VARIANT II TURBO HBA1C KIT-2.0 VARIANT II TURBO HEMOGLOBIN TESTING SYSTEM

K122472 · Bio-Rad Laboratories, Inc., Clinical Systems Divis · LCP · Oct 26, 2012 · Hematology

Device Facts

• Record ID: K122472
• Device Name: VARIANT II TURBO HBA1C KIT-2.0 VARIANT II TURBO HEMOGLOBIN TESTING SYSTEM
• Applicant: Bio-Rad Laboratories, Inc., Clinical Systems Divis
• Product Code: LCP · Hematology
• Decision Date: Oct 26, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7470
• Device Class: Class 2

Intended Use

The Bio-Rad VARIANT™ II TURBO HbA1c Kit-2.0 is intended for the quantitative determination of hemoglobin Ate in human whole blood using ionexchange high performance liquid chromatography (HPLC) on the VARIANT™ II TURBO Hemoglobin Testing System. Measurement of hemoglobin A1c is effective in monitoring long term glycemic control in individuals with diabetes mellitus. The Bio-Rad VARIANT™ II TURBO HbA1c Kit-2.0 is intended for Professional Use Only.

Device Story

The VARIANT™ II TURBO HbA1c Kit-2.0 is an in vitro diagnostic assay used with the VARIANT™ II TURBO Hemoglobin Testing System. The system utilizes ion-exchange high-performance liquid chromatography (HPLC) to separate and quantify hemoglobin A1c in EDTA-anticoagulated human whole blood. The system consists of a chromatographic station and a sampling station, controlled by a PC running Clinical Data Management (CDM) software. It is a fully automated, high-throughput analyzer operated by laboratory professionals in clinical settings. The system processes samples, performs chromatographic separation on a cation exchange cartridge, and calculates HbA1c concentrations. Results are reported in %HbA1c (NGSP), mmol/mol (IFCC), or %HbA1c (JDS). These quantitative results assist healthcare providers in assessing long-term glycemic control for patients with diabetes mellitus.

Clinical Evidence

Bench testing only. Method comparison study (CLSI EP9-A2) compared CDM software v5.1 vs v4.03 using 100 EDTA whole blood samples and 16 spiked samples. Results showed high correlation (R²=0.999) and acceptable bias at decision points (6.0% and 9.0% HbA1c). Interference testing (CLSI EP7-A2) confirmed no significant interference from HbS (≤67%), HbC (≤72%), HbD (≤55%), HbE (≤41%), or β-thalassemia trait (HbA2 up to 10%).

Technological Characteristics

Ion-exchange HPLC; cation exchange matrix. Components: analytical cartridge, prefilters, elution buffers, calibrators, whole blood primer. Electrical safety: BS EN 61010; EMC: BS EN 61326. Software: Clinical Data Management (CDM) v5.1.1. Connectivity: PC-controlled system. NGSP and IFCC certified.

Indications for Use

Indicated for the quantitative determination of hemoglobin A1c in human whole blood to monitor long-term glycemic control in individuals with diabetes mellitus. For professional use only.

Regulatory Classification

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

• VARIANT™ II TURBO HbA1c Kit - 2.0 (K090699)

Submission Summary (Full Text)

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KI22472

# 510(k) Summary for VARIANT™ II TURBO HbA1c Kit - 2.0

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

OCT 26 2012

The assigned 510(k) number is:

Preparation Date: August 8, 2012

## A. Applicant

Bio-Rad Laboratories, Inc. Clinical Systems Group 4000 Alfred Nobel Drive Hercules, CA 94547

Contact Person: Jackie Buckley, Regulatory Affair Representative IV Email: Jackie [e-mail] Phone: [phone] FAX: [phone]

#### B. Device Name and Regulatory Information

Proprietary Name: VARIANT™ II TURBO HbA1c Kit - 2.0 Regulation section: 21 CFR 864.7470, Glycosylated Hemoglobin Assay Device Classification: Class II Product Code: LCP, Assay, Glycosylated Hemoglobin Panel: Hematology

#### C. Predicate Device

VARIANT™ II TURBO HbAre Kit - 2.0 (k)090699

#### D. Intended Use

1. Intended Use:

The Bio-Rad VARIANT™ II TURBO HbA1c Kit-2.0 is intended for the quantitative determination of hemoglobin Ate in human whole blood using ionexchange high performance liquid chromatography (HPLC) on the VARIANT™ II TURBO Hemoglobin Testing System. Measurement of hemoglobin A1c is effective in monitoring long term glycemic control in individuals with diabetes mellitus. The Bio-Rad VARIANT™ II TURBO HbA1c Kit-2.0 is intended for Professional Use Only.

