FreeStyle Libre 3 Continuous Glucose Monitoring System
Device Facts
| Record ID | K212132 |
|---|---|
| Device Name | FreeStyle Libre 3 Continuous Glucose Monitoring System |
| Applicant | Abbott Diabetes Care, Inc. |
| Product Code | QLG · Clinical Chemistry |
| Decision Date | May 26, 2022 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1355 |
| Device Class | Class 2 |
| Attributes | Software as a Medical Device, Pediatric |
Indications for Use
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.
Device Story
Integrated continuous glucose monitoring (iCGM) system; measures interstitial fluid glucose via subcutaneous sensor; uses glucose oxidase electrochemical reaction; converts current to glucose values. Sensor transmits data via Bluetooth Low Energy (BLE) to FreeStyle Libre 3 App on iOS smartphone. Provides real-time glucose measurements, trends, and alarms (Low/High/Signal Loss). Used in home setting by patients; supports therapy decisions. System autonomously communicates with digitally connected devices. Benefits include continuous monitoring without fingersticks, trend tracking, and automated alerts for glycemic management.
Clinical Evidence
Clinical evidence includes three studies (n=385 total) evaluating precision and accuracy. Study 3 (n=100) served as a confirmatory study for design modifications. Primary endpoints included MARD and concurrence rates against YSI laboratory reference (adults/pediatric 6-17) or SMBG (pediatric 4-5). Adult MARD was 9.8% (70-180 mg/dL range); pediatric MARD was 10.1% (70-180 mg/dL range). Alarm performance, sensor stability, and glucose capture rates were validated over 14-day wear.
Technological Characteristics
Amperometric electrochemical sensor using glucose oxidase; silver oxide battery; 14-day wear life; factory calibrated. Connectivity: BLE for data streaming, NFC for sensor activation. Sterilization: Electron beam (ISO 11137-1/2). Compliance: IEC 60601-1, IEC 60601-1-2, IEC 60601-1-11, CISPR 11, AAMI TIR69, ANSI C63.27. Biocompatibility: ISO 10993-1.
Indications for Use
Indicated for management of diabetes in persons age 4 and older. Contraindicated for use with automated insulin dosing (AID) systems, including closed loop and insulin suspend systems. Not for use in pregnant individuals, those on dialysis, or the critically ill.
Regulatory Classification
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.
Special Controls
*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.
Predicate Devices
- FreeStyle Libre 2 Flash Glucose Monitoring System (with FreeStyle Libre 2 App) (K201761)
Related Devices
- K210943 — FreeStyle Libre 2 Flash Glucose Monitoring System (with FreeStyle Libre 2 App) · Abbott Diabetes Care, Inc. · Nov 22, 2021
- K233537 — FreeStyle Libre 3 Continuous Glucose Monitoring System; FreeStyle Libre 2 Flash Glucose Monitoring System · Abbott Diabetes Care, Inc. · Apr 23, 2024
- K201761 — FreeStyle Libre 2 Flash Glucose Monitoring System (with FreeStyle Libre 2 App) · Abbott Diabetes Care, Inc. · Jul 30, 2021
- K213996 — FreeStyle Libre 3 Continuous Glucose Monitoring System · Abbott Diabetes Care, Inc. · May 26, 2022
Submission Summary (Full Text)
{0}
FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY AND INSTRUMENT
## I Background Information:
A 510(k) Number
K212132
B Applicant
Abbott Diabetes Care Inc.
C Proprietary and Established Names
FreeStyle Libre 3 Continuous Glucose Monitoring System
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| QLG | Class II | 21 CFR 862.1355 - Integrated Continuous Glucose Monitoring System | CH - Clinical Chemistry |
## II Submission/Device Overview:
A Purpose for Submission:
Modifications to the cleared FreeStyle Libre 2 Flash Glucose Monitoring System to display real-time glucose data via Bluetooth without scanning the Sensor.
B Measurand:
Glucose in Interstitial Fluid
C Type of Test:
Quantitative, amperometric assay (Glucose Oxidase)
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
{1}
K212132 - Page 2 of 25
## III Intended Use/Indications for Use:
### A Intended Use(s):
See Indications for Use below.
### B Indication(s) for Use:
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.
### C Contraindication(s)
Due to an administrative error, the reference to wear period was erroneously included in the Contraindications section of the previous 510(k) Decision Summary. It is now removed from this section and added to the Special Conditions for Use Statements section below.
The System must not be used with automated insulin dosing (AID) systems, including closed loop and insulin suspend systems.
The System must be removed prior to Magnetic Resonance Imaging (MRI), Computed Tomography (CT) scan, or high-frequency electrical heat (diathermy) treatment. The effect of MRI, CT scans, or diathermy on the performance of the System has not been evaluated. The exposure may damage the Sensor and may impact proper function of the device which could cause incorrect readings.
### D Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
The sensor can be worn up to 14 days. Remember to always have your next Sensor available before your current one ends so you can keep getting your glucose readings.
Do not use the System in people less than 4 years of age. The System is not cleared for use in people under 4 years of age.
Do not use the System if you are pregnant, on dialysis, or critically ill. The System is not cleared for use in these groups and it is not known how different conditions or medications common to these populations may affect performance of the System.
The FreeStyle Libre 3 app installed on a phone is intended for use by a single person. It must not be used by more than one person due to the risk of misinterpreting glucose information.
{2}
Performance of the System when used with other implanted medical devices, such as pacemakers, has not been evaluated.
Taking ascorbic acid (vitamin C) supplements while wearing the Sensor may falsely raise Sensor glucose readings. Taking more than 500 mg of ascorbic acid per day may affect the Sensor readings which could cause you to miss a severe low glucose event. Ascorbic acid can be found in supplements including multivitamins. Some supplements, including cold remedies such as Airborne® and Emergen-C®, may contain high doses of 1000 mg of ascorbic acid and should not be taken while using the Sensor. See your health care professional to understand how long ascorbic acid is active in your body.
Do not ignore symptoms that may be due to low or high blood glucose: if you are experiencing symptoms that are not consistent with the glucose readings, consult your health care professional.
Use your blood glucose meter to make diabetes treatment decisions when you see the symbol during the first 12 hours of wearing a Sensor, if your Sensor glucose reading does not match how you feel or if the reading does not include a number.
For you to receive alarms, they must be on and your device should be within 33 feet of you at all times. The transmission range is 33 feet unobstructed. If you are out of range, you may not receive alarms.
If you suspect that the temperature may exceed 82°F (for example, in an unairconditioned home in summer), you should refrigerate your Sensor Kit. Do not freeze your Sensor Kit.
Do not force close the App. The App must be running in the background to receive alarms. If you force close the App you will not receive alarms. Re-open the App to ensure you will receive alarms.
E Special Instrument Requirements:
N/A
IV Device/System Characteristics:
A Device Description:
The FreeStyle Libre 3 Continuous Glucose Monitoring System is an integrated continuous glucose monitoring system (iCGM) that provides continuous glucose measurements every minute to provide glucose levels, trends, and alerts. 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 iOS operating system. When used with the FSL 3 the proposed mobile app allows the user to activate FSL3 sensors, provides real-time glucose measurements (glucose values) accompanied by trend information (glucose arrows) and historical glucose information (glucose graph) thus allowing the user may make treatment decisions, and connect with cloud-based applications to store as shareable data (e.g. LibreView).
