Tidepool Loop

K203689 · Tidepool Project · QJI · Jan 23, 2023 · Clinical Chemistry

Device Facts

• Record ID: K203689
• Device Name: Tidepool Loop
• Applicant: Tidepool Project
• Product Code: QJI · Clinical Chemistry
• Decision Date: Jan 23, 2023
• 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

Tidepool Loop, a mobile application with algorithm technology, is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) insulin infusion pumps to automatically increase, decrease, and suspend delivery of basal insulin based on iCGM readings and predicted glucose values. It can also recommend, and with the user's confirmation, control the delivery of correction boluses when glucose values are predicted to exceed user configurable thresholds. Tidepool Loop is intended for the management of type 1 diabetes mellitus in persons six years of age and greater. Tidepool Loop is intended for single patient use. Tidepool Loop is Rx - For Prescription Use Only.

Device Story

Tidepool Loop is a mobile application (SaMD) for iPhone/Apple Watch that functions as an interoperable automated glycemic controller (iAGC). It receives real-time glucose data from an iCGM and communicates with an ACE insulin pump via Bluetooth. The algorithm predicts glucose levels up to 6 hours into the future based on CGM readings, insulin delivery history, and user-entered data (carbohydrates, exercise). It automatically adjusts or suspends basal insulin delivery every 5 minutes and recommends correction boluses for user confirmation. Used at home by patients or caregivers, the device aims to improve glycemic control and reduce hypoglycemia. Healthcare providers configure initial therapy settings (e.g., correction ranges, insulin sensitivity). The system includes safety guardrails like a user-configurable Glucose Safety Limit to prevent hypoglycemia. It provides patients with more choice in automated dosing algorithms and integrates into their existing diabetes management strategy.

Clinical Evidence

Clinical evidence provided via the 'Loop Observational Study,' a real-world, prospective, virtual observational study. Sample size included 175 participants in the intended use population (ages 6+). Primary endpoints included safety (incidence of severe hypoglycemia/DKA) and glycemic outcomes (Time in Range 70-180 mg/dL). Results showed improvement in mean Time in Range from 62% at baseline to 70% at 6 months. No unexpected safety signals were identified, though FDA noted the study population was not fully representative of the general population, leading to a required postmarket surveillance study.

Technological Characteristics

Software-only device (SaMD) running on qualified mobile platforms (e.g., iPhone). Uses proprietary algorithm for automated insulin dosing. Interoperability via Bluetooth and IEEE 11073 standards. Features include user-configurable safety limits (67-110 mg/dL) and correction ranges (87-180 mg/dL). Employs rigorous data logging and cybersecurity controls, including penetration testing and software bill of materials. Validated for use only with specific iCGM and ACE pump hardware.

Indications for Use

Indicated for management of type 1 diabetes mellitus in persons 6 years of age and older. For prescription use only. Contraindicated for those unable to notice alerts/alarms, unable to monitor glucose as recommended, unable to maintain contact with healthcare provider, or unable to follow instructions for use. MR Unsafe.

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)

{0}

FDA

U.S. FOOD & DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

INSTRUMENT ONLY

## I Background Information:

A 510(k) Number

K203689

B Applicant

Tidepool Project

C Proprietary and Established Names

Tidepool Loop

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.

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

{1}

B Indication(s) for Use:

Tidepool Loop, a mobile application with algorithm technology, is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) insulin infusion pumps to automatically increase, decrease, and suspend delivery of basal insulin based on iCGM readings and predicted glucose values. It can also recommend, and with the user's confirmation, control the delivery of correction boluses when glucose values are predicted to exceed user configurable thresholds.

Tidepool Loop is intended for the management of type 1 diabetes mellitus in persons six years of age and greater.

Tidepool Loop is intended for single patient use.

Tidepool Loop is Rx - For Prescription Use Only.

C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

Tidepool Loop should not be used by anyone who is unable to notice alerts, alarms, and reminders because of physical limitations.

Tidepool Loop should not be used by anyone that is unable to monitor glucose as recommended by their healthcare provider.

Tidepool Loop should not be used by anyone that is unable to maintain contact with their healthcare provider.

