Federal Register / Vol. 87, No. 49 / Monday, March 14, 2022 / Rules and Regulations 14171 

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. 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 862 

[Docket No. FDA–2021–N–0660] 

Medical Devices; Clinical Chemistry 

and Clinical Toxicology Devices; 

Classification of the Interoperable 

Automated Glycemic Controller 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final amendment; final order. 

SUMMARY: The Food and Drug 

Administration (FDA or we) is 

classifying the interoperable automated 

glycemic controller 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 interoperable 

automated glycemic controller’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 March 14, 

2022. The classification was applicable 

on December 13, 2019. 

FOR FURTHER INFORMATION CONTACT: 

Joshua Balsam, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 3530, Silver Spring, 

MD 20993–0002, 240–402–6521, 

Joshua.Balsam@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Upon request, FDA has classified the 

interoperable automated glycemic 

controller 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 (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 

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 

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 21 U.S.C. 360c(f)(2)(B)(i)). 

As a result, other device sponsors do not 

have to submit a De Novo request or 

premarket approval application in order 

to market a substantially equivalent 

device (see 21 U.S.C. 360c(i), defining 

‘‘substantial equivalence’’). Instead, 

sponsors can use the less-burdensome 

510(k) process, when necessary, to 

market their device. 

II. De Novo Classification 

On July 15, 2019, FDA received 

Tandem Diabetes Care, Inc.’s request for 

De Novo classification of the Control-IQ 

Technology. 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 December 13, 2019, 

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 862.1356.1 We have named the 

generic type of device interoperable 

automated glycemic controller, and it is 

identified as a device intended to 

automatically calculate drug doses 

based on inputs such as glucose and 

other relevant physiological parameters, 

and to command the delivery of such 

drug doses from a connected infusion 

pump. Interoperable automated 

glycemic controllers are designed to 

reliably and securely communicate with 

digitally connected devices to allow 

drug delivery commands to be sent, 

received, executed, and confirmed. 

Interoperable automated glycemic 

controllers are intended to be used in 


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14172 Federal Register / Vol. 87, No. 49 / Monday, March 14, 2022 / Rules and Regulations 

conjunction with digitally connected 

devices for the purpose of maintaining 

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—INTEROPERABLE AUTOMATED GLYCEMIC CONTROLLER RISKS AND MITIGATION MEASURES

Identified risks Mitigation measures 

Patient harm due to inappropriate drug delivery ...................................... Clinical data demonstrating device performance, Certain software validation testing, User training plan, and Certain drug compatibility information in labeling. 

Risk due to poorer or different performance in pediatric populations ..... Clinical data demonstrating device performance in pediatric population; 

and Certain contraindications, warning statements, and precautions 

in labeling. 

Risk due to the inability of the controller to handle different pharmacokinetic/pharmacodynamic characteristics of the drugs.Clinical data demonstrating device performance, Drug compatibility information in labeling, User training plan, and Human factors testing. 

Risk due to lack of compatibility of connected devices ........................... Certain validation of communication specifications, processes, and procedures with digitally connected devices; and Limitations on interoperable devices. 

Risk of connected devices having inadequate performance to allow 

safe use of the controller.

Specifications for performance of connected devices; Certain validation 

of communication specifications, processes, and procedures with 

digitally connected devices; and Limitations on interoperable devices. 

Failure to report device malfunctions or adverse events to the device 

manufacturer.

Plans and procedures for assigning postmarket responsibilities. 

Risk of latent flaws in software ................................................................ Robust software validation testing; Certain validation of communication 

specifications, processes, and procedures with digitally connected 

devices; and Certain verification and validation of risk control measures. 

Failure to provide appropriate treatment due to loss of communication 

with connected devices.

Certain verification and validation of risk control measures; and Certain 

validation of communication specifications, processes, and procedures with digitally connected devices. 

Risk due to insecure transmission of data ............................................... Certain validation of communication specifications, processes, and procedures with digitally connected devices. 

Failure to correctly operate the device ..................................................... Human factors testing, User training plan, Compatible devices listed in 

labeling, and Certain warning statements and precautions in labeling. 

Failure to correctly determine the root cause of device malfunctions ..... Certain verification and validation of logging capability. 

Risk due to data transmission interference/electromagnetic disturbance Certain verification and validation of electrical safety, electromagnetic 

compatibility, and radio frequency wireless 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). 

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 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 § 862.1356 to subpart B to read 

as follows: 

§ 862.1356 Interoperable automated 

glycemic controller. 

