Rule2025-16037
Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of the Pharmacogenetic Assessment System
Primary source
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Published
August 21, 2025
Effective
August 21, 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 pharmacogenetic assessment 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 pharmacogenetic assessment system. We are taking this action because we have determined that classifying the device into class II 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 160 (Thursday, August 21, 2025)</title>
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[Federal Register Volume 90, Number 160 (Thursday, August 21, 2025)]
[Rules and Regulations]
[Pages 40704-40707]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-16037]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 862
[Docket No. FDA-2025-N-2219]
Medical Devices; Clinical Chemistry and Clinical Toxicology
Devices; Classification of the Pharmacogenetic Assessment System
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 pharmacogenetic assessment system into class II
(special
[[Page 40705]]
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 pharmacogenetic assessment system. We are taking
this action because we have determined that classifying the device into
class II 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 August 21, 2025. The classification was
applicable on October 31, 2018.
FOR FURTHER INFORMATION CONTACT: Dina Jerebitski, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 3574, Silver Spring, MD 20993-0002, 301-
796-2411, <a href="/cdn-cgi/l/email-protection#0c4865626d2246697e696e65787f67654c6a686d2264647f226b637a"><span class="__cf_email__" data-cfemail="36725f5857187c534453545f42455d5f76505257185e5e4518515940">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the pharmacogenetic assessment
system 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 (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.
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 June 5, 2018, FDA received 23andMe, Inc.'s request for De Novo
classification of the 23andMe Personal Genome Service (PGS)
Pharmacogenetic Reports. 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 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 October 31, 2018, FDA issued an order to the
requester classifying the device into class II and subsequently issued
a correction dated January 23, 2019. In this final order, FDA is
codifying the classification of the device by adding 21 CFR
862.3364.\1\ We have named the generic type of device ``pharmacogenetic
assessment system,'' and it is identified as a qualitative in vitro
molecular diagnostic system intended to detect nucleic acid variants
isolated from human specimens for the purpose of assessing the presence
of genetic variants that impact the metabolism, exposure, response,
risk of adverse events, dosing, or mechanisms of prescription or over-
the-counter medications. The intended use of the device must not
include an indication for use in supporting or sustaining human life,
being of substantial importance in preventing impairment of human
health, or presenting a potential, unreasonable risk of illness or
injury. 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.
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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.
[[Page 40706]]
Table 1--Pharmacogenetic Assessment System Risks and Mitigation Measures
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Identified risks to health Mitigation measures
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Incorrect test results (false positive Special controls (1), (2), (3),
or false negative results). (4), and (5).
Incorrect interpretation of test Special controls (1)(ii), (2),
results. (3), (4), (5), and (6).
Incorrect action based on test results. Special controls (1)(ii), (2),
(3), (4), and (6).
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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
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 862
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
862 is amended as follows:
PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES
0
1. The authority citation for part 862 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 862.3364 to subpart D to read as follows:
Sec. 862.3364 Pharmacogenetic assessment system.
(a) Identification. A pharmacogenetic assessment system is a
qualitative in vitro molecular diagnostic system intended to detect
nucleic acid variants isolated from human specimens for the purpose of
assessing the presence of genetic variants that impact the metabolism,
exposure, response, risk of adverse events, dosing, or mechanisms of
prescription or over-the-counter medications. The intended use of the
device must not include an indication for use in supporting or
sustaining human life, being of substantial importance in preventing
impairment of human health, or presenting a potential, unreasonable
risk of illness or injury.
(b) Classification. Class II (special controls). A pharmacogenetic
assessment system must comply with the following special controls:
(1) Design verification and validation must include:
(i) Data appropriate, as determined by FDA, to demonstrate the
analytical accuracy and reliability of the device in intended use
specimens, including precision, reproducibility, accuracy, limits of
detection, and interferences. This information must include:
(A) Data demonstrating appropriate, as determined by FDA,
reproducibility for each genotype using each claimed sample type.
