(120 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 System can be used with the FreeStyle Libre 2 Sensor (14 day) or the FreeStyle Libre 2 MediRx Sensor (10 day).
The FreeStyle Libre 2 Flash Glucose Monitoring System is an integrated continuous glucose monitoring (iCGM) system that provides continuous glucose measurements every minute to provide glucose levels, trends, and real-time alarms capability to aid in the management of diabetes. The FreeStyle Libre 2 System consists of two primary components: a Sensor that transmits via Bluetooth Low Energy (BLE), and a BLE enabled display device (Reader). User initiated RFID scanning of the Sensor via Reader provides the user with real-time glucose measurements (glucose values) accompanied by trend information (glucose arrows) and historical glucose information (glucose graph). Users may use the Sensor glucose results and information provided by the System in making treatment decisions. The System also provides configurable alarms designed to warn the user of Low Glucose, High Glucose or Signal Loss. The system is intended for single-patient use at home and requires a prescription.
The Sensor is single use, disposable, and powered by a silver oxide battery. The Sensor is provided as two secondary components, Sensor Applicator and Sensor Pack (electron beam sterilized device) which are used to assemble and apply the Sensor to the back of the user's arm. During Sensor application, the sensor tail is inserted about 5.5 millimeters below the surface of the skin through the guidance of a needle. The needle is retracted back into the applicator after insertion, and the Sensor remains attached to the skin with a medical grade adhesive. The Sensor continuously measures glucose concentration in interstitial fluid and has an 8-hour memory capacity. The Sensor is factory calibrated, does not require fingerstick calibration, and can be worn for up to 14 days.
The Reader is a small handheld device that is powered by a lithium-ion rechargeable battery and uses RFID communication to start new Sensors and to scan Sensors to display and record data and uses BLE communication to issue alarms that notify the user to scan his/her sensor when glucose values pass a high or low glucose threshold. The Reader also has a built-in strip port with blood glucose functionality (that is intended to work with the FreeStyle Precision Neo Blood Glucose test strips, cleared under K171941), and a user interface that includes event logging features.
The proposed subject device is a modified FreeStyle Libre 2 Flash Glucose Monitoring System that adds compatibility with the FreeStyle Libre 2 MediRx Sensor, which can be worn for up to 10 days. The FreeStyle Libre 2 MediRx Sensor design is unchanged from that of the predicate FreeStyle Libre 2 Sensor, which remains compatible with the modified System. In addition, the Sensor glucose algorithm and Reader design of the modified System remain unchanged from those of the predicate.
The alternate 10-day wear duration of the FreeStyle Libre 2 MediRx Sensor is achieved by changing a Sensor configuration parameter at manufacturing, which is detected by the predicate Reader to automatically determine the wear duration and accordingly adjust the user interface display of remaining Sensor wear time and ensure the Sensor cannot report data beyond the configured wear duration. In addition, each Sensor type has an end of life parameter, which determines when the Sensor will automatically shut down. This functionality is already built into the Sensor and Reader and was validated as part of previously conducted software validation under K193371.
Other than the differences related to wear duration, the FreeStyle Libre 2 MediRx Sensor is identical to the predicate Sensor, and the predicate Reader functions as intended with either the predicate FreeStyle Libre 2 Sensor (14 day) or FreeStyle Libre 2 MediRx Sensor (10 day).
The provided text is related to a 510(k) premarket notification for the FreeStyle Libre 2 Flash Glucose Monitoring System, specifically for a modification to include compatibility with a 10-day wear sensor (FreeStyle Libre 2 MediRx Sensor).
The document does not describe an AI/ML-based device where the performance is presented in terms of AI metrics (e.g., accuracy, precision, recall, AUC, etc.) or a multi-reader multi-case (MRMC) study. Instead, it concerns a medical device for continuous glucose monitoring (CGM). The "algorithm" mentioned (Sensor Glucose Algorithm) refers to the internal processing of sensor signals to derive glucose values, not an AI/ML model in the context of clinical decision support or image analysis.
Therefore, many of the requested criteria (e.g., sample size for test/training set in AI context, number of experts for ground truth, adjudication method, MRMC study, standalone performance for AI, type of ground truth for AI) are not applicable to this device's submission.
