Rule2025-11794
Medical Devices; Immunology and Microbiology Devices; Classification of the Herpes Simplex Virus Nucleic Acid-Based Assay for Central Nervous System Infections
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Published
June 26, 2025
Effective
June 26, 2025
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, the Agency, or we) is classifying the herpes simplex virus nucleic acid-based assay for central nervous system infections 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 classification of the herpes simplex virus nucleic acid-based assay for central nervous system infections. 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 121 (Thursday, June 26, 2025)</title>
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[Federal Register Volume 90, Number 121 (Thursday, June 26, 2025)]
[Rules and Regulations]
[Pages 27234-27236]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-11794]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2025-N-1448]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Herpes Simplex Virus Nucleic Acid-Based Assay for
Central Nervous System Infections
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 herpes simplex virus nucleic acid-based assay for
central nervous system infections 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 classification of
the herpes simplex virus nucleic acid-based assay for central nervous
system infections. 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 26, 2025. The classification was
applicable on March 21, 2014.
FOR FURTHER INFORMATION CONTACT: Scott McFarland, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 3572, Silver Spring, MD 20993-0002, 301-
796-6217, <a href="/cdn-cgi/l/email-protection#8bd8e8e4ffffa5c6e8edeaf9e7eae5efcbedefeaa5e3e3f8a5ece4fd"><span class="__cf_email__" data-cfemail="5a0939352e2e7417393c3b28363b343e1a3c3e3b74323229743d352c">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the herpes simplex virus (HSV)
nucleic acid-based assay for central nervous system (CNS) infections 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 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.
II. De Novo Classification
On December 4, 2013, FDA received Focus Diagnostics, Inc.'s request
for De Novo classification of the Simplexa<SUP>TM</SUP> HSV 1 & 2
Direct. 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 general
controls, will provide reasonable assurance of the safety and
effectiveness of the device.
[[Page 27235]]
Therefore, on March 21, 2014, FDA issued an order to the requestor
classifying the device into class II. In this final order, FDA is
codifying the classification of the device by adding 21 CFR
866.3307.\1\ We have named the generic type of device herpes simplex
virus nucleic acid-based assay for central nervous system infections,
and it is identified as a qualitative in vitro diagnostic device
intended for the detection and differentiation of HSV-1 and HSV-2 in
cerebrospinal fluid (CSF) samples from patients suspected of HSV
infections of the CNS. This test is intended as an aid in the diagnosis
of HSV-1 and HSV-2 infections of the CNS. Negative results do not
preclude HSV-1 or HSV-2 infection and should not be used as the sole
basis for treatment or other patient management decisions.
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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--Herpes Simplex Virus Nucleic Acid-Based Assay for Central
Nervous System Infections Risks and Mitigation Measures
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Identified risks to health Mitigation measures
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Risk of false results.................. Special controls (1)(i) (21 CFR
866.3307(b)(1)(i)), (1)(ii)
(21 CFR 866.3307(b)(1)(ii)),
and (1)(iii) (21 CFR
866.3307(b)(1)(iii)).
Failure to correctly interpret test Special control (2) (21 CFR
results. 866.3307(b)(2)).
Failure to correctly operate the Special controls (1)(iv) (21
instrument. CFR 866.3307(1)(iv)) and
(1)(v) (21 CFR
866.3307(b)(1)(v)).
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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
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 21 CFR part 866 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 866.3307 to subpart D to read as follows:
Sec. 866.3307 Herpes simplex virus nucleic acid-based assay for
central nervous system infections.
(a) Identification. A herpes simplex virus nucleic acid-based assay
for central nervous system infections is a qualitative in vitro
diagnostic device intended for the detection and differentiation of
HSV-1 and HSV-2 in cerebrospinal fluid (CSF) samples from patients
suspected of Herpes Simplex Virus (HSV) infections of the central
nervous system (CNS). This test is intended as an aid in the diagnosis
of HSV-1 and HSV-2 infections of the CNS. Negative results do not
preclude HSV-1 or HSV-2 infection 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) Design verification and validation must include:
(i) Detailed documentation for the device description, including
the device components, ancillary reagents required but not provided,
and a detailed explanation of the methodology, including primer design
and selection.
(ii) Detailed documentation from the following analytical and
clinical performance studies: Analytical sensitivity (limit of
detection), reactivity, inclusivity, precision, reproducibility,
interference, cross reactivity, carryover, and cross contamination.
Documentation must include reagent and sample stability
recommendations.
(iii) Detailed documentation from a clinical study. The study,
performed on a study population consistent with the intended use
population, must compare the device performance to the results of two
polymerase chain reaction methods followed by bidirectional sequencing.
(iv) Documentation of an appropriate end user device training
program that will be offered as part of efforts to mitigate the risk of
failure to correctly operate the instrument.
[[Page 27236]]
(v) Quality assurance protocols and detailed documentation for
device software, including standalone software applications and
hardware-based devices that incorporate software.
(2) The labeling required under Sec. 809.10(b) of this chapter
must include:
(i) A detailed explanation of the interpretation of results and
acceptance criteria.
(ii) A limiting statement indicating that negative results do not
preclude HSV-1 or HSV-2 infection and should not be used as the sole
basis for treatment or other patient management decisions.
Dated: June 23, 2025.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-11794 Filed 6-25-25; 8:45 am]
BILLING CODE 4164-01-P
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