Medical Devices; Immunology and Microbiology Devices; Classification of the High Throughput DNA Sequencing for Hereditary Cancer Predisposition Assessment Test System

Issuing agencies

Abstract

The Food and Drug Administration (FDA) is classifying the high throughput DNA sequencing for hereditary cancer predisposition assessment test system 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 high throughput DNA sequencing for hereditary cancer predisposition assessment test system. We are taking this action because we have determined that classifying the device into class II will provide a reasonable assurance of the 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 91 Issue 192 (Tuesday, October 6, 2026)</title>
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[Federal Register Volume 91, Number 192 (Tuesday, October 6, 2026)]
[Rules and Regulations]
[Pages 63487-63491]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-20443]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2026-N-10990]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the High Throughput DNA Sequencing for Hereditary 
Cancer Predisposition Assessment Test System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA) is classifying the high 
throughput DNA sequencing for hereditary cancer predisposition 
assessment test system 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 high 
throughput DNA sequencing for hereditary cancer predisposition 
assessment test system. We are taking this action because we have 
determined that classifying the device into class II will provide a 
reasonable assurance of the 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 October 6, 2026. The classification was 
applicable on September 29, 2023.

FOR FURTHER INFORMATION CONTACT: Jingya Wang, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3250, Silver Spring, MD 20993-0002, 301-837-7257, 
<a href="/cdn-cgi/l/email-protection#92d8fbfcf5ebf3bcc5f3fcf5d2f4f6f3bcfafae1bcf5fde4"><span class="__cf_email__" data-cfemail="87cdeee9e0fee6a9d0e6e9e0c7e1e3e6a9efeff4a9e0e8f1">[email&#160;protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA (the Agency or we) has classified the high 
throughput DNA sequencing for hereditary cancer predisposition 
assessment test system into class II (special controls), which we have 
determined will provide a reasonable assurance of the safety and 
effectiveness of the device. 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 into, and remains 
within, class III and requires premarket approval unless and until FDA 
takes an action to classify or reclassify the device (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 (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

[[Page 63488]]

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 classification 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 premarket 
notification (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 March 29, 2021, FDA received Invitae Corporation's request for 
De Novo classification of the Invitae Common Hereditary Cancers Panel. 
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 the safety and 
effectiveness of the device, 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 section 513(a)(1)(B) of the 
FD&C Act). 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 September 29, 2023, 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 
866.6095.\1\ We have named the generic type of device ``high throughput 
DNA sequencing for hereditary cancer predisposition assessment test 
system,'' and it is identified as a qualitative in vitro diagnostic 
(IVD) system intended for analysis of human DNA extracted from human 
specimens to detect germline mutations in a panel of targeted cancer-
related genes. It is intended to aid in hereditary cancer 
predisposition assessment by qualified health care professionals in 
accordance with professional guidelines. The device is not intended for 
screening, prenatal testing, or as a stand-alone diagnostic test. The 
device is for prescription use only.
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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 risks to health associated with this type of 
device and the measures required to mitigate these risks in table 1.

Table 1--Risks to Health and Mitigation Measures for High Throughput DNA
 Sequencing for Hereditary Cancer Predisposition Assessment Test Systems
------------------------------------------------------------------------
    Identified risks to health               Mitigation measures
------------------------------------------------------------------------
False positive, false negative, or  Certain design verification and
 failure to provide a result.        validation including certain
                                     analytical and clinical studies,
                                     and mutation annotation and
                                     clinical interpretation rules
                                     identified in special control (1).
                                    Certain labeling information
                                     including limitations, device
                                     descriptions, methodology and
                                     protocols, and performance
                                     information identified in special
                                     control (2).
Incorrect interpretation of         Certain design verification and
 variants/alterations by the lab.    validation including certain
                                     analytical and clinical studies,
                                     and mutation annotation and
                                     clinical interpretation rules
                                     identified in special control (1).
                                    Certain labeling information
                                     including limitations, device
                                     descriptions, methodology and
                                     protocols, and performance
                                     information identified in special
                                     control (2).
Incorrect interpretation of test    Certain design verification and
 results by the healthcare           validation including certain
 provider.                           analytical and clinical studies,
                                     and mutation annotation and
                                     clinical interpretation rules
                                     identified in special control (1).
                                    Certain labeling information
                                     including limitations, device
                                     descriptions, methodology and
                                     protocols, and performance
                                     information identified in special
                                     control (2).
------------------------------------------------------------------------

    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 of the device. 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.
    At the time of classification, high throughput DNA sequencing for 
hereditary cancer predisposition assessment test systems are for 
prescription use only. Therefore, these devices are subject to the 
prescription

[[Page 63489]]

labeling requirements for IVD products (see 21 CFR 809.10(a)(4) and 
(b)(5)(ii)).
    Under the FD&C Act, submission of a premarket notification under 
section 510(k) is required to reasonably assure the safety and 
effectiveness of class II devices unless FDA determines that the device 
type should be exempt under section 510(m) of the FD&C Act. At this 
time FDA has not made this determination for high throughput DNA 
sequencing for hereditary cancer predisposition assessment test 
systems. This device is therefore 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 normally 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 management 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.  866.6095 to subpart G to read as follows:


Sec.  866.6095   High throughput DNA sequencing for hereditary cancer 
predisposition assessment test system.

