(262 days)
For in vitro diagnostic use only
VITROS Chemistry Products HbA1c reagent is used on VITROS 5.1 FS Chemistry System, VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the quantitative determination of percent glycated hemoglobin Alc (DCCT/NGSP) and mmol/mol hemoglobin A1c (IFCC) in human whole blood.
The test is to be used as an aid in diabetes, as an aid in identifying patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus.
For in vitro diagnostic use only
VITROS Calibrator Kit 31 is used to calibrate the VITROS 5.1 FS Chemistry System. VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the determination of percent glycated hemoglobin (HbA1c) in human whole blood.
For in vitro diagnostic use only
VITROS Chemistry Products %A1c Performance Verifiers are assayed controls used on the VITROS 5.1 FS Chemistry System, the VITROS 4600 Chemistry System and the VITROS 5600 Integrated System to monitor performance of the VITROS d%A1c and VITROS HbA1c Reagent Kits.
The determination of % glycated hemoglobin (HbA1c) is performed using the VITROS Chemistry Products HbA1c Reagent Kit in conjunction with the VITROS Chemistry Products Calibrator Kit 31 on the VITROS 5,1 FS and VITROS 4600 Chemistry Systems and the VITROS 5600 Integrated System. The VITROS Chemistry Products HbA1c Reagents are two dual chambered packages containing ready-to-use liquid reagents. Whole blood samples are hemolyzed on the VITROS 5,1 FS and VITROS 4600 Chemistry Systems and the VITROS 5600 Integrated System. The concentration of HbA1c and total Hb are measured in the hemolyzed samples, controls and calibrators.
Hemoglobin A1c and Hemoglobin
Whole blood samples are hemolyzed on the VITROS 5,1 FS and VITROS 4600 Chemistry Systems and the VITROS 5600 Integrated System. Calibrators, controls and hemolyzed whole blood samples are mixed with Reagent 1 containing anti-HbA1c antibody to form a soluble antigen-antibody complex. Hemoglobin in the hemolyzed whole blood is converted with Reagent 1 to a hematin derivative that is measured bichromatically at 340 nm and 700 nm. Unbound anti-HbA1c antibody reacts with polyhapten (hexapeptide-glycan, A1c Reagent 2) to form an insoluble antibodypolyhapten immune complex, which is measured turbidimetrically at 340 nm. After a calibration has been performed for each reagent lot, the hemoglobin A1c and Hb concentrations in each unknown sample can be determined using the stored calibration curves and the measured absorbance obtained in the assay of the hemolyzed sample.
%A1c
% A 1c is a derived test calculated from the quantitative measurements of hemoglobin and hemoglobin A1c.
The VITROS® Chemistry Products Calibrator Kit 31 are prepared from a hemolysate derived from human and ovine blood to which surfactants, stabilizer, and preservative have been added. The calibrators are used to calibrate the VITROS 5,1 FS Chemistry System, VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the determination of percent glycated hemoglobin (HbA1c) in human whole blood.
VITROS %A1c Performance Verifiers I and II are prepared from a hemolysate derived from human and ovine blood to which surfactants, stabilizer, and preservatives have been added.
The VITROS® Chemistry Products FS Reconstitution Diluent is a common reagent that is used by multiple assays on VITROS® 5,1 FS Chemistry Systems, VITROS® 4600 Chemistry Systems, and VITROS® 5600 Integrated Systems. There are no active ingredients, the fluid is proceesed water and is supplied in a 5 mL vial for reconstitution of lyophilized materials.
The VITROS® 5,1 FS Chemistry System and VITROS 4600 Chemistry Systems are clinical chemistry instruments that provide automated use of the VITROS® Chemistry Products MicroTip® and MicroSlides® range of products. The VITROS® 5,1 FS System was cleared for market by 510(k) premarket notification (K031924). The VITROS® 4600 Chemistry System is commercialized under the FDA's Guidance for Industry and Staff: Reagent Replacement and Instrument Family Member Policy (December 11, 2003) as a family member of the VITROS 5,1 FS Chemistry System (K031924). The VITROS® 5600 Integrated Systems are clinical laboratory instruments that provide automated use of the VITROS® Chemistry Products MicroTip® and MicroSlides® range of products and VITROS® Immunodiagnostic Products MicroWells® range of products. The VITROS 5600® Integrated System was cleared for market by 510(k) premarket notification (K081543).
