SmartAdjust technology

K203774 · Insulet Corporation · QJI · Jan 27, 2022 · Clinical Chemistry

Device Facts

• Record ID: K203774
• Device Name: SmartAdjust technology
• Applicant: Insulet Corporation
• Product Code: QJI · Clinical Chemistry
• Decision Date: Jan 27, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1356
• Device Class: Class 2
• Attributes: Software as a Medical Device, Therapeutic, Pediatric

Indications for Use

SmartAdjust technology is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, decrease, and pause delivery of insulin based on current and predicted glucose values. SmartAdjust technology is intended for the management of type 1 diabetes mellitus in persons 6 years of age and older. SmartAdjust technology is intended for single patient use and requires a prescription.

Device Story

Software-only medical device (iAGC) residing on Omnipod 5 ACE pump; integrates with iCGM via Bluetooth Low Energy. Inputs: real-time iCGM glucose data; user-defined parameters. Operation: algorithm calculates insulin delivery every 5 minutes; automatically increases, decreases, or suspends insulin based on predicted glucose trends vs. user-customizable target (110–150 mg/dL). Modes: Automated (closed-loop), Automated: Limited (basal-only during sensor loss/warm-up), and Activity (reduced insulin, 150 mg/dL target). Used in ambulatory settings by patients. Output: automated insulin delivery commands to ACE pump. Benefits: improved glycemic control (A1C, time-in-range) and reduced hyperglycemia risk. Healthcare providers use system data for therapy management.

Clinical Evidence

Prospective, multicenter, single-arm study (N=240; 112 children, 128 adolescents/adults). Compared 2-week standard therapy to 3-month Omnipod 5 use. Primary endpoints: A1C and time-in-range (70-180 mg/dL). Results: Significant improvements (p<0.0001) in A1C and time-in-range across all age groups. Safety endpoints: 3 severe hypoglycemia events (not system-related) and 1 DKA event (infusion site failure).

Technological Characteristics

Software-only iAGC; resides on Omnipod 5 ACE pump. Connectivity: Bluetooth Low Energy (BLE) for iCGM data. Interoperability: compatible with iCGM and ACE pumps. Software lifecycle: IEC 62304 compliant. Cybersecurity: penetration testing and software bill of materials provided. Firmware update mechanism: over-the-air.

Indications for Use

Indicated for management of type 1 diabetes mellitus in persons 6 years of age and older. Contraindicated in persons under 6 years old, those requiring <6 units of insulin/day, pregnant women, critically ill patients, patients on dialysis, and those taking hydroxyurea. Requires adequate hearing/vision for alarm recognition.

Regulatory Classification

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 intended to be used in conjunction with digitally connected devices for the purpose of maintaining glycemic control.

Special Controls

*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. (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.

Predicate Devices

• Control-IQ Technology (K200467)

Submission Summary (Full Text)

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FDA

U.S. FOOD &amp; DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

INSTRUMENT ONLY

## I Background Information:

A 510(k) Number

K203774

B Applicant

Insulet Corporation

C Proprietary and Established Names

SmartAdjust technology

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| QJI | Class II | 21 CFR 862.1356 - Interoperable Automated Glycemic Controller | CH - Clinical Chemistry |

## II Submission/Device Overview:

A Purpose for Submission:

New device

B Type of Test:

Not applicable

## III Intended Use/Indications for Use:

A Intended Use(s):

See Indications for Use below.

B Indication(s) for Use:

SmartAdjust technology is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase,

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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decrease, and pause delivery of insulin based on current and predicted glucose values. SmartAdjust technology is intended for the management of type 1 diabetes mellitus in persons 6 years of age and older. SmartAdjust technology is intended for single patient use and requires a prescription.

## C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

SmartAdjust technology should not be used in anyone under the age of 6 years old. SmartAdjust technology should also NOT be used in people who require less than 6 units of insulin per day as the safety of the technology has not been evaluated in this population.

Do not use SmartAdjust technology in pregnant women, critically ill patients, and those on dialysis. The safety of the SmartAdjust technology has not been evaluated in these populations.

Do not use SmartAdjust technology if you are taking hydroxyurea as it could lead to falsely elevated CGM values and result in over-delivery of insulin that can lead to severe hypoglycemia.

Do not use SmartAdjust technology if you do NOT have adequate hearing and/or vision to allow recognition of all functions of the Omnipod 5 System, including alerts, alarms, and reminders.

SmartAdjust technology used with the Omnipod 5 System is designed to use rapid-acting U-100 insulins. The following U-100 rapid-acting insulin analogs have been tested and found to be safe for use in the Pod: NovoLog® (insulin aspart), Humalog® (insulin lispro), and Admelog® (insulin lispro) for use up to 72 hours (3 days). Before using a different insulin with the Omnipod 5 System, check the insulin drug label and consult your healthcare provider. Refer to the insulin labeling and follow your healthcare provider's directions for how often to replace the Pod.

