or false positive results as discussed above.
Electrical, thermal, mechanical, or light-related injury--
While in operation, the device may discharge electricity that could
shock the user or patient. Electrical discharge or exposure to device-
generated heat may cause thermal injury or discomfort. Moving parts may
cause mechanical injury. For devices that utilize energy (e.g., light)
to provide adjunctive diagnostic information, accidental eye exposure
to the energy source could cause eye injury.
Interference with other devices--Individuals with
electrically powered implants could experience an adverse interaction
with the device due to electromagnetic interference or radiofrequency
interference.
Adverse tissue reaction--A patient could experience skin
irritation and/or allergic reaction associated with the use and
operation of the device via the use of non-biocompatible materials in
patient-contacting devices.
Infection/cross contamination--If components of the device
that must be sterile are not adequately sterilized or if reusable
components are not adequately reprocessed between uses, the device may
introduce pathogenic organisms to patients and cause an infection.
VI. Summary of Data Upon Which the Reclassification Is Based
FDA has considered and analyzed the following information: (1) data
in PMA P090012, (2) input from the 2010 Panel on P090012, (3) published
peer-reviewed literature, and (4) FDA's publicly available MDR, MAUDE,
and Medical Device Recall databases. The available evidence
demonstrates that there are public health benefits derived from the use
of computer-aided devices which provide adjunctive diagnostic
information about lesions suspicious for melanoma. In addition, the
nature of the associated risks to health are known, and special
controls can be established to sufficiently mitigate these risks.
FDA is proposing a single generic device type for computer-aided
devices which provide adjunctive diagnostic information about lesions
suspicious for melanoma. Although the different modalities included in
this proposed order have different technological characteristics in
certain respects (e.g., the use of visible and infrared optical
radiation vs. the use of an electrode to measure electrical impedance),
FDA believes that these devices have sufficiently similar purposes,
designs, functions, and other features related to safety and
effectiveness such that the same regulatory controls are necessary and
sufficient to provide reasonable assurance of safety and effectiveness.
FDA believes that a single generic device type is therefore appropriate
for these devices.
On June 9, 2009, FDA filed a PMA (P090012) from MELA Sciences, Inc.
for the MELAFIND, an optical diagnostic device for melanoma detection.
This device is to be used by physicians trained in the clinical
diagnosis and management of skin cancer (i.e., dermatologists) and
further trained in the appropriate use of the device, for use on
clinically atypical cutaneous pigmented lesions with one or more
clinical or historical characteristics of melanoma, excluding those
with a clinical diagnosis of melanoma or likely melanoma. It is
intended to provide adjunctive information to a dermatologist
considering biopsy of a suspicious lesion and is not intended to be
used to confirm a clinical diagnosis of melanoma. Data provided in the
PMA supported that there is a reasonable assurance of safety and
effectiveness of this device when used as indicated above. These data
included the results of a pivotal clinical trial of MELAFIND, which met
its primary safety and effectiveness endpoints by achieving at least 95
percent sensitivity at a 95 percent confidence level to malignant
melanoma among lesions with dermatological diagnoses of ``Melanoma
cannot be ruled out'' or ``Not melanoma'' (the sensitivity achieved in
the study was 98.3 percent), and by achieving a superior pooled
specificity (10.6 percent) compared to the study dermatologists (5.5
percent) for lesions that were not malignant, among lesions with
dermatological diagnoses of ``Melanoma cannot be ruled out'' or ``Not
melanoma.'' Additionally, no direct adverse events (AEs) \3\ were
reported for the patients enrolled in the MELAFIND pivotal study.
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\3\ In this trial, direct adverse events included device-related
adverse events, and did not include false negative results that may
lead to delays in the timely diagnosis of melanoma cancer and
treatment.
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At an advisory committee meeting held on November 18, 2010, the
Panel discussed the MELAFIND PMA. The Panel raised concerns regarding,
among other things, the use of the MELAFIND device by non-
dermatologists, and regarding the use of the device by untrained
operators. The Panel, as well as the PMA, also identified false
negatives as a potential risk that could result in delayed care, which
would be a significant safety concern if unmitigated. When FDA
subsequently approved the device, the approval was limited to use as an
adjunct to physician decision making and by physicians trained in the
clinical diagnosis and management of skin cancer (i.e., dermatologists)
who have also successfully completed a training program for the device.
Notably, lesions that were clinically suspicious for melanoma would not
be evaluated by MELAFIND, and a MELAFIND negative reading would be only
part of the assessment for a clinical decision to biopsy, and would not
replace clinical judgement (Ref. 1).
