
[Federal Register Volume 88, Number 216 (Thursday, November 9, 2023)]
[Rules and Regulations]
[Pages 77198-77200]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-24717]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 864

[Docket No. FDA-2023-N-4487]


Medical Devices; Hematology and Pathology Devices; Classification 
of the Container System for the Processing and Storage of Red Blood 
Cell Components Under Reduced Oxygen Conditions

AGENCY: Food and Drug Administration, Department of Health and Human 
Services (HHS).

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
classifying the container system for the processing and storage of Red 
Blood Cell components under reduced oxygen conditions 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 classification of the container system for the processing and 
storage of Red Blood Cell components under reduced oxygen conditions. 
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.

DATES: This order is effective November 9, 2023. The classification was 
applicable on September 15, 2023.

FOR FURTHER INFORMATION CONTACT: Karen Fikes, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.

SUPPLEMENTARY INFORMATION: 

I. Background

    Upon request, FDA has classified the container system for the 
processing and storage of Red Blood Cell components under reduced 
oxygen conditions 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 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). 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 5, 2022, FDA received Hemanext, Inc.'s request for De 
Novo classification of the Hemanext One. 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,

[[Page 77199]]

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 September 15, 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 
864.9115.\1\ We have named the generic type of device container system 
for the processing and storage of Red Blood Cell components under 
reduced oxygen conditions, identified as a device intended for medical 
purposes that is used to process and store Red Blood Cell components 
and reduce oxygen levels in the storage environment.
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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--Container System for the Processing and Storage of Red Blood
   Cell Components Under Reduced Oxygen Conditions Risks to Health and
                           Mitigation Measures
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         Identified risks to health              Mitigation measures
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Toxicity that can result from contact of     Biocompatibility
 the component materials of the device with   evaluation.
 the red blood cells or patient's body.
Toxicity of leached materials, or residual   Extractables and leachables
 chemical sterilant, when in contact with     testing.
 red blood cells or transfused to patient.
Infection..................................  Sterilization validation;
                                              Endotoxin testing; and
                                              Container closure
                                              evaluation.
Transfusion of poor quality red blood cells  Nonclinical and clinical
 because of inadequate storage conditions     studies; Shelf-life
 or device malfunction.                       testing; and Performance
                                              testing.
Blood exposure because of device             Performance testing.
 malfunction.
Transfusion of poor quality red blood cells  Labeling.
 due to processing of Red Blood Cells
 components collected from donors with
 hemoglobin S.
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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. At the time of 
classification, container system for the processing and storage of Red 
Blood Cell components under reduced oxygen conditions is for 
prescription use only. Prescription devices are exempt from the 
requirement for adequate directions for use for the layperson under 
section 502(f)(1) of the FD&C Act (21 U.S.C. 352(f)(1)) and 21 CFR 
801.5, as long as the conditions of 21 CFR 801.109 are met.

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 21 CFR 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 part 801, regarding labeling, have been approved 
under OMB control number 0910-0485.

List of Subjects in 21 CFR Part 864

    Blood, Medical devices, Packaging and containers.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
864 is amended as follows:

PART 864--HEMATOLOGY AND PATHOLOGY DEVICES

0
1. The authority citation for part 864 continues to read as follows:

    Authority:  21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.


0
2. Add Sec.  864.9115 to subpart J to read as follows:


Sec.  864.9115  Container system for the processing and storage of Red 
Blood Cell components under reduced oxygen conditions.

    (a) Identification. A container system for the processing and 
storage of Red Blood Cell components under reduced oxygen conditions is 
a device intended for medical purposes that is used to process and 
store Red Blood Cell components and reduce oxygen levels in the storage 
environment.
    (b) Classification. Class II (special controls). The special 
controls for this device are:

[[Page 77200]]

    (1) The intended use of the device must specify:
    (i) The Red Blood Cell components that can be processed and stored 
including acceptable anticoagulants and additive solutions;
    (ii) The hold time after Red Blood Cell component collection;
    (iii) The processing capacity (volume) of the device; and
    (iv) The storage temperature and dating period of processed Red 
Blood Cell components.
    (2) Studies must demonstrate that the device is biocompatible and 
include detailed documentation of the biocompatibility evaluation.
    (3) Performance testing and nonclinical studies must include a 
detailed study of leached materials extracted under conditions similar 
to clinical usage of the device, and a toxicologic risk assessment of 
those extracted or leached materials.
    (4) Performance testing must support sterility of the device and 
include sterilization validation, endotoxin testing, and container 
closure integrity evaluation.
    (5) Nonclinical and clinical studies must include evaluation of red 
blood cell quality throughout the duration of storage based on in vitro 
and in vivo studies, including hemolysis and red blood cell survival 
and recovery.
    (6) Performance studies must include:
    (i) Detailed documentation of functional and mechanical testing, 
including evaluation of oxygen and, if applicable, carbon dioxide 
levels during Red Blood Cell components storage; and
    (ii) Detailed documentation of device shelf-life testing 
demonstrating continued sterility, package integrity, and functionality 
over the identified shelf life.
    (7) The labeling must include a contraindication against processing 
Red Blood Cell components collected from donors with hemoglobin S.

    Dated: November 3, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-24717 Filed 11-8-23; 8:45 am]
BILLING CODE 4164-01-P


