Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Rules and Regulations 6419 

TABLE 1—PHOTOPLETHYSMOGRAPH ANALYSIS SOFTWARE FOR OVER-THE-COUNTER USE RISKS AND MITIGATION

MEASURES

Identified risks Mitigation measures 

Poor quality incoming photoplethysmograph (PPG) signal resulting in 

failure to detect irregular heart rhythms.

Clinical performance testing, Human factors testing, and Labeling. 

Misinterpretation and/or over-reliance on device output, leading to: Human factors testing, and Labeling. 

• Failure to seek treatment despite acute symptoms (e.g., fluttering sensation in the chest, lightheadedness, and irregular 

pulse).

• Discontinuing or modifying treatment for chronic heart condition.

False negative resulting in failure to detect irregular heart rhythms and 

delay of further evaluation or treatment.

Clinical performance testing; Software verification, validation, and hazard analysis; Non-clinical performance testing; and Labeling. 

False positive resulting in additional unnecessary medical procedures .. Clinical performance testing; Software verification, validation, and hazard analysis; Non-clinical performance testing; and Labeling. 

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 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 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 

■ 1. The authority citation for part 870 

continues to read as follows: 

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

360j, 360l, 371. 

■ 2. Add § 870.2790 to subpart C to read 

as follows: 

§ 870.2790 Photoplethysmograph analysis 

software for over-the-counter use. 

(a) Identification. A 

photoplethysmograph analysis software 

device for over-the-counter use analyzes 

photoplethysmograph data and provides 

information for identifying irregular 

heart rhythms. This device is not 

intended to provide a diagnosis. 

(b) Classification. Class II (special 

controls). The special controls for this 

device are: 

(1) Clinical performance testing must 

demonstrate the performance 

characteristics of the detection 

algorithm under anticipated conditions 

of use. 

(2) Software verification, validation, 

and hazard analysis must be performed. 

Documentation must include a 

characterization of the technical 

specifications of the software, including 

the detection algorithm and its inputs 

and outputs. 

(3) Non-clinical performance testing 

must demonstrate the ability of the 

device to detect adequate 

photoplethysmograph signal quality. 

(4) Human factors and usability 

testing must demonstrate the following: 

(i) The user can correctly use the 

device based solely on reading the 

device labeling; and 

(ii) The user can correctly interpret 

the device output and understand when 

to seek medical care. 

(5) Labeling must include: 

(i) Hardware platform and operating 

system requirements; 

(ii) Situations in which the device 

may not operate at an expected 

performance level; 

(iii) A summary of the clinical 

performance testing conducted with the 

device; 

(iv) A description of what the device 

measures and outputs to the user; and 

(v) Guidance on interpretation of any 

results. 

Dated: January 26, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–02358 Filed 2–3–22; 8:45 am] 

BILLING CODE 4164–01–P 

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. 

SUMMARY: The Food and Drug 

Administration (FDA or we) is 

classifying the carbon dioxide gas 


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6420 Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Rules and Regulations 

1FDA 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. 

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 lessburdensome 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. 


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Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Rules and Regulations 6421 

TABLE 1—CARBON DIOXIDE GAS CONTROLLED TISSUE EXPANDER RISKS AND MITIGATION MEASURES

Identified risks Mitigation measures 

Pain ........................................................................................................... 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 dioxide 

Under 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 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 patientcontacting 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. 


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6422 Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Rules and Regulations 

(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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 880 

[Docket No. FDA–2021–N–0998] 

Medical Devices; General Hospital and 

Personal Use Devices; Classification 

of the Alternate Controller Enabled 

Infusion Pump 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final amendment; final order. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 

classifying the alternate controller 

enabled infusion pump 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 alternate 

controller enabled infusion pump’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:

Effective date: This order is effective 

February 4, 2022. 

Applicability date: The classification 

was applicable on February 14, 2019. 

FOR FURTHER INFORMATION CONTACT: 

Ryan Lubert, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 3574, Silver Spring, 

MD 20993–0002, 240–402–6357, 

Ryan.Lubert@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Upon request, FDA has classified the 

alternate controller enabled infusion 

pump 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 (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. 

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(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 lessburdensome 510(k) process, when 

necessary, to market their device. 

II. De Novo Classification 

On October 29, 2018, FDA received 

Tandem Diabetes Care, Inc.’s request for 

De Novo classification of the t:slim X2 


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