K Number
K040872
Device Name
VARIANT II HEMOGLOBIN A1C
Date Cleared
2004-04-15

(13 days)

Product Code
Regulation Number
864.7470
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdparty
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). 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 Description
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.
More Information

Not Found

No
The summary describes a device based on HPLC technology for measuring HbA1c and does not mention any AI or ML components.

No.
The device is an in vitro diagnostic device used to measure hemoglobin A1c, which is used for monitoring diabetes, not for treating it.

Yes

Explanation: The device is explicitly stated as being "intended for the percent determination of hemoglobin A1c in human whole blood" and is used to "monitor long-term glucose control in individuals with diabetes mellitus." This directly indicates its role in diagnosing and monitoring a medical condition. Furthermore, it is specified for "In Vitro Diagnostic Use."

No

The device description explicitly states that the system uses the principles of high performance liquid chromatography (HPLC) and a cation exchange cartridge, which are hardware components. The software program is part of a larger hardware system.

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

  • Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "For In Vitro Diagnostic Use."
  • Nature of the Test: The device is intended for the "percent determination of hemoglobin A1c in human whole blood." This involves testing a biological sample (whole blood) outside of the body to provide diagnostic information about a person's health (monitoring long-term glucose control in individuals with diabetes mellitus). This is the core definition of an in vitro diagnostic test.
  • Professional Use Only: The indication for "Professional Use Only" further supports its use in a clinical or laboratory setting for diagnostic purposes.

N/A

Intended Use / Indications for 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).

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.

Product codes

LCP

Device Description

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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Professional Use Only.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

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% HbA1c.

Precision:
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 A1c and NCCLS Evaluation protocol, Vol.12, No. 4, EP5-T2 (Mar. 1992) for the VARIANT II Hemoglobin A1c Program. The protocols for both the VARIANT II TURBO Hemoglobin A1c 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 each 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 A1c and the VARIANT II Hemoglobin A1c Program are equivalent.

Key Results:
Accuracy:
The results are presented in the form of a regression table.

Precision:
Low Patient (HbA1c): n=80, Mean=6.2, Within run=0.82% CV, Total Precision=1.94% CV
High Patient (HbA1c): n=80, Mean=12.5, Within run=0.54% CV, Total Precision=2.58% CV.
(Predicate device results were also provided for comparison)

Linearity:
The linear range as stated in the Instruction of Use on the VARIANT II TURBO Hemoglobin A1c Program is 4.1 to 16.8% HbA1c. The % Recovery for Hemoglobin A1c by the VARIANT II TURBO Hemoglobin A1c Program was essentially the same as the VARIANT II Hemoglobin A1c Program.

Interfering Substances:
Bilirubin: No interference up to 20 mg/dL for both devices.
Lipids (Triglycerides): No interference up to 5680 mg/dL for VARIANT II TURBO Hemoglobin A1c, and up to 6000 mg/dL for VARIANT II Hemoglobin A1c.
EDTA: No interference up to 11X EDTA for both devices.

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 A1c Program.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Mean, Within run %CV, Total Precision %CV, % Recovery.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K984268

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

§ 864.7470 Glycosylated hemoglobin assay.

(a)
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.(b)
Classification. Class II (performance standards).

0

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.
Clinical Diagnostics Group
4000 Alfred Nobel Drive,
Hercules, California 94547
Phone: (510) 741-5309
FAX: (510) 741-6471 |
|------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Jackie Buckley
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
K984268
Bio-Rad Laboratories, Inc. |
| 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).

The Bio-Rad VARIANT II TURBO Hemoglobin
A1c Program is intended for Professional Use Only.
For In Vitro Diagnostic Use. |
| Indications for Use: | Measurement of percent hemoglobin A1c is effective
in monitoring long-term glucose control in
individuals with diabetes mellitus. |

1

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

2

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 A1cVARIANT II Hemoglobin A1c
Low Patient (HbA1c)High Patient (HbA1c)Low Patient (HbA1c)High Patient (HbA1c)
n= (number of samples)808080
Mean6.212.55.413.7
Within run0.82% CV0.54% CV1.46 % CV0.65 % CV
Total Precision1.94% CV2.58 % CV2.14 % CV1.68 % CV

VARIANT II TURBO HbAlc

3

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.

% ContributionVARIANT II TURBO Hemoglobin A1cVARIANT II Hemoglobin A1c
NormalDiabeticTheoretical % HbA1cObserved % HbA1c% RecoveryTheoretical % HbA1cObserved % HbA1c% Recovery
10003.83.81003.53.5100
90105.05.01004.74.7100
80206.36.196.85.95.898.3
67338.07.998.87.67.497.4
505010.210.097.99.89.698.0
336712.512.498.012.111.998.3
208014.414.399.314.113.897.9
010017.317.310017.217.2100

VARIANT II TURBO Hemoglobin A12 and VARIANT II Hemoglobin A1c Lincarity

Interfering Substances:

| Interfering Substance | VARIANT II TURBO
Hemoglobin A1c | VARIANT II Hemoglobin A1c |
|---------------------------|-------------------------------------|-------------------------------------|
| Bilirubin | No interference up to 20 mg/dL | No interference up to 20 mg/dL |
| Lipids
(Triglycerides) | No interference up to 5680
mg/dL | No interference up to 6000
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.

4

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).

5

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 (301) 594-3084. 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 (800) 638-2041 or (301) 443-6597 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

6

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).

The Bio-Rad VARIANT II TURBO Hemoglobin A 1c Program is intended for Professional Use Only. For In Vitro Diagnostic Use.

Measurement of percent hemoglobin A 1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus. |
| Prescriptive Use
(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