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 Description

Tidepool Loop is a mobile application with algorithm technology that works to control an ACE (Alternate Controller Enabled) insulin pump to automatically increase, and suspend delivery of basal insulin based on readings from an iCGM (integrated continuous glucose monitor) and glucose values predicted by Tidepool Loop. Tidepool Loop 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 predicts glucose levels up to 6 hours in the approximate duration of insulin action for U-100 rapid-acting insulin) based on prior iCGM readings, insulin delivery history, and user input (e.g., carbohydrate intake and exercise, and in some cases fingerstick glucose) and uses that prediction to adjust insulin delivery. 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 Tidepool Loop Bolus Recommendation Tool (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. When closed-loop mode is off, such as when it is manually disabled or when there is no active iCGM sensor session, the Tidepool Loop Bolus Recommendation Tool (TLBRT) is disabled. The user will use Tidepool Loop's simple bolus calculator. into which iCGM values are not automatically populated into the glucose field.

Users must manually enter information about carbohydrates to initiate a meal bolus. When closed-loop mode is on, recommended bolus delivery is calculated using the Tidepool Loop Bolus Recommendation Tool (TLBRT) and can be manually adjusted.

The Tidepool Loop app requires that specific, initial therapy settings are established by a health care provider as part of creating the prescription order. These settings include:

Target Correction Ranges for normal operation, Pre-Meal and Workout Presets .
Carb to Insulin Ratios .
Insulin Sensitivity Factors ●
Basal Rates ●
Max Basal Rate ●
Max Bolus .

Tidepool Loop uses two glucose-specific settings that may be different from the user's experience with traditional glucose monitoring or CGM therapy. These are Correction Range and Glucose Safety Limit.

Correction Range is the range of glucose values that the user wants Tidepool Loop to work to bring their glucose to. Correction Range can be set as low as 87 mg/dL and as high as 180 mg/dL. Tidepool Loop will warn the user if values outside the recommended bounds of 100-115 mg/dL are selected. The user can add different Correction Ranges for different times of day. Tidepool Loop supports up to 48 Correction Range segments in a 24-hour period.

Tidepool Loop allows these user-customizable target Correction Ranges:

. Normal operation
Pre-meal Preset
. Workout Preset

Glucose Safety Limit (mg/dL) is a safety feature of the Tidepool Loop algorithm. If the current CGM value or any future predicted glucose value is below this safety limit. Tidepool Loop will suspend insulin delivery in an effort to prevent low glucose. The algorithm will also not recommend a bolus.

Glucose Safety Limit can be set as low as 67 mg/dL. It can be set as high as 110 mg/dL or to the Correction Range minimum, whichever qlucose value is lower. Tidepool Loop will warn the user if values outside Tidepool's recommended bounds of 74 to 80 mg/dL are selected.

The Glucose Safety Limit is also part of the Dosing Safety Threshold, which is part of the Tidepool Loop insulin delivery algorithm. The Dosing Safety Threshold is a period of time that has the same duration as the insulin activity duration (i.e., 6 hours). The Dosing Safety Threshold is equal to the user's Glucose Safety Limit for the first half of the insulin activity duration (i.e., 3 hours), and then increases until it is at the midpoint of the Correction Range at the end of the insulin activity duration (i.e., 6 hours).

Tidepool Loop is designed to be installed on an iPhone running iOS operating systems (version 15 or higher). The Tidepool Loop application includes an optional extension for Apple Watch devices running watchOS operating system (version 6.1 or higher).

AI/ML Overview

The provided text describes the acceptance criteria and the study that proves the Tidepool Loop device meets these criteria. The device is an Interoperable Automated Glycemic Controller (iAGC) intended for the management of type 1 diabetes mellitus.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly present a formal "acceptance criteria" table with corresponding "reported device performance" values in a single, consolidated format. However, the outcomes of the clinical study, particularly for the 'intended user population', implicitly serve as the performance demonstration against the safety and effectiveness expectations.

Based on the "Summary Diabetes Outcomes" and "Summary Safety Outcomes" for the "Study population limited to intended user population" (Page 19), and further elaborated in the "Results (Intended User Population)" section (Page 22), we can construct the following:

Performance Metric (Implicit Acceptance Criteria)	Reported Device Performance (Intended User Population)
Safety Outcomes
Incidence of Severe Hypoglycemia (SH)	Reduced from 192.0 events per 100 person-years (pre-Loop) to 42.3 events per 100 person-years (during Loop use).
Percentage of participants with no SH	92% from baseline-6 months
SH events adjudicated "related to Loop"	1 SH event (out of 23)
Incidence of SH resulting in seizure/loss of consciousness	0 events per 100 person-years
Incidence of Diabetic Ketoacidosis (DKA)	0.0 events per 100 person-years
Glycemic Outcomes (Effectiveness)
Mean Time in Range (TIR) (70-180 mg/dL)	Improved from 62% (baseline) to 70% (1-6 months of use)
Mean Time <54 mg/dL	Low at baseline (0.23%) and largely unchanged during study (0.23% at 6 months)
Mean Time <70 mg/dL	Low at baseline (1.8%) and largely unchanged during study (1.9% at 6 months)
Mean HbA1c	Improved from 7.1% (baseline) to 6.7% (6 months)
Patient Reported Outcomes (Quality of Life/Psychosocial)
INSPIRE composite scores	4.3 and higher out of 5.0 (highly positive)
Recommendation likelihood	75% "very likely" to recommend Loop to others

2. Sample Size Used for the Test Set and Data Provenance

The "test set" for the clinical performance evaluation was derived from an observational study of the "do-it-yourself (DIY) Loop system," which Tidepool Loop is based on.

