(400 days)
SmartAdjust technology is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, 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.
The Omnipod 5 iAGC (SmartAdjust technology) 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 suspend the delivery of insulin via a compatible alternate controller enabled (ACE) pump.
The Omnipod 5 iAGC software is part of the Omnipod 5 Automated Insulin Delivery System, which also includes the Omnipod 5 ACE Pump, Omnipod 5 Bolus Calculator, and an interoperable iCGM. The Omnipod 5 iAGC is intended to be digitally connected to an iCGM and an ACE Pump.
The Omnipod 5 iAGC 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 Omnipod 5 iAGC uses this transmitted iCGM data in its calculations. The Omnipod 5 iAGC can be turned off, and the Omnipod 5 ACE Pump will operate in Manual Mode, which delivers insulin based on HCP- or user-defined Basal Programs.
The Omnipod 5 iAGC 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 Omnipod 5 iAGC 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 preprogrammed basal insulin. When a valid glucose value is received from the iCGM, the Omnipod 5 iAGC will resume delivery of insulin in full Automated Mode. Activity is a user-selected temporary feature intended for use during periods when insulin sensitivity is expected to be higher, such as during exercise. With Activity, the algorithm reduces insulin delivery and sets a temporary glucose target of 150 mg/dL.
Acceptance Criteria and Device Performance for SmartAdjust Technology
The SmartAdjust technology, an interoperable Automated Glycemic Controller (iAGC) for type 1 diabetes management, was evaluated through a clinical study. The acceptance criteria and reported device performance are detailed below.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly list pre-defined quantitative acceptance criteria for all aspects. Instead, the study aims to demonstrate improvements in glycemic control and safety compared to standard therapy. The "Change" columns in the glycemic results tables effectively represent the performance metrics, and a "P < 0.0001" indicates statistical significance for these changes, which serves as an implicit acceptance criterion for improvement.
Here's a summary of the key performance metrics from the clinical study, presented as a comparison to the standard therapy phase:
Glycemic Results Overall (24 hours)
| Characteristic | Acceptance Criteria (Improvement vs. Standard Therapy with P < 0.0001) | Reported Device Performance (Change with Omnipod 5) |
|---|---|---|
| Children (6 to 13.9 years) | ||
| Avg A1C, % | Significant decrease | -0.71%* |
| Avg sensor glucose, mg/dL | Significant decrease | -23* |
| Avg % time 70-180mg/dL | Significant increase | 15.6%* |
| Median % <54mg/dL | No significant increase or decrease (ideally stable or decreasing) | 0.04% |
| Median % <70mg/dL | No significant increase or decrease (ideally stable or decreasing) | 0.06% |
| Avg % >180mg/dL | Significant decrease | -15.1%* |
| Avg % ≥250mg/dL | Significant decrease | -9.4%* |
| Avg % ≥300mg/dL | Significant decrease | -5.1%* |
| Adolescents & Adults (14 to 70 years) | ||
| Avg A1C, % | Significant decrease | -0.38%* |
| Avg sensor glucose, mg/dL | Significant decrease | -8* |
| Avg % time 70-180mg/dL | Significant increase | 9.3%* |
| Median % <54mg/dL | Significant decrease (ideally) | -0.08%* |
| Median % <70mg/dL | Significant decrease (ideally) | -0.89%* |
| Avg % >180mg/dL | Significant decrease | -7.7%* |
| Avg % ≥250mg/dL | Significant decrease | -4.3%* |
| Avg % ≥300mg/dL | Significant decrease | -2.0%* |
Safety Results (Incidence of Adverse Events)
| Adverse Event Type | Acceptance Criteria (Low incidence, comparable to standard, or manageable) | Reported Device Performance (Events per person-month / Count) |
|---|---|---|
| Severe hypoglycemia | Low incidence, ideally no association with device malfunction | 0.004 events per person-month (3 events total, not attributable to system) |
| Diabetic ketoacidosis (DKA) | Low incidence, ideally no association with device malfunction | 0.001 events per person-month (1 event total, from suspected infusion site failure) |
| Other related adverse events | Acceptable and manageable rate | Hypoglycemia (non-severe): 1 (0.4%) / Hyperglycemia: 3 (1.3%) / Prolonged Hyperglycemia: 18 (6.7%) / Other: 16 (6.7%) |
*Change between standard therapy phase and Omnipod 5 System phase was significant (P < 0.0001).
