Rule2025-09639
Medical Devices; Immunology and Microbiology Devices; Classification of the Zika Virus Serological Reagents
Primary source
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Published
May 29, 2025
Effective
May 29, 2025
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, Agency, or we) is classifying the Zika virus serological reagents 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 Zika virus serological reagents' 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.
Full Text
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<title>Federal Register, Volume 90 Issue 102 (Thursday, May 29, 2025)</title>
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[Federal Register Volume 90, Number 102 (Thursday, May 29, 2025)]
[Rules and Regulations]
[Pages 22632-22634]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-09639]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2025-N-1160]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Zika Virus Serological Reagents
AGENCY: Food and Drug Administration, HHS.
ACTION: Final amendment; final order.
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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
classifying the Zika virus serological reagents 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 Zika virus serological reagents' 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 May 29, 2025. The classification was
applicable on May 23, 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, <a href="/cdn-cgi/l/email-protection#3d7954535c1377584f585f54494e56547d5b595c1355554e135a524b"><span class="__cf_email__" data-cfemail="03476a6d622d49667166616a7770686a436567622d6b6b702d646c75">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified Zika virus serological reagents 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 (21 U.S.C. 360c(a)(1)). 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.
II. De Novo Classification
On December 26, 2018, FDA received InBios International, Inc.'s
request for De Novo classification of the ZIKV Detect 2.0 IgM Capture
ELISA. 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 May 23, 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
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CFR 866.3935.\1\ We have named the generic type of device ``Zika virus
serological reagents,'' and it is identified as in vitro diagnostic
devices that consist of antigens or antibodies for the detection of
Zika virus or Zika antibodies in human specimens from individuals who
have signs and symptoms consistent with Zika virus infection and/or
epidemiological risk factors. The detection aids in the diagnosis of
current or recent Zika virus infection or serological status. Negative
results obtained with this test do not preclude the possibility of Zika
virus infection, past or present. Positive results should be
interpreted with consideration of other clinical information and
laboratory findings and should not be used as the sole basis for
treatment or other patient management decisions.
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\1\ FDA notes 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--Zika Virus Serological Reagents Risks and Mitigation Measures
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Identified risks to health Mitigation measures
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Risk of false results........ Certain device description, performance
characteristics, and study details in
labeling; Certain device description,
validation procedures, and studies; and
Certain device limitations in labeling.
Failure to correctly Certain device description, performance
interpret test results. characteristics, and study details in
labeling; and Certain device limitations
in labeling.
Failure to correctly operate Certain device description, performance
the device. characteristics, and study details in
labeling; Certain device description,
validation procedures, and studies; and
Certain device limitations in labeling.
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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 collections of information in 21 CFR part
820, regarding the 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. 866.3935 to subpart D to read as follows:
Sec. 866.3935 Zika virus serological reagents.
(a) Identification. Zika virus serological reagents are in vitro
diagnostic devices that consist of antigens or antibodies for the
detection of Zika virus or Zika antibodies in human specimens from
individuals who have signs and symptoms consistent with Zika virus
infection and/or epidemiological risk factors. The detection aids in
the diagnosis of current or recent Zika virus infection or serological
status. Negative results obtained with this test do not preclude the
possibility of Zika virus infection, past or present. Positive results
should be interpreted with consideration of other clinical information
and laboratory findings and should not be used as the sole basis for
treatment or other patient management decisions.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) The labeling required under Sec. 809.10(b) of this chapter
must include:
(i) An intended use with a detailed description of what the device
detects (Zika IgM antibodies, other Zika antibodies, or Zika antigens),
the type of results provided to the user, the specimen type for which
testing is indicated (e.g., serum, whole blood), the clinical
indications appropriate for test use, and the specific population(s)
for which the test is intended.
(ii) Performance characteristics from analytical and clinical
studies required under paragraphs (b)(2)(ii) and (iii) of this section.
(iii) A detailed explanation of the interpretation of results and
criteria for validity of results (e.g., criteria that internal or
external quality controls must meet in order for a test/test run to be
valid, minimum signal strength that
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the sample has to yield to be interpretable as a valid result).
(iv) Limiting statements indicating that:
(A) Results are not intended to be used as the sole basis for
diagnosis, treatment, or other patient management decisions. The test
results should be interpreted in conjunction with clinical
observations, patient history, epidemiological information, and other
laboratory evidence.
(B) Device results are intended to be followed up according to the
latest professional guidelines (e.g., recommendations from the Centers
for Disease Control and Prevention) for the diagnosis of Zika virus
infection.
(C) Negative test results do not preclude the possibility of Zika
virus infection, past or present.
(D) Specimens can result in false negative results on the device if
collected outside of the appropriate response window for specific Zika
virus antigens or antibodies, as determined by scientific evidence
(e.g., for IgM <7 days post symptom onset (pso) or risk of exposure and
if collected past 84 days pso).
(v) Detailed instructions for use that minimize the risk of
generating a false positive or false negative result (e.g., co-testing
of other matrices).
(2) Design verification and validation must include:
(i) A detailed device description, including all device parts
(e.g., Zika antigen target, other flavivirus antigen target, capture
antibodies), instrument requirements, ancillary reagents required but
not provided, and the technological characteristics, including all pre-
analytical methods for specimen processing.
(ii) Detailed documentation and results from analytical performance
studies including: characterization of the cut-off(s), analytical
sensitivity to a standardized reference material that FDA has
determined is appropriate (e.g., World Health Organization reference
standard or the Centers for Disease Control and Prevention reference
standard), class specificity for human antibodies (e.g., IgM or IgG),
analytical specificity (cross reactivity including cross reactivity to
other flaviviruses), interference, carryover/cross contamination,
specimen stability, hook effect (if applicable), matrix equivalency (if
applicable), freeze-thaw studies (if applicable), and reproducibility.
(iii) Detailed documentation and results from clinical studies,
including the clinical study protocol (with a description of the
testing algorithm and results interpretation table), detailed clinical
study report, including line data of the clinical study results, and
other appropriate statistical analysis. The samples used in the
clinical study must be collected from subjects representative of the
full spectrum of the intended use population (e.g., endemic and non-
endemic regions if both are indicated).
Dated: May 22, 2025.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-09639 Filed 5-28-25; 8:45 am]
BILLING CODE 4164-01-P
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