System Components and Features
Alarms: The FSL3 App can issue the following glucose and system alarms:
K212132 - Page 3 of 25
{3}
- Mandatory Alarms: Urgent Low Glucose, Replace Sensor, Sensor Ended, App Stopped (Force Closed)
- These alarms cannot be turned off or modified and will always sound regardless of the phone's sound and vibe or Do Not Disturb (DND) settings.
- Optional Alarms: Low Glucose Alarm, High Glucose Alarm, Signal Loss Alarm
- For the optional alarms above, the Override DND setting is turned on by default; therefore, the user receives these alarms regardless of the phone's sound, vibe or DND settings. If the user wishes to have the optional alarms follow the phone's sound and vibe settings, the user must turn off Override DND from the App.
**Hardware / Software compatibility**: The FreeStyle Libre 3 Continuous Glucose Monitoring System is intended for use with Field Communication (NFC) and BLE-enabled smartphones running compatible iOS. The FSL3 app is compatible with FSL3 Sensors.
**Secondary Viewers**: LibreView and LibreLinkUp (LLU) provide a cloud-based repository for glucose measurement data and mobile app that allows caregivers to receive and view glucose data (including glucose alarms) from users who use the FSL3 App with their sensor. Secondary viewers are not intended to be used for immediate clinical decision making.
## B Principle of Operation:
The FreeStyle Libre 3 System provides the user with real-time glucose measurements (glucose values) accompanied by trend information (glucose arrows) and historic 12-hour glucose results (glucose graph) that are presented on the App. The real-time glucose measurements and glucose arrows are calculated by the Sensor software based upon glucose sampling, also performed by the Sensor.
The Sensor is designed to measure glucose levels in the user's interstitial fluid through an amperometric electrochemical sensor component. The sensor tail is inserted into the subcutaneous tissue and generates an electrical current via the oxidation of glucose from the interstitial fluid. The FreeStyle Libre 3 System is intended for single patient use. The App can only pair to one Sensor at a time. The Sensor is disposable and may be worn up to 14 days. The Sensor automatically terminates after 14 days of use.
## C Instrument Description Information:
1. **Instrument Name**:
Freestyle Libre 3 Continuous Glucose Monitoring System
2. **Specimen Identification**:
N/A
3. **Specimen Sampling and Handling**:
N/A
K212132 - Page 4 of 25
{4}
4. Calibration:
The sensor is factory calibrated and cannot be calibrated by the user.
5. Quality Control:
N/A
V Substantial Equivalence Information:
A Predicate Device Name(s):
FreeStyle Libre 2 Flash Glucose Monitoring System (with FreeStyle Libre 2 App)
B Predicate 510(k) Number(s):
K201761
C Comparison with Predicate(s):
| Device & Predicate Device(s): | K212132 | K201761 |
| --- | --- | --- |
| Device Trade Name | Freestyle Libre 3
Continuous Glucose Monitoring System | FreeStyle Libre 2 Flash Glucose Monitoring System (with FreeStyle Libre 2 App) |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | 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 | Same |
K212132 - Page 5 of 25
{5}
K212132 - Page 6 of 25
| | 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. | |
| --- | --- | --- |
| General Device Characteristic Differences | | |
| Applicator Assembly | No assembly required | Assembly of sensor to applicator required |
| Primary display device | FreeStyle Libre 3 App | FreeStyle Libre 2 App (iOS) or FreeStyle Libre 2 Reader |
| Transmitter Dimension | 2.9 mm height/ 21 mm diameter | 5 mm height/ 30 mm diameter |
| Information provided with glucose alarm | Alarm type, glucose result and trend arrow | Alarm type |
| Method of Data transfer from Sensor | Bluetooth Low Energy (BLE) for both glucose data and alarms | BLE for glucose alarms. User-initiated scan via NFC required to display glucose data. |
| BLE communication range | 33 feet unobstructed | 20 feet unobstructed |
VI Standards/Guidance Documents Referenced:
- 21 CFR 862.1355 integrated continuous glucose monitoring system (iCGM)) special controls
- ISO 14971- “Medical Devices – Application of risk management to medical devices”
{6}
- ANSI AAMI 60601-1- “Medical electrical equipment – Part 1: General requirements for basic safety”
- AAMI TIR69 – “Risk Management of Radio-frequency Wireless Coexistence for Medical Devices and Systems”
- ANSI AAMI IEC 62366-1 – “Medical devices - Application of usability engineering to medical devices”
- AAMI / ANSI HE75- “Human Factors Engineering - Design of Medical Devices”
- AAMI TIR57: 2016- “Principles for medical device security – Risk management”
- IEC 60601-1-11 - “Medical electrical equipment — Part 1-11: General requirements for basic safety and essential performance — Collateral standard: Requirements for medical electrical equipment and medical electrical systems used in the home healthcare environment”
- ANSI C63.27-2017 - “American National Standard for Evaluation of Wireless Coexistence”
- IEC 60601-1-2 - “General requirements for basic safety and essential performance – Collateral standard: Electromagnetic”
- IEC 62304 - “Medical device software – Software life cycle processes”
- ISO 15223-1- “Medical device – Symbols to be used with medical device labels, labeling and information to be supplied – Pt 1: General Requirements”
- AAMI / ANSI / ISO 10993-1- “Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing within a risk management process”
- ISO 11607-1 - “Packaging for terminally sterilized medical devices - Part 1: Requirements for materials, sterile barrier systems and package”
- ISO 11607-2 - “Packaging for terminally sterilized medical devices - Part 2: Validation requirements for forming, sealing and assembly processes”
- ASTM D4169 - “Standard Practice for Performance Testing of Shipping Containers and System”
- IEC 60417 - “DB Graphical Symbols for Use on Equipment”
- FAA AC no. 91.21-1C - “Use of Portable Electronic Devices Aboard Aircraft”
- FCC Title 47: Part 15 - “Radio Frequency Devices, Conducted Limits, Section 15.225 and Section 15.247”
## VII Performance Characteristics (if/when applicable):
### A Analytical Performance:
#### 1. Precision/Reproducibility:
The iCGM performance was evaluated in clinical studies described below in section C(3) below. A sub-set of study participants wore two sensors concurrently, one on the back of each upper arm, to evaluate device precision for a period of up to 14 days.
For adults, the paired absolute relative difference (PARD) between the two Sensors was 5.9% with coefficient of variation (CV) of 4.2%. For children ages 4-5, PARD was 4.7% with CV of 3.3%. For children ages 6-17, PARD was 8.1% with CV of 5.7%. Paired absolute difference (PAD) is a measurement of absolute difference (in mg/dL) between paired CGM readings, while PARD is the absolute relative difference (in %) between paired CGM readings.