Reproducibility data must be evaluated using specimens collected and
processed in a manner consistent with the device's instructions for
use, or, as determined by FDA, an appropriate alternative sample panel.
(B) Analytical data demonstrating the limits of detection,
including the minimum amount of input deoxy-ribonucleic acid (DNA) that
will consistently produce accurate results.
(C) Data demonstrating no clinically significant effects from
endogenous and exogenous interferents relevant to each intended use
specimen type. Interference data must also include an assessment of
potentially interfering genetic sequences (e.g., variants proximal to
the variant of interest, pseudogenes).
(D) Validation data appropriate, as determined by FDA, to support
specimen collection and handling claims.
(E) Clinical data generated in intended use patient populations
demonstrating the pharmacogenetic association between the genetic
variant tested and any clinical claims or therapy-related
recommendations associated with that genotype.
(ii) Results from an appropriate, as determined by FDA, user
comprehension study that demonstrate the intended user can use the
device safely. The user comprehension study must be designed to include
the following:
(A) Study participants from a statistically sufficient sample size
and a demographically diverse (e.g., age, education level) population
that is representative of the intended use population and naive to use
of the device, and
(B) An evaluation of all result comprehension concepts that are
critical for safe use of the device.
(2) The labeling required under Sec. 809.10 of this chapter must
include:
(i) Clear information, written in language appropriate for the
intended user, that describes instructions for how test results should
be interpreted. These instructions must be supported by valid
scientific evidence and include:
(A) Appropriate explanation of the claimed pharmacogenetic
associations for all variants included in the test, any relevant
variants not included in the test (e.g., that may contribute to false
negative results), and specific considerations by ethnicity, and
(B) Appropriate explanation of non-genetic and non-tested genetic
factors that may impact interpretation of the test results;
[[Page 40707]]
(ii) Detailed descriptions of analytical performance including, as
applicable, precision, reproducibility, accuracy, limits of detection,
and interferences as specified in paragraph (b)(1)(i) of this section,
in language appropriate for the intended user;
(iii) A warning statement that the patient should not use the test
results to stop or change any medication, and that medications should
always be taken as prescribed by a healthcare professional;
(iv) A limiting statement explaining that this test is not intended
to inform the patient about their current state of health, including
whether the patient should or should not take a medication, or how much
of a medication the patient should take, as appropriate;
(v) A warning statement that the test does not diagnose any health
conditions and is not a substitute for visits to a doctor or other
healthcare professional; and
(vi) A prominent and conspicuous limiting statement that the test
provides only a preliminary test result that needs to be confirmed
using an independent pharmacogenetic test without such a limitation
prior to making any medical decisions. Alternatively, appropriate
design verification and validation activities, including the generation
of robust analytical data demonstrating appropriate analytical accuracy
and reliability of test results for each genetic variant included in
the test report, must be performed that demonstrate that the test can
be used to make well-informed clinical decisions.
(3) The test report must include an appropriate description of how
the test results should be used by healthcare providers who may receive
the test results from their patients, as applicable.
(4) Publicly available pre-purchase labeling with unrestricted
access that contains the following information must be provided:
(i) A clear description of the test and its technology, the
genotypes detected, and relevant clinical claims associated with each
genotype;
(ii) A clear description of what information the test will provide.
This includes variant information, the limitations associated with the
test, and any precautionary information about the test the user should
be aware of before purchase; and
(iii) A discussion of answers to frequently asked questions that is
sufficient to provide intended users with an appropriate understanding
of information specific to each pharmacogenetic association that is
claimed.
(5) The genetic test must use a sample collection device that is
FDA-cleared or -approved, or classified as 510(k) exempt, with an
indication for in vitro diagnostic use in DNA testing.
(6) The intended use of the device must not include an indication
for use in supporting or sustaining human life, being of substantial
importance in preventing impairment of human health, or presenting a
potential, unreasonable risk of illness or injury.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-16037 Filed 8-20-25; 8:45 am]
BILLING CODE 4164-01-P
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