← Product Code [LCP](/submissions/HE/subpart-h%E2%80%94hematology-kits-and-packages/LCP) · K082275

# CLOVER A1C/GLYCOSYLATED HEMOGLOBIN MONITOR & BLOOD GLUCOSE MONITOR, MODEL IGM-0023 (K082275)

_Infopia Co, Ltd. · LCP · Jan 14, 2010 · Hematology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-h%E2%80%94hematology-kits-and-packages/LCP/K082275

## Device Facts

- **Applicant:** Infopia Co, Ltd.
- **Product Code:** [LCP](/submissions/HE/subpart-h%E2%80%94hematology-kits-and-packages/LCP.md)
- **Decision Date:** Jan 14, 2010
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 864.7470
- **Device Class:** Class 2
- **Review Panel:** Hematology
- **Attributes:** Pediatric

## Indications for Use

The Clover A1c HbA1c assay is an in vitro diagnostic test that quantitatively measures the percent concentration glycosylated hemoglobin in capillary or venous whole blood samples for clinical laboratory and point of care use. Measurement of percent HbA1c is used to monitor long-term glucose control in individuals with diabetes mellitus. Clover A1c is for in vitro diagnostic use and is not to be used for the diagnosis or screening of diabetes or for neonatal use. The Clover A1c glucose assay is used for the quantitative measurement of concentration of glucose in whole blood taken from the fingertip by healthcare professionals. The test is for prescription use as an aid in the management of diabetes. Clover A1c is for in vitro diagnostic use and is not to be used for the diagnosis or screening of diabetes or for neonatal use.

## Device Story

Clover A1c system is a point-of-care analyzer for quantitative measurement of HbA1c and blood glucose. HbA1c measurement uses boronate affinity method; capillary or venous whole blood sample (4μl) is lysed; boronate resin binds cis-diols of glycated hemoglobin; reflectance photometer measures total hemoglobin and glycated hemoglobin; analyzer calculates ratio. Glucose measurement uses electrochemical amperometric method; glucose oxidase and hexaammineruthenium (III) chloride react with capillary blood; resulting current is proportional to glucose concentration. System includes analyzer, test cartridges (A1c), and test strips (glucose). Healthcare professionals operate device in clinical/POC settings. Output displayed on analyzer screen; used to monitor diabetes management. Device provides quantitative results to assist clinical decision-making regarding glycemic control.

## Clinical Evidence

Clinical performance evaluation conducted to validate accuracy of glycosylated hemoglobin and glucose measurements. Results demonstrated substantial equivalence to predicate devices. No specific sensitivity/specificity metrics provided.

## Technological Characteristics

System includes HbA1c analyzer, test/check cartridges, thermal printer, barcode scanner. HbA1c: boronate affinity assay, photometric measurement. Glucose: electrochemical test strip, oxidase glucose reaction. Standalone device.

## Regulatory Identification

A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.

## Predicate Devices

- Siemens Medical Solutions Diagnostics DCA Vantage (k071466)
- Infopia Co. Ltd., Evolution, Blood Glucose Monitoring System (k072369)

## Submission Summary (Full Text)

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>
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:
k082275

B. Purpose for Submission:
New device

C. Measurand:
Whole blood Glycosylated Hemoglobin (HbA1c) and whole blood Glucose

D. Type of Test:
Quantitative, boronate affinity method for HbA1c and quantitative amperometric glucose oxidase for glucose

E. Applicant:
Infopia Co., Ltd.

F. Proprietary and Established Names:
Clover A1c HbA1c assay
Clover A1c Blood Glucose assay

G. Regulatory Information:
1. Regulation section:
21 CFR 864.7470, Hemoglobin A1c test system
21 CFR 862.1345, Glucose Test System
2. Classification:
Class II
3. Product code:
LCP, Assay, Glycosylated Hemoglobin test
CGA- Glucose Oxidase, Glucose
4. Panel:
Hematology (81), A1c
Chemistry (75), Glucose

H. Intended Use:
1. Intended use(s):
See Indications for use below.
2. Indication(s) for use:
The Clover A1c HbA1c assay is an in vitro diagnostic test that quantitatively

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measures the percent concentration glycosylated hemoglobin in capillary or venous whole blood samples for clinical laboratory and point of care use. Measurement of percent HbA1c is used to monitor long-term glucose control in individuals with diabetes mellitus. Clover A1c is for in vitro diagnostic use and is not to be used for the diagnosis or screening of diabetes or for neonatal use

The Clover A1c glucose assay is used for the quantitative measurement of concentration of glucose in whole blood taken from the fingertip by healthcare professionals. The test is for prescription use as an aid in the management of diabetes. Clover A1c is for in vitro diagnostic use and is not to be used for the diagnosis or screening of diabetes or for neonatal use.