SmartAdjust technology used with the Omnipod 5 System relies on accurate, current CGM values to determine your insulin needs. Always make sure you are using the CGM per manufacturer's instructions and do not extend the sensor wear beyond the recommended duration.

Do NOT attempt to use the SmartAdjust technology with the Omnipod 5 System before you receive training. Inadequate training could put your health and safety at risk.

Device components used with the SmartAdjust technology including the pod, CGM transmitter, and CGM sensor must be removed before Magnetic Resonance Imaging (MRI), Computed Tomography (CT) scan, or diathermy treatment. In addition, the SmartAdjust Controller and smartphone should be placed outside of the precedence room. Exposure to MRI, CT, or diathermy treatment can damage the components.

At the time of device authorization, the compatible integrated continuous glucose monitor (iCGM) is the Dexcom G6 iCGM.

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## IV Device/System Characteristics:

### A Device Description:

SmartAdjust technology (the Omnipod 5 interoperable automated glycemic controller, or iAGC) is a software-only medical device intended for the management of type 1 diabetes mellitus. The Omnipod 5 iAGC uses data from a connected iCGM along with user-defined parameters to predict future glucose trends and automatically increase, decrease, or pause the delivery of insulin via a compatible alternate controller enabled (ACE) pump.

The SmartAdjust technology software is part of the Omnipod 5 Automated Insulin Delivery System, which also includes the Omnipod 5 ACE Pump (K203768), Omnipod 5 Bolus Calculator (K203772), and an integrated continuous glucose monitor (iCGM, Dexcom G6). The SmartAdjust technology is intended to be digitally connected to an iCGM and an ACE Pump.

The SmartAdjust technology software resides on the Omnipod 5 ACE Pump (the Omnipod 5 Pod and Omnipod 5 App). The iAGC software is responsible for controlling insulin delivery via compatible ACE Pump when the system is in Automated Mode. iCGM data is transmitted from the iCGM to the ACE Pump via Bluetooth Low Energy technology. The SmartAdjust technology uses this transmitted iCGM data in its calculations. The SmartAdjust technology can be turned off, and the Omnipod 5 ACE Pump will operate in Manual Mode, which delivers insulin based on healthcare provider (HCP) or user-defined basal programs.

The SmartAdjust technology has three states of operation: Automated Mode, Automated: Limited, and Activity. In Automated Mode, the system calculates insulin delivery every 5 minutes based on the user-customizable glucose target (110–150 mg/dL). Automated: Limited is enabled when the SmartAdjust technology is not receiving data from a connected iCGM for 20 minutes or more and during sensor warm-up. While in Automated: Limited, the user will receive no more than pre-programmed basal insulin. When a valid glucose value is received from the iCGM, the SmartAdjust technology will resume delivery of insulin in full Automated Mode. Activity is a temporary mode which the user may select for various time durations during automated mode up to 24 hours. With Activity, the algorithm reduces insulin delivery, by setting a temporary glucose target to 150 mg/dL. Activity is intended for use during periods when insulin sensitivity is expected to be higher, such as during exercise.

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# B Instrument Description Information:

1. Instrument Name: SmartAdjust technology
2. Specimen Identification: Not applicable
3. Specimen Sampling and Handling: Not applicable
4. Calibration: Not applicable
5. Quality Control: Not applicable

# V Substantial Equivalence Information:

A Predicate Device Name(s): Control-IQ Technology
B Predicate 510(k) Number(s): K200467
C Comparison with Predicate(s):

| Device & Predicate Device(s): | K203774 | K200467 |
| --- | --- | --- |
| Device Trade Name | SmartAdjust Technology | Control-IQ Technology |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | For use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, decrease, and pause delivery of insulin based on current and predicted glucose values. (It) is intended for the management of | Same |

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| | type 1 diabetes mellitus in persons 6 years of age and older. | |
| --- | --- | --- |
| Age Range of intended users | Ages 6 years and older | Same |
| Communication and Pairing | Bluetooth Low Energy (BLE) | Same |
| General Device Characteristic Differences | | |
| Specific Drug/Biologic Use | U-100 insulins: NovoLog, Humalog, and Admelog | U-100 Insulins: NovoLog and Humalog |
| Device Hosting Controller | OP5 Pod (ACE Pump) and Android OS device (locked down PDM or user’s compatible smart phone) | T:slim X2 insulin pump |
| Alarms/Alerts | • Out of Range Alert
• Low Alert
• Maximum Insulin/Delivery Alert | • Out of Range Alert
• Low Alert
• High Alert
• Maximum Insulin/Delivery Alert |
| Target Glucose Range | 110-150 mg/dL | 112.50-160 mg/dL |

VI Standards/Guidance Documents Referenced:

Special controls established under 21 CFR 862.1356.

ISO 14971:2007: Medical Devices - Application of Risk Management to Medical Devices FDA Recognition No: 5-40

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility: Not applicable.
2. Linearity: Not applicable.

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3. Analytical Specificity/Interference:
Not applicable.

