(13 days)
The Bio-Rad VARIANT II TURBO 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 Bio-Rad VARIANT II TURBO Hemoglobin A1c Program is intended for Professional Use Only. For In Vitro Diagnostic Use.
Measurement of percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.
The VARIANT II TURBO Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II TURBO Hemoglobin A1c Program is based on chromatographic separation of Hemoglobin A1c on a cation exchange cartridge.
Acceptance Criteria and Device Performance Study for Bio-Rad VARIANT™ II TURBO Hemoglobin A1c Program
The Bio-Rad VARIANT™ II TURBO Hemoglobin A1c Program achieved substantial equivalence to its predicate device, the VARIANTTM II Hemoglobin A1c Program, based on testing evaluating accuracy, precision, and linearity, and comparison of interfering substances. The study provided data supporting these aspects.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific thresholds for accuracy, precision, or linearity that the new device must meet. Instead, the study's aim was to demonstrate "substantial equivalence" to the predicate device. Therefore, the "acceptance criteria" are implicitly derived from the performance of the predicate device. The "reported device performance" refers to that of the VARIANT™ II TURBO.
| Performance Metric | Acceptance Criteria (Implied from Predicate Performance) | Reported Device Performance (VARIANT™ II TURBO) |
|---|---|---|
| Accuracy (Method Correlation) | Linear Regression (vs. Predicate): Expect a strong linear relationship (similar slope, intercept, and correlation coefficient). | Slope: 1.006 Intercept: -0.016% Correlation Coefficient (r^2): 0.9997 Range of samples: 3.9% to 17.5% HbA1c |
| Precision | Within Run CV: Similar to predicate device. Total Precision CV: Similar to predicate device. | Low Patient (HbA1c ~6.2%): Within run CV: 0.82%, Total Precision: 1.94% CV High Patient (HbA1c ~12.5%): Within run CV: 0.54%, Total Precision: 2.58% CV (For comparison, Predicate Low Patient (HbA1c ~5.4%): Within run CV: 1.46%, Total Precision: 2.14% CV; Predicate High Patient (HbA1c ~13.7%): Within run CV: 0.65%, Total Precision: 1.68% CV) |
| Linearity | % Recovery: Similar to predicate device, maintaining recovery within acceptable limits across the assay range. | % Recovery: Ranged from 96.8% to 100% across theoretical HbA1c values from 3.8% to 17.3%. Linear range as stated in Instruction for Use: 4.1 to 16.8% HbA1c. |
| Interfering Substances | Bilirubin: No interference up to 20 mg/dL. Lipids (Triglycerides): No interference up to 6000 mg/dL. EDTA: No interference up to 11X EDTA. | Bilirubin: No interference up to 20 mg/dL Lipids (Triglycerides): No interference up to 5680 mg/dL EDTA: No interference up to 11X EDTA |
2. Sample Size for Test Set and Data Provenance
- Accuracy (Method Correlation): 201 EDTA whole blood patient samples.
- Precision: 80 samples for the low patient HbA1c control and 80 samples for the high patient HbA1c control for each device (VARIANT II TURBO and VARIANT II). The wording "patient samples" suggests these were human whole blood samples.
- Linearity: Eight EDTA-based blood standards (n=2 for each standard) were used for comparison with the predicate. A separate study for the VARIANT II TURBO's stated linear range used seven standards (n=2 for each standard).
The data provenance is not explicitly stated in terms of country of origin. The samples were "EDTA whole blood patient samples" and "EDTA-based blood standards," implying they were clinical samples or derived from human blood. The studies appear to be prospective, specifically designed to compare the new device to the predicate.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This device is an in-vitro diagnostic (IVD) assay, not an AI/imaging device requiring expert interpretation for ground truth. The "ground truth" for this type of device is the measured value from the predicate device (VARIANT II Hemoglobin A1c Program) and, by extension, the established reference methods to which the predicate device is standardized (DCCT reference method, IFCC, and NGSP certification). No human experts were used to establish ground truth for individual test cases in the context of interpretation.