3. Special conditions for use statement(s):

For prescription use only

Glucose and A1c: not for use in the diagnosis or screening of diabetes or for neonatal use

Glucose: Not for use on critically ill patients, patients in shock, dehydrated patients or hyperosmolar patients.

4. Special instrument requirements:

Infopia CLOVER A1c Analyzer

I. Device Description:

The Clover A1c system includes the analyzer, the combined A1c and glucose operator manual, the A1c test cartridge, the A1c check cartridge, the glucose module, the glucose test strips and the glucose controls (previously cleared under k051285)

J. Substantial Equivalence Information:

1. Predicate device name(s):

Siemens Medical Solutions Diagnostics DCA Vantage

Infopia Co. Ltd., Evolution, Blood Glucose Monitoring System

2. Predicate 510(k) number(s):

k071466 – A1c

k072369 – Glucose

3. Comparison with predicate:

Hemoglobin A1c: The new device and the predicate are both intended for use in the quantitative measurement of A1c in whole blood. Both devices have been certified by the National Glycohemoglobin Standardization Program (NGSP). The predicate device also measures low concentrations of albumin in urine (microalbuminuria) and creatinine in urine; the new device includes a module for measuring glucose. Both devices are spectrophotometers; the predicate uses the latex immunoagglutination inhibition method and the new device uses the boronate affinity method. The predicate measuring range is 2.5 to 14.0%; the measuring range for the new device is 4.0 -14.0%.

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Glucose: Both devices are intended for the quantitative measurement of glucose in whole blood. Both devices have the same detection method (amperometry), enzyme (glucose oxidase), and mediator (Hexaammineruthenium chloride) and measuring range of 20-600 mg/dL. The predicate is intended for use by healthcare professionals and for home use. The new device is intended for clinical laboratory and point of care use. The predicate hematocrit range is 20 - 60%; the hematocrit range for the new device is 20 - 51%

K. Standard/Guidance Document Referenced (if applicable):

ISO 14971:2007 Medical devices- Application of risk management to medical devices.

IEC 61010-1:2001 Safety Requirements for electrical equipment for measurement, control and laboratory use.

IEC 61010-2-101:2002 Safety Requirements for electrical equipment for measurement, control and laboratory use Part 2-101: Particular requirements for In Vitro Diagnostic (IVD) Medical Equipment.

IEC 60601-1:2005 Medical Electrical Equipment Part 1: General requirements for safety.

IEC 61326-1:2006 Electrical equipment for electrical equipment for measurement, control and laboratory use. EMC requirements Part 1: General Requirements.

IEC 61326-2-6:2006 Electrical equipment for electrical equipment for measurement, control and laboratory use. EMC requirements. Particular requirements. In vitro diagnostic (IVD) medical equipment.

CLSI EP09-A2: 2004 Method comparison and bias estimating using patient samples.

CLSI EP06-P2:2005 Evaluation of Linearity Quantitative Analytical Method

CLSI EP05-A2:2005 Evaluation of precision performance of quantitative measurement methods

CLSI EP07-A2 Interference Testing in clinical chemistry

L. Test Principle:

A1c: The CLOVER A1c™ system is a fully automated boronate affinity assay for the determination of the percentage of hemoglobin A1c (HbA1c %) in whole blood. The HbA1c Test Cartridge includes a Cartridge and a reagent pack. The reagent pack is pre-filled with reaction solution and washing solution. The reaction solution contains agents that lyse erythrocytes and bind hemoglobin specifically, as well as a boronate resin that binds cis-diols of glycated hemoglobin. A blood sample size of (4μl) is obtained with the collection area of the reagent pack. The blood is instantly lysed releasing the hemoglobin and the boronate resin binding the glycated hemoglobin. The cartridge is inserted into the CLOVER A1c™ analyzer. The blood sample mixture is rotated to the measurement zone of the cartridge, where the amount of total hemoglobin in the blood sample is measured by the reflectance of the photo sensor LED (Light Emitting Diode) and PD (Photo Diode).

