[Federal Register Volume 82, Number 202 (Friday, October 20, 2017)]
[Rules and Regulations]
[Pages 48762-48764]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-22769]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2017-N-5371]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the Device To Detect and Identify Microbial Pathogen 
Nucleic Acids in Cerebrospinal Fluid

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 device to detect and identify microbial pathogen nucleic acids in 
cerebrospinal fluid into class II (special controls). The special 
controls that will apply to the device type are identified in this 
order and will be part of the codified language for the device to 
detect and identify microbial pathogen nucleic acids in cerebrospinal 
fluid'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 October 20, 2017. The classification was 
applicable on October 8, 2015.

FOR FURTHER INFORMATION CONTACT: Kimberly Sconce, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. 4524, Silver Spring, MD, 20993-0002, 301-
796-6679, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Upon request, FDA has classified the device to detect and identify 
microbial pathogen nucleic acids in cerebrospinal fluid 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 (the 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

[[Page 48763]]

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 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 April 9, 2015, BioFire Diagnostics, LLC submitted a request for 
De Novo classification of the FilmArray[supreg] Meningitis/Encephalitis 
(ME) 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, 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 general controls, will provide reasonable assurance of the 
safety and effectiveness of the device.
    Therefore, on October 8, 2015, FDA issued an order to the requestor 
classifying the device into class II. FDA is codifying the 
classification of the device by adding 21 CFR 866.3970. We have named 
the generic type of device, device to detect and identify microbial 
pathogen nucleic acids in cerebrospinal fluid, and it is identified as 
a qualitative in vitro device intended for the detection and 
identification of microbial-associated nucleic acid sequences from 
patients suspected of meningitis or encephalitis. A device to detect 
and identify microbial pathogen nucleic acids in cerebrospinal fluid is 
intended to aid in the diagnosis of meningitis or encephalitis when 
used in conjunction with clinical signs and symptoms and other clinical 
and laboratory findings.
    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--Device To Detect and Identify Microbial Pathogen Nucleic Acids
          in Cerebrospinal Fluid Risks and Mitigation Measures
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               Identified risks                   Mitigation measures
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Incorrect identification or lack of            Special Controls (1),
 identification of a pathogenic microorganism   (2), (3), (4), and (5).
 by the device can lead to improper patient
 management.
Failure to correctly interpret test results..  Special Controls (6),
                                                (7), (8), and (9).
Failure to correctly operate the instrument..  Special Control (10).
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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. In order 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. 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 
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 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 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.  866.3970 to subpart D to read as follows:


Sec.  866.3970  Device to detect and identify microbial pathogen 
nucleic acids in cerebrospinal fluid.

    (a) Identification. A device to detect and identify microbial 
pathogen nucleic acids in cerebrospinal fluid is a qualitative in vitro 
device intended for the detection and identification of microbial-
associated nucleic acid

[[Page 48764]]

sequences from patients suspected of meningitis or encephalitis. A 
device to detect and identify microbial pathogen nucleic acids in 
cerebrospinal fluid is intended to aid in the diagnosis of meningitis 
or encephalitis when used in conjunction with clinical signs and 
symptoms and other clinical and laboratory findings.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Premarket notification submissions must include detailed device 
description documentation, including the device components, ancillary 
reagents required but not provided, and a detailed explanation of the 
methodology, including primer/probe sequence, design, and rationale for 
sequence selection.
    (2) Premarket notification submissions must include detailed 
documentation from the following analytical studies: Analytical 
sensitivity (limit of detection), inclusivity, reproducibility, 
interference, cross reactivity, and specimen stability.
    (3) Premarket notification submissions must include detailed 
documentation from a clinical study. The study, performed on a study 
population consistent with the intended use population, must compare 
the device performance to results obtained from well-accepted 
comparator methods.
    (4) Premarket notification submissions must include detailed 
documentation for device software, including, but not limited to, 
software applications and hardware-based devices that incorporate 
software.
    (5) The Intended Use statement in the device labeling must include 
a statement that the device is intended to be used in conjunction with 
standard of care culture.
    (6) A detailed explanation of the interpretation of results and 
acceptance criteria must be included in the device's 21 CFR 
809.10(b)(9) compliant labeling.
    (7) The device labeling must include a limitation stating that the 
negative results do not preclude the possibility of central nervous 
system infection.
    (8) The device labeling must include a limitation stating that 
device results are not intended to be used as the sole basis for 
diagnosis, treatment, or other patient management decisions.
    (9) The device labeling must include a limitation stating that 
positive results do not mean that the organism detected is infectious 
or is the causative agent for clinical symptoms.
    (10) As part of the risk management activities performed as part of 
your 21 CFR 820.30 design controls, you must document an appropriate 
end user device training program that will be offered as part of your 
efforts to mitigate the risk of failure to correctly operate the 
instrument.

    Dated: October 13, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-22769 Filed 10-19-17; 8:45 am]
 BILLING CODE 4164-01-P