(17 days)
The D-10TM Hemoglobin A1c Program is intended for the percent determination of hemoglobin Alc in human whole blood using ion-exchange high performance liquid chromatography (HPLC). The D-10 Hemoglobin A1c Program is intended for use only with the Bio-Rad D-10 Hemoglobin Testing System. For In Vitro Diagnostic Use.
The Bio-Rad D-10™ Dual Program system is intended for the percent determination of hemoglobins A1c, A2 and F, and for the detection of abnormal hemoglobins in human whole blood using ion-exchange high performance liquid chromatography (HPLC). The Bio-Rad D-10™ Dual Program is intended for Professional Use Only. For in vitro diagnostic use.
Measurement of the percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus, and measurement of the percent HbA2 and HbF are effective in screening of ß—thalassemias (i.e., hereditary hemolytic anemias characterized by decreased synthesis of one or more types of abnormal hemoglobin polypeptide chains). Detection of hemoglobin variants such as hemoglobins S, C, D and E by HPLC is effective in presumptive identification of these variants.
The Bio-Rad Hemoglobin Testing System is a fully automated analyzer consisting of a single module that rovides an integrated method for sample preparation, and determination of specific hemoglobins in whole blood. The Bio-Rad Hemoglobin Testing System provides an integrated method for the separation and determination of the relative percent of specific hemoglobins (e.g. A2, F and A1c in whole blood). The separation is based on the principles of high performance liquid chromatography. The system can accommodate 1 to 10 samples per run using a single rack currently.
The new feature in this submission is the optional D-10 Rack Loader which will be available for use with the D-10 Hemoglobin Testing System. The D-10 Rack Loader accommodates 5 racks and automatically transports each rack into and out of the D-10 System. The D-10 Rack Loader offers continuous loading, allowing the operator to insert or remove racks during a run.
The Bio-Rad D-10 Hemoglobin Testing System with the D-10 Rack Loader demonstrates substantial equivalence to its predicate devices (D-10 Hemoglobin A1c Program and D-10 Dual Program without the Rack Loader) through method correlation and precision studies.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the demonstration of substantial equivalence to the predicate devices. The study aims to show that the new device, with the rack loader, performs as similarly as possible to the predicate devices. The reported device performance is presented as correlation and precision data against these predicate devices.
D-10 Hemoglobin A1c Program (3-minute run):
| Metric | Acceptance Criteria (Implied: Similar to Predicate) | Reported Device Performance (New Device vs. Predicate) |
|---|---|---|
| Accuracy | High Correlation to Predicate (r² close to 1, slope close to 1, intercept close to 0) | r² = 0.9950, Slope = 0.9415, Intercept = 0.2714 |
| Precision | Similar %CVs to Predicate | See detailed table below |
D-10 Dual Program (6.5-minute run) - HbA1c:
| Metric | Acceptance Criteria (Implied: Similar to Predicate) | Reported Device Performance (New Device vs. Predicate) |
|---|---|---|
| Accuracy | High Correlation to Predicate (r² close to 1, slope close to 1, intercept close to 0) | r² = 0.9956, Slope = 0.9827, Intercept = 0.1208 |
| Precision | Similar %CVs to Predicate | See detailed table below |
D-10 Dual Program (6.5-minute run) - HbA2:
| Metric | Acceptance Criteria (Implied: Similar to Predicate) | Reported Device Performance (New Device vs. Predicate) |
|---|---|---|
| Accuracy | High Correlation to Predicate (r² close to 1, slope close to 1, intercept close to 0) | r² = 0.9975, Slope = 0.9902, Intercept = 0.2476 |
| Precision | Similar %CVs to Predicate | See detailed table below |
D-10 Dual Program (6.5-minute run) - HbF:
| Metric | Acceptance Criteria (Implied: Similar to Predicate) | Reported Device Performance (New Device vs. Predicate) |
|---|---|---|
