Rule2026-15963
Medical Devices; Radiology Devices; Classification of the Fludeoxyglucose F18-Guided Radiation Therapy System
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Published
August 6, 2026
Effective
August 6, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA) is classifying the fludeoxyglucose F18-guided radiation therapy 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 fludeoxyglucose F18-guided radiation therapy 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 91 Issue 150 (Thursday, August 6, 2026)</title>
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[Federal Register Volume 91, Number 150 (Thursday, August 6, 2026)]
[Rules and Regulations]
[Pages 50708-50710]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-15963]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 892
[Docket No. FDA-2026-N-7954]
Medical Devices; Radiology Devices; Classification of the
Fludeoxyglucose F18-Guided Radiation Therapy 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
fludeoxyglucose F18-guided radiation therapy 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 fludeoxyglucose F18-guided radiation therapy
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 6, 2026. The classification was
applicable on February 1, 2023.
FOR FURTHER INFORMATION CONTACT: Lora Weidner, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 3652, Silver Spring, MD 20993-0002, 240-402-6424,
<a href="/cdn-cgi/l/email-protection#feb2918c9fd0a99b979a909b8cbe989a9fd096968dd0999188"><span class="__cf_email__" data-cfemail="3c70534e5d126b59555852594e7c5a585d1254544f125b534a">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA (the Agency or we) has classified the
fludeoxyglucose F18-guided radiation therapy system into class II
(special controls), which we have determined will provide a reasonable
assurance of 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 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
[[Page 50709]]
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 February 23, 2022, FDA received RefleXion Medical Inc's request
for De Novo classification of the RefleXion Medical Radiotherapy System
(RMRS). 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 February 1, 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
892.5060.\1\ We have named the generic type of device ``fludeoxyglucose
F18-guided radiation therapy system,'' and it is identified as a device
that combines the functionality of an emission computed tomography
detection system and a linear accelerator. The device is intended for
use with approved fludeoxyglucose F18. The emission computed tomography
detection system acquires images of positron-emitting fludeoxyglucose
F18 for the purpose of guiding the delivery of megavoltage X-rays for
oncologic treatment with radiation therapy using an FDA-cleared, -
authorized, or -approved linear accelerator.
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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 Fludeoxyglucose F18-
Guided Radiation Therapy Systems
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Identified risks to health Mitigation measures
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Device-specific modifications of Clinical performance testing;
fludeoxyglucose F18 use compared to Labeling; and Analysis of drug
the current approved drug label that and device label differences.
affect safety and effectiveness of
fludeoxyglucose F18.
Postmarket modifications to Design verification and
fludeoxyglucose F18 labeling that validation activities.
affect safety and effectiveness when
used with the device.
Inaccurate therapeutic radiation dose Non-clinical performance
delivery due to intra- or inter- testing; Clinical performance
fractional changes of fludeoxyglucose testing; and Labeling.
F18 biodistribution.
Incompatibility of the linear Non-clinical performance
accelerator and the positron emission testing; Electromagnetic
tomography (PET) scanner leading to compatibility testing;
machine failures during treatment and Electrical safety testing; and
treatment delay. Software verification,
validation, and hazard
analysis.
Inadequate reader and device Labeling; Clinical performance
interpretation of fludeoxyglucose F18 testing; Non-clinical
biodistribution for determining performance testing; Training;
treatment eligibility. and Software verification,
validation, and hazard
analysis.
PET evaluation failure leading to Non-clinical performance
treatment delay and/or excess testing; Clinical performance
radiation exposure from testing; Labeling; and
fludeoxyglucose F18. Software verification,
validation, and hazard
analysis.
Inaccurate therapeutic radiation dose Non-clinical performance
delivery due to machine failure. testing; Labeling; and
Software verification,
validation, and hazard
analysis.
Uncertainty regarding external Non-clinical performance
radiation dose delivered to healthy testing; and Software
tissue. verification, validation, and
hazard analysis.
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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 the 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.
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 fludeoxyglucose F18-guided
radiation therapy 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
[[Page 50710]]
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; the collections of information in 21 CFR part 314
have been approved under OMB control number 0910-0001; the collections
of information in 21 CFR part 201 have been approved under OMB control
number 0910-0572; the collections of information in 21 CFR parts 210
and 211 have been approved under OMB control number 0910-0139; and the
collections of information in 21 CFR part 801 regarding labeling have
been approved under OMB control number 0910-0485.