The cartridge is then rotated so that the washing solution washes out non-glycated hemoglobin from the blood sample, thus the amount of glycated hemoglobin can be photometrically measured. The ratio of glycated hemoglobin with respect to total hemoglobin in the blood sample is calculated.

Glucose: The CLOVER A1c™ blood glucose test is based on the measurement of glucose concentration in human blood. The principle of the test is based on the reaction between

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glucose in the blood sample, glucose oxidase and hexaammineruthenium (III) chloride. The resulting product generates a current that is proportional to the glucose concentration in the sample. The test strip employs an electrochemical signal generating an electrical current that will stimulate a chemical reaction. The reaction is measured and displayed by the analyzer.

## M. Performance Characteristics (if/when applicable):

### 1. Analytical performance:

#### a. Precision/Reproducibility:

A1c precision: The precision of the proposed device was evaluated using a protocol based on the CLSI EP5-A2 guideline. An external reproducibility study was performed in three point-of-care sites with nine operators (three at each site). Normal patient samples (5.0% A1c %) and diabetic patient samples (10% A1c and 12% A1c) were analyzed by each user twice per day over 20 days on two instruments. Patient samples are EDTA human whole blood. The results are summarized below:

|  Patient Sample |  | User 1 | User 2 | User 3  |
| --- | --- | --- | --- | --- |
|  Normal | Mean | 4.9 | 4.9 | 4.9  |
|   |  %CV | 2.0 | 2.2 | 1.8  |
|  High | Mean | 10.0 | 10.0 | 10.0  |
|   |  %CV | 1.3 | 1.1 | 1.3  |
|  Very High | Mean | 12.2 | 12.2 | 12.2  |
|   |  %CV | 0.9 | 1.0 | 1.0  |
|  Patient sample |  | User 1 | User 2 | User 3  |
| --- | --- | --- | --- | --- |
|  Normal | Mean | 4.8 | 4.8 | 4.8  |
|   |  %CV | 1.7 | 1.6 | 1.7  |
|  High | Mean | 10.2 | 10.2 | 10.2  |
|   |  %CV | 0.9 | 0.8 | 0.9  |
|  Very High | Mean | 12.0 | 12.0 | 12.0  |
|   |  %CV | 1.2 | 1.1 | 1.4  |
|  Patient sample |  | User 1 | User 2 | User 3  |
| --- | --- | --- | --- | --- |
|  Normal | Mean | 4.9 | 4.9 | 4.9  |
|   |  %CV | 1.7 | 2.1 | 1.7  |
|  High | Mean | 9.9 | 9.9 | 9.9  |
|   |  %CV | 0.9 | 0.8 | 0.9  |
|  Very High | Mean | 11.9 | 11.9 | 11.9  |
|   |  %CV | 1.4 | 1.5 | 1.4  |

Glucose within-run precision: The precision of the proposed device was evaluated using a protocol based on the CLSI EP5-A2 guideline. Testing with whole blood was conducted in a laboratory using five Clover glucose modules, one lot of five hundred

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test strips from ten vials with five EDTA venous whole blood samples. Each blood sample was spiked to five glucose levels (approximately 40, 80, 125, 200 and 315 mg/dL). Ten measurements were performed for each glucose level. The mean response, standard deviation (SD) and coefficient of variation (% CV) were calculated for each glucose module and each glucose level.

|  Within-Run | Sample 1 | Sample 2 | Sample 3 | Sample 4 | Sample 5  |
| --- | --- | --- | --- | --- | --- |
|  |   |   |   |   |   |
|  Mean, mg/dL | 39.4 | 79.9 | 125.2 | 202.5 | 314.7  |
|  SD, mg/dL | 1.4 | 2.0 | 3.8 | 6.3 | 8.9  |
|  CV % | 3.6 | 2.5 | 3.0 | 3.1 | 2.8  |
|  |   |   |   |   |   |

Glucose between-run precision: - Testing was conducted in a laboratory over 10 days using ten glucose devices, and one lot glucose test strips with low, mid and high glucose control solution. The mean response, standard deviation (SD) and coefficient of variation (% CV) were calculated for each glucose module and each glucose level. The results are summarized in the table below.