Tidepool Loop should not be used during Magnetic Resonance Imaging (MRI), Computed Tomography (CT) scan, Positron Emission Tomography (PET) scan, or high-frequency electrical heat (diathermy) treatment. Components of the Tidepool Loop system may not have been tested in magnetic fields and heat could damage the CGM or insulin pump being used with Tidepool Loop and prevent accurate sensor glucose readings or accurate insulin delivery. This could result in overdelivery or under-delivery of insulin, which can lead to low or high blood glucose. Please follow Healthcare Provider instructions and refer to the individual component manuals for more information.

Do not use Tidepool Loop in children under the age of six years old. Tidepool Loop is not indicated for use by anyone who is under the age of six years old and the performance of the system in children under six is unknown.

Tidepool Loop is not indicated for use by anyone who is pregnant, on dialysis, or critically ill. It is not known how different conditions or medications used in these scenarios may affect performance of the Tidepool Loop system. CGM readings being used by the system may be inaccurate in these cases, meaning the Tidepool Loop App will not have accurate information to use for dosage recommendations. This could result in overdelivery or under-delivery of insulin, which can lead to low and high blood glucose.

Do not take external insulin, such as manual insulin injections or inhaled insulins, while the Tidepool Loop app and insulin pump are operational. Tidepool Loop does not receive

K203689 - Page 2 of 13

{2}

information about insulin taken outside the app. If you choose to take additional insulin with another method while the app and insulin pump are working, overdelivery or under-delivery of insulin may occur, which can lead to low and high blood glucose. Consult with your healthcare provider about how long to wait after manually taking insulin before using Closed Loop Mode with Tidepool Loop.

Do not use Tidepool Loop if you are taking GLP-1 agonists or SGLT-2 inhibitors, metformin, or DPP-4. Tidepool Loop has not been tested in populations using additional diabetes medications and the performance of the system in conjunction with these medications is unknown.

Do not use Tidepool Loop when using hydroxyurea, a medication used in the treatment of diseases including cancer and sickle cell anemia. CGM readings being used by the system may be inaccurate while taking hydroxyurea, meaning the Tidepool Loop App will not have accurate information to use for dosage recommendations. This could result in overdelivery of insulin, which can lead to hypoglycemia. Talk to your healthcare provider about using your BG meter for treatment decisions instead.

ONLY use NovoLog or Humalog U-100 insulin in your Tidepool Loop-compatible insulin pump. Tidepool Loop is designed to automate dosing of NovoLog or Humalog U-100 rapid-acting insulin only.

Speak with your healthcare provider about lifestyle changes that may impact your overall insulin needs and settings, such as weight gain or loss or starting or stopping new activities.

Only the particular iCGM and ACE pump devices specifically designated by Tidepool for compatibility with the Tidepool Loop app may be used with the app.

## IV Device/System Characteristics:

### A Device Description:

Tidepool Loop is a software-only device intended for use by people with Type 1 diabetes. The software algorithm resides on a mobile application that can be downloaded to qualified mobile devices (e.g., iPhone) and connects to a compatible Alternate Controller Enabled insulin pump (ACE pump) and a compatible integrated continuous glucose monitor (iCGM) to automatically increase, decrease, and suspend delivery of basal insulin based on readings from the iCGM and glucose values predicted by Tidepool Loop. By design, Tidepool Loop can only be used with compatible iCGM and ACE Pump devices for which the Tidepool Loop has been validated for use with. Tidepool Loop will not allow use of an unvalidated ACE pump or iCGM. There are controls within the software to prevent use of Tidepool Loop in these cases.

Tidepool Loop uses the Tidepool Loop Bolus Recommendation Tool (TLBRT) in closed loop mode, which can recommend, and, with the user's confirmation, deliver correction boluses when glucose values are predicted to exceed user configurable thresholds. Tidepool Loop predicts glucose levels up to 6 hours in the future based on prior iCGM readings, insulin delivery history, and user input (e.g., carbohydrate intake and exercise), and uses that prediction to adjust insulin delivery. Tidepool Loop requires that users input their specific therapy settings, which are

K203689 - Page 3 of 13

{3}

established with the help of their health care provider before using the device, as part of the prescription process. These settings include:

- Target Correction Ranges for normal operation, pre-meal, and workout presets
- Settings can be programmed as low as 87 mg/dL and as high as 180 mg/dL and different ranges can be added for different times of day.
- Glucose Safety Limit
- Settings can be programmed as low as 67 mg/dL, or as high as 110 mg/dL or the Correction Range minimum, whichever is lower.
- Carb to Insulin Ratios
- Insulin sensitivity factors
- Basal rates
- Max basal rate
- Max bolus

Tidepool Loop can be used to adjust or suspend basal insulin delivery every 5 minutes based on actual CGM sensor and predicted glucose readings. iCGM values are automatically used by the TLBRT when the Tidepool Loop Algorithm technology is active (i.e., when the device is operating in closed-loop mode with an active iCGM sensor session). The TLBRT is disabled when closed-loop mode is off, such as when it is manually disabled, or when there is no active iCGM sensor session. The user will use Tidepool Loop’s simple bolus calculator, into which iCGM values are not automatically populated into the glucose field.

## B Instrument Description Information:

1. Instrument Name: Tidepool Loop
2. Specimen Identification: N/A
3. Specimen Sampling and Handling: N/A
4. Calibration: N/A
5. Quality Control: N/A

## V Substantial Equivalence Information:

### A Predicate Device Name(s): Control-IQ Technology

### B Predicate 510(k) Number(s): K200467

K203689 - Page 4 of 13

{4}

C Comparison with Predicate(s):

| Device & Predicate Device(s): | K203689 | K200467 |
| --- | --- | --- |
| Device Trade Name | Tidepool Loop | Control-IQ Technology |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Same | For use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, decrease, and suspend delivery of basal insulin based on iCGM readings and predicted glucose values. It can also deliver correction boluses when the glucose value is predicted to exceed a predefined threshold. |
| Age Range of intended users | Same | Six years and older |
| Compatible Insulins | Same | Control-IQ technology is indicated for use with NovoLog or Humalog U-100 insulin. |
| General Device Characteristic Differences | | |
| Device Hosting Controller | Mobile device (e.g., qualified iPhone models) | t:slim X2 Insulin Pump |
| Correction Bolus | Requires user confirmation. | Automatic correction bolus. Requires user confirmation for meal bolus. |

VI Standards/Guidance Documents Referenced:

Special controls established under 21 CFR 862.1356

ISO 14971:2012: Medical devices - Application of risk management to medical devices
ANSI/AAMI/IEC 62366-1:2015: Medical devices - Part 1: Application of usability engineering to medical devices

K203689 - Page 5 of 13

{5}

ANSI/AAMI HE75:2009 Human factors engineering, Design of medical devices

ISO/IEEE 11073-40101:2020 Health informatics - Device interoperability Part 40101: Foundational - Cybersecurity - Processes for vulnerability assessment

ISO/IEEE 11073-40102:2020 Health informatics - Device interoperability. Part 40102: Foundational - Cybersecurity - Capabilities for mitigation

## VII Performance Characteristics (if/when applicable):

### A Analytical Performance:

This is a software-only device. The following analytical performance sections are not applicable.

1. **Precision/Reproducibility:** Not applicable.
2. **Linearity:** Not applicable.
3. **Analytical Specificity/Interference:** Not applicable.
4. **Accuracy (Instrument):** Not applicable.
5. **Carry-Over:** Not applicable.

### B Other Supportive Instrument Performance Characteristics Data:

**Summary of Clinical Testing:**

Tidepool Loop was derived from the open source, community-developed Do-It-Yourself (DIY) Loop project. The Loop Observational Study was a real-world, virtual, observational study conducted to collect data on the safety and effectiveness of Loop in both new and existing users to support this premarket notification for Tidepool Loop. Users were recruited to enroll in the observational study and provide their information related to algorithm use. The protocol allowed enrollment of up to 1,250 participants of any age with Type 1 diabetes with a target of at least 300 participants and a minimum of 150 new Loop users.

The study enrolled subjects diagnosed with type 1 diabetes (T1D) who were using insulin (either pump therapy or multiple daily injections [MDI]) and currently used Loop or had plans to begin using Loop for insulin delivery.

Participant baseline data were collected on web-based data collection forms including demographic information, glycemic information (via continuous glucose monitoring data, if available), and quality of life/psychosocial and treatment satisfaction surveys. During the study,

K203689 - Page 6 of 13

{6}

CGM and insulin dosing data were collected continuously and uploaded automatically from the Tidepool Mobile app on a user's own iPhone to the Tidepool cloud, from which it was retrieved by the study coordinating center.