Here's the information about the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Stated) | Reported Device Performance | Device Met Criteria? |
|---|---|---|---|
| Accuracy (Total Error) | ≤6% Total Error | VITROS 5,1 FS Chemistry System: Range from 4.36% to 5.51% for controls and 3.99% to 5.14% for patients.VITROS 4600 Chemistry System: Range from 3.03% to 4.78% for controls and 2.95% to 4.94% for patients.VITROS 5600 Integrated System: Range from 2.79% to 3.52% for controls and 2.77% to 3.88% for patients. | Yes |
| Accuracy (Correlation) | Not explicitly stated as a numerical criterion for approval. | VITROS Chemistry Products HbA1c assay vs. secondary reference laboratory method: Correlation coefficient (r) of 0.996. VITROS Chemistry Products HbA1c assay vs. NGSP Reference (Deming Fit Equations):- VITROS 5,1 FS: -0.08 + 1.01x- VITROS 4600: -0.14 + 1.02x- VITROS 5600: -0.06 + 1.00x | Not applicable (high correlation demonstrated) |
| Precision/Reproducibility | All acceptance criteria for precision were met. (Specific numerical criteria are not detailed in the summary but were likely internally defined and met based on the statement). | Total precision (%CV) for VITROS 5,1 FS: Controls (VITROS PV1 2.03%, BBI 5% 1.83%, BBI 6.5% 2.09%, BBI 8% 2.69%, BBI 12% 2.03%). Patients (5% 2.21%, 6.5% 2.01%, 8% 1.92%, 12% 2.52%). Total precision (%CV) for VITROS 4600: Controls (VITROS PV1 1.32%, BBI 5% 1.19%, BBI 6.5% 1.62%, BBI 8% 1.43%, BBI 12% 2.01%). Patients (5% 1.10%, 6.5% 1.19%, 8% 1.66%, 12% 2.09%). Total precision (%CV) for VITROS 5600: Controls (VITROS PV1 1.18%, BBI 5% 1.41%, BBI 6.5% 1.40%, BBI 8% 1.27%, BBI 12% 1.76%). Patients (5% 1.05%, 6.5% 1.12%, 8% 1.28%, 12% 1.94%). | Yes |
| Linearity/Measuring Range | Not explicitly stated as a numerical criterion for approval. | Linear range for % A1c: 3.034-15.444% (NGSP derived test).Linear range for HbA1c: 9.6-145.3 mmol/mol (SI derived test). (Specific r^2 values are given, all are >0.997). | Yes (linearity shown) |
| Detection Limit (LoD) | Claim of 2.580% NGSP for LoQ | LoB for %A1c: 2.396% NGSP (2.67 mmol/mol SI)LoD for %A1c: 2.580% NGSP (4.68 mmol/mol SI)LoQ for %A1c: 2.580% NGSP (4.68 mmol/mol SI) | Yes |
| Analytical Specificity (Interference) | Bias ≤ 0.5% A1c (≤ 5 HbA1c (mmol/mol)) at ~6.5% A1c; Bias ≤ 0.6% A1c (≤ 7 HbA1c (mmol/mol)) at ~8.5% A1c for listed substances. Hemoglobin variants HbA0, HbA1a, HbA1b, C, D, E, S should not interfere. | Listed Substances (e.g., Acetaminophen, Bilirubin, Glucose): Found not to interfere at specified concentrations.Hemoglobin Variants: HbS up to 41%, HbC up to 38%, HbD up to 38%, HbE up to 26% of total hemoglobin do not interfere. Anti-HbA1c antibodies do not cross-react with HbA0, HbA1a, HbA1b at stated levels. HbF >7% may result in lower than expected values. | Yes (with a caveat for high HbF) |
| NGSP Certification | NGSP certification received. | NGSP certification was received for the VITROS HbA1c assay on all three noted systems. | Yes |
2. Sample Size Used for the Test Set and Data Provenance
- Accuracy (Method Comparison): 357 samples were used. The samples were distributed across the range of the assay.
- Precision/Reproducibility:
- Quality Control Materials (hemolysate and whole blood-based): 20-22 days of testing, samples per data point varied (e.g., 756 or 792 for controls for 3 lots across multiple analyzers).
- Intermediate Precision Study (whole blood patient samples): 4 days of testing, 144 samples per patient level.
- Linearity: Low and high pools were mixed to give 16 intermediate concentration pools.