4. Accuracy (Instrument):
Not applicable.

5. Carry-Over:
Not applicable.

## B Other Supportive Instrument Performance Characteristics Data:

For the evaluation of the system in the clinical studies, the SmartAdjust technology was installed on the Omnipod 5 ACE Pump (Pod) insulin pump with interoperable technology (K203768), which was paired with the Dexcom G6 integrated continuous glucose monitor (iCGM). Details on the performance characteristics of these devices can be found in the public decision summaries for each device.

## Summary of Clinical Testing:

Two clinical studies were conducted to evaluate the SmartAdjust technology in subjects 6-70 years of age with type 1 diabetes. The first study was the pre-pivotal study which was followed by the pivotal study.

## Pre-pivotal

| Study Feature | Description |
| --- | --- |
| Title | Pre-pivotal evaluation of the safety and effectiveness of the Omnipod Horizon Automated Glucose Control System in patients with type 1 diabetes |
| Study Design | Single-arm, multi-center, prospective clinical study |
| Number of Sites | Six (6) US clinical sites |
| Population | 18 subjects aged 6-13.9 years, and 18 subjects aged 14-70 years.
Key Inclusion Criteria
• Age 6-70 years old
• Type 1 diabetes for at least 6 months
• Hemoglobin A1c (HbA1c) <10% at screening
Key Exclusion Criteria
• Use of non-insulin anti-diabetic medication other than metformin |
| Protocol Overview/Synopsis | The study consisted of two phases:
1. 14 day outpatient standard therapy phase followed by;
2. 14 day hybrid closed-loop phase |

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| Study Feature | Description |
| --- | --- |
| | For the standard therapy (ST) phase, current Dexcom G6 iCGM users could provide data from a 14-day period within the last 30 days. For non-G6 users, subjects wore a study iCGM, in blinded mode, to record glucose measurements over 14 days while subjects managed their diabetes at home per their usual routine and remained on their current multiple daily injection (MDI) or pump therapy, and sensor, if applicable.

After completion of the standard therapy phase, subjects were trained on the system and transitioned to the hybrid closed-loop (HCL) phase initiating treatment with the Omnipod Horizon™ System. For the hybrid closed-loop phase, subjects were divided into two groups:

Group 1:
N=16 subjects aged 6.0-70.0 years participated in the hybrid closed-loop phase for the first 2-days while in a supervised hotel/rental house environment and then transitioned to a 12 day outpatient environment.
• N=8 subjects aged 6.0-13.9 years
• N=8 subjects aged 14.0-70.0 years

Group 2:
N=20 subjects aged 6.0-70.0 years participated in the hybrid closed-loop phase in a 14 day outpatient environment with
• N=10 subjects aged 6.0-13.9 years
• N=10 subjects aged 14.0-70.0 years

After all subjects from the first group completed the 2 day hotel phase, the second group of subjects could commence hybrid closed-loop.

All subjects participated in target glucose challenges during the hybrid closed-loop phase. In total, all subjects completed 14 days of hybrid closed-loop, with approximately 72 hours spent at each target blood glucose challenge level of 130 mg/dL, 140 mg/dL and 150 mg/dL.

Clinical site staff received alerts through a remote monitoring system during the study for real-time assessments of subject safety.

After each subject in the pre-pivotal study successfully completed 14 days of hybrid-closed loop, they could immediately enroll into the pivotal study. |

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# Pre-Pivotal Study Safety Results:

There were no serious device-related adverse events reported during the pre-pivotal study. Additionally, there were no subjects with severe hypoglycemia (SH) or diabetic ketoacidosis (DKA) reported during the HCL phase of the pre-pivotal study.

# Pre-Pivotal Study Observed Results:

# CGM Data at Various Target Glucose Settings

Overall (24 hours) CGM results at target glucose settings in children (6 to 13.9 years) from Pre-pivotal study

| Characteristic | 110mg/dL Target Glucose (n=11) | 120mg/dL Target Glucose (n=3) | 130mg/dL Target Glucose (n=18) | 140mg/dL Target Glucose (n=18) | 150mg/dL Target Glucose (n=18) |
| --- | --- | --- | --- | --- | --- |
| Avg % time 70-180 mg/dL (std dev) | 71.2% (10.2%) | 66.8% (12.9%) | 61.5% (7.7%) | 64.8% (11.6%) | 53.5% (11.0%) |
| Avg sensor glucose, mg/dL (std dev) | 155.2 (18.2) | 170 (16) | 174.1 (11.4) | 172.7 (17.2) | 182.9 (15.3) |
| % Time in glucose range | | | | | |
| Median % <54 mg/dL (Q1, Q3) | 0.1% (0.0, 0.4) | 0.2% (0.0, 0.3) | 0.0% (0.0, 0.3) | 0.0% (0.0, 0.0) | 0.0% (0.0, 0.1) |
| Median % <70 mg/dL (Q1, Q3) | 0.9% (0.4, 2.8) | 0.3% (0.2. 2.2) | 0.5% (0.1, 0.8) | 0.1% (0.0, 0.5) | 0.5% (0.0, 0.8) |
| Avg % >180 mg/dL (std dev) | 27.1% (11.4%) | 32.3% (11.9%) | 37.7% (7.9) | 34.6% (12.1%) | 45.9% (11.0%) |
| Avg % ≥250 mg/dL (std dev) | 6.8% (6.3%) | 14.4% (6.2%) | 13.2% (5.8%) | 10.6% (7.3%) | 12.8% (8.1%) |
| Cumulative number of person-days | 47.7 | 8.7 | 73.3 | 56.3 | 61.5 |

