The Bio-Rad VARIANT™ II TURBO Link 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 VARIANT II TURBO Link Hemoglobin A1c Program is for use with the VARIANT II TURBO Link Hemoglobin Testing System interfaced with an automated sample transport system.

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

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

Device Description

The VARIANT II TURBO Link Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II TURBO Link Hemoglobin A lc Program is based on chromatographic separation of Hemoglobin Alc on a cation exchange cartridge. The reagents in the VARIANT II TURBO Link Hemoglobin A 1c Program have the same formulation as the reagents in the VARIANT II TURBO Hemoglobin A1c Program.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Bio-Rad VARIANT™ II TURBO Link Hemoglobin A1c Program, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the comparison to the predicate device. The study aims to demonstrate substantial equivalence by showing similar performance.

Performance Metric	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (VARIANT™ II TURBO Link)
Accuracy	Similar regression analysis to predicate	R² = 0.998, Slope = 0.983, Intercept = 0.225
Precision	Equivalent within-run and total precision	Normal: Within run %CV = 0.62, Total %CV = 1.27
		Diabetic: Within run %CV = 0.47, Total %CV = 0.92
Linearity	Similar linear range	4.1 – 17.6 % HbA1c

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size: 180 EDTA whole blood patient samples for accuracy, and 80 normal and 80 diabetic patient samples for precision.
Data Provenance: Not explicitly stated, but given the context of a 510(k) submission for a US market, it's highly probable the data was collected in the US. The document does not specify if the data was retrospective or prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not provided in the document. For HbA1c measurements, the "ground truth" is typically the reference method itself (HPLC in this case, specifically traced to DCCT and IFCC, and certified by NGSP), rather than expert consensus on individual samples. The study compares the new device's measurements to those of the predicate device (which is also traceable to these standards).

4. Adjudication Method for the Test Set

This information is not applicable as the ground truth is established by a quantitative analytical method (HPLC traceable to standards), not by human interpretation requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance

This question is not applicable. This is a submission for an in vitro diagnostic device (analyzing blood samples) and not an imaging or AI-assisted diagnostic tool that would involve human "readers" or AI assistance in interpretation.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

This device operates as a standalone analytical instrument. The reported performance metrics (accuracy, precision, linearity) are reflective of its standalone performance without human input influencing the measurement itself, beyond standard laboratory procedures for sample handling and instrument operation. The "algorithm" here refers to the underlying HPLC and data processing, which operate automatically.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

The ground truth for the device's performance is established by:

Traceability to recognized reference methods: Diabetes Control and Complications Trial (DCCT) reference method and IFCC.
Certification: via the National Glycohemoglobin Standardization Program (NGSP).
Comparison to a legally marketed predicate device: The VARIANT II TURBO Hemoglobin A1c Program (K040872 and K063400), which itself would adhere to these traceability and certification standards.

Essentially, the ground truth is anchored by widely accepted analytical reference standards for HbA1c measurement.

8. The Sample Size for the Training Set

This information is not applicable/not provided. This is a regulatory submission for a diagnostic instrument, not a machine learning model that undergoes "training." The device's performance is validated through accuracy, precision, and linearity studies directly comparing it to a predicate and reference standards, rather than by training on a dataset.

9. How the Ground Truth for the Training Set Was Established

This question is not applicable for the same reasons as #8.

Summary

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K070819

JUN 2 5 2007

Summary of Safety and Effectiveness for Bio-Rad Laboratories, Inc.

