VARIANT II HEMOGLOBIN A1C

K040872 · Bio-Rad Laboratories, Inc. · LCP · Apr 15, 2004 · Hematology

Device Facts

• Record ID: K040872
• Device Name: VARIANT II HEMOGLOBIN A1C
• Applicant: Bio-Rad Laboratories, Inc.
• Product Code: LCP · Hematology
• Decision Date: Apr 15, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7470
• Device Class: Class 2
• Attributes: 3rd-Party Reviewed

Intended Use

The Bio-Rad VARIANT II TURBO Hemoglobin A₁c Program is intended for the percent determination of hemoglobin A₁c in human whole blood using ion-exchange high performance liquid chromatography (HPLC). For In Vitro Diagnostic Use. The Bio-Rad VARIANT II TURBO Hemoglobin A₁c Program is intended for Professional Use Only. For In Vitro Diagnostic Use. Measurement of percent hemoglobin A₁c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.

Device Story

The VARIANT II TURBO Hemoglobin A1c Program is an in vitro diagnostic system for professional use in clinical settings. It utilizes ion-exchange high-performance liquid chromatography (HPLC) to analyze human anticoagulated whole blood (EDTA) samples. The system separates hemoglobin A1c from other hemoglobin components via a cation exchange cartridge. Detection occurs at 415 nm. The device provides a quantitative measurement of percent hemoglobin A1c, which healthcare providers use to monitor long-term glucose control in diabetic patients. The system is standardized to the Diabetes Control and Complications Trial (DCCT) reference method and the IFCC, and is certified by the National Glycohemoglobin Standardization Program (NGSP).

Clinical Evidence

No clinical trials were performed. Substantial equivalence was established via bench testing, including precision (n=80 per sample type), linearity (n=2 per standard), and method comparison (n=201 patient samples) against the predicate. Regression analysis showed r²=0.9946, slope=0.9792, and intercept=0.185. Interference studies confirmed no impact from bilirubin, lipids, or excess EDTA.

Technological Characteristics

Ion-exchange HPLC system; uses polymeric cation exchange resin-packed analytical and guard cartridges. Energy source: electrical. Connectivity: computer-based data management. Software: Clinical Data Management. Standards: NGSP/IFCC traceable; electrical safety per EN61010-1, EN61010-2-010, EN61010-2-101, EN61326. Dimensions: modular 3-unit system (Sampling Station, Chromatographic Station, Computer).

Indications for Use

Indicated for professional use in monitoring long-term glucose control in individuals with diabetes mellitus via percent determination of HbA1c in human EDTA-anticoagulated 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 (k984268)

Submission Summary (Full Text)

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## APR 1 5 2004

# 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.

40 The assigned 510(k) number is:

| 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: | January 26, 2004 |
| Device Name: | VARIANT™ II TURBO Hemoglobin A1c Program |
| Classification Name: | Assay, Glycosylated Hemoglobin, 81LCP |
| Predicate Device: | VARIANTTM II Hemoglobin A1c Program<br>K984268<br>Bio-Rad Laboratories, Inc. |
| Intended Use: | The Bio-Rad VARIANT II TURBO Hemoglobin<br>A1c Program is intended for the percent<br>determination of hemoglobin A1c in human whole<br>blood using ion-exchange high performance liquid<br>chromatography (HPLC).<br><br>The Bio-Rad VARIANT II TURBO Hemoglobin<br>A1c Program is intended for Professional Use Only.<br>For In Vitro Diagnostic Use. |
| Indications for Use: | Measurement of percent hemoglobin A1c is effective<br>in monitoring long-term glucose control in<br>individuals with diabetes mellitus. |

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### Description of theDevice:

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

## Technical Characteristics Compared to the Predicate:

VARIANT II TURBO Hemoglobin A1c and VARIANT II Hemoglobin A1c programs have the same technical characteristics that are summarized in the table below:

| Characteristics | VARIANT II TURBO<br>Hemoglobin A1c | VARIANT II Hemoglobin A1c |
|----------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Analyte Measured: Reported | %Hemoglobin A1c | %Hemoglobin A1c |
| Intended Use | The Bio-Rad VARIANT II TURBO<br>Hemoglobin A1c Program is<br>intended for the percent<br>determination of hemoglobin A1c in<br>human whole blood using ion-<br>exchange high performance liquid<br>chromatography (HPLC). The Bio-<br>Rad VARIANT II TURBO<br>Hemoglobin A1c Program is<br>intended for Professional Use Only.<br>For In Vitro Diagnostic Use. | The Bio-Rad VARIANT II<br>Hemoglobin A1c Program is intended<br>for the percent determination of<br>hemoglobin A1c in human whole blood<br>using ion-exchange high performance<br>liquid chromatography (HPLC).<br>For In Vitro Diagnostic Use. |
| Assay Principle | Cation exchange high performance<br>liquid chromatography | Cation exchange high performance<br>liquid chromatography |
| Sample Type | Human anticoagulated whole blood<br>(EDTA) | Human anticoagulated whole blood<br>(EDTA) |
| Visible Detection | 415 nm | 415 nm |
| Standardization | Traceable to the Diabetes Control<br>and Complications Trial (DCCT)<br>reference method and IFCC.<br>Certified via the National<br>Glycohemoglobin Standardization<br>Program (NGSP). | Traceable to the Diabetes Control and<br>Complications Trial (DCCT) reference<br>method and IFCC. Certified via the<br>National Glycohemoglobin<br>Standardization Program (NGSP). |

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## Testing To Establish Substantial Equivalence:

#### Accuracy:

Method correlation between VARIANT II TURBO Hemoglobin A1c Program and VARIANT II Hemoglobin A1c Program was evaluated using 201 EDTA whole blood patient samples ranging from 3.9% to 17.5% HbAje. The results are presented in the following regression table.

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#### Precision:

The following table provides comparison data on the precision between VARIANT II TURBO Hemoglobin A1c and VARIANT II Hemoglobin A1c Programs, each utilizing low and high EDTA whole blood patient samples, and both tested against samples with moderate (5.4-6.2) and high (12.5-13.7) % Arc content.

Method precision was performed using a protocol based on the NCCLS Evaluation protocol, Vol.12, No. 4, EP5-A (Feb. 1999) for the VARIANT II TURBO Hemoglobin All and NCCLS Evaluation protocol, Vol.12, No. 4, EP5-T2 (Mar. 1992) for the VARIANT II Hemoglobin Aic Program. The protocols for both the VARIANT II TURBO Hemoglobin Are and VARIANT II Hemoglobin A1c Programs are similar. Using these protocols, 40 runs (2 per day) were performed on one VARIANT II TURBO (or VARIANT II) Hemoglobin Testing System over 20 working days. In each duplicate daily run, one aliquot of low HbA1c and one aliquot of high HbA1c patient samples were cach analyzed per run. Although the precision samples are different, since they were run at different time periods, the precision results between the VARIANT II TURBO Hemoglobin Are and the VARIANT II Hemoglobin Aie Program are equivalent. A summary of combined comparative precision results is presented in the following precision table.

| VARIANT II TURBO Hemoglobin A1c | | VARIANT II Hemoglobin A1c | | |
|---------------------------------|----------------------|---------------------------|----------------------|-----------|
| Low Patient (HbA1c) | High Patient (HbA1c) | Low Patient (HbA1c) | High Patient (HbA1c) | |
| n= (number of samples) | 80 | 80 | 80 | |
| Mean | 6.2 | 12.5 | 5.4 | 13.7 |
| Within run | 0.82% CV | 0.54% CV | 1.46 % CV | 0.65 % CV |
| Total Precision | 1.94% CV | 2.58 % CV | 2.14 % CV | 1.68 % CV |

VARIANT II TURBO HbAlc

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## Linearity:

The following table provides comparison data on the linearity and recovery analyses between VARIANT II TURBO Hemoglobin A1c and VARIANT II Hemoglobin A1c Programs, each utilizing eight EDTA-based blood standards (n=2 for each standard). The % Recovery for Hemoglobin A1e by the VARIANT II TURBO Hemoglobin A1c Program was essentially the same as the VARIANT II Hemoglobin A1c Program. The results are presented in the following linearity table.