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Overall (24 hours) CGM results at target glucose settings in adolescents and adults (14 to 70 years) from Pre-pivotal study

| Characteristic | 110mg/dL Target Glucose (n=12) | 120mg/dL Target Glucose (n=7) | 130mg/dL Target Glucose (n=18) | 140mg/dL Target Glucose (n=18) | 150mg/dL Target Glucose (n=18) |
| --- | --- | --- | --- | --- | --- |
| Avg % time 70-180 mg/dL (std dev) | 72.5% (9.4%) | 70.9% (11.3%) | 75.1% (11.6%) | 67.6% (9.2%) | 63.7% (7.8%) |
| Avg sensor glucose, mg/dL (std dev) | 153.8 (14.8) | 159.7 (11) | 153.8 (14.9) | 165.4 (11.5) | 169.8 (9.4) |
| % Time in glucose range | | | | | |
| Median % <54 mg/dL (Q1, Q3) | 0.0% (0.0, 0.0) | 0.0% (0.0, 0.0) | 0.0% (0.0, 0.2) | 0.0% (0.0, 0.1) | 0.0% (0.0, 0.2) |
| Median % <70 mg/dL (Q1, Q3) | 0.5% (0.0, 1.4) | 0.4% (0.0, 0.6) | 0.9% (0.4, 1.2) | 0.1% (0.0, 0.6) | 0.2% (0.0, 0.9) |
| Avg % >180 mg/dL (std dev) | 26.4% (10.0%) | 28.7% (11.2%) | 23.4% (11.4%) | 31.7% (9.2%) | 35.7% (7.9%) |
| Avg % ≥250 mg/dL (std dev) | 4.1% (3.4%) | 5.2% (5.5%) | 5.0% (4.6%) | 5.1% (4.5%) | 6.0% (4.8%) |
| Cumulative number of person-days | 41.1 | 28 | 58.8 | 58.4 | 60.3 |

## Pivotal Study

The Pivotal study evaluated the safety and effectiveness of the SmartAdjust technology in patients with type 1 diabetes. The study was a single-arm, multi-center, prospective clinical study that enrolled 240 subjects 6-70 years of age, across 17 clinical sites to obtain at least 100 evaluable subjects in the 6.0-13.9 years of age cohort and at least 100 evaluable subjects in the 14.0-70.0 years of age cohort.

The Pivotal study was conducted in three outpatient phases. Phase 1 consisted of a 14 day standard therapy phase followed by Phase 2 which consisted of a 13 week hybrid closed-loop phase. Phase 3 is the extension phase and is currently ongoing.

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| Study Feature | Description |
| --- | --- |
| Title | Evaluating the safety and effectiveness of the Omnipod Horizon Automated Glucose Control System in patients with type 1 diabetes |
| Study Design | Single-arm, multi-center, prospective clinical study |
| Number of Sites | Seventeen (17) US clinical sites |
| Population | 112 subjects aged 6-13.9 years, and 129 subjects aged 14-70 years.

Key Inclusion Criteria
• Age 6-70 years old
• Type 1 for at least 6 months
• HbA1c <10% at screening

Key Exclusion Criteria
• Use of non-insulin anti-diabetic medication other than metformin |
| Sample Size | 240 subjects were enrolled and completed the study |
| Protocol Overview/Synopsis | The study consisted of three phases:
3. 14 day outpatient therapy phase (Phase 1)
4. 13 week outpatient hybrid closed-loop phase (Phase 2)
5. Hybrid closed-loop extension phase (Phase 3)

Current and non-Dexcom G6 iCGM users who did not meet the minimum CGM data requirements participated in Phase 1 (where subjects managed their diabetes at home per their usual routine and remained on their current MDI or pump therapy, and sensor, if applicable). After completion of the standard therapy phase, subjects were trained on the system and transitioned to Phase 2 initiating treatment with the Omnipod Horizon System. Subjects in each cohort (ages 6-13.9 and 14-70 years) participated in prescribed challenges during any consecutive 5-day period during Phase 2 of the hybrid closed-loop phase. Subjects who completed Phase 2 could commence their participation in Phase 3. |