|  Between-day precision | Sample 1 | Sample 2 | Sample 3  |
| --- | --- | --- | --- |
|  Mean, mg/dL | 50 | 109 | 303  |
|  SD, mg/dL | 1.1 | 1.9 | 3.7  |
|  CV, % | 2.3 | 1.7 | 1.2  |

An external reproducibility study was performed in three POC sites with nine operators (three at each site). Three levels of control material was used in all three sites and assayed once each day of testing. Each intended user (physician, nurse, medical assistant or nursing assistant) ran three (3) samples of each control solution (3 low, 3 normal, 3 high) for a total of nine (9) samples per intended user. Twenty-seven (27) samples were run at each site (Hospital ward, ER, ICU). The results obtained on the A1c analyzer and with YSI for site 1 are shown in the table below. Site 2 and site 3 had precision data similar to site 1, with  $\% \mathrm{CV} < 2.5\%$  for all the calculated results.

Site 1

|   |  | User 1 |   | User 2 |   | User 3  |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  | YSI | CLOVER A1c | YSI | CLOVER A1c | YSI | CLOVER A1c  |
|  Low Level | Mean, mg/dL | 49.9 | 50.0 | 50.3 | 50.1 | 49.7 | 49.9  |
|   |  SD, mg/dL | 1.2 | 1.2 | 1.4 | 1.0 | 0.9 | 1.1  |
|   |  CV, % | 2.4 | 2.4 | 2.7 | 1.9 | 1.9 | 2.2  |
|  Normal Level | Mean, mg/dL | 101.1 | 100.9 | 101.0 | 101.3 | 100.9 | 100.7  |
|   |  SD, mg/dL | 1.8 | 1.5 | 1.4 | 1.7 | 1.3 | 1.7  |

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|   | CV, % | 1.8 | 1.5 | 1.4 | 1.7 | 1.3 | 1.6  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  High Level | Mean, mg/dL | 303.4 | 301.9 | 302.0 | 302.4 | 301.7 | 302.3  |
|   |  SD, mg/dL | 4.3 | 3.8 | 4.7 | 4.0 | 3.4 | 3.4  |
|   |  CV, % | 1.4 | 1.3 | 1.6 | 1.3 | 1.1 | 1.1  |

# b. Linearity/assay reportable range:

A1c Linearity: A linearity study across the entire claimed measuring range (4.0 - 14.0%) was evaluated using low (2.9% HbA1c) and high (16.7% HbA1c) patient samples. The low and high patient samples were mixed together in varying ratios to make nine intermediate levels. The samples were run in triplicate on two Clover A1c analyzers. The observed mean values were compared to the theoretical values based upon the dilution factor. The % recovery was calculated with the following formula: Recovery = Observed %HbA1c value / Expected %HbA1c value x 100. The percent recovery between the observed values verses the expected values are shown in the table below.

|  Sample level | Expected %HbA1c | Observed %HbA1c Mean value | % Recovery  |
| --- | --- | --- | --- |
|  Low | 2.9 | - | -  |
|  2 | 4.3 | 4.2 | 98  |
|  3 | 5.7 | 5.5 | 98  |
|  4 | 7.0 | 7.0 | 100  |
|  5 | 8.4 | 8.4 | 100  |
|  6 | 9.8 | 9.9 | 101  |
|  7 | 11.2 | 11.3 | 101  |
|  8 | 12.6 | 12.6 | 100  |
|  9 | 13.9 | 13.9 | 99  |
|  10 | 15.3 | - | -  |
|  High | 16.7 | - | -  |

The results of the study support the sponsor's claimed that the Hb A1c assay is linear from  $4.0\%$  to  $14.0\%$

Glucose linearity: The sponsor evaluated linearity of the device using a protocol based on CLSI EP6-A. EDTA venous blood sample was spiked to two concentrations (high and low). The two concentrations were mixed from 14 glucose concentrations between 7.4 to  $628.0\mathrm{mg / dL}$  (confirmed by YSI) then tested with the CLOVER A1c glucose module and YSI. The CLOVER A1c analyzer displays "Low" with glucose values below  $20\mathrm{mg / dL}$ , "HI" with glucose values over  $600\mathrm{mg / dL}$ . Each glucose level was measured 5 times by the CLOVER A1c glucose module and in duplicate by YSI.

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Regression analysis showed a linear relationship between the CLOVER A1c glucose module and the YSI method: y=1.0004 x+0.5273, R²=0.9999. For all values between 20 and 600 mg/dL, the percent difference between the observed value on the CLOVER and the 1st order value were all less than 3%.