| Accuracy | High Correlation to Predicate (r² close to 1, slope close to 1, intercept close to 0) | r² = 0.9956, Slope = 1.0188, Intercept = -0.3863 |
| Precision | Similar %CVs to Predicate | See detailed table below |
Detailed Precision Tables (New Device with Rack Loader vs. Predicate without Rack Loader):
D-10 HbA1c Program (3 minute):
| New Device (with Rack Loader) | Predicate (without Rack Loader) | |
|---|---|---|
| Normal Sample | ||
| n= | 400 | 80 |
| Mean (%HbA1c) | 5.6 | 5.9 |
| Within run (%CV) | 0.6 | 0.8 |
| Total Precision (%CV) | 1.5 | 1.8 |
| Diabetic Sample | ||
| n= | 400 | 80 |
| Mean (%HbA1c) | 11.0 | 13.1 |
| Within run (%CV) | 0.6 | 0.3 |
| Total Precision (%CV) | 1.4 | 0.9 |
D-10 Dual Program (6.5 minutes) HbA1c:
| New Device (with Rack Loader) | Predicate (without Rack Loader) | |
|---|---|---|
| Normal Sample | ||
| n= | 400 | 80 |
| Mean (%HbA1c) | 5.5 | 5.9 |
| Within run (%CV) | 0.7 | 0.8 |
| Total Precision (%CV) | 1.5 | 1.8 |
| Diabetic Sample | ||
| n= | 400 | 80 |
| Mean (%HbA1c) | 10.6 | 13.1 |
| Within run (%CV) | 0.4 | 0.3 |
| Total Precision (%CV) | 1.2 | 0.9 |
D-10 Dual Program (6.5 minutes) HbA2:
| New Device (with Rack Loader) | Predicate (without Rack Loader) | |
|---|---|---|
| Low Sample | ||
| n= | 400 | 80 |
| Mean (%HbA2) | 2.9 | 2.2 |
| Within run (%CV) | 1.8 | 4.5 |
| Total Precision (%CV) | 3.6 | 5.3 |
| High Sample | ||
| n= | 400 | 80 |
| Mean (%HbA2) | 4.9 | 5.4 |
| Within run (%CV) | 1.2 | 1.7 |
| Total Precision (%CV) | 3.6 | 3.1 |
D-10 Dual Program (6.5 minutes) HbF:
| New Device (with Rack Loader) | Predicate (without Rack Loader) | |
|---|---|---|
| Low Sample | ||
| n= | 400 | 80 |
| Mean (%HbF) | 1.4 | 2.1 |
| Within run (%CV) | 2.1 | 1.7 |
| Total Precision (%CV) | 2.9 | 3.3 |
| High Sample | ||
| n= | 400 | 80 |
| Mean (%HbF) | 6.6 | 8.7 |
| Within run (%CV) | 0.8 | 1.4 |
| Total Precision (%CV) | 1.8 | 2.0 |
2. Sample sizes used for the test set and the data provenance:
-
Accuracy (Method Correlation) Test Sets:
- D-10 HbA1c Program: 40 EDTA whole blood samples.
- D-10 Dual Program (HbA1c): 40 EDTA whole blood samples.
- D-10 Dual Program (HbA2): 39 EDTA whole blood samples.
- D-10 Dual Program (HbF): 39 EDTA whole blood samples.
- Data Provenance: The document does not specify the country of origin of the data. It implies the samples are human anticoagulated whole blood (EDTA) and patient samples (normal and diabetic, low and high concentration for HbA2 and HbF). The study appears to be an internal validation study and implicitly prospective for the "new device" performance, as it compares it concurrently to the "predicate device" performance using the same samples where appropriate for method correlation.
-
Precision Test Sets:
- For the new device (with D-10 Rack Loader), for each analyte (HbA1c, HbA2, HbF) and concentration level (Normal/Diabetic or Low/High), n=400 (two samples run on each of five racks, twice a day over 20 working days, with duplicate aliquots analyzed per run).
- For the predicate device (without D-10 Rack Loader), for each analyte and concentration level, n=80 (two samples run on one rack, twice a day over 20 working days, with duplicate aliquots analyzed per run).
- Data Provenance: Similar to accuracy, the country of origin is not specified. The samples are described as "EDTA whole blood patient samples." The protocol appears to be prospective for establishing precision for both the new and predicate systems under the specific test conditions. The document notes that "precision samples are different, since they were run at different time periods," indicating separate precision studies for the new and predicate configurations.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This device is an in-vitro diagnostic (IVD) test for quantitative measurement of hemoglobin components. The "ground truth" for method correlation and precision studies is typically established by comparing the new device's measurements against a recognized reference method or a legally marketed predicate device (as in this case).
