VARIANT II TURBO HBA1C KIT KIT-20 AND WASH/DILUENT SOLUTION SET, MODELS 270-2455, 270-2730

K090699 · Bio-Rad Laboratories, Inc. · LCP · Jul 27, 2009 · Hematology

Device Facts

• Record ID: K090699
• Device Name: VARIANT II TURBO HBA1C KIT KIT-20 AND WASH/DILUENT SOLUTION SET, MODELS 270-2455, 270-2730
• Applicant: Bio-Rad Laboratories, Inc.
• Product Code: LCP · Hematology
• Decision Date: Jul 27, 2009
• 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 percent determination of hemoglobin A₁c in human whole blood using ion-exchange high-performance liquid chromatography (HPLC). Bio-Rad VARIANT™ II TURBO HbA₁c kit is intended for Professional Use Only. Measurement of percent hemoglobin A₁c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.

Device Story

The VARIANT II TURBO HbA1c Kit - 2.0 is an in vitro diagnostic assay for professional use in clinical laboratories. It utilizes cation-exchange high-performance liquid chromatography (HPLC) to separate and quantify hemoglobin A1c from human anticoagulated whole blood (EDTA). The system processes samples through an analytical cartridge using sodium perchlorate buffers; detection occurs at 415 nm. The device provides a quantitative percentage of HbA1c, which clinicians use to monitor long-term glycemic control in diabetic patients. The system is standardized to DCCT and IFCC reference methods and certified by the NGSP. It is designed for high-throughput testing, with the kit supporting 2500 tests per cartridge.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (within-device CV 0.91-1.15%). Linearity confirmed per CLSI EP6-A (3.5-19.0% HbA₁c). Interference testing performed for bilirubin, lipids, EDTA, labile A₁c, carbamylated hemoglobin, and HbF. Method comparison against predicate (n=52) showed correlation coefficient of 0.994. No clinical studies performed.

Technological Characteristics

Cation-exchange HPLC; sodium perchlorate buffer system; 415 nm optical detection; linear range 3.5–19.0% HbA1c; standardized to DCCT/IFCC/NGSP; professional use; EDTA whole blood sample input.

Indications for Use

Indicated for monitoring long-term glucose control in individuals with diabetes mellitus via measurement of percent hemoglobin A1c in human whole blood.

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 Hemoglobin A₁c Program (k070452)

Submission Summary (Full Text)

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JUL 2,7 2009

# Summary of Safety and Effectiveness

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.

The assigned 510(k) number is:_ < 090699

| Submitter: | Bio-Rad Laboratories<br>Clinical Diagnostics Group<br>4000 Alfred Nobel Drive,<br>Hercules, California 94547<br>Phone: [phone]<br>FAX: [phone] | |
|------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| Contact Person: | Jackie Buckley<br>Regulatory Affairs Representative III | |
| Date of Summary Preparation: | March 12, 2009 | |
| Device Name: | VARIANT™ II TURBO HbA1c Kit - 2.0<br>(Catalog number 270-2455) | |
| Classification Name: | Assay, Glycosylated Hemoglobin, LCP | |
| Predicate Device: | VARIANT™ II Hemoglobin A1c Program<br>(k)070452<br>Bio-Rad Laboratories<br>(Catalog number 270-2101NU) | |
| Intended Use: | The Bio-Rad VARIANT II TURBO HbA1c Kit -<br>2.0 is intended for the percent determination of<br>hemoglobin Alc in human whole blood using ion-<br>exchange high performance liquid chromatography<br>(HPLC). | |
| | The Bio-Rad VARIANT II TURBO HbAlc Kit -<br>2.0 is intended for Professional Use Only. | |
| Indications for Use: | Measurement of percent hemoglobin A1c is<br>effective in monitoring long-term glucose control in<br>individuals with diabetes mellitus. | |

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#### Description of the Device:

The VARIANT II TURBO Hemoglobin-Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II TURBO HbA1c kit -2.0 is based on chromatographic separation of Hemoglobin A1c on a cation exchange cartridge.