K212132 - Page 7 of 25
{7}
Precision by subject age group (total subjects n=385)
| Subject age group | Coefficient of Variation (%) | Paired Absolute Difference (mg/dL) | Paired Absolute Relative Difference (%) | Number of Subjects | Number of Paired Readings |
| --- | --- | --- | --- | --- | --- |
| Adults (18+) | 4.8 | 10.3 | 6.8 | 201 | 249388 |
| Pediatric 4-5 years | 3.5 | 9.4 | 4.9 | 11 | 17152 |
| Pediatric 6-17 years | 5.5 | 12.5 | 7.8 | 169 | 175994 |
2. Linearity:
See Assay Reportable Range below.
3. Analytical Specificity/Interference:
Previously established in K193371. Refer to warnings in the labeling for risks associated with ascorbic acid (vitamin C) interference.
4. Assay Reportable Range:
The reportable range for the FreeStyle Libre 3 System is 40 to 400 mg/dL. Data supporting this claimed measurement range was generated in the clinical study described in Section C(3) below.
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
The FreeStyle Libre 2 sensor has a storage shelf-life of 3 months. Shelf-life was evaluated at 36°–82° Fahrenheit within the humidity range of 10% - 90%.
6. Detection Limit:
If a glucose measurement is less than 40 mg/dL, the result will be displayed by the system as 'LO'. If the glucose measurement exceeds 400 mg/dL, the result will be displayed as 'HI'. Data supporting this claimed measurement range was generated in the clinical study described in Section C(3) below.
7. Assay Cut-Off:
See Assay Reportable Range and Detection Limit above.
8. Accuracy (Instrument):
Not applicable
K212132 - Page 8 of 25
{8}
9. Carry-Over:
Not applicable
## B Comparison Studies:
1. Method Comparison with Predicate Device:
Not applicable. Accuracy is determined by comparing device values to an FDA cleared laboratory grade glucose measurement method.
2. Matrix Comparison:
Not applicable. Interstitial fluid is the only indicated matrix.
## C Clinical Studies:
1. Clinical Sensitivity:
Not applicable.
2. Clinical Specificity:
See section A(3) above.
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
The FreeStyle Libre 3 Continuous Glucose Monitoring System is physically identical to the predicate FreeStyle Libre 2 Flash Glucose Monitoring System (with the Libre 2 App) except for the differences in sensor transmission dimensions as noted in Section V.C above. Therefore, pivotal clinical studies for the FreeStyle Libre 2 Flash Glucose Monitoring System (Studies 1 and 2 in the table below) was leveraged. Additionally, Abbott Diabetes Care conducted a confirmatory clinical study (referred to as Study 3 hereafter) to evaluate the clinical impact of the design modifications made to the device hardware.
K212132 - Page 9 of 25
{9}
| Study Element | Study 1 | Study 2 | Study 3 |
| --- | --- | --- | --- |
| Subject Population | Adult
18 + years of age
Type 1 or Type 2 Diabetes | Pediatric
4 – 17 years of age
Type 1 or Type 2 Diabetes | Adult and Pediatric
4 + years of age
Type 1 or Type 2 Diabetes |
| Sample size | 146 subjects | 139 subjects, of which 8 subjects were between ages 4 and 5 | Adult: 56 subjects
Pediatric: 44 subjects 17 years of age or younger, of which 5 subjects were between ages 4 and 5 |
| Glycemic Challenging | Yes | | No |
Study 3 was conducted at 4 centers in the US with 100 adult and pediatric subjects in total (83.0 % Type 1, 17.0% Type 2). All subjects required insulin to manage their diabetes. 56 adult subjects were aged 18 and older, 39 pediatric subjects were aged six to seventeen and 5 pediatric subjects were aged four to five. 81 subjects were analyzed during the beginning of the Sensor wear period (day 1, 2 or 3), 46 subjects were analyzed during the early middle period (day 7 or 8), 47 subjects were analyzed during the late middle period (day 9 or 12), and 34 subjects were analyzed during the end period (day 13 or 14).
Subjects aged six and older had their venous blood glucose analyzed for up to 16 hours over one or two separate visits to the clinical center. Each visit lasted up to eight hours. The venous blood samples were analyzed using a laboratory reference method, the Yellow Springs Instrument Life Sciences 2300 STAT Plus™ Glucose & Lactate Analyzer (YSI). Self-monitoring blood glucose meter (SMBG) was used as the comparator method for subjects 4-5 years of age.
Glucose values were obtained from the system and from the comparator at the same or similar time. Data from Study 1 (the adult Libre 2 study) was combined with data from the adult cohort in Study 3, and data from Study 2 (the pediatric Libre 2 study) was combined with data from the pediatric cohort in Study 3.
For values below 70 mg/dL, absolute differences in mg/dL were compared to the comparator method. For values of 70 mg/dL and above, percentage differences compared to the comparator method were calculated.
K212132 - Page 10 of 25
{10}
Percent and Point Accuracy by iCGM Glucose Range (Adult; n=200, combined)
| CGM Glucose Range (mg/dL) | No. Pair | Percent within 15 mg/dL (95% LCL) | Percent within 40 mg/dL (95% LCL) | Percent within 15% (95% LCL) | Percent within 40% (95% LCL) | Mean Bias, mg/dL (95 % UCL*) |
| --- | --- | --- | --- | --- | --- | --- |
| <70 | 3667 | 88.1 (86.2) | 99.2 (98.9) | | | -4.7 (-3.4) |
| 70-180 | 11128 | | | 79.8 (77.7) | 99.7 (99.6) | -5.7 (-4.4) |
| >180 | 8708 | | | 92.6 (91.1) | 100.0 (99.9) | -5.0 (-3.1) |
* 95 % LCL is the lower bound of the 95 % confidence limit and the 95% UCL is the upper bound of the 95% confidence limit
Percent and Point Accuracy by iCGM Glucose Range (Pediatric* n=168, Combined)
| CGM Glucose Range (mg/dL) | No. Pair | Percent within 15 mg/dL (95% LCL) | Percent within 40 mg/dL (95% LCL) | Percent within 15% (95% LCL) | Percent within 40% (95% LCL) | Mean Bias, mg/dL (95 % UCL) |
| --- | --- | --- | --- | --- | --- | --- |
| <70 | 1068 | 82.3 (77.5) | 98.1 (96.8) | | | -8.9 (-6.1) |
| 70-180 | 4149 | | | 78.8 (75.9) | 99.4 (99.1) | -5.1 (-3.3) |
| >180 | 3397 | | | 90.4 (88.4) | 99.7 (99.5) | -1.5 (1.2) |
*Includes children 6-17 years of age. No YSI Comparator measurements were obtained for children 4-5 years of age.