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 240 subjects. This included 112 children (6 to 13.9 years) and 128 adolescents and adults (14 to 70 years).
- Data Provenance: The data was collected from a multicenter, prospective clinical study conducted across 17 investigational sites. The document does not explicitly state the country of origin, but given the FDA submission, it is highly likely the study was conducted in the United States or in accordance with international good clinical practice standards acceptable to the FDA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The study involved a prospective clinical trial in human subjects with Type 1 Diabetes. In this context, the "ground truth" for glycemic control and safety are direct measures from the subjects (A1C, sensor glucose readings, adverse event reporting) rather than expert consensus on images or interpretations. Therefore, there were no "experts" establishing a ground truth for a test set in the traditional sense of medical image analysis. Clinical endpoints were measured directly from the study participants.
4. Adjudication Method for the Test Set
The document does not describe an explicit adjudication method for a "test set" in the context of expert review, as the ground truth was derived from direct clinical measurements. However, adverse events and clinical outcomes would have been reviewed and documented by clinical investigators and potentially an independent medical monitor or data safety monitoring board, which is standard for clinical trials.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. This type of study is typically relevant for interpretative medical devices (e.g., imaging AI) where human readers interpret cases with and without AI assistance. The SmartAdjust technology is a therapeutic device that directly controls insulin delivery, and its effectiveness is measured by clinical outcomes (e.g., A1C, time in range) in patients.
6. Standalone Performance Study
Yes, a standalone study was conducted. The clinical study described is a standalone performance study of the SmartAdjust technology (Omnipod 5 iAGC) in automated mode, meaning the algorithm was operating without human intervention for insulin delivery adjustments. The study compared the device's performance against a "standard therapy phase" which served as a baseline. The algorithm made automatic adjustments based on iCGM data, and the outcomes were observed directly in patients.
7. Type of Ground Truth Used
The ground truth used was outcomes data from human subjects. Specifically:
- Glycemic Control: Measured by laboratory-assessed A1C, and continuous glucose monitor (CGM) data (e.g., average sensor glucose, percentage of time in various glucose ranges: 70-180 mg/dL, <54 mg/dL, <70 mg/dL, >180 mg/dL, ≥250 mg/dL, ≥300 mg/dL).
- Safety: Measured by the incidence of severe hypoglycemia and diabetic ketoacidosis (DKA), as well as other adverse events reported during the clinical trial.
8. Sample Size for the Training Set
The document does not provide information on the sample size for the training set. This is typical for device submissions where the algorithm's development (training) might involve proprietary data and methods not usually detailed in the 510(k) summary. The clinical study focuses on the validation and performance of the fully developed device.
9. How the Ground Truth for the Training Set Was Established
The document does not specify how the ground truth for any potential training set was established. Given the nature of an automated glycemic controller, it's plausible that the training could involve:
- Simulated physiological models of diabetes.
- Retrospective data from patients with T1D (e.g., CGM data, insulin delivery logs, meal information).
- Rule-based logic derived from clinical guidelines and expert knowledge, rather than a "trained" machine learning model in the conventional sense.
Without further information in the submission, the exact method for establishing ground truth for training cannot be determined.