(a) Identification. An interoperable 

automated glycemic controller is a 

device intended to automatically 

calculate drug doses based on inputs 

such as glucose and other relevant 

physiological parameters, and to 

command the delivery of such drug 

doses from a connected infusion pump. 

Interoperable automated glycemic 

controllers are designed to reliably and 

securely communicate with digitally 

connected devices to allow drug 

delivery commands to be sent, received, 

executed, and confirmed. Interoperable 

automated glycemic controllers are 


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Federal Register / Vol. 87, No. 49 / Monday, March 14, 2022 / Rules and Regulations 14173 

intended to be used in conjunction with 

digitally connected devices for the 

purpose of maintaining glycemic 

control. 

(b) Classification. Class II (special 

controls). The special controls for this 

device are: 

(1) Design verification and validation 

must include: 

(i) An appropriate, as determined by 

FDA, clinical implementation strategy, 

including data demonstrating 

appropriate, as determined by FDA, 

clinical performance of the device for its 

intended use, including all of its 

indications for use. 

(A) The clinical data must be 

representative of the performance of the 

device in the intended use population 

and in clinically relevant use scenarios 

and sufficient to demonstrate 

appropriate, as determined by FDA, 

clinical performance of the device for its 

intended use, including all of its 

indications for use. 

(B) For devices indicated for use with 

multiple therapeutic agents for the same 

therapeutic effect (e.g., more than one 

type of insulin), data demonstrating 

performance with each product or, 

alternatively, an appropriate, as 

determined by FDA, clinical 

justification for why such data are not 

needed. 

(C) When determined to be necessary 

by FDA, the strategy must include 

postmarket data collection to confirm 

safe real-world use and monitor for rare 

adverse events. 

(ii) Results obtained through a human 

factors study that demonstrates that an 

intended user can safely use the device 

for its intended use. 

(iii) A detailed and appropriate, as 

determined by FDA, strategy to ensure 

secure and reliable means of data 

transmission with other intended 

connected devices. 

(iv) Specifications that are 

appropriate, as determined by FDA, for 

connected devices that shall be eligible 

to provide input to (e.g., specification of 

glucose sensor performance) or accept 

commands from (e.g., specifications for 

drug infusion pump performance) the 

controller, and a detailed strategy for 

ensuring that connected devices meet 

these specifications. 

(v) Specifications for devices 

responsible for hosting the controller, 

and a detailed and appropriate, as 

determined by FDA, strategy for 

ensuring that the specifications are met 

by the hosting devices. 

(vi) Documentation demonstrating 

that appropriate, as determined by FDA, 

measures are in place (e.g., validated 

device design features) to ensure that 

safe therapy is maintained when 

communication with digitally 

connected devices is interrupted, lost, 

or re-established after an interruption. 

Validation testing results must 

demonstrate that critical events that 

occur during a loss of communications 

(e.g., commands, device malfunctions, 

occlusions, etc.) are handled and logged 

appropriately during and after the 

interruption to maintain patient safety. 

(vii) A detailed plan and procedure 

for assigning postmarket responsibilities 

including adverse event reporting, 

complaint handling, and investigations 

with the manufacturers of devices that 

are digitally connected to the controller. 

(2) Design verification and validation 

documentation must include 

appropriate design inputs and design 

outputs that are essential for the proper 

functioning of the device that have been 

documented and include the following: 

(i) Risk control measures to address 

device system hazards; 

(ii) Design decisions related to how 

the risk control measures impact 

essential performance; and 

(iii) A traceability analysis 

demonstrating that all hazards are 

adequately controlled and that all 

controls have been validated in the final 

device design. 

(3) The device shall include 

appropriate, as determined by FDA, and 

validated interface specifications for 

digitally connected devices. These 

interface specifications shall, at a 

minimum, provide for the following: 

(i) Secure authentication (pairing) to 

connected devices; 

(ii) Secure, accurate, and reliable 

means of data transmission between the 

controller and connected devices; 

(iii) Sharing of necessary state 

information between the controller and 

any connected devices (e.g., battery 

level, reservoir level, sensor use life, 

pump status, error conditions); 

(iv) Ensuring that the controller 

continues to operate safely when data is 

received in a manner outside the 

bounds of the parameters specified; 

(v) A detailed process and procedures 

for sharing the controller’s interface 

specification with connected devices 

and for validating the correct 

implementation of that protocol; and 

(vi) A mechanism for updating the 

controller software, including any 

software that is required for operation of 

the controller in a manner that ensures 

its safety and performance. 