The results of the study support the sponsor’s claimed that the glucose assay is linear from 20-600 mg/dL.

c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The Clover A1c device has been certified by the National Glycohemoglobin Standardization Program (NGSP). NGSP certifications are renewed annually. Current NGSP certifications are found on the web at http://www.ngsp.org/prog/index.html

Glucose assay is traceable to the YSI method by method comparison. Stability for glucose controls was established in k051285.

d. Detection limit:
A1c - The reportable range for the assay is 4.0 to 14.0% HbA1c. See section 1. b, linearity/reportable range above.

Glucose - The detection limit is 20 mg/dL. See linearity/assay reportable range above.

e. Analytical specificity:

A1c Interference: Interference testing was performed using a protocol based on CLSI EP7-A. Studies were performed to assess common or known substances that could interfere with the Clover A1c device. The interfering substances were evaluated in normal (5.2%) and abnormal (9.5%) samples. Two levels of EDTA whole blood sample pools were spiked with interfering substance. The sponsor states that recovery within 10% of the control results was considered to be non-significant. The following compounds, at the levels indicated, were shown to have no significant interference on the Clover A1c test results: Acetaminophen: 20mg/dL, Bilirubin: 40mg/dL, Acetylsalicylic acid: 60mg/dL Caffeine: 6mg/dL, Glyburide: 0.19mg/dL, Ascorbic acid: 6mg/dL, Hydroxyzine dihydrochloride: 30mg/dL, Triglyceride: 3000 mg/dL, and Urea: 500 mg/dL.

To evaluate the effect of labile glycated hemoglobin and Hemoglobin variants (S, C, D, E, and F), two EDTA whole blood samples representing normal and abnormal A1c levels were split into aliquots. The samples were treated with various concentration of glucose (200-1000 mg/dL for 3 hours at 37°C), producing labile HbA1c. Hemoglobin variants were tested using samples provided by the NGSP known to contain variants S, C, D, E, and F. Control samples were prepared in the same manner, but were treated with an equal volume of diluents used to prepare the glucose stock solution in place of the 450 mg/dL glucose stock solution. The sponsor states recovery within 10% of the control sample was considered to be non-significant interfering.

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Based on the data, the sponsor claims no significant interference for labile glycated hemoglobin and Hb S, C, D, E, and F.

NGSP has hemoglobin variants interference information for methods at http://www.ngsp.org/prog/index.

Glucose Interference: Common interferences were evaluated by spiking venous blood with glucose to three concentrations based on CLSI EP7-P of low (less than 60 mg/dL), normal (110 mg/dL), and high (greater than 350 mg/dL). The glucose samples were spiked with the potentially interfering compounds and run in replicates of 5. Bias was calculated as the mean percent difference in glucose reading between the test and control concentration groups. The sponsor's acceptance criterion was <±10% difference to be considered as no significant interference. Based on the data, the sponsor claims no significant interference for the substances and concentrations shown in the table below:

|  Compound | Concentration tested up to (mg/dL)  |
| --- | --- |
|  Acetaminophen | 20  |
|  Bilirubin | 40  |
|  Gentistic acid | 50  |
|  Uric acid | 20  |
|  Levo-Dopa | 13  |
|  Creatinine | 30  |
|  Methyl-Dopa | 2.5  |
|  Tolazamide | 5  |
|  Dopamine | 13  |
|  Ascorbate | 6  |
|  Glutathione | 3  |
|  Ibuprofen | 50  |
|  Salicylic acid | 60  |
|  Tetracycline | 1.5  |
|  Tolbutamide | 100  |
|  Urea | 500  |
|  Cholesterol | 500  |
|  TG | 3000  |
|  Galactose | 50  |
|  Xylose | 10  |
|  Maltose | 300  |

Glucose Hematocrit Study - The sponsor performed hematocrit studies comparing the Clover device result at various hematocrits (20, 30, 40 and 51%) across the glucose measuring range to the Clover device at a normal hematocrit and to a YSI 2300 analyzer.

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All of the comparisons to the reference analyzer and to a normal hematocrit showed a bias within +/- 10 mg/dL for values < 75 mg/dL and +/-10% for values ≥75 mg/dL.