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Baseline characteristics including demographics at enrollment (N=240)

| Characteristic | Children (6 to 13.9 years) | Adults (14 to 70 years) |
| --- | --- | --- |
| n | 112 | 128 |
| Age (years) ± SD | 10.3 ± 2.2 | 36.9 ± 13.9 |
| Duration of diabetes (years) | 4.7 ± 2.6 | 17.9 ± 11.6 |
| HbA1c§ | 7.67% ± 0.95% | 7.16% ± 0.86% |
| Daily insulin dose (U/kg)¥ | 0.85 ± 0.24 | 0.61 ± 0.22 |
| Body mass index (BMI) | 18.6 ± 3.2 | 26.6 ± 4.7 |
| Female sex | 60 (53.6%) | 78 (60.9%) |
| Previous¶ or current continuous glucose monitor (CGM) use | 108 (96.4%) | 126 (98.4%) |
| Previous¶ or current pump use | 100 (89.3%) | 115 (89.8%) |
| Race / Ethnicity‡ | | |
| White | 110 (98.2%) | 118 (92.2%) |
| Hispanic or Latino | 8 (7.1%) | 10 (7.8%) |
| Black or African American | 5 (4.5%) | 5 (3.9%) |
| Asian | 3 (2.7%) | 2 (1.6%) |
| Native Hawaiian or other Pacific Islander | 1 (0.9%) | 0 (0.0%) |
| American Indian or Alaska Native | 0 (0.0%) | 4 (3.1%) |

Plus-minus values are average ± standard deviation; results reported with number in brackets afterwards represent number of subjects (% of subjects)
§ Glycated hemoglobin determined from laboratory assessment
¥ Baseline total daily insulin dose was determined from data collected during the standard therapy phase
¶ Previous use is defined as having used the device for any duration in the past
‡ Race and ethnicity were reported by the subjects. Groups are not mutually exclusive

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# Pivotal Study Safety Results

One (1) DKA, and 3 SH events were reported during the study and included:
- One (1) DKA and 1 SH occurred in the aged 6.0-13.9 years cohort
- Two (2) SH occurred in the 14.0-70.0 years cohort.

The DKA event was indicated as possibly related to the study device and not related to the study procedures while all other serious adverse events were indicated as not related to the device and not related to the study procedures.

The table below provides a full list of the adverse events that occurred during the 3-month Omnipod 5 System treatment phase. There were 3 severe hypoglycemia events not attributable to the Omnipod 5 System automated insulin delivery or system malfunction and 1 DKA event from a suspected infusion site failure. Other related, but non-glycemic adverse events included infection or irritation at infusion site (2 children, 2 adults).

Adverse events during the Omnipod 5 System phase

| Adverse Event Type | Children (6 to 13.9 years) (n=112) | Adults (14 to 70 years) (n=128) | Total (6 to 70 years) (N=240) |
| --- | --- | --- | --- |
| Primary Safety Endpoints | | | |
| Hypoglycemia ‡ | 1 | 0 | 1 |
| Severe Hypoglycemia § | 1 | 2 | 3 |
| DKA | 1 | 0 | 1 |
| Hyperglycemia † | 1 | 2 | 3 |
| Prolonged Hyperglycemia ** | 13 | 5 | 18 |
| Other | 8 | 8 | 16 |

† Hypoglycemia resulting in a serious adverse event, but otherwise not meeting the definition of severe hypoglycemia
§ Required the assistance of another person
|| Hyperglycemia requiring evaluation, treatment or guidance from intervention site, or hyperglycemia resulting in a serious adverse event
** Meter blood glucose measuring ≥300mg/dL and ketones &gt;1.0mmol/L

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# Pivotal Study Observed Results

The tables below include information on the primary and secondary glycemic results from the standard therapy phase compared to the 3-month Omnipod 5 System treatment phase. The primary results of the study included change in average HbA1c% and % time in range (70-80mg/dL).

CGM results overall (24 hours)

| Characteristic | Children (6 to 13.9 years) (n=112) | | | Adolescents & Adults (14 to 70 years) (n=128) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Standard Therapy | Omnipod 5 | Change | Standard Therapy | Omnipod 5 | Change |
| Avg HbA1c% (std dev) | 7.67% (0.95%) | 6.99% (0.63%) | -0.71% | 7.16% (0.86%) | 6.78% (0.68%) | -0.38% |
| Avg % time 70-180mg/dL (std dev) | 52.5% (15.6%) | 68.0% (8.1%) | 15.6% | 64.7% (16.6%) | 73.9% (11.0%) | 9.3% |
| Avg sensor glucose, mg/ dL (std dev) | 183 (32) | 160 (15) | -23 | 161 (28) | 154 (17) | -8 |
| Avg standard deviation of sensor glucose, mg/dL (std dev) | 68 (13) | 60 (10) | -9 | 57 (14) | 49 (11) | -8 |
| Avg coefficient of variation of sensor glucose, % (std dev) | 37.5% (5.1%) | 37.0% (3.9%) | -0.4% | 35.2% (5.7%) | 31.7% (4.7%) | -3.5% |
| % Time in Glucose Range | | | | | | |
| Median % <54mg/dL (Q1, Q3) | 0.10% (0.00, 0.41) | 0.23% (0.08, 0.42) | 0.04% | 0.22% (0.00, 0.77) | 0.17% (0.06, 0.28) | -0.08% |
| Median % <70mg/dL (Q1, Q3) | 1.38% (0.42, 2.67) | 1.48% (0.65, 2.23) | 0.06% | 2.00% (0.63, 4.06) | 1.09% (0.46, 1.75) | -0.89% |
| Avg % >180mg/dL (std dev) | 45.3% (16.7%) | 30.2% (8.7%) | -15.1% | 32.4% (17.3%) | 24.7% (11.2%) | -7.7% |
| Avg % ≥250mg/dL (std dev) | 19.1% (13.1%) | 9.6% (5.4%) | -9.4% | 10.1% (10.5%) | 5.8% (5.5%) | -4.3% |
| Avg % ≥300mg/dL (std dev) | 8.5% (8.9%) | 3.5% (2.9%) | -5.1% | 3.7% (5.5%) | 1.7% (2.5%) | -2.0% |