Total Participants Enrolled: 1,127
Participants Initiating Study: 872 (606 in Cohort A - new users, 266 in Cohort B - existing users)
Sample Size for Intended User Population (Primary Analysis Set): 175 participants (This subset met the criteria of being ≥6 years old, using Humalog or Novolog insulin only, and making use of the Tidepool Loop guardrails at least 90% of the time).
Data Provenance:
- Country of Origin: Not explicitly stated, but the study was conducted by the Jaeb Center for Health Research (a US-based entity) and involved the "DIY Loop system" which has a global user base. Given the context of FDA submission, the data is likely predominantly from the United States or a multinational study supporting US regulatory needs.
- Retrospective or Prospective: The study was an observational, single-arm study that collected data prospectively after enrollment. Weekly web-based surveys were used for Adverse Events, and CGM/insulin dosing data was collected continuously and uploaded automatically. Historical data (e.g., pre-Loop SH events) were also collected as baseline.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not describe the establishment of a "ground truth" for the test set in the traditional sense of expert radiologists annotating images. Instead, for clinical outcomes:

Safety Adjudication: Severe Hypoglycemia (SH) events were adjudicated.
- Number of Experts: Events were reviewed "both by the Jaeb Center for Health Research and by Tidepool staff, including review with Tidepool's Chief Medical Advisor." This implies at least two entities/individuals, with the Chief Medical Advisor being a qualified medical expert. Specific number beyond this is not provided.
- Qualifications of Experts: The Chief Medical Advisor is a medical expert. The Jaeb Center for Health Research is a reputable clinical research organization focused on diabetes, implying their staff involved in adjudication would have relevant clinical expertise. Specific individual qualifications (e.g., "radiologist with 10 years of experience") are not provided as this is not an imaging study.

4. Adjudication Method for the Test Set

Method: For Severe Hypoglycemia events, the review was performed "both by the Jaeb Center for Health Research and by Tidepool staff, including review with Tidepool's Chief Medical Advisor." This indicates a consensus-based review. The phrasing "adjudicated as 'Related to Loop'" suggests a systematic process for attributing events. It's not a typical "2+1" or "3+1" for initial findings, but rather an expert review of reported events for causality.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This describes a clinical trial design relevant to diagnostic imaging interpretation studies, where different readers interpret cases with and without AI assistance. The Tidepool Loop study is a clinical observational study of an automated insulin delivery system, not an imaging device.
Effect size of human readers improving with AI vs without AI assistance: Not applicable as this was not an MRMC study and the device does not assist human interpretation of diagnostic images. The study rather focused on how the automated system (Tidepool Loop / DIY Loop) directly impacts glycemic control and safety in real patients. The improved glycemic outcomes (TIR, HbA1c) and reduced incidence of severe hypoglycemia demonstrate the direct therapeutic effect of the AI algorithm.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, in essence. The "Tidepool Loop" product is an "Interoperable Automated Glycemic Controller (iAGC)" which runs an algorithm to automatically adjust basal insulin delivery and recommend boluses. While the user confirms boluses, the core automated function (basal adjustment) is algorithm-driven.
Clinical Study Design: The clinical study evaluated the "DIY Loop" system, which is based on the same algorithm as Tidepool Loop, in "real-world, unsupervised, patient-driven use." This implies the study assessed the performance of the algorithm in situ as it was used by patients, with its automated functions and interactions. The primary glycemic and safety outcomes (TIR, HbA1c, SH, DKA) were derived directly from the overall system's performance, which is predominantly driven by the algorithm.

7. The Type of Ground Truth Used

Clinical Outcomes / Patient Reported Data / Expert Adjudication: The "ground truth" for this device's performance was established through:
- Clinical Measurements: HbA1c (blood samples) and Continuous Glucose Monitoring (CGM) data.
- Patient-Reported Outcomes: Weekly web-based surveys for adverse events (severe hypoglycemia, DKA, hospitalization) and device issues. Psychosocial/quality of life aspects were collected via validated questionnaires (e.g., INSPIRE).
- Expert Consensus/Review: Adjudication of Severe Hypoglycemia events as described in point 4.

8. The Sample Size for the Training Set

The document does not provide information on the training set or its size for the Tidepool Loop algorithm. The clinical study described is a validation study for regulatory submission, assessing the performance of an already developed algorithm (modeled on DIY Loop) in a real-world setting. Training data for such algorithms are typically much larger and often proprietary to the developer.

9. How the Ground Truth for the Training Set Was Established

Since information on the training set is not provided, how its ground truth was established is also not detailed in this document. Given it's a medical device algorithm, training data would likely involve large datasets of CGM readings, insulin delivery, meal data, and corresponding verified glucose outcomes, potentially derived from clinical studies or real-world usage data with rigorous data curation and annotation.

Summary

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Image /page/0/Picture/0 description: The image shows the logo for the U.S. Food & Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the FDA name on the right. The symbol is a stylized representation of a human figure, while the FDA name is written in blue and includes the words "U.S. Food & Drug Administration".

January 23, 2023

Tidepool Project Howard Look CEO 3340 Hillview Ave Palo Alto, California 94304

Re: K203689

Trade/Device Name: Tidepool Loop Regulation Number: 21 CFR 862.1356 Regulation Name: Interoperable Automated Glycemic Controller Regulatory Class: Class II Product Code: QJI Dated: May 26, 2022 Received: May 26, 2022

Dear Howard Look:

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.

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FDA's substantial equivalence determination also included the review of your specific procedures, validation strategies, and pre-specified acceptance criteria for software, cybersecurity, device interoperability, human factors, labeling, and training materials for modifications as described in SOP-0016, "Tidepool Loop Connected Device Integration and Validation Process and Plan," and SOP-0018, "Tidepool Loop Regulatory Determination Process." Under 21 CFR 807.81(a)(3), a new premarket submission is required if there is a major change or modification in the intended use of a device, or if there is a change or modification in a device that could significantly affect the safety or effectiveness of the device, e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process. Changes made that are inconsistent with the modifications described in SOP-0016 and SOP-0018 that were reviewed in this submission could be significations that could 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)). Additional information about changes to software that may require a new premarket submission is provided in FDA's guidance, Deciding When to Submit a 510(k) for a Change to an Existing Device, and Deciding When to Submit a 510(k) for a Software Change to an Existing Device.

