[Federal Register Volume 89, Number 179 (Monday, September 16, 2024)]
[Rules and Regulations]
[Pages 75489-75491]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-20895]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 862

[Docket No. FDA-2024-N-4058]


Medical Devices; Clinical Chemistry and Clinical Toxicology 
Devices; Classification of the Clozapine Test System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is

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classifying the clozapine 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 clozapine 
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.

DATES: This order is effective September 16, 2024. The classification 
was applicable on April 16, 2020.

FOR FURTHER INFORMATION CONTACT: Joseph Kotarek, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3504, Silver Spring, MD 20993-0002, 301-796-2718, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the clozapine test system as class 
II (special controls), which we have determined will provide a 
reasonable assurance of safety and effectiveness.
    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.
    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 
510(k) process, when necessary, to market their device.

II. De Novo Classification

    On May 24, 2019, FDA received Saladax Biomedical, Inc.'s request 
for De Novo classification of the MyCare Psychiatry Clozapine Assay 
Kit. 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. FDA has determined that general controls 
will provide reasonable assurance of the safety and effectiveness of 
the device.
    Therefore, on April 16, 2020, 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 
862.3245.\1\ We have named the generic type of device clozapine test 
system, and it is identified as a device intended to measure clozapine 
in human specimens. Measurements obtained by this device are used in 
monitoring levels of clozapine to ensure appropriate therapy in 
patients with treatment-resistant schizophrenia.
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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 following risks to health associated 
specifically with this type of device and the measures required to 
mitigate these risks in table 1.

      Table 1--Clozapine Test System Risks and Mitigation Measures
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    Identified risks to health               Mitigation measures
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Incorrect test results............  Certain design verification and
                                     validation activities and Certain
                                     labeling information.

[[Page 75491]]

 
Incorrect interpretation of test    Certain design verification and
 results.                            validation activities and Certain
                                     labeling 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. 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 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 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.  862.3245 to subpart D to read as follows:


Sec.  862.3245  Clozapine test system.

    (a) Identification. A clozapine test system is a device intended to 
measure clozapine in human specimens. Measurements obtained by this 
device are used in monitoring levels of clozapine to ensure appropriate 
therapy in patients with treatment-resistant schizophrenia.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Design verification and validation must include the following:
    (i) Precision study data that demonstrates precision that is 
clinically appropriate, as determined by FDA, for the clozapine test 
system. Precision studies must include a minimum of three samples 
containing different concentrations of clozapine including near medical 
decision points and throughout the expected therapeutic range of 
clozapine. Samples near the medical decision points must be clinical 
specimens collected from patients taking clozapine;
    (ii) Method comparison data that demonstrates accuracy that is 
clinically acceptable, as determined by FDA, for the clozapine test 
system;
    (iii) Data from studies that demonstrate that the device is free 
from clinically significant interference, as determined by FDA, from 
commonly co-administered medications that are used in patients with 
treatment-resistant schizophrenia; and
    (iv) Data from studies that demonstrate that the device is free 
from clinically significant cross-reactivity, as determined by FDA, 
from major circulating metabolites found in the intended use 
population.
    (2) The labeling required under Sec.  809.10 of this chapter must 
include a limiting statement conveying that the assay should only be 
used in conjunction with information available from clinical 
evaluations and other diagnostic procedures and that results from the 
assay alone should not be used in making treatment decisions.

    Dated: September 10, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-20895 Filed 9-13-24; 8:45 am]
BILLING CODE 4164-01-P