Most of the primary and secondary results are presented as averages (avg) with standard deviation (std dev) values in brackets. Time in range $&lt; 70\mathrm{mg / dL}$ and $&lt; 54\mathrm{mg / dL}$ is reported as medians with interquartile ranges in brackets(Q1,Q3). The median is the middle umber in an ascending list of numbers and the interquartile range represents the middle $50\%$ of values.

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CGM results overnight (12:00AM to 6:00AM)

| | Children (6 to 13.9 years) (n=112) | | | Adolescents & Adults (14 to 70 years) (n=128) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Standard Therapy | Omnipod 5 | Change | Standard Therapy | Omnipod 5 | Change |
| Avg % time 70-180mg/dL (std dev) | 55.3% (19.0%) | 78.1% (10.8%) | 22.9% | 64.3% (19.5%) | 78.1% (13.9%) | 13.8% |
| Avg sensor glucose, mg/dL (std dev) | 177 (35) | 149 (17) | -29 | 160 (34) | 149 (21) | -11 |
| Avg standard deviation of sensor glucose, mg/dL (std dev) | 61 (15) | 48 (12) | -13 | 56 (17) | 44 (13) | -12 |
| Avg coefficient of variation of sensor glucose, % (std dev) | 34.6% (7.1%) | 31.9% (5.6%) | -2.8% | 35.0% (7.9%) | 28.9% (5.8%) | -6.2% |
| Percentage time in glucose range, % | | | | | | |
| Median % <54mg/dL (Q1,Q3) | 0.00% (0.00, 0.30) | 0.09% (0.02, 0.32) | 0.02% | 0.00% (0.00, 1.06) | 0.09% (0.02, 0.30) | 0.00% |
| Median % <70mg/dL (Q1,Q3) | 0.78% (0.00, 2.84) | 0.78% (0.37, 1.49) | 0.01% | 2.07% (0.50, 5.54) | 0.82% (0.31, 1.62) | -0.86% |
| Avg % >180mg/dL (std dev) | 42.2% (20.0%) | 20.7% (10.8%) | -21.5% | 32.1% (20.2%) | 20.7% (14.1%) | -11.3% |
| Avg % ≥250mg/dL (std dev) | 16.3% (15.0%) | 5.4% (5.1%) | -10.9% | 10.6% (12.7%) | 4.8% (7.0%) | -5.7% |
| Avg % ≥300mg/dL (std dev) | 6.7% (9.1%) | 1.8 (2.5%) | -4.8% | 4.2% (8.0%) | 1.5% (3.1%) | -2.7% |

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# CGM results at various target glucose settings in Pivotal study

The tables below provide information on the results at various self-selected Target Glucose settings during the 3-month Omnipod 5 System phase of the pivotal study. Of the customizable BG targets, the most selected was $110\mathrm{mg / dL}$ .

Overall (24 hours) CGM Results at Target Glucose Settings in Children (6 to 13.9 years) from Pivotal Study

| Characteristic | 110mg/dL Target Glucose (n=98) | 120mg/dL Target Glucose (n=74) | 130mg/dL Target Glucose (n=47) | 140mg/dL Target Glucose (n=12) | 150mg/dL Target Glucose* (n=9) |
| --- | --- | --- | --- | --- | --- |
| Avg % time 70-180 mg/dL (std dev) | 68.4% (9.1%) | 67.5% (9.7%) | 64.2% (14.3%) | 59.2% (16.9%) | 53.3% (18.2%) |
| Avg sensor glucose, mg/dL (std dev) | 159 (17) | 163 (16) | 169 (24) | 178 (24) | 183.6 (23.9) |
| % Time in glucose range | | | | | |
| Median % <54 mg/dL (Q1, Q3) | 0.22% (0.06, 0.49) | 0.18% (0.05, 0.33) | 0.09% (0.00, 0.21) | 0.04% (0.00, 0.34) | 0.00% (0.00, 0.00) |
| Median % <70 mg/dL (Q1, Q3) | 1.51% (0.76, 2.38) | 1.16% (0.58, 1.94) | 0.71% (0.26, 1.63) | 0.59% (0.05, 1.52) | 0.12% (0.00, 0.21) |
| Avg % >180 mg/dL (std dev) | 29.7% (9.6%) | 31.1% (10.0%) | 34.5% (14.8%) | 39.9% (16.6%) | 46.4% (18%) |
| Avg % ≥250 mg/dL (std dev) | 9.7% (5.8%) | 10.0% (6.3%) | 11.8% (9.0%) | 14.6% (11.1%) | 13.3% (11.9%) |
| Cumulative number of person-days | 6,289 | 2,716 | 941 | 99 | 73 |

