iLet® Dosing Decision Software

K232224 · Beta Bionics, Inc. · QJI · Sep 22, 2023 · Clinical Chemistry

Device Facts

• Record ID: K232224
• Device Name: iLet® Dosing Decision Software
• Applicant: Beta Bionics, Inc.
• Product Code: QJI · Clinical Chemistry
• Decision Date: Sep 22, 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

The iLet Dosing Decision Software is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps. A self-monitoring of blood glucose (SMBG) meter may also be used for manual input of blood glucose values to continue insulin dosing for a limited period of time when input from the iCGM is temporarily not available. The iLet Dosing Decision Software autonomously determines and commands an increase, decrease, maintenance, or suspension of all basal doses of insulin and autonomously determines and commands correction doses of insulin based on input from an iCGM, and it autonomously determines and commands meal doses of insulin based on meal announcements. iLet Dosing Decision Software is intended for the management of type 1 diabetes mellitus in people 6 years of age or older. iLet Dosing Decision Software is intended for single patient use and requires a prescription.

Device Story

iLet Dosing Decision Software functions as part of Bionic Pancreas system; integrates with iCGM and ACE pump. Inputs: real-time glucose data from iCGM; user-provided body mass; qualitative meal announcements (breakfast, lunch, dinner). Operation: autonomously calculates/commands basal insulin adjustments, correction doses, and meal doses based on glucose trends and user inputs. Features 'BG-Run mode' for temporary operation during CGM signal loss. Used by patients with type 1 diabetes; managed via iLet Go App (iOS) for data sharing and updates. Output: insulin delivery commands to ACE pump. Benefits: automated glycemic control; reduced user burden for dosing decisions; improved time-in-range.

Clinical Evidence

13-week, single-arm extension study of 46 pediatric/adolescent participants (6-17 years) with T1D using iLet with Fiasp. Primary endpoints included HbA1c and CGM metrics. Results showed HbA1c decrease of 0.56% from baseline; Time-in-Range (70-180 mg/dL) increased by 12.0%; mean glucose decreased by 18 mg/dL. Hypoglycemic events (Time <54 mg/dL) decreased by 0.15% and Time <70 mg/dL decreased by 0.82%.

Technological Characteristics

Software-based glycemic controller; interoperable with iCGM and ACE pumps. Requires initialization with patient body mass. Supports U-100 lispro, U-100 aspart, and U-100 Fiasp. Connectivity via iLet Go App (iOS) for cloud data sharing and over-the-air updates. Operates on proprietary algorithm for autonomous insulin dosing.

Indications for Use

Indicated for management of type 1 diabetes mellitus in patients 6 years of age or older. Requires use with compatible iCGM and ACE pump.

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

• iLet® Dosing Decision Software (K220916)

Submission Summary (Full Text)

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FDA

U.S. FOOD &amp; DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

## I Background Information:

A 510(k) Number

K232224

B Applicant

Beta Bionics, Inc.

C Proprietary and Established Names

iLet® Dosing Decision Software

D Regulatory Information

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

## E Purpose for Submission:

Modifications to the device Instructions for Use to add U-100 Fiasp, in the Fiasp PumpCart prefilled cartridge, as a compatible insulin for ages 6 years and older.

## II Intended Use/Indications for Use:

A Intended Use(s):

See Indications for Use below.

B Indication(s) for Use:

The iLet Dosing Decision Software is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps. A self-monitoring of blood glucose (SMBG) meter may also be used for manual input of blood glucose values to continue insulin dosing for a limited period of time when input from the iCGM is temporarily not available.

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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The iLet Dosing Decision Software autonomously determines and commands an increase, decrease, maintenance, or suspension of all basal doses of insulin and autonomously determines and commands correction doses of insulin based on input from an iCGM, and it autonomously determines and commands meal doses of insulin based on meal announcements.

iLet Dosing Decision Software is intended for the management of type 1 diabetes mellitus in people 6 years of age or older. iLet Dosing Decision Software is intended for single patient use and requires a prescription.

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

Rx – For prescription use only.

