[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