Rule2022-28035
Medical Devices; Immunology and Microbiology Devices; Classification of the Human Leukocyte Antigen Typing Companion Diagnostic Test
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
December 27, 2022
Effective
December 27, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, Agency, or we) is classifying the human leukocyte antigen typing companion diagnostic test 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 human leukocyte antigen typing companion diagnostic test'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 87 Issue 247 (Tuesday, December 27, 2022)</title>
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[Federal Register Volume 87, Number 247 (Tuesday, December 27, 2022)]
[Rules and Regulations]
[Pages 79251-79253]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-28035]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2021-N-0851]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Human Leukocyte Antigen Typing Companion
Diagnostic Test
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 human leukocyte antigen typing companion diagnostic
test 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 human leukocyte antigen typing companion
diagnostic test'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 December 27, 2022. The classification
was applicable on November 28, 2022.
FOR FURTHER INFORMATION CONTACT: Karen Fikes, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 72, Rm. 7301, Silver Spring, MD, 20993-0002, 240-
402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the human leukocyte antigen typing
companion diagnostic test 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 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. 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
less-burdensome 510(k) process, when necessary, to market their device.
II. De Novo Classification
On July 1, 2022, One Lambda, Inc., submitted a request for De Novo
classification of the SeCORE CDx HLA Sequencing 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 28, 2022, 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
866.5960.\1\ We have named the generic type of device human leukocyte
antigen typing companion diagnostic test, and it is identified as a
prescription genotyping or phenotyping in vitro diagnostic product
intended for use as an aid in identifying patients who have specific
human leukocyte antigen (HLA) allele(s) or express specific HLA
antigen(s) and may benefit from treatment with a corresponding
therapeutic product or are likely to be at increased risk for serious
adverse
[[Page 79252]]
reactions as a result of treatment with a corresponding therapeutic
product.
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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--Human Leukocyte Antigen Typing Companion Diagnostic Test Risks
and Mitigation Measures
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Identified risks Mitigation measures
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Inaccurate test results (false positive Labeling, design verification
or false negative results) can result and validation, clinical
in adverse health consequences. validity data, bridging study.
Failure of software to correctly Software verification and
interpret test results can result in validation.
adverse health consequences.
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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. In order 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 21 CFR 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 part 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. 866.5960 to subpart F to read as follows:
Sec. 866.5960 Human leukocyte antigen typing companion diagnostic
test.
(a) Identification. A human leukocyte antigen (HLA) typing
companion diagnostic (CDx) test is a prescription genotyping or
phenotyping in vitro diagnostic product intended for use as an aid in
identifying patients who have specific HLA allele(s) or express
specific HLA antigen(s) and may benefit from treatment with a
corresponding therapeutic product or are likely to be at increased risk
for serious adverse reactions as a result of treatment with a
corresponding therapeutic product.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) The intended use of the device must specify the target HLA
allele(s) or antigen(s), the patient population(s), and the
corresponding therapeutic product(s).
(2) Design verification and validation must include:
(i) Detailed documentation of an analytical accuracy study that
uses well-characterized samples including clinical samples from
intended use population(s) focusing on the target allele(s) needed for
patient selection;
(ii) Detailed documentation of precision studies (repeatability,
reproducibility) that evaluate possible sources of variation that may
affect test results;
(iii) Detailed documentation of a study determining range of input
sample concentrations that meet performance specifications;
(iv) Detailed description of the ambiguity resolution method, if
applicable;
(v) For a sequencing-based assay, documentation of coverage and
predefined coverage threshold of target genomic regions, pertinent
variant types, and sequence contexts;
(vi) For multiplex assays, documentation of a risk assessment and
design specifications that are in place to prevent incorrect reactivity
assignment;
(vii) Description of a plan on how to ensure the performance of the
device does not change when new HLA alleles are identified, and/or when
reactivity assignments are changed; and
(viii) Detailed description of device software including standalone
software, or software and bioinformatics analysis pipeline, if
applicable, incorporated in the instruments, and documentation of
software including the level of concern and associated risks, software
requirement specifications, software design specifications (e.g.,
algorithms, alarms and device limitations), hazard analysis,
traceability matrix, verification and validation testing, unresolved
anomalies, hardware requirements, and effective cybersecurity
management.
(3) Clinical validity data (which may include summary reports from
clinical trials, comparison studies using clinical samples, or through
an alternative approach determined to be appropriate by FDA),
demonstrating the following, as applicable:
(i) Which patients identified by the HLA CDx test are most likely
to benefit from the corresponding therapeutic product; and
(ii) Which patients identified by the HLA CDx test are likely to be
at increased risk for serious adverse reactions as a result of
treatment with the corresponding therapeutic product.
(4) If the HLA test used in the clinical trials is different from
the HLA CDx test
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in the premarket notification submission, the submission must include
results of a bridging study, or an alternative approach determined to
be appropriate by FDA.
Dated: December 20, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-28035 Filed 12-23-22; 8:45 am]
BILLING CODE 4164-01-P
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</html>Indexed from Federal Register on December 27, 2022.
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