(322 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 iOS 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.
Here's a breakdown of the acceptance criteria and study information for the FreeStyle Libre 3 Continuous Glucose Monitoring System, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't provide a specific table of numerical acceptance criteria for clinical performance (like MARD values with defined thresholds). Instead, it states that the device "met the iCGM special controls requirements per 21 CFR 862.1355." However, it does list several performance characteristics that were "confirmed to support substantial equivalence," implying that specific acceptance criteria were met for each. Without the actual criteria for each, here's a general table based on the information provided:
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Sterility | Sterility Assurance Level (SAL) of 10^-6 | Achieved SAL of 10^-6 with minimum sterilization dose of 25 kGy (established by VDmax25 method described in ISO 11137-2). |
| Shelf-Life & Packaging | Seal integrity, user accessibility, and device functionality met | Attributes related to seal integrity, user accessibility, & device functionality (including sterile barrier system integrity) met acceptance criteria after subjecting units to worst-case sealing, sterilization, shipping, storage, handling, and transit challenges. |
| Electrical Safety | Compliance to IEC 60601-1, IEC 60601-1-6, IEC 60601-1-11 | Demonstrated compliance to IEC 60601-1: 2005(r)2012, IEC 60601-1-6:2010+A1:2013, and IEC 60601-1-11:2015. |
| Electromagnetic | Withstand EMI and emissions (IEC 60601-1-2, CISPR 11) | Verified system withstands EMI and emissions in compliance with IEC 60601-1-2 and IEC CISPR 11. Wireless coexistence testing confirmed functionality within acceptable limits in presence of common radiating electronic devices (FDA Guidance, AAMI TIR69, ANSI C63.27). Complied with FCC Part 15.225, Part 15.247, and FAA Advisory Circular RTCA DO-160. |
| Mechanical Engineering | Mechanical, electrical, and functional testing met | Test results showed mechanical, electrical, and functional testing all met acceptance criteria at system and component level. |
| Biocompatibility | Compliance with ISO 10993-1 and FDA Guidance | Evaluation and testing performed in accordance with ISO10993-1 and FDA Guidance. |
| Software V&V | Met established specifications and IEC 62304 | Results of executed protocols met acceptance criteria, supporting the System's embedded software is acceptable for intended use (in accordance with IEC 62304 and FDA Guidance). |
| Cybersecurity | Analysis of confidentiality, integrity, availability, risk mgmt. | Provided cybersecurity risk management documentation (analysis of confidentiality, integrity, availability for data, info, & software per FDA Draft Guidance). Risk assessment performed for identified threats/vulnerabilities, and appropriate risk mitigation controls implemented/tested. |
| Clinical performance | Met iCGM special controls requirements per 21 CFR 862.1355 | A bridging clinical study demonstrated comparability of performance to the predicate FreeStyle Libre 2 System, and the combined System accuracy of the FreeStyle Libre 3 and FreeStyle Libre 2 System met the iCGM special controls. |
| Human Factors | Met usability requirements for intended use (ANSI/AAMI/IEC 62366) | Risk analysis of design and user interface (in accordance with ANSI/AAMI/IEC 62366, IEC 60601-1-6, and FDA Guidance) demonstrated design changes met usability requirements. |
| Interoperability | Alignment with FDA Guidance "Design Considerations..." | Incorporated an approach for interoperability developed in alignment with FDA Guidance. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The document mentions "a bridging clinical study" but does not explicitly state the number of subjects or data points used in this study.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). The phrasing "bridging clinical study" generally implies a prospective study designed to bridge results from a previous study or device.
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 document. For glucose monitoring systems, ground truth is typically established using a highly accurate reference method (e.g., YSI glucose analyzer) rather than expert consensus on images.
4. Adjudication Method for the Test Set
This information is not provided in the document.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- No MRMC study was mentioned. The FreeStyle Libre 3 is a Continuous Glucose Monitoring (CGM) system, which provides direct glucose readings to the user, not an AI system that assists human "readers" in interpreting diagnostic images or data where MRMC studies are typically performed. The device is intended to replace blood glucose testing for treatment decisions, not to aid human interpretation of complex medical cases.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Yes, a standalone performance assessment was done. The document states, "The subject device calculates glucose information identically to the predicate device, 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." This refers to the accuracy of the algorithm itself in determining glucose values from the sensor data. The "clinical performance" testing directly assesses the device's accuracy without human intervention influencing the glucose measurement.
7. The Type of Ground Truth Used
- Reference Glucose Methods: While not explicitly named, for CGM devices, the standard ground truth for clinical accuracy studies is typically venous blood samples analyzed by a laboratory reference method, such as a YSI glucose analyzer. The document states accuracy was demonstrated, which implies comparison to such a reference.
8. The Sample Size for the Training Set
- Not provided. The document describes a "bridging clinical study" for performance validation but does not detail the size of any training sets used for algorithm development. It does state that the "Sensor Glucose Algorithm established for the predicate device" is the same, implying the algorithm's core might have been trained previously for the FreeStyle Libre 2.
9. How the Ground Truth for the Training Set was Established
- Not provided. Given that the subject device uses the "ADC Glucose Algorithm established for the predicate device," the ground truth establishment for any original training would have likely involved comparisons to laboratory reference glucose measurements in clinical studies. However, details of such a training process or ground truth for a training set are not in this document.
§ 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.