(157 days)
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 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 (herein referred to as the 'FreeStyle Libre 3 System' or 'System') is an integrated continuous glucose monitoring system (iCGM) that provides real time continuous glucose measurements every minute to provide glucose levels, trends, and alarms. The System requires a prescription and is intended for home use. The System consists of the following components: a Sensor which transmits via Bluetooth Low Energy (BLE), and a mobile application, FreeStyle Libre 3 App, downloaded to a compatible smartphone running on Android operating system. The FreeStyle Libre 3 System 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 make treatment decisions based in part on the Sensor glucose results provided by the System. The System also provides fixed and configurable alarms designed to warn the user of Low Glucose, High Glucose, or Signal Loss.
The document details the FreeStyle Libre 3 Continuous Glucose Monitoring System and its performance testing to support substantial equivalence to its predicate device, the FreeStyle Libre 2 Flash Glucose Monitoring System.
Here's an analysis of the acceptance criteria and study information provided:
1. Table of Acceptance Criteria and Reported Device Performance
The document states that a bridging clinical study was conducted, and the "combined System accuracy of the FreeStyle Libre 3 System and FreeStyle Libre 2 System met the iCGM special controls requirements per 21 CFR 862.1355." However, specific numerical acceptance criteria (e.g., MARD percentage, accuracy at different glucose ranges) and the exact reported performance of the FreeStyle Libre 3 System are not explicitly listed in a detailed table within the provided text segments. Instead, a general statement of meeting the iCGM special controls is given.
To fill this, we must infer that the implicit acceptance criteria are those defined by the iCGM special controls (21 CFR 862.1355) for integrated continuous glucose monitoring systems. These typically include accuracy metrics like MARD (Mean Absolute Relative Difference) against a reference method, as well as performance across different glucose ranges (hypoglycemic, euglycemic, hyperglycemic). Without the actual study report, we cannot provide specific numbers for the FreeStyle Libre 3's performance or exact acceptance criteria.
General Interpretation of iCGM Special Controls (Implicit Acceptance Criteria):
iCGM special controls generally require demonstration of:
- Accuracy: Sufficient accuracy across the glucose range (e.g., MARD values below a certain threshold when compared to a laboratory reference).
- Safety: Acceptable safety profile with minimal adverse events.
- Performance in various conditions: Performance evaluated across different patient populations, wear sites, and duration of use.
- Alarm performance: Accuracy and reliability of hypoglycemia and hyperglycemia alarms.
- Interoperability: Functionality with digitally connected devices.
2. Sample Size Used for the Test Set and Data Provenance
The document states: "ADC conducted a bridging clinical study to demonstrate comparability of the performance of the FreeStyle Libre 3 System to the predicate FreeStyle Libre 2 System, cleared under K210943."
- Sample Size for Test Set: Not explicitly stated in the provided text.
- Data Provenance: Not explicitly stated in the provided text (e.g., country of origin, retrospective or prospective). It is implied to be prospective as it's a clinical study for FDA clearance.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the text. For CGM devices, the "ground truth" (reference glucose values) is typically established using a highly accurate laboratory reference method (e.g., YSI glucose analyzer) on blood samples, not expert consensus interpreting images or clinical cases. Therefore, the concept of "experts establishing ground truth" in the way it applies to image interpretation is not directly applicable here. The ground truth would be the laboratory-measured glucose values.
4. Adjudication Method for the Test Set
The concept of an "adjudication method" (like 2+1 or 3+1) is primarily relevant for studies where multiple human readers interpret data (e.g., radiology images) and a consensus or tie-breaking mechanism is needed for the ground truth. For a CGM device, the ground truth is established by a quantitative, objective measurement (laboratory blood glucose). Therefore, an adjudication method in this context is not applicable/not mentioned as it's not a reader study.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. The FreeStyle Libre 3 is a standalone device that measures glucose; it does not involve human readers interpreting its output in a diagnostic context that would warrant an MRMC study. The "comparative effectiveness" mentioned refers to its performance against a predicate device and standard laboratory methods, not a comparison of human reader performance with and without AI assistance.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, a standalone study was done. The entire premise of the submission is to demonstrate the performance of the FreeStyle Libre 3 System as a standalone integrated continuous glucose monitoring device. The bridging clinical study, designed to show "comparability of the performance of the FreeStyle Libre 3 System to the predicate FreeStyle Libre 2 System," inherently evaluates the algorithm's performance without direct human intervention in the glucose measurement and calculation process. The FreeStyle Libre 3 delivers "real-time continuous glucose measurements every minute" and its "System accuracy" was evaluated.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for a CGM device is typically a highly accurate laboratory reference method (e.g., YSI glucose analyzer) performed on venous blood samples taken concurrently with the CGM readings. While not explicitly stated, this is the standard for CGM accuracy studies.
8. The Sample Size for the Training Set
The document mentions that the "Sensor Glucose Algorithm established for the predicate device" is the same for the FreeStyle Libre 3. It also states that the FreeStyle Libre 3 contains a "software algorithm for conversion of the raw glucose measurements from the Sensor to calculate glucose results." This implies the algorithm was developed and trained prior to this submission, likely using data from previous FreeStyle Libre sensor generations.
The sample size for the training set is not provided in this document.
9. How the Ground Truth for the Training Set was Established
Given that the "Sensor Glucose Algorithm" is the same as the predicate device, it can be inferred that the ground truth for training this algorithm was established similarly to the predicate device's clearance. This would typically involve pairing sensor readings with laboratory reference blood glucose measurements (e.g., YSI) taken from human subjects during previous clinical studies. The specific details of how this ground truth was established for the training set are not provided in the given text.
§ 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.