(132 days)
The Bio-Rad VARIANT™ II TURBO HbA1c Kit -2.0 is intended for the percent determination of hemoglobin A1c in human whole blood using ion-exchange high-performance liquid chromatography (HPLC). Bio-Rad VARIANT™ II TURBO HbA1c kit is intended for Professional Use Only.
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 HbA1c kit -2.0 is based on chromatographic separation of Hemoglobin A1c on a cation exchange cartridge.
The Bio-Rad VARIANT™ II TURBO HbA1c Kit - 2.0 is substantially equivalent to the predicate device, VARIANT™ II Hemoglobin A1c Program (k)070452. The study demonstrating this equivalence focused on accuracy, precision, linearity, and interfering substances.
1. Table of Acceptance Criteria and Reported Device Performance:
The document implicitly compares the new device's performance against its predicate and generally acceptable analytical performance for HbA1c testing. Explicit "acceptance criteria" are not given as numerical targets, but rather the performance is compared to the predicate device to establish "substantial equivalence." The reported performance of the new device is considered equivalent or better than the predicate for these metrics.
| Performance Metric | VARIANT II TURBO HbA1c Kit - 2.0 Reported Performance | Predicate Device (VARIANT II Hemoglobin A1c Program) Performance | Acceptance Criteria (Implied: Substantial Equivalence to Predicate) |
|---|---|---|---|
| Accuracy (Method Correlation) | |||
| Range of values tested | 2.6% to 19.0% HbA1c | 2.6% to 19.0% HbA1c (same samples used for comparison) | Performance comparable to predicate device across this range |
| Regression Table | Not explicitly provided, but results used for "correlation" for substantial equivalence. | See above | Not explicitly provided, but considered acceptable if correlation is strong. |
| Precision | |||
| Low Patient (HbA1c) n=240 | Mean: 5.6%, Within run (%CV): 0.78%, Within Device Precision (%CV): 1.15% | Mean: 5.5%, Within run (%CV): 0.9%, Within Device Precision (%CV): 1.60% | Equivalent precision to the predicate device. |
| High Patient (HbA1c) n=240/160 (new/predicate) | Mean: 11.4%, Within run (%CV): 0.39%, Within Device Precision (%CV): 0.91% | Mean: 8.8%, Within run (%CV): 0.6%, Within Device Precision (%CV): 1.38% | Equivalent precision to the predicate device. |
| Linearity | |||
| Linear Range | 3.5 – 19.0 % HbA1c | 3.1 – 18.5 % HbA1c | Comparable or expanded linear range to the predicate device. |
| Interfering Substances | |||
| Bilirubin | No interference up to 20 mg/dL | No interference up to 20 mg/dL | No significant interference up to tested levels. |
| Lipids (Triglycerides) | No interference up to 6000 mg/dL | No interference up to 6000 mg/dL | No significant interference up to tested levels. |
| EDTA | No interference up to 11X EDTA | No interference up to 11X EDTA | No significant interference up to tested levels. |
| Hemoglobin F | 25% (new device) | 15% (predicate device) | Acceptable performance for common interferents. Note: The new device has a higher tolerance for HbF. |
| HbS, HbC, HbE, HbD trait samples on %A1c | Demonstrated some differences (>±10%) from boronate affinity method in a subset of samples (e.g., 2/7 for HbAD-trait, 2/11 for HbAS-trait, 1/12 for HbAE-trait, 3/9 for HbAC-trait). | No interference (predicate) | Acceptable performance, with identified limitations for certain hemoglobin variants as disclosed. |
2. Sample size used for the test set and the data provenance:
- Accuracy (Method Correlation): 40 EDTA whole blood patient samples and 12 samples prepared by mixing EDTA whole blood patient samples with Lyphochek® Hemoglobin A1c Linearity Set samples. Total = 52 samples.
- Precision:
- VARIANT II TURBO HbA1c Kit - 2.0: 240 samples for "Low Patient (HbA1c)" and 240 samples for "High Patient (HbA1c)". (These numbers seem to refer to the total number of measurements, not unique patient samples. The text states "low and high EDTA whole blood patient samples", implying at least two unique patient samples were used, each tested multiple times across devices and days.)
- VARIANT II Hemoglobin A1c Program: 240 samples for "Low Patient (HbA1c)" and 160 samples for "High Patient (HbA1c)".
- Data Provenance: Not explicitly stated, but given the manufacturer's location (Bio-Rad Laboratories, California), it is reasonable to infer the data is from the US. The samples were "EDTA whole blood patient samples" and "Lyphochek® Hemoglobin A1c Linearity Set samples." The study is prospective for testing the new device.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
Not applicable. This device is an in vitro diagnostic (IVD) for quantitative measurement of HbA1c. The "ground truth" for the test set is established by the reference method (the predicate device) or by other analytical methods like boronate affinity for interference studies, not by clinical expert consensus.
4. Adjudication method for the test set:
Not applicable. As an IVD, adjudication by clinical experts is not relevant for technical performance studies. The comparison is against a reference method or predetermined analytical specifications.