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January 27, 2022
Insulet Corporation Katie Pacheco Director of Regulatory Affairs, Digital Health 100 Nagog Park Acton, MA 01720
Re: K203774
Trade/Device Name: SmartAdjust technology Regulation Number: 21 CFR 862.1356 Regulation Name: Interoperable Automated Glycemic Controller Regulatory Class: Class II Product Code: OJI Dated: September 2, 2021 Received: September 3, 2021
Dear Katie Pacheco:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal
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statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kellie B. Kelm, Ph.D. Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K203774
Device Name SmartAdjust technology
Indications for Use (Describe)
Smart Adjust technology is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, 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.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| > Prescription Use (Part 21 CFR 801 Subpart D) | ___ Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(K) SUMMARY
| Date Prepared: | January 26, 2022 |
|---|---|
| Submitter Name: | Insulet Corporation |
| Submitter Address: | 100 Nagog Park, Acton, MA, 01720 |
| FDA Establishment Owner/OperatorNumber: | 9056196 |
| FDA Establishment Registration Number: | 3014585508 |
| Contact Person: | Katie PachecoDirector, Regulatory Affairs, Digital Health |
| Phone: | 978 932 0027 |
| Fax: | 978 600 0120 |
| Device Trade/Proprietary Name: | SmartAdjust technology |
| Device Common Name: | Omnipod 5 iAGC |
| Regulation Description | Interoperable Automated Glycemic Controller |
| Review Panel(s): | Clinical Chemistry |
| Product Code(s): | QJI |
| Regulation Numbers: | 21 CFR 862.1356 |
| Submission Type: | Traditional 510(k) |
| Device Class: | Class II |
| Device Predicate: | K200467, Control-IQ Technology |
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Device Description:
The Omnipod 5 iAGC (SmartAdjust technology) 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 suspend the delivery of insulin via a compatible alternate controller enabled (ACE) pump.
The Omnipod 5 iAGC software is part of the Omnipod 5 Automated Insulin Delivery System, which also includes the Omnipod 5 ACE Pump, Omnipod 5 Bolus Calculator, and an interoperable iCGM. The Omnipod 5 iAGC is intended to be digitally connected to an iCGM and an ACE Pump.
The Omnipod 5 iAGC 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 Omnipod 5 iAGC uses this transmitted iCGM data in its calculations. The Omnipod 5 iAGC can be turned off, and the Omnipod 5 ACE Pump will operate in Manual Mode, which delivers insulin based on HCP- or user-defined Basal Programs.
The Omnipod 5 iAGC 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 Omnipod 5 iAGC 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 preprogrammed basal insulin. When a valid glucose value is received from the iCGM, the Omnipod 5 iAGC will resume delivery of insulin in full Automated Mode. Activity is a user-selected temporary feature intended for use during periods when insulin sensitivity is expected to be higher, such as during exercise. With Activity, the algorithm reduces insulin delivery and sets a temporary glucose target of 150 mg/dL.
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Summary of Technological Characteristics Compared to Predicate Device:
The subject device and predicate device use similar operating principles to achieve the intended therapeutic effect. The subject device has the same intended use and similar indications for use, principles of operation, and use environment as the predicate device. The subject device and predicate device are both interoperable automated glycemic controllers that integrate with compatible integrated continuous glucose monitors (iCGM) and ACE Pumps to automatically increase, decrease, and suspend the delivery of insulin based on iCGM data and predicted glucose readings.
The differences between predicate and subject device include the glucose targets, device(s) that host the controller, compatible bolus calculator, and alarm features/functionality. The differences do not raise different questions about safety and effectiveness and the performance data, human factors validation, and clinical data demonstrate the Omnipod 5 iAGC is substantially equivalent to its predicate device. Table 1 below illustrates the equivalence of the subject device to the predicate.