*Glycemic measures reported at the 150 mg/dL Target Glucose setting only included those with Activity mode turned OFF.

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Overall (24 hours) CGM results at various target glucose settings in adolescents and adults (14 to 70 years) from Pivotal study

| Characteristic | 110 mg/dL Target Glucose (n=121) | 120 mg/dL Target Glucose (n=54) | 130 mg/dL Target Glucose* (n=9) |
| --- | --- | --- | --- |
| Avg % time 70-180 mg/dL (std dev) | 75.6%
(9.9%) | 73.4%
(12.1%) | 63.6%
(25.9%) |
| Avg sensor glucose, mg/dL (std dev) | 151
(15) | 156
(18) | 172
(33) |
| % Time in glucose range | | | |
| Median % <54 mg/dL (Q1, Q3) | 0.16%
(0.05, 0.26) | 0.11%
(0.00, 0.33) | 0.00%
(0.00, 0.00) |
| Median % <70 mg/dL (Q1, Q3) | 0.99%
(0.47, 1.67) | 0.91%
(0.31, 1.68) | 0.26%
(0.05, 0.63) |
| Avg % >180 mg/dL (std dev) | 23.1%
(10.2%) | 25.4%
(12.3%) | 35.9%
(26.1%) |
| Avg % ≥250 mg/dL (std dev) | 5.1%
(4.6%) | 5.8%
(6.4%) | 9.6%
(12.3%) |
| Cumulative number of person-days | 9,278 | 1,827 | 178 |

*Results for the 140 mg/dL and 150 mg/dL (with Activity mode OFF) Target Glucose settings in adults are not shown due to too few subjects selecting them (n≤2).

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Change in insulin requirements during the Pivotal study

| | Children (6 to 13.9 years) (n=112) | | | Adolescents & Adults (14 to 70 years) (n=128) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Standard Therapy | Omnipod 5 | Change | Standard Therapy | Omnipod 5 | Change |
| Avg total daily insulin, U/kg (std dev) | 0.85 (0.24) | 0.92 (0.25) | 0.07 | 0.61 (0.22) | 0.59 (0.21) | -0.02 |
| Avg total daily basal insulin, U/kg (std dev) | 0.36 (0.13) | 0.47 (0.15) | 0.10 | 0.31 (0.11) | 0.30 (0.11) | -0.01 |
| Avg total daily bolus insulin, U/kg (std dev) | 0.48 (0.18) | 0.45 (0.13) | -0.03 | 0.31 (0.16) | 0.29 (0.12) | -0.01 |

## Body mass index results

The table below provides information on the average body mass index (BMI), which is a measure of weight adjusted for height; and BMI z-score, which is a measure of weight adjusted for height, sex, and age, during the standard therapy phase and the 3-month treatment phase in children.

| Characteristic | Children (6 to 13.9 years) n=112 | | |
| --- | --- | --- | --- |
| | Standard Therapy | SmartAdjust Technology | Change |
| BMI, kg/m² (std dev) | 18.6 (3.2) | 19.2 (3.6) | 0.54 |
| BMI z-score (std dev) | 0.4 (0.8) | 0.4 (0.8) | 0.03 |

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# Change in HbA1c from the Pivotal study

The table below provides information on the average change in HbA1c% from baseline to the end of the 3-month Omnipod 5 System treatment phase analyzed by baseline HbA1c% in children (6 to 13.9 years) and adolescents and adults (14 to 70 years). Adolescents, adults, and children experienced a reduction in HbA1c after 3 months of Omnipod 5 System use regardless of baseline HbA1c &lt; 8% or ≥ 8% category.

Subgroup analysis of change in average HbA1c(%) by baseline HbA1c(%)

| Adolescents & Adults | Baseline HbA1c <8% (n=105) | | | Baseline HbA1c ≥8% (n=23) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Baseline | Omnipod 5 | Change | Baseline | Omnipod 5 | Change |
| HbA1c% (std dev)‡ | 6.86% (0.59%) | 6.60% (0.53%) | -0.27% | 8.55% (0.42%) | 7.63% (0.67%) | -0.91% |
| Children | Baseline HbA1c <8% (n=73) | | | Baseline HbA1c ≥8% (n=39) | | |
| | Baseline | Omnipod 5 | Change | Baseline | Omnipod 5 | Change |
| HbA1c% (std dev) | 7.11% (0.50%) | 6.69% (0.44%) | -0.45% | 8.73% (0.63%) | 7.56% (0.54%) | -1.18% |

‡Average HbA1c values are reported with standard deviation values in brackets.

