Rule2026-07863
Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of the Setmelanotide Eligibility Gene Variant Detection System
Primary source
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Published
April 22, 2026
Effective
April 22, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, the Agency, or we) is classifying the setmelanotide eligibility gene variant detection system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for classification of the setmelanotide eligibility gene variant detection system. We are taking this action because we have determined that classifying the device into class II will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.
Full Text
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<title>Federal Register, Volume 91 Issue 77 (Wednesday, April 22, 2026)</title>
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[Federal Register Volume 91, Number 77 (Wednesday, April 22, 2026)]
[Rules and Regulations]
[Pages 21376-21379]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-07863]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 862
[Docket No. FDA-2026-N-3900]
Medical Devices; Clinical Chemistry and Clinical Toxicology
Devices; Classification of the Setmelanotide Eligibility Gene Variant
Detection System
AGENCY: Food and Drug Administration, HHS.
ACTION: Final amendment; final order.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
classifying the setmelanotide eligibility gene variant detection system
into class II (special controls). The special controls that apply to
the device type are identified in this order and will be part of the
codified language for classification of the setmelanotide eligibility
gene variant detection system. We are taking this action because we
have determined that classifying the device into class II will provide
a reasonable assurance of safety and effectiveness of the device. We
believe this action will also enhance patients' access to beneficial
innovative devices, in part by reducing regulatory burdens.
DATES: This order is effective April 22, 2026. The classification was
applicable on January 21, 2022.
FOR FURTHER INFORMATION CONTACT: Jessica Chu, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 3524, Silver Spring, MD 20993-0002, 301-796-9056,
<a href="/cdn-cgi/l/email-protection#38725d4b4b515b59167b504d785e5c591650504b165f574e"><span class="__cf_email__" data-cfemail="39735c4a4a505a58177a514c795f5d581751514a175e564f">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA (the Agency or we) has classified the
setmelanotide eligibility gene variant detection system into class II
(special controls), which we have determined will provide a reasonable
assurance of safety and
[[Page 21377]]
effectiveness of the device. In addition, we believe this action will
enhance patients' access to beneficial innovation, in part by reducing
regulatory burdens by placing the device into a lower device class than
the automatic class III assignment.
The automatic assignment of class III occurs by operation of law
and without any action by FDA, regardless of the level of risk posed by
the new device. Any device that was not in commercial distribution
before May 28, 1976, is automatically classified into, and remains
within, class III and requires premarket approval unless and until FDA
takes an action to classify or reclassify the device (21 U.S.C.
360c(f)(1)). We refer to these devices as ``postamendments devices''
because they were not in commercial distribution prior to the date of
enactment of the Medical Device Amendments of 1976, which amended the
Federal Food, Drug, and Cosmetic Act (FD&C Act).
FDA may take a variety of actions in appropriate circumstances to
classify or reclassify a device into class I or II. We may issue an
order finding a new device to be substantially equivalent under section
513(i) of the FD&C Act (21 U.S.C. 360c(i)) to a predicate device that
does not require premarket approval. We determine whether a new device
is substantially equivalent to a predicate device by means of the
procedures for premarket notification under section 510(k) of the FD&C
Act (21 U.S.C. 360(k)) and part 807 (21 CFR part 807).
FDA may also classify a device through ``De Novo'' classification,
a common name for the process authorized under section 513(f)(2) of the
FD&C Act (see also part 860, subpart D (21 CFR part 860, subpart D)).
Section 207 of the Food and Drug Administration Modernization Act of
1997 (Pub. L. 105-115) established the first procedure for De Novo
classification. Section 607 of the Food and Drug Administration Safety
and Innovation Act (Pub. L. 112-144) modified the De Novo
classification process by adding a second procedure. A device sponsor
may utilize either procedure for De Novo classification.
Under the first procedure, the person submits a premarket
notification (510(k)) for a device that has not previously been
classified. After receiving an order from FDA classifying the device
into class III under section 513(f)(1) of the FD&C Act, the person then
requests a classification under section 513(f)(2).
Under the second procedure, rather than first submitting a 510(k)
and then a request for classification, if the person determines that
there is no legally marketed device upon which to base a determination
of substantial equivalence, that person requests a classification under
section 513(f)(2) of the FD&C Act.
Under either procedure for De Novo classification, FDA is required
to classify the device by written order within 120 days. The
classification will be according to the criteria under section
513(a)(1) of the FD&C Act. Although the device was automatically placed
within class III, the De Novo classification is considered to be the
initial classification of the device.