    (a) Identification. A high throughput DNA sequencing for hereditary 
cancer predisposition assessment test system is a qualitative in vitro 
diagnostic (IVD) system intended for analysis of human DNA extracted 
from human specimens to detect germline mutations in a panel of 
targeted cancer-related genes. It is intended to aid in hereditary 
cancer predisposition assessment by qualified health care professionals 
in accordance with professional guidelines. The device is not intended 
for screening, prenatal testing, or as a stand-alone diagnostic test. 
The device is for prescription use only.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Design verification and validation must include:
    (i) A description of genomic coverage that includes:
    (A) A list of all genes, variant types, and target regions within 
each gene that the device detects;
    (B) Summary information regarding the clinical significance of each 
gene, including references;
    (C) A description of the genes with high clinical significance that 
are detected by the device, defined as genes for which the test 
result(s) may lead to prophylactic screening, confirmatory procedures, 
or treatment that may incur morbidity or mortality; and
    (D) A description of any within-gene targeted regions that cannot 
be reported.
    (ii) Specifications for specimen requirements, including any 
specimen collection devices, handling, and storage.
    (iii) Specifications of the DNA extraction method and criteria for 
DNA quality and quantity that are prerequisite to performing the assay.
    (iv) Detailed documentation of the methodology and protocols for 
each step of the test, including reagents, instrumentation, and 
software required. The documentation must include the analysis 
algorithms used for mutation detection and annotation, and specify the 
quality metrics, variant calling thresholds, and filters at each step 
of the test, including the criteria for run failures, batch failures, 
specimen failures, invalid calls (e.g., failed quality control), and 
``no calls'' (i.e., absence of a result), as applicable.
    (v) Description of required instrumentation and equipment, and any 
ancillary reagents, instrumentation, or equipment.
    (vi) Detailed documentation of device software, including software 
applications and hardware-based devices that incorporate software. The 
documentation must include verification, validation, hazard analysis, 
and risk assessment activities.
    (vii) Documentation of internal and external controls that are 
recommended or provided and control procedures. The documentation must 
identify those control elements that are incorporated into the testing 
procedure.
    (viii) Detailed documentation pertaining to the probability of test 
failure based on data from clinical samples, description of scenarios 
in which a test can fail, and any risk mitigations, including follow-up 
actions to be taken.
    (ix) Detailed documentation of the rules, procedures, tools, and 
criteria used for establishing mutation-hereditary disease 
relationships and mutation annotation, evaluation, and classification 
(e.g., pathogenic, likely pathogenic, variant of unknown significance, 
benign, and likely benign).
    (x) Detailed documentation of any internal or external database(s) 
or decision rules used for mutation annotation, including:
    (A) The protocol(s) used for variant interpretation, including 
training of personnel, monitoring accuracy of decision, resolution of 
discordant interpretations, and updating interpretations;
    (B) Detailed documentation of the basis for interpretation, 
including the use of alternate databases, literature, and guidelines, 
and the basis for risk reporting;
    (C) Methods for data preservation and security; and
    (D) Data formats and nomenclature.
    (xi) Information that demonstrates the performance characteristics 
of the device, evaluated either specifically for each gene/mutation or, 
when determined to be acceptable and appropriate by FDA, using a 
representative approach based on other mutations of the same type, 
including:
    (A) Data that adequately support the intended specimen type(s) 
(e.g., whole blood), specimen handling protocol, and DNA extraction 
method.
    (B) A summary of the evidence that demonstrates how the analytical 
quality metrics and thresholds used to