List of Subjects in 21 CFR Part 892
Medical devices, Radiation protection, X-rays.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
892 is amended as follows:
PART 892--RADIOLOGY DEVICES
0
1. The authority citation for part 892 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 892.5060 to subpart F to read as follows:
Sec. 892.5060 Fludeoxyglucose F18-guided radiation therapy system.
(a) Identification. A fludeoxyglucose F18-guided radiation therapy
system is a device that combines the functionality of an emission
computed tomography detection system and a linear accelerator. The
device is intended for use with approved fludeoxyglucose F18. The
emission computed tomography detection system acquires images of
positron-emitting fludeoxyglucose F18 for the purpose of guiding the
delivery of megavoltage X-rays for oncologic treatment with radiation
therapy using an FDA-cleared, -authorized, or -approved linear
accelerator.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) An analysis must be provided of any effects on safety or
effectiveness based on differences that exist in the use (i.e.,
concentration, rate of administration, route of administration; region,
organ, or system of the body; or patient population) of fludeoxyglucose
F18 with the device compared to the current approved drug labeling; and
adequate justification, including support from clinical performance
testing and labeling, must be provided that the differences do not
adversely affect the safety and effectiveness of fludeoxyglucose F18
when used with the device.
(2) Design verification and validation activities must include
monitoring of changes to the labeling and formulation of
fludeoxyglucose F18, and addressing such changes so that they do not
adversely affect the safety and effectiveness of the device and
fludeoxyglucose F18 when used with the device.
(3) Clinical performance testing must demonstrate that the system
performs as intended under anticipated conditions of use, including
demonstrating: adequate reader performance for distinguishing patients
with eligible versus ineligible radiopharmaceutical biodistribution on
imaging; reproducibility across fractions; and sufficient signal
strength to meet system sensitivity requirements. Clinical performance
testing under anticipated conditions of use must evaluate: dose ranging
for identification of lowest safe and adequate dose; and all adverse
events.
(4) Non-clinical performance testing under anticipated conditions
of use must demonstrate:
(i) Compatibility of the linear accelerator and the tomography
scanner;
(ii) Adequate positron emission tomography (PET) imaging
performance for patient selection in comparison with a legally marketed
diagnostic scanner's output;
(iii) Adequacy of the chosen imaging metrics for inter- and intra-
fractional treatment delivery; and
(iv) Dosimetric concurrence between delivered dose distributions
and treatment plan, including comparison of delivery isolating
difference between guidance on and off conditions.
(5) Performance testing must demonstrate the electrical safety and
electromagnetic compatibility of any electrical components.
(6) Software verification, validation, and hazard analysis must be
performed for any software components of the device. Software
documentation must include a detailed description of the dose delivery
tracking algorithms, including the dose calculation methods, treatment
boundaries, treatment delivery fluence calculation methods, system
latency for moving targets, interface for post-treatment review,
limitations of the algorithm, and accompanying verification and
validation testing to ensure device and algorithm functionality as
informed by the software requirements and hazard analysis.
(7) A training program must be included to ensure users can
correctly interpret images to determine patient eligibility.
(8) The labeling must include the following:
(i) A detailed description of the patient population included in
clinical testing specifying age, primary cancer type, cancer stage, and
target volume locations and sizes;
(ii) A dedicated imaging agent section which includes a description
of the use of fludeoxyglucose F18 with the device and a statement in
the indications for use informing users where full prescribing
information is available for fludeoxyglucose F18 in the current
approved drug labeling and in the device labeling;
(iii) Detailed instructions for use of fludeoxyglucose F18 with the
device to guide radiation therapy, including: uptake time needed, time
window to deliver treatment, physician review of pre-delivery safety
checks, image interpretation, tissue targeted for fludeoxyglucose F18
uptake, pre-treatment image criteria to determine patient eligibility,
and other differences compared to the current approved fludeoxyglucose
F18 drug labeling;
(iv) A detailed summary of the performance testing required under
paragraphs (b)(3) and (b)(4) of this section, including test methods,
dataset characteristics, and results;
(v) A detailed description of the user workflow; and
(vi) An instruction for users to plan for an alternative treatment
if pre-treatment evaluation fails.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-15963 Filed 8-5-26; 8:45 am]
BILLING CODE 4164-01-P
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