#### Technical Characteristics Compared to the Predicate:

The new VARIANT II TURBO HbA1c Kit – 2.0 (270-2455) and the predicate VARIANT II Hemoglobin A1c Program (270-2101NU) have the same technical characteristics that are summarized in the table below:

| Characteristics | VARIANT II TURBO HbA1c - 2.0<br>(270-2455) | VARIANT II Hemoglobin A1c<br>(270-2101NU) (k)070452 |
|-----------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Analyte Measured: Reported | %Hemoglobin A1c | %Hemoglobin A1c |
| Intended Use | The Bio-Rad VARIANT II TURBO HbA1c<br>Kit - 2.0 is intended for the percent<br>determination of hemoglobin A1c in human<br>whole blood using ion-exchange high<br>performance liquid chromatography (HPLC).<br>The Bio-Rad VARIANT II TURBO HbA1c<br>Kit - 2.0 is intended for Professional Use<br>Only. | The Bio-Rad VARIANT II Hemoglobin A1c<br>Program is intended for the percent determination<br>of hemoglobin A1c in human whole blood using<br>ion-exchange high performance liquid<br>chromatography (HPLC).<br>The Bio-Rad VARIANT Hemoglobin A1c<br>Program is intended for Professional Use Only. |
| Assay Principle | Cation exchange high performance liquid<br>chromatography | Cation exchange high performance liquid<br>chromatography |
| Sample Type | Human anticoagulated whole blood (EDTA) | Human anticoagulated whole blood (EDTA) |
| Visible Detection | 415 nm | 415 nm |
| Total Area Range | 1.0 - 3.5 million μvolt•second | 1.5 - 4.5 million μvolt•second |
| Calibration Frequency | After installation of the analytical<br>cartridge | After installation of the analytical cartridge and<br>once every 30 days |
| Kit size | 2500 tests | 1000 test |
| Cartridges Included in Kit | 1 Cartridge (2500 tests) | 1 Cartridge (1000 tests) |
| Buffer A and Buffer B formulation | Sodium Perchlorate Buffer | Tris-Bis Buffer |
| Standardization | Traceable to the Diabetes Control and<br>Complications Trial (DCCT) reference<br>method and IFCC. Certified via the National<br>Glycohemoglobin Standardization Program<br>(NGSP). | Traceable to the Diabetes Control and<br>Complications Trial (DCCT) reference method<br>and IFCC. Certified via the National<br>Glycohemoglobin Standardization Program<br>(NGSP). |

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#### Testing To Establish Substantial Equivalence:

#### Accuracy:

Method correlation between the VARIANT II TURBO HbA1c Kit - 2.0 (270-2455) and VARIANT II Hemoglobin A1c Program (270-2101NU) was compared using 40 EDTA whole blood patient samples and 12 samples prepared by mixing EDTA whole blood patient samples with Lyphochek® Hemoglobin A1c Linearity Set samples in various ratios. The range of values on the VARIANT II TURBO HbA1c Kit -2.0 was from 2.6% to 19.0% HbA1c. The results are presented in the following regression table.

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| | | | | |

#### Precision:

The following table provides comparison data on the precision between the VARIANT II TURBO HoA1c Kit - 2.0 (270-2455) and VARIANT II Hemoglobin A1c (270-2101NU) Programs, each utilizing low and high EDTA whole blood patient samples, and both tested against samples with moderate (5.5/5.6) and high (8.8/11.4) % A1c content.

Method precision was performed using a protocol based on the NCCLS Evaluation protocol, Vol.24, No. 25, EP5-A2 for the VARIANT II TURBO HbA Ic Kit - 2.0 and the VARIANT II Hemoglobin A1c (270-2101NU). The protocols for both the VARIANT II TURBO HbA1c Kit -- 2.0 and the VARIANT II Hemoglobin A1c Programs are similar.

For the VARIANT II TURBO HbA1c Kit - 2.0 and the VARIANT II Hemoglobin A1c Program protocol, six VARIANT II TURBO and six VARIANT II Hemoglobin Testing Systems at three Bio-Rad sites were utilized. Each site was provided with the same sample set and performed two replicates of each sample on each of 2 runs per day for 10 davs.