| Element ofComparison | Subject Device: Omnipod 5Interoperable AutomatedGlycemic Controller (iAGC) | Predicate Device: TandemDiabetes Care, Inc. Control-IQTechnology (K200467) |
|---|---|---|
| Element ofComparison | Subject Device: Omnipod 5Interoperable AutomatedGlycemic Controller (iAGC) | Predicate Device: Tandem DiabetesCare, Inc. Control-IQTechnology(K200467) |
| Indications forUse | SmartAdjust technology isintended for use with compatibleintegrated continuous glucosemonitors (iCGM) and alternatecontroller enabled (ACE) pumps toautomatically increase, decrease,and pause delivery of insulin basedon current and predicted glucosevalues. SmartAdjust technology isintended for the management oftype 1 diabetes mellitus in persons6 years of age and older.SmartAdjust technology is intendedfor single patient use and requires aprescription. | Control-IQ technology is intended foruse with compatible integratedcontinuous glucose monitors (iCGM) andalternate controller enabled (ACE)pumps to automatically increase,decrease, and suspend delivery of basalinsulin based on iCGM readings andpredicted glucose values. It can alsodeliver correction boluses when theglucose value is predicted to exceed apredefined threshold.Control-IQ technology is intended for themanagement of Type 1 diabetes mellitusin persons 6 years of age and greater.Control-IQ technology is intended forsingle patient use and requires aprescription.Control-IQ technology is indicated foruse with NovoLog or Humalog U-100insulin. |
| Age Range ofIntended Users | Ages 6 and older | Ages 6 and older |
| Environment ofuse | Ambulatory use | Ambulatory use |
| SpecificDrug/BiologicUse | U-100 InsulinSystem has been tested withNovoLog®, Humalog®, andAdmelog® | U-100 InsulinSystem has been tested withNovoLog® and Humalog® |
| PrescriptionStatus | Prescription Device | Prescription Device |
| Principles ofOperation | Algorithmic software deviceintended to automatically increase,decrease, and suspend delivery ofinsulin based on iCGM readingsand predicted glucose values | Algorithmic software device intended toautomatically increase, decrease, andsuspend delivery of insulin based oniCGM readings and predicted glucosevalues |
| Labeling | Package Labels, User's Guide(contains Instructions for Use),Quick Start Guide | Package Labels, User's Guide(contains Instructions for Use) |
| Communicationand Pairing | Bluetooth Low Energy (BLE)wireless technology | Bluetooth Low Energy (BLE) wirelesstechnology |
| Device HostingController | Omnipod 5 ACE Pump | T:slim X2 insulin pump |
| DigitallyConnectedDevices | Cleared iCGM and ACE Pump,which includes an Android OSdisplay device (Insulet-providedController phone or user'scompatible smartphone) | Cleared iCGM and ACE Pump |
| SystemFunctionalityModes | • SmartAdjust technology enabled- Automated Mode (closed-loop,automatically increase,decrease, and suspend deliveryof insulin based on current andpredicted glucose values)• SmartAdjust technology notenabled - Manual Mode (openloop, basal delivery based onuser-defined programs) | • Control IQ technology enabled (closedloop, automatically increase, decrease,and suspenddelivery of insulin basedon iCGM readings and predictedglucose values. Can deliver automaticcorrection bolus when glucose value ispredicted to exceed a predefinedthreshold).• Control IQ technology not enabled(open loop, basal delivery based onuser defined programs) |
| Alarms/Alerts | Out of Range AlertLow AlertMaximum Insulin/Delivery Alert | Out of Range AlertLow AlertHigh AlertMaximum Insulin/Delivery Alert |
| Alert/AlarmDisplay | ACE Pump alarms/alerts will bedisplayed and communicated totheuser via visual, audible, and/orvibratory cues. | ACE Pump alarms/alerts will be displayedand communicated tothe user via visual,audible, and/or vibratory cues. |
| Mechanism ofSoftware Update | Firmware over the Air | Firmware over the Air |
| History Storage | Up to 90 days (user insulin history) | At least 90 days |
| Target GlucoseControl Range | 110-150 mg/dl, user-customizable | 112.50-160 mg/dl, not user-customizable |
Table 1. Substantial Equivalence Comparison
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Standards Compliance
The Omnipod 5 iAGC complies with the following standards as documented in the applicable test reports provided in this 510(k) submission.
- IEC 62366:2015 Medical Devices Part 1: Application of Usability Engineering .
- HE75:2009 Human Factors Engineering Design of Medical Devices ●
- ISO 14971:2007 Medical devices Application of Risk Management to Medical . Devices
- IEC 62304 Ed. 1.1 2015 Medical device software Software life cycle processes .
- . ISO 14155:2011 - Clinical investigation of medical devices for human subjects -Good clinical practice
Summary of Non-Clinical Performance Data
The information presented in this 510(k) demonstrates the safety and effectiveness of the Omnipod 5 iAGC with a compatible ACE Pump and iCGM. Performance testinq with the Omnipod 5 iAGC included the following:
- . Risk Management: Risk management was completed in accordance with ISO 14971:2007. Verification activities, as required by the risk analysis, demonstrated that the predetermined acceptance criteria were met and the devices are safe for use.