4. Adjudication Method for the Test Set
Not applicable. As an IVD assay measuring an analyte, there is no human adjudication process involved in confirming the output of the device. The comparison is quantitative between the new device and the predicate device's measurements.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is relevant for imaging or diagnostic interpretation tasks where human readers' performance is being evaluated, often with and without AI assistance. This document describes an IVD assay, not an AI-powered diagnostic interpretation tool.
6. Standalone (Algorithm Only) Performance
Yes, the studies evaluate the standalone performance of the VARIANT™ II TURBO Hemoglobin A1c Program by directly comparing its measurements to those of the predicate device (VARIANT™ II Hemoglobin A1c Program). The device itself is an automated HPLC system that provides a direct measurement, and its performance is assessed independently of human intervention during the measurement process, although it is intended for "Professional Use Only."
7. Type of Ground Truth Used
The ground truth used for comparisons was the measured values from the predicate device (VARIANT™ II Hemoglobin A1c Program). Both the predicate and the new device are standardized to recognized reference methods:
- Traceable to the Diabetes Control and Complications Trial (DCCT) reference method.
- Traceable to IFCC (International Federation of Clinical Chemistry and Laboratory Medicine).
- Certified via the National Glycohemoglobin Standardization Program (NGSP).
Therefore, the ground truth is based on a combination of established reference methods and direct comparison to a legally marketed equivalent device.
8. Sample Size for the Training Set
This document does not describe a machine learning or AI-based device that would typically have a "training set." The VARIANT™ II TURBO Hemoglobin A1c Program is an HPLC system. Therefore, the concept of a "training set" in the context of AI is not applicable here. The device's operational parameters and calibration would be established through internal development and validation, but not through an external "training set" of data in the AI sense.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the AI sense for this HPLC device.
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APR 1 5 2004
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.
40 The assigned 510(k) number is:
| Submitter: | Bio-Rad Laboratories, Inc.Clinical Diagnostics Group4000 Alfred Nobel Drive,Hercules, California 94547Phone: (510) 741-5309FAX: (510) 741-6471 |
|---|---|
| Contact Person: | Jackie BuckleyRegulatory Affairs Representative |
| Date of Summary Preparation: | January 26, 2004 |
| Device Name: | VARIANT™ II TURBO Hemoglobin A1c Program |
| Classification Name: | Assay, Glycosylated Hemoglobin, 81LCP |
| Predicate Device: | VARIANTTM II Hemoglobin A1c ProgramK984268Bio-Rad Laboratories, Inc. |
| Intended Use: | The Bio-Rad VARIANT II TURBO HemoglobinA1c Program is intended for the percentdetermination of hemoglobin A1c in human wholeblood using ion-exchange high performance liquidchromatography (HPLC).The Bio-Rad VARIANT II TURBO HemoglobinA1c Program is intended for Professional Use Only.For In Vitro Diagnostic Use. |
| Indications for Use: | Measurement of percent hemoglobin A1c is effectivein monitoring long-term glucose control inindividuals with diabetes mellitus. |
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Description of theDevice:
The VARIANT II TURBO Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II TURBO Hemoglobin A1c Program is based on chromatographic separation of Hemoglobin A1c on a cation exchange cartridge.