(4) The device design must ensure 

that a record of critical events is stored 

and accessible for an adequate period to 

allow for auditing of communications 

between digitally connected devices, 

and to facilitate the sharing of pertinent 

information with the responsible parties 

for those connected devices. Critical 

events to be stored by the controller 

must, at a minimum, include: 

(i) Commands issued by the 

controller, and associated confirmations 

the controller receives from digitally 

connected devices; 

(ii) Malfunctions of the controller and 

malfunctions reported to the controller 

by digitally connected devices (e.g., 

infusion pump occlusion, glucose 

sensor shut down); 

(iii) Alarms and alerts and associated 

acknowledgements from the controller 

as well as those reported to the 

controller by digitally connected 

devices; and 

(iv) Connectivity events (e.g., 

establishment or loss of 

communications). 

(5) The device must only receive 

glucose input from devices cleared 

under § 862.1355 (integrated continuous 

glucose monitoring system), unless FDA 

determines an alternate type of glucose 

input device is designed appropriately 

to allow the controller to meet the 

special controls contained within this 

section. 

(6) The device must only command 

drug delivery from devices cleared 

under § 880.5730 of this chapter 

(alternate controller enabled infusion 

pump), unless FDA determines an 

alternate type of drug infusion pump 

device is designed appropriately to 

allow the controller to meet the special 

controls contained within this section. 

(7) An appropriate, as determined by 

FDA, training plan must be established 

for users and healthcare providers to 

assure the safety and performance of the 

device when used. This may include, 

but not be limited to, training on device 

contraindications, situations in which 

the device should not be used, notable 

differences in device functionality or 

features compared to similar alternative 

therapies, and information to help 

prescribers identify suitable candidate 

patients, as applicable. 

(8) The labeling required under 

§ 809.10(b) of this chapter must include: 

(i) A contraindication for use in 

pediatric populations except to the 

extent clinical performance data or 

other available information 

demonstrates that it can be safely used 

in pediatric populations in whole or in 

part. 

(ii) A prominent statement identifying 

any populations for which use of this 

device has been determined to be 

unsafe. 

(iii) A prominent statement 

identifying by name the therapeutic 

agents that are compatible with the 

controller, including their identity and 

concentration, as appropriate. 


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14174 Federal Register / Vol. 87, No. 49 / Monday, March 14, 2022 / Rules and Regulations 

(iv) The identity of those digitally 

connected devices with which the 

controller can be used, including 

descriptions of the specific system 

configurations that can be used, per the 

detailed strategy submitted under 

paragraph (b)(1)(iii) of this section. 

(v) A comprehensive description of 

representative clinical performance in 

the hands of the intended user, 

including information specific to use in 

the pediatric use population, as 

appropriate. 

(vi) A comprehensive description of 

safety of the device, including, for 

example, the incidence of severe 

hypoglycemia, diabetic ketoacidosis, 

and other relevant adverse events 

observed in a study conducted to satisfy 

paragraph (b)(1)(i) of this section. 

(vii) For wireless connection enabled 

devices, a description of the wireless 

quality of service required for proper 

use of the device. 

(viii) For any controller with 

hardware components intended for 

multiple patient reuse, instructions for 

safely reprocessing the hardware 

components between uses. 

Dated: March 8, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–05303 Filed 3–11–22; 8:45 am] 

BILLING CODE 4164–01–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 312 

[EPA–HQ–OLEM–2021–0946 FRL–9334–02– 

OLEM] 

Standards and Practices for All 

Appropriate Inquiries 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Direct final rule. 

SUMMARY: EPA is taking direct final 

action to amend the Standards and 

Practices for All Appropriate Inquiries 

to reference a standard practice recently 

made available by ASTM International, 

a widely recognized standards 

developing organization. Specifically, 

this direct final rule amends the All 

Appropriate Inquiries Rule to reference 

ASTM International’s E1527–21 

‘‘Standard Practice for Environmental 

Site Assessments: Phase I 

Environmental Site Assessment 

Process’’ and allow for its use to satisfy 

the requirements for conducting all 

appropriate inquiries under the 

Comprehensive Environmental 

Response, Compensation and Liability 

Act. 

DATES: This rule is effective on May 13, 

2022, without further notice, unless 

EPA receives adverse comment by April 

13, 2022. If EPA receives such comment, 

we will publish a timely withdrawal in 

the Federal Register informing the 

public that this rule will not take effect. 