Failure to submit a new premarket submission for the changes described above would constitute adulteration and misbranding under sections 501(t)(1)(B) and 502(0) of the Act, respectively. Your device is also subject to, among other requirements, the quality systems (QS) regulation (21 CFR 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 820.90 Nonconforming product; and 820.100 Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 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 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 mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn

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(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.

Marianela Perez-torres -S

Marianela Perez-Torres, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known) K203689

Device Name

Tidepool Loop

Indications for Use (Describe)

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.

Type of Use (Select one or both, as applicable)
-------------------------------------------------

☒ Prescription Use (Part 21 CER 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

I. Sponsor Information:

Sponsor:	Mailing address:Tidepool Project555 Bryant St. #429Palo Alto CA 94301Registration facility address:Tidepool Project3340 Hillview Ave.Palo Alto, CA 94304
Contact Person:	Howard Look, CEO
Email:	regulatory@tidepool.org
Phone:	650-353-2352

II. Device Name

Device Classification Name:	Interoperable Automated Glycemic Controller (iAGC)
Device Classification	Class II, 21 CFR 862.1356
Product Code:	QJI
Device Proprietary Name:	Tidepool Loop

III. Predicate Device Information

Device Name	Control – IQ Technology
Manufacturer:	Tandem Diabetes Care, Inc.
Premarket Notification #:	K200467
Classification Name:	Interoperable Automated Glycemic Controller (iAGC)
Classification:	Class II, 21 CFR 862.1356
Product Code:	QJI

IV. Date Summary Prepared: January 23, 2023

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V. Description of Device

The Tidepool Loop app requires that specific, initial therapy settings are established by a health care provider as part of creating the prescription order. These settings include:

Target Correction Ranges for normal operation, Pre-Meal and Workout Presets .
Carb to Insulin Ratios .
Insulin Sensitivity Factors ●
Basal Rates ●
Max Basal Rate ●
Max Bolus .

Tidepool Loop Traditional 510(k) Premarket Notification, K203689 January 23, 2023

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Tidepool Loop allows these user-customizable target Correction Ranges:

. Normal operation
Pre-meal Preset
. Workout Preset

Image /page/6/Figure/7 description: The image shows the Tidepool Loop Algorithm 1.0.0. The algorithm is based on therapy settings, glucose momentum and recent history, carbohydrates, and insulin. The graph shows glucose levels over time, with the x-axis representing time and the y-axis representing glucose levels in mg/dL. The graph includes a target range, a glucose safety limit, and the duration of insulin action.

Principle of Operation of Tidepool Loop Algorithm

Tidepool Loop Traditional 510(k) Premarket Notification, K203689 January 23, 2023

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VI. Indications for Use

Tidepool Loop, a mobile application with alqorithm technology, is intended for use with compatible integrated continuous dlucose monitors (iCGM) and alternate controller enabled (ACE) insulin infusion pumps to automatically increase, 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.

Contraindications

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 by anyone who is unwilling or unable to follow the . instructions for use and intended uses of compatible insulin pumps and continuous glucose monitor devices.
MR Unsafe - Tidepool Loop should not be used during Maqnetic 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.

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VII. Comparison to Predicate Device

Tidepool Loop is substantially equivalent to the predicate device, Control-IQ Technology, currently legally marketed under K200467.

Tidepool Loop and Control-IQ are similar in that they have:

the same general intended use, ●
the same indications for use, .
the same or similar technological characteristics, .
the same principle of operation. .

The devices primarily differ in that:

Control-IQ currently operates only on Tandem's t:slim X2 insulin pump, while Tidepool . Loop operates on iPhone devices;
Control-IQ automatically delivers correction boluses, while Tidepool Loop only . recommends correction boluses if a user elects to open the Bolus Entry screen:
. Tidepool Loop predicts glucose values farther into the future than Control-IQ;
. Tidepool Loop allows for more user-configurable correction ranges and other settings than Control-IQ.

Specific differences between Tidepool Loop and its predicate device are detailed in the table below.