# Study results by baseline treatment

The table below provides information on the average glycemic results at baseline (or during standard therapy phase) and the 3-month Omnipod 5 System treatment phase analyzed by baseline treatment (standard therapy). Standard therapy consisted of multiple daily insulin injections (MDI) or insulin pump use.

Subgroup analysis of average results by baseline treatment in children (6 to 13.9 years)

| Characteristic | MDI (n=13) | | Insulin Pump (n=99) | |
| --- | --- | --- | --- | --- |
| | Standard Therapy | Omnipod 5 | Standard Therapy | Omnipod 5 |
| % Time in range 70-180mg/dL | 52% | 69% | 53% | 68% |
| % Time <70mg/dL‡ | 1.54% | 1.41% | 1.38% | 1.49% |
| HbA1c% | 7.7% | 6.7% | 7.7% | 7.0% |

‡ Values presented for % Time &lt;70mg/dL are medians, the remaining values in the table are averages.

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Subgroup analysis of average results by baseline treatment in adolescents and adults (14 to 70 years)

| Characteristic | MDI (n=20) | | Insulin Pump (n=105) | |
| --- | --- | --- | --- | --- |
| | Standard Therapy | Omnipod 5 | Standard Therapy | Omnipod 5 |
| % Time in range 70- 180mg/dL | 60% | 72% | 66% | 74% |
| % Time <70mg/dL‡ | 2.38% | 0.79% | 1.93% | 1.16% |
| HbA1c% | 7.6% | 7.0% | 7.1% | 6.7% |

## SmartAdjust technology (Auto Mode) use

The table below provides information on the average % of time study subjects used the Omnipod 5 System in Automated Mode.

Percent time spent in Automated Mode

| | Children (6 to 13.9 years) n=112 | Adults (14 to 70 years) n=128 |
| --- | --- | --- |
| % Time in Automated Mode (std dev) | 95.2% (4.0%) | 94.8% (6.0%) |

a. Human Factors Testing

Human factors validation tests were conducted with the Omnipod 5 App installed on a compatible mobile device with interoperable technology. A total of 7 formative studies were conducted; after each study, information was fed back into the design of the User Interface. The final device design was evaluated in the summative study performed with 64 representative participants interacting with the device in a simulated use environment. All study participants received training that was consistent with the training that patients would receive with the commercial product. Usability evaluations assessed comprehension and usability of the device for critical device tasks. Results of the study demonstrated that the device could be used safely by intended users in the intended use environment when used in combination with a digitally connected device.

b. Insulin Compatibility:

The SmartAdjust technology used with the Omnipod 5 System is designed to use rapid-acting U-100 insulins including: NovoLog® (insulin aspart), Humalog® (insulin lispro), and Admelog® (insulin lispro). These insulins were used in the pivotal clinical study for this device and no other insulins have been tested for use with the device.

c. Data Logging:

Software verification testing has demonstrated the device records timestamped critical events, including information related to its state, user inputs, and device settings, as required by the special controls.

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d. Interoperability:
A plan and approach for interoperability were provided according to the FDA Guidance “Design Considerations and Pre-market Submission Recommendations for Interoperable Medical Devices - Guidance for Industry and Food and Drug Administration Staff” and determined to be adequate to support and clearly specify expectations, requirements, and interface specifications to potential interoperable devices. In addition, the plans provided by the sponsor covered their approach to working with connected device companies regarding contractual issues, interfaces for data communication and exchange, and post-market reporting procedures and responsibilities (e.g., who is responsible for investigating and reporting complaints, malfunctions, and adverse events). The sponsor additionally provided validated software protocols intended to ensure secure, accurate, and reliable communication with digital interfacing devices, as well as failsafe design features to mitigate the risks associated with interruption of communication with digitally connected devices. These protocols were reviewed and found to be adequate.

e. Cybersecurity:
Detailed information on cybersecurity of the device was reviewed and found to be acceptable. The sponsor also provided a software bill of materials, which provided details on all software used in the device and the hardware platform that the device was installed on. This included all manufacturer-developed, commercially licensed, open source, and off-the-shelf software components (including firmware as relevant), along with an identification of the hardware runtime environment in which each resides, with relevant version and/or model information, as well as details on whether each component was actively supported by its manufacturer or legacy licensed.

f. Postmarket Surveillance Study
There is uncertainty remaining regarding the risk/benefit profile of the device when used in the broader intended use population. While the premarket clinical study provided to support the 510(k) showed some benefits, it was not adequately powered to assess differences in the rates of safety events (e.g., diabetic ketoacidosis and severe hypoglycemia). Accordingly, a postmarket surveillance study will be ordered by FDA to confirm understanding of safety.

VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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