Rule2026-08812
Medical Devices; Immunology and Microbiology Devices; Classification of the Circulating Tumor Cell Enrichment Device
Primary source
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Published
May 6, 2026
Effective
May 6, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA) is classifying the circulating tumor cell enrichment device 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 circulating tumor cell enrichment device. 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 87 (Wednesday, May 6, 2026)</title>
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[Federal Register Volume 91, Number 87 (Wednesday, May 6, 2026)]
[Rules and Regulations]
[Pages 24343-24345]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-08812]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. FDA-2026-N-4643]
Medical Devices; Immunology and Microbiology Devices;
Classification of the Circulating Tumor Cell Enrichment Device
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
circulating tumor cell enrichment device 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 circulating tumor cell enrichment device. 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 May 6, 2026. The classification was
applicable on May 24, 2022.
FOR FURTHER INFORMATION CONTACT: Soma Ghosh, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 3316, Silver Spring, MD 20993-0002, 240-402-5333,
<a href="/cdn-cgi/l/email-protection#97c4f8faf6b9d0fff8e4ffd7f1f3f6b9ffffe4b9f0f8e1"><span class="__cf_email__" data-cfemail="15467a78743b527d7a667d557371743b7d7d663b727a63">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA (the Agency or we) has classified the circulating
tumor cell enrichment device 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 classification is considered to be the
initial classification of the device.
[[Page 24344]]
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 September 28, 2020, FDA received ANGLE Europe Ltd.'s request for
De Novo classification of the Parsortix PC1 Device. 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 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 May 24, 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
866.6110.\1\ We have named the generic type of device ``circulating
tumor cell enrichment device,'' and it is identified as in vitro
diagnostic device used to enrich circulating tumor cells from the
peripheral blood of patients diagnosed with cancer for subsequent in
vitro diagnostic testing.
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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 the Circulating
Tumor Cell Enrichment Device
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Identified risks to health Mitigation measures
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Failure to identify circulating tumor Use of certain specimen
cells (CTCs) that are present in the collection devices identified
sample leading to delays in patient in special control (1).
management. Certain labeling information
identified in special control
(2), including limitations,
device descriptions, training
specifications, explanation of
procedures, and performance
information identified in
special control (3).
Certain design verification and
validation identified in
special control (3), including
documentation of certain
analytical studies and
clinical studies.
No results obtained using downstream Certain labeling information
testing leading to delays in patient identified in special control
management. (2), including limitations,
device descriptions, training
specifications, explanation of
procedures, and performance
information identified in
special control (3).
Incorrect evaluation of CTCs using Certain labeling information
downstream analyses leading to identified in special control
associated risk of false test results (2), including limitations,
and improper patient management. device descriptions,
explanation of procedures, and
performance information
identified in special control
(3).
Failure to correctly operate the device Certain labeling information
leading to delays in patient identified in special control
management and associated risk to (2), including limitations,
downstream analyses resulting in false device descriptions, and
test results and improper patient explanation of procedures.
management.
Bloodborne pathogen transmission from Certain labeling information
blood waste/blood sample. identified in special control
(2), including limitations,
device descriptions, and
explanation of procedures.
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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 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 circulating tumor cell
enrichment devices. 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
[[Page 24345]]
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. 866.6110 to subpart G to read as follows:
Sec. 866.6110 Circulating tumor cell enrichment device.
(a) Identification. A circulating tumor cell enrichment device is
an in vitro diagnostic device used to enrich circulating tumor cells
from the peripheral blood of patients diagnosed with cancer for
subsequent in vitro diagnostic testing.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Any device used for specimen collection and transport must be
FDA-cleared, -approved, or -classified as 510(k) exempt for the
collection of human specimens; alternatively, the sample collection
device must be cleared in a premarket submission as a part of this
device.
(2) The labeling required under Sec. 809.10(b) of this chapter
must include:
(i) Detailed specifications and procedures for sample collection,
processing, and storage.
(ii) An intended use statement that includes:
(A) The intended specimen type(s) for which acceptable, as
determined by FDA, validation data has been provided (e.g., peripheral
whole blood).
(B) The identification of, or the specifications for, the
collection device or devices to be used for sample collection.
(C) Information on the device output(s) (e.g., circulating tumor
cells (CTCs), other blood cells).
(D) The specific tumor type(s) for which the device is intended to
be used.
(E) A statement for general downstream diagnostic assays and that
end users need to validate use with any subsequent tests and collection
devices.
(F) A statement that the standalone device is not intended for
diagnostic, prognostic, or monitoring use with CTCs, including as an
aid in any disease management and/or treatment decisions.
(iii) Prominent and conspicuous limiting statements clearly
explaining:
(A) The use of the device is intended for the collection of CTCs
from previously diagnosed cancer patients.
(B) The standalone device is not intended for cell enumeration.
(C) The users for whom the device is intended, including any
training specifications.
(D) The performance characteristics of this device have not been
established for general downstream diagnostic assays and that end users
need to validate use with any subsequent tests and collection devices.
(E) An insufficient number of CTCs or even no circulating tumor
cells may be collected.
(F) Results from the standalone device do not provide information
to the patient regarding their current state of health.
(G) The standalone device does not diagnose any health conditions
and is not a substitute for visits to a doctor or other healthcare
professional.
(H) The device is intended only for enriching CTC content in
specimens so that the enriched specimens can then be used in further
processing/analysis using additional independent methods.
(I) The variability of the number of CTCs and other cells harvested
by the device may impact the success of any subsequent analysis.
(iv) A troubleshooting section that includes clear instructions for
resolving any common device-related issues.
(v) A description of the device mechanism of action to enrich CTCs.
(vi) A detailed summary of the analytical and clinical performance
studies required under paragraph (b)(3) of this section.
(3) Design verification and validation must include the following:
(i) Documentation of studies that provide:
(A) Data demonstrating acceptable, as determined by FDA, analytical
device performance using samples representative of the range of those
with which the device is intended for use. The number of specimens
tested must be sufficient to obtain estimates of device performance
that is representative of the device performance within the full
spectrum of the device's intended use.
(B) Data demonstrating acceptable precision, as determined by FDA,
to adequately evaluate intra-run, inter-run, and total variability
across operator, instrument, lot, day, and site, as applicable.
(C) Data demonstrating the detection limit of the device.
(D) Recovery study data demonstrating the range of the device.
(E) Data demonstrating appropriate validation of device design
features and specifications such that the device reproducibly and
reliably collects and isolates CTCs. At a minimum, the data must
include:
(1) Data, as appropriate for the intended use, including estimates
of within-lot, within-device, and lot-to-lot variability, demonstrating
that samples collected from the intended use population using the
device provide CTCs that are suitable, as determined by FDA, for the
intended downstream testing.
(2) Data demonstrating that the device output has no contamination
or minimal levels of contamination from other sources, and that any
such contamination does not interfere with the recovery of CTCs.
(3) Data demonstrating that the presence of clinically relevant
levels of potential interfering substances in the intended specimen
type(s) and intended use population, including endogenous and exogenous
substances, does not interfere with the recovery of CTCs.
(4) Data demonstrating that blood samples collected for use with
the device remain stable under certain storage conditions (e.g.,
temperature, time) and do not impact the output of representative
downstream testing.
(ii) Documentation of clinical studies using the device on intended
use clinical specimens that demonstrate the device can enrich or
capture an appropriate number of CTCs, as determined by FDA, to support
the intended use of the device.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-08812 Filed 5-5-26; 8:45 am]
BILLING CODE 4164-01-P
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</html>Indexed from Federal Register on May 6, 2026.
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