[Federal Register Volume 89, Number 159 (Friday, August 16, 2024)]
[Rules and Regulations]
[Pages 66556-66558]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-18264]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2024-N-3358]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the Device To Detect and Identify Selected Microbial 
Agents That Cause Acute Febrile Illness

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
classifying the device to detect and identify selected microbial agents 
that cause acute febrile illness 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 selected microbial agents that cause acute febrile 
illness'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 August 16, 2024. The classification was 
applicable on November 20, 2020.

FOR FURTHER INFORMATION CONTACT: Bryan Grabias, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3260, Silver Spring, MD 20993-0002, 240-402-9563, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the device to detect and identify 
selected microbial agents that cause acute febrile illness 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 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 (see 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 common name for the process authorized under section 513(f)(2) of the 
FD&C Act (see also 21 CFR part 860, subpart D). Section 207 of the Food 
and Drug Administration Modernization Act of 1997 (Pub. L. 105-115) 
established the first procedure for De Novo classification. Section 607 
of the Food and Drug Administration Safety and Innovation Act (Pub. L. 
112-144) modified the De Novo application process by adding a second 
procedure. 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

[[Page 66557]]

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.
    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 section 513(f)(2)(B)(i) of the FD&C 
Act). 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 section 513(i) of the FD&C Act, 
defining ``substantial equivalence''). Instead, sponsors can use the 
less-burdensome 510(k) process, when necessary, to market their device.

II. De Novo Classification

    On June 26, 2020, FDA received BioFire Defense, LLC's request for 
De Novo classification of the FilmArray Global Fever 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 the 
general controls, will provide reasonable assurance of the safety and 
effectiveness of the device.
    Therefore, on November 20, 2020, 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 
866.3966.\1\ We have named the generic type of device as a device to 
detect and identify selected microbial agents that cause acute febrile 
illness, and it is identified as an in vitro device intended for the 
detection and identification of microbial agents in human clinical 
specimens from patients with signs and symptoms of acute febrile 
illness who are at risk for exposure or who may have been exposed to 
these agents. It is intended to aid in the diagnosis of acute febrile 
illness in conjunction with other clinical, epidemiologic, and 
laboratory data, including patient travel, pathogen endemicity, or 
other risk factors.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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 Selected Microbial Agents That
        Cause Acute Febrile Illness Risks and Mitigation Measures
------------------------------------------------------------------------
            Identified risks                   Mitigation measures
------------------------------------------------------------------------
Risk of an inaccurate test result        Certain labeling information,
 (false positive or false negative        including certain limiting
 result) leading to improper patient      statements and performance
 management.                              information; Certain design
                                          verification and validation,
                                          including certain analytical
                                          studies and clinical studies;
                                          and Use of certain specimen
                                          collection devices.
Misinterpretation of test results        Certain labeling information,
 leading to misdiagnosis and associated   including certain limiting
 risk of false test results.              statements and performance
                                          information; and Certain
                                          design verification and
                                          validation, including certain
                                          analytical studies and
                                          clinical studies.
Failure to correctly operate the device  Certain labeling information,
 leading to inaccurate test results.      including certain limiting
                                          statements and performance
                                          information; Certain design
                                          verification and validation,
                                          including certain analytical
                                          studies and clinical studies;
                                          and Use of certain specimen
                                          collection devices.
------------------------------------------------------------------------

    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 and guidance. 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. 3501-3521). The collections 
of information in part 860, subpart D, regarding De Novo classification 
have been approved under OMB control number 0910-0844; the

[[Page 66558]]

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.  866.3966 to read as follows:


Sec.  866.3966  Device to detect and identify selected microbial agents 
that cause acute febrile illness.

    (a) Identification. A device to detect and identify selected 
microbial agents that cause acute febrile illness is identified as an 
in vitro device intended for the detection and identification of 
microbial agents in human clinical specimens from patients with signs 
and symptoms of acute febrile illness who are at risk for exposure or 
who may have been exposed to these agents. It is intended to aid in the 
diagnosis of acute febrile illness in conjunction with other clinical, 
epidemiologic, and laboratory data, including patient travel, pathogen 
endemicity, or other risk factors.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Any sample collection device used must be FDA-cleared, -
approved, or -classified as 510(k) exempt (standalone or as part of a 
test system) for the collection of specimen types claimed by this 
device; alternatively, the sample collection device must be cleared in 
a premarket submission as a part of this device.
    (2) The labeling required under Sec.  809.10(b) of this chapter 
must include:
    (i) An intended use that includes a detailed description of targets 
the device detects and measures, the results provided to the user, the 
clinical indications appropriate for test use, and the specific 
population(s) for which the device is intended.
    (ii) Limiting statements indicating:
    (A) Not all pathogens that cause febrile illness are detected by 
this test and negative results do not rule out the presence of other 
infections;
    (B) Evaluation of more common causes of acute febrile illness 
should be considered prior to evaluation with this test;
    (C) Test results are to be interpreted in conjunction with other 
clinical, epidemiologic, and laboratory data available to the 
clinician; and
    (D) When using this test, consider patient travel history and 
exposure risk, as some pathogens are more common in certain 
geographical locations.
    (iii) A detailed device description, including reagents, 
instruments, ancillary materials, all control elements, and a detailed 
explanation of the methodology, including all pre-analytical methods 
for processing of specimens.
    (iv) Detailed discussion of the performance characteristics of the 
device for all claimed specimen types as shown by the analytical and 
clinical studies required under paragraphs (b)(3)(ii) and (iii) of this 
section, except specimen stability performance characteristics.
    (v) A statement that nationally notifiable results are to be 
reported to public health authorities in accordance with local, state, 
and federal law.
    (3) Design verification and validation must include:
    (i) A detailed device description (e.g., all device parts, control 
elements incorporated into the test procedure, reagents required but 
not provided, the principle of device operation and test methodology), 
and the computational path from collected raw data to reported result 
(e.g., how collected raw signals are converted into a reported result).
    (ii) Detailed documentation of analytical studies, including those 
demonstrating Limit of Detection (LoD), inclusivity, cross-reactivity, 
microbial interference, interfering substances, competitive inhibition, 
carryover/cross contamination, specimen stability, within lab 
precision, and reproducibility, as appropriate.
    (iii) Detailed documentation and performance results from a 
clinical study that includes prospective (sequentially collected) 
samples for each claimed specimen type and, when determined to be 
appropriate by FDA, additional characterized clinical 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 FDA-accepted comparator methods. Documentation from the 
clinical studies must include the clinical study protocol (including a 
predefined statistical analysis plan), study report, testing results, 
and results of all statistical analyses.
    (iv) A detailed description of the impact of any software, 
including software applications and hardware-based devices that 
incorporate software, on the device's functions.

    Dated: August 12, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-18264 Filed 8-15-24; 8:45 am]
BILLING CODE 4164-01-P