Comparison Table, Tidepool Loop vs. Tandem Control-IQ

Characteristic	Control-IQ Technology (K200467)	Tidepool Loop(this submission, K203689)
Regulatory Information
Product Code	QJI	QJI
Regulation Name	21 CFR 862.1356, InteroperableAutomated Glycemic Controller	21 CFR 862.1356,Interoperable Automated GlycemicController
Indications for Use, User Population
Indication ForUse	Control-IQ technology is intended foruse with compatible integratedcontinuous glucose monitors (ICGM)and alternate 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 the	Tidepool Loop is a mobile applicationand algorithm technology that isintended for use with compatibleintegrated continuous glucose monitors(iCGM) and alternate controller enabled(ACE) pumps to automatically increase,decrease, and suspend delivery of basalinsulin based on iCGM readings andpredicted glucose values. It can also
	glucose value is predicted to exceed apredefined threshold.Control-IQ technology is intended forthe management of Type 1 diabetesmellitus in persons 6 years of age andgreater.Control-IQ technology is intended forsingle patient use and requires aprescription.Control-IQ technology is indicated foruse with NovoLog or Humalog U-100insulin.	recommend and deliver correctionboluses when glucose values arepredicted to exceed user configurablethresholds.Tidepool Loop is intended for themanagement of Type 1 diabetes mellitusin persons six years of age and greater.Tidepool Loop is intended for singlepatient use.Tidepool Loop is Rx - For Prescription UseOnly.
Target PatientPopulation	Type 1 diabetes mellitus in persons sixyears of age and greater.	Type 1 diabetes mellitus in persons sixyears of age and greater.
PrincipalOperator	Prescription only device with the patientor caregiver as the principal operator	Prescription only device with the patient orcaregiver as the principal operator
Use Location	At home	At home
Number of Users	Single user only	Single user only
Technological Characteristics
Principle ofOperation	Control-IQ technology predicts glucoselevels 30 minutes in the future basedon prior iCGM readings, insulin deliveryhistory, and user input (e.g.,carbohydrate intake, exercise, andsleep schedule ) and uses thatprediction to adjust insulin delivery.Control-IQ technology can be used toadjust or suspend basal insulin deliveryevery 5 minutes and automaticallydeliver correction boluses of insulinbased on actual and predicted CGMsensor readings.Users must manually deliver mealboluses they can calculate using theintegrated bolus calculator and canmanually adjust insulin delivery (changebasal rates and deliver insulin boluses)	Tidepool Loop predicts glucose levels upto 6 hours in the future (theapproximate duration of insulin actionfor U-100 rapid-acting insulin) based onprior iCGM readings, insulin deliveryhistory, and user input (e.g., carbohydrateintake and exercise) and uses thatprediction to adjust insulin delivery.Tidepool Loop can be used to adjust orsuspend basal insulin delivery every 5minutes and deliver correction boluses ofinsulin based on actual and predictedCGM sensor readings.Users must manually deliver meal bolusesthey can calculate using the TidepoolLoop Bolus Recommendation Tool(TLBRT) and can manually adjust insulindelivery (change basal rates and deliver
	when the Control-IQ technology isactive		insulin boluses) when Tidepool Loop isactive.
Type of Algorithm	Hybrid Closed Loop - predictive control		Hybrid Closed Loop - predictive control
Compatible iCGM	Dexcom G6		Dexcom G6
Compatible ACEPump	Tandem X2 Pump		An ACE pump that has the specificationsand meets the pre-specified acceptancecriteria for software, cybersecurity, deviceinteroperability, human factors, labeling,and training materials as described inSOP-0016, "Tidepool Loop ConnectedDevice Integration and Validation Processand Plan," and SOP-0018, "Tidepool LoopRegulatory Determination Process."Tidepool Loop must not be distributed untilthe pre-specified acceptance criteria in theSOPs are met.
Device Design orMaterial	Control-IQ Technology is software in amedical (SiMD) device, installed on aTandem t:slim X2 pump		Tidepool Loop is a mobile applicationand a Software as Medical Device(SaMD) installed on a host mobiledevice
AlgorithmPlatform	Tandem X2 Pump		iPhone
User ExperiencePlatform	Tandem X2 Pump		iPhone and Apple Watch
InsulinCompatibility	Novolog or Humalog U-100		Same
Functional Characteristics
User-controlledTarget RangeSettings	Not customizable.Default: 112.5 - 160 mg/dLSleep Mode 112.5 - 120 mg/dLExercise Mode 140 - 160 mg/dL		Customizable settingsCorrection Range:87 - 180 mg/dLPre-Meal Range:Glucose Safety Limit (which can be setfrom 67-110 mg/dL) - 130 mg/dLWorkout Range:
		the higher of 85 mg/dL or the GlucoseSafety Limit (which can be set from67-110 mg/dL) - 250 mg/dL
Auto-populatingbolusrecommendationbased on iCGMvalue:
In closed loopmodeIn open loopmode	YesNo	YesNo
Data List &Logging	Yes	Yes
Daily ActivityRecords	Yes	Yes
Average DataDisplay	Yes	Yes
Changing PumpSettings	Yes	Yes
Invite others toview datathroughauthorization	Yes	Yes
Passwordrequired	Yes	Yes
Performance Characteristics
BenchPerformance	Control-IQ performance was verifiedand validated through softwareverification testing including specialcontrols, cybersecurity, wireless, andconnected devices compatibility testing.	Tidepool Loop performance was verifiedand validated through software verificationtesting including special controls,cybersecurity, wireless, and connecteddevices compatibility testing.
ClinicalPerformance	Control-IQ clinical performance wassupported by1) 168 participants in a 6-monthrandomized trial, with 112 in theintervention arm and 56 in the controlarm.2) 101 pediatric participants in a4-month randomized trial, with 78 in the	Tidepool Loop clinical performance issupported by representative 1,250participants in a 15 months durationreal-world, observational, single armstudy of DIY Loop including bothpediatric and adult participants.
	intervention arm and 23 in the control arm.
PatientPreference	Control-IQ assessed PatientPreferences through written statementsand also obtained through discussionwith patients and patient advocacygroups at public forums regardingpatient experiences with automatedinsulin dosing systems and digitallyconnected diabetes devices.	Tidepool Loop assessed PatientPreference through written or videotestimonials.
RiskAssessment	Control-IQ performed Risk Assessmentincluding detailed hazard analysisbased on ISO 14971.	Tidepool Loop performed RiskAssessment including detailed hazardanalysis based on ISO 14971.
Labeling
Training	Control-IQ provides mandatory usertraining before the user can use theirdevice.	Tidepool Loop includes mandatory in-applearning and setup (user training) beforethe user can use Tidepool Loop.
User Guide	Control-IQ electronic User Guideincludes all special controls, clinicalperformance information and otherinformation needed per cybersecurityand interoperability requirements.	Tidepool Loop electronic User Guide alsoincludes all special controls, clinicalperformance information and otherinformation needed per cybersecurity andinteroperability requirements.

Differences with the predicate device are shown in bold italic.

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VIII. Standards Compliance

Tidepool Loop complies with the following standards as documented in the applicable test reports provided in this 510(k) submission:

Special controls established under 21 CFR 862.1356. ●
. ISO 14971:2019: Medical Devices - Application of Risk Management to Medical Devices FDA Recognition No: 5-125
ANSI/AAMI/IEC 62366-1:2015: Medical Devices - Part 1: Application Of Usability Engineering To Medical Devices, FDA Recognition No: 5-114
ANSI/AAMI/IEC HE75:2009: Human factors engineering, design of medical ● devices FDA Recognition No:5-57
IEEE 802.15.1-2005, IEEE Standard for Information technology-- Local and . metropolitan area networks-- Specific requirements-- Part 15.1a: Wireless Medium Access Control (MAC) and Physical Layer (PHY) specifications for Wireless Personal Area Networks (WPAN)
Bluetooth Core Specification (Bluetooth SIG) .