VARIANT™ II TURBO Link Hemoglobin A1c Program

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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:

Submitter:	Bio-Rad Laboratories, Inc.Clinical Diagnostics Group4000 Alfred Nobel Drive,Hercules, California 94547Phone: (510) 741-5309FAX: (510) 741-6471
Contact Person:	Jackie BuckleyRegulatory Affairs Representative
Date of Summary Preparation:	March 23, 2007
Device Name:	VARIANT™ II TURBO Link Hemoglobin A1c Program
Classification Name:	Assay, Glycosylated Hemoglobin, 81LCP
Predicate Device(s):	VARIANT™ II TURBO Hemoglobin A1c Program(k) 040872Bio-Rad Laboratories, Inc.VARIANT™ II TURBO Hemoglobin A1c Program run on theVARIANT II TURBO Hemoglobin Testing System with CDM 4.0(k) 063400Bio-Rad Laboratories, Inc.
Intended Use:	The Bio-Rad VARIANT™ II TURBO Link Hemoglobin A1cProgram is intended for the percent determination of hemoglobinA1c in human whole blood using ion-exchange high performanceliquid chromatography (HPLC).The VARIANT II TURBO Link Hemoglobin A1c Program is foruse with the VARIANT II TURBO Link Hemoglobin TestingSystem interfaced with an automated sample transport system.The Bio-Rad VARIANT II TURBO Link Hemoglobin A1c Programis for Professional Use Only.

Bio-Rad Laboratories, Inc.
VARIANT II TURBO Link Hemoglobin A1c Program
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Indications for Use:

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

Description of the Device:

Technical Characteristics Compared to the Predicate:

The VARIANT II TURBO Link Hemoglobin A1c Program and the predicate VARIANT II TURBO Hemoglobin Alc Program have the same technical characteristics that are summarized in the table below:

Characteristics	VARIANT II TURBO LinkHemoglobin A1c Program	VARIANT II TURBO HemoglobinA1c Program (k)040872 andVARIANT II TURBO HemoglobinA1c Program run withCDMTM 4.0(k) 063400
Analyte Measured: Reported	%Hemoglobin A1c	%Hemoglobin A1c
Intended Use	The Bio-Rad VARIANT II TURBOLink hemoglobin A1c Program isintended for the percentdetermination of hemoglobin A1c inhuman whole blood using ion-exchange high-performance liquidchromatography (HPLC).The VARIANT II TURBO LinkHemoglobin A1c Program is for usewith the VARIANT II TURBOLink Hemoglobin Testing Systeminterfaced with an automatedsample transport system.The Bio-Rad VARIANT II TURBOlink Hemoglobin A1c Program isfor Professional Use Only.	The Bio-Rad VARIANT II TURBOHemoglobin A1c Program is intendedfor the percent determination ofhemoglobin A1c in human whole bloodusing ion-exchange high performanceliquid chromatography (HPLC).The Bio-Rad VARIANT II TURBOHemoglobin A1c Program is intendedfor Professional Use Only. For In VitroDiagnostic Use.
Assay Principle	Cation exchange high performanceliquid chromatography	Cation exchange high performanceliquid chromatography
Reagents in kit	The reagent formulations are thesame as the predicate. In additionBuffer A can be purchased as aseparate kit and Buffer B can bepurchased individually.	Kit contains Analytical cartridge,Guard cartridge, Buffer A, Buffer B,Wash/Diluent Solution Set (soldseparately), Whole Blood Primer, andCalibrator/Diluent Set

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Characteristics	VARIANT II TURBO LinkHemoglobin A1c Program	VARIANT II TURBO HemoglobinA1c Program (k)040872and (k) 063400
Sample Type	Human anticoagulated whole blood(EDTA)	Human anticoagulated whole blood(EDTA)
Sample transport mode ofoperation	Continuous feed, batch or STATmode of closed EDTA sample tubesfrom automated sample transportsystem.	Batch mode of closed EDTA sampletubes
Automated sample transportsystem	The VARIANT II TURBO LinkHemoglobin Testing Systemrequires an external automatedsample transport system such asthe Sysmex® HST-N(Hemoglobin Sample Transport)System.	The VARIANT II TURBOHemoglobin Testing System iscomplete with an automated sampleconveyor system.
Standardization	Traceable to the Diabetes Controland Complications Trial (DCCT)reference method and IFCC.Certified via the NationalGlycohemoglobin StandardizationProgram (NGSP).	Traceable to the Diabetes Control andComplications Trial (DCCT)reference method and IFCC.Certified via the NationalGlycohemoglobin StandardizationProgram (NGSP).