- Detection Limit: 500 determinations based on 5 low-level samples.
- Analytical Specificity (Interference): Specific numbers of patient samples for Hb variants were tested (e.g., 70 for HbA1a/A1b, 22 for HbA2, 31 for HbC, 21 for HbD, 30 for HbE, 40 for HbS, 43 for HbF). The list of interfering substances does not specify sample size per substance but indicates testing was done “for each substance tested” on control and test substance pools.
- Data Provenance: The document implies the data was generated specifically for this 510(k) submission (prospective), likely from internal studies or contract research organizations. The country of origin for the data is not explicitly stated, but the submission is to the US FDA by Ortho-Clinical Diagnostics, Inc. in Rochester, New York, suggesting US-based studies unless otherwise specified. The reference method for accuracy was a "secondary reference laboratory of the NGSP," implying a credible, standardized source.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- The ground truth for the accuracy study was established using a "secondary reference laboratory of the NGSP." The number and specific qualifications of experts within this laboratory are not specified in this document. However, the NGSP (National Glycohemoglobin Standardization Program) implies adherence to a highly standardized and validated reference method for HbA1c, which inherently involves expert-level procedures and validation.
4. Adjudication Method
- For the analytical performance studies (accuracy, precision, linearity, detection limits, analytical specificity), an adjudication method is not typically described as it would be for clinical image interpretation or diagnostic performance involving human assessment. The "ground truth" is established by highly controlled and validated laboratory reference methods. The comparison is quantitative against these reference methods.
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 diagnostic imaging AI devices where human reader performance is being assessed and compared with and without AI assistance. The VITROS Chemistry Products HbA1c Reagent Kit is an in vitro diagnostic assay, not an imaging AI device with a human-in-the-loop component for interpretation.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- Yes, the performance data presented is for the standalone device (the VITROS Chemistry Products HbA1c Reagent Kit and associated systems/calibrators/verifiers) without human-in-the-loop performance being a variable. The studies assess the analytical performance of the assay itself.
7. Type of Ground Truth Used
- The ground truth used for relevant studies (e.g., accuracy) was:
- Reference Method: Traceability to the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) Reference Method, and certification by the National Glycohemoglobin Standardization Program (NGSP) which is traceable to the Diabetes Control and Complications Trial (DCCT) Reference Method. This represents a highly standardized and validated laboratory-based reference standard.
8. Sample Size for the Training Set
- This information is not provided. For an in vitro diagnostic reagent kit, there isn't typically a "training set" in the machine learning sense. The device's "training" or optimization would happen during its development phase using various experimental designs and samples, rather than a distinct, documented "training set" like in AI/ML performance studies. The document focuses on the validation or test set performance.
9. How the Ground Truth for the Training Set Was Established
- As mentioned above, a "training set" in the AI/ML context isn't directly applicable here. The development of the assay (analogous to "training") would involve extensive R&D, chemical optimization, and preliminary testing against known samples and reference methods. The ground truth for these developmental internal studies would be established using similar highly accurate and traceable laboratory reference methods.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
June 4, 2015
ORTHO CLINICAL DIAGNOSTICS BRADLEY BOYER SENIOR REGULATORY ASSOCIATE 100 INDIGO CREEK DRIVE ROCHESTER NY 14626
Re: K142595
Trade/Device Name: VITROS Chemistry Products HbA1c Reagent Kit, VITROS Chemistry Products Calibrator Kit 31, VITROS Chemistry Products %Alc Performance Verifiers I And II Regulation Number: 21 CFR 862.1373 Regulation Name: Glycosvlated hemoglobin assay Regulatory Class: II Product Code: PDJ, JIT, JJY Dated: April 27, 2015 Received: April 28, 2015
Dear Bradley Boyer:
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Katherine Serrano -S
For:
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K142595
Device Name
VITROS Chemistry Products HbA1c Reagent Kit VITROS Chemistry Products Calibrator Kit 31 VITROS Chemistry Products %A1c Performance Verifiers I and II
Indications for Use (Describe)
For in vitro diagnostic use only
VITROS Chemistry Products HbA1c reagent is used on VITROS 5.1 FS Chemistry System, VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the quantitative determination of percent glycated hemoglobin Alc (DCCT/NGSP) and mmol/mol hemoglobin A1c (IFCC) in human whole blood.
The test is to be used as an aid in diabetes, as an aid in identifying patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus.
