Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes a software upgrade for an existing HPLC system, primarily focused on migrating to a newer operating system and database. There is no mention of AI or ML in the intended use, device description, or performance studies.

Therapeutic

No
This device is for in vitro diagnostic use, intended to measure specific hemoglobin components to aid in the diagnosis and monitoring of conditions like diabetes and beta-thalassemia. It does not directly treat or prevent a disease, which would classify it as a therapeutic device.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states "For in vitro diagnostic use" for all three assays (Hemoglobin A1c, Beta-thalassemia, and Total GHb Program). Additionally, it describes the use of these measurements for monitoring glucose control in diabetes mellitus and screening for β-thalassemia, which are all diagnostic applications.

SaMD (Software as a Medical Device)

No

The device is described as a software upgrade (CDM 4.0) for the Bio-Rad VARIANT II Hemoglobin Testing System, which is a hardware system utilizing HPLC. The software is intended for use only with this specific hardware system.

IVD (In Vitro Diagnostic)

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

Here's why:

Explicit Statement: The "Intended Use / Indications for Use" section for all three assays explicitly states "For in vitro diagnostic use."
Nature of the Assays: The assays described (Hemoglobin A1c, Beta-thalassemia, Total GHb) are designed to analyze components of human whole blood to provide information for diagnosis, monitoring, or screening of medical conditions (diabetes mellitus and β-thalassemia). This aligns with the definition of an in vitro diagnostic device, which is intended for use in the examination of specimens derived from the human body to provide information for diagnostic, monitoring, or compatibility purposes.
Device Description: The device description explains that the system uses HPLC to separate and measure hemoglobins in human whole blood, which is a common technique used in clinical laboratories for in vitro diagnostic testing.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Intended Use:

This software submission covers three assays with three different intended uses:

Hemoglobin A1c:

The 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).

The VARIANT II Hemoglobin Alc Program is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.

Beta-thalassemia:

The VARIANT II Beta thalassemia Short Program is intended for the separation and area percent determinations of hemoglobin A2 and F, and as an aid in the identification of abnormal hemoglobins in human whole blood using ionexchange high-performance liquid chromatography (HPLC).

The VARIANT II Beta-thalassemia Short Program is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.

Total GHb:

The VARIANT II Total GHb Program is intended for the separation and area percent determination of total glycated hemoglobin (GHb) in human whole blood using ion-exchange high-performance liquid chromatography (HPLC).

The VARIANT II Total GHb Program with is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.

Indications for Use:

This software submission covers three assays and has two different Indications for Use:

HbA1c & GHb: Measurement of percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.
HbA2 and HbF: Measurement of the percent hemoglobin A2 and F are effective in screening of β-thalassemia (i.e. hereditary hemolytic anemias characterized by decreased synthesis of one or more types of abnormal hemoglobin polypeptide chains).

Product codes (comma separated list FDA assigned to the subject device)

LCP, JPD

Device Description

The VARIANT II Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II Hemoglobin A1c and Beta-thalassemia Short Program are based on chromatographic separation of hemoglobins on a cation exchange cartridge. The Total GHb Program is based on principles of boronate affinity high pressure liquid chromatography to separate glycated hemoglobin from non-glycated hemoglobin.

The new feature in this submission is the upgrade in CDM software. The current software (3.5) requires Windows NT and Object Store N.T. These products are nearing the end of their lifecycle. CDM 4.0 software is needed to transfer the CDM software to Microsoft XP Operating System and Object Store version 4.0.

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

Not Found

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: VARIANT II Hemoglobin HbA1c Program
Method correlation between Bio-Rad VARIANT II Hemoglobin A1c Program with CDM 4.0 and V ARIANT II Hemoglobin A1c Program with CDM 3.5 was evaluated using 40 EDTA whole blood samples ranging from (4.7% -12.9%) HbA1c.
Regression Method: Least Squares, n=40, r2=0.9978, Slope=1.0119, Intercept=0.0002

Precision: VARIANT II Hemoglobin A1c Program
Method precision was performed using a protocol based on the NCCLS Evaluation protocol, EP5-A for the VARIANT II Hemoglobin A1c Program with CDM 4.0 and 3.5. The protocols for both VARIANT II Hemoglobin A1c Program with CDM 4.0 and 3.5 are similar. In each duplicate daily run for both verification studies, duplicate aliquots of normal HbA1c 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 with CDM 3.5 was over 20 working days while the data for VARIANT II 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 Hemoglobin A1c Program with CDM 4.0 and CDM 3.5 are equivalent.

