[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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    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