VARIANT II HEMOGLOBIN A1C PROGRAM WITH MODELS 270-2101NU

K070452 · Bio-Rad Laboratories, Inc. · LCP · May 7, 2007 · Hematology

Device Facts

• Record ID: K070452
• Device Name: VARIANT II HEMOGLOBIN A1C PROGRAM WITH MODELS 270-2101NU
• Applicant: Bio-Rad Laboratories, Inc.
• Product Code: LCP · Hematology
• Decision Date: May 7, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7470
• Device Class: Class 2

Intended Use

The Bio-Rad VARIANT II Hemoglobin A1c Program is intended for the percent determination of hemoglobin A1c in human whole blood using ion-exchange high-performance liquid chromatography (HPLC). The Bio-Rad VARIANT II Hemoglobin A1c Program 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 Hemoglobin A1c Program 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 in human anticoagulated whole blood (EDTA). The system processes samples to measure absorbance at 415 nm. The resulting data is used by healthcare providers to monitor long-term glucose control in patients with diabetes mellitus. The device provides quantitative results that assist clinicians in assessing glycemic management over time.

Clinical Evidence

Bench testing only. Precision study (n=240 normal, n=160 diabetic) across 6 instruments/3 labs showed total precision (%CV) of 2.53% (normal) and 2.84% (diabetic). Linearity verified across 3.1%–18.5% HbA1c range (slope 0.998). Interference studies confirmed no significant impact from bilirubin, HbF, labile A1c, lipemia, or EDTA. Method comparison against predicate (n=50) yielded correlation coefficient of 0.9958.

Technological Characteristics

Cation exchange HPLC; automated analyzer. Components: analytical cartridge, prefilters, buffers, wash/diluent, calibrator set. Software: Clinical Data Management (CDM) for system control. Standardization: DCCT/IFCC/NGSP traceable. Sterilization: N/A (reagent kit). Connectivity: PC-controlled system.

Indications for Use

Indicated for monitoring long-term glucose control in individuals with diabetes mellitus.

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 (K984268)

Submission Summary (Full Text)

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# 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:_ 070452__

| Submitter: | Bio-Rad Laboratories, Inc.<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 |
| Date of Summary Preparation: | February 14, 2007 |
| Device Name: | VARIANT™ II Hemoglobin A1c Program<br>(Catalog number 270-2101NU) |
| Classification Name: | Assay, Glycosylated Hemoglobin, 81LCP |
| Predicate Device: | VARIANT™ II Hemoglobin A1c Program<br>K984268<br>Bio-Rad Laboratories, Inc.<br>(Catalog number 270-2101) |
| Intended Use: | 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 II Hemoglobin A1c<br>Program 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 Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II Hemoglobin A1c Program is based on chromatographic separation of Hemoglobin A1c on a cation exchange cartridge.

## Technical Characteristics Compared to the Predicate:

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

| Characteristics | VARIANT II Hemoglobin A1c<br>(270-2101NU) | VARIANT II Hemoglobin A1c<br>(270-2101) (k)984268 |
|------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Analyte Measured: Reported | %Hemoglobin A1c | %Hemoglobin A1c |
| Intended Use | The Bio-Rad VARIANT II Hemoglobin A1c<br>Program 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 Hemoglobin A1c<br>Program 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>For In Vitro Diagnostic Use. |
| 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 | 1.5 – 4.5 million μvolt·second | 1.0 – 4.0 million μvolt·second |
| Calibration Frequency | After installation of the analytical<br>cartridge and once every 30 days | After installation of the analytical cartridge |
| Reconstituted Calibrator Stability | 30 days | 7 days |
| Calibrator Reconstitution Volume | 7 mL | 5 mL |
| Cartridges Included in Kit | 1 Cartridge (1000 tests) | 2 Cartridges (500 tests each) |
| 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 new VARIANT II Hemoglobin A1c Program (270-2101NU) and current VARIANT II Hemoglobin A1c Program (270-2101) was evaluated using 42 EDTA whole blood patient samples ranging from 4.2% to 10.9% HbA12. 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 new VARIANT II Hemoglobin A1c (270-2101NU) and VARIANT II Hemoglobin A1c (270-2101) Programs, each utilizing low and high EDTA whole blood patient samples, and both tested against samples with moderate (5.4/5.5) and high (8.8- 13.7) % A1c content.

