[Federal Register Volume 83, Number 115 (Thursday, June 14, 2018)]
[Rules and Regulations]
[Pages 27699-27702]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-12760]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2018-N-1928]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the Brain Trauma Assessment Test

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 brain trauma assessment test 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 brain trauma 
assessment test'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 June 14, 2018. The classification was 
applicable on February 14, 2018.

FOR FURTHER INFORMATION CONTACT: Erin Cutts, Center for Devices and 
Radiological Health, Food and Drug

[[Page 27700]]

Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5618, Silver 
Spring, MD 20993-0002, 301-796-6307, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Upon request, FDA has classified the brain trauma assessment test 
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 established the first procedure for De Novo classification 
(Pub. L. 105-115). Section 607 of the Food and Drug Administration 
Safety and Innovation Act modified the De Novo application process by 
adding a second procedure (Pub. L. 112-144). 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 in order 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 August 28, 2017, Banyan Biomarkers, Inc., submitted a request 
for De Novo classification of the Banyan BTI. 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 February 14, 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 866.5830. We have named 
the generic type of device brain trauma assessment test, and it is 
identified as a device that consists of reagents used to detect and 
measure brain injury biomarkers in human specimens. The measurements 
aid in the evaluation of patients with suspected mild traumatic brain 
injury in conjunction with other clinical information to assist in 
determining the need for head imaging per current standard of care.
    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--Brain Trauma Assessment Test Risks and Mitigation Measures
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            Identified risks                   Mitigation measures
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Inaccurate test results that provide     General controls and special
 false positive or false negative         control (1) (21 CFR
 results.                                 866.5830(b)(1)).
Failure to correctly interpret test      General controls and special
 results can lead to false positive or    control (2) (21 CFR
 false negative results.                  866.5830(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

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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. 3501-3520). 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; 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 866

    Biologics, Laboratories, 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 
866 is amended as follows:

PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES

0
1. The authority citation for part 866 continues to read as follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.


0
2. Add Sec.  866.5830 to subpart F to read as follows:


Sec.  866.5830   Brain trauma assessment test.

    (a) Identification. A brain trauma assessment test is a device that 
consists of reagents used to detect and measure brain injury biomarkers 
in human specimens. The measurements aid in the evaluation of patients 
with suspected mild traumatic brain injury in conjunction with other 
clinical information to assist in determining the need for head imaging 
per current standard of care.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) The 21 CFR 809.10(b) compliant labeling must include detailed 
descriptions of and results from performance testing conducted to 
evaluate precision, accuracy, linearity, analytical sensitivity, 
interference, and cross-reactivity. This information must include the 
following:
    (i) Performance testing of device precision must, at minimum, use 
one unmodified clinical specimen from the intended use population with 
concentration of the brain injury biomarker(s) near the medical 
decision point. Contrived specimens that have been generated from 
pooling of multiple samples or spiking of purified analyte to cover the 
measuring range may be used, but the contrived samples must be prepared 
to mimic clinical specimens as closely as possible. This testing must 
evaluate repeatability and reproducibility using a protocol from an 
FDA-recognized standard.
    (ii) Device performance data must be demonstrated through a 
clinical study and must include the following:
    (A) Data demonstrating clinical validity including the clinical 
sensitivity and specificity, and positive and negative predictive value 
of the test in the intended use population of patients with suspected 
mild traumatic brain injury (i.e., Glasgow Coma Score (GCS) of 13-15), 
or equivalent standard of care for determination of severity of 
traumatic brain injury (TBI).
    (B) Study must be performed using the operators and in settings 
that are representative of the types of operators and settings for 
which the device is intended to be used.
    (C) All eligible subjects must meet the well-defined study 
inclusion and exclusion criteria that define the intended use 
population. The prevalence of diseased or injured subjects in the study 
population must reflect the prevalence of the device's intended use 
population, or alternatively, statistical measures must be used to 
account for any bias due to enrichment of subpopulations of the 
intended use population.
    (D) All eligible subjects must have undergone a head computerized 
tomography (CT) scan or other appropriate clinical diagnostic standard 
used to determine the presence of an intracranial lesion as part of 
standard of care and must also be evaluated by the subject device. All 
clinical diagnostic standards used in the clinical study must follow 
standard clinical practice in the United States.
    (E) Relevant demographic variables and baseline characteristics 
including medical history and neurological history. In addition, head 
injury characteristics, neurological assessments, and physical evidence 
of trauma must be provided for each subject. This information includes 
but is not limited to the following: Time since head injury, time from 
head injury to CT scan, time from head injury to blood draw, GCS score 
or equivalent, experience of loss of consciousness, presence of 
confusion, episodes of vomiting, post-traumatic amnesia 
characteristics, presence of post-traumatic seizures, drug or alcohol 
intoxication, mechanism of injury, acute intracranial lesion type, 
neurosurgical lesion, and cranial fracture.
    (F) Each CT scan or other imaging result must be independently 
evaluated in a blinded manner by at least two board-certified 
radiologists to determine whether it is positive or negative as defined 
by the presence or absence of acute intracranial lesions. This 
independent review must be conducted without access to test results of 
the device. Prior to conducting the review, the criteria and procedures 
to be followed for scoring the images must be established, including 
the mechanism for determining consensus.
    (G) All the clinical samples must be tested with the subject device 
blinded to the TBI status and the neurological-lesion-status of the 
subject.
    (H) Details on how missing values in data are handled must be 
provided.
    (I) For banked clinical samples, details on storage conditions and 
storage period must be provided. In addition, a specimen stability 
study must be conducted for the duration of storage to demonstrate 
integrity of archived clinical samples. The samples evaluated in the 
assay test development must not be used to establish the clinical 
validity of the assays.
    (iii) Performance testing of device analytical specificity must 
include the most commonly reported concomitant medications present in 
specimens from the intended use population. Additionally, potential 
cross-reacting endogenous analytes must be evaluated at the highest 
concentration reported in specimens from the intended use population.
    (iv) Expected/reference values generated by testing a statistically 
appropriate number of samples from apparently healthy normal 
individuals.

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    (2) The 21 CFR 809.10(a) and (b) compliant labeling must include 
the following limitations:
    (i) A limiting statement that this device is not intended to be 
used a stand-alone device but as an adjunct to other clinical 
information to aid in the evaluation of patients who are being 
considered for standard of care neuroimaging.
    (ii) A limiting statement that reads ``A negative result is 
generally associated with the absence of acute intracranial lesions. An 
appropriate neuroimaging method is required for diagnosis of acute 
intracranial lesions.''
    (iii) As applicable, a limiting statement that reads ``This device 
is for use by laboratory professionals in a clinical laboratory 
setting.''

    Dated: June 8, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-12760 Filed 6-13-18; 8:45 am]
 BILLING CODE 4164-01-P