VARIANT II HEMOGLOBIN A1C PROGRAM

K984268 · Bio-Rad · LCP · Dec 17, 1998 · Hematology

Device Facts

• Record ID: K984268
• Device Name: VARIANT II HEMOGLOBIN A1C PROGRAM
• Applicant: Bio-Rad
• Product Code: LCP · Hematology
• Decision Date: Dec 17, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7470
• Device Class: Class 2

Intended Use

The VARIANT™ II Hemoglobin A1c Program is intended for the determination of hemoglobin A1c in human whole blood using ion-exchange high performance liquid chromatography (HPLC). The VARIANT™ II Hemoglobin A1c Program is intended for use only with the Bio-Rad VARIANT™ II Hemoglobin Testing System. For in vitro diagnostic use only.

Device Story

The VARIANT™ II Hemoglobin A1c Program is an automated HPLC system for quantitative measurement of Hemoglobin A1c in human whole blood. It utilizes cation exchange chromatography to separate hemoglobin variants and glycated hemoglobin fractions. The system processes primary sample tubes via front-end automation, diluting whole blood in an aqueous medium. Unlike the predicate, which used a hemolysis reagent to remove Schiff base, this system separates the Schiff base from HbA1c during the analytical chromatographic step. The system measures absorbance at 415nm and 690nm. Results are provided as a quantitative area percent, reflecting mean blood glucose levels over the preceding ~120 days. Used in clinical laboratory settings, the system assists healthcare providers in monitoring long-term glycemic control in patients. Clinical Data Management Software facilitates result processing and reporting.

Clinical Evidence

Bench testing only. Precision evaluated per NCCLS EP5-T2 using low, medium, and high patient samples; within-run %CV ranged 1.04-1.93%, between-run %CV 0.92-2.40%, and total precision 2.00-4.10%. Accuracy correlation study against the predicate device (NCCLS EP9-T) yielded an r² of 0.9885. The system meets National Glycohemoglobin Standardization Program (NGSP) precision requirements.

Technological Characteristics

Cation exchange chromatography; quantitative area percent measurement; 415nm/690nm detection wavelengths. Features front-end automation for primary sample tubes. Includes Clinical Data Management Software. System is networked/integrated for laboratory use.

Indications for Use

Indicated for the determination of hemoglobin A1c in human whole blood for the assessment of glycemic control. For in vitro diagnostic use.

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™ HbA1c Program (K926469)

Submission Summary (Full Text)

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K984268

DEC 1 7 1998

# 510(k) Summary of Safety and Effectiveness

Submitter:

Hercules, California 94547 Phone: [phone] FAX:

> Juliet Carrara Regulatory Affairs/Quality Assurance Manager

Date of Summary Preparation:

Device Name:

Contact Person:

Classification Name:

Predicate Device:

Statement of Intended Use:

November 23, 1998

Bio-Rad Laboratories, Inc.

4000 Alfred Nobel Drive

VARIANT™ II HbA1c Program

Assay, Glycosylated Hemoglobin, 81 LCP

VARIANT™ HbA1c Program K926469 Bio-Rad Laboratories Hercules, CA 94547

The VARIANT™ II Hemoglobin AJc Program is intended for the determination of hemoglobin A1c in human whole blood using ion-exchange high performance liquid chromatography (HPLC).

The VARIANT™ II Hemoglobin A1c Program is intended for use only with the Bio-Rad VARIANT™ II Hemoglobin Testing System.

For in vitro diagnostic use only.

### Description of Device

The VARIANT™ II Hemoglobin A1c Program is based on chromatographic separation of HbAr on a cation exchange cartridge. The analytical system of instrument and reagent kit provides a means of measuring Hemoglobin A1c, formed by the non-enzymatic attachment of circulating blood glucose to the N terminal valine of the B-chain of the hemoglobin molecule (HbAo). Attachment of glucose to hemoglobin is achieved in a two

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step process. The first step is the formation of an unstable aldimine (Schiff base, labile, or pre-A1c), a reversible reaction between the carbonyl group of glucose and the N terminal valine of the ß-chain of hemoglobin. The amount of Schiff base formed is directly proportional to the blood glucose concentration. The second step is the much slower and irreversible conversion of the Schiff base intermediate to the stable "ketoamine" product (Hemoglobin Alc). The percentage of Hemoglobin A1c in whole blood is dependent on the level of sustained blood glucose and indicative of mean blood glucose over the lifetime of red blood cells (~ 120 days).