Although the precision samples are different, since they were run at different time periods, the precision results between the VARIANT II TURBO Hemoglobin A1c (270-2255) and the current VARIANT II Hemoglobin A1c Program (270-2101NU) are equivalent. A summary of combined comparative precision results is presented in the following precision table.

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#### VARIANT II TURBO HbA1c Kit - 2.0 (270-2455) and VARIANT II Hemoglobin A1c (270-2101NU) Precision

| VARIANT II TURBO HbA1c Kit - 2.0<br>(270-2455) | | VARIANT II Hemoglobin A1c<br>(270-2101NU) | | |
|------------------------------------------------|----------------------|-------------------------------------------|----------------------|------|
| Low Patient (HbA1c) | High Patient (HbA1c) | Low Patient (HbA1c) | High Patient (HbA1c) | |
| n= (number of samples) | 240 | 240 | 240 | 160 |
| Mean | 5.6 | 11.4 | 5.5 | 8.8 |
| Within run (%CV) | 0.78 | 0.39 | 0.9 | 0.6 |
| Within Device Precision (%CV) | 1.15 | 0.91 | 1.60 | 1.38 |

#### Linearity:

| | VARIANT II TURBO HbA1c Kit –<br>2.0 (210-2455) | VARIANT II Hemoglobin A1c<br>Program (210-2101NU) |
|--------------|------------------------------------------------|---------------------------------------------------|
| Linear Range | 3.5 – 19.0 % HbA1c | 3.1 – 18.5 % HbA1c |

### Interfering Substances:

| Interfering Substance | VARIANT II TURBO HbA1c<br>Kit-2.0 (270-2455) | VARIANT II Hemoglobin A1c<br>(270-2101NU) |
|---------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------|
| Bilirubin | No interference up to 20 mg/dL | No interference up to 20 mg/dL |
| Lipids<br>(Triglycerides) | No interference up to 6000<br>mg/dL | No interference up to 6000<br>mg/dL |
| EDTA | No interference up to 11X EDTA | No interference up to 11X EDTA |
| Hemoglobin F | 25% | 15% |
| Interference from HbS, HbC,<br>HbE, HbD trait samples on %A1c | Two out of 7 hemoglobin AD-<br>trait, 2 out of 11 hemoglobin AS-<br>trait, 1 out of 12 hemoglobin AE-<br>trait, and 3 out of 9 hemoglobin<br>AC-trait patient samples at the<br>clinically significant levels of 6%<br>and 9% HbA1c exhibited<br>differences of more than ±10%<br>from values obtained using<br>boronate affinity reference<br>method | No interference |

#### Conclusion:

When considering the similarities of the intended use, the general characteristics of the two assays, the use of the same technology and the similar correlation, accuracy and linearity between the two methods, it can be concluded that the VARIANT II TURBO HbA1c Kit - 2.0 (270-2455) is substantially equivalent to the cleared and currently marketed predicate, VARIANT II Hemoglobin A1c Program (270-2101NU):

Bio-Rad Laboratories, Inc. VARIANT II TURBO HbA1c Kit -2.0 Page 3 of 4

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

Bio-Rad Laboratories, Inc. c/o Jackie H. Buckley 4000 Alfred Nobel Dr. Hercules, CA 94547

JUL 2 7 2009

Re: k090699

> Trade/Device 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: June 17, 2009 Received: June 18, 2009

Dear Jackie Buckley:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, 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 approval of a premarket approval application (PMA). You may, 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, good manufacturing 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 affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In 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 not mean 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 Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting of medical devicerelated adverse events) (21 CFR 803); and good manufacturing 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 contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at [phone]. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Courtney C. Harper, Ph.D. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known): k090699

Device Name: VARIANT II TURBO™ HbAje Kit - 2.0

Indications For Use:

The Bio-Rad VARIANT™ II TURBO HbA1c Kit -2.0 is intended for the percent determination of hemoglobin Att in human whole blood using ion-exchange highperformance liquid chromatography (HPLC). Bio-Rad VARIANT™ II TURBO HbAic kit is intended for Professional Use Only.

Measurement of percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.

AND/OR Prescription Use × (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 807 Subpart C)

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

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

Curl Benam

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

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510(k) K090699