Do not use the iLet Dosing Decision Software if you are unable or unwilling to test blood glucose (BG) levels with an SMBG meter when input from the iCGM is not available.

Do not use the iLet Dosing Decision Software if you are unable or unwilling to recognize and respond to iLet safety alerts.

Do not use the iLet System if you are taking hydroxyurea, also known as Hydrea. This medication is sometimes used in the treatment of blood disorders and some kinds of cancer. The use of hydroxyurea can result in falsely elevated sensor glucose readings. The iLet System relies on sensor glucose readings to adjust insulin, provide insulin doses, and provide high and low glucose alerts. If the iLet System receives sensor readings that are higher than actual glucose levels, it could result in missed hypoglycemia alerts and potential errors in diabetes management, such as too much insulin being delivered. Hydroxyurea can also result in errors when reviewing, analyzing, and interpreting historical patterns for assessing glucose control.

Do not use the iLet ACE Pump and Dosing Decision Software in people under 6 years of age. The iLet ACE Pump and Dosing Decision Software have not been studied in these populations.

Do not use the iLet Dosing Decision Software in people who are pregnant, on dialysis or critically ill. The iLet Dosing Decision Software has not been studied in these populations.

The system should NOT be used in hospitalized people as the safety of the technology has not been evaluated in this population.

The iLet Dosing Decision Software is only for use with insulin U-100 lispro (Humalog), insulin U-100 aspart (Novolog), or insulin U-100 aspart (Fiasp).

Do not use the iLet Dosing Decision Software with the U-100 Fiasp in individuals under 18 years of age. The iLet Dosing Decision Software has not been studied with the U-100 Fiasp in these populations.

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The iLet Dosing Decision Software is only for use with the Dexcom G6 iCGM. When using the iLet device, wear an iCGM.

Remove the iLet device, steel infusion set, CGM sensor, and CGM transmitter before undergoing radiation therapy, Magnetic Resonance Imaging (MRI), Computed Tomography (CT) scan, or diathermy treatment procedures. Exposure of the iLet device, steel infusion set, CGM sensor, or CGM transmitter to any of these may damage them.

Do not expose your iLet device, steel infusion set, CGM transmitter, or CGM sensor to equipment used in procedures for Pacemaker/Automatic Implantable Cardioverter Defibrillator (AICD) placement or reprogramming, Cardiac Catheterization, or Nuclear Stress Test.

The iLet Go App is compatible with the iOS platform. The iLet Go App provides the ability to perform over-the-air updates and / or pull data from an iLet device to share with the Beta Bionics Cloud. The iLet Go App is not currently compatible with Android or other platforms.

If your CGM is offline for an extended period of time, dosing will stop and you should switch to alternative therapy until you are able to reconnect to a CGM sensor. A countdown timer will appear before dosing would stop.

## III Device Description

The iLet Dosing Decision software is part of the iLet Bionic Pancreas and is intended for use by people with diabetes. The iLet Dosing Decision software works in conjunction with a compatible alternate controller enabled (ACE) pump. The iLet Dosing Decision Software requires initialization with the user's body mass (body weight), as well as meal announcements. When initiating a meal announcement with the iLet Dosing Decision Software, the user qualitatively approximates carbohydrate content (meal size) relative to the usual carbohydrate content for each of the three meal types (breakfast, lunch, or dinner). The iLet Dosing Decision Software autonomously determine the size of the insulin dose in response to a meal announcement by the user.

The iLet Dosing Decision software works to control glucose to a user-set glucose target of "lower" (110 mg/dL), "usual" (120 mg/dL), or "higher" (130 mg/dL) within the device settings. Users can also set glucose targets specific for sleep.

The iLet Dosing Decision software also includes a feature, called "BG-Run mode", which enables the device to continue insulin delivery in the event CGM-data is unavailable. Use of the feature, however, should be temporary and always for the shortest duration possible, with the goal to resume CGM-guided insulin dosing as soon as possible.