Method precision was performed using a protocol based on the NCCLS Evaluation protocol, Vol.24, No. 25, EP5-A2 (2004) for the new VARIANT II Hemoglobin A1c (270-2101NU) and NCCLS Evaluation protocol, Vol.12, No. 4, EP5-T2 (Mar. 1992) for the current VARIANT II Hemoglobin Air Program (270-2101). The protocols for both the new VARIANT II Hemoglobin A1c and current VARIANT II Hemoglobin A1c Programs are similar.

For the new VARIANT II Hemoglobin A1c Program protocol, 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/day for 10 days.

For the current VARIANT II Hemoglobin A1c Program protocol, 40 runs (2 per day) were performed on one VARIANT II Hemoglobin Testing System over 20 working days. In each duplicate daily run, one aliquot of low HbAIc and one aliquot of high HbA1c patient samples were each analyzed per run.

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

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#### VARIANT II Hemoglobin A1c (270-2101NU) and VARIANT II Hemoglobin A1c (270-2101) Precision

| New VARIANT II Hemoglobin A1c<br>(270-2101NU) | | VARIANT II Hemoglobin A1c<br>(270-2101) | | |
|-----------------------------------------------|----------------------|-----------------------------------------|----------------------|------|
| Low Patient (HbA1c) | High Patient (HbA1c) | Low Patient (HbA1c) | High Patient (HbA1c) | |
| n= (number of samples) | 240 | 160 | 80 | 80 |
| Mean | 5.5 | 8.8 | 5.4 | 13.7 |
| Within run (%CV) | 0.9 | 0.6 | 1.46 | 0.65 |
| Within Device<br>Precision (%CV) | 1.60 | 1.38 | NA | NA |
| Total Precision (%CV) | NA | NA | 2.14 | 1.68 |

### Linearity:

| | VARIANT II Hemoglobin A1c<br>Program (210-2101NU) | VARIANT II Hemoglobin A1c<br>Program (270-2101) |
|--------------|---------------------------------------------------|-------------------------------------------------|
| Linear Range | 3.1 - 18.5 % HbA1c | 1.3 - 18.9 % HbA1c |

#### Interfering Substances:

| Interfering Substance | VARIANT II Hemoglobin A1c<br>(270-2101NU) | VARIANT II Hemoglobin A1c<br>(270-2101) |
|---------------------------|-------------------------------------------|-----------------------------------------|
| 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 | 10% | 15% |

#### 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 new VARIANT II Hemoglobin Alc Program (270-2101NU) is substantially equivalent to the cleared and currently marketed predicate, VARIANT II Hemoglobin A1c Program (270-2101).

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo features a stylized eagle with three bars representing its wings, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle. The logo is black and white.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

MAY -7 2007

Re: k070452

> Trade Name: Variant II Hemoglobin A1c Program Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP, KRZ Dated: February 14, 2007 Received: February 16, 2007

Dear Ms. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, 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" (21CFR Part 807.97). 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 [phone] or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Jean M. Cooper, M.S., D.v.M.

Jean M. Cooper, M.S., D.V.M. 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): k070452

Device Name: VARIANT II Hemoglobin A1c Program

Indications For Use:

The Bio-Rad VARIANT II Hemoglobin A1c Program is intended for the percent determination of hemoglobin A1c in human whole blood using ion-exchange highperformance liquid chromatography (HPLC).

The Bio-Rad VARIANT II Hemoglobin A1c Program is intended for Professional Use Only.

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

Prescription Use × (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 IF NEEDED)

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

Sign-Off

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