Participants completed weekly web-based surveys about Adverse Events (severe hypoglycemia, DKA, hospitalization) and device issues. Participants were followed for up to 12 months, with updates obtained after 3, 6, and 12 months that included web-based surveys on patient-reported outcomes and psychosocial/quality-of-life aspects related to Loop use. Focus groups were also completed.

| Study Feature | Description |
| --- | --- |
| Title | An Observational Study of Individuals with Type 1 Diabetes Using the Loop System for Automated Insulin Delivery: The Loop Observational Study (LOS) |
| Objectives | To collect data on the efficacy, safety, usability, and quality of life/psychosocial effects of the Loop System. |
| Sample Size | Up to 1250* |
| Treatment Groups | Users new to Loop (cohort A) and existing users (cohort B) |
| Study Duration | Up to 12 months of Loop use, with 3-month, 6-month, and 9-month assessments |

* This is a real-world evidence-based data collection and some subjects were lost to follow-up.

# Baseline Demographics

The observational study included participants that are not part of the intended user population (i.e. $\geq 6$ years old, using Humalog or Novolog insulin only, and making use of the Tidepool Loop guardrails (Correction Range $87 - 180\mathrm{mg / dL}$ and Glucose Safety Limit $67 - 110\mathrm{mg / dL}$ ). Cohort A and Cohort B included participants who used settings that are outside of the final Tidepool Loop setting ranges. The table below summarizes these different populations. Due to the observational nature of the study and rolling enrollment, not all participants were eligible to meet the 9-month and/or 12-month follow-ups.

| | Study population not limited to intended user population | | Study population limited to intended user population(Ages 6 and up, settings within allowable Tidepool Loop ranges for at least 90% of the time during study follow-up) |
| --- | --- | --- | --- |
| | New Users(Cohort A) | Existing Users(Cohort B) | |
| N | 606 | 266 | 175 |
| Age, median years (range) | 16 (1-72) | 34 (13-76) | 23 (6-71) |
| Sex, % female | 56 | 52 | 56 |
| Race | 91% White, 4%Hispanic/Latinx, 2% Multiracial, 2% Asian, <1%Black | 94% White, 2%Hispanic/Latinx, 2% Asian, 1%Multiracial, <1%Black | 91% White, 5%Hispanic/Latinx, 2%Multiracial, 1% Asian, <1%Black |

K203689 - Page 7 of 13

{7}

| | Study population not limited to intended user population | | Study population limited to intended user population (Ages 6 and up, settings within allowable Tidepool Loop ranges for at least 90% of the time during study follow-up) |
| --- | --- | --- | --- |
| | New Users (Cohort A) | Existing Users (Cohort B) | |
| Education, % bachelor’s degree or beyond | 85 | 89 | 88 |
| Household Income, % > $100,000 | 71 | 78 | 68 |

# Primary Study Safety Results

The Loop Observational Study did not exclude subjects with a prior history of severe hypoglycemia (SH) or diabetic ketoacidosis (DKA). The majority of severe adverse events observed during the study were experienced by the minority of participants who also had at least one severe hypoglycemic event in the three months before using DIY Loop. The tables below summarize the incidence of severe hypoglycemic events at baseline (i.e., at enrollment) and follow-up by age group in the intended use population.

Severe Hypoglycemia (SH) for Participants in Intended Use Population

| | Overall | 6-13 Years | 14-17 Years | ≥18 years |
| --- | --- | --- | --- | --- |
| Overall | N=175 | N=76 | N=19 | N=80 |
| SH (Baseline – 6 months) | | | | |
| Total # of events | 23.00 | 11.00 | 5.00 | 7.00 |
| # Events per participant | | | | |
| 0 | 161 (92%) | 69 (91%) | 17 (89%) | 75 (94%) |
| 1 | 6 (3%) | 3 (4%) | 0 (0%) | 3 (4%) |
| 2 | 7 (4%) | 4 (5%) | 1 (5%) | 2 (3%) |
| ≥3 | 1 (<1%) | 0 (0%) | 1 (5%) | 0 (0%) |
| Incidence rate (per 100 person-years) | 42.3 | 44.7 | 88.8 | 29.0 |
| SH (3 months Prior to Enrollment) | | | | |
| Total # of events | 84 | 50 | 2 | 32 |
| # Events per participant | | | | |
| 0 | 149 (85%) | 63 (83%) | 17 (89%) | 69 (86%) |
| 1 | 12 (7%) | 6 (8%) | 2 (11%) | 4 (5%) |
| 2 | 4 (2%) | 1 (1%) | 0 (0%) | 3 (4%) |
| ≥3 | 10 (6%) | 6 (8%) | 0 (0%) | 4 (5%) |
| Incidence rate (per 100 person-years) | 192.0 | 263.2 | 42.1 | 160.0 |
| Participants with 0 Events in the 3 Months Prior to Enrollment | N=149 | N=63 | N=17 | N=69 |