Glucose Altitude Study – A study was conducted to evaluate the effect of altitude on the Clover device. Venous blood was collected from volunteers and allowed to undergo glycolysis at room temperature to lower the endogenous glucose to approximately 40 mg/dL. Glucose values ranging from 42 mg/dL to 550 mg/dL were measured by Clover A1c glucose device in the altitude chamber at sea level and 10,000 feet conditions. The glucose values were confirmed with the YSI glucose analyzer. The meter readings obtained at 10,000 feet were compared to the meter readings at sea level and the % bias was determined at each level. Results recovered within ± 15 mg/dL at blood glucose levels of < 75 mg/dL and ± 15% at glucose levels > 75 mg/dL when compared to the readings near sea level. The labeling states that the Clover device can be used at elevations up to, but not higher than 10,000 feet above sea level.

f. Assay cut-off: Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

% HbA1c accuracy – A method comparison study was performed with 150 EDTA venous whole blood patient samples in three point of care sites (POC) sites by 9 intended users (three at each site). The testing was performed by comparing the venous whole blood results of 150 samples (50 at each site) that spanned the claimed assay range to the results obtained by the predicate, DCA vantage. Samples ranged from 4.3% -13.6% as measured by the predicate. 150 capillary samples were then collected and compared to the results obtained on the DCA vantage. The linear regressions are as follows:

|  Number of patient samples | Site | EDTA Venous blood | Capillary blood  |
| --- | --- | --- | --- |
|  50 | 1 | Y = 1.0011x + 0.0461
R² = 0.9851 | Y = 1.013x - 0.1683
R² = 0.9870  |
|  50 | 2 | Y = 0.9813x + 0.1305
R² = 0.9889 | Y = 0.9814x + 0.1519
R² = 0.9862  |
|  50 | 3 | Y = 0.9743x + 0.1746
R² = 0.9925 | Y = 1.0026x - 0.0649
R² = 0.9877  |
|  150 | All sites | Y = 0.9858x + 0.1151
R² = 0.9883 | Y = 0.999x - 0.0279
R² = 0.9868  |

Glucose accuracy: A method comparison study was performed with 150 capillary fingerstick patient samples in three points of care (POC) sites by nine intended users (three at each site). The testing was performed by comparing the fingertip results of 150

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samples (50 at each site) that spanned the claimed assay range to the results obtained by YSI 2300 and the predicate. Samples ranged from 20 to  $600\mathrm{mg / dL}$ . The samples that were less than  $50\mathrm{mg / dL}$  and greater than  $400\mathrm{mg / dL}$  were allowed to hydrolyze or were spiked to the desired glucose levels. The linear regressions are as follows:

|  Number of Samples | Sample type | Capillary blood  |   |
| --- | --- | --- | --- |
|   |  | Y S I | Predicate  |
|  50 | Site 1 | y = 0.9858x + 4.0206R2 = 0.9913 | y = 1.0039x + 0.391R2 = 0.9938  |
|  50 | Site 2 | y = 1.0127x - 2.4949R2 = 0.9946 | y = 0.99x + 4.6637R2 = 0.9884  |
|  50 | Site 3 | y = 1.0056x - 2.5383R2 = 0.9897 | y = 0.9924x + 2.0203R2 = 0.9915  |
|  150 | All sites | y = 1.0012x - 0.2741R2 = 0.9917 | y = 0.9957x + 2.2539R2 = 0.9912  |

System accuracy results for glucose concentrations  $< 75\mathrm{mg / dL}$

|  Within ± 5mg/dL 11/11 (100%) | Within ± 10 mg/dL 11/11 (100%) | Within ± 15 mg/dL 11/11 (100%)  |
| --- | --- | --- |

System accuracy results for glucose concentrations  $\geq 75\mathrm{mg / dL}$

|  Within ± 5 % | Within ± 10 % | Within ± 15 % | Within ± 20 %  |
| --- | --- | --- | --- |
|  106/139 (76%) | 135/139 (97%) | 139/139 (100%) | 139/139 (100%)  |

# b. Matrix comparison:

A1c: Venous whole blood samples (EDTA, heparin, citrate and fluoride/oxalate) collected from 25 donors were assayed on the Clover A1c and compared to the predicate (DCA Vantage). Fingertip capillary whole blood samples were then collected and compared to the results obtained on the DCA vantage. Samples ranged from  $4.0 - 14.0\%$ . The results of the studies are presented below:

|   | Heparin vs EDTA | Citrate vs EDTA | fluoride/oxalate vs EDTA  |
| --- | --- | --- | --- |
|   | y = 0.9999x - 0.0715 R² = 0.9996 | y = 0.9914x + 0.0726 R² = 0.9992 | y = 0.999x + 0.0008 R² = 0.9995  |
|   | EDTA vs Capillary | Heparin vs Capillary | Citrate vs Capillary | fluoride/oxalate vs Capillary  |
| --- | --- | --- | --- | --- |

