The Bio-Rad VARIANT™ II TURBO Hemoglobin Alc 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 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.

The new feature in this submission is the upgrade in CDM software. The current software (CDM 3.6T) requires Windows NT. This product is nearing the end of its lifecycle. CDM 4.0 software is needed to transfer the CDM software to Microsoft XP Operating System.

AI/ML Overview

The provided text describes the acceptance criteria and the study conducted to demonstrate the substantial equivalence of the VARIANT™ II TURBO Hemoglobin A1c Program with CDM 4.0 software to its predicate device (VARIANT II TURBO Hemoglobin A1c Program with CDM 3.6T).

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as numerical targets that the device needed to meet independently for clinical accuracy. Instead, the study's goal was to demonstrate that the new device's performance was substantially equivalent to the predicate device. Therefore, the "reported device performance" is a comparison to the predicate device.

Performance Metric	Acceptance Criteria (Implied: Substantially Equivalent to Predicate)	Reported Device Performance (Comparison to Predicate)
Accuracy (Method Correlation)	High correlation (r^2) to predicate device, slope near 1, intercept near 0.	r^2 = 0.9991 (for 40 samples ranging 4.4% -11.6% HbA1c) Slope = 1.0174 Intercept = 0.0559
Precision (Within run %CV)	Equivalent to predicate device.	Normal Sample: New device: 0.9% CV; Predicate: 0.8% CV Diabetic Sample: New device: 0.9% CV; Predicate: 0.5% CV
Precision (Total Precision %CV)	Equivalent to predicate device.	Normal Sample: New device: 1.2% CV; Predicate: 1.9% CV Diabetic Sample: New device: 1.9% CV; Predicate: 2.6% CV

2. Sample Sizes and Data Provenance

Accuracy (Test Set):
- Sample size: 40 EDTA whole blood samples.
- Data provenance: Not specified (e.g., country of origin). The samples were described as "whole blood samples," suggesting they were human clinical samples. It's retrospective in the sense that these samples likely existed prior to the test for the software upgrade.
Precision (Test Set):
- Sample size:
  - New device (CDM 4.0): 40 for Normal Sample, 40 for Diabetic Sample. (Note: These refer to the 'n' in the precision table, likely representing the number of data points or runs contributing to the precision calculation, not unique individuals).
  - Predicate device (CDM 3.6T): 80 for Normal Sample, 80 for Diabetic Sample.
- Data Provenance: Not specified (e.g., country of origin). Human EDTA whole blood patient samples were used. The samples for the new device and predicate were run at "different time periods," implying they may not be the exact same set of physical samples, but rather samples representative of similar clinical conditions. This suggests a retrospective analysis of previously run precision studies for the predicate, and a new prospective study for the updated device, using similar protocols.

3. Number of Experts and Qualifications for Ground Truth

Not Applicable. This is an in-vitro diagnostic (IVD) device, specifically a lab instrument measuring a biochemical marker (HbA1c). The ground truth is established by the analytical method itself (HPLC), not by expert interpretation of images or clinical data. The "ground truth" for comparison is the measurement obtained by the predicate device.

4. Adjudication Method for the Test Set

Not Applicable. As mentioned above, this is an IVD device for quantitative measurement. There is no human interpretation or adjudication involved in determining the "ground truth" or the device's output. The comparison is objective, based on analytical results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not Applicable. This device is an automated laboratory instrument. There are no human readers involved in the primary function (measuring HbA1c), so no MRMC study was performed or is relevant.

6. Standalone (Algorithm Only) Performance Study

Yes, in essence. The study assessed the performance of the "VARIANT™ II TURBO Hemoglobin A1c Program run on the VARIANT II TURBO Hemoglobin Testing System using CDM 4.0" as a standalone system by comparing its results to results from the predicate system. The core software (CDM 4.0) is the "algorithm" here, and its performance is evaluated in direct comparison to the previous software version (CDM 3.6T) on essentially the same hardware.

7. Type of Ground Truth Used

The ground truth used for comparison was the analytical measurement obtained from the predicate device (VARIANT II TURBO Hemoglobin A1c Program with CDM 3.6T). For the accuracy study, the individual sample results from the new device were compared against individual sample results from the predicate. For precision, the statistical measures (Mean, %CV) of replicate measurements were compared between the new device and the predicate.