- The document does not mention the use of human experts (e.g., radiologists) to establish ground truth. The ground truth for this type of device is the quantitative value determined by the existing, validated methods (the predicate devices).
4. Adjudication method for the test set:
- Not applicable. This is a quantitative IVD device. "Adjudication" typically refers to resolving discrepancies between human readers or between an algorithm and human readers, often in image-based diagnostics. Here, the comparison is between two analytical methods (new device vs. predicate device).
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:
- Not applicable. This is not a diagnostic imaging device involving human readers or AI assistance in interpretation. It is a fully automated analytical instrument.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the entire study pertains to the standalone performance of the Bio-Rad D-10 Hemoglobin Testing System with the D-10 Rack Loader. The device itself is an automated analyzer, meaning its performance is "algorithm only" in the sense that the measurement process is automated, without human intervention in the result generation beyond sample loading and instrument operation. The comparison is against the standalone performance of predicate automated analyzers.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for evaluating the new device's performance is the measurements obtained from the existing, legally marketed predicate devices (Bio-Rad D-10 Hemoglobin A1c Program and D-10 Dual Program without the D-10 Rack Loader).
- For HbA1c, the predicate device (and by extension the new device) is traceable to the Diabetes Control and Complications Trial (DCCT) reference method and IFCC, and certified by the National Glycohemoglobin Standardization Program (NGSP). This constitutes a high-order reference for HbA1c.
- For HbA2 and HbF, the document states, "The Joint Committee on Traceability in Laboratory Medicine has not identified a higher order reference method or reference material for the quantitation of HbA2 and HbF," implying the predicate device's established performance serves as the practical ground truth for comparison.
8. The sample size for the training set:
- This document describes performance studies (accuracy and precision) for a new version of an existing device (adding a rack loader). It does not explicitly mention a "training set" in the context of machine learning model development. For IVD devices, validation typically involves performance studies on clinical samples, rather than a separate "training" and "test" set as seen in AI/ML. The samples used for method correlation and precision testing serve as the validation data for the device's performance.
9. How the ground truth for the training set was established:
- Not applicable, as a distinct "training set" for an AI/ML model is not described in the context of this IVD device submission. The device's underlying principles (ion-exchange high performance liquid chromatography) are well-established analytical methods, not derived from machine learning. The comparison is made against the established performance of predicate devices.
{0}------------------------------------------------
Koboool/
Attachment 4
JAN 2 0 2006
Summary of Safety and Effectiveness Bio-Rad Laboratories, Inc.
{1}------------------------------------------------
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______________________________________________________________________________________________________________________________________________
| 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: | December 30, 2005 |
| Device Name: | Bio-Rad D-10 TM Dual ProgramBio-Rad D-10 TM Hemoglobin A1c Programon the D-10 Hemoglobin System with D-10 RackLoader |
| Classification Name: | HbA 1c : Assay, Glycosylated Hemoglobin[21CFR 864.7470 / Prod. Code LCP] andHbA 2 : Hemoglobin A 2 Quantitation[21CFR 864.7400 / Prod. Code: JPD] |
| Predicate Devices: | D-10 Hemoglobin A1c ProgramBio-Rad Laboratories, Inc.[K031043, August 27, 2003]D-10 Dual ProgramBio-Rad Laboratories, Inc[K041444, June 9, 2004] |
{2}------------------------------------------------
Indications for Use Statements and Intended Uses:
The D-10TM Hemoglobin A1c Program is intended for the percent determination of hemoglobin Alc in human whole blood using ion-exchange high performance liquid chromatography (HPLC).
The D-10 Hemoglobin A1c Program is intended for use only with the Bio-Rad D-10 Hemoglobin Testing System. For In Vitro Diagnostic Use.
The Bio-Rad D-10™ Dual Program system is intended for the percent determination of hemoglobins A1c, A2 and F, and for the detection of abnormal hemoglobins in human whole blood using ion-exchange high performance liquid chromatography (HPLC).
The Bio-Rad D-10™ Dual Program is intended for Professional Use Only. For in vitro diagnostic use.
Measurement of the percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus, and measurement of the percent HbA2 and HbF are effective in screening of ß—thalassemias (i.e., hereditary hemolytic anemias characterized by decreased synthesis of one or more types of abnormal hemoglobin polypeptide chains).
