(90 days)
The FreeStyle Libre 2 Flash Glucose Monitoring System is a continuous glucose monitoring (CGM) device with real time alarms capability indicated for the management of diabetes in persons age 4 and older. It is intended to replace blood glucose testing for diabetes treatment decisions, unless otherwise indicated.
The System also detects trends and tracks patterns and aids in the detection of episodes of hyperglycemia and hypoglycemia, facilitating both acute and long-term therapy adjustments. Interpretation of the System readings should be based on the glucose trends and several sequential readings over time.
The System is also intended to autonomously communicate with digitally connected devices. The System can be used alone or in conjunction with these digitally connected devices where the user manually controls actions for therapy decisions.
The FreeStyle Libre 3 Continuous Glucose Monitoring System is a real time continuous glucose monitoring (CGM) device with alarms capability indicated for the management of diabetes age 4 and older. It is intended to replace blood glucose testing for diabetes treatment decisions, unless otherwise indicated.
The System also detects trends and tracks patterns and aids in the detection of episodes of hyperglycemia and hypoglycemia, facilitating both acute and long-term therapy adjustments. Interpretation of the System readings should be based on the glucose trends and several sequential readings over time.
The System is also intended to autonomously communicate with digitally connected devices. The System can be used alone or in conjunction with these digitally connected devices where the user manually controls actions for therapy decisions.
The FreeStyle Libre 2 and FreeStyle Libre 3 are integrated continuous glucose monitoring (iCGM) Systems designed to be used alone or in conjunction with digitally connected devices. The FreeStyle Libre 2 System consists of a Sensor and either a Reader or the FreeStyle Libre 2 App downloaded to a compatible smartphone as a primary display device. The FreeStyle Libre 3 System consists of a Sensor and the FreeStyle Libre 3 App downloaded to a compatible smartphone as a primary display device. Both Systems can communicate glucose data and other information wirelessly and securely to and from these digitally connected devices as described below:
- Wireless communication from the FreeStyle Libre 2 Sensor or FreeStyle Libre 3 Sensor directly to an interoperable receiver device, which connects with the Sensor using the near field communication (NFC) and Bluetooth Low Energy wireless interfaces provided by the Sensor
- The FreeStyle Libre 2 App or FreeStyle Libre 3 App communicates through the cloud to another software device, such as LibreView.
Compared to the respective predicate devices, the proposed subject devices include an additional software component, the Libre Data Sharing API. The Libre Data Sharing API is a cloud-based application programming interface (API) that enables communication of glucose data including alarms through the cloud from the FreeStyle Libre 2 System or FreeStyle Libre 3 System to authorized client software on digitally connected devices. The data transmitted by the API to authorized client software can be used for specific and permitted use cases, including nonmedical device applications, medical device data analysis, CGM secondary display alarm, active patient monitoring, and treatment decisions. Use of the Libre Data Sharing API and the CGM information it transmits is limited by the indications for use of the iCGM systems with which it is used.
The Libre Data Sharing API does not have any command or control over the client software, nor does it allow for the client software to have any command or control over the FreeStyle Libre 2 or FreeStyle Libre 3 Systems. Additionally, glucose data and alarms from the connected iCGM system are not modified or manipulated by the Libre Data Sharing API through its transmission to the authorized client software.
The display device of the connected FreeStyle Libre 2 or FreeStyle Libre 3 Systems, which directly receives the data from the Sensor, continues to serve as a primary display device for the glucose data and alarms. The current components of the FreeStyle Libre 2 and FreeStyle Libre 3 Systems (sensor/applicator and primary display devices) have not been modified as a result of the added the Libre Data Sharing API.
This document is a 510(k) Summary for the FreeStyle Libre 2 Flash Glucose Monitoring System and FreeStyle Libre 3 Continuous Glucose Monitoring System. It describes the devices and argues for their substantial equivalence to previously cleared predicate devices.
Here's an analysis of the acceptance criteria and study information provided in the document:
1. Acceptance Criteria and Reported Device Performance:
The document doesn't present a table of numerical acceptance criteria with corresponding performance statistics. Instead, it argues for substantial equivalence based on the technological characteristics and intended use being the same as the predicate devices, with the addition of the Libre Data Sharing API.