Percent and Point Accuracy by Comparator Method (CM) Glucose Range (Adults)
| CM Glucose Range (mg/dL) | No. Pair | Percent within 15 mg/dL (95% LCL) | Percent within 40 mg/dL (95% LCL) | Percent within 15% (95% LCL) | Percent within 40% (95% LCL) | Mean Bias, mg/dL (95 % UCL) |
| --- | --- | --- | --- | --- | --- | --- |
| <70 | 913 | 95.6 (93.8) | 99.9 (99.7) | | | 1.7 (2.6) |
| 70-180 | 4168 | | | 76.7 (73.6) | 99.1 (98.7) | -4.6 (-3.5) |
| >180 | 3533 | | | 89.0 (86.7) | 99.8 (99.6) | -8.0 (-6.1) |
K212132 - Page 11 of 25
{11}
Percent and Point Accuracy by Comparator Method (CM) Glucose Range (Pediatric*)
| CM Glucose Range (mg/dL) | No. Pair | Percent within 15 mg/dL (95% LCL) | Percent within 40 mg/dL (95% LCL) | Percent within 15% (95% LCL) | Percent within 40% (95% LCL) | Mean Bias, mg/dL (95 % UCL) |
| --- | --- | --- | --- | --- | --- | --- |
| <70 | 913 | 95.6 (93.8) | 99.9 (99.7) | | | 2.2 (3.5) |
| 70-180 | 4168 | | | 76.7 (73.6) | 99.1 (98.7) | -3.5 (-1.9) |
| >180 | 3533 | | | 89.0 (86.7) | 99.8 (99.6) | -5.2 (-2.3) |
*Includes children 6-17 years of age. No YSI Comparator measurements were obtained for children 4-5 years of age.
Percent of iCGM values within 20% of Comparator Glucose Values
| CGM Glucose Range(mg/dL) | No. Pair | No. Subject | Percent within 20% (95% LCL) |
| --- | --- | --- | --- |
| Adult (18 years and up) | 23503 | 200 | 91.0 (89.9) |
| Pediatric (6- 17 years) | 8614 | 168 | 90.2 (88.3) |
| Pediatric (4-5 years old)* | 413 | 13 | 85.2 (81.3) |
* Subjects 4-5 years old were compared to an SMBG meter
Percent values within 15%/15 mg/dL, 20%/20 mg/dL and 40%/40 mg/dL stratified by glucose ranges of <54, 54-69, 70-180. 181-250 and >250 mg/dL for iCGM and laboratory comparator were also provided. For pediatric subjects ages 4-5, values were compared to SMBG.
Accuracy to Comparator within iCGM Glucose Ranges (Adult; n=200, combined)
| CGM Glucose Level †(mg/dL) | Number of CGM-Reference Pairs | Percent Within ±15 mg/dL | Percent Within ±20 mg/dL | Percent Within ±40 mg/dL | Percent Within ±15% | Percent Within ±20% | Percent Within ±40% | Mean bias (mg/dL) | MARD *(%) |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| <54 | 543 | 84.7 | 92.6 | 99.4 | | | | -6.7 | 14.2 |
| 54-69 | 3124 | 88.7 | 93.7 | 99.0 | | | | -3.6 | 11.0 |
| 70-180 | 11128 | | | | 79.8 | 88.8 | 99.3 | -4.9 | 9.8 |
| 181-250 | 4112 | | | | 90.9 | 96.0 | 99.9 | -7.7 | 7.2 |
| >250 | 4596 | | | | 94.1 | 98.0 | 100.0 | -5.9 | 6.0 |
* Mean Absolute Relative Difference
K212132 - Page 12 of 25
{12}
Accuracy to Comparator within iCGM Glucose Ranges (Pediatric*)
| CGM Glucose Level^{†}(mg/dL) | Number of CGM-Reference Pairs | Percent Within ±15 mg/dL | Percent Within ±20 mg/dL | Percent Within ±40 mg/dL | Percent Within ±15% | Percent Within ±20% | Percent Within ±40% | Mean bias (mg/dL) | MARD (%) |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| <54 | 153 | 68.6 | 75.8 | 95.4 | | | | -12.1 | 18.8 |
| 54-69 | 915 | 84.6 | 88.9 | 96.7 | | | | -5.6 | 12.6 |
| 70-180 | 4149 | | | | 78.8 | 87.8 | 98.9 | -4.9 | 10.1 |
| 181-250 | 1640 | | | | 87.9 | 95.4 | 99.7 | -7.1 | 7.7 |
| >250 | 1757 | | | | 92.7 | 97.8 | 99.8 | -2.1 | 6.9 |
* Includes children 6-17 years of age. No YSI measurements were obtained for children 4-5 years of age.
Accuracy to Comparator within Comparator Glucose Ranges (Adult; n=200, Combined)
| CM Glucose Level (mg/dL) | Number of CGM-Reference Pairs | Percent Within ±15 mg/dL | Percent Within ±20 mg/dL | Percent Within ±40 mg/dL | Percent Within ±15% | Percent Within ±20% | Percent Within ±40% | Mean bias (mg/dL) | MARD (%) |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| <54 | 446 | 91.0 | 97.5 | 100.0 | | | | 7.4 | 15.5 |
| 54-69 | 3111 | 94.5 | 98.5 | 100.0 | | | | 1.4 | 10.3 |
| 70-180 | 10748 | | | | 80.2 | 88.7 | 99.5 | -4.5 | 9.7 |
| 181-250 | 4122 | | | | 89.7 | 95.1 | 99.8 | -7.3 | 7.5 |
| >250 | 5076 | | | | 91.3 | 96.1 | 99.7 | -11.5 | 6.9 |
Accuracy to Comparator within Comparator Glucose Ranges (Pediatric*; n=168, Combined)
| CM Glucose Level (mg/dL) | Number of CGM-Reference Pairs | Percent Within ±15 mg/dL | Percent Within ±20 mg/dL | Percent Within ±40 mg/dL | Percent Within ±15% | Percent Within ±20% | Percent Within ±40% | Mean bias (mg/dL) | MARD (%) |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| <54 | 140 | 91.4 | 96.4 | 99.3 | | | | 7.6 | 16.4 |
| 54-69 | 773 | 96.4 | 98.7 | 100.0 | | | | 1.0 | 9.4 |
| 70-180 | 4168 | | | | 76.7 | 85.7 | 98.3 | -4.2 | 10.7 |
| 181-250 | 1559 | | | | 86.8 | 92.9 | 99.1 | -5.0 | 8.1 |
| >250 | 1974 | | | | 90.8 | 97.7 | 99.9 | -9.9 | 7.4 |
K212132 - Page 13 of 25
{13}
* Includes children 6-17 years of age. No YSI measurements were obtained for children 4-5 years of age.
Concurrence of iCGM values compared to the comparator method across the entire measuring range was also evaluated. iCGM glucose ranges of <40, 40-60, 61-80, 81-120, 121-160, 161-200, 201-250, 251-300, 351-400 and >400 mg/dL were evaluated against the comparator glucose ranges and percent of iCGM values within those ranges were reported.