Detection of hemoglobin variants such as hemoglobins S, C, D and E by HPLC is effective in presumptive identification of these variants.
{3}------------------------------------------------
New Device Description
The Bio-Rad Hemoglobin Testing System is a fully automated analyzer consisting of a single module that rovides an integrated method for sample preparation, and determination of specific hemoglobins in whole blood. The Bio-Rad Hemoglobin Testing System provides an integrated method for the separation and determination of the relative percent of specific hemoglobins (e.g. A2, F and A1c in whole blood). The separation is based on the principles of high performance liquid chromatography. The system can accommodate 1 to 10 samples per run using a single rack currently.
The new feature in this submission is the optional D-10 Rack Loader which will be available for use with the D-10 Hemoglobin Testing System. The D-10 Rack Loader accommodates 5 racks and automatically transports each rack into and out of the D-10 System. The D-10 Rack Loader offers continuous loading, allowing the operator to insert or remove racks during a run.
Technical Characteristics Compared to Predicate
The Bio-Rad D-1018 Hemoglobin A1c Program and the D-10 Dual Program run on the D-10 Hemoglobin Testing System with D-10 Rack Loader have the same basic technical characteristics as the predicates D-10 Hemoglobin A1c Program (k) 031043 and D-10 Dual Program (k)041444 run on the D-10 Hemoglobin Testing System. There are three main differences between the D-10 Hemoglobin Testing System with the new D-10 Rack Loader. The technical characteristics are summarized in the following tables:
{4}------------------------------------------------
D-10™ Hemoglobin A1c (k)031043
| Summary of Technological Characteristic Similarities in Comparison to Predicate Device | ||
|---|---|---|
| Characteristics | New Device: | Predicate Device: |
| D-10TM Hemoglobin A1c Program run on the | D-10TM Hemoglobin A1c Program run on the | |
| D-10 Hemoglobin Testing System with | D-10 Hemoglobin Testing System without the | |
| D-10 Rack Loader | D-10 Rack Loader | |
| Intended Use(s) | The Bio-Rad Hemoglobin A1c Program isintended for the percent determination ofhemoglobin A1c in human whole blood usingion-exchange high-performance liquidchromatography (HPLC). The D-10Hemoglobin A1c Program is intended for useonly with the Bio-Rad D-10 HemoglobinTesting System.For In Vitro Diagnostic Use. | The Bio-Rad Hemoglobin A1c Program isintended for the percent determination ofhemoglobin A1c in human whole blood usingion-exchange high-performance liquidchromatography (HPLC). The D-10Hemoglobin A1c Program is intended for useonly with the Bio-Rad D-10 HemoglobinTesting System.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 n monitoring long-term glucose controlin individuals with diabetes mellitus. |
| Assay Principle | Cation exchange high performance liquidchromatography | Cation exchange high performance liquidchromatography |
| Sample Type | Human anticoagulated whole blood (EDTA) | Human anticoagulated whole blood (EDTA) |
| Visible Detection | 415 nm | 415 nm |
| 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. |
| Results | Quantitative Area % HbA1c | Quantitative Area % HbA1c |
| Time to processsample | 3.0 minutes | 3.0 minutes |
{5}------------------------------------------------
D-10™ Hemoglobin A1c (k)031043
.
.