8. Sample Size for the Training Set

Not specified / Not applicable in the traditional sense of AI training. This submission describes a software upgrade for an existing analytical instrument, primarily focusing on migrating the operating system and making minor adjustments to data management. There is no mention of a machine learning or AI algorithm being trained on a specific dataset. The "development" of the CDM 4.0 software likely involved traditional software engineering and testing, not a data-driven training process in the way AI models are trained.

9. How Ground Truth for the Training Set Was Established

Not applicable. As noted above, there's no indication of a machine learning or AI training set as part of this submission. The "ground truth" for software functionality and performance would have been established through standard software development and verification/validation processes against predefined specifications for the new operating system and database changes.

Summary

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Summary of Safety and Effectiveness

DEC - 1 2006

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: K_()(23 Y CO_

Submitter:	Bio-Rad Laboratories, Inc.Clinical System Division4000 Alfred Nobel Drive,Hercules, California 94547Phone: (510) 741-5309FAX: (510) 741-6471
Contact Person:	Jackie BuckleyRegulatory Affairs Representative
Date of Summary Preparation:	Nov. 8, 2006
Device Name:	VARIANT™ II TURBO Hemoglobin A1c Program runon the VARIANT II TURBO Hemoglobin TestingSystem using Clinical Management System (CDM) 4.0
Classification Name:	HbA1c: Assay, Glycosylated Hemoglobin[21CFR 864.7470 / Prod. Code LCP]
Predicate Devices:	VARIANT II TURBO Hemoglobin A1cBio-Rad Laboratories, Inc.[K040872, April 15, 2004]

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Intended Use:

The 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.

New Device Description

Technical Characteristics Compared to Predicate

The VARIANT™ II TURBO Hemoglobin A1c Program run on the VARIANT™ II TURBO Hemoglobin Testing System with CDM 4.0 has the same basic technical characteristics as the predicate VARIANT II TURBO Hemoglobin A1c Program (k) 040872. The technical characteristics between the two submissions are summarized in the following tables:

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Summary of Technological Characteristic Similarities in Comparison to Predicate Device
Characteristics	New Device:VARIANT II TURBO Hemoglobin A1cProgram run on the VARIANT II TURBOHemoglobin Testing System using CDM 4.0	Predicate Device: (k) 040872VARIANT II TURBO Hemoglobin A1cProgram run on the VARIANT II TURBOHemoglobin Testing System using CDM 3.6T
Intended Use(s)	The VARIANT II TURBO Hemoglobin A1c isintended for the percent determination ofhemoglobin A1c in human whole blood usingion-exchange high-performance liquidchromatography (HPLC).The Bio-Rad VARIANT II TURBOHemoglobin A1c Program is intended forProfessional Use Only.For In Vitro Diagnostic Use.	The VARIANT II TURBO Hemoglobin A1c isintended for the percent determination ofhemoglobin A1c in human whole blood usingion-exchange high-performance liquidchromatography (HPLC).The Bio-Rad VARIANT II TURBOHemoglobin A1c Program is intended forProfessional Use Only.For In Vitro Diagnostic Use.
Indication(s) for Use	Measurement of the percent hemoglobin A1c iseffective in monitoring long-term glucosecontrol in individuals with diabetes mellitus.	Measurement of the percent hemoglobin A1c iseffective in monitoring long-term glucosecontrol in individuals with diabetes mellitus.
Assay Principle	Cation exchange high performance liquidchromatography	Cation exchange high performance liquidchromatography
CDM Softwareversion	4.0	3.6T
Microsoft software	Windows XP	Windows NT
Object Store version	6.0	4.0
Backup and Restore	Use Windows operation to write only data toCD-R	Used Easy CD writer Read/Write
DatabaseManagement	Delete data directly from database	Substitute database with a blank database

VARIANT™ II TURBOHemoglobin A1c (k)040872

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Testing To Establish Substantial Equivalence:

Accuracy:

VARIANT II TURBO Hemoglobin HbA1c Program (3 minute)

Method correlation between Bio-Rad VARIANT II TURBO Hemoglobin A1c Program with CDM 4.0 and VARIANT II TURBO Hemoglobin A1c Program with CDM 3.6T was evaluated using 40 EDTA whole blood samples ranging from (4.4% -11.6%) HbA1c. The results are presented in the following table:

VARIANT II TURBO Hemoglobin A1c Program Correlation
Regression Method	n	r2	Slope	Intercept
Least Squares	40	0.9991	1.0174	0.0559

VARIANT II TUDDO Uomoclobin 41a Drogram ----------

Precision:

VARIANT II TURBO Hemoglobin A1c Program

The following precision table provides comparison data on the precision between VARIANT II TURBO Hemoglobin A1c Program with CDM 4.0 vs. CDM 3.6T each utilizing EDTA whole blood patient samples.