We believe this De Novo classification will enhance patients'
access to beneficial innovation, in part by reducing regulatory
burdens. When FDA classifies a device into class I or II via the De
Novo process, the device can serve as a predicate for future devices of
that type, including for 510(k)s (see section 513(f)(2)(B)(i) of the
FD&C Act). As a result, other device sponsors do not have to submit a
De Novo request or premarket approval application to market a
substantially equivalent device (see section 513(i) of the FD&C Act,
defining ``substantial equivalence''). Instead, sponsors can use the
less burdensome 510(k) process, when necessary, to market their device.
II. De Novo Classification
On September 7, 2021, FDA received PreventionGenetics, LLC's
request for De Novo classification of the POMC/PCSK1/LEPR CDx Panel.
FDA reviewed the request in order to classify the device under the
criteria for classification set forth in section 513(a)(1) of the FD&C
Act.
We classify devices into class II if general controls by themselves
are insufficient to provide reasonable assurance of safety and
effectiveness of the device, but there is sufficient information to
establish special controls that, in combination with the general
controls, provide reasonable assurance of the safety and effectiveness
of the device for its intended use (see section 513(a)(1)(B) of the
FD&C Act). After review of the information submitted in the request, we
determined that the device can be classified into class II with the
establishment of special controls. FDA has determined that these
special controls, in addition to the general controls, will provide
reasonable assurance of the safety and effectiveness of the device.
Therefore, on January 21, 2022, FDA issued an order to the
requester classifying the device into class II. In this final order,
FDA is codifying the classification of the device by adding 21 CFR
862.1164.\1\ We have named the generic type of device ``setmelanotide
eligibility gene variant detection system,'' and it is identified as a
qualitative in vitro diagnostic device intended to detect germline
variants within genes isolated from human specimens for the purpose of
identifying patients with obesity who may benefit from treatment with
setmelanotide in accordance with the approved therapeutic product
labeling.
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\1\ FDA notes that the ``ACTION'' caption for this final order
is styled as ``Final amendment; final order,'' rather than ``Final
order.'' Beginning in December 2019, this editorial change was made
to indicate that the document ``amends'' the Code of Federal
Regulations. The change was made in accordance with the Office of
Federal Register's (OFR) interpretations of the Federal Register Act
(44 U.S.C. chapter 15), its implementing regulations (1 CFR 5.9 and
parts 21 and 22), and the Document Drafting Handbook.
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FDA has identified the risks to health associated with this type of
device and the measures required to mitigate these risks in table 1.
Table 1--Risks to Health and Mitigation Measures for Setmelanotide
Eligibility Gene Variant Detection System
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Identified risks to health Mitigation measures
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Incorrect performance of the test Certain design verification and
leading to false positive results validation activities,
(causing patients to receive drug including documentation of
treatment inappropriately) or false certain studies.
negative results (causing patients to Certain labeling information,
miss an opportunity for drug including certain limiting
treatment). statements and performance
information.
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Incorrect interpretation of genetic Certain design verification and
data leading to false positive results validation activities,
(causing patients to receive drug including documentation of
treatment inappropriately) or false certain studies and variant
negative results (causing patients to interpretation and
miss an opportunity for drug classification procedures.
treatment). Certain labeling information,
including certain limiting
statements and performance
information.
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FDA has determined that special controls, in combination with the
general controls, address these risks to health and provide reasonable
assurance of safety and effectiveness of the device. For a device to
fall within this classification, and thus avoid automatic
classification in class III, it would have to comply with the special
controls named in this final order. The necessary special controls
appear in the regulation codified by this final order.
Under the FD&C Act, submission of a premarket notification under
section 510(k) (21 U.S.C. 360(k)) is required to reasonably assure the
safety and effectiveness of class II devices unless FDA determines that
the device type should be exempt under section 510(m) of the FD&C Act.
At this time FDA has not made this determination for setmelanotide
eligibility gene variant detection systems. This device is therefore
subject to premarket notification requirements under section 510(k) of
the FD&C Act.
III. Analysis of Environmental Impact
The Agency has determined under 21 CFR 25.34(b) that this action is
of a type that does not normally have a significant effect on the human
environment. Therefore, neither an environmental assessment nor an
environmental impact statement is required.