The linear range as stated in the Instruction of Use on the VARIANT II TURBO Hemoglobin AJc Program is 4.1 to 16.8% HbAJe which was performed on a separate study, each using a total of seven standards (n=2 for each standard) below, at, and substantially above blood levels of typical normal levels of Hemoglobin A16 and found in normal and diabetic patients.

| % Contribution | | VARIANT II TURBO Hemoglobin A1c | | | VARIANT II Hemoglobin A1c | | |
|----------------|----------|---------------------------------|------------------|------------|---------------------------|------------------|------------|
| Normal | Diabetic | Theoretical % HbA1c | Observed % HbA1c | % Recovery | Theoretical % HbA1c | Observed % HbA1c | % Recovery |
| 100 | 0 | 3.8 | 3.8 | 100 | 3.5 | 3.5 | 100 |
| 90 | 10 | 5.0 | 5.0 | 100 | 4.7 | 4.7 | 100 |
| 80 | 20 | 6.3 | 6.1 | 96.8 | 5.9 | 5.8 | 98.3 |
| 67 | 33 | 8.0 | 7.9 | 98.8 | 7.6 | 7.4 | 97.4 |
| 50 | 50 | 10.2 | 10.0 | 97.9 | 9.8 | 9.6 | 98.0 |
| 33 | 67 | 12.5 | 12.4 | 98.0 | 12.1 | 11.9 | 98.3 |
| 20 | 80 | 14.4 | 14.3 | 99.3 | 14.1 | 13.8 | 97.9 |
| 0 | 100 | 17.3 | 17.3 | 100 | 17.2 | 17.2 | 100 |

#### VARIANT II TURBO Hemoglobin A12 and VARIANT II Hemoglobin A1c Lincarity

#### Interfering Substances:

| Interfering Substance | VARIANT II TURBO<br>Hemoglobin A1c | VARIANT II Hemoglobin A1c |
|---------------------------|-------------------------------------|-------------------------------------|
| Bilirubin | No interference up to 20 mg/dL | No interference up to 20 mg/dL |
| Lipids<br>(Triglycerides) | No interference up to 5680<br>mg/dL | No interference up to 6000<br>mg/dL |
| EDTA | No interference up to 11X EDTA | No interference up to 11X EDTA |

#### 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 Hemoglobin A1c Program is substantially equivalent to the cleared and currently marketed predicate, VARIANT II Hemoglobin Alc Program.

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## DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle-like symbol with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the symbol.

## APR 1 5 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Bio-Rad Laboratories, Inc. c/o Mr. Alfredo J. Quattrone California Department of Health Services Food & Drug Branch 1500 Capitol Avenue Mailstop 7602 Sacramento, CA 95814

k040872 Re:

Trade/Device Name: VARIANT™ II TURBO Hemoglobin A1c Program Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP Dated: March 31, 2004 Reccived: April 2, 2004

Dear Mr. Quattrone:

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 markcted 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 (sec 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 adviscd 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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#### Page 2

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 http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Seain M. Cooper, MS, DVM.

Jean M. Cooper, MS, 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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# Statement of Indications for Use

| 510(k) Number: | k040872 |
|------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name: | VARIANT ^TM II TURBO Hemoglobin A _1c Program |
| Indications for Use: | The Bio-Rad VARIANT II TURBO Hemoglobin A _1c Program is intended for the percent determination of hemoglobin A _1c in human whole blood using ion-exchange high-performance liquid chromatography (HPLC).<br><br>The Bio-Rad VARIANT II TURBO Hemoglobin A _1c Program is intended for Professional Use Only. For <i>In Vitro</i> Diagnostic Use.<br><br>Measurement of percent hemoglobin A _1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus. |
| Prescriptive Use<br>(Per 21 CFR 801.109) | OR Over-The-counter Use |

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED Concurrence of CDRH, Office of Device Evaluation (ODE)

Carol C. Benson
Division Sign-Off

Office of in Vitro Diagnostic

Device Evaluation and Safety

510(k) K040872

VARIANT II TURBO HbAIc Confidential

Date Revised 2/26/04