Technical Characteristics Compared to the Predicate:
VARIANT II TURBO Hemoglobin A1c and VARIANT II Hemoglobin A1c programs have the same technical characteristics that are summarized in the table below:
| Characteristics | VARIANT II TURBOHemoglobin A1c | VARIANT II Hemoglobin A1c |
|---|---|---|
| Analyte Measured: Reported | %Hemoglobin A1c | %Hemoglobin A1c |
| Intended Use | The Bio-Rad VARIANT II TURBOHemoglobin A1c Program isintended for the percentdetermination of hemoglobin A1c inhuman whole blood using ion-exchange high performance liquidchromatography (HPLC). The Bio-Rad VARIANT II TURBOHemoglobin A1c Program isintended for Professional Use Only.For In Vitro Diagnostic Use. | The Bio-Rad VARIANT IIHemoglobin A1c Program is intendedfor the percent determination ofhemoglobin A1c in human whole bloodusing ion-exchange high performanceliquid chromatography (HPLC).For In Vitro Diagnostic Use. |
| Assay Principle | Cation exchange high performanceliquid chromatography | Cation exchange high performanceliquid chromatography |
| Sample Type | Human anticoagulated whole blood(EDTA) | Human anticoagulated whole blood(EDTA) |
| Visible Detection | 415 nm | 415 nm |
| Standardization | Traceable to the Diabetes Controland Complications Trial (DCCT)reference method and IFCC.Certified via the NationalGlycohemoglobin StandardizationProgram (NGSP). | Traceable to the Diabetes Control andComplications Trial (DCCT) referencemethod and IFCC. Certified via theNational GlycohemoglobinStandardization Program (NGSP). |
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Testing To Establish Substantial Equivalence:
Accuracy:
Method correlation between VARIANT II TURBO Hemoglobin A1c Program and VARIANT II Hemoglobin A1c Program was evaluated using 201 EDTA whole blood patient samples ranging from 3.9% to 17.5% HbAje. The results are presented in the following regression table.
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Precision:
The following table provides comparison data on the precision between VARIANT II TURBO Hemoglobin A1c and VARIANT II Hemoglobin A1c Programs, each utilizing low and high EDTA whole blood patient samples, and both tested against samples with moderate (5.4-6.2) and high (12.5-13.7) % Arc content.
Method precision was performed using a protocol based on the NCCLS Evaluation protocol, Vol.12, No. 4, EP5-A (Feb. 1999) for the VARIANT II TURBO Hemoglobin All and NCCLS Evaluation protocol, Vol.12, No. 4, EP5-T2 (Mar. 1992) for the VARIANT II Hemoglobin Aic Program. The protocols for both the VARIANT II TURBO Hemoglobin Are and VARIANT II Hemoglobin A1c Programs are similar. Using these protocols, 40 runs (2 per day) were performed on one VARIANT II TURBO (or VARIANT II) Hemoglobin Testing System over 20 working days. In each duplicate daily run, one aliquot of low HbA1c and one aliquot of high HbA1c patient samples were cach analyzed per run. Although the precision samples are different, since they were run at different time periods, the precision results between the VARIANT II TURBO Hemoglobin Are and the VARIANT II Hemoglobin Aie Program are equivalent. A summary of combined comparative precision results is presented in the following precision table.
| VARIANT II TURBO Hemoglobin A1c | VARIANT II Hemoglobin A1c | |||
|---|---|---|---|---|
| Low Patient (HbA1c) | High Patient (HbA1c) | Low Patient (HbA1c) | High Patient (HbA1c) | |
| n= (number of samples) | 80 | 80 | 80 | |
| Mean | 6.2 | 12.5 | 5.4 | 13.7 |
| Within run | 0.82% CV | 0.54% CV | 1.46 % CV | 0.65 % CV |
| Total Precision | 1.94% CV | 2.58 % CV | 2.14 % CV | 1.68 % CV |
VARIANT II TURBO HbAlc
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Linearity:
The following table provides comparison data on the linearity and recovery analyses between VARIANT II TURBO Hemoglobin A1c and VARIANT II Hemoglobin A1c Programs, each utilizing eight EDTA-based blood standards (n=2 for each standard). The % Recovery for Hemoglobin A1e by the VARIANT II TURBO Hemoglobin A1c Program was essentially the same as the VARIANT II Hemoglobin A1c Program. The results are presented in the following linearity table.
