Rule2025-08146
Medical Devices; Immunology and Microbiology Devices; Classification of the Cytomegalovirus Nucleic Acid Detection Device for Congenital Cytomegalovirus Infection
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Published
May 9, 2025
Effective
May 9, 2025
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, Agency, or we) is classifying the cytomegalovirus nucleic acid detection device for congenital cytomegalovirus infection 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 cytomegalovirus nucleic acid detection device for congenital cytomegalovirus infection'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.
Full Text
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<title>Federal Register, Volume 90 Issue 89 (Friday, May 9, 2025)</title>
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[Federal Register Volume 90, Number 89 (Friday, May 9, 2025)]
[Rules and Regulations]
[Pages 19634-19636]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-08146]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2025-N-0725]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Cytomegalovirus Nucleic Acid Detection Device for
Congenital Cytomegalovirus Infection
AGENCY: Food and Drug Administration, Department of Health and Human
Services (HHS).
ACTION: Final amendment; final order.
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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
classifying the cytomegalovirus nucleic acid detection device for
congenital cytomegalovirus infection 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
cytomegalovirus nucleic acid detection device for congenital
cytomegalovirus infection'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 May 9, 2025. The classification was
applicable on November 30, 2018.
FOR FURTHER INFORMATION CONTACT: Ryan Lubert, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 3414, Silver Spring, MD 20993-0002, 240-402-6357,
<a href="/cdn-cgi/l/email-protection#a4d6ddc5ca8ac8d1c6c1d6d0e4c2c0c58accccd78ac3cbd2"><span class="__cf_email__" data-cfemail="b5c7ccd4db9bd9c0d7d0c7c1f5d3d1d49bddddc69bd2dac3">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the cytomegalovirus nucleic acid
detection device for congenital cytomegalovirus infection 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
[[Page 19635]]
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 July 30, 2018, FDA received Meridian Bioscience, Inc.'s request
for De Novo classification of the Alethia CMV Assay Test System. 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 November 30, 2018, 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
866.3181.\1\ We have named the generic type of device ``cytomegalovirus
nucleic acid detection device for congenital cytomegalovirus
infection,'' and it is identified as an in vitro diagnostic device
intended for the qualitative detection of cytomegalovirus
deoxyribonucleic acid (DNA) in clinical samples from newborn babies to
aid in the diagnosis of congenital cytomegalovirus infection. Negative
results do not preclude infection and should not be used as the sole
basis for diagnosis, treatment, or other patient management decisions.
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 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--Cytomegalovirus Nucleic Acid Detection Device for Congenital
Cytomegalovirus Infection Risks and Mitigation Measures
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Identified risks to health Mitigation measures
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Risk of false results........ General Controls and Special Controls (1)
(21 CFR 866.3181(b)(1)) and (2) (21 CFR
866.3181(b)(2)).
Failure to correctly General Controls and Special Controls
interpret test results. (1)(i) (21 CFR 866.3181(b)(1)(i)), (iv)
(21 CFR 866.3181(b)(1)(iv)), (v) (21 CFR
866.3181(b)(1)(v)), and (vi) (21 CFR
866.3181(b)(1)(vi)).
Failure to correctly operate General Controls and Special Controls (1)
the device. (21 CFR 866.3181(b)(1)) and (2) (21 CFR
866.3181(b)(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 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.
[[Page 19636]]
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. 866.3181 to subpart D to read follows:
Sec. 866.3181 Cytomegalovirus nucleic acid detection device for
congenital cytomegalovirus infection.
(a) Identification. A cytomegalovirus nucleic acid detection device
for congenital cytomegalovirus infection is an in vitro diagnostic
device intended for the qualitative detection of cytomegalovirus DNA in
clinical samples from newborn babies to aid in the diagnosis of
congenital cytomegalovirus infection. Negative results do not preclude
infection and should not be used as the sole basis for diagnosis,
treatment, or other patient management decisions. 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, the type of results provided to the user, the clinical
indications appropriate for test use, and the specific population(s) to
be tested.
(ii) A detailed device description, including all device
components, instrument requirements, ancillary reagents required but
not provided, and an explanation of the methodology, including all pre-
analytical methods for specimen processing.
(iii) Performance characteristics from analytical and clinical
studies required under paragraphs (b)(2)(ii) and (iii) of this section.
(iv) A detailed explanation of the interpretation of results and
criteria for validity of results.
(v) A limiting statement that device results are not intended to be
used as the sole basis for diagnosis, treatment, or other patient
management decisions.
(vi) As applicable, a limiting statement and specific sample
collection recommendations to indicate that breast milk can result in
false positive results for saliva samples if samples are collected less
than 1 hour after breastfeeding. Sample collection a minimum of 1 hour
from breastfeeding must be recommended.
(vii) Detailed instructions for use that minimize the risk of
generating a false result.
(2) Design verification and validation must include:
(i) Detailed device description documentation, including
methodology from obtaining sample to result, design of primer/probe
sequences, rationale for sequence selection, and computational path
from collected raw data to reported result (e.g., how collected raw
signals are converted into a reported result).
(ii) Detailed documentation of analytical studies including
characterization of the cutoff, analytical sensitivity (limit of
detection), inclusivity, reproducibility, interference, cross
reactivity, instrument and method carryover/cross contamination, and
sample stability and handling.
(iii) Detailed documentation from a clinical study documenting
sensitivity and specificity of the device; if the number of positive
samples in the clinical study is insufficient to properly estimate
device sensitivity, additional pre-selected positive samples must be
evaluated to supplement the study. Clinical study subjects must be
consistent with the intended use population (i.e., infants younger than
21 days of age), and device results must be compared to FDA-accepted
comparator methods. Documentation from the clinical study must include
the clinical study protocol, the clinical study report, testing
results, and results of all statistical analyses.
(iv) Detailed documentation for device software, including software
applications and hardware-based devices that incorporate software.
Dated: May 5, 2025.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-08146 Filed 5-8-25; 8:45 am]
BILLING CODE 4164-01-P
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