Accuracy: VARIANT II Beta thalassemia Short Program
Method correlation between Bio-Rad VARIANT II Beta thalassemia Short with CDM 4.0 and V ARIANT II Beta thalassemia Short with CDM 3.5 was evaluated using 40 EDTA whole blood samples ranging from (2.0 - 7.0% %) HbA2 and (0.2 - 11.1%) HbF.

HbA2 Correlation: Regression Method: Least Squares, n=40, r2=0.9924, Slope=1.0070, Intercept=-0.0034
HbF Correlation: Regression Method: Least Squares, n=40, r²=0.9991, Slope=0.9806, Intercept=0.0192

Precision: VARIANT II Beta thalassemia Short Program
Method precision was performed using a protocol based on the NCCLS Evaluation protocol, EP5-A for the VARIANT II Beta thalassemia Short with CDM 4.0 and 3.5. The protocols for both VARIANT II Beta thalassemia Short with CDM 4.0 and 3.5 are similar. In each duplicate daily run for both verification studies, duplicate aliquots of normal HbA1c 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 with CDM 3.5 was over 20 working days while the data for VARIANT II 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 Beta thalassemia Short with CDM 4.0 and CDM 3.5 are equivalent.

Accuracy: VARIANT II Total GHb Program
Method correlation between Bio-Rad VARIANT II Total GHb Program with CDM 4.0 and VARIANT II Total GHb Program with CDM 3.5 was evaluated using 40 EDTA whole blood samples ranging from (4.5 - 16.2%) GHb.
Regression Method: Least Squares, n=40, r2=0.9991, Slope=1.0054, Intercept=0.042

Precision: VARIANT II Total GHb Program
Method precision was performed using a protocol based on the NCCLS Evaluation protocol. EP5-A for the VARIANT II Total GHb Program with CDM 4.0 and 3.5. The protocol poth V ARIANT II Total GHb Program with CDM 4.0 and 3.5 are similar. In each duplicate daily run for both verification studies, duplicate aliquots of normal HbA lc and diabetic HbA lc patient samples and controls were each analyzed per run. The position of the precision specialisms in each run was randomized to simulate normal laboratory conditions. The precision data for the V ARIANT II with CDM 3.5 was over 20 working days while the data for VARIANT II 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 Total GHb Program with CDM 4.0 and CDM 3.5 are equivalent.

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

Not Found

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, K991127, K003280

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

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).

Summary

0

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: K_06 3643

| Submitter: | Bio-Rad Laboratories, Inc.
Clinical System Division
4000 Alfred Nobel Drive,
Hercules, California 94547
Phone: (510) 741-5309
FAX: (510) 741-6471
DEC 27 2006 |
|------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Jackie Buckley
Regulatory Affairs Representative III |
| Date of Summary Preparation: | December 4, 2006 |
| Device Name: | VARIANTTM II Hemoglobin A1c, VARIANTTM II Beta-
thalassemia, and VARIANTTM II Total GHb Programs
run on the VARIANT II Hemoglobin Testing System
using Clinical Management System (CDM) 4.0 |
| Classification Name: | HbA1c: Assay, Glycosylated Hemoglobin
[21CFR 864.7470 / Prod. Code LCP]
HbA2: Hemoglobin A2 Quantitation
[21CFR 864.7400/Prod. Code :JPD] |
| Predicate Devices: | VARIANTTM II Hemoglobin A1c Program
Bio-Rad Laboratories, Inc.
[K984268, December 17, 1998] |
| | VARIANTTM II Beta thalassemia Short Program
Bio-Rad Laboratories, Inc.
[K991127, June 10, 1999] |
| | VARIANTTM II Total GHb Program
Bio-Rad Laboratories, Inc.
[K003280, December 19, 2000] |

1

Intended Use:

This software submission covers three assays with three different intended uses:

Hemoglobin A1c:

The 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).