The linear range as stated in the Instruction of Use on the VARIANT II TURBO Hemoglobin AJc Program is 4.1 to 16.8% HbAJe which was performed on a separate study, each using a total of seven standards (n=2 for each standard) below, at, and substantially above blood levels of typical normal levels of Hemoglobin A16 and found in normal and diabetic patients.
| % Contribution | VARIANT II TURBO Hemoglobin A1c | VARIANT II Hemoglobin A1c | |||||
|---|---|---|---|---|---|---|---|
| Normal | Diabetic | Theoretical % HbA1c | Observed % HbA1c | % Recovery | Theoretical % HbA1c | Observed % HbA1c | % Recovery |
| 100 | 0 | 3.8 | 3.8 | 100 | 3.5 | 3.5 | 100 |
| 90 | 10 | 5.0 | 5.0 | 100 | 4.7 | 4.7 | 100 |
| 80 | 20 | 6.3 | 6.1 | 96.8 | 5.9 | 5.8 | 98.3 |
| 67 | 33 | 8.0 | 7.9 | 98.8 | 7.6 | 7.4 | 97.4 |
| 50 | 50 | 10.2 | 10.0 | 97.9 | 9.8 | 9.6 | 98.0 |
| 33 | 67 | 12.5 | 12.4 | 98.0 | 12.1 | 11.9 | 98.3 |
| 20 | 80 | 14.4 | 14.3 | 99.3 | 14.1 | 13.8 | 97.9 |
| 0 | 100 | 17.3 | 17.3 | 100 | 17.2 | 17.2 | 100 |
VARIANT II TURBO Hemoglobin A12 and VARIANT II Hemoglobin A1c Lincarity
Interfering Substances:
| Interfering Substance | VARIANT II TURBOHemoglobin A1c | VARIANT II Hemoglobin A1c |
|---|---|---|
| Bilirubin | No interference up to 20 mg/dL | No interference up to 20 mg/dL |
| Lipids(Triglycerides) | No interference up to 5680mg/dL | No interference up to 6000mg/dL |
| EDTA | No interference up to 11X EDTA | No interference up to 11X EDTA |
Conclusion:
When considering the similarities of the intended use, the general characteristics of the two assays, the use of the same technology and the similar correlation, accuracy and linearity between the two methods, it can be concluded that the VARIANT II TURBO Hemoglobin A1c Program is substantially equivalent to the cleared and currently marketed predicate, VARIANT II Hemoglobin Alc Program.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle-like symbol with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the symbol.
APR 1 5 2004
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Bio-Rad Laboratories, Inc. c/o Mr. Alfredo J. Quattrone California Department of Health Services Food & Drug Branch 1500 Capitol Avenue Mailstop 7602 Sacramento, CA 95814
K040872 Re:
Trade/Device Name: VARIANT™ II TURBO Hemoglobin A1c Program Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP Dated: March 31, 2004 Reccived: April 2, 2004
Dear Mr. Quattrone:
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 markcted 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 (sec 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 adviscd that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. 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/dsma/dsmamain.html.
Sincerely yours,
Seain M. Cooper, MS, DVM.
Jean M. Cooper, MS, 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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Statement of Indications for Use
| 510(k) Number: | K040872 |
|---|---|
| Device Name: | VARIANT TM II TURBO Hemoglobin A 1c Program |
| Indications for Use: | The Bio-Rad VARIANT II TURBO Hemoglobin A 1c Program is intended for the percent determination of hemoglobin A 1c in human whole blood using ion-exchange high-performance liquid chromatography (HPLC).The Bio-Rad VARIANT II TURBO Hemoglobin A 1c Program is intended for Professional Use Only. For In Vitro Diagnostic Use.Measurement of percent hemoglobin A 1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus. |
| Prescriptive Use(Per 21 CFR 801.109) | OR Over-The-counter Use |
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED Concurrence of CDRH, Office of Device Evaluation (ODE)
Carol C. Benson
Division Sign-Off
Office of in Vitro Diagnostic
Device Evaluation and Safety
510(k) K040872
VARIANT II TURBO HbAIc Confidential
Date Revised 2/26/04
§ 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).