Document ID: FDA-2021-N-0807-0001
Agency: fda
Document Type: Rule
Title: Medical Devices; Immunology and Microbiology Devices; Classification of the System for Detection of Microorganisms and Antimicrobial Resistance Using Reporter Expression
Posted Date: 2022-02-04T05:00Z

[Federal Register Volume 87, Number 24 (Friday, February 4, 2022)]
[Rules and Regulations]
[Pages 6415-6417]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-02368]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2021-N-0807]

Medical Devices; Immunology and Microbiology Devices; 
Classification of the System for Detection of Microorganisms and 
Antimicrobial Resistance Using Reporter Expression

AGENCY: Food and Drug Administration, Department of Health and Human 
Services (HHS).

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA or we) is classifying 
the system for detection of microorganisms and antimicrobial resistance 
using reporter expression 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 system for detection of 
microorganisms and antimicrobial resistance using reporter expression'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.

DATES: This order is effective February 4, 2022. The classification was 
applicable on December 5, 2019.

FOR FURTHER INFORMATION CONTACT: Tobin Hellyer, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3272, Silver Spring, MD 20993-0002, 301-796-6154, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the system for detection of 
microorganisms and antimicrobial resistance using reporter expression 
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 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 device 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

[[Page 6416]]

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 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. 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 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 19, 2019, FDA received Roche Molecular Systems, Inc.'s 
request for De Novo classification of the cobas vivoDx MRSA. 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 December 5, 2019, FDA issued an order to the 
requester classifying the device into class II. In this final order, 
FDA is codifying the classification of the device by adding 21 CFR 
866.1655.\1\ We have named the generic type of device system for 
detection of microorganisms and antimicrobial resistance using reporter 
expression, and it is identified as an in vitro diagnostic device 
intended for the detection and identification of live microorganisms 
and the detection of associated antimicrobial drug susceptibility or 
resistance in specimens from patients at risk of colonization or 
suspected of infection.
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    \1\ FDA notes that the ACTION caption for this final order is 
styled as ``Final amendment; final order,'' rather than ``Final 
order.'' Beginning in December 2019, this editorial change was made 
to indicate that the document ``amends'' the Code of Federal 
Regulations. The change was made in accordance with the Office of 
Federal Register's (OFR) interpretations of the Federal Register Act 
(44 U.S.C. chapter 15), its implementing regulations (1 CFR 5.9 and 
parts 21 and 22), and the Document Drafting Handbook.
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    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--System for Detection of Microorganisms and Antimicrobial
   Resistance Using Reporter Expression Risks and Mitigation Measures
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            Identified risks                   Mitigation measures
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Failure to use the device correctly....  Certain labeling information
                                          identified in special controls
                                          (b)(1) and (3), and Certain
                                          design verification and
                                          validation identified in
                                          special control (b)(4)(vii).
False positive or negative results.....  Certain labeling information
                                          identified in special controls
                                          (b)(1) and (3), Use of certain
                                          specimen collection and
                                          transport devices identified
                                          in special control (b)(2), and
                                          Certain design verification
                                          and validation identified in
                                          special control (b)(4).
Failure to interpret results correctly.  Certain labeling information
                                          identified in special controls
                                          (b)(1) and (3), and Certain
                                          design verification and
                                          validation identified in
                                          special control (b)(4)(vii).
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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 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

[[Page 6417]]

(OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). 
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; the collections of information in 
21 CFR 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.  866.1655 to subpart B to read as follows:

Sec.  866.1655  System for detection of microorganisms and 
antimicrobial resistance using reporter expression.

    (a) Identification. A system for detection of microorganisms and 
antimicrobial resistance using reporter expression is an in vitro 
diagnostic device intended for the detection and identification of live 
microorganisms and the detection of associated antimicrobial drug 
susceptibility or resistance in specimens from patients at risk of 
colonization or suspected of infection.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) The intended use for the device in the labeling required under 
Sec.  809.10 of this chapter must include a detailed description of the 
targets 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) Any device used for specimen collection and transport must be 
FDA-cleared, approved, or -classified as 510(k) exempt (standalone or 
as part of a test system) for the collection of the specimen types 
claimed by this device and for the maintenance of viability of the 
targeted microorganisms; alternatively, the specimen collection device 
must be cleared in a premarket submission as a part of this device.
    (3) The labeling required under Sec.  809.10(b) of this chapter 
must include:
    (i) A detailed description of the device, including reagents, 
instruments, ancillary materials, applicable specimen collection and 
transport device(s) and control elements, and a detailed explanation of 
the methodology, including all pre-analytical methods for handling and 
processing of specimens and controls to maintain organism viability;
    (ii) Detailed descriptions of the test procedure, including the 
preparation and maintenance of quality controls and the interpretation 
of test results;
    (iii) Detailed discussion of the performance characteristics of the 
device for all claimed organisms and specimen types based on analytical 
studies, including evaluation of analytical sensitivity, inclusivity, 
cross-reactivity, potentially interfering substances and 
microorganisms, contamination, specimen stability, precision, and 
reproducibility;
    (iv) Detailed discussion of the performance characteristics of the 
device observed in a clinical study performed on a population that is 
consistent with the intended use population in comparison to the 
results obtained by a reference or comparator method determined to be 
acceptable by FDA, for microbial detection, identification, and 
antimicrobial susceptibility testing; and
    (v) A limiting statement indicating that a negative test result 
does not preclude colonization or infection with organisms that do not 
express detectable levels of the reporter that is identified by the 
device.
    (4) Design verification and validation must include:
    (i) A detailed description of the device, including an explanation 
of the technology, hardware, software, and consumables, as well as an 
explanation of the result algorithms and method(s) of data processing 
from signal acquisition to result assignment;
    (ii) A detailed description of the impact of any software, 
including software applications and hardware-based devices that 
incorporate software, on the device's functions;
    (iii) Detailed documentation of the analytical and clinical studies 
required in paragraphs (b)(3)(iii) and (iv) of this section, including 
the study protocols containing descriptions of the test methods, 
prescribed methods of data analysis and acceptance criteria, final 
study reports, and data line listings;
    (iv) Detailed documentation of quality control procedures, 
including an explanation of how quality control materials were 
selected, the recommended frequency of testing, methods of control 
preparation, acceptance criteria for performance and the results from 
quality control testing performed during the analytical and clinical 
studies required under paragraphs (b)(3)(iii) and (iv) of this section;
    (v) Detailed documentation of studies performed to establish 
onboard and in-use reagent stability, including the test method(s), 
data analysis plans, acceptance criteria, final study reports, and data 
line listings;
    (vi) Detailed documentation of studies to establish reagent shelf-
life for the assay kit and each applicable specimen collection and 
transport device, including study protocols containing descriptions of 
the test method(s), data analysis plans, and acceptance criteria; and
    (vii) Documentation of an appropriate end user device training 
program that will be offered as part of efforts to assure appropriate 
conduct of the assay and to mitigate the risk associated with false 
results, including failure to use the device correctly or correctly 
interpret results.

    Dated: January 25, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-02368 Filed 2-3-22; 8:45 am]
BILLING CODE 4164-01-P