Concurrence Analysis by CGM Glucose Level (Adult; n=200, Combined)
| CGM Glucose Level (mg/dL) | CM Glucose Level (mg/dL) | | | | | | | | | | | N |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | <40 | 40-60 | 61-80 | 81-120 | 121-160 | 161-200 | 201-250 | 251-300 | 301-350 | 351-400 | >400 | |
| <40† | 20.0 | 20.0 | 40.0 | 20.0 | . | . | . | . | . | . | . | 5 |
| 40-60 | 0.4 | 52.0 | 43.7 | 3.8 | . | 0.1 | . | . | . | . | . | 1950 |
| 61-80 | . | 17.8 | 62.2 | 19.6 | 0.4 | 0.0 | . | . | . | . | . | 3317 |
| 81-120 | . | 0.2 | 9.2 | 70.5 | 19.4 | 0.7 | 0.1 | . | . | . | . | 4147 |
| 121-160 | . | . | 0.1 | 8.4 | 71.1 | 19.1 | 1.0 | 0.2 | 0.1 | . | . | 3883 |
| 161-200 | . | . | . | . | 10.4 | 66.4 | 22.1 | 1.0 | 0.2 | . | . | 2806 |
| 201-250 | . | . | . | . | . | 8.6 | 67.8 | 22.0 | 1.5 | 0.1 | . | 2804 |
| 251-300 | . | . | . | . | . | 0.1 | 8.8 | 67.6 | 21.7 | 1.7 | 0.1 | 2469 |
| 301-350 | . | . | . | . | . | . | 0.4 | 13.9 | 68.9 | 15.8 | 1.1 | 1580 |
| 351-400 | . | . | . | . | . | . | . | 0.5 | 27.8 | 62.9 | 8.8 | 547 |
| >400† | . | . | . | . | . | . | . | . | 2.4 | 63.4 | 34.1 | 123 |
Concurrence Analysis by CGM Glucose Level (Pediatric*; n=168, Combined)
| CGM Glucose Level (mg/dL) | CM Glucose Level (mg/dL) | | | | | | | | | | | N |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | <40 | 40-60 | 61-80 | 81-120 | 121-160 | 161-200 | 201-250 | 251-300 | 301-350 | 351-400 | >400 | |
| <40† | . | 33.3 | 66.7 | . | . | . | . | . | . | . | . | 3 |
| 40-60 | 0.5 | 47.5 | 41.3 | 9.6 | 0.9 | 0.2 | . | . | . | . | . | 554 |
| 61-80 | . | 11.4 | 59.7 | 26.8 | 2.0 | . | . | . | . | . | . | 1025 |
| 81-120 | . | 0.2 | 8.2 | 67.4 | 22.8 | 1.3 | 0.1 | . | . | . | . | 1590 |
| 121-160 | . | . | . | 9.1 | 71.1 | 18.4 | 1.3 | . | . | . | . | 1437 |
| 161-200 | . | . | . | 0.1 | 15.5 | 66.0 | 18.2 | 0.2 | . | . | . | 1094 |
| 201-250 | . | . | . | . | 0.3 | 10.6 | 59.1 | 29.0 | 1.0 | 0.1 | . | 1157 |
| 251-300 | . | . | . | . | . | 0.1 | 13.6 | 63.8 | 21.3 | 1.2 | . | 933 |
| 301-350 | . | . | . | . | . | . | 0.3 | 24.4 | 58.4 | 16.7 | 0.2 | 616 |
| 351-400 | . | . | . | . | . | 1.0 | . | 0.5 | 34.1 | 59.1 | 5.3 | 208 |
| >400† | . | . | . | . | . | . | . | 4.4 | 6.7 | 33.3 | 55.6 | 45 |
*Includes children 6-17 years of age. No YSI measurements were obtained for children 4-5 years of age.
† Levels out of System dynamic range.
K212132 - Page 14 of 25
{14}
Concurrence Analysis by CM Glucose Level (Adult; n=200, Combined)
| CM Glucose Level (mg/dL) | CGM Glucose Level (mg/dL) | | | | | | | | | | | N |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | <40† | 40-60 | 61-80 | 81-120 | 121-160 | 161-200 | 201-250 | 251-300 | 301-350 | 351-400 | >400† | |
| <40 | 12.5 | 87.5 | . | . | . | . | . | . | . | . | . | 8 |
| 40-60 | 0.1 | 62.9 | 36.6 | 0.4 | . | . | . | . | . | . | . | 1612 |
| 61-80 | 0.1 | 25.8 | 62.5 | 11.5 | 0.1 | . | . | . | . | . | . | 3301 |
| 81-120 | 0.0 | 1.9 | 16.3 | 73.5 | 8.2 | . | . | . | . | . | . | 3977 |
| 121-160 | . | . | 0.3 | 20.8 | 71.4 | 7.5 | . | . | . | . | . | 3871 |
| 161-200 | . | 0.0 | 0.0 | 0.9 | 25.7 | 64.8 | 8.4 | 0.1 | . | . | . | 2876 |
| 201-250 | . | . | . | 0.1 | 1.4 | 22.2 | 68.2 | 7.8 | 0.2 | . | . | 2787 |
| 251-300 | . | . | . | . | 0.3 | 1.1 | 24.3 | 65.6 | 8.6 | 0.1 | . | 2543 |
| 301-350 | . | . | . | . | 0.3 | 0.3 | 2.2 | 29.3 | 59.5 | 8.3 | 0.2 | 1830 |
| 351-400 | . | . | . | . | . | . | 0.3 | 6.0 | 34.8 | 48.0 | 10.9 | 716 |
| >400 | . | . | . | . | . | . | . | 1.8 | 16.4 | 43.6 | 38.2 | 110 |
Concurrence Analysis by CM Glucose Level (Pediatric*; n=168)
| CM Glucose Level (mg/dL) | CGM Glucose Level (mg/dL) | | | | | | | | | | | N |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | <40† | 40-60 | 61-80 | 81-120 | 121-160 | 161-200 | 201-250 | 251-300 | 301-350 | 351-400 | >400† | |
| <40 | . | 100.0 | . | . | . | . | . | . | . | . | . | 3 |
| 40-60 | 0.3 | 68.5 | 30.5 | 0.8 | . | . | . | . | . | . | . | 384 |
| 61-80 | 0.2 | 23.5 | 62.8 | 13.4 | . | . | . | . | . | . | . | 974 |
| 81-120 | . | 3.5 | 18.0 | 70.0 | 8.6 | 0.1 | . | . | . | . | . | 1532 |
| 121-160 | . | 0.3 | 1.3 | 22.9 | 64.6 | 10.7 | 0.2 | . | . | . | . | 1583 |
| 161-200 | . | 0.1 | . | 1.8 | 23.4 | 63.7 | 10.8 | 0.1 | . | 0.2 | . | 1134 |
| 201-250 | . | . | . | 0.2 | 1.8 | 19.3 | 66.2 | 12.3 | 0.2 | . | . | 1033 |
| 251-300 | . | . | . | . | . | 0.2 | 30.9 | 54.8 | 13.8 | 0.1 | 0.2 | 1085 |
| 301-350 | . | . | . | . | . | . | 1.7 | 30.9 | 55.9 | 11.0 | 0.5 | 644 |
| 351-400 | . | . | . | . | . | . | 0.4 | 4.3 | 40.7 | 48.6 | 5.9 | 253 |
| >400 | . | . | . | . | . | . | . | . | 2.7 | 29.7 | 67.6 | 37 |
*Includes children 6-17 years of age. No YSI measurements were obtained for children 4-5 years of age.
K212132 - Page 15 of 25
{15}
Trend Accuracy
Trend accuracy describes the accuracy of the sensor during times of rapidly changing glucose and is characterized by slopes, such as from >2mg/dL/min to <-2 mg/dL/min. Trend accuracy was assessed by the concurrence rate of the glucose rate of change from the iCGM and the corresponding comparator values for each iCGM-comparator measurement pair.