FDA also performed a literature search to evaluate data related to
optical diagnostic devices for melanoma detection and electrical
impedance spectrometers. Published data were found in the literature
relevant to optical diagnostic devices for melanoma detection and
electrical impedance spectrometers.
The clinical performance of an electrical impedance spectrometer
was assessed in a multicenter, prospective, blinded clinical trial
published in 2014 (Ref. 9). This study focused on the safety and
effectiveness of the device for distinguishing benign skin lesions from
melanoma. Eligible skin lesions in the study were examined with the
device, photographed, excised, and subjected to histopathological
evaluation. One thousand, nine hundred and fifty one patients with 2416
lesions were enrolled; 1943 lesions were eligible and evaluable for the
primary efficacy end point,\4\ including 265 melanomas. The sensitivity
of the device was measured to be 96.6 percent with a specificity of
34.4 percent, meeting the pre-specified study co-primary endpoints of
sensitivity >=0.90 to detect malignant melanoma and non-randomness
(odds ratio greater than 1) to aid physicians in melanoma assessment. A
total of 36 AEs were observed in 28 patients (1.5 percent), out of
which only 3 AEs (occurring on three patients (0.2 percent)) were
defined as definitely related to the device. No serious AEs, serious
adverse device effects, or unanticipated adverse device effects were
observed. The study concluded that the electrical impedance
[[Page 39030]]
spectrometer was accurate and safe as a support tool for the detection
of cutaneous melanoma by physicians trained in the clinical diagnosis
of skin cancer.
---------------------------------------------------------------------------
\4\ The study had two co-primary analyses: a one-sided exact 95
percent confidence bound of the sensitivity in detecting cutaneous
melanoma of >90 percent%; and nonrandom result at the given
sensitivity, i.e., sensitivity + specificity >1.0.
---------------------------------------------------------------------------
In addition, literature reviews of melanoma detection technologies
conclude that optical diagnostic devices for melanoma detection and
electrical impedance spectrometers are effective as adjunctive sources
of information for physicians trained in the clinical diagnosis and
management of skin cancer considering biopsy of lesions suspicious for
melanoma when they have high sensitivity (e.g., over 90 percent) (Refs.
10-13). These reviews acknowledge that the specificity of these devices
can be relatively low, but conclude that the low specificity and low
positive predictive value is acceptable when there is very high
sensitivity and negative predictive value associated with these
devices. Data cited in these reviews support that these devices
generally are more sensitive than visual inspection of suspicious
lesions without magnification, and that when they are more sensitive
than visual inspection, the benefits of using these devices to provide
adjunctive information outweigh the risks related to false positives
resulting in unnecessary biopsies because the adjunctive information
provided by the device can facilitate detection of melanoma that may
otherwise go undetected. One review concludes that the use of these
devices as part of the biopsy decision making process increases the
overall sensitivity for malignant melanoma detection, which justifies
the low specificity and high biopsy number due to improved detection of
malignant melanoma (Ref. 10).
The totality of the literature reviewed indicates that false
results and unnecessary biopsies are among the potential risks related
to the use of computer-aided devices which provide adjunctive
diagnostic information about lesions suspicious for melanoma (Refs. 1-
2, 9-10). The literature reviewed support that these risks can be
successfully mitigated by ensuring that the devices are highly
sensitive, specifying that the devices are intended to be used to
provide adjunctive information for clinical decision making rather than
for giving a conclusive diagnosis, and ensuring that the user
population are physicians trained in the clinical diagnosis and
management of skin cancer and that labeling includes information on the
appropriate training for these physicians to use the device (Refs. 11-
13).
Finally, a search of FDA's publicly available MDR database revealed
no medical device reports for product codes OYD and ONV, the product
codes included in this reclassification. A search of FDA's publicly
available recall database revealed no entries for devices under the ONV
product code and a single entry for a device approved under the OYD
product code, posted on May 20, 2015. This Class II recall was
conducted due to a software change for the device's user interface that
lacked the requisite FDA approval. This recall affected approximately
65 units of the device and was terminated on May 4, 2016. A search of
FDA's publicly available MAUDE database revealed no entries for devices
under the OYD product code and a single entry for a device approved
under the ONV product code. A review of the single entry in the MAUDE
database for the ONV product code revealed that the product code was
misidentified in the report, as evidenced by the fact that the event
date for the entry was May 14, 2014, which was before FDA had approved
any devices under this product code.
