[Federal Register Volume 87, Number 24 (Friday, February 4, 2022)]
[Rules and Regulations]
[Pages 6419-6422]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-02357]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 878

[Docket No. FDA-2021-N-0948]


Medical Devices; General and Plastic Surgery Devices; 
Classification of the Carbon Dioxide Gas Controlled Tissue Expander

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 or we) is classifying 
the carbon dioxide gas

[[Page 6420]]

controlled tissue expander 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 carbon dioxide 
gas controlled tissue expander'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 February 4, 2022. The classification was 
applicable on December 21, 2016.

FOR FURTHER INFORMATION CONTACT: Tajanay Ki, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 4553, Silver Spring, MD 20993-0002, 301-796-6441, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the carbon dioxide gas controlled 
tissue expander 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, 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 established the first procedure for De Novo classification 
(Pub. L. 105-115). Section 607 of the Food and Drug Administration 
Safety and Innovation Act modified the De Novo application process by 
adding a second procedure (Pub. L. 112-144). 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.
    We believe this De Novo classification will enhance patients' 
access to beneficial innovation. 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 c(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 December 8, 2015, FDA received AirXpanders' request for De Novo 
classification of the AeroForm[supreg] Tissue Expander 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 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 December 21, 2016, 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 
878.3510.\1\ We have named the generic type of device carbon dioxide 
gas-controlled tissue expander, and it is identified as a prescription 
device intended for temporary subcutaneous or submuscular implantation 
to stretch the skin for surgical applications, specifically to develop 
surgical flaps and additional tissue coverage. The device is made of an 
inflatable elastomer shell and is filled with carbon dioxide gas. The 
device utilizes a remote controller to administer doses of carbon 
dioxide gas from an implanted canister inside the device.
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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.

[[Page 6421]]



    Table 1--Carbon Dioxide Gas Controlled Tissue Expander Risks and
                           Mitigation Measures
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            Identified risks                   Mitigation measures
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Pain...................................  Labeling; and
     From overexpansion with      Software verification,
     carbon dioxide.                      validation and hazard
                                          analysis.
Tissue damage..........................  In-vivo performance testing;
                                          Labeling; and
     From overexpansion with     Software verification,
     carbon dioxide.                      validation and hazard
                                          analysis.
Prolonged treatment time...............  In-vivo performance testing;
     Due to under expansion       Non-clinical performance
     because of carbon dioxide            testing; Labeling; and
     permeation.
     Due to overexpansion with   Software verification,
     carbon dioxide.                      validation and hazard
                                          analysis.
Re-operation...........................  In-vivo performance testing and
                                          Non-clinical performance
                                          testing.
     Due to no expansion
     because of device failure
     Due to overexpansion with
     carbon dioxide
Under expansion, overexpansion, or no    Electromagnetic compatibility,
 expansion.                               electrical safety, and
                                          wireless compatibility
                                          testing; Labeling;
     Due to interference with    Software verification,
     other devices.                       validation and hazard
                                          analysis;
     Due to user error.........  Human factors testing; and
                                          Patient training.
Adverse tissue reaction................  Biocompatibility evaluation.
Infection..............................  Sterilization validation and
                                          Shelf life testing.
------------------------------------------------------------------------

    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. In order 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, carbon dioxide gas controlled tissue 
expanders are 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. 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 
the guidance document ``De Novo Classification Process (Evaluation of 
Automatic Class III Designation)'' 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 878

    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 
878 is amended as follows:

PART 878--GENERAL AND PLASTIC SURGERY DEVICES

0
1. The authority citation for part 878 continues to read as follows:

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

0
2. Add Sec.  878.3510 to subpart D to read as follows:


Sec.  878.3510   Carbon dioxide gas controlled tissue expander.

    (a) Identification. A carbon dioxide gas controlled tissue expander 
is a prescription device intended for temporary subcutaneous or 
submuscular implantation to stretch the skin for surgical applications, 
specifically to develop surgical flaps and additional tissue coverage. 
The device is made of an inflatable elastomer shell and is filled with 
carbon dioxide gas. The device utilizes a remote controller to 
administer doses of carbon dioxide gas from an implanted canister 
inside the device.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) In-vivo performance testing must be conducted to obtain the 
adverse event profile associated with use, and demonstrate that the 
device performs as intended under anticipated conditions of use.
    (2) The patient-contacting components of the device must be 
demonstrated to be biocompatible.
    (3) Performance data must demonstrate the sterility of patient-
contacting components of the device.
    (4) Non-clinical performance testing must demonstrate that the 
device performs as intended under anticipated conditions of use. The 
following performance characteristics must be tested:
    (i) Cycle testing of expander showing that there are no leaks or 
tears after repeated cycling;
    (ii) Mechanical assessment of implanted carbon dioxide 
(CO2) canister including high impact testing;
    (iii) Leak testing of expander showing that device does not leak 
CO2;
    (iv) Assessment of gas permeability during expansion and after full 
expansion; and
    (v) Mechanical assessment of expander (tensile set, breaking force, 
shell joint test, and fused or adhered joint testing).
    (5) Performance data must be provided to demonstrate the 
electromagnetic compatibility, electrical safety, and wireless 
compatibility of the device.

[[Page 6422]]

    (6) Software verification, validation, and hazard analysis must be 
performed.
    (7) Performance data must support shelf life by demonstrating 
continued sterility of the device or the sterile components, package 
integrity, and device functionality over the identified shelf life.
    (8) Human factors testing and analysis must validate that the 
device design and labeling are sufficient for the end user.
    (9) Physician labeling must include:
    (i) The operating parameters, name, and model number of the 
indicated external dosage controller;
    (ii) Information on how the device operates and the typical course 
of treatment;
    (iii) Information on the population for which the device has been 
demonstrated to be effective;
    (iv) A detailed summary of the device technical parameters; and
    (v) Provisions for choosing an appropriate size implant that would 
be exchanged for the tissue expander.
    (10) Patient labeling must include:
    (i) Warnings, precautions, and contraindications, and adverse 
events/complications;
    (ii) Information on how the device operates and the typical course 
of treatment;
    (iii) The probable risks and benefits associated with the use of 
the device;
    (iv) Post-operative care instructions; and
    (v) Alternative treatments.
    (11) Patient training must include instructions for device use, 
when it may be necessary to contact a physician, and cautionary 
measures to take when the device is implanted.

    Dated: January 26, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-02357 Filed 2-3-22; 8:45 am]
BILLING CODE 4164-01-P