For in vitro diagnostic use only
VITROS Calibrator Kit 31 is used to calibrate the VITROS 5.1 FS Chemistry System. VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the determination of percent glycated hemoglobin (HbA1c) in human whole blood.
For in vitro diagnostic use only
VITROS Chemistry Products %A1c Performance Verifiers are assayed controls used on the VITROS 5.1 FS Chemistry System, the VITROS 4600 Chemistry System and the VITROS 5600 Integrated System to monitor performance of the VITROS d%A1c and VITROS HbA1c Reagent Kits.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| X Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
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: K142595
1. Submitter Information and Preparation Date
| Submitter Name: | Ortho-Clinical Diagnostics, Inc. |
|---|---|
| Address: | 100 Indigo Creek Drive |
| Rochester, New York 14626-5101 | |
| Phone: | (585) 453-3421 |
| Fax: | (585) 453-3368 |
| Email: | bboyer@its.jnj.com |
| Contact Person: | Bradley P. Boyer |
| Preparation Date: | September 12, 2014. Updated June 3, 2015 |
2. Device Name
Trade or Proprietary Names:
VITROS® Chemistry Products HbA1c Reagent Kit VITROS® Chemistry Products Calibrator Kit 31 VITROS® Chemistry Products %A1c Performance Verifiers I and II
Common Names:
HbA1c assay and controls
Classification Names:
Glycosylated Hemoglobin assay (21 CFR 862.1373) Class II Calibrators (21 CFR 862.1150) Class II Quality Control material (assayed and unassayed) (21 CFR 862.1660) Class I (general controls). Since these devices (VITROS® %A1c Performance Verifiers I & II) are assayed controls, they meet the reserved criteria under Section 510(1) of the Food, Drug, and Cosmetic Act.
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Product Code PDJ, JJY, JIT
3. Predicate Devices
The VITROS® Chemistry Products HbA1c assay (defined as VITROS® Chemistry Products HbA1c Reagent Kit and VITROS® Chemistry Products Calibrator Kit 31) is substantially equivalent to the Roche Tina Quant HbA1c Dx.Gen.2 assay (K121291).
The VITROS® Chemistry Products Calibrator Kit 31 is substantially equivalent to the Roche C.f.a.s HbA1c (K052101).
The VITROS® Chemistry Products %A1c Performance Verifiers are substantially equivalent to the VITROS® Chemistry Products %A1c Performance Verifiers that were previously cleared (K041764).
4. Device Description
The determination of % glycated hemoglobin (HbA1c) is performed using the VITROS Chemistry Products HbA1c Reagent Kit in conjunction with the VITROS Chemistry Products Calibrator Kit 31 on the VITROS 5,1 FS and VITROS 4600 Chemistry Systems and the VITROS 5600 Integrated System. The VITROS Chemistry Products HbA1c Reagents are two dual chambered packages containing ready-to-use liquid reagents. Whole blood samples are hemolyzed on the VITROS 5,1 FS and VITROS 4600 Chemistry Systems and the VITROS 5600 Integrated System. The concentration of HbA1c and total Hb are measured in the hemolyzed samples, controls and calibrators.
Hemoglobin A1c and Hemoglobin
Whole blood samples are hemolyzed on the VITROS 5,1 FS and VITROS 4600 Chemistry Systems and the VITROS 5600 Integrated System. Calibrators, controls and hemolyzed whole blood samples are mixed with Reagent 1 containing anti-HbA1c antibody to form a soluble antigen-antibody complex. Hemoglobin in the hemolyzed whole blood is converted with Reagent 1 to a hematin derivative that is measured bichromatically at 340 nm and 700 nm. Unbound anti-HbA1c antibody reacts with polyhapten (hexapeptide-glycan, A1c Reagent 2) to form an insoluble antibodypolyhapten immune complex, which is measured turbidimetrically at 340 nm. After a calibration has been performed for each reagent lot, the hemoglobin A1c and Hb
{5}------------------------------------------------
concentrations in each unknown sample can be determined using the stored calibration curves and the measured absorbance obtained in the assay of the hemolyzed sample.
%A1c
% A 1c is a derived test calculated from the quantitative measurements of hemoglobin and hemoglobin A1c.
The VITROS® Chemistry Products Calibrator Kit 31 are prepared from a hemolysate derived from human and ovine blood to which surfactants, stabilizer, and preservative have been added. The calibrators are used to calibrate the VITROS 5,1 FS Chemistry System, VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the determination of percent glycated hemoglobin (HbA1c) in human whole blood.
