(20 days)
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).
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.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Bio-Rad VARIANTT II Hemoglobin Testing System with CDM 4.0.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria in this submission are implicit, established by demonstrating substantial equivalence to predicate devices (CDM 3.5 versions of the programs). The key performance metrics evaluated are accuracy (method correlation) and precision.
Here's the table:
| Device | Program | Performance Metric | Acceptance Criteria (Implicit - based on predicate performance) | Reported Device Performance (CDM 4.0 vs. CDM 3.5 Predicate) |
|---|---|---|---|---|
| VARIANT™ II Hemoglobin Testing System | Hemoglobin A1c Program | Accuracy (Method Correlation)Least Squares Regression | r² close to 1, slope close to 1, intercept close to 0 (indicating good correlation with predicate) | r² = 0.9978Slope = 1.0119Intercept = 0.0002 |
| Precision (Within-run %CV) | Normal & Diabetic samples show comparable precision to predicate | Normal Sample: 1.1% (CDM 4.0) vs. 1.5% (CDM 3.5)Diabetic Sample: 1.2% (CDM 4.0) vs. 0.7% (CDM 3.5) | ||
| Precision (Total Precision %CV) | Normal & Diabetic samples show comparable precision to predicate | Normal Sample: 2.6% (CDM 4.0) vs. 2.1% (CDM 3.5)Diabetic Sample: 2.7% (CDM 4.0) vs. 1.7% (CDM 3.5) | ||
| VARIANT™ II Hemoglobin Testing System | Beta thalassemia Short Program (HbA2) | Accuracy (Method Correlation)Least Squares Regression | r² close to 1, slope close to 1, intercept close to 0 | r² = 0.9924Slope = 1.0070Intercept = -0.0034 |
| VARIANT™ II Hemoglobin Testing System | Beta thalassemia Short Program (HbF) | Accuracy (Method Correlation)Least Squares Regression | r² close to 1, slope close to 1, intercept close to 0 | r² = 0.9991Slope = 0.9806Intercept = 0.0192 |
| VARIANT™ II Hemoglobin Testing System | Beta thalassemia Short Program (Precision) | Precision (Within-run %CV) | (Data format unclear in provided text for direct comparison of specific %CV values for HbA2 and HbF for CDM 4.0 vs. 3.5, but overall statement is "equivalent") | Stated as "equivalent" between CDM 4.0 and CDM 3.5, though specific numbers are hard to extract due to formatting issues in the provided text. |
| Precision (Total Precision %CV) | (Data format unclear in provided text for direct comparison of specific %CV values for HbA2 and HbF for CDM 4.0 vs. 3.5, but overall statement is "equivalent") | Stated as "equivalent" between CDM 4.0 and CDM 3.5, though specific numbers are hard to extract due to formatting issues in the provided text. | ||
| VARIANT™ II Hemoglobin Testing System | Total GHb Program | Accuracy (Method Correlation)Least Squares Regression | r² close to 1, slope close to 1, intercept close to 0 | r² = 0.9991Slope = 1.0054Intercept = 0.042 |
| Precision (Within-run %CV) | (Data format unclear in provided text for direct comparison of specific %CV values for CDM 4.0 vs. 3.5, but overall statement is "equivalent") | Stated as "equivalent" between CDM 4.0 and CDM 3.5, though specific numbers are hard to extract due to formatting issues in the provided text. | ||
| Precision (Total Precision %CV) | (Data format unclear in provided text for direct comparison of specific %CV values for CDM 4.0 vs. 3.5, but overall statement is "equivalent") | Stated as "equivalent" between CDM 4.0 and CDM 3.5, though specific numbers are hard to extract due to formatting issues in the provided text. |
2. Sample Size Used for the Test Set and Data Provenance
- Hemoglobin A1c Program (Accuracy): 40 EDTA whole blood samples.
- Beta thalassemia Short Program (Accuracy): 40 EDTA whole blood samples.
- Total GHb Program (Accuracy): 40 EDTA whole blood samples.