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 an in vitro diagnostic device, not an imaging or AI reader device. There are no "human readers" in the context of this study that would be assisted by AI.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the studies described are standalone performance evaluations of the device (VARIANT II TURBO HbA1c Kit - 2.0) against its predicate and other analytical standards. The device is an automated HPLC system; thus, its performance is inherently "standalone" in this context.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth or reference for comparison were:
- Accuracy: The predicate device, VARIANT II Hemoglobin A1c Program (270-2101NU), considered a legally marketed and established method.
- Precision: Internal replicates and measurements across multiple devices and days.
- Linearity: Presumably, known concentrations of HbA1c (e.g., from linearity sets or spiked samples).
- Interfering Substances: For the interference studies with hemoglobin variants (HbS, HbC, HbE, HbD), a boronate affinity reference method was used as the "ground truth" for comparison.
8. The sample size for the training set:
Not applicable. This device is not an AI/ML algorithm that requires a "training set." It is a chemical-based analysis system (HPLC).
9. How the ground truth for the training set was established:
Not applicable, as there is no training set for this type of device.
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JUL 2,7 2009
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:_ < 090699
| Submitter: | Bio-Rad LaboratoriesClinical Diagnostics Group4000 Alfred Nobel Drive,Hercules, California 94547Phone: (510) 741-5309FAX: (510) 741-3954 | |
|---|---|---|
| Contact Person: | Jackie BuckleyRegulatory Affairs Representative III | |
| Date of Summary Preparation: | March 12, 2009 | |
| Device Name: | VARIANT™ II TURBO HbA1c Kit - 2.0(Catalog number 270-2455) | |
| Classification Name: | Assay, Glycosylated Hemoglobin, LCP | |
| Predicate Device: | VARIANT™ II Hemoglobin A1c Program(k)070452Bio-Rad Laboratories(Catalog number 270-2101NU) | |
| Intended Use: | The Bio-Rad VARIANT II TURBO HbA1c Kit -2.0 is intended for the percent determination ofhemoglobin Alc in human whole blood using ion-exchange high performance liquid chromatography(HPLC). | |
| The Bio-Rad VARIANT II TURBO HbAlc Kit -2.0 is intended for Professional Use Only. | ||
| Indications for Use: | Measurement of percent hemoglobin A1c iseffective in monitoring long-term glucose control inindividuals with diabetes mellitus. |
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Description of the Device:
The VARIANT II TURBO Hemoglobin-Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II TURBO HbA1c kit -2.0 is based on chromatographic separation of Hemoglobin A1c on a cation exchange cartridge.
Technical Characteristics Compared to the Predicate:
The new VARIANT II TURBO HbA1c Kit – 2.0 (270-2455) and the predicate VARIANT II Hemoglobin A1c Program (270-2101NU) have the same technical characteristics that are summarized in the table below:
| Characteristics | VARIANT II TURBO HbA1c - 2.0(270-2455) | VARIANT II Hemoglobin A1c(270-2101NU) (k)070452 |
|---|---|---|
| Analyte Measured: Reported | %Hemoglobin A1c | %Hemoglobin A1c |
| Intended Use | The Bio-Rad VARIANT II TURBO HbA1cKit - 2.0 is intended for the percentdetermination of hemoglobin A1c in humanwhole blood using ion-exchange highperformance liquid chromatography (HPLC).The Bio-Rad VARIANT II TURBO HbA1cKit - 2.0 is intended for Professional UseOnly. | The Bio-Rad VARIANT II Hemoglobin A1cProgram is intended for the percent determinationof hemoglobin A1c in human whole blood usingion-exchange high performance liquidchromatography (HPLC).The Bio-Rad VARIANT Hemoglobin A1cProgram is intended for Professional Use Only. |
| 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 |
| Total Area Range | 1.0 - 3.5 million μvolt•second | 1.5 - 4.5 million μvolt•second |
| Calibration Frequency | After installation of the analyticalcartridge | After installation of the analytical cartridge andonce every 30 days |
| Kit size | 2500 tests | 1000 test |
| Cartridges Included in Kit | 1 Cartridge (2500 tests) | 1 Cartridge (1000 tests) |
| Buffer A and Buffer B formulation | Sodium Perchlorate Buffer | Tris-Bis Buffer |
| Standardization | Traceable to the Diabetes Control andComplications Trial (DCCT) referencemethod and IFCC. Certified via the NationalGlycohemoglobin Standardization Program(NGSP). | Traceable to the Diabetes Control andComplications Trial (DCCT) reference methodand IFCC. Certified via the NationalGlycohemoglobin Standardization Program(NGSP). |
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Testing To Establish Substantial Equivalence:
Accuracy:
Method correlation between the VARIANT II TURBO HbA1c Kit - 2.0 (270-2455) and VARIANT II Hemoglobin A1c Program (270-2101NU) was compared using 40 EDTA whole blood patient samples and 12 samples prepared by mixing EDTA whole blood patient samples with Lyphochek® Hemoglobin A1c Linearity Set samples in various ratios. The range of values on the VARIANT II TURBO HbA1c Kit -2.0 was from 2.6% to 19.0% HbA1c. The results are presented in the following regression table.