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. ISO/IEEE 11073, Health informatics - Medical / health device communication standards
ANSI IEEE C63.27, American National Standard For Evaluation Of Wireless Coexistence
AAMI TIR69, Risk Management Of Radio-Frequency Wireless Coexistence For ● Medical Devices And Systems

In addition, the following standard was used in the design and development of Tidepool Loop:

ANSI/AAMI/UL 2800-1: 2019, Standard for Safety for Medical Device Interoperability, . FDA Recognition No: 13-109

IX. Non-Clinical Performance Testing

The information presented in this 510(k) submission demonstrates the safety and effectiveness of Tidepool Loop with compatible ACE pump and iCGM devices. Non-clinical performance testing included the following:

Risk Management: Risk management was performed and documented in accordance with ISO 14971:2019. 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 iAGC. In particular, this hazard analysis accounted for the risks associated with interoperability between the software device and the third-party digital devices it communicates with which met predefined criteria. 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.
Human Factors Validation: A human factors (HF) validation study was conducted in accordance with ANSI/AAMI/IEC 62366-1:2015 and ANSI/AAMI/IEC HE75:2009. The study was conducted to confirm that intended users can safely and effectively use the Tidepool Loop Mobile Application. The final device design was evaluated in a summative study performed with 51 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 including those tasks that involved information from a connected device with representative interoperable technology. Results of the study demonstrated that the device could be used safely by intended users in the intended use environment.
. Patient Perspective Data: Patient Perspective data collected by Tidepool included summarized information provided by the patients in written statements and also obtained through discussion with patients and patient advocacy groups at public forums regarding

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patient experiences with Tidepool Loop and digitally connected diabetes devices. Patients value that Tidepool Loop will allow them, in conjunction with their healthcare providers, to have more choice in the automated insulin dosing alqorithm that integrates with other elements of their diabetes management strategy and works best for their body and their care.

Software Verification and Validation: Software verification and validation testing was performed in accordance with IEC 62304:2014 and with FDA guidance, General Principles of Software Validation, issued January 11, 2002. Software testing focused on the iAGC functionality described by the iAGC special controls as defined at 21 CFR 862.1356 including interaction with iCGM and ACE insulin pump devices. Tidepool Loop was installed on compatible iPhone devices (black box testing), and was also tested extensively using automated simulation and emulation environments (white box automated testing). Testing was also performed to ensure that Tidepool Loop's functions through compatible host devices incorporating wireless technologies IEEE 802.15 (Bluetooth) and IEEE 802.11 (WiFi) performed as designed and intended.
Given the modular nature of iAGC. ACE pumps, and iCGM devices, Tidepool isolated the implementation of an ACE pump or iCGM from the iAGC implementation using a plug-in model. This allowed Tidepool to verify the iAGC functionality of Tidepool Loop independent of a specific connected diabetes device. Therefore, the approach to verification was divided into two stages for each interoperable device type as shown in the figure below, a Generic Test Plan and Specific Test Plan(s).

Image /page/14/Figure/3 description: The image shows a diagram of the Tidepool Loop App (iAGC) and its verification and validation process. The app interacts with iCGM and ACE Pump, each having specific test plans. Generic test plans are also in place, and the diagram indicates that the Tidepool Backend is an unregulated part of the system. The diagram also mentions 510(k), suggesting a regulatory aspect to the app's development or approval process.

Tidepool Loop Interoperability Verification Approach

A generic test plan for iCGM was defined and executed using a software simulator implementation of an iCGM. The simulator is a test fixture that enables the tester to generate different types of CGM data and error conditions without using a physical iCGM device. The iCGM simulator was used to verify the correct qlucose-related functionality of Tidepool Loop for the purposes of this submission. A plan for ensuring that connected devices meet Tidepool's specifications, and that appropriate risk management, verification, and validation activities for each connected iCGM device are conducted appropriately was provided.

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A generic test plan for ACE pumps was defined and executed using a software simulator that allowed the tester to manipulate the simulated pump state including initiating, suspending and resuming insulin delivery, adjusting reservoir levels and battery power, and triggering error conditions. A plan for ensuring that connected devices meet Tidepool's specifications, and that appropriate risk management, verification, and validation activities for each connected ACE pump device are conducted appropriately was provided.

Finally, Tidepool relied heavily on automated testing to catch errors and regressions. Automated tests are run with every software change and with every software build and include confirmation that hazard mitiqations were effectively implemented. Verification testing was comprised of the following:

Automated functional tests: These tests used simulated iCGM and ACE pump devices, as described above, on simulated iPhone devices. These tests were executed automatically and continuously every time Tidepool Loop was built from source code. The full suite of automated tests leverages multiple continuous integration and testing platforms, including CircleCl and Detox. At the time of this premarket submission, over 2,900 automated test cases covering varying aspects of every software build were conducted.
. Manual functional tests: These per-feature tests used real or simulated iCGM and ACE pump devices on a subset of supported iPhone devices and Apple Watch devices. These tests were developed and executed as part of the development of each feature.
Final manual functional test: This test included the overall iAGC functionality with . focus on the following areas:
- o Features that were identified by risk assessment as requiring mitigations to reduce risk to acceptable level .
- o User interface areas or features that cannot be adequately covered by automated tests due to complexity and/or time constraints
Data Logging: Software verification testing demonstrated that Tidepool Loop records ● timestamped critical events, including information related to its state, user inputs, and device settings, as required by the iAGC special controls.
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. The plan specified expectations, requirements, and interface specifications for potential interoperable devices. In addition, the plan covered Tidepool's 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). Validated software protocols were submitted, intended to ensure secure, accurate,

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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 documented testing of Tidepool Loop with a manufacturer-provided protype pump using IEEE 11073-10419 and Bluetooth SIG and a commercial, cleared iCGM with a manufacturer-provided SDK. Testing coverage is summarized in the table below.