- Precision Studies (all programs): Although specific sample numbers are sometimes noted as
n=40orn=80for the combined precision data, it's important to note these refer to the number of individual measurements or patient samples, not necessarily distinct patients. The studies involved analyzing "duplicate aliquots of normal HbA1c and diabetic HbA1c patient samples and controls" over several days. - Data Provenance: The document states "EDTA whole blood samples" and "patient samples and controls." It does not specify the country of origin or if the data was retrospective or prospective. Given the context of method correlation and precision, it's likely these were carefully selected samples to cover the analytical range, and are prospective in nature for the purpose of the study.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This submission is for an in vitro diagnostic device (IVD) that measures specific biomarkers (HbA1c, HbA2, HbF, GHb) using analytical techniques (HPLC). The "ground truth" for such devices is typically established through a reference method or a highly accurate existing method.
In this case, the device's performance is compared against its predicate device (the older CDM 3.5 version of the same program). The predicate device itself would have been validated against a reference method.
- No external human experts were explicitly used to establish "ground truth" for the test set in this particular comparative study. The ground truth is the measurement obtained from the predicate device (CDM 3.5).
- The standardization for HbA1c and GHb is stated as "Traceable to the Diabetes Control and Complications Trial (DCCT) reference method and IFCC. Certified via the National Glycohemoglobin Standardization Program (NGSP) for HbA1c." This indicates that the values obtained by both the new and predicate devices are ultimately traceable to established clinical reference standards, which is how the "ground truth" of the concentration values is ensured.
4. Adjudication Method for the Test Set
Not applicable. This is not a study involving human interpretation of images or data that would require adjudication. It's a quantitative measurement device, and the comparison is statistical (regression and precision).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No. This is an in vitro diagnostic device for quantitative measurement, not an AI or imaging device requiring human reader interpretation or MRMC studies.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are standalone performance evaluations of the device (system including software) in terms of its analytical accuracy and precision. There is no human-in-the-loop aspect being evaluated here, as the device is designed for automated measurement.
7. The Type of Ground Truth Used
The "ground truth" for the performance evaluation in this 510(k) submission is the measurements obtained from the predicate device (the Bio-Rad VARIANT II Hemoglobin Testing System running CDM 3.5). The new device (CDM 4.0) is compared directly to the predicate to demonstrate substantial equivalence, meaning it performs similarly.
Underlying this, the initial "ground truth" for quantitative values for HbA1c is linked to reference methods (DCCT and IFCC) and certification (NGSP). For HbA2 and HbF, the ground truth is also tied to established quantitative analysis using HPLC.
8. The Sample Size for the Training Set
The document does not describe a "training set" in the context of machine learning or AI. This device is an analytical instrument with associated software. The software (CDM 4.0) is an upgrade to manage the data and system on a new operating system, not a machine learning algorithm that is "trained."
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no "training set" in the machine learning sense for this device. The software update primarily concerns operating system compatibility and database management, not the underlying analytical algorithm itself.
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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: K_06 3643
| Submitter: | Bio-Rad Laboratories, Inc.Clinical System Division4000 Alfred Nobel Drive,Hercules, California 94547Phone: (510) 741-5309FAX: (510) 741-6471DEC 27 2006 |
|---|---|
| Contact Person: | Jackie BuckleyRegulatory 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 Programsrun on the VARIANT II Hemoglobin Testing Systemusing 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 ProgramBio-Rad Laboratories, Inc.[K984268, December 17, 1998] |
| VARIANTTM II Beta thalassemia Short ProgramBio-Rad Laboratories, Inc.[K991127, June 10, 1999] | |
| VARIANTTM II Total GHb ProgramBio-Rad Laboratories, Inc.[K003280, December 19, 2000] |
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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
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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:
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VARIANT™ II Hemoglobin A1c (k) 984268
| Summary of Technological Characteristic Similarities in Comparison to Predicate Device | ||
|---|---|---|
| Characteristics | New Device:VARIANT II Hemoglobin A1c Program runon the VARIANT II Hemoglobin TestingSystem using CDM 4.0 | Predicate Device:(k)984268VARIANT II Hemoglobin A1c Program runon the VARIANT II Hemoglobin TestingSystem using CDM 3.5 |
| Intended Use(s) | The VARIANT II Hemoglobin A1c is intendedfor the percent determination of hemoglobinA1c in human whole blood using ion-exchangehigh-performance liquid chromatography(HPLC).For In Vitro Diagnostic Use. | The VARIANT II Hemoglobin A1c is intendedfor the percent determination of hemoglobinA1c in human whole blood using ion-exchangehigh-performance liquid chromatography(HPLC).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 | 3.5 |