K203689 - Page 8 of 13

{8}

K203689 - Page 9 of 13

| SH (Baseline – 6 months) | | | | |
| --- | --- | --- | --- | --- |
| Total # of events | 10 | 5 | 3 | 2 |
| # Events per participant | | | | |
| 0 | 143 (96%) | 60 (95%) | 16 (94%) | 67 (97%) |
| 1 | 3 (2%) | 1 (2%) | 0 (0%) | 2 (3%) |
| 2 | 2 (1%) | 2 (3%) | 0 (0%) | 0 (0%) |
| ≥3 | 1 (<1%) | 0 (0%) | 1 (6%) | 0 (0%) |
| Incidence rate (per 100 person-years) | 21.7 | 23.9 | 63.6 | 9.8 |
| Participants with ≥1 Event in the 3 Months Prior to Enrollment | N=26 | N=13 | N=2 | N=11 |
| SH (Baseline – 6 months) | | | | |
| Total # of events | 13 | 6 | 2 | 5 |
| # Events per participant | | | | |
| 0 | 18 (69%) | 9 (69%) | 1 (50%) | 8 (73%) |
| 1 | 3 (12%) | 2 (15%) | 0 (0%) | 1 (9%) |
| 2 | 5 (19%) | 2 (15%) | 1 (50%) | 2 (18%) |
| ≥3 | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Incidence rate (per 100 person-years) | 154.7 | 163.9 | 218.3 | 130.6 |

## Primary Study Observed Results

The data below describe how the device performed during the observational study.

Overall Glycemic Outcomes During First 6 months of Follow-Up

| | Cohort A | | Cohort B | |
| --- | --- | --- | --- | --- |
| | Baseline | First 6 months¹ | Baseline | First 6 months¹ |
| # Participants² | 418 | 543 | 169 | 207 |
| % Time in Range (70-180 mg/dL), Mean ± SD | 67 ± 16 | 73 ± 13 | 78 ± 11 | 79 ± 11 |
| % Time > 180 mg/dL, Mean ± SD | 29 ± 17 | 24 ± 14 | 19 ± 13 | 18 ± 12 |
| Mean Glucose (mg/dL), Mean ± SD | 156 ± 30 | 147 ± 12 | 139 ± 22 | 137 ± 21 |
| % Time <70 mg/dL, Median (Quartiles) | 2.9 (1.2, 5.1) | 2.8 (1.3, 4.6) | 2.6 (1.4, 4.6) | 2.7 (1.5, 5.4) |
| % Time <54 mg/dL, Median (Quartiles) | 0.40 (0.12, 0.95) | 0.36 (0.14, 0.79) | 0.34 (0.15, 0.72) | 0.36 (0.15, 0.78) |
| # of participants with HbA1c near timepoint | 387 | 386 | 106 | 122 |
| HbA1c (%), Mean ± SD³ | 6.8 ± 1.0 | 6.6 ± 0.8 | 6.3 ± 0.7 | 6.3 ± 0.7 |

{9}

First 6 month metrics are calculated based on data obtained from the date of the first Loop record to 182 days since first Loop record
2Participants must have had at least 7 days of CGM data available at baseline and at least 14 days of CGM data during months 1-6 to be included in the analyses
3 This is a real-world evidence-based data collection and HbA1c results were self-reported.