Method precision was performed using a protocol based on the NCCLS Evaluation protocol, EP5-A for the VARIANT II TURBO Hemoglobin A1c Program with CDM 4.0 and 3.6T. The protocols for both VARIANT II TURBO Hemoglobin A1c Program with CDM 4.0 and 3.6T are similar. In each duplicate daily run for both verification studies, duplicate aliquots of normal HbAlc and diabetic HbA1c patient samples and controls were each analyzed per run. The position of the precision specimens in each run was randomized to simulate normal laboratory conditions. The precision data for the VARIANT II TURBO with CDM 3.6T was over 20 working days while the data for VARIANT II TURBO with CDM 4.0 was over 10 working days.

Although precision samples are different, since they were run at different time periods, the precision results between the VARIANT II TURBO Hemoglobin A1c Program with CDM 4.0 and CDM 3.6T are equivalent. A summary of combined comparative precision results are presented in the following precision table.

VARIANT II TURBO HbA1c with CDM 4.0 vs. VARIANT II TURBO HbA1c with CDM 3.6T - Precision

	VII TURBO HbA1cwith CDM 4.0		VII TURBO HbA1cwith CDM 3.6T
	Normal Sample	Diabetic Sample	Normal Sample	Diabetic Sample
n= (number of samples)	40	40	80	80
Mean (%HbA1c)	5.4	9.7	6.2	12.5
Within run (%CV)	0.9	0.9	0.8	0.5
Total Precision (%CV)	1.2	1.9	1.9	2.6

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Conclusion:

The similarities of the intended use and the general performance characteristics and results of the newly described and evaluated VARIANT II TURBO Hemoglobin A1c Program run on the VARIANT II TURBO Hemoglobin Testing System with CDM 4.0 are nearly identical to or logical extensions of those for cleared predicate program systems [i.e., VARIANT II TURBO Hemoglobin Alc Program run on the VARIANT II TURBO Hemoglobin Testing System with CDM 3.6T (k)040872]. Thus, one may conclude, based on the use of the same HPLC technology, and the nearly equivalent results obtained for the correlation and precision versus the corresponding results obtained with the predicate system that the new VARIANT II TURBO Hemoglobin A1c Program run on the VARIANT II TURBO Hemoglobin Testing System with CDM 4.0 is substantially equivalent to the cleared and currently marketed predicate system.

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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 circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing protection and care. The eagle is depicted in a simple, abstract design with bold lines.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Jackic Buckley Bio-Rad Laboratories, Inc. Clinical System Division 4000 Alfred Nobel Drive Hercules, California 94547

DEC - 1 2006

Re: K063400

Trade/Device Name: Varient II Turbo Hemoglobin Alc Program, Hemoglobin Testing System With CDM 4.0 Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP, LDM Dated: November 8, 2006 Received: November 9, 2006

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) 276-0484. 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/industry/support/index.html.

Sincerely yours,

Alberto Gutt

Alberto Gutierrez, Ph.D. 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):________k063400

Variant II Turbo Hemoglobin A1c Program, Hemoglobin Testing Device Name:_ System With CDM 4.0

Indications For Use:

The Bio-Rad VARIANT II TURBO Hemoglobin A1C Program with CDM 4.0 is intended THE DIO Rad VARIANT PROGED in A1c in human whole blood using ionexchange high-performance liquid chromatography (HPLC).

The Bio-Rad VARIANT II TURBO Hemoglobin A1C Program with CDM 4.0 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

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 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)

Carol Benson
Division Sign-Off

Division Sign-Off

Page 1 of 1

Office of In Vitro Diagnostic Device Evaluation and Safety

K06340

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).