Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Rules and Regulations 6417 

(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 

parts 801 and 809 regarding labeling, 

have been approved under OMB control 

number 0910–0485. 

List of Subjects in 21 CFR Part 866 

Biologics, Laboratories, 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 866 is 

amended as follows: 

PART 866—IMMUNOLOGY AND 

MICROBIOLOGY DEVICES 

■ 1. The authority citation for part 866 

continues to read as follows: 

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

360j, 360l, 371. 

■ 2. Add § 866.1655 to subpart B to read 

as follows: 

§ 866.1655 System for detection of 

microorganisms and antimicrobial 

resistance using reporter expression. 

(a) Identification. A system for 

detection of microorganisms and 

antimicrobial resistance using reporter 

expression is an in vitro diagnostic 

device intended for the detection and 

identification of live microorganisms 

and the detection of associated 

antimicrobial drug susceptibility or 

resistance in specimens from patients at 

risk of colonization or suspected of 

infection. 

(b) Classification. Class II (special 

controls). The special controls for this 

device are: 

(1) The intended use for the device in 

the labeling required under § 809.10 of 

this chapter must include a detailed 

description of the targets the device 

detects, the type of results provided to 

the user, the clinical indications 

appropriate for test use, and the specific 

population(s) for which the device is 

intended. 

(2) Any device used for specimen 

collection and transport must be FDAcleared, approved, or -classified as 

510(k) exempt (standalone or as part of 

a test system) for the collection of the 

specimen types claimed by this device 

and for the maintenance of viability of 

the targeted microorganisms; 

alternatively, the specimen collection 

device must be cleared in a premarket 

submission as a part of this device. 

(3) The labeling required under 

§ 809.10(b) of this chapter must include: 

(i) A detailed description of the 

device, including reagents, instruments, 

ancillary materials, applicable specimen 

collection and transport device(s) and 

control elements, and a detailed 

explanation of the methodology, 

including all pre-analytical methods for 

handling and processing of specimens 

and controls to maintain organism 

viability; 

(ii) Detailed descriptions of the test 

procedure, including the preparation 

and maintenance of quality controls and 

the interpretation of test results; 

(iii) Detailed discussion of the 

performance characteristics of the 

device for all claimed organisms and 

specimen types based on analytical 

studies, including evaluation of 

analytical sensitivity, inclusivity, crossreactivity, potentially interfering 

substances and microorganisms, 

contamination, specimen stability, 

precision, and reproducibility; 

(iv) Detailed discussion of the 

performance characteristics of the 

device observed in a clinical study 

performed on a population that is 

consistent with the intended use 

population in comparison to the results 

obtained by a reference or comparator 

method determined to be acceptable by 

FDA, for microbial detection, 

identification, and antimicrobial 

susceptibility testing; and 

(v) A limiting statement indicating 

that a negative test result does not 

preclude colonization or infection with 

organisms that do not express detectable 

levels of the reporter that is identified 

by the device. 

(4) Design verification and validation 

must include: 

(i) A detailed description of the 

device, including an explanation of the 

technology, hardware, software, and 

consumables, as well as an explanation 

of the result algorithms and method(s) 

of data processing from signal 

acquisition to result assignment; 

(ii) A detailed description of the 

impact of any software, including 

software applications and hardwarebased devices that incorporate software, 

on the device’s functions; 

(iii) Detailed documentation of the 

analytical and clinical studies required 

in paragraphs (b)(3)(iii) and (iv) of this 

section, including the study protocols 

containing descriptions of the test 

methods, prescribed methods of data 

analysis and acceptance criteria, final 

study reports, and data line listings; 

(iv) Detailed documentation of quality 

control procedures, including an 

explanation of how quality control 

materials were selected, the 

recommended frequency of testing, 

methods of control preparation, 

acceptance criteria for performance and 

the results from quality control testing 

performed during the analytical and 

clinical studies required under 

paragraphs (b)(3)(iii) and (iv) of this 

section; 

(v) Detailed documentation of studies 

performed to establish onboard and inuse reagent stability, including the test 

method(s), data analysis plans, 

acceptance criteria, final study reports, 

and data line listings; 

(vi) Detailed documentation of studies 

to establish reagent shelf-life for the 

assay kit and each applicable specimen 

collection and transport device, 

including study protocols containing 

descriptions of the test method(s), data 

analysis plans, and acceptance criteria; 

and 

(vii) Documentation of an appropriate 

end user device training program that 

will be offered as part of efforts to assure 

appropriate conduct of the assay and to 

mitigate the risk associated with false 

results, including failure to use the 

device correctly or correctly interpret 

results. 

Dated: January 25, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–02368 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 870 

[Docket No. FDA–2021–N–0913] 

Medical Devices; Cardiovascular 

Devices; Classification of the 

Photoplethysmograph Analysis 

Software for Over-the-Counter Use 

AGENCY: Food and Drug Administration, 

Department of Health and Human 

Services (HHS). 

ACTION: Final amendment; final order. 


lotter on DSK11XQN23PROD with RULES1
6418 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. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 

classifying the photoplethysmograph 

analysis software for over-the-counter 

use 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 

photoplethysmograph analysis software 

for over-the-counter use’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 September 11, 2018. 

FOR FURTHER INFORMATION CONTACT: 

Jennifer Kozen, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 2272, Silver Spring, 

MD 20993–0002, 301–796–5813, 

Jennifer.Shih@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Upon request, FDA has classified the 

photoplethysmograph analysis software 

for over-the-counter use 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 (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(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 August 9, 2018, FDA received 

Apple Inc.’s request for De Novo 

classification of the Irregular Rhythm 

Notification Feature. 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 September 11, 2018, 

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 870.2790.1 We have named the 

generic type of device 

photoplethysmograph analysis software 

for over-the-counter use, and it is 

identified as a device that analyzes 

photoplethysmograph data and provides 

information for identifying irregular 

heart rhythms. This device is not 

intended to provide a diagnosis. 

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 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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