[[Page 63490]]

determine the acceptability of reporting support the minimum accuracy 
requirements.
    (C) Data to adequately support device accuracy using clinical 
specimens representing all indicated specimen types, mutation types, 
and size ranges intended to be detected and reported by the device. 
Accuracy data must fulfill the following:
    (1) Accuracy of the device must be evaluated with clinical 
specimens collected in accordance with the device labeling and selected 
without bias, or well-characterized human cell line samples, when 
determined to be acceptable and appropriate by FDA.
    (2) Accuracy must be evaluated by comparison to bidirectional 
Sanger sequencing or other orthogonal methods identified as appropriate 
by FDA. Performance criteria for both the comparator method(s) and the 
device must be predefined and appropriate to the device's intended use. 
Detailed study protocols must be documented.
    (3) A sufficient number of specimens must be tested. For BRCA1 and 
BRCA2 genes, a minimum of 120 variant positive specimens must be 
tested. For other genes with high clinical significance, at least 40 
variant-positive specimens must be tested per gene, including 
representative specimens for each indicated variant type based on a 
justification determined to be appropriate and acceptable by FDA. For 
remaining genes detected by the device, testing must include variant 
positive specimens representing each variant type, unless the variant 
type has a prevalence of less than 0.01 percent. Specimen selection 
must be prioritized based on clinical significance. The selected 
specimens must be representative of zygosity and challenging genomic 
context (e.g., guanine-cytosine content, near tandem repeats and 
homopolymer stretches, pseudogene), and must cover the range of sizes 
(for insertions, deletions, copy number variant (CNV) amplifications 
and CNV deletions) intended to be detected and reported by the device.
    (4) Except as permitted by FDA under paragraph (b)(1)(xi)(C)(5) of 
this section, tested specimens must be selected based on results 
obtained from the orthogonal method. Positive percent agreement (PPA) 
and negative percent agreement (NPA) must be calculated and 
demonstrated for each variant type detected and reported by the device, 
as well as for clinically relevant variants. PPA is calculated as the 
number of variants that are tested positive by both the device and the 
orthogonal method (true ``positives'' (TP)) divided by the number of 
variants tested positive as determined by the orthogonal method (TP 
plus false negatives (FN) by the device). NPA is calculated as the 
number of variants that are tested negative (wild type) by both the 
device and the orthogonal method (true ``negatives'' (TN)) divided by 
the number of variants tested negative (wild type) by the orthogonal 
method (TN plus false positives (FP) by the device). Point estimates 
for PPA and NPA must be calculated along with 95 percent two-sided 
confidence intervals (CI). Uncertainty of the point estimate must be 
within an acceptable range, as identified by FDA, and must be 
demonstrated using the 95 percent CI.
    (5) When it is determined by FDA to be appropriate and acceptable 
to select samples based on the results obtained with the device, 
accuracy must be presented as technical positive predictive value 
(TPPV) and technical negative predictive value (TNPV). TPPV relates to 
the likelihood that a variant call is a true positive and reflects the 
number of false positives per test. TPPV is calculated as the number of 
variants that are tested positive by both the device and the orthogonal 
method (TP) divided by the number of variants tested positive by the 
device (TP plus FP). TNPV relates to the likelihood that a variant call 
is a true negative and reflects the number of false negatives per test. 
TNPV is calculated as the number of variants that are tested negative 
by both the device and the orthogonal method (TN) divided by the number 
of variants tested negative by the device (TN plus FN).
    (6) Any ``no calls'' or invalid calls in the study must be reported 
separately. The percent of final ``no calls'' or invalid calls must be 
clinically justifiable.
    (7) Accuracy as a function of each performance metric (e.g., 
coverage depth, base quality scores) must be documented to provide 
evidence of the accuracy of the overall run.
    (8) Detailed documentation for accuracy of the device must include 
information and results for the overall study, each mutation type, and 
each gene. The accuracy must further be described based upon 
stratification within each mutation type by zygosity, genomic context, 
and size (for indels and CNVs). Overall accuracy for reporting of 
substitutions must be >=99.0 percent; insertions and deletions, >=99.0 
percent; CNVs, >=99.0 percent for positive agreement (PPA, TPPV); and 
>=99.9 percent for negative agreement (NPA, TNPV).
    (D) Documentation of the data to adequately support device 
precision using clinical specimens representing all specimen types, 
mutation types, and sizes intended to be detected and reported by the 
device. The precision study must fulfill the following:
    (1) The study must be performed using multiple instruments and 
multiple operators, on multiple non-consecutive days, and using 
multiple reagent lots. If the device is to be performed at more than 
one site, different sites must be included and reproducibility across 
sites must be evaluated.
    (2) Representative clinical specimens of each mutation type must be 
tested (both positive and negative), considering clinical significance, 
prevalence, zygosity, genomic context, and size (for indels and CNVs). 
The precision for CNV detection must be demonstrated on the gene level 
for genes with high clinical significance. Alternatively, a 
justification for why such data are not needed must be found acceptable 
and appropriate by FDA.
    (3) The study must assess the performance of all steps, including 
DNA extraction, unless a separate extraction study is performed.
    (4) The study must use predefined performance criteria. Agreement 
estimates such as PPA/NPA and average positive agreement/average 
negative agreement must be provided, including point estimates and 95 
percent confidence intervals. Documentation from the precision study 
must be demonstrated for the overall precision study, in addition to 
each mutation type, each gene, and each sample. Precision must further 
be demonstrated upon stratification within each mutation type by 
zygosity, genomic context, and size (for indels and CNVs). The overall 
precision point estimates for each variant type must be >99.0 percent.
    (5) Any ``no calls'' or invalid calls in the study must be included 
in precision study results and reported separately. The percent of ``no 
calls'' or invalid calls and key quality control metrics parameters 
(e.g., coverage, sequencing score) must be summarized and based on 
stratification in the same way as the precision estimates.
    (E) Documentation of the nucleic acid assay input range and the 
evidence to adequately support the range.
    (F) Detailed documentation of additional analytical validation 
studies, including endogenous and exogenous interfering substances, 
specimen and reagent stability, cross-reactivity, carryover and cross-
contamination, guard-banding, and index misassignment, as applicable. 
If specimens are pooled, index cross-contamination must be evaluated 
and