Concurrence Analysis by Glucose Rate of Change (Adult; n=200, Combined)
| CGM (mg/dL/min) | CM (mg/dL/min) | | | | | | N |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | <-2 | [-2, -1) | [-1, 0) | [0, 1] | (1, 2] | >2 | |
| <-2 | 34.5 | 44.9 | 18.0 | 2.3 | 0.3 | . | 345 |
| -2 to -1 | 6.9 | 46.6 | 41.2 | 4.0 | 0.8 | 0.5 | 1210 |
| -1 to 0 | 1.0 | 7.7 | 68.0 | 19.9 | 2.3 | 1.0 | 11735 |
| 0 to 1 | 0.7 | 2.8 | 26.0 | 50.3 | 14.3 | 5.8 | 7270 |
| 1 to 2 | 0.2 | 1.7 | 7.7 | 32.7 | 38.0 | 19.8 | 1322 |
| >2 | 0.1 | 0.4 | 3.1 | 14.9 | 33.2 | 48.4 | 941 |
Concurrence Analysis by Glucose Rate of Change (Pediatric*; n=168, Combined)
| CGM (mg/dL/min) | CM (mg/dL/min) | | | | | | N |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | <-2 | [-2, -1) | [-1, 0) | [0, 1] | (1, 2] | >2 | |
| <-2 | 41.7 | 44.3 | 10.9 | 3.1 | . | . | 192 |
| -2 to -1 | 10.5 | 50.3 | 33.1 | 5.0 | 0.4 | 0.7 | 543 |
| -1 to 0 | 1.7 | 10.1 | 62.7 | 20.5 | 3.4 | 1.5 | 3481 |
| 0 to 1 | 1.1 | 4.5 | 24.6 | 49.0 | 13.4 | 7.5 | 2923 |
| 1 to 2 | 0.2 | 2.5 | 9.5 | 29.0 | 38.1 | 20.7 | 603 |
| >2 | . | 1.0 | 3.9 | 14.8 | 29.9 | 50.4 | 488 |
* Includes children 6-17 years of age. No YSI comparator measurements were obtained for children 4-5 years of age.
Agreement when iCGM reads "LO" or "HI"
The FreeStyle Libre 3 Glucose Monitoring System reports glucose readings between 40 and 400 mg/dL. When the system determines that the glucose reading is below 40 mg/dL, it will display 'LO' whenever the sensor is scanned. When the system determines that the glucose reading is above 400 mg/dL, it will display 'HI' whenever the sensor is scanned. Because the system does not display glucose values below 40 mg/dL or above 400 mg/dL, the comparisons to the actual blood glucose levels (as determined by the comparator) when the iCGM value is classified as 'LO' or 'HI' are evaluated separately. The cumulative percentages of when the comparator values were less than certain glucose values (for 'LO') and when comparator values were more that certain glucose values (for 'HI') are presented in the tables below.
Concurrence Analysis with 'LO' CGM Reading (Adult; n=200, Combined)
| CGM-CMPairs | CM (mg/dL) | | | | | N |
| --- | --- | --- | --- | --- | --- | --- |
| | <50 | <60 | <70 | <80 | ≥80 | |
| n | 1 | 2 | 2 | 4 | 1 | 5 |
| Cumulative % | 20.0 | 40.0 | 40.0 | 80.0 | 20.0 | |
K212132 - Page 16 of 25
{16}
Concurrence Analysis with 'LO' CGM Reading (Pediatric*; n=168, Combined)
| CGM-CMPairs | CM (mg/dL) | | | | | N |
| --- | --- | --- | --- | --- | --- | --- |
| | <50 | <60 | <70 | <80 | ≥80 | |
| n | 0 | 1 | 3 | 3 | 0 | 3 |
| Cumulative % | 0.0 | 33.3 | 100.0 | 100.0 | 0.0 | |
*includes children 6-17 years of age. No YSI comparator measurements were obtained for children 4-5 years of age
Concurrence Analysis with 'HI' CGM Reading (Adult; n=200, Combined)
| CGM-CMPairs | CM (mg/dL) | | | | N |
| --- | --- | --- | --- | --- | --- |
| | >350 | >300 | >250 | ≤250 | |
| n | 120 | 123 | 123 | 0 | 123 |
| Cumulative % | 97.6 | 100.0 | 100.0 | 0.0 | |
Concurrence Analysis with 'HI' CGM Reading (Pediatric*; n=168, Combined)
| CGM-CMPairs | CM (mg/dL) | | | | N |
| --- | --- | --- | --- | --- | --- |
| | >350 | >300 | >250 | ≤250 | |
| n | 40 | 43 | 45 | 0 | 45 |
| Cumulative % | 88.9 | 95.6 | 100.0 | 0.0 | |
*includes children 6-17 years of age. No comparator measurements were obtained for children 4-5 years of age
## Alarm Performance
The tables in this section show the accuracy of the System's Low and High Glucose Alarms. The Alarm Rate tells the user how often the alarm is right or wrong. The Detection Rate tells the user how often the System is able to recognize and notify the user about a low or high glucose event (within 15 minutes before or after the event).
## Low Glucose Alarm Performance
True Alarm Rate: Percentage of time the alarm issued, and blood glucose was below the alarm level within 15 minutes before or after the alarm.
False Alarm Rate: Percentage of time the alarm issued, and blood glucose was not below the alarm level within 15 minutes before or after the alarm.
Detection Rate: Percentage of time blood glucose was below the alarm level and the alarm issued within 15 minutes before or after the glucose event.
Missed Detection Rate: Amount of time blood glucose was below the alarm level and the alarm didn't issue within 15 minutes before or after the glucose event.
K212132 - Page 17 of 25
{17}
Low Glucose Alarm Performance (Adult; n=200, Combined)
| Low Glucose Alarm level (mg/dL) | Alarm Rate | | | Detection Rate | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Number of Events (n) | True Alarm Rate (%) | False Alarm Rate (%) | Number of Events (n) | Correct Detection Rate (%) | Missed Detection Rate (%) |
| 60 | 10267 | 70.9 | 29.1 | 1546 | 75.8 | 24.2 |
| 70 | 22568 | 84.3 | 15.7 | 3747 | 89.0 | 11.0 |
| 80 | 35140 | 90.3 | 9.7 | 4977 | 97.0 | 3.0 |
| 90 | 45665 | 92.3 | 7.7 | 5972 | 98.4 | 1.6 |
Low Glucose Alarm Performance (Pediatric*; n=168 combined)
| Low Glucose Alarm level (mg/dL) | Alarm Rate | | | Detection Rate | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Number of Events (n) | True Alarm Rate (%) | False Alarm Rate (%) | Number of Events (n) | Correct Detection Rate (%) | Missed Detection Rate (%) |
| 60 | 2988 | 60.5 | 39.5 | 386 | 86.8 | 13.2 |
| 70 | 6886 | 77.1 | 22.9 | 995 | 92.8 | 7.2 |
| 80 | 10901 | 82.3 | 17.7 | 1399 | 96.2 | 3.8 |
| 90 | 14710 | 90.0 | 10.0 | 1822 | 97.5 | 2.5 |
* Includes children 6-17 years of age. No YSI Comparator measurements were obtained for children 4-5 years of age.