Based on our review of the information described above, FDA has
determined that special controls, in addition to general controls, are
necessary to provide a reasonable assurance of safety and effectiveness
for computer-aided devices which provide adjunctive diagnostic
information about lesions suspicious for melanoma, and that sufficient
information exists to establish such special controls. Therefore, FDA,
on its own initiative, is proposing to reclassify these devices from
class III into class II (special controls), and subject to premarket
notification (510(k)) requirements.
VII. Proposed Special Controls
FDA believes that the following proposed special controls would
mitigate each of the risks to health described in section V and that
these special controls, in addition to general controls, would provide
a reasonable assurance of safety and effectiveness for computer-aided
devices which provide adjunctive diagnostic information about lesions
suspicious for melanoma.
The risk of false positive results and false negative results can
be mitigated through clinical performance testing, which may include,
for example, stand-alone test(s) with acceptable performance thresholds
(e.g., sensitivity and specificity), side-by-side comparison(s), and/or
a reader study, as applicable, as well as non-clinical performance
testing. The clinical performance testing must demonstrate that the
device improves assisted-read detection and/or diagnostic
characterization of lesions suspicious for melanoma compared to
characterization of lesions without the device in the indicated user
population(s) when used in accordance with the instructions for use.
The non-clinical performance testing, among other things, must
demonstrate that the device performs as intended under anticipated
conditions of use. The risk of false positive results and false
negative results can be further mitigated by special controls that
require information in labeling to provide detailed instructions for
use and inform the user of the expected device performance on a dataset
representative of the intended population.
The risk associated with use error and inappropriate use of a
computer-aided device which provide adjunctive diagnostic information
about lesions suspicious for melanoma can be mitigated by requiring
that the following information be included in the device labeling: (1)
the intended patient population (e.g., gender, Fitzpatrick Skin Type);
(2) anatomical site(s); (3) type(s) of lesions; (4) compatible imaging
hardware; and (5) compatible image acquisition parameters needed for
the device to achieve its intended use. This risk can be further
mitigated by special controls that require the device labeling to
inform intended users of foreseeable situations in which the device is
likely to fail or not to operate at its expected performance level. The
risk resulting from not following the intended reading protocol can be
mitigated by requiring that the device labeling include a device
description and information needed to facilitate the clinical
interpretation of all device outputs, and by special controls requiring
that the device labeling provide a description of user training
required prior to use. This risk can be further mitigated by special
controls that require a human factors assessment to demonstrate that
intended users can correctly use the device according to the intended
use following user training.
The risk of device failure or malfunction can be mitigated by
requiring non-clinical performance testing and software verification,
validation, and hazard analysis, and by requiring that information
needed to facilitate the clinical interpretation of all device outputs
be included in the labeling (e.g., negative/positive result, risk
score). This risk can be further mitigated by special controls that
require the device labeling to inform intended users of foreseeable
situations in which the device is likely to fail or
[[Page 39031]]
not to operate at its expected performance level.
The risk of electrical, thermal, mechanical, and light-related
hazards leading to user injury or discomfort can be mitigated by
special controls that require testing that demonstrates: (1)
electrical, mechanical, and thermal safety; (2) software verification,
validation and hazard analysis; and (3) device labeling that includes
instructions on appropriate usage and maintenance of the device. The
risk of eye injury due to energy (e.g., light) exposure can be
mitigated by special controls that require labeling that warns users
about exclusion of lesions close to the eye and unsafe energy exposure
to the eyes.
The risk that the device may interfere with other devices due to
radiofrequency or electromagnetic interference can be mitigated by
requiring testing that demonstrates electromagnetic compatibility.
The risk of adverse tissue reaction for patient-contacting devices
can be mitigated by special controls that require elements of the
device that may contact the patient to be demonstrated to be
biocompatible and labeling that includes, in addition to user
qualifications needed for safe use of the device, instructions for
device maintenance and validated methods and instructions for
reprocessing of any reusable components.
The risks of infection and cross contamination for patient-
contacting components can be mitigated by special controls that require
sterilization validation, shelf-life testing, and labeling that
includes validated methods and instructions for reprocessing of any
reusable components.
Table 1 shows how FDA believes each risk to health described in
section V would be mitigated by the proposed special controls.
Table 1--Risks to Health and Mitigation Measures for Computer-Aided
Devices Which Provide Adjunctive Diagnostic Information About Lesions
Suspicious for Melanoma
------------------------------------------------------------------------
Identified risk to health Mitigation measures
------------------------------------------------------------------------
False negative or false Clinical performance testing, non-
positive results. clinical performance testing, labeling.
Use error/improper device use Human factors assessment; labeling,
including a description of user
training.