However, I can extract information related to the device's clinical performance evaluation based on the provided text, which supports its substantial equivalence.
Here's a summary of the relevant information:
1. Acceptance Criteria and Device Performance:
The document states: "Clinical data from the adult and pediatric iCGM clinical studies that supported clearance of the predicate device were re-analyzed to show that use of the subject device with the FreeStyle Libre 2 MediRx Sensor for a 10-day wear duration meets the iCGM special controls for clinical performance set forth in 21 CFR 862.1355."
This indicates that the acceptance criteria are based on the iCGM special controls outlined in 21 CFR 862.1355. The document does not provide a specific table of numerical acceptance criteria or reported device performance metrics (e.g., MARD values, clinical accuracy zones) for the FreeStyle Libre 2 MediRx Sensor in this specific 510(k) submission. It relies on the re-analysis of data from the predicate device's clearance.
| Acceptance Criteria (General) | Reported Device Performance (as stated) |
|---|---|
| Meets iCGM special controls for clinical performance set forth in 21 CFR 862.1355 for 10-day wear duration. | "Clinical data from the adult and pediatric iCGM clinical studies that supported clearance of the predicate device were re-analyzed to show that use of the subject device with the FreeStyle Libre 2 MediRx Sensor for a 10-day wear duration meets the iCGM special controls..." |
2. Sample Size and Data Provenance for the Test Set:
- Sample Size Used for Test Set: Not explicitly stated for this particular 510(k). The clinical performance is based on "re-analyzed" data from "clinical studies that supported clearance of the predicate device (K193371)." To find specific sample sizes, one would need to refer to the original K193371 submission.
- Data Provenance: Not explicitly stated regarding country of origin. The data is based on "clinical studies that supported clearance of the predicate device." It's retrospective in the sense that existing data was re-analyzed for the new sensor configuration.
3. Number of Experts and Qualifications for Ground Truth:
- This question is not applicable in the context of this device. The "ground truth" for a glucose monitoring system is typically a high-accuracy reference method for blood glucose (e.g., YSI analyzer in a controlled lab setting), not expert consensus from radiologists or similar.
4. Adjudication Method for the Test Set:
- Not applicable for this type of device. Adjudication methods like '2+1' or '3+1' are common in image analysis studies where human readers provide interpretations and discrepancies are resolved. This is a continuous glucose monitoring device where performance is measured against reference glucose values.
5. MRMC Comparative Effectiveness Study:
- No, an MRMC comparative effectiveness study was not done as described for AI assistance. This device is a direct-to-patient glucose monitoring system, not an AI-assisted diagnostic tool that human readers would use to improve their performance.
6. Standalone Performance:
- Yes, in essence, standalone performance was done. The device itself provides glucose readings without human interpretation or intervention in the measurement process. The "re-analysis" of clinical data to meet iCGM special controls essentially evaluates this standalone performance of the FreeStyle Libre 2 MediRx Sensor. The output of the device (glucose value) is directly compared against a reference method.
7. Type of Ground Truth Used:
- The ground truth used for glucose monitoring devices is typically central laboratory reference glucose measurements (e.g., from a YSI glucose analyzer) taken from blood samples during clinical studies. The document states a re-analysis of "clinical studies," implying the use of such a reference method from the predicate device's trials.
8. Sample Size for the Training Set:
- Not explicitly stated/applicable in the context of AI/ML training. The "Sensor Glucose Algorithm" mentioned is likely a deterministic or model-based algorithm, not a trainable deep learning model in the sense of a "training set" for AI. If the algorithm involves parameters that were "trained" or optimized, the document does not specify the sample size used for this internal process. The primary evaluation here is of the modified sensor with an unchanged algorithm.
9. How the Ground Truth for the Training Set Was Established:
- Not explicitly stated/applicable in the context of AI/ML training. As above, the ground truth for any underlying algorithm development would refer to the reference glucose measurements used to build or validate that algorithm, but this is not typically referred to as a "training set" in the AI sense for this type of device. The document explicitly states: "the Sensor glucose algorithm... of the modified System remain unchanged from those of the predicate."
§ 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.