- 2. Indications for Use: Same as above
- 3. Special conditions for use statement(s):

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For Prescription Use Only

4. Special instrument requirements:

For use with the Bio-Rad VARIANT™II TURBO Hemoglobin Testing System

# E. Description of Device:

The VARIANT II TURBO Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II TURBO HbA12 Kit - 2.0 is based on chromatographic separation of Hemoglobin A10 on a cation exchange cartridge. The VARIANT II TURBO HbA1c Kit - 2.0 contains an analytical cartridge, 5 prefilters, Elution Buffer A and B, Calibrator Level 1, Calibrator Level 2, Whole Blood Primer, sample vials and a CD-ROM with test parameters.

The VARIANT II TURBO Hemoglobin Testing System provides an integrated method for sample preparation, separation and the quantitative determination of HbAle in EDTA human whole blood. The VARIANT II TURBO Hemoglobin Testing System is a fully automated, high-throughput hemoglobin analyzer. It consists of two modules - the VARIANT II Chromatographic Station (VCS) and the VARIANT II Sampling Station (VSS). There have been hardware updates due to obsolescence of parts and firmware updates to support the replacement hardware components.

A personal computer is used to control the VARIANT II TURBO Hemoglobin Testing System using updated Clinical Data Management (CDM) software version 5.1.1.

# F. Summary of the device technological characterizes:

The VARIANT II TURBO HbA1c- 2.0 Kit and modified System have the same characteristics as the predicate, VARIANT II TURBO HbAtc- 2.0 Kit (k)090699. Comparisons of features are provided in the table below:

| Feature | Predicate: | Modified device: |
|-----------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Bio-Rad VARIANT TM II TURBO<br>HbA1c Kit -2.0<br>(k)090699 | Bio-Rad VARIANT TM II TURBO<br>HbA1c Kit -2.0 |
| Similarities | | |
| Technology | Ion-exchange high performance liquid chromatography | |
| Sample type | Anticoagulated whole blood (EDTA) | |
| Calibrator | Human anticoagulated whole blood treated with EDTA | |
| Calibration frequency | Once every 500 injections/ 2500 injections total column life | |
| Certification | Certified by the NGSP as traceable to the Diabetes Control and<br>Complications Trial (DCCT) Reference method. | |
| Certification | Certified by the IFCC as traceable to the IFCC Reference<br>Measurement Procedure. | |
| Instrument Control | Windows Operating System with Proprietary Assay Software | |
| Kit configuration | One analytical cartridge, 5 prefilters, Elution Buffer A and B,<br>Calibrator Level 1, Calibrator Level 2, Whole Blood Primer,<br>sample vials and a CD-ROM with test parameters. | |
| Feature | Predicate:<br>Bio-Rad VARIANT™ II TURBO<br>HbA1c Kit -2.0<br>(k)090699 | Modified device:<br>Bio-Rad VARIANT™ II TURBO<br>HbA1c Kit -2.0 |
| Chemistry | Cation Exchange Matrix | |
| Safety Standards for<br>Electrical Equipment<br>for IVD Use | BS EN 61010 Certified | |
| Electromagnetic<br>Compatibility | BS EN 61326 Certified | |
| | Differences | |
| Reporting units | % HbA1c (NGSP) | % HbA1c (NGSP), mmol/mol<br>HbA1c (IFCC), or %HbA1c (JDS) |
| Intended Use | Intended for the percent<br>determination of HbA1c in human<br>whole blood using ion-exchange<br>HPLC.<br>Measurement of percent HbA1c is<br>effective in monitoring long-term<br>glucose control in individuals<br>with diabetes mellitus. | Intended for the quantitative<br>determination of HbA1c in<br>human whole blood using ion-<br>exchange HPLC on the<br>VARIANT II TURBO<br>Hemoglobin Testing System.<br>Measurement of percent HbA1c<br>is effective in monitoring long-<br>term glucose control in<br>individuals with diabetes<br>mellitus. |
| Interference from<br>variants (HbD,<br>HbE, HbS, HbC) | Hemoglobin variants: Two out of<br>7 hemoglobin AD-trait, 2 out of<br>11 hemoglobin AS-trait, 1 out of<br>12 hemoglobin AE-trait, and 3<br>out of 9 hemoglobin AC-trait<br>patient samples at the clinically<br>significant levels of 6% and 9%<br>HbA1c exhibited differences of<br>more than ±10% from values<br>obtained using boronate affinity<br>reference method. | No significant interference was<br>observed at the following<br>concentrations:<br>• HbS ≤67%<br>• HbC ≤72%<br>• HbD ≤55%<br>• HbE ≤41% |
| Interference from<br>HbA2 | No claim previously | β-thalassemia trait, as indicated<br>by increased HbA2<br>concentrations up to 10%, does<br>not interfere with the assay. |
| Expected Range<br>From American<br>Diabetes Association<br>Standard of Care | Hemoglobin A1c Ranges<br>Hemoglobin<br>A1c (%)<br>>8<br><7<br><6 | Hemoglobin A1c Ranges<br>Hemoglobin<br>A1c (%)<br><8<br><7<br><6.5 |
| | Degree of<br>Glucose<br>Control<br>Action<br>Suggested<br>Goal<br>Non-Diabetic<br>Goal | Glycemic<br>Goal<br>Less<br>Stringent<br>Goal<br>General Goal<br>More<br>Stringent |