- . Human Factors Validation: Insulet executed a comprehensive human factors and usability engineering process that followed and complied with the FDA-recognized standards IEC 62366:2015-1 and HE75:2009 as well as the FDA's guidance document, Applying Human Factors and Usability Engineering to Medical Devices lssued February 3, 2016. A robust validation evaluation was performed to demonstrate safe and effective use of the Omnipod 5 iAGC with intended users in the expected use environments, including associated training and accompanying documentation. The results of the validation demonstrate that the iAGC has been found to be safe and effective for the intended users, uses, and use environments.
- . Software Validation: Software verification and validation testing was performed in accordance with IEC 62304:2015 and FDA's quidance document. General Principles of Software Validation - Issued January 11, 2002.
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- 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.
- Interoperability: Interoperability documentation was provided according to the FDA . quidance. Design Considerations and Pre-market Submission Recommendations for Interoperable Medical Devices - Guidance for Industry and Food and Drug Administration Staff - Issued September 6, 2017 and specifies validated interface specifications to potential interoperable devices and partnership agreements regarding contractual issues, interfaces for data communication and exchange, and post-market reporting procedures and responsibilities.
- . Cybersecurity: A cybersecurity analysis was performed for the Omnipod 5 iAGC using the FDA guidance, Content of Premarket Submissions for Management of Cybersecurity in Medical devices - Issued October 18, 2020, and the principles outlined in the FDA guidance, Postmarket Management of Cybersecurity in Medical Devices, - Issued December 28, 2020. Insulet has provided a software bill of materials and penetration testing.
- Special Controls: Evaluation of the Special Controls for this device (regulation 21 . CFR 862.1356) assures the safety and effectiveness of the device.
Summary of Clinical Performance Data
A clinical study was performed with the Omnipod 5 iAGC per ISO 14155:2011 with the objective to assess the safety and effectiveness of the system. This single-arm, multicenter, prospective study enrolled 240 subjects – 112 children (6 to 13.9 years) and 128 adolescents and adults (14 to 70 years). A 2-week standard therapy phase (usual insulin reqimen) was followed by 3 months of the Omnipod 5 System use in Automated Mode. Upon completion of the 3-month phase, subjects continued into an optional Automated Mode extension, which is currently onqoing. The primary effectiveness analysis consisted of A1C and sensor glucose time in range (70-180 mg/dL) results. The primary safety endpoints included the incidence of severe hypoglycemia and diabetic ketoacidosis (DKA). An analysis of the secondary endpoints and additional metrics was also performed. An analysis of the primary, and safety results is presented in the tables below.
Of the 240 subjects enrolled across 17 investigational sites, 98% completed the 3-month Omnipod 5 phase of the trial (111 children and 124 adolescents and adults). The study
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population consisted of people with type 1 diabetes for at least 6 months. All subjects were required to have an A1C < 10.0% at screening. Key exclusion criteria included: taking oral or injectable steroids or diabetes medications other than metformin and insulin; history of severe hypoglycemia or DKA in the past 6 months; and history of cardiovascular disease. Select baseline characteristics of the subjects at the start of the 3-month Omnipod 5 treatment phase are provided in the table below.
| Children | Adolescents & Adults | |
|---|---|---|
| Characteristic | (6 to 13.9 years) | (14 to 70 years) |
| N | 112 | 128 |
| Age (years) ± SD | 10.3 ± 2.2 | 36.9 ± 13.9 |
| A1C§ | 7.67% ± 0.95% | 7.16% ± 0.86% |
| Multiple daily injections asStandard Therapy, n (%) | 13 (11.6%) | 20 (15.6%) |
Baseline Characteristics at Omnipod 5 Treatment Phase Initiation (N=240)
Plus-minus values are average ±standard deviation (SD)
§ Glycated hemoglobin determined from laboratory assessment.