Testing To Establish Substantial Equivalence:

Accuracy:

Method correlation between the VARIANT II TURBO Link Hemoglobin Alc Program and VARIANT II TURBO Hemoglobin A1c Program was evaluated using 180 EDTA whole blood patient samples ranging from 4.2% to 14.0% HbA1c. The results are presented in the following regression table.

RegressionMethod	n	R²	Slope	Intercept
Least Squares	180	0.998	0.983	0.225

Precision:

The following table provides comparison data on the precision between the VARIANT II TURBO Link Hemoglobin Alc and VARIANT II TURBO Hemoglobin A1c Programs, each utilizing low and high EDTA whole blood patient samples, and both tested against samples with normal (6.0,6.2) and high (9.4,12.5) % A1c content.

Method precision was performed using a protocol based on the NCCLS Evaluation protocol, Vol.24, No. 25, EP5-A2 (2004) for the VARIANT II TURBO Link Hemoglobin A1c and VARIANT II TURBO Hemoglobin Alc Programs. The protocols for both the VARIANT II TURBO Link Hemoglobin A1c and VARIANT II TURBO Hemoglobin Alc Programs are similar.

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Using these protocols, 40 runs (2 per day) were performed on one VARIANT II TURBO Link (or VARIANT II TURBO) Hemoglobin Testing System over 20 working days. In each duplicate daily run, one aliquot of normal and one aliquot of diabetic 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 Link Hemoglobin Alc and the VARIANT II TURBO Hemoglobin Alc Program are equivalent. A summary of combined comparative precision results is presented in the following precision table.

VARIANT II TURBO Link Hemoglobin A1c Program		VARIANT II TURBO Hemoglobin A1c Program
	Normal Patient (HbA1c)	Diabetic Patient (HbA1c)	Normal Patient (HbA1c)	Diabetic Patient (HbA1c)
n= (number of samples)	80	80	80	80
Mean	6.01	9.43	6.2	12.5
Within run (%CV)	0.62	0.47	0.82	0.54
Total Precision (%CV)	1.27	0.92	1.94	2.58

VARIANT II TURBO Link Hemoglobin A1c and VARIANT II TURBO Hemoglobin A1c Precision

Linearity:

	VARIANT II TURBO LinkHemoglobin A1c Program	VARIANT II TURBO HemoglobinA1c Program
Linear Range	4.1 – 17.6 % HbA1c	4.1 – 16.8 % HbA1c

Conclusion:

When considering the similarities of the intended use, the general characteristics of 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 Link Hemoglobin A1c Program is substantially equivalent to the cleared and currently marketed predicate, VARIANT II TURBO Hemoglobin A10 Program.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three overlapping wings. The eagle is positioned to the right of a circular border containing the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA".

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 2 5 2007

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

K070819 Re: Trade Name: Variant II Turbo Link Hemoglobin Testing System Regulation Number: 21 CFR 864.7470 Glycosylated hemoglobin assay Regulation Name: Regulatory Class: Class II Product Code: LCP, KRZ Dated: March 23, 2007 Received: March 26, 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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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 (240) 276-0490. 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 (240) 276-3150 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.

Yean 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): K070819

Device Name: VARIANT II TURBO Link Hemoglobin A1c Program

Indications For Use:

The Bio-Rad VARIANT II TURBO Link Hemoglobin A1c Program is intended for the percent determination of hemoglobin A1c in human whole blood using ion-exchange high-performance liquid chromatography (HPLC). Measurement of percent hemoglobin A 1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.

The VARIANT II TURBO Link Hemoglobin A1c Program is for use with the VARIANT II TURBO Link Hemoglobin Testing System interfaced with an automated sample transport system.

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

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)

Patricia Bernhardt
Division Sign-Off (for Carol Bensa)

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of

510(k) K070819

Regulation Number and Section

§ 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).