Testing	Interoperability withACE Pump	Interoperability withiCGM	Tidepool Loop iAGC
Verification(benchtesting)	Tidepool-developedACE pump softwaresimulator.	Tidepool-developediCGM softwaresimulator.	Tidepool Loopsoftware verificationbench testing.
	Tidepool-developedPumpManager forIEEE 11073-10419and Bluetooth SIGcompliant insulinpump.	Manufacturer-providediCGM hardwareemulator board(proprietarycommunicationinterface).
	Manufacturer-providedpump hardware emulatorboards (IEEE11073-10419 andBluetooth SIG compliantinterface).	Manufacturer-provided iCGM SDK(proprietarycommunicationinterface).
Validation(simulatedconditionsof use)	Manufacturer-providedprototype pump,communicating with iAGCvia IEEE 11073-10419and Bluetooth SIGcompliant interface.	Manufacturer-provided cleared iCGMdevices, communicatingwith iAGC viaManufacturer-provided SDK withproprietarycommunicationinterface.	Tidepool Loopsoftware installed onrepresentative iOSdevices, capable ofcommunicating usingBluetooth LE to:
			Manufacturer-provided:a) prototype pumpb) hardware emulationenvironment
			Manufacturer-provided:a) cleared iCGMb) hardware emulationenvironment

Cybersecurity:A cybersecurity analysis was performed for Tidepool Loop using FDA .

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guidance, Content of Premarket Submissions for Management of Cybersecurity in Medical Devices, issued October 18, 2020, and the principles outlined in FDA guidance, Postmarket Management of Cybersecurity in Medical Devices, issued December 28, 2020. Tidepool performed threat modeling of the interactions between Tidepool Loop app and the Tidepool Platform and applied mitigations as detailed in the hazard analysis and V&V report.

Tidepool provided a software bill of materials, which provided details on all software used in the device. This included all manufacturer-developed, commercially licensed, open source, and off-the- shelf software components, alonq 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.

In addition, results of internal and third-party penetration testing, using existing devices and configurations, were provided.

X. Clinical Testing

Study Overview and Design: The Jaeb Center for Health Research, in collaboration with clinical research centers and Tidepool, conducted an observational study to collect data on the do-it-yourself (DIY) Loop system (ClinicalTrials.gov Identifier: NCT03838900). This study collected and analyzed data on the efficacy, safety, usability, and quality of life/psychosocial effects of the DIY Loop System. The study enrolled subjects diagnosed with type 1 diabetes (T1D) who were using insulin (either pump therapy or multiple daily injections [MDI]) and currently using DIY Loop or had plans to begin using DIY Loop for insulin delivery.

Subjects/Enrollment: 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 as new DIY Loop users. Study participants were divided into two cohorts:

Cohort A individuals new to using DIY Loop (had not started Loop or had used it for <7 days prior to enrollment)
Cohort B existing DIY Loop users .

A total of 1,127 participants were enrolled into the study with 799 in Cohort A, defined as new DIY Loop users, and 328 in Cohort B, defined as existing DIY Loop users. Of the enrolled participants, 255 were determined to be ineligible resulting in 872 initiating the study with 606 participants in Cohort A and 266 in Cohort B.

There was no required length of follow-up for study participants, however minimum exposure targets were exceeded. Due to the rolling nature of enrollment, not all participants were eligible to meet the 9 month and/or 12 month follow-ups. In Cohort A, 88% of participants (n=535/606) reached the 6-month observational time point. In Cohort B, 83% of participants (n=222/266) reached the 9-month observational time point.

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A total of 483 person-years of DIY Loop exposure (over 175,000 person-days) were collected in 872 participants.

Investigational Device: This observational study examined DIY Loop in real-world, unsupervised, patient-driven use. Tidepool Loop is based on the same algorithm as DIY Loop, with specific design changes to enhance safety, such as adding settings quardrails.

Data Collection: CGM and insulin dosing data were collected continuously and uploaded automatically from a user's own iPhone. The Tidepool Mobile app securely sent this data to Tidepool's cloud, from where it was retrieved by the Jaeb Center for Health Research and replicated in the Jaeb Center's database.

Users completed weekly web-based surveys about Adverse Events (severe hypoqlycemia, DKA, hospitalization) and device issues. Participants were followed for up to 12 months with general updates obtained after 3, 6, and 12 months. Blood samples were collected for HbA1c measurement after 3 months for Cohort A and after 6 and 12 months for both cohorts; results were self-reported by the participant. At 3 and 6 months, more extensive web-based surveys collected patient-reported outcomes and psychosocial/quality of life aspects related to DIY Loop use. Focus groups were also completed.

Data Analysis: The primary effectiveness analysis consisted of A1C and sensor glucose time in range (70-180 mg/dL) results. The primary safety analysis included the incidence of severe hypodycemia and diabetic ketoacidosis (DKA). A summary of the primary effectiveness and safety results is presented in the table below.

Subject Demographics and Key Outcomes: The observational study included participants that may not be part of the intended user population, which is defined as > 6 years old, using Humalog or Novolog insulin only, and making use of the Tidepool Loop guardrails (Correction Range 87-180 mg/dL and Glucose Safety Limit 67-110 mg/dL) at least 90% of the time. Cohorts A and B included participants who used DIY Loop settings that are not possible in Tidepool Loop. The table below summarizes these different populations. The results are discussed in detail following the table.