The VARIANT II Hemoglobin Alc Program is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.

Beta-thalassemia:

The VARIANT II Beta thalassemia Short Program is intended for the separation and area percent determinations of hemoglobin A2 and F, and as an aid in the identification of abnormal hemoglobins in human whole blood using ionexchange high-performance liquid chromatography (HPLC).

The VARIANT II Beta-thalassemia Short Program is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.

Total GHb:

The VARIANT II Total GHb Program is intended for the separation and area percent determination of total glycated hemoglobin (GHb) in human whole blood using ion-exchange high-performance liquid chromatography (HPLC).

The VARIANT II Total GHb Program with is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.

Indications for Use:

This software submission covers three assays and has two different Indications for Use:

HbA1c & GHb:	Measurement of percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.
HbA2 and HbF:	Measurement of the percent hemoglobin A2 and F are effective in screening of β-thalassemia (i.e. hereditary hemolytic anemias characterized by decreased synthesis of one or more types of abnormal hemoglobin polypeptide chains).

New Device Description

The VARIANT II Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II Hemoglobin A1c and Beta-thalassemia Short Program are based on chromatographic separation of hemoglobins on a cation exchange cartridge. The Total GHb Program is based on principles of boronate affinity high pressure liquid chromatography to separate glycated hemoglobin from non-glycated hemoglobin.

Bio-Rad Laboratories, Inc. 4-A-2

2

The new feature in this submission is the upgrade in CDM software. The current software (3.5) requires Windows NT and Object Store N.T. These products are nearing the end of their lifecycle. CDM 4.0 software is needed to transfer the CDM software to Microsoft XP Operating System and Object Store version 4.0.

Technical Characteristics Compared to Predicate

The VARIANT™ II Hemoglobin A1c Program run on the VARIANT II Hemoglobin Testing System with CDM 4.0 has the same basic technical characteristics as the predicate VARIANT II Hemoglobin A1c Program (k) 984268. The technical characteristics between the two submissions are summarized in the following tables on pages 4-A-3 to 4-A-6:

3

VARIANT™ II Hemoglobin A1c (k) 984268

Summary of Technological Characteristic Similarities in Comparison to Predicate Device
Characteristics	New Device:
VARIANT II Hemoglobin A1c Program run
on the VARIANT II Hemoglobin Testing
System using CDM 4.0	Predicate Device:(k)984268
VARIANT II Hemoglobin A1c Program run
on the VARIANT II Hemoglobin Testing
System using CDM 3.5
Intended Use(s)	The VARIANT II Hemoglobin A1c 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 VARIANT II Hemoglobin A1c 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.
Indication(s) for Use	Measurement of the percent hemoglobin A1c is
effective in monitoring long-term glucose
control in individuals with diabetes mellitus.	Measurement of the percent hemoglobin A1c is
effective in monitoring long-term glucose
control in individuals with diabetes mellitus.
Assay Principle	Cation exchange high performance liquid
chromatography	Cation exchange high performance liquid
chromatography
CDM Software
version	4.0	3.5
Microsoft software	Windows XP	Windows NT
Object Store version	6.0	4.0
Backup and Restore	Use Windows operation to write only data to
CD-R	Used Easy CD writer Read/Write
Database
Management	Delete data directly from database	Substitute database with a blank database
Standardization for
HbA1c	Traceable to the Diabetes Control and
Complications Trial (DCCT) reference method
and IFCC. Certified via the National
Glycohemoglobin Standardization Program
(NGSP) for HbA1c.	Traceable to the Diabetes Control and
Complications Trial (DCCT) reference method
and IFCC. Certified via the National
Glycohemoglobin Standardization Program
(NGSP) for HbA1c.
Firmware upgrade
to VARIANT II
VCS and VSS	VCS 41.300 VSS 51.381	VCS 41.295 VSS 51.373
Summary of Technological Characteristic Similarities in Comparison to Predicate Device
Characteristics	New Device:
VARIANT II Beta thalassemia Short
Program run on the VARIANT II
Hemoglobin Testing System using CDM 4.0	Predicate Device: (k)991127
VARIANT II Beta thalassemai Short
Program run on the VARIANT II
Hemoglobin Testing System using CDM 3.5
Intended Use(s)	The VARIANT II Beta thalassemia Short
Program is intended for the separation and area
percent determinations of hemoglobin A2 and
F, and as an aid in the identification of
abnormal hemoglobins in human whole blood
using ion-exchange high-performance liquid
chromatography (HPLC).
The VARIANT II B-thalassemia Short
Program is intended for use only with the Bio-
Rad VARIANT II Hemoglobin Testing
System.
For In Vitro Diagnostic Use.	The VARIANT II Beta thalassemia Short
Program is intended for the separation and area
percent determinations of hemoglobin A2 and F,
and as an aid in the identification of abnormal
hemoglobins in human whole blood using ion-
exchange high-performance liquid
chromatography (HPLC).
The VARIANT II B-thalassemia Short Program
is intended for use only with the Bio-Rad
VARIANT II Hemoglobin Testing System.
For In Vitro Diagnostic Use.
Indication(s) for Use	Measurement of the percent hemoglobin A2 and
F are effective in screening of β-thalassemia
(i.e. hereditary hemolytic anemias
characterized by decreased synthesis of one or
more types of abnormal hemoglobins
polypeptide chains).	Measurement of the percent hemoglobin A2 and
F are effective in screening of β-thalassemia (i.e.
hereditary hemolytic anemias characterized by
decreased synthesis of one or more types of
abnormal hemoglobins polypeptide chains).
Assay Principle	Cation exchange high performance liquid
chromatography	Cation exchange high performance liquid
chromatography
CDM Software
version	4.0	3.5
Microsoft software	Windows XP	Windows NT
Object Store version	6.0	4.0
Backup and Restore	Use Windows operation to write only data to
CD-R	Used Easy CD writer Read/Write
Database
Management	Delete data directly from database	Substitute database with a blank database
Firmware upgrade
to VARIANT II
VCS and VSS	VCS 41.300 VSS 51.381	VCS 41.295 VSS 51.373
Summary of Technological Characteristic Similarities in Comparison to Predicate Device
Characteristics	New Device:
VARIANT II Total GHb Program run on
the VARIANT II Hemoglobin Testing
System using CDM 4.0	Predicate Device: (k) 003280
VARIANT II Total GHb Program run on the
VARIANT II Hemoglobin Testing System
using CDM 3.5
Intended Use(s)	The VARIANT II Total GHb Program is
intended for the separation and area percent
determination of total glycated hemoglobin
(GHb) in whole blood using boronate affinity
high-performance liquid chromatography
(HPLC).

For In Vitro Diagnostic Use. | The VARIANT II Total GHb Program is
intended for the separation and area percent
determination of total glycated hemoglobin
(GHb) in whole blood using boronate affinity
high-performance liquid chromatography
(HPLC).

For In Vitro Diagnostic Use. |
| Indication(s) for Use | Measurement of the percent hemoglobin A1c is
effective in monitoring long-term glucose
control in individuals with diabetes mellitus. | Measurement of the percent hemoglobin A1c is
effective in monitoring long-term glucose
control in individuals with diabetes mellitus. |
| Assay Principle | Affinity high performance liquid
chromatography | Affinity high performance liquid
chromatography |
| CDM Software
version | 4.0 | 3.5 |
| Microsoft software | Windows XP | Windows NT |
| Object Store version | 6.0 | 4.0 |
| Backup and Restore | Use Windows operation to write only data to
CD-R | Used Easy CD writer Read/Write |
| Database
Management | Delete data directly from database | Substitute database with a blank database |
| Standardization | Traceable to the Diabetes Control and
Complications Trial (DCCT) reference method
and IFCC. Certified via the National
Glycohemoglobin Standardization Program
(NGSP) for HbA1c. | Traceable to the Diabetes Control and
Complications Trial (DCCT) reference method
and IFCC. Certified via the National
Glycohemoglobin Standardization Program
(NGSP) for HbA1c. |
| Firmware upgrade
to VARIANT II
VCS and VSS | VCS 41.300 VSS 51.381 | VCS 41.295 VSS 51.373 |