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Bio-Rad Laboratories, Inc. VARIANT™ II TURBO HbA1c Kit -2.0

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| Feature | Predicate:<br>Bio-Rad VARIANT™ II TURBO<br>HbA1c Kit -2.0<br>(k)090699 | Modified device:<br>Bio-Rad VARIANT™ II TURBO<br>HbA1c Kit -2.0 | | | | |
|---------|------------------------------------------------------------------------|------------------------------------------------------------------|--|--|--|--|
| | | <5.7 Goal Non-Diabetic<br>Goal | | | | |
| | From American Diabetes<br>Association Standard of Care<br>(2001) | From American Diabetes<br>Association Standard of Care<br>(2012) | | | | |

## Method Comparison:

This study was performed following CLSI guideline EP9-A2 Method Comparison and Bias Estimation Using Patient Samples. To demonstrate the correlation between CDM Software Versions 5.1 and 4.03, the VARIANT II TURBO HbA1c Kit - 2.0 was run on the VARIANT II TURBO Hemoglobin Testing System using both software versions. The protocol consisted of 100 EDTA whole blood human samples and 16 samples prepared by mixing EDTA whole blood samples with either purified HbAo or purified HbA1c. The samples were run as a single injection and the ranges of values are presented in Table 2 below.

The purpose of this study was to demonstrate that the modified version of software (v5.1) did not produce a clinically significant effect on HbA1c results with the use of +/- 10% relative bias at 6% and 9% HbAic as evaluation limits. The Bias Estimation data is presented in Table 1 and acceptable error at the decision points were met. The linear regression correlation data is presented in Table 2.

| Criteria | First Decision Point | Second Decision Point |
|-------------------------------|----------------------|-----------------------|
| Decision point | 6.0 %HbA1c | 9.0 %HbA1c |
| Predicted value by regression | 6.01 | 8.99 |
| Predicted bias by regression | 0.2% | -0.1% |
| Upper 95% confidence limit | 0.5% | 0.1% |
| Lower 95% confidence limit | -0.1% | -0.3% |

Table 1: Bias Estimation at two Decision Points of %HbArc (NGSP)

#### Table 2: Linear Regression Data

| | Regression Equation | R2 | Sample Range |
|-----------------|---------------------|-------|-----------------|
| %HbA1c (NGSP) | Y=0.99x + 0.06 | 0.999 | 3.5 - 19.5% |
| mmol/mol (IFCC) | Y=0.99x + 0.48 | | 15-190 mmol/mol |
| %HbA1c (JDS) | Y=0.99x + 0.06 | | 3.1 - 19.3% |

# Analytical specificity:

Hemoglobin variant Interference study:

This study was performed following CLSI EP7-A2: Guidelines Interference Testing in Clinical Chemistry; Approved Guidelines, Second Edition.

