[Federal Register Volume 87, Number 34 (Friday, February 18, 2022)]
[Rules and Regulations]
[Pages 9237-9239]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-03504]



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

[[Page 9237]]



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.

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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, 
[email protected].

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

[[Page 9238]]

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.
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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.
---------------------------------------------------------------------------

    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    General Controls and special
 or falsely low inaccurate glucose        controls (1) (21 CFR
 values or inaccurate alerts may lead     862.1355(b)(1)), (2) (21 CFR
 to inappropriate treatment decisions.    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    General Controls and special
 based on falsely high or falsely low     controls (1) (21 CFR
 inaccurate values or inaccurate alerts   862.1355(b)(1)), (2) (21 CFR
 due to poorer or different performance   862.1355(b)(2)), (3) (21 CFR
 in pediatric populations.                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        General Controls and special
 treatment decisions when glucose         controls (1)(vii) (21 CFR
 values are unavailable due to sensor     862.1355(b)(1)(vii)), (2) (21
 signal dropout or loss of                CFR 862.1355(b)(2)), (3) (21
 communication with digitally connected   CFR 862.1355(b)(3)), (6) (21
 devices.                                 CFR 862.1355(b)(6)), and (7)
                                          (21 CFR 862.1355(b)(7)).
Patient harm due to insecure             General Controls and special
 transmission of data.                    control (2) (21 CFR
                                          862.1355(b)(2)).
Use of an iCGM as part of another        General Controls and special
 digitally connected medical device       controls (2) (21 CFR
 system, such as an automated insulin     862.1355(b)(2)), (6) (21 CFR
 dosing (AID) system, when the iCGM has   862.1355(b)(6)), and (7) (21
 inadequate analytical or clinical        CFR 862.1355(b)(7)).
 performance to support the intended
 use of the digitally connected device.
------------------------------------------------------------------------

    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

0
1. The authority citation for part 862 continues to read as follows:

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


0
2. Add Sec.  862.1355 to subpart B to read as follows:


Sec.  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.

[[Page 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 real-time 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 Sec.  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