VITROS %A1c Performance Verifiers I and II are prepared from a hemolysate derived from human and ovine blood to which surfactants, stabilizer, and preservatives have been added.
The VITROS® Chemistry Products FS Reconstitution Diluent is a common reagent that is used by multiple assays on VITROS® 5,1 FS Chemistry Systems, VITROS® 4600 Chemistry Systems, and VITROS® 5600 Integrated Systems. There are no active ingredients, the fluid is proceesed water and is supplied in a 5 mL vial for reconstitution of lyophilized materials.
The VITROS® 5,1 FS Chemistry System and VITROS 4600 Chemistry Systems are clinical chemistry instruments that provide automated use of the VITROS® Chemistry Products MicroTip® and MicroSlides® range of products. The VITROS® 5,1 FS System was cleared for market by 510(k) premarket notification (K031924). The VITROS® 4600 Chemistry System is commercialized under the FDA's Guidance for Industry and Staff: Reagent Replacement and Instrument Family Member Policy (December 11, 2003) as a family member of the VITROS 5,1 FS Chemistry System (K031924). The VITROS® 5600 Integrated Systems are clinical laboratory instruments that provide automated use of the VITROS® Chemistry Products MicroTip® and MicroSlides® range of products and VITROS® Immunodiagnostic Products MicroWells® range of products. The VITROS 5600® Integrated System was cleared for market by 510(k) premarket notification (K081543).
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5. Indications for Use VITROS® Chemistry Products HbA1c Reagent Kit:
For in vitro diagnostic use only.
VITROS Chemistry Products HbA1c reagent is used on VITROS 5,1 FS Chemistry System, VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the quantitative determination of percent glycated hemoglobin A1c (DCCT/NGSP) and mmol/mol hemoglobin A1c (IFCC) in human whole blood. The test is to be used as an aid in diagnosis of diabetes, as an aid in identifying patients who may be at risk for developing diabetes mellitus and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus.
VITROS® Chemistry Products Calibrator Kit 31:
For in vitro diagnostic use only.
VITROS Calibrator Kit 31 is used to calibrate the VITROS 5,1 FS Chemistry System, VITROS 4600 Chemistry System and the VITROS 5600 Integrated System for the determination of percent glycated hemoglobin (HbA1c) in human whole blood.
VITROS® Chemistry Products %A1c Performance Verifiers I & II:
For in vitro diagnostic use only.
VITROS Chemistry Products %A1c Performance Verifiers are assayed controls used on the VITROS 5,1 FS Chemistry System, the VITROS 4600 Chemistry System and the VITROS 5600 Integrated System to monitor performance of the VITROS d%A1c and VITROS HbA1c Reagent Kits.
6. Comparison of Technological Characteristics to Predicate Device
VITROS® Chemistry Products HbA1c Reagent and VITROS® Chemistry Products Calibrator Kit 31 (HbA1c assay) are substantially equivalent to the COBAS Integra 800 Tina Quant HbA1c Dx.Gen.2 assay (K121291) (predicate device) which was cleared by the FDA for IVD use.
The VITROS® Chemistry Products Calibrator Kit 31 is substantially equivalent to the Roche C.f.a.s HbA1c (K052101).
The VITROS® Chemistry Products %A1c Performance Verifiers I and II are substantially equivalent to the VITROS® Chemistry Products %A1c Performance
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Verifiers I and II (K041764) (predicate device) which was cleared by the FDA for IVD use.
- Similarities and differences of the assays performed using the Table 1 VITROS® Chemistry Products HbA1c assay and the COBAS Integra 800 Tina Quant HbA1c Dx.Gen.2 assay.
