This section of the FEDERAL REGISTER

contains regulatory documents having general

applicability and legal effect, most of which

are keyed to and codified in the Code of

Federal Regulations, which is published under

50 titles pursuant to 44 U.S.C. 1510.

The Code of Federal Regulations is sold by

the Superintendent of Documents.

Rules and Regulations Federal Register

9237 

Vol. 87, No. 34 

Friday, February 18, 2022 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 862 

[Docket No. FDA–2021–N–1343] 

Medical Devices; Clinical Chemistry 

and Clinical Toxicology Devices; 

Classification of the Integrated 

Continuous Glucose Monitoring 

System 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final amendment; final order. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 

classifying the integrated continuous 

glucose monitoring system 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 

integrated continuous glucose 

monitoring system’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 

18, 2022. The classification was 

applicable on March 27, 2018. 

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 

integrated continuous glucose 

monitoring system 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 (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 December 8, 2017, FDA received 

Dexcom, Inc.’s request for De Novo 

classification of the Dexcom G6 

Continuous Glucose Monitoring 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 


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9238 Federal Register / Vol. 87, No. 34 / Friday, February 18, 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. 

assurance of the safety and effectiveness 

of the device. 

Therefore, on March 27, 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 862.1355.1 We have named the 

generic type of device ‘‘integrated 

continuous glucose monitoring system 

(iCGM),’’ and it is intended to 

automatically measure glucose in bodily 

fluids continuously or frequently for a 

specified period of time. iCGM systems 

are designed to reliably and securely 

transmit glucose measurement data to 

digitally connected devices, including 

automated insulin dosing systems, and 

are intended to be used alone or in 

conjunction with these digitally 

connected medical devices for the 

purpose of managing a disease or 

condition related to glycemic control. 

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—INTEGRATED CONTINUOUS GLUCOSE MONITORING SYSTEM RISKS AND MITIGATION MEASURES

Identified risks Mitigation measures 

Clinical action based on falsely high or falsely low inaccurate glucose 

values or inaccurate alerts may lead to inappropriate treatment decisions.

General Controls and special controls (1) (21 CFR 862.1355(b)(1)), (2) 

(21 CFR 862.1355(b)(2)), (3) (21 CFR 862.1355(b)(3)), (4) (21 CFR 

862.1355(b)(4)), (5) (21 CFR 862.1355(b)(5)), (6) (21 CFR 

862.1355(b)(6)), and (7) (21 CFR 862.1355(b)(7)). 

Clinical action in pediatric patients based on falsely high or falsely low 

inaccurate values or inaccurate alerts due to poorer or different performance in pediatric populations.

General Controls and special controls (1) (21 CFR 862.1355(b)(1)), (2) 

(21 CFR 862.1355(b)(2)), (3) (21 CFR 862.1355(b)(3)), (4) (21 CFR 

862.1355(b)(4)), (5) (21 CFR 862.1355(b)(5)), (6) (21 CFR 

862.1355(b)(6)), and (7) (21 CFR 862.1355(b)(7)). 

The inability to make appropriate treatment decisions when glucose 

values are unavailable due to sensor signal dropout or loss of communication with digitally connected devices.

General Controls and special controls (1)(vii) (21 CFR 

862.1355(b)(1)(vii)), (2) (21 CFR 862.1355(b)(2)), (3) (21 CFR 

862.1355(b)(3)), (6) (21 CFR 862.1355(b)(6)), and (7) (21 CFR 

862.1355(b)(7)). 

Patient harm due to insecure transmission of data ................................. General Controls and special control (2) (21 CFR 862.1355(b)(2)). 

Use of an iCGM as part of another digitally connected medical device 

system, such as an automated insulin dosing (AID) system, when the 

iCGM has inadequate analytical or clinical performance to support 

the intended use of the digitally connected device.

General Controls and special controls (2) (21 CFR 862.1355(b)(2)), (6) 

(21 CFR 862.1355(b)(6)), and (7) (21 CFR 862.1355(b)(7)). 

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. 

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 systems 

regulations, 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 862 

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 862 is 

amended as follows: 

PART 862—CLINICAL CHEMISTRY 

AND CLINICAL TOXICOLOGY 

DEVICES 

■ 1. The authority citation for part 862 

continues to read as follows: 

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

360j, 360l, 371. 

■ 2. Add § 862.1355 to subpart B to read 

as follows: 

§ 862.1355 Integrated continuous glucose 

monitoring system. 

(a) Identification. An integrated 

continuous glucose monitoring system 

(iCGM) is intended to automatically 

measure glucose in bodily fluids 

continuously or frequently for a 

specified period of time. iCGM systems 

are designed to reliably and securely 

transmit glucose measurement data to 

digitally connected devices, including 

automated insulin dosing systems, and 

are intended to be used alone or in 

conjunction with these digitally 

connected medical devices for the 

purpose of managing a disease or 

condition related to glycemic control. 


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Federal Register / Vol. 87, No. 34 / Friday, February 18, 2022 / Rules and Regulations 9239 

(b) Classification. Class II (special 

controls). The special controls for this 

device are: 

(1) Design verification and validation 

must include the following: 

(i) Robust clinical data demonstrating 

the accuracy of the device in the 

intended use population. 

(ii) The clinical data must include a 

comparison between iCGM values and 

blood glucose values in specimens 

collected in parallel that are measured 

on an FDA-accepted laboratory-based 

glucose measurement method that is 

precise and accurate, and that is 

traceable to a higher order (e.g., an 

internationally recognized reference 

material and/or method). 