:
| Summary of Technological Characteristic Differences in Comparison to Predicate Device | ||
|---|---|---|
| Characteristics | New Device:D-10™ Hemoglobin A1c Program run on theD-10 Hemoglobin Testing System withD-10 Rack Loader | Predicate Device:D-10™ Hemoglobin A1c Program run on theD-10 Hemoglobin Testing System without theD-10 Rack Loader |
| Software version | 3.5 | 3.00 |
| Number of Racks thatcan be run. | 5 Racks of 10 EDTA whole blood tubes | 1 rack of 10 EDTA whole blood tubes |
| Rack insertion intoD-10 HemoglobinTesting System | Automated | Manual |
| D-10TM Dual Program (k)0414444Summary of Technological Characteristic Similarities in Comparison to Predicate Device | ||
| Characteristics | New Device: | Predicate Device: |
| Intended Uses | Bio-Rad D-10TM Dual Program run on the D-10 Hemoglobin Testing System withD-10 Rack LoaderThe Bio-Rad D-10 Dual Program system is intendedfor the percent determination of hemoglobins A1c,A2 and F, and for the detection of abnormalhemoglobins in human whole blood using ion-exchange high performance liquid chromatography(HPLC).The Bio-Rad D-10 Dual Program is intended forProfessional Use Only. For in vitro diagnostic use. | Bio-Rad D-10TM Dual Program run on the D-10Hemoglobin Testing System withoutD-10 Rack LoaderThe Bio-Rad D-10 Dual Program system is intendedfor the percent determination of hemoglobins A1c, A2and F, and for the detection of abnormal hemoglobinsin human whole blood using ion-exchange highperformance liquid chromatography (HPLC).The Bio-Rad D-10 Dual 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 glucose control inindividuals with diabetes mellitus, and measurementof the percent HbA2 and HbF are effective inmonitoring of β-thalassemia (i.e., hereditaryhemolytic anemias characterized by decreasedsynthesis of one or more types of abnormalhemoglobin polypeptide chains).Detection of hemoglobin variants such ashemoglobins S, C, D and E by HPLC is effective inpresumptive identification of these variants. | Measurement of the percent hemoglobin A1c iseffective in monitoring long-term glucose control inindividuals with diabetes mellitus, and measurementof the percent HbA2 and HbF are effective inmonitoring of β-thalassemia (i.e., hereditaryhemolytic anemias characterized by decreasedsynthesis of one or more types of abnormalhemoglobin polypeptide chains).Detection of hemoglobin variants such ashemoglobins S, C, D and E by HPLC is effective inpresumptive identification of these variants. |
| Assay Principle | Cation exchange high performance liquidchromatography | Cation exchange high performance liquidchromatography |
| Sample Type | Human anticoagulated whole blood (EDTA) | Human anticoagulated whole blood (EDTA) |
| Visible Detection | 415 nm | 415 nm |
| Standardization | Traceable to the Diabetes Control andComplications Trial (DCCT) reference method andIFCC. Certified via the National GlycohemoglobinStandardization Program (NGSP) for HbA1c.The Joint Committee on Traceability in LaboratoryMedicine has not identified a higher order referencemethod or reference material for the quantitation ofHbA2 and HbF | Traceable to the Diabetes Control and ComplicationsTrial (DCCT) reference method and IFCC. Certifiedvia the National Glycohemoglobin StandardizationProgram (NGSP) for HbA1c.The Joint Committee on Traceability in LaboratoryMedicine has not identified a higher order referencemethod or reference material for the quantitation ofHbA2 and HbF |
| Results | Quantitative Area % HbA2, F and A1c | Quantitative Area % HbA2, F and A1c |
| Time to process sample | 6.5 minutes | 6.5 minutes |
:
:
{6}------------------------------------------------
D-10™ Dual Program (k)0414444
{7}------------------------------------------------
D-10™ Dual Program (k)0414444
.
| Summary of Technological Characteristic Differences in Comparison to Predicate Device | ||
|---|---|---|
| Characteristics | New Device:D-10TM Hemoglobin A1c Program run on theD-10 Hemoglobin Testing System withD-10 Rack Loader | Predicate Device:D-10TM Hemoglobin A1c Program run on theD-10 Hemoglobin Testing System without theD-10 Rack Loader |
| Software version | 3.5 | 3.00 |
| Number of Racks thatcan be run. | 5 Racks of 10 EDTA whole blood tubes | 1 rack of 10 EDTA whole blood tubes |
| Rack insertion intoD-10 HemoglobinTesting System | Automated | Manual |
.
:
{8}------------------------------------------------
Testing To Establish Substantial Equivalence:
Note: The D-10 Hemoglobin Testing System currently contains one rack for 10 Note. The D-10 Hemoglobin Techanges. Throughout this decument the EDTA Will indicate either the D-10 Hemoglobin A1c Program or D-10 Dual Program text will mithout the D-10 Rack Loader on the D-10 Hemoglobin Testing are run. The D-10 Rack Loader is an optional accessory item to the D-10 System. The D-10 Rack Dodater 1. alows for 5 racks of 10 EDTA Whole Blood Tubes to be run automatically while the system is running in mid size laboratories.