Overall Glycemic Outcomes for Intended Use Population During First 6 Months of Follow-Up

| | Baseline | First 6 months |
| --- | --- | --- |
| # of Participants | 128 | 171 |
| % Time in Range (70-180 mg/dL), Mean ± SD | 62 ± 15 | 70 ± 13 |
| % Time > 180 mg/dL, Mean ± SD | 35 ± 16 | 27 ± 13 |
| Mean Glucose (mg/dL), Mean ± SD | 166 ± 29 | 153 ± 22 |
| % Time <70 mg/dL, Median (Quartiles) | 1.8 (0.8, 3.8) | 1.9 (0.9, 3.5) |
| % Time <54 mg/dL, Median (Quartiles) | 0.23 (0.07, 0.66) | 0.23 (0.09, 0.54) |
| # of participants with HbA1c near timepoint | 125 | 136 |
| HbA1c (%),Mean ± SD | 7.1 ± 0.9 | 6.7 ± 0.8 |

Glycemic Outcomes for Intended Use Population During First 6 Months of Follow-Up, Separated by Age

| | Age 6-13 | | Age 14-17 | | Age 18+ | |
| --- | --- | --- | --- | --- | --- | --- |
| | Baseline | First 6 months | Baseline | First 6 months | Baseline | First 6 months |
| # of Participants | 58 | 75 | 14 | 18 | 56 | 78 |
| % Time in Range (70-180 mg/dL), Mean ± SD | 60 ± 12 | 68 ± 11 | 58 ± 17 | 63 ± 14 | 65 ± 18 | 75 ± 13 |
| % Time > 180 mg/dL, Mean ± SD | 37 ± 13 | 29 ± 11 | 39 ± 18 | 35 ± 14 | 33 ± 19 | 23 ± 14 |
| Mean Glucose (mg/dL), Mean ± SD | 168 ± 20 | 155 ± 19 | 176 ± 45 | 167 ± 29 | 162 ± 31 | 148 ± 22 |
| % Time <70 mg/dL, Median (Quartiles) | 2.1 (1.1, 3.9) | 2.5 (1.2, 4.0) | 2.3 (1.3, 3.3) | 1.7 (0.6, 3.5) | 1.3 (0.8, 3.8) | 1.3 (0.7, 2.8) |
| % Time <54 mg/dL, Median (Quartiles) | 0.28 (0.09, 0.65) | 0.27 (0.14, 0.61) | 0.36 (0.18, 0.67) | 0.28 (0.13, 0.67) | 0.17 (0.04, 0.69) | 0.17 (0.07, 0.40) |
| # of participants with HbA1c near timepoint | 57 | 66 | 12 | 14 | 56 | 56 |
| HbA1c (%),Mean ± SD | 7.2 ± 0.6 | 6.8 ± 0.7 | 7.5 ± 1.3 | 7.3 ± 1.0 | 7.0 ± 1.0 | 6.5 ± 0.8 |

K203689 - Page 10 of 13

{10}

K203689 - Page 11 of 13

# Human Factors

Human factors validation tests were conducted with Tidepool Loop installed on an iPhone. A total of 9 formative studies were conducted; after each study, information was fed back into the design of the User Interface. The summative human factors validation study was performed on the final device design with fifty-one representative participants which included adults, and children with their caregivers. All study participants received training that was consistent with the training that patients would receive with the commercial product and interacted with the device in a simulated use environment. 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.

# User and Provider Training

Physician and user training as per the sponsor provided training materials is important to ensure safe use of the device. The sponsor provided training materials for healthcare providers who will prescribe this device and manage patients who use this device. The training covers how the device works, details of the clinical study, setting up the device, and information on how to assess patient results with the device.

A training plan for device users was also provided. The plan provides resources for various types of users including new pump users, users switching from a different pump, and users upgrading from a partner pump without Tidepool Loop to the same or similar partner ACE pump with Tidepool Loop. The training includes initial start-up, troubleshooting, maintenance, and management of the device. Training includes a follow-up 3-5 days after the initial training and subsequent communication with that person's healthcare provider to ensure ongoing follow-up care.

# Hazard Analysis:

A comprehensive hazard analysis was provided for this device, in which design inputs and outputs, risks, and risk mitigations for software and interoperable hardware components associated with the safe and effective functioning of the device were reviewed. The hazard analysis provided in this submission accounted for the unique design elements, intended use, and risks of the Tidepool Loop System design. In particular, this hazard analysis accounted for the risks associated with interoperability between the software device developed by the sponsor and commercial off-the-shelf (COTS) hardware device it was installed on, as well as with other third-party interoperable devices. This analysis identified hazards which could reasonably be anticipated to impact the proper use of the device, traced all identified risks to adequate design controls, and demonstrated that design features were appropriately implemented and validated.

