Rule2024-21086
Medical Devices; Immunology and Microbiology Devices; Classification of the Quantitative Viral Nucleic Acid Test for Transplant Patient Management
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Published
September 17, 2024
Effective
September 17, 2024
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, Agency, or we) is classifying the quantitative viral nucleic acid test for transplant patient management 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 quantitative viral nucleic acid test for transplant patient management'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.
Full Text
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<title>Federal Register, Volume 89 Issue 180 (Tuesday, September 17, 2024)</title>
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[Federal Register Volume 89, Number 180 (Tuesday, September 17, 2024)]
[Rules and Regulations]
[Pages 75953-75955]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2024-21086]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2024-N-4084]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Quantitative Viral Nucleic Acid Test for
Transplant Patient Management
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 quantitative viral nucleic acid test for transplant
patient management 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 quantitative viral
nucleic acid test for transplant patient management'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 17, 2024. The classification
was applicable on July 30, 2020.
FOR FURTHER INFORMATION CONTACT: Silke Schlottmann, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 3258, Silver Spring, MD 20993-0002, 301-
796-9551, <a href="/cdn-cgi/l/email-protection#fba89297909ed5a8989397948f8f969a9595bb9d9f9ad5939388d59c948d"><span class="__cf_email__" data-cfemail="b4e7ddd8dfd19ae7d7dcd8dbc0c0d9d5dadaf4d2d0d59adcdcc79ad3dbc2">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the quantitative viral nucleic
acid test for transplant patient management 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 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 March 2, 2020, FDA received Roche Molecular Systems, Inc.'s
request for De Novo classification of the cobas EBV. 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 July 30, 2020, FDA issued an order to the requester
classifying the device into class II. In
[[Page 75954]]
this final order, FDA is codifying the classification of the device by
adding 21 CFR 866.3183.\1\ We have named the generic type of device
quantitative viral nucleic acid test for transplant patient management,
and it is identified as a device intended for prescription use in the
detection of viral pathogens by measurement of viral deoxyribonucleic
acid (DNA) or ribonucleic acid (RNA) using specified specimen
processing, amplification, and detection instrumentation. The test is
intended for use as an aid in the management of transplant patients
with active viral infection or at risk for developing viral infections.
The test results are intended to be interpreted by qualified healthcare
professionals in conjunction with other relevant 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--Quantitative Viral Nucleic Acid Test for Transplant Patient
Management Risks and Mitigation Measures
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Identified risks to health Mitigation measures
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Risk of false results........ Certain warnings, limitations, results
interpretation information, and
explanation of procedures in labeling;
and
Certain device descriptions and
specifications, analytical studies,
clinical studies, and risk analysis in
design verification and validation.
Failure to correctly Certain warnings, limitations, results
interpret test results. interpretation information, and
explanation of procedures in labeling.
Failure to correctly operate Certain warnings, limitations, results
the device. interpretation information, and
explanation of procedures 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 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. 866.3183 to subpart D to read as follows:
Sec. 866.3183 Quantitative viral nucleic acid test for transplant
patient management.
(a) Identification. A quantitative viral nucleic acid test for
transplant patient management is identified as a device intended for
prescription use in the detection of viral pathogens by measurement of
viral DNA or RNA using specified specimen processing, amplification,
and detection instrumentation. The test is intended for use as an aid
in the management of transplant patients with active viral infection or
at risk for developing viral infections. The test results are intended
to be interpreted by qualified healthcare professionals in conjunction
with other relevant clinical and laboratory findings.
(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) A prominent statement that the device is not intended for use
as a donor screening test for the presence of viral nucleic acid in
blood or blood products.
(ii) Limitations which must be updated to reflect current clinical
practice. These limitations must include, but are not limited to,
statements that indicate:
(A) Test results are to be interpreted by qualified licensed
healthcare professionals in conjunction with clinical signs and
symptoms and other relevant laboratory results; and
(B) Negative test results do not preclude viral infection or tissue
invasive viral disease and that test results must not be the sole basis
for patient management decisions.
