[Federal Register Volume 89, Number 172 (Thursday, September 5, 2024)]
[Rules and Regulations]
[Pages 72315-72317]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-19824]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 864

[Docket No. FDA-2024-N-3971]


Medical Devices; Hematology and Pathology Devices; Classification 
of the Heparin and Direct Oral Factor Xa Inhibitor Drug Test System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA or we) is classifying 
the heparin and direct oral factor Xa inhibitor drug test system 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 heparin and direct oral factor Xa inhibitor 
drug test system'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 September 5, 2024. The classification 
was applicable on September 17, 2020.

FOR FURTHER INFORMATION CONTACT: Min Wu, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3459, Silver Spring, MD 20993-0002, 301-348-1886, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the heparin and direct oral factor 
Xa inhibitor drug test system as class II (special controls), which we 
have determined will provide a reasonable assurance of safety and 
effectiveness.
    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

[[Page 72316]]

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 part 860, subpart D (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 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 
510(k) process, when necessary, to market their device.

II. De Novo Classification

    On June 25, 2019, FDA received Instrumentation Laboratory Co.'s 
request for De Novo classification of the HemosIL Liquid Anti-Xa. 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 September 17, 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 
864.7295.\1\ We have named the generic type of device heparin and 
direct oral factor Xa inhibitor drug test system, and it is identified 
as a drug test system intended for the detection of heparin and direct 
oral factor Xa inhibitors in human specimens collected from patients 
taking heparin or direct oral factor Xa inhibitors. The device is 
intended to aid in the management of therapy in conjunction with other 
clinical and laboratory findings.
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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--Heparin and Direct Oral Factor Xa Inhibitor Drug Test System;
                      Risks and Mitigation Measures
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       Identified risks to health              Mitigation measures
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False positive/false negative/failed to  Certain analytical studies and
 provide a result for diagnostics.        clinical studies in design
                                          verification and validation,
                                          and Certain labeling
                                          information.
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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 (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 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

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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 864

    Blood, Medical devices, Packaging and containers.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
864 is amended as follows:

PART 864--HEMATOLOGY AND PATHOLOGY DEVICES

0
1. The authority citation for part 864 continues to read as follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.


0
2. Add Sec.  864.7295 to subpart H to read as follows:


Sec.  864.7295   Heparin and direct oral factor Xa inhibitor drug test 
system.

    (a) Identification. A heparin and direct oral factor Xa inhibitor 
drug test system is intended for the detection of heparin and direct 
oral factor Xa inhibitors in human specimens collected from patients 
taking heparin or direct oral factor Xa inhibitors. This device is 
intended to aid in the management of therapy in conjunction with other 
clinical and laboratory findings.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Design verification and validation must include the following:
    (i) Detailed documentation of analytical device performance studies 
and results demonstrating acceptable analytical performance with a 
sufficient number of specimens tested in order to obtain unbiased 
estimates of analytical performance. This documentation shall include 
the following as appropriate to the technology, specimen types tested, 
and intended use of the device:
    (A) Studies and results for that demonstrate device precision 
including repeatability and reproducibility, using quality controls and 
clinical samples, when appropriate. Precision studies must assess 
specimens for each indicated drug at concentrations throughout the 
measuring range of the device including near clinically relevant 
levels, as appropriate. The study must evaluate different sources of 
variability including, as appropriate, between-run, between-operator, 
between-lot, between-instrument, between-day, and between-site;
    (B) Studies and results that demonstrate that the device is free 
from clinically significant interference, from endogenous and exogenous 
interferents associated with the target population(s), and interferents 
that are specific for, or related to, the technology or methodology of 
the device;
    (C) Data to demonstrate appropriate specimen stability for the 
intended sample matrices under the intended conditions for specimen 
collection, handling, and storage described in the device labeling;
    (D) Studies and results that demonstrate the linear range, limit of 
blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ), 
as applicable to the technology of the device; and
    (E) For any devices intended for use for near patient testing, 
studies and results that demonstrate the robustness of the device in 
the hands of the intended user, including the entire testing procedure, 
pre-analytical specimen processing steps, and results interpretation.
    (ii) Detailed documentation of clinical performance testing in 
which the performance is analyzed relative to a comparator that FDA has 
determined is appropriate. Specimens must be representative of the 
intended use population(s) and must cover the full range of the device 
output and any clinically relevant decision points as appropriate.
    (2) The labeling required under Sec.  809.10(b) of this chapter 
must include:
    (i) Identification of any known interferents, including all 
endogenous, exogenous, technology-specific, and patient population-
specific interferents, specific to the test outputs. The information 
must include the concentration(s) or level(s) of the interferent at 
which clinically significant interference was found to occur, and the 
concentration range or levels at which interference was not found to 
occur;
    (ii) A prominent statement that the device is not intended for use 
in monitoring patients taking heparin or direct oral factor Xa 
inhibitors; and
    (iii) Limiting statements indicating, as applicable:
    (A) That the device should only be used in conjunction with 
information available from clinical evaluations and other diagnostic 
procedures; and
    (B) That the device is not specific to the direct oral factor Xa 
inhibitor that has been evaluated and may detect the presence of other 
direct factor Xa inhibitors that have not been evaluated.

    Dated: August 29, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-19824 Filed 9-4-24; 8:45 am]
BILLING CODE 4164-01-P