(200 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 2 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, including automated insulin dosing (AID) systems. The System can be used alone or in conjunction with these digitally connected devices for the purpose of managing diabetes.
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 2 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, including automated insulin dosing (AID) systems. The System can be used alone or in conjunction with these digitally connected devices for the purpose of managing diabetes.
The FreeStyle Libre 2 Flash Glucose Monitoring System (with modified Sensor tail), hereinafter also referred to as 'modified FSL2 System' and FreeStyle Libre 3 Continuous Glucose Monitoring System (with modified Sensor tail), hereinafter also referred to as 'modified FSL3 System' are integrated continuous glucose monitoring (iCGM) systems that provide continuous glucose measurements every minute to provide glucose levels, trends, and real-time alarms capability to aid in the management of diabetes. The Systems also provide configurable alarms designed to warn the user of Low Glucose or Signal Loss. The user may make treatment decisions based in part on the Sensor glucose results provided by the Systems require a prescription and are intended for home use.
The FreeStyle Libre 2 System consists of the FreeStyle Libre 2 Sensor and either the FreeStyle Libre 2 Reader or the FreeStyle Libre 2 App downloaded to a compatible smartphone as a primary display device. The FreeStyle Libre 3 System consists of the FreeStyle Libre 3 Sensor and the FreeStyle Libre 3 App downloaded to a compatible smartphone as a primary display device.
Both the FreeStyle Libre 2 and FreeStyle Libre 3 Systems are compatible with the Libre Data Sharing API cleared in K223537. 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 Abbott FreeStyle Libre 2 Flash Glucose Monitoring System and FreeStyle Libre 3 Continuous Glucose Monitoring System sought clearance for modified sensor tails to reduce vitamin C interference, extend sensor wear to 15 days, and enable compatibility with automated insulin dosing (AID) systems.
Here's an analysis of the acceptance criteria and supporting studies:
1. Table of Acceptance Criteria & Reported Device Performance:
The document doesn't explicitly list a table of "acceptance criteria" with specific numeric targets for device performance. Instead, it states that the devices meet the iCGM special controls for clinical performance set forth in 21 CFR 862.1355. This regulation broadly outlines requirements for accuracy, reliability, and safety of integrated Continuous Glucose Monitoring systems.
However, based on the provided text, we can infer some key performance objectives and the reported outcome:
| Acceptance Criteria (Inferred from Changes & Regulations) | Reported Device Performance |
|---|---|
| Accuracy across measuring range (15-day wear) | The clinical study demonstrated that the subject devices meet the iCGM special controls for clinical performance. Specific accuracy metrics (e.g., MARD) are not provided in this summary but would be part of the full submission. |
| Reduced Vitamin C Interference | An additional clinical study evaluated the effects of high doses of vitamin C, and the results showed the devices met iCGM special controls. Labeling was updated to reflect Vitamin C interference at doses >1000 mg/day (improved from >500 mg/day for the predicate). |
| Extended Sensor Wear Duration (from 14 to 15 days) | The subject devices (modified FreeStyle Libre 2 and 3 Sensors) are designed for a 15-day wear duration, and performance was evaluated throughout this duration in the clinical study. |
| Compatibility with Automated Insulin Dosing (AID) systems | Interoperability testing and an interoperability communication plan were provided to ensure secure and reliable data transfer with digitally connected devices, including AID systems. |
| Software Functionality and Safety | Software regression testing was conducted in accordance with established specifications and IEC 62304. Results met acceptance criteria. |
| Non-clinical Performance | Non-clinical performance testing was conducted as per internal design control process requirements, and results met acceptance criteria. |
| Known Performance of Unaffected Aspects | Sterilization, biocompatibility, shelf life stability, packaging integrity/shipping integrity, mechanical engineering, electrical safety and electromagnetic compatibility, and human factors were established in predicate/reference devices and are not affected. Cybersecurity for FSL3 also relies on existing data. |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size: The clinical study evaluated performance in adult (18 years and older) and pediatric (2 to 17 years) participants with diabetes. Specific numbers of participants within these age groups are not provided in this summary.
- Data Provenance: The document does not specify the country of origin. It indicates the studies were clinical studies, implying a prospective nature.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
The document mentions that the clinical study evaluated performance with respect to reference venous plasma sample YSI measurements.
- Ground Truth Providers: YSI measurements are obtained from laboratory instruments, which are considered the gold standard for glucose measurement. The "experts" involved would be trained lab technicians and medical professionals responsible for collecting and processing blood samples and operating the YSI instrumentation.
- Qualifications: Not explicitly stated, but they would be certified laboratory personnel and healthcare providers responsible for patient care and sample collection within a clinical study setting.
4. Adjudication Method for the Test Set:
Not applicable. The ground truth was established by YSI laboratory measurements, not subjective expert review or adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
A Human-in-the-loop or MRMC study is not applicable for this device type (Continuous Glucose Monitoring System). The device provides continuous glucose values, and its performance is assessed against a laboratory reference, not human interpretation of images or other data that would involve multiple readers.
6. Standalone Performance:
Yes, the studies described are primarily focused on the standalone performance of the algorithm (as embedded in the device) in measuring glucose levels against a reference method (YSI venous plasma samples). The "clinical study" directly assesses how well the device's sensor and algorithm perform without direct human intervention in the glucose reading process itself, other than the placement and use of the device by participants.
7. Type of Ground Truth Used:
The ground truth used was venous plasma sample YSI measurements. This is a highly accurate and accepted laboratory reference method for glucose concentration.
8. Sample Size for the Training Set:
The document does not specify the sample size for the training set used for the device's glucose algorithm. It mentions that the "ADC Glucose Algorithm established for the predicate device" is used, implying that the core algorithm was developed and trained previously, and this submission focuses on modifications and re-validation.
9. How the Ground Truth for the Training Set Was Established:
The document does not specify how the ground truth for the training set of the ADC Glucose Algorithm was established. However, given that the clinical performance evaluation uses venous plasma YSI measurements as ground truth, it is highly probable that similar high-accuracy reference methods would have been employed during the development and training of the original algorithm.
§ 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.