[Federal Register Volume 82, Number 198 (Monday, October 16, 2017)]
[Rules and Regulations]
[Pages 47965-47967]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-22287]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2017-N-5296]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the Nucleic Acid-Based Device for the Amplification, 
Detection, and Identification of Microbial Pathogens Directly From 
Whole Blood Specimens

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 nucleic acid-based device for the amplification, detection, and 
identification of microbial pathogens directly from whole blood 
specimens 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 nucleic acid-based device for the 
amplification, detection, and identification of microbial pathogens 
directly from whole blood specimens' 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 16, 2017. The classification was 
applicable on September 22, 2014.

FOR FURTHER INFORMATION CONTACT: Steven Tjoe, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 4550, Silver Spring, MD 20993-0002, 301-796-5866, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Upon request, FDA has classified the nucleic acid-based device for 
the amplification, detection, and identification of microbial pathogens

[[Page 47966]]

directly from whole blood specimens 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 to a predicate device that does not require 
premarket approval (see 21 U.S.C. 360c(i)). 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 and part 807 (21 U.S.C. 360(k) and 21 CFR part 807, respectively).
    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 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 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 PMA 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 May 27, 2014, T2 Biosystems, Inc., submitted a request for 
classification of the T2Candida Panel and T2Dx[supreg] Instrument. 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 September 22, 2014, 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 866.3960. We have named 
the generic type of device nucleic acid-based device for the 
amplification, detection, and identification of microbial pathogens 
directly from whole blood specimens, and it is identified as a 
qualitative in vitro device intended for the amplification, detection, 
and identification of microbial-associated nucleic acid sequences from 
patients with suspected bloodstream infections. This device is intended 
to aid in the diagnosis of bloodstream infection when used in 
conjunction with clinical signs and symptoms and other 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--Nucleic Acid-Based Device for the Amplification, Detection, and
     Identification of Microbial Pathogens Directly From Whole Blood
                 Specimens Risks and Mitigation Measures
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            Identified risks                   Mitigations measures
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Incorrect identification of a            Special Controls (1), (2), (3),
 pathogenic microorganism by the device   (4), and (5).
 can lead to improper patient
 management.
Failure to correctly interpret test      Special Control (6).
 results.
Failure to correctly operate the         Special Controls (7) and (8).
 instrument.
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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

[[Page 47967]]

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.  866.3960 to subpart D to read as follows:


Sec.  866.3960  Nucleic acid-based device for the amplification, 
detection, and identification of microbial pathogens directly from 
whole blood specimens.

    (a) Identification. A nucleic acid-based device for the 
amplification, detection, and identification of microbial pathogens 
directly from whole blood specimens is a qualitative in vitro device 
intended for the amplification, detection, and identification of 
microbial-associated nucleic acid sequences from patients with 
suspected bloodstream infections. This device is intended to aid in the 
diagnosis of bloodstream infection when used in conjunction with 
clinical signs and symptoms and other 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 and clinical performance 
studies: Analytical sensitivity (limit of detection), reactivity, 
inclusivity, precision, reproducibility, interference, cross 
reactivity, carryover, and cross contamination.
    (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 reference 
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 device labeling must include limitations regarding the need 
for culture confirmation of negative specimens, as appropriate.
    (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) Premarket notification submissions must include details on an 
end user device training program that will be offered while marketing 
the device, as appropriate.
    (8) 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 10, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-22287 Filed 10-13-17; 8:45 am]
 BILLING CODE 4164-01-P