	Study population not limited tointended user population		Study population limited tointended user population
	New Users(Cohort A)	Existing Users(Cohort B)	(Ages 6 and up, settings withinallowable Tidepool Loop rangesat least 90% of the time duringstudy follow-up)
N	606	266	175
Demographics
Age	16 Years (median)1-72 Years (range)	34 Years (median)13-76 Years (range)	23 years (mean)6-71 (range)
Sex	56% Female	52% Female	56% Female

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
Education	85% - Bachelor'sDegree or Beyond	89% - Bachelor'sDegree or Beyond	88% - Bachelor's Degree orBeyond
Household Income ≥$100,000	71%	78%	68%
Summary Diabetes Outcomes
HbA1c at baseline(mean)	6.8%	6.3%	7.1%
HbA1c after 6 months ofusing DIY Loop (mean)	6.6%	6.4%	6.7%
Time in Range(70-180 mg/dL)at baseline (mean)	67%	78%	62%
Time in Range(70-180 mg/dL)1-6 months of using DIYLoop (mean)	74%	79%	70%
Summary Safety Outcomes
All Adverse Events	No DKA events71 SH events	No DKA events24 SH events	No DKA events23 SH events
Severe Hypoglycemia(SH)during study	92% no SH frombaseline to 12months.22.6 SH eventsper 100 personyears compared to181.5 events per100 person yearsprior to usingLoop.	95% no SH frombaseline to 12months.14.2 SH events per100 person years.	92% no SH from baseline to 6months.42.3 SH events per 100 personyears compared to 192.0 eventsper 100 person years prior tousing Loop.

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Results/Cohort A (New Users): A total of 314 person-years of DIY Loop exposure were collected in 606 participants. Participants had a median age of 16 years, with a range from 1-72 Years.

. Primary Safety Analysis: 92% of Cohort A participants reported no severe hypoglycemia (SH) from baseline-12 months. In the remaining 8% of participants, 71 SH
Tidepool Loop Traditional 510(k) Premarket Notification, K203689 January 23, 2023

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events occurred in 47 participants. The overall incidence rate of SH was 22.6 events per 100 person-years, a substantially lower rate than what was reported at baseline before using DIY Loop (181.5 events per 100 person-years). No SH events were adjudicated as "Related to Loop" in Cohort A. Eleven SH events resulted in seizure or loss of consciousness, translating to an incidence rate of 3.5 events per 100 person-years. One DKA event occurred in Cohort A from baseline-12 months, resulting in a total incidence rate of 0.3 DKA events per 100 person-years; this was also a substantially lower rate than what was reported at baseline before using DIY Loop (17.2 events per 100 person-years).

Primary Glycemic Outcomes: Mean time-in-range 70-180 mg/dL (TIR) increased from . 67% at baseline to 73% from 1-6 months (p<0.001). TIR increased in both adults and children, across the full range of baseline HbA1c levels, and with both high and moderate income levels. Time <54 mg/dL and <70 mg/dL were both low at baseline (medians of 0.40% and 2.9%, respectively), but still improved during the study (p<0.001). Mean HbA1c was 6.8% at baseline and decreased to 6.6% after 6 months (P<0.001) of using DIY Loop. Multiple sensitivity analyses suggested that the results were robust and not impacted by missing data.
Quality of Life Outcomes: Study participants took eight validated questionnaires . throughout the study, capturing important psychosocial and quality of life outcomes. The Insulin Dosing Systems: Perceptions, Ideas, Reflections and Expectations (INSPIRE) measures were completed by adults, parents, and children; results in Cohort A showed composite scores of 4.3 and higher out of a possible 5.0 - indicating highly positive psychosocial and quality of life outcomes associated with the use of DIY Loop. The INSPIRE questionnaires were recently qualified by the FDA through the Medical Device Development Tool program (Submission Number: Q191073).

In Cohort A, statistically significant improvements were also seen with DIY Loop in the Diabetes Distress Scale - Management Burden; Fear of Hypoglycemia (Worry Scale); Hypoqlycemia Confidence; and the Pittsburgh Sleep Quality Index. These validated questionnaires appear to corroborate the CGM and HbA1c metrics discussed earlier. No significant changes were observed in the Diabetes Technology Attitudes; Technology Use for Problem Solving; and the Risk Taking Survey. In Cohort A, 75% of participants said they were "very likely" (a "5" on a 1-5 scale) to recommend Loop to another person with type 1 diabetes.

Results/Cohort B (Existing Users), a total of 169 person-years of DIY Loop exposure were collected in 266 participants. Participants had a median age of 34 years, with a range from 3-76 Years. Outcomes for Cohort B are descriptive and do not include p-values, as users were already on DIY Loop at baseline.

. Primary Safety Analysis: 95% of Cohort B participants reported no severe hypoglycemia (SH) from baseline-12 months. In the remaining 5% of participants, 24 SH events occurred over the study, resulting in an overall incidence rate 14.2 SH events per 100 person-years. Four SH events were adjudicated as "related to Loop" in Cohort B. Seven SH events resulted in seizure or loss of consciousness, translating to an

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incidence rate of 4.1 events per 100 person-years. No DKA events occurred in Cohort B, resulting in a total incidence rate of 0.0.

Primary Glycemic Outcomes: Mean time-in-range 70-180 mg/dL (TIR) was 78% at baseline (already using Loop) and maintained at 78%-79% from 1-12 months. Time <54 mq/dL and <70 mg/dL were both low at baseline (medians of 0.34% and 2.6%, respectively) and remained at similar levels during the study. Mean HbA1c was 6.3% at baseline and was maintained at 6.4% at six months and 6.2% at 12 months.
Quality of Life Outcomes: INSPIRE results in Cohort B showed composite scores of . 4.3 and higher out of a possible 5.0 - indicating highly positive psychosocial and quality of life outcomes associated with the use of DIY Loop. Other measures of Cohort B's quality of life remained consistent from Baseline-12 months; these data were also consistent with Cohort A's results while on DIY Loop. In Cohort B, 79% of participants said they were "very likely" (a "5" on a 1-5 scale) to recommend Loop to another person with type 1 diabetes

Results (Intended User Population): A total of 175 patients met the definition of 'intended user population'. Participants had a median age of 23 years, with a range from 6-71 years.

