FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

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.

Device Description

The FreeStyle Libre 2 Flash Glucose Monitoring System (herein referred to as the 'FreeStyle Libre 2 System or 'System') is an integrated continuous glucose monitoring system (iCGM) that provides continuous glucose measurements every minute to provide glucose levels, trends and alerts. 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 provides the user with real-time glucose measurements (glucose values) accompanied by trend information (glucose arrows) and historical glucose information (glucose graph). The user may use the sensor glucose results and information provided by the System in making treatment decisions. The System also provides configurable alerts and alarms designed to warn the user of Low Glucose, High Glucose or Signal Loss.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the studies conducted for the FreeStyle Libre 2 Flash Glucose Monitoring System, based on the provided document:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Specific Criteria/Metric	Reported Device Performance (Adult)	Reported Device Performance (Pediatric 6-17)	Reported Device Performance (Pediatric 4-5)
Accuracy (Overall)	Percent of iCGM values within 20% of YSI reference	90.2% (95% LCL: 88.7%)	90.3% (95% LCL: 88.1%)	85.4% (95% LCL: 80.3%) (SMBG as comparator)
Accuracy (Point/Percent, iCGM Range 250 mg/dL)	% within 15%	75.9% (70-180mg/dL), 89.1% (181-250mg/dL), 94.0% (>250mg/dL)	78.0% (70-180mg/dL), 86.0% (181-250mg/dL), 92.2% (>250mg/dL)	N/A (SMBG used for 4-5)
Accuracy (Point/Percent, YSI Range 250 mg/dL)	% within 15%	76.5% (70-180mg/dL), 87.9% (181-250mg/dL), 90.9% (>250mg/dL)	74.3% (70-180mg/dL), 86.6% (181-250mg/dL), 90.2% (>250mg/dL)	N/A (SMBG used for 4-5)
Precision	Mean Coefficient of Variation (Mean %CV)	5.7%	5.8%	4.8%
Low Glucose Alarm (e.g., 70 mg/dL)	True Alarm Rate	86.0%	80.3%	N/A
	False Alarm Rate	14.0%	19.7%	N/A
	Correct Detection Rate	89.3%	93.5%	N/A
	Missed Detection Rate	10.7%	6.5%	N/A
High Glucose Alarm (e.g., 200 mg/dL)	True Alarm Rate	99.2%	98.0%	N/A
	False Alarm Rate	0.8%	2.0%	N/A
	Correct Detection Rate	97.1%	98.0%	N/A
	Missed Detection Rate	2.9%	2.0%	N/A
Sensor Stability (MARD)	Mean Absolute Relative Difference (MARD) throughout wear duration	9.9% (Beginning), 8.5% (Early Middle), 8.8% (Late Middle), 9.1% (End)	10.7% (Beginning), 8.0% (Early Middle), 9.7% (Late Middle), 10.2% (End)	N/A
Sensor Life	Survival Rate by Day 14	71.1%	78.1%	N/A
Glucose Reading Availability	Capture Rate over wear duration	Ranges from 98.1% to 98.6%	Ranges from 94.6% to 96.0%	N/A
Reportable Range	40 to 400 mg/dL	Supported by clinical study data (display 'LO' or 'HI' outside range)	Supported by clinical study data (display 'LO' or 'HI' outside range)	Supported by clinical study data (display 'LO' or 'HI' outside range)
Ascorbic Acid Interference	Max average sensor bias after 3x1000mg doses	Less than 20 mg/dL (after second and third 1000mg doses)	Not explicitly stratified by age for this study, assumed adults.	N/A

Study Information

Sample Size and Data Provenance:
- Clinical Accuracy Studies (Study 1 & Study 2):
  - Study 1 (Adults): 146 subjects (91.1% Type 1, 8.9% Type 2 diabetes, all requiring insulin).
  - Study 2 (Pediatric): 139 subjects (98.6% Type 1, 1.4% Type 2 diabetes, all requiring insulin).
  - Age Groups in Study 2 (for YSI comparison): 77 pediatric subjects for 180 mg/dL range. Specific breakdown for 4-5 and 6-17 years where YSI was used.
  - Age Groups in Study 2 (for SMBG comparison): 8 pediatric subjects (4-5 years old) only had SMBG as comparator.
  - Data Provenance: Prospective, multi-center studies conducted at five (adult) and four (pediatric) centers in the United States.
- Ascorbic Acid Interference Study: 60 subjects (adults, age 18 and older) with diabetes, across 4 sites.
- Precision Study (from Clinical Studies):
  - Adults (18+): 146 subjects, 26,791 paired readings.
  - Pediatric 4-5 years: 7 subjects, 248 paired readings.
  - Pediatric 6-17 years: 130 subjects, 10,623 paired readings.
Number of Experts and Qualifications for Ground Truth:
- The document implies that the ground truth for glucose values was established using a "laboratory glucose reference" (YSI) analyzer. While YSI analyzers are highly accurate, the document does not explicitly state the number of experts or their qualifications for establishing the ground truth. It refers to the YSI as the comparator method, which is a laboratory instrument, not human experts. For pediatric subjects aged 4-5 years, Self-Monitoring Blood Glucose (SMBG) tests were used as the comparator method.
Adjudication Method for the Test Set:
- Not applicable in the traditional sense of medical image adjudication. The "ground truth" was established by a laboratory reference method (YSI for most cases, SMBG for some pediatric cases). There's no indication of an adjudication process involving multiple human readers to resolve discrepancies in ground truth measurements. The comparison is between the device and the reference instrument.
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, an MRMC comparative effectiveness study was not done. This type of study typically involves human readers interpreting cases with and without AI assistance. The FreeStyle Libre 2 is a standalone diagnostic device that measures glucose directly, so its performance is compared against a reference standard (YSI, SMBG), not human interpretation with or without AI.
Standalone (Algorithm Only) Performance:
- Yes, the studies primarily assessed standalone performance. The device automatically provides continuous glucose measurements. The "iCGM glucose values" are the output of the algorithm. The intent is for the device to replace blood glucose testing for treatment decisions, which is a standalone use case. Human interpretation of trends and patterns is part of the overall management, but the device's accuracy itself is assessed in a standalone manner against the reference.
Type of Ground Truth Used:
- Laboratory Reference and Self-Monitoring Blood Glucose (SMBG):
  - For adult subjects and pediatric subjects aged 6-17 years, the primary ground truth was established by YSI glucose measurements. YSI (Yellow Springs Instrument) is a common laboratory method considered a highly accurate reference for glucose.
  - For pediatric subjects aged 4-5 years, the ground truth was established by SMBG (Self-Monitoring Blood Glucose) tests.
Sample Size for the Training Set:
- The document mentions "clinical evaluation" and "pivotal clinical studies" but does not explicitly state the sample size of a training set specifically for algorithm development or machine learning. The provided clinical studies (Study 1 and Study 2) describe the test sets used for performance evaluation, not necessarily for training the algorithm. CGM devices typically use complex calibration algorithms developed with extensive internal data that is not always detailed in 510(k) summaries.
How the Ground Truth for the Training Set Was Established:
- As the document does not provide details on a specific training set or its size, it also does not elaborate on how the ground truth for such a set was established. We can infer that similar high-accuracy laboratory reference methods (like YSI) would have been used during the development and calibration phases of the device, prior to the validation studies described in the submission.

Summary

Regulation Number and Section

§ 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.