(iii) The clinical data must be 

obtained from a clinical study designed 

to fully represent the performance of the 

device throughout the intended use 

population and throughout the 

measuring range of the device. 

(iv) Clinical study results must 

demonstrate consistent analytical and 

clinical performance throughout the 

sensor wear period. 

(v) Clinical study results in the adult 

population must meet the following 

performance requirements: 

(A) For all iCGM measurements less 

than 70 milligrams/deciliter (mg/dL), 

the percentage of iCGM measurements 

within ±15 mg/dL of the corresponding 

blood glucose value must be calculated, 

and the lower one-sided 95 percent 

confidence bound must exceed 85 

percent. 

(B) For all iCGM measurements from 

70 mg/dL to 180 mg/dL, the percentage 

of iCGM measurements within ±15 

percent of the corresponding blood 

glucose value must be calculated, and 

the lower one-sided 95 percent 

confidence bound must exceed 70 

percent. 

(C) For all iCGM measurements 

greater than 180 mg/dL, the percentage 

of iCGM measurements within ±15 

percent of the corresponding blood 

glucose value must be calculated, and 

the lower one-sided 95 percent 

confidence bound must exceed 80 

percent. 

(D) For all iCGM measurements less 

than 70 mg/dL, the percentage of iCGM 

measurements within ±40 mg/dL of the 

corresponding blood glucose value must 

be calculated, and the lower one-sided 

95 percent confidence bound must 

exceed 98 percent. 

(E) For all iCGM measurements from 

70 mg/dL to 180 mg/dL, the percentage 

of iCGM measurements within ±40 

percent of the corresponding blood 

glucose value must be calculated, and 

the lower one-sided 95 percent 

confidence bound must exceed 99 

percent. 

(F) For all iCGM measurements 

greater than180 mg/dL, the percentage 

of iCGM measurements within ±40 

percent of the corresponding blood 

glucose value must be calculated, and 

the lower one-sided 95 percent 

confidence bound must exceed 99 

percent. 

(G) Throughout the device measuring 

range, the percentage of iCGM 

measurements within ±20 percent of the 

corresponding blood glucose value must 

be calculated, and the lower one-sided 

95 percent confidence bound must 

exceed 87 percent. 

(H) When iCGM values are less than 

70 mg/dL, no corresponding blood 

glucose value shall read above 180 mg/ 

dL. 

(I) When iCGM values are greater than 

180 mg/dL, no corresponding blood 

glucose value shall read less than 70 

mg/dL. 

(J) There shall be no more than 1 

percent of iCGM measurements that 

indicate a positive glucose rate of 

change greater than 1 mg/dL per minute 

(/min) when the corresponding true 

negative glucose rate of change is less 

than ¥2 mg/dL/min as determined by 

the corresponding blood glucose 

measurements. 

(K) There shall be no more than 1 

percent of iCGM measurements that 

indicate a negative glucose rate of 

change less than ¥1 mg/dL/min when 

the corresponding true positive glucose 

rate of change is greater than 2 mg/dL/ 

min as determined by the corresponding 

blood glucose measurements. 

(vi) Data demonstrating similar 

accuracy and rate of change 

performance of the iCGM in the 

pediatric population as compared to 

that in the adult population, or 

alternatively a clinical and/or technical 

justification for why pediatric data are 

not needed, must be provided and 

determined by FDA to be acceptable and 

appropriate. 

(vii) Data must demonstrate that 

throughout the claimed sensor life, the 

device does not allow clinically 

significant gaps in sensor data 

availability that would prevent any 

digitally connected devices from 

achieving their intended use. 

(2) Design verification and validation 

must include a detailed strategy to 

ensure secure and reliable means of 

iCGM data transmission to provide realtime glucose readings at clinically 

meaningful time intervals to devices 

intended to receive the iCGM glucose 

data. 

(3) Design verification and validation 

must include adequate controls 

established during manufacturing and at 

product release to ensure the released 

product meets the performance 

specifications as defined in paragraphs 

(b)(1) and (b)(2) of this section. 

(4) The device must demonstrate 

clinically acceptable performance in the 

presence of clinically relevant levels of 

potential interfering substances that are 

reasonably present in the intended use 

population, including but not limited to 

endogenous substances and metabolites, 

foods, dietary supplements, and 

medications. 

(5) The device must include 

appropriate measures to ensure that 

disposable sensors cannot be used 

beyond its claimed sensor wear period. 

(6) Design verification and validation 

must include results obtained through a 

usability study that demonstrates that 

the intended user can use the device 

safely and obtain the expected glucose 

measurement accuracy. 

(7) The labeling required under 

§ 809.10(b) of this chapter must include 

a separate description of the following 

sensor performance data observed in the 

clinical study performed in 

conformance with paragraph (b)(1) of 

this section for each intended use 

population, in addition to separate 

sensor performance data for each 

different iCGM insertion or use sites 

(e.g., abdomen, arm, buttock): 

(i) A description of the accuracy in 

the following blood glucose 

concentration ranges: less than 54 mg/ 

dL, 54 mg/dL to less than 70 mg/dL, 70 

to 180 mg/dL, greater than 180 to 250 

mg/dL, and greater than 250 mg/dL. 

(ii) A description of the accuracy of 

positive and negative rate of change 

data. 

(iii) A description of the frequency 

and duration of gaps in sensor data. 

(iv) A description of the true, false, 

missed, and correct alert rates and a 

description of the available glucose 

concentration alert settings, if 

applicable. 

(v) A description of the observed 

duration of iCGM life for the device. 

Dated: February 11, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–03504 Filed 2–17–22; 8:45 am] 

BILLING CODE 4164–01–P 


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