## IV Substantial Equivalence Information:

### A Predicate Device Name(s):

iLet® Dosing Decision Software

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B Predicate 510(k) Number(s):

K220916

C Comparison with Predicate(s):

| Device & Predicate Device(s): | K232224 | K220916 |
| --- | --- | --- |
| Device Trade Name | iLet® Dosing Decision Software | iLet® Dosing Decision Software |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Intended 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, as well as command correction doses, based on glucose values. | Same |
| General Device Characteristic Differences | | |
| Fiasp Age Indication | 6 years and older | 18 years and older |

V Standards/Guidance Documents Referenced:

ISO 14155:2020 - Clinical investigation of medical devices for human subjects - Good clinical practice

VI Performance Characteristics:

A. Analytical Performance

The analytical performance of the iLet Dosing Decision Software was previously established and described in the public decision summary for K220916.

B. Other Supportive Instrument Performance Characteristics Data

1. Summary of Clinical Testing

The sponsor conducted a 13-week, single-arm extension study for 48 subjects aged 6 to 17

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years old with type 1 diabetes (T1D) at 16 clinical sites within the United States who had participated in the Standard Care Group (SC/control group) in the Bionic Pancreas (BP) Pivotal trial, a prior 13-week multi-center, parallel group randomized control trial (RCT). In the extension study, the RCT SC group was given the opportunity to use the insulin-only configuration of the iLet BP system. All participants 6-17 years old (at time of consent for the RCT) used study-provided U-100 Fiasp® PumpCart® (insulin aspart) in a pre-filled 1.6mL cartridge during the Extension Study.

## Observed Results

| Mean Change in HbA1c from Baseline to 13 Weeks (6 – 17 Years) | | | |
| --- | --- | --- | --- |
| | Baseline (SC) | Week 13 (BP-F) | Change from Baseline to Week 13 |
| Overall (SD) | N = 45 | N = 43 | N = 42* |
| | 7.8 (1.1) | 7.2 (0.7) | -0.56 (0.69) |
| 6 – 12 Years (SD) | N = 23 | N = 22 | N = 21 |
| | 8.0 (0.9) | 7.2 (0.5) | -0.65 (0.68) |
| 13 – 17 Years (SD) | N = 22 | N = 21 | N = 21 |
| | 7.6 (1.3) | 7.1 (0.8) | -0.47 (0.71) |

*Out of 46 subjects 6 – 17 years old who were on Fiasp, 1 subject had missing HbA1c data at baseline and 3 subjects had missing HbA1c data during follow-up for a total of 4 subjects missing data, therefore change from baseline to Week 13 was analyzed in a total of 42 subjects.

| CGM Outcomes (6 – 17 Years) | | | |
| --- | --- | --- | --- |
| | Baseline (SC) | Week 13 (BP-F) | Change from Baseline to Week 13 |
| Overall | N = 46 | N = 45 | N = 45 |
| Hours of CGM Data (SD) | 2042 (132) | 1877 (270) | - |
| % Time in Range 70 – 180 mg/dL (SD) | 51% (16%) | 63% (10%) | 12.0% (11.8%) |
| Mean glucose (mg/dL) (SD) | 187 (34) | 168 (16) | -18 (24) |
| % Time > 180 mg/dL (SD) | 46% (17%) | 35% (10%) | -11.2% (12.3%) |
| % Time >250 mg/dL (SD) | 21.2% (14.7%) | 11.6% (6.5%) | -9.8% (10.7%) |
| % Time <70 mg/dL (SD) | 3.1 (2.5) | 1.7 (1.5) | -1.5 (1.8) |
| % Time <54 mg/dL (SD) | 0.67% (0.90%) | 0.54% (0.51%) | -0.15% (0.69%) |
| 6 – 12 Years | N = 24 | N = 24 | N = 24 |
| Hours of CGM Data (SD) | 2035 (150) | 1902 (319) | - |