. Primary Safety Analysis: 92% of the intended use population participants reported no severe hypoglycemia (SH) from baseline-6 months. In the remaining 8% of participants, 23 SH events occurred over the study, resulting in an overall incidence rate of 42.3 SH events per 100 person-years compared to 192.0 events per 100 person-years prior to using Loop. 1 SH event was adjudicated as "related to Loop" in this population. No SH events resulted in seizure or loss of consciousness, translating to an incidence rate of 0 events per 100 person-years. No DKA events occurred in this population, resulting in a total incidence rate of 0.0.
. Primary Glycemic Outcomes: Mean time-in-range 70-180 mg/dL (TIR) was 62% at baseline and improved to 70% from 1-6 months. Time <54 mg/dL and <70 mq/dL were both low at baseline (medians of 0.23% and 1.8%, respectively) and were largely unchanged during the study (0.23% and 1.9% at 6 months). Mean HbA1c was 7.1% at baseline and improved to 6.7% at six months.

Adverse Events (AE): Users completed weekly web-based surveys about Adverse Events (severe hypoglycemia, DKA, hospitalization) and device issues. Participants were followed for up to 12 months with general updates obtained after 3, 6 and 12 months.

No DKA events were attributed to the use of DIY Loop in any of the study groups, as shown in the summary table above.

Adverse Events (Cohorts A and B): The data suggest that the use of DIY Loop was associated with a lower reported rate of severe hypoglycemia (SH) in Cohort A - over both 6-Month and 12-Month study time points – as compared to the baseline report of SH in the 3 months prior to starting Loop. The percentage of Loop users experiencing a severe hypoglycemia event within the first 3 months of the study (5%) was similar to the 6% 3-month frequency reported in the real-world T1D Exchange clinic registry.

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It is difficult to compare AE rates between DIY Loop Study and recent controlled studies due to different study designs, methodology, data collection process and sample size. Regardless, a comparison was done for illustrative purposes only. Although the overall incidence rate of severe hypoglycemia was higher than in recent controlled studies of existing AID, this study had no exclusion criteria, whereas most previous AID studies excluded individuals with recent severe hypoglycemia or gave investigators discretion to exclude individuals if, in the opinion of the investigator, the individual's participation would put the individual or the study at risk. The difference could also reflect this study's frequent ascertainment of severe hypoglycemia through a weekly text prompt or differences in study design: the Loop study was real-world and virtual compared with other studies that had structured protocols with close clinical oversight of closed-loop system use by study staff (including system setup and maintenance). The difference is also possibly reflective of the high pre-study risk of this cohort for severe hypoglycemia, possibly driven by a more hyperglycemia-avoidant approach to diabetes management.

Adverse Events/Severe Hypoglycemia (Intended Use Population): Severe hypoglycemic event data were specifically analyzed for the "intended use" sub-population. That population is defined as individuals in the study from both cohorts that are ≥6 years old, using Humalog or Novolog insulin only, and making use of the Tidepool Loop guardrails at least 90% of the time during study follow-up.

The table below summarizes the incidence of severe hypoglycemic events at baseline and follow-up by age group in the intended use population. Given the small sample sizes and potential lack of statistical significance for these cohorts, the Tidepool team individually analyzed each adverse event from the Observational Study of Loop in detail. Each event was reviewed both by the Jaeb Center for Health Research and by Tidepool staff, including review with Tidepool's Chief Medical Advisor. These data show that:

(1) the majority of severe adverse events observed during the study were experienced by the minority of participants who also had at least one severe hypoqlycemic event in the three months before using DIY Loop; and,

(2) for those participants who reported at least one severe adverse event in the three months prior to using DIY Loop, their incident rates of severe hypoglycemic events were reduced from baseline; and,

(3) across the intended use population, the incidence rate of Severe Hypoqlycemia events was reduced from 192 events per 100 person-years in the 3 months prior to using DIY Loop, to 42 events per 100 person-years for the 6 months after starting on DIY Loop.

In other words, those participants who had severe hypoglycemic events before using Loop were more likely to continue to have SH events, but to have fewer of them.

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	Overall	6-13 Years	14-17 Years	≥18 Years
Overall	N=175	N=76	N=19	N=80
Severe Hypoglycemia(Baseline - 6 Months)
Total # of events	23	11	5	7
# 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 100person-years)	42.3	44.7	88.8	29.0
Severe Hypoglycemia(3 Months Prior to Baseline)
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 Event in the 3Months Prior to Enrollment	N=149	N=63	N=17	N=69
Severe Hypoglycemia(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 Events in the 3Months Prior to Enrollment	N=26	N=13	N=2	N=11
Severe Hypoglycemia(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

Severe Hypoglycemia for Participants ≥6 Years Old

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Applicability to Tidepool Loop's design considered all identified DIY Loop known use problems, Tidepool adapted its design as necessary to mitigate those known use problems, and the design was tested as part of detailed Verification and Validation Testing. The changes in Tidepool Loop were made specifically to enhance Tidepool Loop's safety profile and to comply with US FDA's iAGC (interoperable Automated Glycemic Controller) requirements.

Therefore, Tidepool believes that the DIY Loop clinical data adequately addresses the safety and benefit/risk profile of Tidepool Loop, and is further supported by robust nonclinical data.

XI. Conclusions

Tidepool Loop 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, Control-IQ Technology (K200467). 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.

Tidepool believes that the non-clinical and clinical performance data described above supports the determination of substantial equivalence. This data demonstrates implementation of design considerations relative to data logging, interoperability, and cybersecurity design as required by the Special Controls for this device ( 21 CFR 862.1356). Human factors and clinical validation demonstrated that Tidepool Loop performed as designed and intended users, uses, and use environments.

Regulation Number and Section

§ 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.