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|  y = 0.9973x +
0.0123
R² = 0.9997 | y = 0.9969x + 0.087
R² = 0.9993 | y = 1.0052x -
0.0545
R² = 0.9992 | y = 0.9978x +
0.0157
R² = 0.9993  |
| --- | --- | --- | --- |

A1c: The sponsor concluded that the following anti-coagulants can be used with their A1c device: EDTA, heparin, citrate, and fluoride/oxalate.

Glucose: Not applicable; the Glucose device is only indicated for capillary whole blood.

3. Clinical studies:
a. Clinical Sensitivity: Not applicable
b. Clinical specificity: Not applicable
c. Other clinical supportive data (when a. and b. are not applicable): Not applicable

4. Clinical cut-off: Not applicable

5. Expected values/Reference range:

The hemoglobin A1c Expected Value Range is cited from literature (American Diabetes Association. Standards of Medical Care for Patients with Diabetes Mellitus. Diabetes Care 2001, 24 (Suppl. 1), 33-43). Hemoglobin A1c > 8% Action is suggested. Hemoglobin A1c < 7% is the goal. Hemoglobin A1c < 6% is non-diabetic level.

Glucose Expected Value Range is cited from the literature (American Diabetes Association Clinical Practice Recommendations 2004, Diabetes Care Supplement 1, p. S9.)

The normal fasting adult glucose range for a non-diabetic is 70 – 105 mg/dL. One to two hours after a meal, normal blood glucose levels should be less than 140 mg/dL

N. Instrument Name:

Clover A1c Analyzer for measuring Hemoglobin A1c and Glucose

O. System Descriptions:

1. Modes of Operation:

Each A1c cartridge and each glucose test strip is single use and must be replaced with a new cartridge or strip for additional readings. The user performs the A1c and glucose assays by following the prompts on the Analyzer display.

Does the applicant's device contain the ability to transmit data to a computer?
Yes ☐ X ☐ or No ☐

Does the applicant's device transmit data to a computer using wireless transmission?:
Yes ☐ or No ☐ X.

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2. Software:
FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:
Yes ☐ X ☐ or No ☐

3. Specimen Identification:
There is no sample identification function with this device. Samples are applied directly to the test cartridge or test strip as they are collected.

4. Specimen Sampling and Handling:
The glucose device is intended to be used with capillary whole blood from the finger. Since the whole blood sample is applied directly to the test strip there are no special handling or storage issues for glucose.
The A1c device is intended to be used with capillary whole blood from the finger and venous whole blood samples. Acceptable anticoagulants are EDTA, heparin, citrate and fluoride/oxalate, and these blood samples may be stored at -94 °F to 41 °F for two weeks or up to 77 °F for one week. Stored blood should be whole blood, not as hemolysate.
Allow blood samples to reach room temperature, 68 - 77 °F. Anti-coagulated blood should be mixed well prior to testing.

5. Calibration:
For glucose, a color tag on the back of the test strips provides lot specific calibration information. The analyzer automatically read and displays the strip code on the screen. The user must check to make sure that the strip code on the bottle matches with the strip code displays on the analyzer before assaying any glucose test. No calibration by the user is required.
The A1c assay is factory calibrated. No calibration by the user is required.

6. Quality Control:
Glucose control solutions at three different concentrations can be assayed with this device and are sold with the kit. When a test strip is inserted into the glucose test module, the control mode can be activated. This prevents control results from being stored in the internal memory. An acceptable range for each control level is printed on the test strip vial label. The user is cautioned not to use the module if the control result falls outside these ranges. For A1c, two levels of commercially available A1c controls are recommended in the labeling.

P. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

Q. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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**Source:** [https://fda.innolitics.com/submissions/CH/subpart-h%E2%80%94hematology-kits-and-packages/LCP/K082275](https://fda.innolitics.com/submissions/CH/subpart-h%E2%80%94hematology-kits-and-packages/LCP/K082275)

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