Accuracy:
D-10 Hemoglobin HbA1c Program (3 minute)
Method correlation between Bio-Rad D-10 Hemoglobin AIc Program with D-10 Rack Loader Method Correlation betwoon Die naam without D-10 Rack Loader was evaluated using 40 EDTA and D-10 Hemogroom 1170 Frogram -14.3% HbA1c. The results are presented in the following table:
| D-10 Hemoglobin A1c Program Correlation for HbA1c | ||||
|---|---|---|---|---|
| Regression Method | n | r2 | Slope | Intercept |
| Least Squares | 40 | 0.9950 | 0.9415 | 0.2714 |
Householding A1e Drogram Correlation for HbA1c
D-10 Dual Program -Hemoglobin A1c (6.5 minute)
Method correlation between Bio-Rad D-10 Dual Program with D-10 Rack Loader and D-10 Dual Mothou correlated. 10 Rack was evaluated using 40 EDTA whole blood samples ranging from 5.1% to 14.3% HbA10. The results are presented in the following table:
D-10 Dual Program Correlation for HbA1c
| Regression Method | n | r2 | Slope | Intercept |
|---|---|---|---|---|
| Least Squares | 40 | 0.9956 | 0.9827 | 0.1208 |
D-10 Dual Program - Hemoglobin A2 (6.5 minute)
Method correlation between Bio-Rad D-10 Dual Program with D-10 Rack Loader and D-10 Dual Program without Rack Loader was evaluated with 39 EDTA whole blood samples ranging from 2.1% - 11.8% HbA2. The results are presented in the following table:
| D-10 Dual Program Correlation for HbA2 | ||||
|---|---|---|---|---|
| -- | ---------------------------------------- | -- | -- | -- |
| Regression Method | n | r2 | Slope | Intercept |
|---|---|---|---|---|
| Least Squares | 39 | 0.9975 | 0.9902 | 0.2476 |
D-10 Dual Program - Hemoglobin F (6.5 minute)
Method correlation between Bio-Rad D-10 Dual Program with D-10 Rack Loader and D-10 Dual Program without D-10 Rack Loader was evaluated with 39 EDTA whole blood samples ranging from 0.8% - 17.3% HbF. The results are presented in the following table:
| D-10 Dual Program Correlation for HBF | ||||
|---|---|---|---|---|
| Regression Method | n | r2 | Slope | Intercept |
| Least Squares | 39 | 0.9956 | 1.0188 | -0.3863 |
D 16TM Dual Program Correlation for HhF
Bio-Rad Laboratories, Inc.
{9}------------------------------------------------
Precision:
D-10 Hemoglobin A1c Program (3 minute)
The following precision table provides comparison data on the precision between D-10 Hemoglobin A 1c Program with the D-10 and Rack Loader and the D-10 Hemoglobin A Ic Program without the D-10 Rack Loader, each utilizing EDTA whole blood patient samples.
Method precision was performed using a protocol based on the NCCLS Evaluation protocol, EP5-A2 for the D-10 Hemoglobin A1c Program with D-10 Rack Loader and NCCLS Evaluation protocol EP5-T2 for the D-I0 Hemoglobin A1c Program without Rack Loader. The protocols for both the D-10 Hemoglobin A1c Program with D-10 Rack Loader and D-10 Hemoglobin A1c Programs without D-10 Rack Loader are similar. Using these protocols, two samples were run on one rack, twice a day over 20 working days on one D-10 Hemoglobin Testing System without D-10 Rack Loader. On the D-10 Hemoglobin Testing System with D-10 Rack Loader, the protocol requires two samples run on each of five racks, twice a day over 20 working days. In each duplicate daily run for both verification studies, duplicate aliquots of normal HbA 1c and diabetic HbAlc 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 D-10 Hemoglobin A1c Program with D-10 Rack Loader and the D-10 Hemoglobin A1c Program without D-10 Rack Loader are equivalent. A summary of combined comparative precision results is presented in the following precision table.
| D-10 HbA1c with D-10 Rack Loader vs. D-10 HbA1c without D-10 Rack Loader - | |
|---|---|
| Precision |
| D-10 HbA1cwith D-10 Rack Loader | D-10 HbA1cwithout D-10 Rack Loader | |||
|---|---|---|---|---|
| Normal Sample | Diabetic Sample | Normal Sample | Diabetic Sample | |
| n= (number of samples) | 400 | 400 | 80 | 80 |
| Mean (%HbA1c) | 5.6 | 11.0 | 5.9 | 13.1 |
| Within run (%CV) | 0.6 | 0.6 | 0.8 | 0.3 |
| Total Precision (%CV) | 1.5 | 1.4 | 1.8 | 0.9 |
D-10 Dual Program - HbA1c (6.5 minutes)
The following precision table provides comparison data on the precision between D-10 Dual Program (HbA1c) with Rack Loader and the D-10 Duq1 Program (HbA1c) without the D-10 Rack Loader, each utilizing EDTA whole blood patient samples.