| DeviceCharacteristic | VITROS® HbA1c assay(New device) | COBAS Integra 800 Tina QuantHbA1c Dx.Gen.2 assay(Predicate device) |
|---|---|---|
| Intended Use | For in vitro diagnostic use only.VITROS Chemistry ProductsHbA1c reagent is used onVITROS 5,1 FS ChemistrySystem, VITROS 4600 ChemistrySystem and the VITROS 5600Integrated System for thequantitative determination ofpercent glycated hemoglobin A1c(DCCT/NGSP) and mmol/molhemoglobin A1c (IFCC) in humanwhole blood.The test is to be used as an aid indiagnosis of diabetes and as an aidin identifying patients who may beat risk for developing diabetesmellitus, and for the monitoring oflong-term blood glucose control inindividuals with diabetes mellitus. | This test is to be used as an aid indiagnosis of diabetes and as an aidin identifying patients who may beat risk for developing diabetes.The COBAS INTEGRA 800Tina-quant Hemoglobin A1cDxGen.2 assay is an in vitrodiagnostic reagent systemintended for quantitativedetermination of mmol/molhemoglobin A1c (IFCC) and %hemoglobin A1c (DCCT/NGSP)in whole blood on the RocheCOBAS INTEGRA 800 clinicalchemistry analyzer. HbA1cdeterminations are useful formonitoring of long-term bloodglucose control in individuals withdiabetes mellitus. |
| Calibration | Traceable to the IFCC(International Federation ofClinical Chemistry andLaboratory Medicine) ReferenceMethod | Same |
| Certification | This method is certified by theNational GlycohemoglobinStandardization Program (NGSP) | Same |
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| DeviceCharacteristic | VITROS® HbA1c assay(New device) | COBAS Integra 800 Tina QuantHbA1c Dx.Gen.2 assay(Predicate device) |
|---|---|---|
| Test Principle | Whole blood samples are lysed.Hemoglobin is converted to ahematin derivative that ismeasured bichromatically.HbA1c is measured byturbidimetric inhibition.%A1c is derived from thequantitative measurements ofhemoglobin and hemoglobin A1c. | Same |
| Results | The final result is expressed asmmol/mol HbA1c or %A1c(NGSP) | Same |
| Sample type | EDTA Whole Blood | Li-heparin, Na-heparin, K2-EDTA, K3-EDTA, potassiumfluoride/Na2-EDTA, NaF/sodiumEDTA and NaF/potassium oxalate |
| Measuring Range | 4-14 %A1c NGSP units20-130 HbA1c (mmol/mol) SI units | 4.3 -24.8 HbA1c% |
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- Table 2 Similarities and differences of the device characteristics between the VITROS® Chemistry Products Calibrator Kit 31 with the predicate device Roche C.f.a.s HbA1c
| DeviceCharacteristic | VITROS® HbA1c assay | COBAS Integra 800 Tina QuantHbA1c Dx.Gen.2 assay |
|---|---|---|
| Calibrator Kit 31(New device) | C.f.a.s HbA1c calibrator(Predicate device)K052101 | |
| Intended Use | For in vitro diagnostic use only.VITROS Calibrator Kit 31 is usedto calibrate the VITROS 5,1 FSChemistry System, VITROS 4600Chemistry System and theVITROS 5600 Integrated Systemfor the determination of percentglycated hemoglobin (HbA1c) inhuman whole blood. | For use in the calibration of theHemoglobin A1c assay |
| Levels | 1 level diluted automatically by thesystem to achieve 4 levels | 1 level diluted automatically bythe system |
| Traceability | Traceable to the IFCC (InternationalFederation of Clinical Chemistry andLaboratory Medicine) ReferenceMethod | same |
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- Table 3 Similarities and differences of the device characteristics between the VITROS® Chemistry Products %A1c Performance Verifiers I & II with the predicate device VITROS® Chemistry Products %A1c Performance Verifiers I & II
| DeviceCharacteristic | VITROS® %A1c PerformanceVerifiers(New Device) | VITROS® %A1c PerformanceVerifiers(Predicate Device) |
|---|---|---|
| Analytes Reported | Hb, A1c, %A1c (derived) | Same |
| Vial Volume | 1 mL when reconstituted | Same |
| Number of vials | 3 vials each level | Same |
| Intended Use | For in vitro diagnostic use only.VITROS Chemistry Products%A1c Performance Verifiers areassayed controls used on theVITROS 5,1 FS ChemistrySystem, the VITROS 4600Chemistry System and theVITROS 5600 Integrated Systemto monitor performance of theVITROS d%A1c and VITROSHbA1c Reagent Kits. | Same, except only for use with theVITROS d%A1c Reagent Kit |
| Product Type | Assayed Control | Same |
| Presentation | Lyophillized | Same |
| Number of levels | Two | Same |
| Nominal Values | PV I: Hb 14g/dL, HbA1c0.69g/dLPV II Hb 14g/dL, HbA1c1.48g/dL | Same |
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7. Performance Data:
Analytical Performance
- Method comparison with NGSP device: a.