[[Page 75955]]
(iii) A detailed explanation of the interpretation of results and
acceptance criteria must be provided and include specific warnings
regarding the potential for variability in viral load measurement when
samples are measured by different devices. Warnings must include the
following statement, where applicable: ``Due to the potential for
variability in [analyte] measurements across different [analyte]
assays, it is recommended that the same device be used for the
quantitation of [analyte] when managing individual patients.''
(iv) A detailed explanation of the principles of operation and
procedures for assay performance.
(2) Design verification and validation must include the following:
(i) Detailed documentation of the device description, including all
parts that make up the device, ancillary reagents required for use with
the assay but not provided, an explanation of the methodology, design
of the primer/probe sequences, rationale for the selected gene target,
and specifications for amplicon size, guanine-cytosine content, and
degree of nucleic acid sequence conservation. The design and nature of
all primary, secondary and tertiary quantitation standards used for
calibration must also be described.
(ii) A detailed description of the impact of any software,
including software applications and hardware-based devices that
incorporate software, on the device's functions;
(iii) Documentation and characterization (e.g., determination of
the identity, supplier, purity, and stability) of all critical reagents
and protocols for maintaining product integrity throughout its labeled
shelf-life.
(iv) Stability data for reagents provided with the device and
indicated specimen types, in addition to the basis for the stability
acceptance criteria at all time points chosen across the spectrum of
the device's indicated life cycle, which must include a time point at
the end of shelf life.
(v) All stability protocols, including acceptance criteria.
(vi) Final lot release criteria along with documentation of an
appropriate justification that lots released at the extremes of the
specifications will meet the claimed analytical and clinical
performance characteristics as well as the stability claims.
(vii) Risk analysis and documentation demonstrating how risk
control measures are implemented to address device system hazards, such
as Failure Mode Effects Analysis and/or Hazard Analysis. This
documentation must include a detailed description of a protocol
(including all procedures and methods) for the continuous monitoring,
identification, and handling of genetic mutations and/or novel viral
stains (e.g., regular review of published literature and annual in
silico analysis of target sequences to detect possible primer or probe
mismatches). All results of this protocol, including any findings, must
be documented.
(viii) Analytical performance testing that includes:
(A) Detailed documentation of the following analytical performance
studies: limit of detection, upper and lower limits of quantitation,
inclusivity, precision, reproducibility, interference, cross
reactivity, carry-over, quality control, specimen stability studies,
and additional studies as applicable to specimen type and intended use
for the device;
(B) Identification of the viral strains selected for use in
analytical studies, which must be representative of clinically relevant
circulating strains;
(C) Inclusivity study results obtained with a variety of viral
genotypes as applicable to the specific assay target and supplemented
by in silico analysis;
(D) Reproducibility studies that include the testing of three
independent production lots;
(E) Documentation of calibration to a reference standard that FDA
has determined is appropriate for the quantification of viral DNA or
RNA (e.g., a recognized consensus standard); and
(F) Documentation of traceability performed each time a new lot of
the standardized reference material to which the device is traceable is
released, or when the field transitions to a new standardized reference
material.
(ix) Clinical performance testing that includes:
(A) Detailed documentation from either a method comparison study
with a comparator that FDA has determined is appropriate, or results
from a prospective clinical study demonstrating clinical validity of
the device;
(B) Data from patient samples, with an acceptable number of the
virus-positive samples containing an analyte concentration near the
lower limit of quantitation and any clinically relevant decision
points. If an acceptable number of virus-positive samples containing an
analyte concentration near the lower limit of quantitation and any
clinically relevant decision cannot be obtained, contrived samples may
be used to supplement sample numbers when appropriate, as determined by
FDA;
(C) The method comparison study must include predefined maximum
acceptable differences between the test and comparator method across
all primary outcome measures in the clinical study protocol; and
(D) The final release test results for each lot used in the
clinical study.
Dated: September 12, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-21086 Filed 9-16-24; 8:45 am]
BILLING CODE 4164-01-P
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</html>Indexed from Federal Register on September 17, 2024.
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