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Two fresh, EDTA non-variant human blood sample pools at 6.5% and 8.0-9.0% HbA1c were collected. Fresh, EDTA human homozygous blood samples for each of the 4 hemoglobin variants (e.g. E, D, S, and C) was obtained for dilution. For the interference testing of each variant, a series of test sample pools were prepared by the dilution of a homozygous variant patient sample (as interferent) in the non-variant patient sample pool. The samples were run in duplicate on two VARIANT II TURBO Hemoglobin Testing Systems. The conclusion of this study demonstrated that no interference was observed at the following concentrations: HbS ≤ 67%, HbC ≤ 72%, HbD ≤ 55%, and HbE < 41%.

### 8. Conclusion:

When considering the similarities of the intended use, the general features and characteristics of the assay, the use of the same technology, it can be concluded that the VARIANT II TURBO HbA1e Kit - 2.0 is substantially equivalent to the cleared and currently marketed predicate, VARIANT II TURBO HbA1c Kit - 2.0 (k090699).

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# DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or a stylized human figure.

10903 New Hampshire Avenue Silver Spring, MD 20993

Bio-Rad Laboratories, Inc. Clinical System Division c/o Jackie Buckley Regulatory Affairs Representative IV 4000 Alfred Nobel Drive Hercules, CA 94547

OCT 2 6 2012

k122472 Re:

Trade Name: VARIANT II TURBO HbA1c Kit – 2.0 Regulation Number: 21 CFR §864.7470 Regulation Name: Glycosylated Hemoglobin Assay Regulatory Class: Class II Product Code: LCP Dated: August 10, 2012 Received: August 14, 2012

Dear Ms. Buckley:

We have reviewed your Section 510(k) premarket notification of intent to market the We have fevenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices the indications for ace commerce prior to May 28, 1976, the enactment date of the marketed in interstate commits, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require with the provisions of the Poural Poola, 2007, 1997, 1997, 1997, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, pro ristories facturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations (1 Mrs), it may be sacreer to our a in Title 21, Code of Federal Regulations (CFR), Parts arroomig your addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does I loase of as that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other requirements of the reveals with all the Act's requirements, including, but not I coderal agencies: " o a nd listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 11mical to: registration and issues of medical device-related adverse events) (21 007), medical de rece reportains (iig practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please If you desire specific advice for your devices and Radiological Health at [phone].
Contact the Office of In Vitro Diagnostic Devices and Radiological Health at (301) 7 Also, please note the regulation entitled, "Misbranding by reference to premarket notification" Also, please note the regulation entired, and securities please contact CDRH'S (21 CFR Fall 807.97). For questions regarding prises
Office of Surveillance and Biometric's (OSB's) Division of Postmarks Surveillance at (301) Office of Surveiner and Dromers of (322-57 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 CFR Part 803), please go to http://www.fda.gov/Medical

CFK I all 805), prease go to http://www.brunes.org/w/index.php?title=Office of Surveillance and Biometrics/Division of Postmarket Surveillance...

You may obtain other general information on your responsibilities under the Act from the You may outlail other general mionnation on Jour Copyright (800 638-2041 or [phone] or at its Internet address http://www.fda/gov/MedicalDevices/ResourcesforYou/Industry/default.html

Sincerely yours,

Courtney H. Lias, Ph.D Director Division of Chemistry and Toxicology Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known): K122472

Device Name: VARIANTTM II TURBO HbA16 Kit -- 2.0

Indications for Use:

The Bio-Rad VARIANT™ II TURBO HbA1c Kit - 2.0 is intended for the quantitative determination of hemoglobin A1c in human whole blood using ion-exchange highperformance liquid chromatography (HPLC) on the VARIANT™ II TURBO Hemoglobin Testing System. Measurement of hemoglobin A16 is effective in monitoring long-term glycemic control in individuals with diabetes mellitus. The Bio-Rad VARIANT II TURBO HbA1e Kit – 2.0 is intended for Professional Use Only.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Raul Lemo

Division Sign-ON Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) k122472

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