Device failure/malfunction... Non-clinical performance testing,
labeling, software verification,
validation, and hazard analysis.
Electrical, thermal, Electrical, mechanical, and thermal
mechanical, or light-related safety testing, labeling, software
injury. verification, validation, and hazard
analysis.
Interference with other Electromagnetic compatibility testing.
devices.
Adverse tissue reaction...... Biocompatibility evaluation, labeling.
Infection and cross Sterilization validation, shelf-life
contamination. testing, labeling.
------------------------------------------------------------------------
If this proposed order is finalized, optical diagnostic devices for
melanoma detection and electrical impedance spectrometers will be
reclassified into class II (special controls) as computer-aided devices
which provide adjunctive diagnostic information about lesions
suspicious for melanoma and will be subject to premarket notification
requirements under section 510(k) of the FD&C Act. Firms submitting a
510(k) for such a device will be required to comply with the particular
mitigation measures set forth in the special controls. FDA believes
that adherence to the special controls, in addition to the general
controls, is necessary to provide a reasonable assurance of safety and
effectiveness of computer-aided devices which provide adjunctive
diagnostic information about lesions suspicious for melanoma.
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. 3501-3521) is not required. This proposed order refers
to previously approved FDA collections of information. 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 proposal become
effective 30 days after the date of its publication in the Federal
Register.
XI. Codification of Orders
Under section 513(f)(3) of the FD&C Act, FDA may issue final orders
to reclassify devices. 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 newly codified
orders. Therefore, under section 513(f)(3) of the FD&C Act, in the
proposed order, we are proposing to codify computer-aided devices which
provide adjunctive diagnostic information about lesions suspicious for
melanoma in the new 21 CFR 878.1820, under which computer-aided devices
which provide adjunctive diagnostic information about lesions
suspicious for melanoma would be reclassified into class II.
XII. References
The following references marked with an asterisk (*) are on display
at 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 also are available electronically at https://www.regulations.gov. References without asterisks are not on public
display at https://www.regulations.gov because they have copyright
restriction. Some may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. 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. P090012 Summary of Safety and Effectiveness Data, available at:
https://www.accessdata.fda.gov/cdrh_docs/pdf9/P090012B.pdf.
2. A. Hauschild, et al. ``To Excise or Not: Impact of MELAFIND on
German Dermatologists' Decisions to Biopsy
[[Page 39032]]
Atypical Lesions.'' Journal der Deutschen Dermatologischen
Gesellschaft. 12(7):606-614. June 2014.
3. R.R. Winkelmann, et al. ``Enhancement of International
Dermatologists' Pigmented Skin Lesion Biopsy Decisions Following
Dermoscopy with Subsequent Integration of Multispectral Digital Skin
Lesion Analysis.'' Journal of Clinical and Aesthetic Dermatology.
9(7):53-5. July 2016.
4. R. Wells, et al. ``Comparison of Diagnostic and Management
Sensitivity to Melanoma Between Dermatologists and MELAFIND: A Pilot
Study.'' Archives of Dermatology. 148(9):1083-4. September 2012.
5. L.F. di Ruffano, et al. ``Computer[hyphen]Assisted Diagnosis
Techniques (Dermoscopy and Spectroscopy[hyphen]Based) for Diagnosing
Skin Cancer in Adults.'' Cochrane Skin Cancer Diagnostic Test
Accuracy Group; Cochrane Database System Review. 4;12(12). December
2018.
* 6. FDA, November 18, 2010, Meeting of the General and Plastic
Surgery Devices Panel Meeting Materials (available at https://wayback.archive-it.org/7993/20170403223449/https:/www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/GeneralandPlasticSurgeryDevicesPanel/ucm205684.htm).
* 7. FDA, November 18, 2010, Meeting of the General and Plastic
Surgery Devices Panel, 24-Hour Summary (available at https://wayback.archive-it.org/7993/20170403223449/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/GeneralandPlasticSurgeryDevicesPanel/UCM234481.pdf).
* 8. P090012 Approval Order, available at https://www.accessdata.fda.gov/cdrh_docs/pdf9/P090012A.pdf.
9. J. Malvehy, et al. ``Clinical Performance of the NEVISENSE System
in Cutaneous Melanoma Detection: An International, Multicentre,
Prospective and Blinded Clinical Trial on Efficacy and Safety.''
British Journal of Dermatology. 171(5):1099-1107. May 2014.
10. R.P. Braun, et al. ``Electrical Impedance Spectroscopy in Skin
Cancer Diagnosis.'' Dermatologic Clinics. 35(4):489-493. October
2017.