Glycemic 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. Children, adolescents, and adults experienced improvements in overall A1C and time in range after 3 months of Omnipod 5 System use. This was achieved with a reduction of time >180 mg/dL in adolescents, adults, and children as well as a reduction in median time <70 mg/dL in adolescents and adults.
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Glycemic Results Overall (24 hours)
| Children (6 to 13.9 years)(n=112) | Adolescents & Adults (14 to 70 years)(n=128) | ||||||
|---|---|---|---|---|---|---|---|
| Characteristic | StandardTherapy | Omnipod 5 | Change | StandardTherapy | Omnipod 5 | Change | |
| Avg A1C, %(std dev) | 7.67%(0.95%) | 6.99%(0.63%) | -0.71%* | 7.16%(0.86%) | 6.78%(0.68%) | -0.38%* | |
| Avg sensor glucose,mg/dL(std dev) | 183(32) | 160(15) | -23* | 161(28) | 154(17) | -8* | |
| Percentage Time in Glucose Range | |||||||
| 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%* | |
| 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%* | |
| Avq % ≥300mg/dL(std dev) | 8.5%(8.9%) | 3.5%(2.9%) | -5.1%* | 3.7%(5.5%) | 1.7%(2.5%) | -2.0%* |
*Change between standard therapy phase and Omnipod 5 System phase was significant (P < 0.0001).
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Glycemic Results Overnight (12:00AM to 6:00AM)
| Children (6 to 13.9 years)(n=112) | Adolescents & Adults (14 to 70years)(n=128) | |||||
|---|---|---|---|---|---|---|
| Characteristic | StandardTherapy | Omnipod 5 | Change | StandardTherapy | Omnipod 5 | Change |
| Percentage time in glucose range, % | ||||||
| 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%* |
| 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%* |
*Change between standard therapy phase and Omnipod 5 System phase was significant (P < 0.0001).
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Safety Results
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 adolescents/adults).
| Adverse Event Type | Children(6 to 13.9 years)(n=112) | Adolescents & Adults(14 to 70 years)(n=128) | Total(6 to 70 years)(N=240) |
|---|---|---|---|
| Primary Safety Endpoints(events per person-month) | |||
| Severe hypoglycemia | 0.003 | 0.005 | 0.004 |
| Diabetic ketoacidosis | 0.003 | 0.000 | 0.001 |
| Hypoglycemia ‡ | 1 (0.9%) | 0 (0.0%) | 1 (0.4%) |
| Severe Hypoglycemia § | 1 (0.9%) | 2 (1.6%) | 3 (1.3%) |
| DKA | 1 (0.9%) | 0 (0.0%) | 1 (0.4%) |
| Hyperglycemia II | 1 (0.9%) | 2 (1.6%) | 3 (1.3%) |
| Prolonged Hyperglycemia ** | 13 (10.7%) | 5 (3.1%) | 18 (6.7%) |
| Other | 8 (7.1%) | 8 (6.3%) | 16 (6.7%) |
Adverse Events during the Omnipod 5 Treatment Phase
Results reported with number in brackets afterwards represent number of events (% of subjects).
- Hypoglycemia resulting in a serious adverse event, but otherwise not meeting the definition of severe hypoglycemia.
& Required the assistance of another person.
II 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 >1.0mmol/L
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Substantial Equivalence Conclusion
The Omnipod 5 iAGC has the same intended use and similar indications for use as the predicate device and is intended to be used in the same environment as the predicate device. While there are minor differences in technological characteristics between the subject and predicate devices, these differences do not raise different questions about safety and effectiveness.
The non-clinical and clinical performance data described above supports the determination of substantial equivalence to the predicate device. This data demonstrates sufficient implementation of design considerations relative to data logging, interoperability, and cybersecurity design as required by the Special Controls for this device (regulation 21 CFR 862.1356). Human factors and clinical validation successfully demonstrate that the Omnipod 5 iAGC has been found to be safe and effective for the intended users, uses, and use environments. Therefore, the Omnipod 5 iAGC is substantially equivalent to the predicate device.
§ 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 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.
(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.