# Testing To Establish Substantial Equivalence

To establish substantial equivalence to an existing device, and thus establish the safety and effectiveness, the VARIANT™ II HbAlc Program has been compared to the VARIANT™ HbA1c Program (K926469). A review of the intended use of each system shows them to be the same, in that, they both measure Hemoglobin A1c in a sample of whole blood using cation exchange high performance liquid chromatography.

### Technical Characteristics Compared to Predicate

| | VARIANT™ II HbA1c | VARIANT™ HbA1c |
|---------------------------------|-----------------------------------------------------|-----------------------------------------------------|
| Separation Mechanism | Cation exchange<br>chromatography | Cation exchange<br>chromatography |
| Sample Preparation | Direct dilution of whole<br>blood in aqueous medium | Direct dilution of whole<br>blood in aqueous medium |
| Measurement Type | Quantitative area percent | Quantitative area percent |
| Use of Controls | Two levels of control per<br>run | Two levels of control per<br>run |
| Visible Detection<br>Wavelength | 415nm / 690nm | 415nm / 690nm |

Both systems have the same technical characteristic as presented in the table below:

The VARIANT™ II HbA1c Program has added front end automation and Clinical Data Management Software capabilities. The front end automation allows sampling from primary sample tubes. The predicate used a hemolysis reagent during sample preparation to remove Schiff base. The VARIANT™ II HbA1c Program separates Schiff base from HbAlc in the analysis step.

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The performance of the VARIANT™ II HbA Ic Program was evaluated for precision, measuring range, and accuracy. The precision studies were done using a modified protocol based on the NCCLS Evaluation protocol, Vol. 12, No 4, EP5-T2. Using this protocol, precision of the system was determined using a low, medium, and high patient whole blood sample. The Within-run %CV for the low was 1.51%, for the medium 1.93%, and for the high patient 1.04%. The Between run %CV for the low was 2.40%, for the medium 2.01%, and for the high patient 0.92%. Total precision was 4.10% for the low, 3.36% for the medium, and 2.00% for the high patient. The VARIANT™ II HbA1c Program meets the precision requirements of the National Glycohemoglobin Standardization Program (NGSP).

A correlation study, to determine accuracy of the VARIANT™ II HbA1c Program, was done against the VARIANT™ HbA1c Program. The study followed NCCLS Document EP9-T. The "r2" for the correlation was 0.9885.

When considering the similarities of the intended use, general characteristics of the two assays, the use of the same technology and the excellent correlation between the two methods, it can be concluded that the VARIANT™ II HbA1c Program and the VARIANT™ HbA 1c Program are substantially equivalent. Based on the establishment of substantial equivalence, the safety and effectiveness of the VARIANT™ II HbA1c Program is confirmed.

7

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## DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/2 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three tail feathers, representing the department's commitment to health, human services, and well-being. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle.

DEC 17 1998

Ms. Juliet Carrara Manager, Regulatory Affairs and Quality Assurance Bio-Rad Laboratories, Diagnostic Group 4000 Alfred Nobel Drive Hercules, California 94547-1803

Re : K984268 Trade Name: VARIANT II HbAlc Program Regulatory Class: II Product Code: LCP Dated: November 23, 1998 November 30, 1998 Received:

Dear Ms. Carrara:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Druq Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Reqister. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance, at its toll-free number [phone] or [phone], or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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# Statement of Indications for Use

510(k) Number:

Device Name:

Indications for Use:

K984268

Bio-Rad VARIANT™II Hemoglobin A16 Program

The VARIANT™ II Hemoglobin A1c Program is intended for the determination of hemoglobin Ate in human whole blood using ion-exchange high performance liquid chromatography (HPLC).

The VARIANT™ II Hemoglobin A16 Program is intended for use only with the Bio-Rad VARIANT™ II Hemoglobin Testing System.

For in vitro diagnostic use only.

(Division Sign-Off)
Division of Clinical Laboratory Devides
510(k) Number. K984268

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

Prescriptive Use
(Per 21 CFR 801.109)

OR Over-The-Counter Use