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|---|---|---|---|---|
Precision:
The following table provides comparison data on the precision between the VARIANT II TURBO HoA1c Kit - 2.0 (270-2455) and VARIANT II Hemoglobin A1c (270-2101NU) Programs, each utilizing low and high EDTA whole blood patient samples, and both tested against samples with moderate (5.5/5.6) and high (8.8/11.4) % A1c content.
Method precision was performed using a protocol based on the NCCLS Evaluation protocol, Vol.24, No. 25, EP5-A2 for the VARIANT II TURBO HbA Ic Kit - 2.0 and the VARIANT II Hemoglobin A1c (270-2101NU). The protocols for both the VARIANT II TURBO HbA1c Kit -- 2.0 and the VARIANT II Hemoglobin A1c Programs are similar.
For the VARIANT II TURBO HbA1c Kit - 2.0 and the VARIANT II Hemoglobin A1c Program protocol, six VARIANT II TURBO and six VARIANT II Hemoglobin Testing Systems at three Bio-Rad sites were utilized. Each site was provided with the same sample set and performed two replicates of each sample on each of 2 runs per day for 10 davs.
Although the precision samples are different, since they were run at different time periods, the precision results between the VARIANT II TURBO Hemoglobin A1c (270-2255) and the current VARIANT II Hemoglobin A1c Program (270-2101NU) are equivalent. A summary of combined comparative precision results is presented in the following precision table.
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VARIANT II TURBO HbA1c Kit - 2.0 (270-2455) and VARIANT II Hemoglobin A1c (270-2101NU) Precision
| VARIANT II TURBO HbA1c Kit - 2.0(270-2455) | VARIANT II Hemoglobin A1c(270-2101NU) | |||
|---|---|---|---|---|
| Low Patient (HbA1c) | High Patient (HbA1c) | Low Patient (HbA1c) | High Patient (HbA1c) | |
| n= (number of samples) | 240 | 240 | 240 | 160 |
| Mean | 5.6 | 11.4 | 5.5 | 8.8 |
| Within run (%CV) | 0.78 | 0.39 | 0.9 | 0.6 |
| Within Device Precision (%CV) | 1.15 | 0.91 | 1.60 | 1.38 |
Linearity:
| VARIANT II TURBO HbA1c Kit –2.0 (210-2455) | VARIANT II Hemoglobin A1cProgram (210-2101NU) | |
|---|---|---|
| Linear Range | 3.5 – 19.0 % HbA1c | 3.1 – 18.5 % HbA1c |
Interfering Substances:
| Interfering Substance | VARIANT II TURBO HbA1cKit-2.0 (270-2455) | VARIANT II Hemoglobin A1c(270-2101NU) |
|---|---|---|
| Bilirubin | No interference up to 20 mg/dL | No interference up to 20 mg/dL |
| Lipids(Triglycerides) | No interference up to 6000mg/dL | No interference up to 6000mg/dL |
| EDTA | No interference up to 11X EDTA | No interference up to 11X EDTA |
| Hemoglobin F | 25% | 15% |
| Interference from HbS, HbC,HbE, HbD trait samples on %A1c | Two out of 7 hemoglobin AD-trait, 2 out of 11 hemoglobin AS-trait, 1 out of 12 hemoglobin AE-trait, and 3 out of 9 hemoglobinAC-trait patient samples at theclinically significant levels of 6%and 9% HbA1c exhibiteddifferences of more than ±10%from values obtained usingboronate affinity referencemethod | No interference |
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 HbA1c Kit - 2.0 (270-2455) is substantially equivalent to the cleared and currently marketed predicate, VARIANT II Hemoglobin A1c Program (270-2101NU):
Bio-Rad Laboratories, Inc. VARIANT II TURBO HbA1c Kit -2.0 Page 3 of 4
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Image /page/4/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three curved lines representing its body and wings. The eagle is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA", which is arranged in a circular fashion around the logo.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
Bio-Rad Laboratories, Inc. c/o Jackie H. Buckley 4000 Alfred Nobel Dr. Hercules, CA 94547
JUL 2 7 2009
Re: K090699
Trade/Device Name: VARIANT II TURBO HbA1c Kit-2.0 Regulation Number: 21 CFR § 864.7470 Regulation Name: Glycosylated Hemoglobin Assay Regulatory Class: Class II Product Code: LCP Dated: June 17, 2009 Received: June 18, 2009
Dear Jackie 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); medical device reporting of medical devicerelated adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
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 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney C. Harper, Ph.D. Acting 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): K090699
Device Name: VARIANT II TURBO™ HbAje Kit - 2.0
Indications For Use:
The Bio-Rad VARIANT™ II TURBO HbA1c Kit -2.0 is intended for the percent determination of hemoglobin Att in human whole blood using ion-exchange highperformance liquid chromatography (HPLC). Bio-Rad VARIANT™ II TURBO HbAic kit is intended for Professional Use Only.
Measurement of percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.
AND/OR Prescription Use × (Part 21 CFR 801 Subpart D)
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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510(k) K090699
§ 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).