[Federal Register Volume 89, Number 174 (Monday, September 9, 2024)]
[Rules and Regulations]
[Pages 72982-72984]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-20254]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 862

[Docket No. FDA-2024-N-4086]


Medical Devices; Clinical Chemistry and Clinical Toxicology 
Devices; Classification of the Blood Collection Device for Cell-Free 
Nucleic Acids

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
classifying the blood collection device for cell-free nucleic acids 
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 the blood collection device for cell-free nucleic 
acids' classification. We are taking this action because we have 
determined that classifying the device into class II (special controls) 
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 September 9, 2024. The classification 
was applicable on August 7, 2020.

FOR FURTHER INFORMATION CONTACT: Lindsey Coe, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3556, Silver Spring, MD 20993-0002, 240-402-5267, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the blood collection device for 
cell-free nucleic acids as class II (special controls), which we have 
determined will provide a reasonable assurance of safety and 
effectiveness.
    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 (see 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

[[Page 72983]]

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 21 CFR 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.
    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 
510(k) process, when necessary, to market their device.

II. De Novo Classification

    On January 10, 2020, FDA received Streck, Inc.'s request for De 
Novo classification of the Cell-Free DNA BCT. 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 21 U.S.C. 360c(a)(1)(B)). 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 August 7, 2020, 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 
862.1676.\1\ We have named the generic type of device blood collection 
device for cell-free nucleic acids, and it is identified as intended 
for medical purposes to collect, store, transport, and handle blood 
specimens and to stabilize and isolate cell-free nucleic acid 
components prior to further 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 following risks to health associated 
specifically with this type of device and the measures required to 
mitigate these risks in table 1.

 Table 1--Blood Collection Device for Cell-Free Nucleic Acids Risks and
                           Mitigation Measures
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        Identified risks to health               Mitigation measures
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Blood pathogen exposure/Injury............  Certain design verification
                                             and validation.
Failure to collect and transport sample...  Certain design verification
                                             and validation.
Insufficient sample quantity and quality..  Certain design verification
                                             and validation.
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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 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.  862.1676 to subpart B to read as follows:

[[Page 72984]]

Sec.  862.1676  Blood collection device for cell-free nucleic acids.

    (a) Identification. A blood collection device for cell-free nucleic 
acids is a device intended for medical purposes to collect, store, 
transport, and handle blood specimens and to stabilize and isolate 
cell-free nucleic acid components prior to further testing.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Design verification and validation documentation must include 
appropriate design inputs and design outputs that are essential for the 
proper functioning of the device for its intended use, including all of 
its indications for use, and must include the following:
    (i) Documentation demonstrating that appropriate, as determined by 
FDA, measures are in place (e.g., validated device design features and 
specifications) to ensure that users of blood collection device for 
cell-free nucleic acids devices are not exposed to undue risk of 
bloodborne pathogen exposure and operator injury during use of the 
device, including blood collection, transportation, and centrifugation 
processes.
    (ii) Documentation demonstrating that appropriate, as determined by 
FDA, measures are in place (e.g., validated device design features and 
specifications) to ensure that the device reproducibly and reliably 
collects, transports, stabilizes, and isolates cell-free nucleic acids 
of sufficient yield and quality suitable for downstream applications as 
appropriate for its intended use. At a minimum, these measures must 
include:
    (A) Data demonstrating that blood samples collected in the device 
have reproducible cell-free nucleic acid yields that are suitable, as 
determined by FDA, for downstream testing as appropriate for the 
intended use, including estimates of within-lot, within-device, and 
lot-to-lot variability;
    (B) Data demonstrating that cell-free nucleic acid yields isolated 
from blood specimens collected into the device do not add clinically 
significant bias to test results obtained using the downstream 
application(s) described in the intended use. For devices indicated for 
use with multiple downstream applications, data demonstrating 
acceptable performance for each type of claimed use or, alternatively, 
an appropriate, as determined by FDA, clinical justification for why 
such data are not needed;
    (C) Data demonstrating that the device appropriately stabilizes 
cell-free nucleic acids after sample collection, during storage, and 
during transport over the claimed shelf life of the device;
    (D) Data demonstrating that samples collected in the device have 
minimal levels of contamination with other types of nucleic acids 
present in cells or cellular components, and that these levels of 
contamination do not interfere with downstream testing;
    (E) Data from analytical or clinical studies that demonstrate that, 
when used as intended, the device consistently draws a blood sample 
volume that is within the indicated fill range;
    (F) Data from analytical or clinical studies that demonstrate that, 
when used as intended, cell-free nucleic acid yield, stability, and 
quality are not significantly impacted by interference due to other 
parts of the device (such as reduced or excess active ingredient) or 
specimen collection and processing procedures (such as hemolysis, 
centrifugation, or mixing of blood with anticoagulant or additives); 
and
    (G) Data from analytical studies that demonstrate that the device 
is suitable for its intended use across all storage and sample handling 
conditions described in the device labeling, including device shelf 
life and shipping conditions (e.g., temperature, humidity, duration).
    (iii) A protocol, reviewed and determined acceptable by FDA, that 
specifies the verification and validation activities that will be 
performed for anticipated device modifications to reevaluate 
performance claims or performance specifications. This protocol must 
include a process for assessing whether a modification to technology, 
engineering, performance, materials, specifications, or indications for 
use, or any combination thereof, could significantly affect the safety 
or effectiveness of the device. The protocol must include assessment 
metrics, acceptance criteria, and analytical methods for the 
performance testing of changes.

    Dated: September 4, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-20254 Filed 9-6-24; 8:45 am]
BILLING CODE 4164-01-P