## High Glucose Alarm Performance
True Alarm Rate: Percentage of time the alarm issued, and blood glucose was above the alarm level within 15 minutes before or after the alarm.
False Alarm Rate: Percentage of time the alarm issued, and blood glucose was not above the alarm level within 15 minutes before or after the alarm.
Detection Rate: Percentage of time blood glucose was above the alarm level and the alarm issued within 15 minutes before or after the glucose event.
Missed Detection Rate: Amount of time blood glucose was above the alarm level and the alarm didn't issue within 15 minutes before or after the glucose event.
K212132 - Page 18 of 25
{18}
High Glucose Alarm Performance (Adult; n=200, Combined)
| High Glucose Alarm level (mg/dL) | Alarm Rate | | | Detection Rate | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Number of Events (n) | True Alarm Rate (%) | False Alarm Rate (%) | Number of Events (n) | Correct Detection Rate (%) | Missed Detection Rate (%) |
| 120 | 139120 | 99.0 | 1.0 | 14957 | 98.0 | 2.0 |
| 140 | 119404 | 98.7 | 1.3 | 12928 | 97.5 | 2.5 |
| 180 | 86584 | 98.7 | 1.3 | 9523 | 96.8 | 3.2 |
| 200 | 73754 | 98.7 | 1.3 | 8173 | 96.7 | 3.3 |
| 220 | 61864 | 98.3 | 1.7 | 6935 | 96.7 | 3.3 |
| 240 | 50803 | 98.0 | 2.0 | 5861 | 95.5 | 4.5 |
| 300 | 22019 | 96.2 | 3.8 | 2740 | 90.2 | 9.8 |
High Glucose Alarm Performance (Pediatric*; n=168, Combined)
| High Glucose Alarm level (mg/dL) | Alarm Rate | | | Detection Rate | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Number of Events (n) | True Alarm Rate (%) | False Alarm Rate (%) | Number of Events (n) | Correct Detection Rate (%) | Missed Detection Rate (%) |
| 120 | 47334 | 98.9 | 1.1 | 5953 | 97.2 | 2.8 |
| 140 | 40247 | 97.8 | 2.2 | 5131 | 97.0 | 3.0 |
| 180 | 27357 | 98.1 | 1.9 | 3742 | 97.0 | 3.0 |
| 200 | 22790 | 97.4 | 2.6 | 3205 | 97.6 | 2.4 |
| 220 | 18537 | 97.7 | 2.3 | 2770 | 96.8 | 3.2 |
| 240 | 14640 | 97.6 | 2.4 | 2372 | 95.2 | 4.8 |
| 300 | 6219 | 90.9 | 9.1 | 989 | 91.0 | 9.0 |
* Includes children 6-17 years of age. No YSI comparator measurements were obtained for children 4-5 years of age.
## Sensor Stability
Sensor stability describes the performance of the sensor over the sensor lifetime. Sensors can be worn for up to 14 days. Performance was estimated by calculating the mean of the absolute relative differences between iCGM and comparator measurement and percentage of device readings within 15 mg/dL or 15% (15/15%), 20 mg/dL or 20% (20/20%) and 40 mg/dL or 40% (40/40%) of the comparator values during the beginning, early middle, late middle, and end of the wear period. These times were defined as follows:
- Beginning (Adult Days 1-3, Pediatric: Days 1-2)
- Early Middle (Adult: Days 7-8, Pediatric: Days 7-8),
- Late Middle (Adult: Days 9-12, Pediatric: Days 9-12), and
- End (Adult: Days 13-14, Pediatric: Days 13-14).
K212132 - Page 19 of 25
{19}
The mean absolute relative difference (MARD) and agreement rates with the comparator method were evaluated over 14-day life of the sensor. For these tables the adult data for FreeStyle Libre 2 study were combined with the adult data for FreeStyle Libre 3. The same approach was also implemented for pediatric subjects.
Sensor Accuracy Relative to Comparator Over the Wear Duration (Adult; n=200)
| Wear Period | Number of CGM-reference pairs | MARD (%) | Within ±15% / ±15mg/dL | Within ±20% / ±20mg/dL | Within ±40% / ±40mg/dL |
| --- | --- | --- | --- | --- | --- |
| Beginning | 8753 | 9.6 | 84.2 | 91.1 | 99.4 |
| Early Middle | 5540 | 8.4 | 88.2 | 94.7 | 99.8 |
| Late Middle | 4753 | 8.3 | 87.9 | 93.8 | 99.7 |
| End | 4457 | 8.8 | 86.8 | 93.2 | 99.9 |
Sensor Accuracy Relative to Comparator Over the Wear Duration (Pediatric*; n=168)
| Wear Period | Number of CGM-reference pairs | MARD (%) | Within ±15% / ±15mg/dL | Within ±20% / ±20mg/dL | Within ±40% / ±40mg/dL |
| --- | --- | --- | --- | --- | --- |
| Beginning | 2695 | 10.2 | 80.3 | 88.6 | 98.6 |
| Early Middle | 2031 | 9.0 | 85.5 | 90.9 | 98.4 |
| Late Middle | 1947 | 8.9 | 86.4 | 94.1 | 99.6 |
| End | 1941 | 9.5 | 84.1 | 91.7 | 99.4 |
* Includes children 6-17 years of age. No YSI Comparator measurements were obtained for children 4-5 years of age.
## Sensor Life
The Sensor can be worn for up to 14 days. To estimate how long a Sensor will work over the wear duration, 101 Sensors were evaluated in Study 3 to determine how many days of readings each Sensor provided. Of the 56 Sensors used in adults, 66.1% lasted until the final day; while of the 45 sensors used in pediatric patients, 71.1% lasted until the final day. Abbott performed a retrospective analysis and concluded that the survival rate of the FSL3 in Study 3 was negatively affected by a software configuration unique to the investigational device, and that the actual survival rates should be higher.
K212132 - Page 20 of 25
{20}
A subsequent study was conducted in adults to assess the impact of this software configuration on early sensor shut-off as well as to determine the survival rate after eliminating for physical factors (e.g., getting caught in car seat belt, accidental knocking off the sensor etc.). A total of 34 of the 39 (87.2%) of the sensors gave glucose results over the entire intended wear period of 14 days. After correcting for several factors, the actual survival rate was 94.4 %.
## Glucose Reading Availability
The capture rates for real-time glucose values in Study 3 for adults and pediatric population are provided below.
