[Federal Register Volume 84, Number 50 (Thursday, March 14, 2019)]
[Rules and Regulations]
[Pages 9226-9228]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-04719]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2019-N-0360]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Device To Detect and Identify Microorganisms and
Associated Resistance Marker Nucleic Acids Directly in Respiratory
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 device to detect and identify microorganisms and associated
resistance marker nucleic acids directly in respiratory 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 device to detect and identify microorganisms
and associated resistance marker nucleic acids directly in respiratory
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 March 14, 2019. The classification was
applicable on April 3, 2018.
FOR FURTHER INFORMATION CONTACT: Dina Jerebitski, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 4450, Silver Spring, MD 20993-0002, 301-
796-4221, [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the device to detect and identify
microorganisms and associated resistance marker nucleic acids directly
in respiratory 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 (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) (21 U.S.C.
360(k)) of the FD&C
[[Page 9227]]
Act and Part 807 (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 510(k) process, when
necessary, to market their device.
II. De Novo Classification
On September 11, 2017, Curetis GmbH submitted a request for De Novo
classification of the Unyvero LRT Application. 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 3, 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 866.3985. We have named
the generic type of device ``device to detect and identify
microorganisms and associated resistance marker nucleic acids directly
in respiratory specimens,'' and it is identified as an in vitro
diagnostic device intended for the detection and identification of
microorganisms and associated resistance markers in respiratory
specimens collected from patients with signs or symptoms of respiratory
infection. The device is intended to aid in the diagnosis of
respiratory infection in conjunction with clinical signs and symptoms
and other laboratory findings. These devices do not provide
confirmation of antibiotic susceptibility since mechanisms of
resistance may exist other than those detected by the device.
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 Microorganisms and Associated
Resistance Marker Nucleic Acids Directly in Respiratory Specimens Risks
and Mitigation Measures
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Identified risks Mitigation measures
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Incorrect identification or General Controls and Special Controls (1)
lack of identification of a (21 CFR 866.3985(b)(1)), (2) (21 CFR
pathogenic microorganism by 866.3985(b)(2)), (3) (21 CFR
the device can lead to 866.3985(b)(3)), and (4) (21 CFR
improper patient management. 866.3985(b)(4)).
Failure to correctly General Controls and Special Controls (1)
interpret test results. (21 CFR 866.3985(b)(1)), (2)(iii) (21
CFR 866.3985(b)(2)(iii)), (2)(iv) (21
CFR 866.3985(b)(2)(iv)), (2)(v) (21 CFR
866.3985(b)(2)(v)), (2)(vi) (21 CFR
866.3985(b)(2)(vi)), (2)(vii) (21 CFR
866.3985(b)(2)(vii)), (2)(viii) (21 CFR
866.3985(b)(2)(viii)), and (3) (21 CFR
866.3985(b)(3)).
Failure to correctly operate General Controls and Special Controls (1)
the instrument. (21 CFR 866.3985(b)(1)), (2)(i) (21 CFR
866.3985(b)(2)(i)), (4)(ii) (21 CFR
866.3985(b)(4)(ii)), (4)(iii) (21 CFR
866.3985(b)(4)(iii)), and (4)(iv) (21
CFR 866.3985(b)(4)(iv)).
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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).
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
[[Page 9228]]
(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 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
part 820, regarding quality system regulation, 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. 866.3985 to subpart D to read as follows:
Sec. 866.3985 Device to detect and identify microorganisms and
associated resistance marker nucleic acids directly in respiratory
specimens.
(a) Identification. A device to detect and identify microorganisms
and associated resistance marker nucleic acids directly from
respiratory specimens is an in vitro diagnostic device intended for the
detection and identification of microorganisms and associated
resistance markers in respiratory specimens collected from patients
with signs or symptoms of respiratory infection. The device is intended
to aid in the diagnosis of respiratory infection in conjunction with
clinical signs and symptoms and other laboratory findings. These
devices do not provide confirmation of antibiotic susceptibility since
mechanisms of resistance may exist other than those detected by the
device.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) The intended use for the 21 CFR 809.10 labeling must include a
detailed description of what the device detects, the type of results
provided to the user, the clinical indications appropriate for test
use, and the specific population(s) for which the device is intended.
(2) The 21 CFR 809.10(b) labeling must include:
(i) A detailed device description, including all device components,
control elements incorporated into the test procedure, instrument
requirements, ancillary reagents required but not provided, and a
detailed explanation of the methodology, including all pre-analytical
methods for processing of specimens.
(ii) Performance characteristics from analytical studies,
including, but not limited to, limit of detection, inclusivity,
reproducibility, cross reactivity, interfering substances, competitive
inhibition, carryover/cross contamination, specimen stability, and
linearity, as applicable.
(iii) A limiting statement that the device is intended to be used
in conjunction with clinical history, signs and symptoms, and results
of other diagnostic tests, including culture and antimicrobial
susceptibility testing.
(iv) A detailed explanation of the interpretation of test results
for clinical specimens and acceptance criteria for any quality control
testing.
(v) A limiting statement that negative results for microorganisms
do not preclude the possibility of infection, and should not be used as
the sole basis for diagnosis, treatment, or other patient management
decisions.
(vi) If applicable, a limiting statement that detected
microorganisms may not be the cause of lower respiratory tract
infection and may be indicative of colonizing or normal respiratory
flora.
(vii) If applicable, a limiting statement that detection of
resistance markers cannot be definitively linked to specific
microorganisms and that the source of a detected resistance marker may
be an organism not detected by the assay, including colonizing flora.
(viii) If applicable, a limiting statement that detection of
antibiotic resistance markers may not correlate with phenotypic gene
expression.
(3) The 21 CFR 809.10(b) labeling and any test report generated by
the device must include a limiting statement that negative results for
resistance markers do not indicate susceptibility of detected
microorganisms.
(4) Design verification and validation must include:
(i) Performance characteristics from clinical studies that include
prospective (sequential) samples and, if appropriate, additional
characterized samples. The study must be performed on a study
population consistent with the intended use population and compare the
device performance to results obtained from an FDA accepted reference
method and/or FDA accepted comparator method, as appropriate. Results
from the clinical studies must include the clinical study protocol
(including predefined statistical analysis plan, if applicable),
clinical study report, and results of all statistical analyses.
(ii) A detailed device description including the following:
(A) Thorough description of the assay methodology including, but
not limited to, primer/probe sequences, primer/probe design, and
rationale for target sequence selection, as applicable.
(B) Algorithm used to generate a final result from raw data (e.g.,
how raw signals are converted into a reported result).
(iii) A detailed description of device software, including, but not
limited to, validation activities and outcomes.
(iv) As part of the risk management activities, an appropriate end
user device training program must be offered as an effort to mitigate
the risk of failure from user error.
Dated: March 8, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019-04719 Filed 3-13-19; 8:45 am]
BILLING CODE 4164-01-P