ADDRESSES: Submit your comments, 

identified by Docket ID No. [EPA–HQ– 

OLEM–2021–0946] at https://

www.regulations.gov. Follow the on-line 

instructions for submitting comments. 

Once submitted, comments cannot be 

edited or removed from regulations.gov. 

The EPA may publish any comment 

received to its public docket. Do not 

submit electronically any information 

you consider to be Confidential 

Business Information (CBI) or other 

information whose disclosure is 

restricted by statute. Multimedia 

submissions (audio, video, etc.) must be 

accompanied by a written comment. 

The written comment is considered the 

official comment and should include 

discussion of all points you wish to 

make. The EPA will generally not 

consider comments or comment 

contents located outside of the primary 

submission (i.e., on the web, cloud, or 

other file sharing system). For 

additional submission methods, the full 

EPA public comment policy, 

information about CBI and multimedia 

submissions, and general guidance on 

making effective comments, please visit 

https://www2.epa.gov/dockets/ 

commenting-epa-dockets. 

FOR FURTHER INFORMATION CONTACT: For 

more detailed information on specific 

aspects of this rule, contact Patricia 

Overmeyer, Office of Brownfields and 

Land Revitalization (5105T), U.S. 

Environmental Protection Agency, 1200 

Pennsylvania Avenue NW, Washington, 

DC 20460–0002, 202–566–2774, or 

Overmeyer.patricia@epa.gov. 

SUPPLEMENTARY INFORMATION: 

Throughout this document, ‘‘we,’’ ‘‘us,’’ 

and ‘‘our’’ refer to the EPA. 

Table of Contents 

I. Why is the EPA using a direct final rule 

II. Does this action apply to me? 

III. What should I consider as I prepare my 

comments for the EPA? 

IV. Statutory Authority 

V. Background 

VI. What action is the EPA taking? 

VII. Statutory and Executive Order Reviews 

I. Why is the EPA using a direct final 

rule? 

EPA is publishing this direct final 

rule without prior proposal because the 

Agency views this as a noncontroversial 

action and anticipates no adverse 

comment given that this action will 

provide flexibility for grant recipients 

and other entities that may benefit from 

the use of the ASTM E1527–21 

standard. We believe that this action is 

reasonable and can be promulgated 

without consideration of public 

comment because it allows for the use 

of a generally accepted business 

standard developed by a recognized 

standards developing organization. The 

standard was reviewed by EPA and 

determined to be equivalent to the 

Agency’s all appropriate inquiries 

requirements. This action does not 

disallow the use of the previously 

recognized standards (ASTM E1527–13 

or ASTM E2247–16), and it does not 

alter the requirements of the previously 

promulgated All Appropriate Inquiries 

Rule. In addition, this action will 

potentially increase flexibility for some 

parties who may make use of the new 

standard, without placing any 

additional burden on those parties who 

prefer to use either the ASTM E1527–13 

standard, the ASTM E2247–16 standard, 

or follow the requirements of the All 

Appropriate Inquiries Rule when 

conducting all appropriate inquiries. 

Although we view this action as 

noncontroversial, in the ‘‘Proposed 

Rules’’ section in this issue of the 

Federal Register, we are publishing a 

separate proposed rule containing the 

clarification summarized above. That 

proposed rule will serve as the proposal 

to be revised if adverse comments are 

received. If EPA does not receive 

adverse comment in response to this 

direct final rule prior to April 13, 2022, 

this rule will become effective on May 

13, 2022, without further notice. If EPA 

receives adverse comment, we will 

publish a timely withdrawal of this 

direct final rule in the Federal Register, 

informing the public that the rule will 

not take effect. We will address all 

public comments in a subsequent final 

rule. We will not institute a second 

comment period on this action. Any 

parties interested in commenting must 

do so at this time and before April 13, 

2022. 

II. Does this action apply to me? 

This action offers certain parties the 

option of using an available industry 

standard to conduct all appropriate 

inquiries. Parties purchasing potentially 

contaminated properties may use the 

ASTM E1527–21 standard practice to 

comply with the all appropriate 

inquiries requirements of the 

Comprehensive Environmental 

Response, Compensation, and Liability 

Act (CERCLA). This rule does not 

require any entity to use this standard. 

Any party who wants to claim 

protection from liability under one of 

CERCLA’s landowner liability 


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