[[Page 63491]]

demonstrate that pooling does not negatively impact test performance.
    (G) Specimen type and matrix comparison data must be generated if 
more than one specimen type or anticoagulant can be tested with the 
device, including failure rates for the different specimen types.
    (xii) Information that adequately supports the variant annotation 
and clinical interpretation of the test must include:
    (A) A summary documenting the clinical significance for each gene 
on the test panel, including the associated conditions/cancers, the 
most prevalent and representative mutations, and summary of clinical 
evidence with references, including expected frequency in the general 
population and different ethnicities, and risks of developing the 
disease in relevant ethnic populations and the general population.
    (B) Detailed documentation of the data to adequately support the 
performance of the variant annotation algorithms (e.g., concordance 
studies between the device generated variant classifications and 
externally established variant classifications, manual classifications 
by medical professionals, or classifications generated from clinical 
test reports).
    (C) Documentation of any procedures or protocols for incorporation 
of any updates of valid scientific evidence into variant classification 
algorithms.
    (2) The labeling required under Sec.  809.10 of this chapter must 
include the following, as applicable:
    (i) The intended use must include a description of the intended 
specimen type(s) and matrix (e.g., whole blood), the validated germline 
mutation types (e.g., single nucleotide variant, insertion, deletion, 
CNV), and a statement that the test is for hereditary cancer 
predisposition assessment and to aid in identifying hereditary genetic 
variants potentially associated with a diagnosed cancer.
    (ii) The name of the testing facility or facilities (e.g., for 
single-site assays).
    (iii) A summary of device description in accordance with paragraphs 
(b)(1)(i) through (b)(1)(viii) of this section.
    (iv) A section that provides summary information on how the test 
works, how to interpret the results of the test, and an explanation on 
the database(s) used for mutation annotation.
    (v) A summary of the information that demonstrates the performance 
characteristics of the device as required under paragraph (b)(1)(xi) of 
this section.
    (vi) The following limiting statements:
    (A) A statement that the test is not intended for use as a stand-
alone diagnostic to diagnose cancer or other health conditions, and is 
not intended for use for prenatal testing nor as a cancer screening 
test.
    (B) A statement that the test is specifically designed for 
heritable germline mutations and is not appropriate for the detection 
of somatic mutations.
    (C) A description of the intended test population.
    (D) A statement that the risk of cancer or disease for an 
individual cannot be predicted.
    (E) A statement that: test results should be interpreted in the 
context of clinical findings, family history, lifestyle, environment, 
and other factors; molecular testing may not detect all possible 
mutations leading to cancer predisposition; a negative result does not 
rule out the possibility that the individual has an unidentified 
variant leading to cancer; and for more information, physicians 
ordering the test may wish to consult with a clinical medical 
geneticist or genetic counselor.
    (F) A statement that other factors, such as ethnicity, may affect 
whether the test results are relevant for a particular patient and may 
also affect how their genetic health results are interpreted.
    (G) A statement describing the situations that a patient should not 
receive the test (e.g., a patient with bone marrow transplant).
    (H) A statement describing the challenging genomic contexts that 
may have reduced performance, where results should be interpreted with 
care.
    (I) A statement disclosing the genetic coverage of the test, 
including any gaps in coverage.
    (J) Statements describing testing conditions that were identified 
to cause test failures (e.g., low specimen volume, poor DNA quality).
    (vii) For variants detected and reported by the device under the 
category of ``variants of uncertain significance'' or equivalent 
designation, a limiting statement that the clinical significance has 
not been demonstrated with adequate clinical evidence in accordance 
with established guidelines (e.g., professional guidelines).
    (viii) For variants detected and reported by the device under the 
category of ``variants with evidence of clinical significance'' or 
equivalent designation, reference(s) for physicians to access internal 
or external information concerning decision rules or conclusions about 
the level of evidence for clinical significance.

Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-20443 Filed 10-5-26; 8:45 am]
BILLING CODE 4164-01-P


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