Medical Devices; Immunology and Microbiology Devices; Classification of the Hematopoietic Cell Enrichment Kit

Issuing agencies

Abstract

The Food and Drug Administration (FDA) is classifying the hematopoietic cell enrichment kit 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 hematopoietic cell enrichment kit. 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 195 (Friday, October 9, 2026)</title>
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[Federal Register Volume 91, Number 195 (Friday, October 9, 2026)]
[Rules and Regulations]
[Pages 64609-64611]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-20725]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2026-N-10994]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the Hematopoietic Cell Enrichment Kit

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 
hematopoietic cell enrichment kit 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 hematopoietic cell enrichment kit. 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 9, 2026. The classification was 
applicable on November 6, 2023.

FOR FURTHER INFORMATION CONTACT: Allen Williams, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3248, Silver Spring, MD 20993-0002, 301-796-4806, 
<a href="/cdn-cgi/l/email-protection#7d3c11111813532a141111141c100e3d1b191c5315150e531a120b"><span class="__cf_email__" data-cfemail="b9f8d5d5dcd797eed0d5d5d0d8d4caf9dfddd897d1d1ca97ded6cf">[email&#160;protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA (the Agency or we) has classified the 
hematopoietic cell enrichment kit 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 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.

[[Page 64610]]

II. De Novo Classification

    On December 12, 2022, FDA received STEMCELL Technologies Canada 
Inc.'s request for De Novo classification of the EasySep Human Bone 
Marrow CD138 Positive Selection 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 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 November 6, 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 
866.6120.\1\ We have named the generic type of device ``hematopoietic 
cell enrichment kit,'' and it is identified as an in vitro diagnostic 
device intended for the selection and enrichment of specific 
hematopoietic cells from human whole blood and/or bone marrow collected 
from patients with hematological malignancies using immunomagnetic 
bead-based selection. It is intended for use with diagnostic assays as 
part of the pre-analytical workflow.
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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 Hematopoietic Cell
                             Enrichment Kits
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       Identified risks to health              Mitigation measures
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Failure to perform as expected due to    Use of certain specimen
 errors in enrichment, contributing to    collection devices.
 false positive or false negative        Certain design verification and
 results, or failure to produce results   validation, including certain
 in downstream assays.                    studies and risk mitigation
                                          analysis.
                                         Certain labeling information,
                                          including limitations, device
                                          descriptions, methodology and
                                          protocols, and performance
                                          information.
Incorrect interpretation of enrichment   Certain labeling information,
 results by the lab.                      including limitations, device
                                          descriptions, methodology and
                                          protocols, and performance
                                          information.
                                         Certain design verification and
                                          validation, including certain
                                          studies and risk mitigation
                                          analysis.
------------------------------------------------------------------------

    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 hematopoietic cell 
enrichment kits. 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.  866.6120 to subpart G to read as follows:


Sec.  866.6120   Hematopoietic cell enrichment kit.

    (a) Identification. A hematopoietic cell enrichment kit is an in 
vitro diagnostic device intended for the selection and enrichment of 
specific

[[Page 64611]]

hematopoietic cells from human whole blood and/or bone marrow collected 
from patients with hematological malignancies using immunomagnetic 
bead-based selection. It is intended for use with diagnostic assays as 
part of the pre-analytical workflow.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Any sample collection device used must be FDA-cleared, -
approved, or -classified as 510(k) exempt (stand-alone or as part of a 
test system) for the collection of the sample types with which this 
device is intended to be used; alternatively, the sample collection 
device must be cleared in a premarket submission as a part of this 
device.
    (2) The intended use statement must include:
    (i) The intended use specimen type (i.e., human whole blood and/or 
bone marrow) for each malignancy for which acceptable enrichment has 
been demonstrated and documented using the minimum volume required to 
ensure a 95 percent accurate call rate when the cell concentration is 
at the limit of detection, per the device labeling.
    (ii) A detailed description of the cell enrichment target(s).
    (iii) A statement that the end-user is responsible for validation 
of this device for use with the assay.
    (3) The labeling required under Sec.  809.10(b) of this chapter 
must include:
    (i) Detailed specifications and procedures, appropriately supported 
by replicate and stability data, for sample collection, processing, and 
storage, including acceptable ranges of deviation.
    (ii) A detailed device description, including all device parts 
(e.g., instruments and associated user manuals, antibody(ies), 
reagents, and consumables) and their use within the enrichment 
procedure.
    (iii) Prominent and conspicuous limiting statements clearly 
explaining:
    (A) Any end-user validation required for use with specific tests 
and collection devices.
    (B) Bone marrow stability is severely compromised after 48 hours 
(or, alternatively, a different timeframe supported by appropriate 
specimen stability data required under paragraph (4)(i)(E) of this 
section).
    (C) The device is intended only for enriching hematopoietic cell 
specimens for use in further processing or analysis using additional 
independent methods.
    (D) Results from the device do not provide information regarding 
any health conditions.
    (E) The device is not intended for cell enumeration.
    (F) A detailed summary of the studies required under paragraph 
(b)(4) of this section.
    (4) Design verification and validation must include:
    (i) Detailed documentation of the following studies for each 
intended specimen type and malignancy combination, including the study 
protocols containing descriptions of the test methods, prescribed 
methods of data analysis and acceptance criteria, final study reports, 
and data line listings:
    (A) Recovery study data demonstrating the range of the device.
    (B) A study demonstrating the device limit of detection by 
demonstrating the minimum number of cells within a prespecified volume 
that the device is capable of enriching and the percent enrichment when 
the concentration of cells is established, using a flow cytometry 
reference method determined to be acceptable by FDA.
    (C) A study demonstrating device reproducibility, including 
multiple operators at each site using the specified enrichment 
method(s) and protocol. The evaluation must include multiple runs, 
different instruments, and three different reagent lots. The study must 
include specimens with low, medium, and high starting enrichment target 
levels and result in enrichment and acceptable precision at each level. 
The study must include specimens containing different genetic 
alterations representative of the cancer indication or condition.
    (D) A study demonstrating device specificity, including 
interference, to evaluate the impact on cell enrichment.
    (E) Studies performed to support the stability of samples using the 
indicated specimen collection method(s) under various storage times, as 
applicable.
    (ii) Detailed documentation of studies performed to demonstrate on-
board and in-use reagent stability, including studies to demonstrate 
reagent shelf life.
    (iii) A shipping-stability study, separate from the on-board and 
in-use reagent stability study, that demonstrates acceptable stability 
of the parts that comprise the device.

Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-20725 Filed 10-8-26; 8:45 am]
BILLING CODE 4164-01-P


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