11. D.N. Dorrell and L.C. Strowd. ``Skin Cancer Detection
Technology.'' Dermatologic Clinics. 37(4):527-536. October 2019.
12. C. Fink and H.A. Haenssle. ``Non-Invasive Tools for the
Diagnosis of Cutaneous Melanoma.'' Skin Research and Technology, pp.
261-271, 23 (3) (2017).
13. R.R. Winkelmann, A.S. Farberg, A.M. Glazer, et al. ``Noninvasive
Technologies for the Diagnosis of Cutaneous Melanoma.'' Dermatologic
Clinics, pp. 453-456, 35 (4) (2017).
List of Subjects in 21 CFR Part 878
Medical devices.
Therefore, under the Federal Food, Drug, and Cosmetic Act, and
under authority delegated to the Commissioner of Food and Drugs, FDA
proposes that 21 CFR part 878 be amended as follows:
PART 878--GENERAL AND PLASTIC SURGERY DEVICES
0
1. The authority citation for part 878 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 878.1820 to subpart B to read as follows:
Sec. 878.1820 Computer-aided devices which provide adjunctive
diagnostic information about lesions suspicious for melanoma.
(a) Identification. A computer-aided device which provides
adjunctive diagnostic information about lesions suspicious for melanoma
is a device that is used to aid in the decision-making process for
melanoma detection. The device is intended for prescription use by a
physician trained in the clinical diagnosis and management of skin
cancer (e.g., a dermatologist) on skin lesions with one or more
clinical or historical characteristics of melanoma, and is based on a
computer algorithm to analyze optical or other physical properties of a
skin lesion. The algorithm returns a classification of the skin lesion
regarding melanoma when a physician trained in the clinical diagnosis
and management of skin cancer chooses to obtain additional information
when considering biopsy. The device is not for use as a stand-alone
diagnostic.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Clinical performance testing must demonstrate that the device
improves assisted-read detection or diagnostic characterization of
lesions suspicious for melanoma compared to characterization of lesions
without the device in the indicated user population(s) when used in
accordance with the instructions for use.
(2) Non-clinical performance testing must demonstrate that the
device performs as intended under anticipated conditions of use. Such
testing must include testing of safety features intended to mitigate
device specific hazards and must demonstrate:
(i) Electromagnetic compatibility, and electrical, mechanical, and
thermal safety.
(ii) Continued sterility and package integrity of components that
must be sterile, as well as continued device functionality, over the
identified shelf life of the device.
(3) Sterilization validation must be conducted for components that
must be sterile.
(4) The elements of the device that may contact the patient must be
demonstrated to be biocompatible.
(5) Software verification, validation, and hazard analysis must be
performed.
(6) A human factors assessment must demonstrate that the intended
user can correctly use the device according to the intended use
following user training.
(7) Labeling must include:
(i) A description of the device and information needed to
facilitate clinical interpretation of all device outputs.
(ii) Information regarding the intended patient population and
anatomical site(s), type(s) of lesions, compatible hardware, and
compatible image acquisition parameters used with the device in order
to achieve the intended use.
(iii) A summary of any clinical testing conducted to demonstrate
how the device functions in providing information about the skin
lesion. The summary must include the following:
(A) A description of each device output and clinical
interpretation.
(B) Any performance measures, including sensitivity and
specificity.
(C) Relevant characteristics of the patients studied in the
clinical validation (including age, gender, race or ethnicity, disease
category), inclusion and exclusion criteria, and a summary of
validation results.
(D) The expected performance of the device for all intended use
populations.
(iv) A statement that the device is not intended for use as a
stand-alone diagnostic.
(v) User qualifications needed for safe use of the device,
including a description of user training required prior to use, and a
statement that the device is intended to be used by a physician trained
in the clinical diagnosis and management of skin cancer (e.g., a
dermatologist).
(vi) Warnings and cautions to mitigate any device specific hazards,
including the following:
(A) Identifying foreseeable situations in which the device is
likely to fail or not to operate at its expected performance level; and
(B) For devices that utilize energy to provide adjunctive
diagnostic information, unless available information demonstrates that
the specific warnings and cautions do not apply, a statement warning
users about exclusion of lesions close to the eye and unsafe energy
exposure to the eyes.
(vii) Instructions for device maintenance and validated methods and
instructions for reprocessing of any reusable components.
[[Page 39033]]
Dated: June 24, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-13954 Filed 6-29-22; 8:45 am]
BILLING CODE 4164-01-P