| 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 |
| Standardization forHbA1c | Traceable to the Diabetes Control andComplications Trial (DCCT) reference methodand IFCC. Certified via the NationalGlycohemoglobin Standardization Program(NGSP) for HbA1c. | Traceable to the Diabetes Control andComplications Trial (DCCT) reference methodand IFCC. Certified via the NationalGlycohemoglobin Standardization Program(NGSP) for HbA1c. |
| Firmware upgradeto VARIANT IIVCS 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 ShortProgram run on the VARIANT IIHemoglobin Testing System using CDM 4.0 | Predicate Device: (k)991127VARIANT II Beta thalassemai ShortProgram run on the VARIANT IIHemoglobin Testing System using CDM 3.5 |
| Intended Use(s) | The VARIANT II Beta thalassemia ShortProgram is intended for the separation and areapercent determinations of hemoglobin A2 andF, and as an aid in the identification ofabnormal hemoglobins in human whole bloodusing ion-exchange high-performance liquidchromatography (HPLC).The VARIANT II B-thalassemia ShortProgram is intended for use only with the Bio-Rad VARIANT II Hemoglobin TestingSystem.For In Vitro Diagnostic Use. | The VARIANT II Beta thalassemia ShortProgram is intended for the separation and areapercent determinations of hemoglobin A2 and F,and as an aid in the identification of abnormalhemoglobins in human whole blood using ion-exchange high-performance liquidchromatography (HPLC).The VARIANT II B-thalassemia Short Programis intended for use only with the Bio-RadVARIANT II Hemoglobin Testing System.For In Vitro Diagnostic Use. |
| Indication(s) for Use | Measurement of the percent hemoglobin A2 andF are effective in screening of β-thalassemia(i.e. hereditary hemolytic anemiascharacterized by decreased synthesis of one ormore types of abnormal hemoglobinspolypeptide chains). | Measurement of the percent hemoglobin A2 andF are effective in screening of β-thalassemia (i.e.hereditary hemolytic anemias characterized bydecreased synthesis of one or more types ofabnormal hemoglobins polypeptide chains). |
| Assay Principle | Cation exchange high performance liquidchromatography | Cation exchange high performance liquidchromatography |
| CDM Softwareversion | 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 toCD-R | Used Easy CD writer Read/Write |
| DatabaseManagement | Delete data directly from database | Substitute database with a blank database |
| Firmware upgradeto VARIANT IIVCS 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 onthe VARIANT II Hemoglobin TestingSystem using CDM 4.0 | Predicate Device: (k) 003280VARIANT II Total GHb Program run on theVARIANT II Hemoglobin Testing Systemusing CDM 3.5 |
| Intended Use(s) | The VARIANT II Total GHb Program isintended for the separation and area percentdetermination of total glycated hemoglobin(GHb) in whole blood using boronate affinityhigh-performance liquid chromatography(HPLC).For In Vitro Diagnostic Use. | The VARIANT II Total GHb Program isintended for the separation and area percentdetermination of total glycated hemoglobin(GHb) in whole blood using boronate affinityhigh-performance liquid chromatography(HPLC).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 | Affinity high performance liquidchromatography | Affinity high performance liquidchromatography |
| CDM Softwareversion | 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 toCD-R | Used Easy CD writer Read/Write |
| DatabaseManagement | Delete data directly from database | Substitute database with a blank database |
| Standardization | Traceable to the Diabetes Control andComplications Trial (DCCT) reference methodand IFCC. Certified via the NationalGlycohemoglobin Standardization Program(NGSP) for HbA1c. | Traceable to the Diabetes Control andComplications Trial (DCCT) reference methodand IFCC. Certified via the NationalGlycohemoglobin Standardization Program(NGSP) for HbA1c. |
| Firmware upgradeto VARIANT IIVCS and VSS | VCS 41.300 VSS 51.381 | VCS 41.295 VSS 51.373 |
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VARIANTIM II Beta thalassemia Short Program (k)991127
{5}------------------------------------------------
VARIANT™ II GHb (k)003280
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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 |
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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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| Mean (%HbA2) | ||||
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Bio-Rad Laboratories, Inc.
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| Mean (%HbF) | 0.0 | |||
| Within run (%CV) | ||||
| Total Precision (%CV) |
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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| n= (number of samples | ||||
| Mean (%GHb) | ||||
| Within run (%CV) | ||||
| Total Precision ' |
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.
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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
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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 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)
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Olan Cooper, Ms., DWM
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K063643
§ 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).