[Federal Register Volume 87, Number 249 (Thursday, December 29, 2022)]
[Rules and Regulations]
[Pages 80038-80040]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-28168]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 870

[Docket No. FDA-2022-N-3186]


Medical Devices; Cardiovascular Devices; Classification of the 
Extracorporeal System for Carbon Dioxide Removal

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 extracorporeal system for carbon dioxide removal 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 extracorporeal system for carbon dioxide 
removal's 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.

DATES: This order is effective December 29, 2022. The classification 
was applicable on November 13, 2021.

FOR FURTHER INFORMATION CONTACT: Alejandra Cambonchi, Center for 
Devices and Radiological Health, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 66, Rm. 2253, Silver Spring, MD 20993-0002, 
301-796-0552, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Upon request, FDA has classified the extracorporeal system for 
carbon dioxide removal as class II (special controls), which we have 
determined will provide a reasonable assurance of safety and 
effectiveness. In addition, we believe this action will enhance 
patients' access to beneficial innovation, in part 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 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. 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 
less-burdensome 510(k) process, when necessary, to market their device.

II. De Novo Classification

    On August 30, 2021, FDA received ALung Technologies, Inc.'s request 
for De Novo classification of the Hemolung Respiratory Assist System. 
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 November 13, 2021, 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 
870.4150.\1\ We have named the generic type of device extracorporeal 
system for carbon dioxide removal, and

[[Page 80039]]

it is identified as a system of devices and accessories that provides 
assisted extracorporeal carbon dioxide removal from the patient's blood 
in patients with acute respiratory failure, where other available 
treatment options have failed, and continued clinical deterioration is 
expected or the risk of death is imminent. The main devices and 
accessories of the system include, but are not limited to, the console 
(hardware), software, and disposables, including, but not limited to, a 
gas exchanger, blood pump, cannulae, tubing, filters, and other 
accessories (e.g., monitors, detectors, sensors, connectors).
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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--Extracorporeal System for Carbon Dioxide Removal Risks and
                           Mitigation Measures
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       Identified risks                   Mitigation measures
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Bleeding, Thrombocytopenia,    In Vivo Evaluation, Non-clinical
 Hemolysis, Thrombosis.         performance testing, and Labeling.
Infection....................  In Vivo Evaluation, Sterility, Shelf-life
                                testing, and Labeling.
Adverse Tissue and/or          In Vivo Evaluation, Biocompatibility, and
 Hematologic Reaction.          Labeling.
Mechanical Failure...........  In Vivo Evaluation, Non-clinical
                                performance testing, Labeling, and
                                Software Validation, verification, and
                                hazard analysis.
Hemodynamic Instability......  In Vivo Evaluation, Non-clinical
                                performance testing, and Labeling.
Hypothermia..................  In Vivo Evaluation, Non-clinical
                                performance testing, and Labeling.
Mechanical Injury to Access    In Vivo Evaluation, Non-clinical
 Vessels.                       performance testing, and Labeling.
Inadequate gas exchange......  In Vivo Evaluation, Non-clinical
                                performance testing, and Labeling.
Hemodilution.................  In Vivo Evaluation, Non-clinical
                                performance testing, and Labeling.
Gas embolism.................  In Vivo Evaluation, Non-clinical
                                performance testing, and Labeling.
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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. We encourage sponsors to consult with us if they wish to 
use a non-animal testing method they believe is suitable, adequate, 
validated, and feasible. We will consider if such an alternative method 
could be assessed for equivalency to an animal test method. 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 21 CFR part 860, subpart D, regarding De Novo 
classification have been approved under OMB control number 0910-0844; 
the collections of information in 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, regarding labeling, have been approved 
under OMB control number 0910-0485.

List of Subjects in 21 CFR Part 870

    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 
870 is amended as follows:

PART 870--CARDIOVASCULAR DEVICES

0
1. The authority citation for part 870 continues to read as follows:

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


0
2. Add Sec.  870.4150 to subpart E to read as follows:


Sec.  870.4150  Extracorporeal system for carbon dioxide removal.

    (a) Identification. An extracorporeal system for carbon dioxide 
removal is a system of devices and accessories that provides assisted 
extracorporeal carbon dioxide removal from the patient's blood in 
patients with acute respiratory failure, where other available 
treatment options have failed, and continued clinical deterioration is 
expected or the risk of death is imminent. The main devices and 
accessories of the system include, but are not limited to, the console 
(hardware), software, and disposables, including, but not limited to, a 
gas exchanger, blood pump, cannulae, tubing, filters, and other 
accessories (e.g., monitors, detectors, sensors, connectors).
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) In vivo evaluation, which may include animal testing and 
clinical data, of the devices and accessories in the circuit must 
demonstrate their performance over the intended duration of use, 
including a detailed summary of the in vivo evaluation pertinent to the 
use of the devices and accessories to demonstrate their effectiveness.
    (2) The technological characteristics of the device must ensure 
that the geometry and design parameters are consistent with the 
intended use, and that the devices and accessories in the circuit are 
compatible.
    (3) Non-clinical performance testing of the devices and accessories 
in the circuit must demonstrate that the device performs as intended 
under anticipated conditions of use. The following performance 
characteristics must be tested:
    (i) Mechanical integrity;
    (ii) Durability; and

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    (iii) Reliability.
    (4) All patient contacting components of the device must be 
demonstrated to be biocompatible.
    (5) Performance testing must demonstrate the electrical safety and 
electromagnetic compatibility (EMC) of any electrical components.
    (6) Software validation, verification, and hazard analysis must be 
performed.
    (7) Performance testing must demonstrate the sterility of all 
patient-contacting components.
    (8) Performance testing must support the shelf life of the device 
by demonstrating continued sterility and device functionality over the 
identified shelf life.
    (9) Labeling must include the following:
    (i) A detailed summary of the non-clinical and in vivo evaluations 
pertinent to use of the device and accessories in the circuit;
    (ii) Adequate instructions with respect to circuit setup, 
performance characteristics with respect to compatibility among 
different devices and accessories in the circuit, and maintenance 
during a procedure; and
    (iii) A shelf life.

    Dated: December 21, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-28168 Filed 12-28-22; 8:45 am]
BILLING CODE 4164-01-P