IV. Paperwork Reduction Act of 1995
This final order establishes special controls that refer to
previously approved collections of information found in other FDA
regulations and guidance. These collections of information are subject
to review by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). The collections
of information in part 860, subpart D, regarding De Novo classification
have been approved under OMB control number 0910-0844; the collections
of information in 21 CFR part 814, subparts A through E, regarding
premarket approval have been approved under OMB control number 0910-
0231; the collections of information in part 807, subpart E, regarding
premarket notification submissions have been approved under OMB control
number 0910-0120; the collections of information in 21 CFR part 820
regarding quality management system regulation have been approved under
OMB control number 0910-0073; and the collections of information in 21
CFR parts 801 and 809, regarding labeling have been approved under OMB
control number 0910-0485.
List of Subjects in 21 CFR Part 862
Medical devices.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
862 is amended as follows:
PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES
0
1. The authority citation for part 862 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 862.1164 to subpart B to read as follows:
Sec. 862.1164 Setmelanotide eligibility gene variant detection
system.
(a) Identification. A setmelanotide eligibility gene variant
detection system is a qualitative in vitro diagnostic device intended
to detect germline variants within genes isolated from human specimens
for the purpose of identifying patients with obesity who may benefit
from treatment with setmelanotide in accordance with the approved
therapeutic product labeling.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Design verification and validation must include:
(i) Detailed documentation of studies that provide data bridging
the efficacy of setmelanotide in the clinical trial patient population
identified by the clinical trial assay(s) to the efficacy of
setmelanotide in the device intended use population identified by the
device using the clinical trial samples, or through an alternative
approach determined to be appropriate by FDA.
(ii) Detailed documentation of studies that provide data
demonstrating the accuracy of the device using clinical specimens
representing the intended use specimen type(s) and intended use variant
type(s) from the intended use population, including the clinical trial
samples, or through an alternative approach determined to be
appropriate by FDA. Accuracy of the device must be evaluated at the
variant level and sample level, through evaluation of variant and non-
variant sequences at the nucleotide level as well as variant
interpretation, by comparison to validated bidirectional Sanger
sequencing methods or through other methods determined to be
appropriate by FDA. If the device will be used at more than one site,
the data must demonstrate accuracy across multiple intended use sites.
(iii) Detailed documentation of studies that provide data
demonstrating the precision of the device for the intended use specimen
type(s) and intended use variant type(s) from the intended use
population. Precision must be evaluated at the variant level and sample
level, through evaluation of variant and non-variant sequences at the
nucleotide level as well as variant interpretation, using multiple
reagent lots, operators, and instruments over multiple days, or through
an alternative precision study design determined to be appropriate by
FDA. If the device will be used at more than one site, data must
demonstrate adequate, as determined by FDA, reproducibility across
multiple intended use sites.
(iv) Detailed documentation of studies that provide data
demonstrating the analytical specificity of the device for the intended
use specimen type(s), including an evaluation of cross-reactivity and
cross contamination.
(A) Cross-reactivity (e.g., from homologous regions, paralogs,
pseudogenes, repeated sequences, high GC (Guanine and Cytosine) content
regions, segmental duplications, and other types of cross-reactive
sequences) must be evaluated to assess the detection of unintended
alleles or
[[Page 21379]]
incorrect calls in the target regions covered by the device; and
(B) Cross-contamination must be evaluated to detect carryover and
co-mingling of input specimens throughout the process (e.g., from
sample collection and library preparation to variant interpretation).
(v) Detailed documentation of studies that provide data
demonstrating adequate, as determined by FDA, stability of the
specimens used in the design validation studies in paragraphs (b)(1)(i)
through (iv) of this section, as applicable.
(vi) Detailed documentation of information demonstrating adequate,
as determined by FDA, analytical quality metrics and thresholds.
(vii) Detailed documentation of information demonstrating adequate,
as determined by FDA, procedures that will be performed for variant
interpretation and classification, including the procedures that will
be performed for variant interpretation and classification changes that
may occur as new scientific information becomes available. The
information must indicate how the personnel performing such
interpretation and classification are trained.
(2) The labeling required under Sec. 809.10(b) of this chapter and
any test report generated must include:
(i) Limiting statements that:
(A) Explain that the classification and interpretation of variants
identified reflects the current state of scientific understanding at
the time the results are issued.
(B) Explain variants could change classification as new scientific
information becomes available, which may impact patient eligibility for
therapeutic treatment; and
(C) If applicable, explain sufficient scientific information is not
available to assign pathogenicity to variants of uncertain significance
(VUS).
(ii) A detailed summary of the performance testing, including
results, required under paragraphs (b)(1)(i) through (iv) of this
section.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-07863 Filed 4-21-26; 8:45 am]
BILLING CODE 4164-01-P
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