(68 days)
Control-IQ+ technology is 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 based on iCGM readings and predicted glucose values. It can also deliver correction boluses when the glucose value is predicted to exceed a predefined threshold.
Control-IQ+ technology is intended for the management of Type 1 diabetes mellitus in persons 2 years of age and greater and of Type 2 diabetes mellitus in persons 18 years of age and greater.
Control-IQ+ technology is intended for single patient use and requires a prescription.
The Subject Device, Control-IQ+ technology ("Control-IQ+") is a software-only device intended for the management of type 1 and type 2 diabetes mellitus. The device controls insulin delivery from a compatible alternate controller enabled insulin pump (ACE pump) based on inputs provided by a compatible integrated continuous glucose monitor (iCGM) and inputs provided by the user (e.g., carbohydrate intake, exercise, and sleep schedule). Control-IQ+ technology is meant to be installed on a compatible ACE pump.
Control-IQ+ technology has three different modes: Normal, Sleep, and Exercise. The glucose targets are not individually customizable in these modes but can change based on the mode selected. During Normal mode, Control-IQ+ technology aims to control glucose within a target range of 112.5 – 160 mg/dL, during Sleep mode the target range is 112.5 – 120 mg/dL, and during Exercise mode the target range is 140 – 160 mg/dL.
Control-IQ+ technology includes an integrated feature whereby iCGM values are automatically populated into the glucose field of the integrated bolus calculator when Control-IQ+ technology is active (i.e., the device is operating in closed-loop mode). This feature is disabled when Control-IQ is turned off.
Control-IQ+ technology requires users to input their weight and their total daily insulin requirement, which should be established with the help of a health care provider before using the device.
This FDA 510(k) clearance letter describes the acceptance criteria and study for the Control-IQ+ technology, an interoperable automated glycemic controller.
It's important to note that this device is a software-only device (Control-IQ+ technology), and the primary change described in this 510(k) is the addition of a new compatible insulin (Lyumjev U-100 Insulin) for use with the existing Control-IQ technology. The clearance relies heavily on the substantial equivalence to a predicate device (K243823, Control-IQ+ technology) and a clinical study demonstrating the safety and effectiveness of the new compatible insulin with the existing Control-IQ system.
Here's the breakdown of the acceptance criteria and study proving device performance:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a "table of acceptance criteria" for the Control-IQ+ technology's performance in terms of glucose control metrics (e.g., time in range, hypoglycemia rates) for this specific 510(k) submission. Instead, the "acceptance" for this submission appears to be based on demonstrating non-inferiority or better safety when using the new insulin (Lyumjev) with the already cleared Control-IQ system, compared to established benchmarks.
The primary "performance" mentioned is related to safety, specifically the rates of severe hypoglycemia and DKA.
| Acceptance Criteria (Implied) | Reported Device Performance (with Lyumjev) |
|---|---|
| Frequency of severe hypoglycemia comparable to or lower than T1D Exchange clinic registry data | Rates of severe hypoglycemia were lower than in the T1D Exchange clinic registry data. |
| Frequency of DKA events comparable to or lower than T1D Exchange clinic registry data | Rates of DKA were lower than in the T1D Exchange clinic registry data. |
| Well-tolerated with few adverse effects | The use of Lyumjev with t:slim X2 insulin pump with Control-IQ technology was well tolerated with few adverse effects. |
| No increase in hypoglycemia | No increase in hypoglycemia observed. |
| Statistical comparison meeting prespecified success criteria | The statistical comparison met the prespecified success criteria. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 179 participants with type 1 diabetes.
- 70 adults (18-75 years old)
- 109 pediatric participants (6-17 years old)
- Data Provenance: The study was a "single-arm prospective safety trial." While the exact country of origin isn't specified, FDA clearances typically involve studies conducted in the US or under protocols recognized by the FDA. The T1D Exchange clinic registry is a US-based registry, suggesting a likely US context for the study.
- Retrospective/Prospective: Prospective. The study involved an initial (~16-day) Humalog Lead-in Period and a subsequent (13-week) Lyumjev Treatment Period.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This type of device (automated glycemic controller) does not typically involve expert review for "ground truth" in the same way an imaging or diagnostic AI might. The "ground truth" for glucose control is direct physiological measurements (iCGM readings) and clinical outcomes (hypoglycemia, DKA). Therefore, specific numbers or qualifications of experts for establishing ground truth are not applicable in this context. The study design itself serves to establish the performance and safety against clinical outcomes.
4. Adjudication Method for the Test Set
Adjudication methods (e.g., 2+1, 3+1) are typically used in studies involving subjective expert interpretation of data (e.g., radiologists reviewing images). For a system controlling insulin delivery based on CGM data, adjudication of such a type is not applicable. Clinical events (severe hypoglycemia, DKA) are typically adjudicated by an independent clinical endpoint committee or medical monitors based on predefined criteria, but the document does not specify this level of detail.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done.
MRMC studies are relevant for diagnostic aids where human readers interpret data (e.g., images) with and without AI assistance to measure improvement in reader performance. Control-IQ+ technology directly controls insulin delivery; it is not an assistive diagnostic tool for human interpretation.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)
The device is an "Interoperable Automated Glycemic Controller," meaning it operates to "automatically increase, decrease, and suspend delivery of basal insulin based on iCGM readings and predicted glucose values." It also delivers "correction boluses." This indicates that the core function is standalone (algorithm-only) in its closed-loop operation. While users can input data (carbohydrate intake, exercise, sleep schedule) and the device is intended for "single patient use" with a "prescription," the control logic itself functions automatically without continuous human intervention in real-time decision-making for insulin delivery adjustment. The study evaluates the system performance which includes this automated functionality.
7. The Type of Ground Truth Used
The ground truth used for this study was primarily:
- Physiological data: iCGM readings for glucose values.
- Clinical Outcomes Data: Rates of severe hypoglycemia and DKA events. These were compared against "reported frequencies from the T1D Exchange clinic registry" as a benchmark for safety.
8. The Sample Size for the Training Set
The document does not provide information regarding the sample size used for the training set of the Control-IQ+ technology. This 510(k) is for a modification (new compatible insulin) to an already cleared device, implying the core algorithm was trained and validated previously.
9. How the Ground Truth for the Training Set Was Established
The document does not provide information on how the ground truth for the training set of the original Control-IQ algorithm was established. Given the nature of an automated glycemic controller, it would typically involve extensive simulations, in-silico testing, and potentially prior clinical trials where continuous glucose monitoring (CGM) data, insulin delivery data, and corresponding blood glucose measurements were collected and used to train and validate the control algorithms. However, this specific 510(k) submission focuses on the safety and effectiveness of a new component (Lyumjev insulin) with the existing system rather than the initial foundational algorithm development.
§ 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.