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 Department of Health and Human Services Food and Drug Administration 21 CFR Part 878
[Docket No. FDA-2021-N-0948]
 AGENCY: Food and Drug Administration, Department of Health and Human Services (HHS).
 ACTION: Final amendment; final order.
 SUMMARY: The Food and Drug Administration (FDA or we) is classifying the carbon dioxide gas 
                        ( print 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, 
                        *Tajanay.Ki@fda.hhs.gov.*


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® 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. 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.
                    ( print page 6421) Table 1—Carbon Dioxide Gas Controlled Tissue Expander Risks and Mitigation Measures
Identified risks
Mitigation measuresPain
Labeling; and• From overexpansion with carbon dioxide
Software verification, validation and hazard analysis.Tissue damage
In-vivo performance testing; Labeling; and• From overexpansion with carbon dioxide
Software verification, validation and hazard analysis.Prolonged treatment time
In-vivo performance testing;• Due to under expansion because of carbon dioxide permeation
Non-clinical performance testing; Labeling; and• Due to overexpansion with carbon dioxide
Software verification, 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 dioxideUnder expansion, overexpansion, or no expansion
Electromagnetic compatibility, electrical safety, and wireless compatibility testing; Labeling;• Due to interference with other devices
Software verification, 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
 1.The authority citation for part 878 continues to read as follows: Authority:
                        21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371. 2.Add § 878.3510 to subpart D to read as follows: § 878.3510
  (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.
                            ( print 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.


# Footnotes

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. Back to Citation


[FR Doc. 2022-02357 Filed 2-3-22; 8:45 am] BILLING CODE 4164-01-P