Method precision was performed using a protocol based on the NCCLS Evaluation protocol EP5-A2 for the D-10 Dual Program with D-10 Rack Loader and NCCLS Evaluation protocol EPS-A for the D-10 Dual Program without Rack Loader. The protocols for both the D-1010 Dual Program with D-10 Rack Loader and D-10 Dual Program without D-10 Rack Loader are similar. Using these protocols, two samples were run on one rack, twice a day over 20 working days on one D-10 Hemoglobin Testing System. On the D-10 Hemoglobin Testing System with D-10 Rack Loader, the protocol requires two samples run on each of five racks, twice a day over 20 working days. In each duplicate daily run for both verification studies, duplicate aliquots of normal HbAL and diabetic HbA1c patient samples were each analyzed per run. Although the precision samples are different, since they were run at different time periods, the precision results between the D-10
Bio-Rad Laboratories, Inc.
{10}------------------------------------------------
Dual Program with D-10 Rack Loader and the D-10 Dual Program without D-10 Rack Loader are equivalent. A summary of combined comparative precision results is presented in the following precision table.
| D-10 Dual (6.5 Minutes)HbA1c Program with D-10 RackLoader | D-10 Dual (6.5 Minutes)HbA1c Program without D-10Rack Loader | ||||
|---|---|---|---|---|---|
| Normal Sample | Diabetic Sample | Normal Sample | Diabetic Sample | ||
| n= (number of samples) | 400 | 400 | 80 | 80 | |
| Mean (%HbA1c) | 5.5 | 10.6 | 5.9 | 13.1 | |
| Within run (%CV) | 0.7 | 0.4 | 0.8 | 0.3 | |
| Total Precision (%CV) | 1.5 | 1.2 | 1.8 | 0.9 |
D-10 Dual Program (HbA1c) with D-10 Rack Loader vs. D-10 Dual Program (HbA1c) without D-10 Rack Loader - Precision
D-10 Dual Program HbA2 (6.5 minutes)
The following precision table provides comparison data on the precision between D-10 Dual Program (HbA2) with D-10 Rack Loader and D-10 Dual Programs (HbA2) without D-10 Rack Loader, each utilizing EDTA whole blood patient samples.
Method precision was performed using a protocol based on the NCCLS Evaluation protocol EPS-A2 for the D-10 Dual Program with D-10 Rack Loader and NCCLS Evaluation protocol EP5-A for the D-10 Dual Program without Rack Loader. The protocols for both the D-10 Dual Program with D-10 Rack Loader and D-10 Dual Program without D-10 Rack Loader are similar. Using these protocols, two samples were run on one rack, twice a day 40 runs over 20 working days were performed on one D-10 Hemoglobin Testing System. On the D-10 Hemoglobin Testing System with D-10 Rack Loader, the protocol requires two samples run on each of five racks, twice a day over 20 working days. In each duplicate daily run for both verification studies, duplicate aliquots of low HbA2 and high HbA2 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 D-10 Dual Program with D-10 Rack Loader and the D-10 Dual Program without D-10 Rack Loader are equivalent. A summary of combined comparative precision results is presented in the following precision table.
{11}------------------------------------------------
Precision: (continued)
D-10 Dual Program (HbA2) with D-10 Rack Loader vs. D-10 Dual Program (HbA2) without D-10 Rack Loader - Precision
| D-10 Dual Program (6.5 Minutes)HbA2 run with D-10 Rack Loader | VARIANT II β-thalassemia ShortHbA2 run without D-10 Rack Loader | |||
|---|---|---|---|---|
| Low Sample | High Sample | Low Sample | High Sample | |
| n= (number of samples) | 400 | 400 | 80 | 80 |
| Mean (%HbA2) | 2.9 | 4.9 | 2.2 | 5.4 |
| Within run (%CV) | 1.8 | 1.2 | 4.5 | 1.7 |
| Total Precision (%CV) | 3.6 | 3.6 | 5.3 | 3.1 |
D-10 Dual Program -- HbF (6.5 minutes)
The following precision table provides comparison data on the precision between D-10 Dual Program (HbF) with the D-10 Rack Loader and the D-10 Dual Program (HbF) without D-10 Rack Loader, each utilizing EDTA whole blood patient samples.
