[Federal Register Volume 90, Number 89 (Friday, May 9, 2025)]
[Rules and Regulations]
[Pages 19625-19627]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-08148]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 862
[Docket No. FDA-2025-N-0780]
Medical Devices; Clinical Chemistry and Clinical Toxicology
Devices; Classification of the Voriconazole Test System
AGENCY: Food and Drug Administration, Department of Health and Human
Services (HHS).
ACTION: Final amendment; final order.
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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
classifying the voriconazole test 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
the voriconazole test system's classification. We are taking this
action because we have determined that classifying the device into
class II (special controls) 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 May 9, 2025. The classification was
applicable on May 5, 2017.
FOR FURTHER INFORMATION CONTACT: Dina Jerebitski, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 3574, Silver Spring, MD 20993-0002, 301-
796-2411, [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the voriconazole test system as
class II (special controls), which we have determined will provide a
reasonable assurance of safety and effectiveness. 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 as, and remains
within, class III and requires premarket approval unless and until FDA
takes an action to classify or reclassify the device (see 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 (see 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 application
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 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
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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 July 15, 2016, FDA received ARK Diagnostics, Inc.'s request for
De Novo classification of the ARK Voriconazole II Assay Test System.
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, 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 21 U.S.C. 360c(a)(1)(B)). 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 May 5, 2017, 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
862.3970.\1\ We have named the generic type of device ``voriconazole
test system,'' and it is identified as a device intended to measure
voriconazole in human serum. Measurements obtained by this device are
used in monitoring levels of voriconazole to ensure appropriate
therapy.
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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
the 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 following risks to health associated
specifically with this type of device and the measures required to
mitigate these risks in table 1.
Table 1--Voriconazole Test System Risks and Mitigation Measures
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Identified risks to health Mitigation measures
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Clinical action (e.g., dose General control and special
adjustments) based on falsely elevated controls (1) (21 CFR
inaccurate voriconazole results may 862.3970(b)(1)) and (2) (21
lead to decreased clinical efficacy of CFR 862.3970(b)(2)).
the drug and consequently poorer
clinical outcomes.
Clinical action (e.g., dose General and special controls
adjustments) based on falsely low (1) (21 CFR 862.3970(b)(1))
inaccurate voriconazole results may and (2) (21 CFR
lead to an increased risk of toxicity. 862.3970(b)(2)).
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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. 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 order. This device is 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 individually or cumulatively 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 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, subpart 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 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. 862.3970 to subpart D to read as follows:
Sec. 862.3970 Voriconazole test system.
(a) Identification. A voriconazole test system is a device intended
to measure voriconazole in human serum. Measurements obtained by this
device are used in monitoring levels of voriconazole to ensure
appropriate therapy.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Design verification and validation must include the following
information:
(i) Data demonstrating the precision of the voriconazole test
system. Precision studies must include a minimum of three samples
containing different
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concentrations of voriconazole, including near medical decision points
at the high and low end of the expected therapeutic range. Samples with
concentrations near medical decision points must be individual or
pooled clinical specimens, collected from patients taking voriconazole.
(ii) Method comparison data demonstrating accuracy of the
voriconazole test system. Method comparison data must be collected at
three laboratory sites. The comparator method must not be subject to
bias due to nonspecific detection of voriconazole.
(iii) Data from interference studies performed to evaluate
potential interference from co-administered medications used for
conditions in which voriconazole is indicated.
(iv) Data from studies performed to evaluate cross reactivity of
the major metabolite, N-oxide voriconazole.
(2) The labeling required under Sec. 809.10(b) of this chapter
must include a warning statement as follows: ``This assay should only
be used in conjunction with information available from clinical
evaluations and other diagnostic procedures.''
Dated: May 5, 2025.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-08148 Filed 5-8-25; 8:45 am]
BILLING CODE 4164-01-P