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| 6 – 12 Years | N = 24 | N = 24 | N = 24 |
| --- | --- | --- | --- |
| % Time in Range
70 – 180 mg/dL (SD) | 49% (15%) | 62% (6%) | 13.1% (13.6%) |
| Mean glucose (mg/dL)
(SD) | 187 (30) | 166 (1) | .20 (26) |
| % Time > 180 mg/dL
(SD) | 47% (16%) | 35% (6%) | .12.6% (14.1%) |
| % Time >250 mg/dL
(SD) | 22.5% (12.6%) | 11.4% (3.8%) | -11.1 (11.2%) |
| % Time <70 mg/dL
(SD) | 3.43% (2.83%) | 2.91% (1.54%) | -0.52% (2.15%) |
| % Time <54 mg/dL
(SD) | 0.88% (1.09%) | 0.77% (0.54%) | -0.10% (0.84%) |
| 13 – 17 Years | N = 22 | N = 21 | N = 21 |
| Hours of CGM Data
(SD) | 2049 (113) | 1848 (203) | - |
| % Time in Range
70 – 180 mg/dL (SD) | 52% (18%) | 63% (12%) | 10.8% (9.4%) |
| Mean glucose (mg/dL)
(SD) | 186 (39) | 170 (21) | -16 (23) |
| % Time > 180 mg/dL
(SD) | 45% (19%) | 36% (13%) | -9.7% (9.9%) |
| % Time >250 mg/dL
(SD) | 19.8% (16.9%) | 11.8% (8.7%) | -8.4% (10.2%) |
| % Time <70 mg/dL
(SD) | 2.31% (2.39%) | 1.24% (0.64%) | -1.16% (2.10%) |
| % Time <54 mg/dL
(SD) | 0.45% (0.58%) | 0.27% (0.19%) | -0.20% (0.48%) |

Safety Results

| Summary of Adverse Events (6 – 17 Years) | | | |
| --- | --- | --- | --- |
| | Overall | 6 – 12 Years | 13 – 17 Years |
| Number of participants | 46 | 24 | 22 |
| Severe Hypoglycemic (SH) Events^{a} | | | |
| Number of Events | 0 | 0 | 0 |
| Participants with ≥1 event | 0 (0%) | 0 (0%) | 0 (0%) |
| Number of events per subject | | | |
| 0 | 46 (100%) | 24 (100%) | 22 (100%) |
| 1 | 0 (0%) | 0 (0%) | 0 (0%) |
| Incident rate per 100 person-years | 0 | 0 | 0 |
| Diabetic Ketoacidosis Events^{b} | | | |

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| Number of Events | 1 | 1 | 0 |
| --- | --- | --- | --- |
| Participants with ≥1 event | 1 (2%) | 1 (4%) | 0 (0%) |
| Number of events per subject | | | |
| 0 | 45 (98%) | 23 (96%) | 22 (100%) |
| 1 | 1 (2%) | 1 (4%) | 0 (0%) |
| Incident rate per 100 person-years | 8.9 | 16.9 | 0.0 |
| Other Serious Adverse Events (SAEs)c | | | |
| Number of Events | 1 | 0 | 1 |
| Participants with ≥1 event | 1 (2%) | 0 (0%) | 1 (5%) |
| Number of events per subject | | | |
| 0 | 45 (98%) | 24 (100%) | 21 (95%) |
| 1 | 1 (2%) | 0 (0%) | 1 (5%) |
| Incident rate per 100 person-years | 8.9 | 0.0 | 18.9 |

a - A severe hypoglycemic event is defined as a hypoglycemic event that a) required assistance of another person due to altered consciousness, and b) required another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

b - A hyperglycemic event is classified as DKA if the following are present: a) symptoms such as polyuria, polydipsia, nausea, or vomiting; b) serum ketones &gt;1.5 mmol/L or large/moderate urine ketones; c) either arterial blood pH &lt;7.30 or venous pH &lt;7.24 or serum bicarbonate &lt;15; and d) treatment provided in a health care facility.

c - A serious adverse event is defined as any untoward medical occurrence that a) results in death, b) is life-threatening, c) requires inpatient hospitalization of prolongation of existing hospitalization, d) results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions (sight threatening), e) is a congenital anomaly or birth defect, or f) is considered a significant medical event by the investigator based on medical judgment.

## VII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

## VIII Conclusion:

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

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