Rule2025-16038
Medical Devices; Immunology and Microbiology Devices; Classification of the Mutation Detection Test for Myeloproliferative Neoplasms
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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 mutation detection test for myeloproliferative neoplasms 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 mutation detection test for myeloproliferative neoplasms. 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 40721-40724]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-16038]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2025-N-2424]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Mutation Detection Test for Myeloproliferative
Neoplasms
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 mutation detection test for myeloproliferative
neoplasms 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 mutation detection
test for myeloproliferative neoplasms. We are taking this action
because we
[[Page 40722]]
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 March 27, 2017.
FOR FURTHER INFORMATION CONTACT: Ryan Lubert, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 3574, Silver Spring, MD 20993-0002, 240-402-6357,
<a href="/cdn-cgi/l/email-protection#603219010e4e2c1502051214200604014e0808134e070f16"><span class="__cf_email__" data-cfemail="94c6edf5fabad8e1f6f1e6e0d4f2f0f5bafcfce7baf3fbe2">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the mutation detection test for
myeloproliferative neoplasms device 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 July 1, 2016, FDA received QIAGEN Manchester Ltd.'s request for
De Novo classification of the ipsogen JAK2 RGQ PCR Kit. 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 March 28, 2017, 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
866.6070.\1\ We have named the generic type of device ``mutation
detection test for myeloproliferative neoplasms,'' and it is identified
as an in vitro diagnostic device intended for the detection of the JAK2
V617F/G1849T allele in genomic DNA extracted from whole blood. The test
is intended for use as an adjunct to evaluation of suspected
polycythemia vera, in conjunction with other clinicopathological
factors.
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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--Mutation Detection Test for Myeloproliferative Neoplasms Risks
and Mitigation Measures
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Identified risks to health Mitigation measures
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False negative results.................... Special controls (1) and
(2).
False positive results.................... Special controls (1) and
(2).
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FDA has determined that special controls, in combination with the
general controls, address these risks to
[[Page 40723]]
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 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. 866.6070 to subpart G to read as follows:
Sec. 866.6070 Mutation detection test for myeloproliferative
neoplasms.
(a) Identification. A mutation detection test for
myeloproliferative neoplasms is an in vitro diagnostic device intended
for the detection of the JAK2 V617F/G1849T allele in genomic DNA
extracted from whole blood. The test is intended for use as an adjunct
to evaluation of suspected polycythemia vera in conjunction with other
clinicopathological factors.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Design verification and validation must include:
(i) A detailed description of all components in the test, including
the following:
(A) A detailed description, including illustrations or photographs
of non-standard equipment or methods, of the test components, including
all required reagents, instrumentation, and equipment.
(B) Detailed documentation of the device software, including
standalone software applications and hardware-based devices that
incorporate software.
(C) A detailed description of methodology and assay procedures
including appropriate internal and external quality controls that are
recommended or provided. The description must identify those control
elements that are incorporated into the testing procedure.
(D) A detailed specification for sample collection, processing, and
storage.
(E) A description of the criteria for test result interpretation
and reporting including result outputs, analytical sensitivity of the
assay, and the values that will be reported.
(ii) Information that demonstrates the performance characteristics
of the test, including:
(A) For indications for use based on a threshold established in a
predicate device of this generic type, device performance data from
either a method comparison study to the predicate device or through a
clinical study demonstrating clinical validity using well-characterized
prospectively or retrospectively obtained clinical specimens, as
appropriate, representative of the intended use population.
(B) For indications for use based on a threshold not established in
a predicate device of this generic type, device performance data from a
clinical study demonstrating clinical validity using well-characterized
prospectively or retrospectively obtained clinical specimens, as
appropriate, representative of the intended use population.
(C) Device reproducibility data generated, using a minimum of three
sites, of which at least two sites must be external sites, with two
operators at each site. Each site must conduct a study that includes at
least two operators per site, two runs per operator per day over a
minimum of three non-consecutive days evaluating a sample panel that
contains allelic frequencies that span the claimed measuring range, and
include the clinical threshold allelic frequency. Pre-specified
acceptance criteria must be provided and followed.
(D) Information on device traceability and a description of the
value assignment process for calibrators and controls.
(E) Device precision data using clinical samples and controls to
evaluate the within-lot, between-lot, within-run, between-run, and
total variation.
(F) Device linearity data generated from samples covering the
device measuring range and for any standards used in the quantitation
of allelic frequencies.
(G) Device analytic sensitivity data, including limit of blank and
limit of detection.
(H) Device specificity data, including interference and cross-
contamination.
(I) Device and clinical specimen stability data, including real-
time stability (long-term storage and in-use stability) and stability
evaluating various storage times, temperatures, and freeze-thaw
conditions, as appropriate.
(iii) Identification of risk mitigation elements used by the
device, including a detailed description of all additional procedures,
methods, and practices incorporated into the instructions for use that
mitigate risks associated with testing using the device.
(2) The labeling required under Sec. 809.10(b) of this chapter
must include:
(i) An intended use statement, including an indication for use that
includes the variant(s)
for which the assay was designed and validated, for example, JAK2
G1849T.
(ii) A detailed description of the performance studies conducted to
[[Page 40724]]
comply with paragraph (b)(1)(ii) of this section and a summary of the
results.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-16038 Filed 8-20-25; 8:45 am]
BILLING CODE 4164-01-P
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</html>Indexed from Federal Register on August 21, 2025.
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