Document ID: FDA-2017-N-5657-0001
Agency: fda
Document Type: Rule
Title: Medical Devices; Immunology and Microbiology Devices; Classification of the Device To Detect and Measure Non-Microbial Analyte(s) in Human
Clinical Specimens To Aid in Assessment of Patients With Suspected Sepsis
Posted Date: 2017-10-24T04:00Z

[Federal Register Volume 82, Number 204 (Tuesday, October 24, 2017)]
[Rules and Regulations]
[Pages 49098-49100]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-22994]

[[Page 49098]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2017-N-5657]

Medical Devices; Immunology and Microbiology Devices; 
Classification of the Device To Detect and Measure Non-Microbial 
Analyte(s) in Human Clinical Specimens To Aid in Assessment of Patients 
With Suspected Sepsis

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 measure non-microbial analyte(s) in human 
clinical specimens to aid in assessment of patients with suspected 
sepsis 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 device to detect and measure non-
microbial analyte(s) in human clinical specimens to aid in assessment 
of patients with suspected sepsis'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 24, 2017. The classification was 
applicable on February 20, 2016.

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 device to detect and measure 
non-microbial analyte(s) in human clinical specimens to aid in 
assessment of patients with suspected sepsis 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 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 March 4, 2015, B[middot]R[middot]A[middot]H[middot]M[middot]S 
GmbH, part of Thermo Fisher Scientific, submitted a request for De Novo 
classification of the B[middot]R[middot]A[middot]H[middot]M[middot]S 
PCT sensitive KRYPTOR. 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 February 20, 2016, 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 866.3215. We have named 
the generic type of device, device to detect and measure non-microbial 
analyte(s) in human clinical specimens to aid in assessment of patients 
with suspected sepsis, and it is identified as an in vitro device 
intended for the detection and qualitative and/or quantitative 
measurement of one or more non-microbial analytes in human clinical 
specimens to aid in the

[[Page 49099]]

assessment of patients with suspected sepsis 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 Measure Non-Microbial Analyte(s) in Human
   Clinical Specimens To Aid in Assessment of Patients With Suspected
                  Sepsis Risks and Mitigation Measures
------------------------------------------------------------------------
                                            Mitigation measures/21 CFR
            Identified risks                         section
------------------------------------------------------------------------
Incorrect determination of               Special Controls (2), (3), and
 procalcitonin (PCT) value, including     (7) (21 CFR 866.3215(b)(2); 21
 false positives and false negatives,     CFR 866.3215(b)(3); and 21 CFR
 by the device can lead to improper       866.3215(b)(7)).
 patient management.
Incorrect interpretation of device       Special Controls (1), (4), (5),
 results by end user can lead to          (6), and (7) (21 CFR
 improper patient management.             866.3215(b)(1); 21 CFR
                                          866.3215(b)(4); 21 CFR
                                          866.3215(b)(5); 21 CFR
                                          866.3215(b)(6); and 21 CFR
                                          866.3215(b)(7)).
Manual calculation error of final        Special Control (7) (21 CFR
 results.                                 866.3215(b)(7)).
------------------------------------------------------------------------

    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 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.  866.3215 to subpart D to read as follows:

Sec.  866.3215   Device to detect and measure non-microbial analyte(s) 
in human clinical specimens to aid in assessment of patients with 
suspected sepsis.

    (a) Identification. A device to detect and measure non-microbial 
analyte(s) in human clinical specimens to aid in assessment of patients 
with suspected sepsis is identified as an in vitro device intended for 
the detection and qualitative and/or quantitative measurement of one or 
more non-microbial analytes in human clinical specimens to aid in the 
assessment of patients with suspected sepsis 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 the device's 
detailed Indications for Use statement describing what the device 
detects and measures, the results provided to the user, whether the 
measure is qualitative and/or quantitative, the clinical indications 
for which the test is to be used, and the specific population(s) for 
which the device use is intended.
    (2) Premarket notification submissions must include detailed 
documentation of the device description, including (as applicable), all 
device components, software, ancillary reagents required but not 
provided, explanation of the device principle and methodology, and for 
molecular devices include detailed documentation of the primer/probe 
sequence, design, and rationale for sequence selection.
    (3) Premarket notification submissions must include detailed 
documentation of applicable analytical studies, such as, analytical 
sensitivity (Limit of Detection, Limit of Blank, and Limit of 
Quantitation), precision, reproducibility, analytical measuring range, 
interference, cross-reactivity, and specimen stability.
    (4) Premarket notification submissions must include detailed 
documentation of a prospective clinical study or, if appropriate, 
results from an equivalent sample set. This detailed documentation must 
include the following information:
    (i) Results must demonstrate adequate device performance relative 
to a well-accepted comparator.
    (ii) Clinical sample results must demonstrate consistency of device 
output throughout the device measuring range likely to be encountered 
in the Intended Use population.
    (iii) Clinical study documentation must include the original study 
protocol (including predefined statistical analysis plan), study report 
documenting support for the Indications for Use(s), and results of all 
statistical analyses.
    (5) Premarket notification submissions must include evaluation of 
the level of the non-microbial analyte in asymptomatic patients with 
demographic characteristics (e.g., age, racial, ethnic, and gender 
distribution) similar to the Intended Use population.
    (6) As part of the risk management activities performed under 21 
CFR 820.30 design controls, you must document an appropriate end user 
device training program that will be

[[Page 49100]]

offered as part of your efforts to mitigate the risk of failure to 
correctly operate the instrument.
    (7) 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, and a detailed explanation of the 
interpretation of the limitations of the samples (e.g., collected on 
day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) 
compliant labeling.

    Dated: October 18, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-22994 Filed 10-23-17; 8:45 am]
 BILLING CODE 4164-01-P