4

VARIANTIM II Beta thalassemia Short Program (k)991127

5

VARIANT™ II GHb (k)003280

6

Testing To Establish Substantial Equivalence:

Accuracy:

VARIANT™ II Hemoglobin HbA1c Program

Method correlation between Bio-Rad VARIANT II Hemoglobin A1c Program with CDM 4.0 and V ARIANT II Hemoglobin A1c Program with CDM 3.5 was evaluated using 40 EDTA whole blood samples ranging from (4.7% -12.9%) HbA1c. The results are presented in the following table:

VARIANT II Hemoglobin A1c Program Correlation
Regression Method	n	r2	Slope	Intercept
Least Squares	40	0.9978	1.0119	0.0002

VADIANT II Hamaclahin A1a Buaguam Carrelatio

Precision:

VARIANT II Hemoglobin A1c Program

The following precision table provides comparison data on the precision between VARIANT II Hemoglobin A1c Program with CDM 4.0 vs. CDM 3.5 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 Hemoglobin A1c Program with CDM 4.0 and 3.5. The protocols for both VARIANT II Hemoglobin A1c Program with CDM 4.0 and 3.5 are similar. In each duplicate daily run for both verification studies, duplicate aliquots of normal HbA1c 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 with CDM 3.5 was over 20 working days while the data for VARIANT II 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 Hemoglobin A1c Program with CDM 4.0 and CDM 3.5 are equivalent. A summary of combined comparative precision results are presented in the following precision table.

VARIANT II HbA1c with CDM 4.0 vs. VARIANT II HbA1c with CDM 3.5 - Precision

	VII HbA1c with CDM 4.0		VII HbA1c with CDM 3.5T
	Normal Sample	Diabetic Sample	Normal Sample	Diabetic Sample
n= (number of samples)	40	40	80	80
Mean (%HbA1c)	5.4	10.4	5.4	13.7
Within run (%CV)	1.1	1.2	1.5	0.7
Total Precision (%CV)	2.6	2.7	2.1	1.7

7

Accuracy:

VARIANT™ II Beta thalassemia Short Program

Method correlation between Bio-Rad VARIANT II Beta thalassemia Short with CDM 4.0 and V ARIANT II Beta thalassemia Short with CDM 3.5 was evaluated using 40 EDTA whole blood samples ranging from (2.0 - 7.0% %) HbA2 and (0.2 - 11.1%) HbF. The results are presented in the following tables:

VARIANT II Beta thalassemia Short Correlation (HbA2)
------------------------------------------------------	--	--	--

Regression Method	n	r2	Slope	Intercept
Least Squares	40	0.9924	1.0070	-0.0034

VARIANT II Beta thalassemia Short Correlation (HbF)

Regression Method	n	r²	Slope	Intercept
Least Squares	40	0.9991	0.9806	0.0192

Precision:

VARIANT II Beta thalassemia Short Program

The following precision table provides comparison data on the precision between VARIANT II Beta thalassemia Short with CDM 4.0 vs. CDM 3.5 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 Beta thalassemia Short with CDM 4.0 and 3.5. The protocols for both VARIANT II Beta thalassemia Short with CDM 4.0 and 3.5 are similar. In each duplicate daily run for both verification studies, duplicate aliquots of normal HbA1c 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 with CDM 3.5 was over 20 working days while the data for VARIANT II 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 Beta thalassemia Short with CDM 4.0 and CDM 3.5 are equivalent. A summary of combined comparative precision results are presented in the following precision tables.

VARIANT II Beta thalassemia Short with CDM 4.0 vs. VARIANT II Beta thalassemia Short with CDM 3.5 - Precision

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Bio-Rad Laboratories, Inc.