The key acceptance criteria, implicitly, are that the devices continue to perform according to specifications and meet their technological and performance criteria, as demonstrated by verification and validation, aligning with the predicate devices' cleared performance.
| Acceptance Criteria Category (Implicit) | Reported Device Performance |
|---|---|
| Technological Characteristics | Identical to predicate devices (amperometric measurement, glucose oxidase chemical reaction). |
| Intended Use / Indications for Use | Same as predicate devices. The Libre Data Sharing API enables communication of iCGM data for specific, permitted use cases, but does not change the core indications. |
| Primary Display Device Function | Unchanged. Continues to act as the primary display and issue glucose alarms. |
| Safety and Effectiveness | No impact from the Libre Data Sharing API. The API has no command/control over client software or the iCGM systems, and glucose data/alarms are not modified during transmission. |
| Adherence to Special Controls | Conforms to iCGM special controls per 21 CFR 862.1355. |
2. Sample Size and Data Provenance:
The document states: "The proposed subject devices with the Libre Data Sharing API were verified and validated according to ADC's internal design control process and in accordance with the applicable special controls for integrated continuous glucose monitoring systems. The testing demonstrated that the subject devices conform to the iCGM special controls per 21 CFR 862.1355 and that they performed according to specifications and met their technological and performance criteria."
- Sample Size: The document does not specify the sample sizes used for the test set or the training set. It refers broadly to "performance testing" and "data provided in this pre-market notification."
- Data Provenance: The document does not explicitly state the country of origin or whether the studies were retrospective or prospective. Given it's a 510(k) submission for a medical device, it's highly likely that the underlying performance data comes from clinical studies, often multi-site and prospective, but this document does not detail them. The focus of this 510(k) is specifically on the added software component (Libre Data Sharing API) and its impact on substantial equivalence, rather than re-proving the core glucose monitoring accuracy which would have been established in previous 510(k) clearances.
3. Number of Experts and Qualifications for Ground Truth:
The document concerns the addition of a data sharing API to existing glucose monitoring systems. It does not mention the use of experts to establish ground truth in the context of a reader study for the new component. The primary ground truth for glucose monitoring devices is typically derived from lab reference methods (e.g., YSI analyzer for blood glucose), rather than expert adjudication of images or clinical assessments.
4. Adjudication Method for the Test Set:
Not applicable in the context of this submission. The submission is about an API for device data sharing, not a diagnostic imaging or clinical assessment device requiring expert adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC study was not conducted or mentioned. This type of study is relevant for AI-assisted diagnostic tools that impact human reader performance, typically in radiology or pathology. This submission is for a continuous glucose monitoring system and an API to share its data.
6. Standalone (Algorithm Only) Performance:
The document states: "The Libre Data Sharing API does not have any command or control over the client software, nor does it allow for the client software to have any command or control over the FreeStyle Libre 2 and FreeStyle Libre 3 Systems. Additionally, glucose data and alarms from the FreeStyle Libre 2 and FreeStyle Libre 3 Systems are not modified or manipulated by the Libre Data Sharing API through its secured transmission to the authorized client software."
This implies that the core algorithm performance (i.e., glucose measurement accuracy) of the FreeStyle Libre 2 and 3 systems, which operates independently of the Libre Data Sharing API, has already been established in previous clearances (K210943, K213996, K212132). This submission focuses on the safety and effectiveness of the data sharing mechanism, not the standalone performance of the glucose measurement algorithms themselves. The API itself is primarily a data transmission layer, not a
diagnostic algorithm.
7. Type of Ground Truth Used:
For the underlying glucose monitoring systems (FreeStyle Libre 2 and 3), the ground truth for performance studies is typically laboratory reference measurements (e.g., plasma glucose values obtained from a YSI glucose analyzer) against which the accuracy of the interstitial glucose readings are compared. The document does not specifically detail how the ground truth was established for the "performance testing" related to the API, as the API's function is data transmission, not direct measurement. The ground truth for the API's performance would likely focus on the integrity, security, and timeliness of data transfer.
8. Sample Size for the Training Set:
The document does not specify the sample size for any training set. This submission is for a device modification (adding an API), not a de novo AI/ML algorithm that typically undergoes distinct training and test phases. The core glucose algorithms were already developed and cleared.
9. How the Ground Truth for the Training Set was Established:
Not applicable, as this submission pertains to an API for data sharing and refers to "verification and validation" for "performance testing" of the modified device, rather than the development and training of a new algorithm requiring a specific ground truth establishment for a training set. The underlying glucose measurement algorithms would have had their own ground truth established during their prior development and clearance, likely using reference lab methods.
§ 862.1355 Integrated continuous glucose monitoring system.
(a)
Identification. An integrated continuous glucose monitoring system (iCGM) is intended to automatically measure glucose in bodily fluids continuously or frequently for a specified period of time. iCGM systems are designed to reliably and securely transmit glucose measurement data to digitally connected devices, including automated insulin dosing systems, and are intended to be used alone or in conjunction with these digitally connected medical devices for the purpose of managing a disease or condition related to glycemic control.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include the following:
(i) Robust clinical data demonstrating the accuracy of the device in the intended use population.
(ii) The clinical data must include a comparison between iCGM values and blood glucose values in specimens collected in parallel that are measured on an FDA-accepted laboratory-based glucose measurement method that is precise and accurate, and that is traceable to a higher order (
e.g., an internationally recognized reference material and/or method).(iii) The clinical data must be obtained from a clinical study designed to fully represent the performance of the device throughout the intended use population and throughout the measuring range of the device.