# Data Logging

The sponsor provided software and bench testing to demonstrate that the device is able to record critical events, including information related to its state (e.g., commanded delivery rates/volumes, all algorithm calculations, open loop / closed loop mode, power on/off events), user inputs, and device settings. In addition, the sponsor detailed the specific information that they would collect from all interoperable components connected to the Tidepool Loop including the iCGM and ACE pump components and described how Tidepool Loop will collect data from those devices, how it stores that data, and how that data can be shared with the user, with Tidepool, and with health care practitioners and caregivers. All log entries are time stamped, and

{11}

the logs are either generated when the events occur or every five minutes in the case of recording algorithm calculations. These protocols were reviewed and found to be adequate.

## 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 for potential interoperable devices. Specifically, the sponsor has established plans for both proprietary and standards-based (leveraging relevant IEEE 11073 and Bluetooth SIG) plug-ins for interfacing with ACE pumps and iCGMs. Further, the sponsor has performed software and bench testing to verify and validate that these interface control specifications meet the special controls and their controller’s requirements for performance, communications, and data logging. 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 approach was determined to acceptably align with FDA-recognized ANSI/AAMI/UL 2800-1:2019 Standard for Safety for Medical Device Interoperability.

The sponsor additionally provided 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 executed in the comprehensive software testing performed by the sponsor which included software test suites, hardware emulators, hardware prototype testing, and software integration testing.

By design, Tidepool Loop can only be used with compatible iCGM and ACE Pump devices with which it has been validated for use. Tidepool Loop will not allow use of an unvalidated ACE pump or iCGM. There are controls within the software to prevent use of Tidepool Loop in these cases. To support the future integration of compatible ACE pumps and iCGMs with Tidepool Loop, the sponsor also provided protocols (SOP-0016, “Tidepool Loop Connected Device Integration and Validation Process and Plan,” and SOP-0018, “Tidepool Loop Regulatory Determination Process”) outlining their validation strategy for determining compatibility of new devices with the Tidepool Loop. The protocols included pre-specified procedures, validation strategies, and acceptance criteria for software, cybersecurity, device interoperability, human factors, labeling, and training materials, with the anticipated features and specifications of ACE pumps and iCGMs as these are anticipated changes foreseen at the time of the submission. These protocols, along with the software testing conducted on software test suites, hardware simulators and hardware emulators, were found to be adequate to support the robustness of the sponsor’s software test protocols to validate future integration of digitally connected devices that meet the pre-specified specifications and acceptance criteria. Tidepool Loop must not be distributed until the pre-specified acceptance criteria in the SOPs are met. FDA has determined that when a modification is made in accordance with SOP-0016, “Tidepool Loop Connected Device Integration and Validation Process and Plan,” and SOP-0018, “Tidepool Loop Regulatory Determination Process” and validation strategy described in this 510(k), then the modification would not significantly affect safety or effectiveness of the device and no new 510(k) would be required. Changes made that are inconsistent with the modifications described in SOP-0016 and SOP-0018 that were reviewed in this submission could be significant modifications that could

K203689 - Page 12 of 13

{12}

significantly affect the safety and/or effectiveness of this device (e.g., such changes could compromise the clinical functionality or performance specifications that are directly associated with the intended use of the device), in which case a new premarket submission would be required (see 21 CFR 807.81(a)(3)).

## Cybersecurity

Detailed information on cybersecurity of the device was reviewed and found to be acceptable. The sponsor provided detailed information relating to the penetration testing conducted as part of their cybersecurity evaluation. The sponsor provided a software bill of materials, which provided details on all software used in the device and the COTS hardware platform that the Software-as-a-Medical-device (SAMD) was installed on. This included all manufacturer-developed, commercially licensed, open source, partner 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.

## 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, the study included mostly white device users with relatively high levels of education and income relative to the general use population, and it was not adequately powered to assess differences in the rates of safety events (e.g., diabetic ketoacidosis and severe hypoglycemia). Furthermore, adolescents were underrepresented in the study. 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.

K203689 - Page 13 of 13