[Federal Register Volume 90, Number 104 (Monday, June 2, 2025)]
[Rules and Regulations]
[Pages 23281-23283]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-09883]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2025-N-1263]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Device To Detect Bacterial Protease Activity in
Chronic Wound Fluid
AGENCY: Food and Drug Administration, HHS.
ACTION: Final amendment; final order.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
classifying the device to detect bacterial protease activity in chronic
wound fluid 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 bacterial protease
activity in chronic wound fluid'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 in part
by reducing regulatory burdens.
DATES: This order is effective June 2, 2025. The classification was
applicable on December 2, 2019.
FOR FURTHER INFORMATION CONTACT: Dina Jerebitski, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 3574, Silver Spring, MD 20993-0002, 301-
796-2411, [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the device to detect bacterial
protease activity in chronic wound fluid 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 (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 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.
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 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.
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II. De Novo Classification
On March 23, 2018, FDA received Alere Scarborough, Inc.'s request
for De Novo classification of the WOUNDCHEK Bacterial Status device.
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 2, 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
866.3231.\1\ We have named the generic type of device as a device to
detect bacterial protease activity in chronic wound fluid, and it is
identified as a lateral flow prescription in vitro diagnostic device
that may include a sterile swab. The device is intended for use in
patients as an aid in assessing the risk for non-healing of chronic
venous, diabetic foot, and pressure ulcers associated with wounds where
there are no signs of wound infection and where patients are
asymptomatic for clinical signs 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--Device To Detect Bacterial Protease Activity in Chronic Wound
Fluid Risks and Mitigation Measures
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Identified risks to health Mitigation measures
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Risk of false test results... Use of certain specimen collection and
transport devices identified in special
control (1), Certain labeling
information identified in special
control (2), and Certain design
verification and validation activities
identified in special control (3).
Failure to correctly Certain labeling information identified
interpret test results. in special control (2).
Failure to correctly operate Certain labeling information identified
the device. in special control (2).
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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 final 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 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. 866.3231 to subpart D to read as follows:
Sec. 886.3231 Device to detect bacterial protease activity in chronic
wound fluid.
(a) Identification. A device to detect bacterial protease activity
in chronic wound fluid is a lateral flow prescription in vitro
diagnostic device that may include a sterile swab. The device is
intended for use in patients as an aid in assessing the risk for non-
healing of chronic venous, diabetic foot, and pressure ulcers
associated with wounds where there are no signs of wound infection and
where patients are asymptomatic for clinical signs of infection.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Any swab used to collect a patient specimen must be FDA-
cleared, -approved, or -classified as 510(k) exempt (standalone or as
part of a test system) for the collection of wound fluid specimens;
alternatively, the
[[Page 23283]]
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 the following statements:
(A) A statement that the device detects and measures bacterial
proteases from a swab saturated with wound fluid.
(B) A statement that the device provides a qualitative output to
aid the user in assessing the risk for non-healing of wounds (e.g.,
chronic venous, diabetic foot and pressure ulcers).
(C) A description of the clinical indications for test use.
(D) The specific population(s) for which the device is intended.
(E) A description of the recommended training (e.g., knowledge and
experience) for safe and effective use of the device and to minimize
the risks of incorrect results and misinterpretation.
(ii) A detailed description of the performance characteristics of
the device from the analytical and clinical studies required under
paragraphs (b)(3)(ii) and (iii) of this section.
(iii) A detailed explanation of the interpretation of results.
(iv) A warning statement describing situations where the device has
not been validated or may not perform as identified in the labeling
(e.g., not for use with wounds which are >=6 months of age and >=1
cm\2\ in size).
(v) The following limiting statements:
(A) That the device is not intended to provide a risk assessment of
chronic wound infection status or aid in the diagnosis of infection in
chronic wounds, nor is the device intended for monitoring the
effectiveness of anti-infective therapy.
(B) That a negative result does not exclude the presence of
bacterial proteases. Therefore, the results should be used in
conjunction with clinical findings to make an accurate assessment of
risk of nonhealing. The test result should be interpreted in
conjunction with other risk factors, along with clinical and laboratory
data available to the clinician.
(C) That the device has been validated using wound fluid samples
only. Other sample types (e.g., whole blood from venous or capillary
draws, other body fluids) have not been evaluated.
(D) That skin flora may secrete bacterial proteases therefore, swab
contact with intact skin should be avoided as this may yield false
positive results.
(vi) Labeling must include a brief reference sheet for healthcare
professionals that includes the intended use, summary of clinical
performance, results from analytical testing on normal skin and human
proteases, and warning and limiting statements.
(3) Design verification and validation must include the following:
(i) A detailed device description (e.g., all device parts, control
elements incorporated into the test procedure, reagents required but
not provided, and the principle of device operation and test
methodology).
(ii) Detailed documentation and results from analytical studies,
including the limit of detection, inclusivity, cross-reactivity,
microbial interference, analytical sensitivity for normal skin flora
and human proteases, interfering substances, specimen stability,
within-lab precision, and reproducibility.
(iii) Detailed documentation and results from a clinical study that
includes prospective (sequentially collected) samples for the intended
specimen type that are representative of the intended use
population(s). The clinical study must compare the device performance
to results obtained from a reference or comparator method that FDA has
determined is appropriate.
Dated: May 27, 2025.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-09883 Filed 5-30-25; 8:45 am]
BILLING CODE 4164-01-P