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VARIANT II Beta thalassemia Short with CDM 4.0 vs. VARIANT II HbA1c with CDM 3.5 - Precision (continue)

Accuracy:

VARIANT™ II Total GHb Program

Method correlation between Bio-Rad VARIANT II Total GHb Program with CDM 4.0 and VARIANT II Total GHb Program with CDM 3.5 was evaluated using 40 EDTA whole blood samples ranging from (4.5 - 16.2%) GHb. The results are presented in the following table:

1			VARIANT II Total GHb Program Correlation
---	--	--	------------------------------------------	--

Regression Method	n	r2	Slope	Intercept
Least Squares	40	0.9991	1.0054	0.042

Precision:

VARIANT II Total GHb Program

The following precision table provides comparison data on the precision between VARIANT II Total GHb Program with CDM 4.0 vs. CDM 3.5 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 Total GHb Program with CDM 4.0 and 3.5. The protocol poth V ARIANT II Total GHb Program with CDM 4.0 and 3.5 are similar. In each duplicate daily run for both verification studies, duplicate aliquots of normal HbA lc and diabetic HbA lc patient samples and controls were each analyzed per run. The position of the precision specialisms in each run was randomized to simulate normal laboratory conditions. The precision data for the V ARIANT II with CDM 3.5 was over 20 working days while the data for VARIANT II with CDM 4.0 was over 10 working days.

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Although precision samples are different, since they were run at different time periods, the precision results between the VARIANT II Total GHb Program with CDM 4.0 and CDM 3.5 are equivalent. A summary of combined comparative precision results are presented in the following precision table.

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VARIANT II Total GHb with CDM 4.0 vs. VARIANT II Total GHb with CDM 3.5 -Precision

Conclusion:

The similarities of the intended use and the general performance characteristics and results of the newly described and evaluated VARIANT II Hemoglobin A1c , VARIANT II Betathalassemia and VARIANT II Total GHb Programs run on the VARIANT II 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 Hemoglobin A1c, VARIANT II Beta-thalassemia and VARIANT II Total GHb run on CDM 3.5]. 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 Hemoglobin A1c, VARIANT II Beta-thalassemia and VARIANT II Total GHb Program runs on the VARIANT II Hemoglobin Testing System with CDM 4.0 is substantially equivalent to the cleared and currently marketed predicate system.

10

Image /page/10/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle. The eagle is black and white, and the text is in a simple, sans-serif font. The logo is simple and recognizable.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

DEC 2 7 2006

Re: K063643

Trade/Device Name: Variant II TM Hemoglobin A1c Program, Variant™ Betathalassemia and Variant ™ II Total Ghb run on the Variant ™ II Hemoglobin Testing System with CDM 4.0 Regulation Number: 21 CFR 864.7400, 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay; Hemoglobin A2 assay Regulatory Class: Class II Product Code: LCP, JPD Dated: December 7, 2006 Received: December 8, 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

11

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 yours.

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): K063643

Device Name: VARIANT™ II Hemoglobin A1c Program. VARIANT™ II Betathalassemia and VARIANT™ II Total GHb run on the VARIANT™ II Hemoglobin Testing System with CDM 4.0

Indications For Use:

Hemoglobin A1c

The Bio-Rad VARIANT II Hemoglobin A1c Program with CDM 4.0 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 Hemoglobin A1c Program with CDM 4.0 is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.

Total GHb

The VARIANT II Total GHb Program with CDM 4.0 is intended for the separation and area percent determination of total glycated hemoglobin (GHb) in whole blood using boronate affinity high performance liquid chromatography (HPLC),

The VARIANT II Total GHb Program with CDM 4.0 is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.

Measurement of percent hemoglobin A1C is effective in monitoring long-term glucose control in individuals with diabetes mellitus.

Beta-thalassemia

The VARIANT II Beta-thalassemia Short Program with CDM 4.0 is intended for the separation and area percent determinations of hemoglobins A2 and F, and as an aid in the identification of abnormal hemoglobins in whole blood using ion-exchange high performance liquid chromatography.

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The VARIANT II Beta-thalassemia Short Program with CDM 4.0 is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitto diagnosticu use.

Measurement of percent HbA2 and HbF are used for evaluation of Beta-thalassemia, a hereditary hemolytic anemia.

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)

Page 1 of _1 _________________________________________________________________________________________________________________________________________________________________

Olan Cooper, Ms., DWM
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K063643