[Federal Register Volume 83, Number 212 (Thursday, November 1, 2018)]
[Rules and Regulations]
[Pages 54875-54876]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-23911]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 862

[Docket No. FDA-2018-N-3694]


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

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA or we) is classifying 
the meprobamate 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 meprobamate 
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 November 1, 2018. The classification was 
applicable on April 20, 2018.

FOR FURTHER INFORMATION CONTACT: Ryan Lubert, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 4545, Silver Spring, MD 20993-0002, 240-402-6357, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Upon request, FDA has classified the meprobamate 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 (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 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. 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 shall 
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 21 U.S.C. 360c(f)(2)(B)(i)). 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 21 U.S.C. 360c(i), defining ``substantial equivalence''). 
Instead, sponsors can use the less-burdensome 510(k) process, when 
necessary, to market their device.

II. De Novo Classification

    On February 21, 2017, Lin-Zhi International, Inc. submitted a 
request for De Novo classification of the LZI Carisoprodol Metabolite 
(Meprobamate) Enzyme Immunoassay. 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 April 20, 2018, FDA issued an order to the requester 
classifying the device into class II. FDA is codifying the 
classification of the device by adding 21 CFR 862.3590. We have named 
the generic type of device meprobamate test system, and it is 
identified as a device intended to measure meprobamate in human 
specimens. Measurements obtained by this device are used to detect the 
presence of meprobamate to diagnose the use or overdose of meprobamate 
or structurally-related drug compounds (e.g., prodrugs).
    FDA has identified the following risks to health associated 
specifically with this type of device and the measures

[[Page 54876]]

required to mitigate these risks in Table 1.

     Table 1--Meprobamate Test System Risks and Mitigation Measures
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            Identified risks                   Mitigation measures
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Clinical action based on incorrect test  Special controls (1) (21 CFR
 results (false positive results, false   862.3590(b)(1)), (2) (21 CFR
 negative results) may lead to            862.3590(b)(2)), and (3) (21
 inappropriate clinical decision making.  CFR 862.3590(b)(3)).
Incorrect understanding of the device    Special controls (2) (21 CFR
 and test system and results may lead     862.3590(b)(2)) and (3) (21
 to inappropriate clinical decision       CFR 862.3590(b)(3)).
 making.
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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.
    At the time of classification, meprobamate test systems are for 
prescription use only.

III. Analysis of Environmental Impact

    We have 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. 3501-3520). The collections 
of information in the guidance document ``De Novo Classification 
Process (Evaluation of Automatic Class III Designation)'' 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 regulations, 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.  862.3590 to subpart D to read as follows:


Sec.  862.3590  Meprobamate test system.

    (a) Identification. A meprobamate test system is a device intended 
to measure meprobamate in human specimens. Measurements obtained by 
this device are used to detect the presence of meprobamate to diagnose 
the use or overdose of meprobamate or structurally-related drug 
compounds (e.g., prodrugs).
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Design verification and validation must include:
    (i) Robust data demonstrating the accuracy of the device when used 
in the intended specimen matrix. The accuracy data must include a 
comparison between the meprobamate test system results and meprobamate 
results that are measured on an FDA-accepted measurement method that is 
specific and accurate (e.g., gas or liquid chromatography combined with 
tandem mass spectrometry).
    (ii) Robust analytical data demonstrating the performance 
characteristics of the device, including, but not limited to, 
specificity, cross-reactivity to relevant endogenous and exogenous 
substances, and the reproducibility of analyte detection around the 
cutoff(s).
    (2) The intended use of the device must not include an indication 
for use in monitoring therapeutic drug concentrations or informing 
dosing adjustment decisions.
    (3) Your 21 CFR 809.10 labeling must include the following:
    (i) If indicated for use as a screening test to identify 
preliminary results for further confirmation, the intended use must 
state ``This assay provides only a preliminary analytical result. A 
more specific alternative chemical confirmatory method (e.g., gas or 
liquid chromatography and mass spectrometry) must be used to obtain a 
confirmed analytical result. Clinical consideration and professional 
judgment must be exercised with any drug of abuse test, particularly 
when the preliminary test result is positive.''
    (ii) A limiting statement that reads as follows: ``This test should 
not be used to monitor therapeutic drug concentrations or to inform 
dosing adjustment decisions.''

    Dated: October 29, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-23911 Filed 10-31-18; 8:45 am]
 BILLING CODE 4164-01-P