(iv) Clinical study results must demonstrate consistent analytical and clinical performance throughout the sensor wear period.
(v) Clinical study results in the adult population must meet the following performance requirements:
(A) For all iCGM measurements less than 70 milligrams/deciliter (mg/dL), the percentage of iCGM measurements within ±15 mg/dL of the corresponding blood glucose value must be calculated, and the lower one-sided 95 percent confidence bound must exceed 85 percent.
(B) For all iCGM measurements from 70 mg/dL to 180 mg/dL, the percentage of iCGM measurements within ±15 percent of the corresponding blood glucose value must be calculated, and the lower one-sided 95 percent confidence bound must exceed 70 percent.
(C) For all iCGM measurements greater than 180 mg/dL, the percentage of iCGM measurements within ±15 percent of the corresponding blood glucose value must be calculated, and the lower one-sided 95 percent confidence bound must exceed 80 percent.
(D) For all iCGM measurements less than 70 mg/dL, the percentage of iCGM measurements within ±40 mg/dL of the corresponding blood glucose value must be calculated, and the lower one-sided 95 percent confidence bound must exceed 98 percent.
(E) For all iCGM measurements from 70 mg/dL to 180 mg/dL, the percentage of iCGM measurements within ±40 percent of the corresponding blood glucose value must be calculated, and the lower one-sided 95 percent confidence bound must exceed 99 percent.
(F) For all iCGM measurements greater than180 mg/dL, the percentage of iCGM measurements within ±40 percent of the corresponding blood glucose value must be calculated, and the lower one-sided 95 percent confidence bound must exceed 99 percent.
(G) Throughout the device measuring range, the percentage of iCGM measurements within ±20 percent of the corresponding blood glucose value must be calculated, and the lower one-sided 95 percent confidence bound must exceed 87 percent.
(H) When iCGM values are less than 70 mg/dL, no corresponding blood glucose value shall read above 180 mg/dL.
(I) When iCGM values are greater than 180 mg/dL, no corresponding blood glucose value shall read less than 70 mg/dL.
(J) There shall be no more than 1 percent of iCGM measurements that indicate a positive glucose rate of change greater than 1 mg/dL per minute (/min) when the corresponding true negative glucose rate of change is less than −2 mg/dL/min as determined by the corresponding blood glucose measurements.
(K) There shall be no more than 1 percent of iCGM measurements that indicate a negative glucose rate of change less than −1 mg/dL/min when the corresponding true positive glucose rate of change is greater than 2 mg/dL/min as determined by the corresponding blood glucose measurements.
(vi) Data demonstrating similar accuracy and rate of change performance of the iCGM in the pediatric population as compared to that in the adult population, or alternatively a clinical and/or technical justification for why pediatric data are not needed, must be provided and determined by FDA to be acceptable and appropriate.
(vii) Data must demonstrate that throughout the claimed sensor life, the device does not allow clinically significant gaps in sensor data availability that would prevent any digitally connected devices from achieving their intended use.
(2) Design verification and validation must include a detailed strategy to ensure secure and reliable means of iCGM data transmission to provide real-time glucose readings at clinically meaningful time intervals to devices intended to receive the iCGM glucose data.
(3) Design verification and validation must include adequate controls established during manufacturing and at product release to ensure the released product meets the performance specifications as defined in paragraphs (b)(1) and (b)(2) of this section.
(4) The device must demonstrate clinically acceptable performance in the presence of clinically relevant levels of potential interfering substances that are reasonably present in the intended use population, including but not limited to endogenous substances and metabolites, foods, dietary supplements, and medications.
(5) The device must include appropriate measures to ensure that disposable sensors cannot be used beyond its claimed sensor wear period.
(6) Design verification and validation must include results obtained through a usability study that demonstrates that the intended user can use the device safely and obtain the expected glucose measurement accuracy.
(7) The labeling required under § 809.10(b) of this chapter must include a separate description of the following sensor performance data observed in the clinical study performed in conformance with paragraph (b)(1) of this section for each intended use population, in addition to separate sensor performance data for each different iCGM insertion or use sites (
e.g., abdomen, arm, buttock):(i) A description of the accuracy in the following blood glucose concentration ranges: less than 54 mg/dL, 54 mg/dL to less than 70 mg/dL, 70 to 180 mg/dL, greater than 180 to 250 mg/dL, and greater than 250 mg/dL.
(ii) A description of the accuracy of positive and negative rate of change data.
(iii) A description of the frequency and duration of gaps in sensor data.
(iv) A description of the true, false, missed, and correct alert rates and a description of the available glucose concentration alert settings, if applicable.
(v) A description of the observed duration of iCGM life for the device.