Method precision was performed using a protocol based on the NCCLS Evaluation protocol EP5-A2 for the D-10 Dual Program with D-10 Rack Loader and NCCLS Evaluation protocol EP5-A for the D-10 Dual Program without Rack Loader. The protocols for both the D-10 Dual Program with D-10 Rack Loader and D-10 Dual Program without D-10 Rack Loader are similar. Using these protocols, two samples were run on one rack, twice a day over 20 working days on one D-10 Hemoglobin Testing System. On the D-10 Hemoglobin Testing System with D-10 Rack Loader, the protocol requires two samples run on each of five racks, twice a day over 20 working days. In each duplicate daily run for both verification studies, duplicate aliquots of low HbF and high HbF 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 D-10 Dual Program with D-10 Rack Loader and the D-10 Dual Program without D-10 Rack Loader are equivalent. A summary of combined comparative precision results is presented in the following. precision table.
D-10 Dual Program (HbF) with D-10 Rack Loader vs. D-10 Dual Program (HbF) without D-10 Rack Loader - Precision
| D-10 Dual Program (6.5 minutes)HbF with D-10 Rack Loader | D-10 Dual Program (6.5 minutes)HbF without D-10 Rack Loader | |||
|---|---|---|---|---|
| Low Sample | High Sample | Low Sample | High Sample | |
| n= (number of samples) | 400 | 400 | 80 | 80 |
| Mean (%HbF) | 1.4 | 6.6 | 2.1 | 8.7 |
| Within run (%CV) | 2.1 | 0.8 | 1.7 | 1.4 |
| Total Precision (%CV) | 2.9 | 1.8 | 3.3 | 2.0 |
{12}------------------------------------------------
Conclusion:
The similarities of the intended use and the general performance characteristics and results of the rne shimarities of the mendou ass and and and gold in A1c Program and D-10 Dual Program with Ilowiy doser loca and brand be management Testing system are nearly identical to or logical D 10 Nack Louder on the two cleared predicate program systems [i.e., the Bio-Rad D-10 Hemoglobin Aie Program and the Bio-Rad Dual Program]. Thus, one may conclude, based on the use of the same HPLC technology, and the nearly equivalent results obtained for the the use of the same II 12 corresponding results obtained with the two predicate eoreanshall provision versas no obin A1c Program and D-10 Dual Program with D-10 Bystems the D-10 Hemoglobin Testing system is substantially equivalent to these 2 cleared and currently marketed predicate systems.
{13}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/13/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird with outstretched wings, rendered in black. The bird is positioned within a circular border, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES. USA" is arranged around the circumference of the circle.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Jackie Buckley Regulatory Affairs Representative Bio-Rad Laboratories, Inc. Clinical Systems Division 4000 Alfred Nobel Dr. Hercules, CA 94547
JAN 2 0 2006
K060001 Re:
Trade/Device Name: Bio-Rad D-10TM Dual Program and D-10 Hemoglobin A1c Program run on the D-10 Hemoglobin Testing System with D-10 Rack Loader Regulation Number: 21 CFR§864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP, JPD Dated: December 30, 2005 Received: January 3, 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).
{14}------------------------------------------------
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 Gutz
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
{15}------------------------------------------------
Indications for Use
510(k) Number (if known): K060001
Bio-Rad D-10™ Dual Program and D-10 Hemoglobin A1c Device Name: Program run on the D-10 Hemoglobin Testing System with D-10 Rack Loader Measurements of percent HbA1c are effective in monitoring Indications For Use: long-term glucose control in individuals with diabetes mellitus. Measurement of percent HbA2 and HbF are used for evaluation ß - thalassemia, a hereditary hemolytic anemia. Detection of hemoglobin variants such as S, C, D and E are effective in presumptive identification.
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)
Ann Chopper
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
Page 1 of ____________________________________________________________________________________________________________________________________________________________________
3 . Koloodol
§ 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).