Glucose Reading Capture Rate Over Wear Duration (Adult; n=56)
| Day of Wear | Number of Sensors | Capture Rate (%) |
| --- | --- | --- |
| 1 | 56 | 99.8 |
| 2 | 56 | 99.9 |
| 3 | 56 | 99.8 |
| 4 | 56 | 99.9 |
| 5 | 55 | 100.0 |
| 6 | 53 | 99.5 |
| 7 | 53 | 100.0 |
| 8 | 50 | 100.0 |
| 9 | 50 | 100.0 |
| 10 | 49 | 100.0 |
| 11 | 46 | 99.6 |
| 12 | 43 | 100.0 |
| 13 | 39 | 99.9 |
| 14 | 38 | 100.0 |
K212132 - Page 21 of 25
{21}
Glucose Reading Capture Rate Over Wear Duration (Pediatric; n=45)
| Day of Wear | Number of Sensors | Capture Rate (%) |
| --- | --- | --- |
| 1 | 45 | 99.8 |
| 2 | 43 | 99.9 |
| 3 | 43 | 99.8 |
| 4 | 43 | 99.7 |
| 5 | 43 | 99.8 |
| 6 | 43 | 99.9 |
| 7 | 43 | 99.9 |
| 8 | 43 | 99.8 |
| 9 | 42 | 99.8 |
| 10 | 41 | 99.8 |
| 11 | 39 | 99.4 |
| 12 | 37 | 99.6 |
| 13 | 34 | 99.4 |
| 14 | 32 | 99.9 |
D Clinical Cut-Off:
Not applicable.
E Expected Values/Reference Range:
Not applicable.
F Other Supportive Instrument Performance Characteristics Data:
Human Factors
Human factors and usability testing of the FreeStyle Libre 3 System was conducted to determine whether the user interface design and labeling would impact the performance of the device. Human factors testing was conducted in accordance with:
- Applying Human Factors and Usability Engineering to Medical Devices, Guidance to FDA Staff and Industry, February 3, 2016
- ANSI/AAMI/IEC 62366: Medical devices - Application of Usability Engineering to Medical Devices
- IEC 60601-1-6: Medical electrical equipment - Part 1-6: General requirements for basic safety and essential performance - Collateral standard: Usability
K212132 - Page 22 of 25
{22}
Specific use scenarios and tasks the user would have to carry out correctly in order to use the device safely were identified. An analysis of hazards and risks was conducted on the FreeStyle Libre 3 System to determine safety risks associated with use of the system or were leveraged from K201761 if applicable.
## Software Verification and Validation
Software verification and validation testing was conducted to confirm that the software used in the FreeStyle Libre 3 System performed in accordance with established specifications, EN 62304 and FDA Guidance document “Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices,” May 11, 2005. Evaluation activities included unit, system integration (SIT), and system level testing which verified functionality of the device against established software requirements. Results of the software executed protocols for FreeStyle Libre 3 met the acceptance criteria and therefore supports that the System’s iOS App software is acceptable for its intended use.
## Biocompatibility
Biocompatibility testing was performed in accordance with ISO10993-10 on housing, sheath, cap, sharp, sensor shell and sensor tail. Biological evaluation included cytotoxicity, genotoxicity, irritation, sensitization, and system toxicity testing. All biocompatibility testing met the acceptance criteria.
## Sterilization
The sterile subassembly underwent electron beam sterilization validation per ISO11137-1 and ISO 11137-2. Sterilization validation confirmed that the Sterility Assurance Level (SAL) of $10^{-6}$ is achieved. All sterilization testing conducted met the acceptance criteria and supports sterility of the patient contact components of the device.
## Shelf-Life Stability
The Sensor Kit shelf-life stability testing supports a shelf life of 3 months. Additional testing was conducted to support sensor kit storage temperature range of $36^{\circ}\mathrm{F}$ and $82^{\circ}\mathrm{F}$. Results demonstrated no impact to sensor stability when stored at these storage temperatures.
## Packaging Integrity/Shipping Integrity
Device shelf life and packaging integrity over the shelf life was demonstrated by subjecting test units to worst case sealing parameters, sterilization parameters, and shipping configuration. Integrity testing included activities and requirements to demonstrate compliance to ISO 11607-1, ISO 11137-1 and ISO 11137-2. Attributes related to seal integrity, user accessibility, and device functionality including sterile barrier system integrity met acceptance criteria.
## Electromagnetic Compatibility
Electromagnetic compatibility (EMC) testing was performed for the FreeStyle Libre 3 System to verify that the system is able to withstand the electromagnetic interference and emissions in compliance with IEC 60601-1-2 and IEC CISPR 11. The FreeStyle Libre 3 System also demonstrated compliance with Federal Communication Commission (FCC) Regulations Part 15.225 and Part 15.247, and Federal Aviation Administration (FAA) Advisory Circular RTCA DO-160.
K212132 - Page 23 of 25
{23}
K212132 - Page 24 of 25
## Electrical Safety
The basic safety and essential performance of the Sensor of the FreeStyle Libre 3 System was conducted to demonstrate compliance to IEC 60601-1: 2005(r)2012, IEC 60601-1-6:2010+A1:2013, and IEC 60601-1-11:2015.
## Environmental Testing
Environmental testing on the FreeStyle Libre 3 System was performed in accordance with IEC 60601-1 to ensure the device specifications for operating temperature, operating humidity, operating pressure, impact resistance, vibration resistance, shock resistance, drop resistance, and storage conditions were met.
## Interoperability
The FreeStyle Libre 3 System incorporates an approach for interoperability developed in alignment with FDA guidance, “Design Considerations and Pre-market Submission Recommendations for Interoperable Medical Devices,” September 6, 2017, which includes expectations, requirements, and interface specifications to potential interoperable devices. In addition, the ADC approach to interoperability includes working with connected device companies regarding contractual approaches, interfaces for data communication and exchange, and post-market reporting procedures and responsibilities with respect to managing complaints (e.g., who is responsible for investigating and reporting complaints, malfunctions, and adverse events).
## Cybersecurity
ADC has provided cybersecurity risk management documentation for the System that includes analysis of confidentiality, integrity, and availability for data, information and software related to the System accordance with FDA Draft Guidance “Content of Premarket Submissions for Management of Cybersecurity in Medical Devices.” For each identified threat and vulnerability risk event scenario, risk assessment of impact to confidentiality integrity, and availability was performed and documented within the cybersecurity risk management documentation. Appropriate risk mitigation controls have been implemented and tested.
In addition, ADC has controls and processes in place to ensure continued support for keeping the device secure and to ensure that the device firmware, software and components are malware free. Additional controls are also in place in manufacturing through distribution to ensure that the medical device firmware and software are malware free from point of origin to the hands of the end user.
## Wireless Coexistence
The FreeStyle Libre 3 System underwent coexistence testing in the presence of common RF interfering devices that are likely to be encountered by users in a home environment. Wireless coexistence testing was performed to confirm that the Patch remains functional and perform within acceptable limits while in the presence of common radiating electronic devices in accordance with FDA Guidance “Radio Frequency Wireless Technology in Medical Devices.” A representative set of devices known to operate in the same frequency band (2.4 GHz) was selected. The subject device underwent coexistence testing consistent with AAMI TIR69 and ANSI C63.27 and included test challenges from in-band interference sources defined in ANSI C63.27 as well as other expected wireless interference sources from the intended use environment. The test results showed that the FreeStyle Libre 3 System could tolerate interference generated by these RF interfering devices and still meet the target performance criteria.
{24}
K212132 - Page 25 of 25
## Mechanical Engineering
The subject device underwent performance testing at the System level as well as on individual components of the Sensor Applicator. The test results showed that mechanical, electrical, and functional testing all met the acceptance criteria.
## VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
## IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