A Method Comparison Study (Accuracy) was performed comparing the VITROS® Chemistry Products HbA1c assay with testing in a secondary reference laboratory of the NGSP. The testing followed CLSI Protocol EP912 and was performed on each of the VITROS systems.
A total of 357 samples which were within the claimed measuring range of both assays were measured in both the VITROS Chemistry Products HbA1c assay and the secondary reference laboratory assay. The samples were distributed across the range of the assay. The relationship between the two methods was as follows:
VITROS Chemistry Products HbA1c assay = 1.00 x secondary reference laboratory method-0.06 (% NGSP) with a correlation coefficient (r) of 0.996.
On all lots and on all VITROS systems the VITROS HbA1c assay has met the requirements of the National Glycohemoglobin Standardization Program and is traceable to the Diabetes Control and Complications Trial Reference Method.
Bias and % Bias versus the reference method on each VITROS System were calculated at 5.0, 6.5, 8.0 and 12% NGSP and are presented in the following tables along with the calculated %Total Error.
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Special Controls require Total Error to be ≤6%. Total error was assessed on each VITROS system.
Deming regression analysis was performed for each of the 3 analyzer types. Total Error values at the requested decision levels are shown.
| FluidType | DecisionLevel(%NGSP) | Bias(%NGSP) | % Bias | %CV | %TE* | %TE^ | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| VITROS 5,1 FS | Control | 5.0 | -0.040 | -0.798 | 1.83 | 4.39 | 4.36 | |||||||||||||||||||||
| Control | 6.5 | -0.029 | -0.447 | 2.09 | 4.54 | 4.52 | ||||||||||||||||||||||
| Control | 8.0 | -0.018 | -0.228 | 2.69 | 5.51 | 5.50 | ||||||||||||||||||||||
| Control | 12.0 | 0.011 | 0.089 | 2.03 | 4.08 | 4.08 | ||||||||||||||||||||||
| Patient | 5.0 | -0.040 | -0.798 | 2.21 | 5.14 | 5.10 | Patient | 6.5 | -0.029 | -0.447 | 2.01 | 4.39 | 4.37 | Patient | 8.0 | -0.018 | -0.228 | 1.92 | 4.00 | 3.99 | Patient | 12.0 | 0.011 | 0.089 | 2.52 | 5.03 | 5.04 | |
| Patient | 5.0 | -0.040 | -0.798 | 2.21 | 5.14 | 5.10 | ||||||||||||||||||||||
| Patient | 6.5 | -0.029 | -0.447 | 2.01 | 4.39 | 4.37 | ||||||||||||||||||||||
| Patient | 8.0 | -0.018 | -0.228 | 1.92 | 4.00 | 3.99 | ||||||||||||||||||||||
| Patient | 12.0 | 0.011 | 0.089 | 2.52 | 5.03 | 5.04 |
VITROS 5,1 FS Chemistry System – Deming
TE = |Bias| + 1.96SD
^%TE = |%Bias| + 1.96*%CV*(1+%Bias)
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VITROS 4600 Chemistry System - Deming
| FluidType | DecisionLevel(%NGSP) | Bias(%NGSP) | % Bias | %CV | %TE* | %TE^ | |
|---|---|---|---|---|---|---|---|
| VITROS 4600 | Control | 5.0 | -0.040 | -0.805 | 1.19 | 3.14 | 3.13 |
| Control | 6.5 | -0.011 | -0.164 | 1.62 | 3.34 | 3.34 | |
| Control | 8.0 | 0.019 | 0.236 | 1.43 | 3.03 | 3.04 | |
| Control | 12.0 | 0.098 | 0.814 | 2.01 | 4.75 | 4.78 | |
| Patient | 5.0 | -0.040 | -0.805 | 1.10 | 2.97 | 2.95 | |
| Patient | 6.5 | -0.011 | -0.164 | 1.19 | 2.50 | 2.49 | |
| Patient | 8.0 | 0.019 | 0.236 | 1.66 | 3.50 | 3.50 | |
| Patient | 12.0 | 0.098 | 0.814 | 2.09 | 4.91 | 4.94 |
TE = |Bias| + 1.96SD
^%TE = |%Bias| + 1.96*%CV*(1+%Bias)
VITROS 5600 Integrated System – Deming
| FluidType | DecisionLevel(%NGSP) | Bias(%NGSP) | % Bias | %CV | %TE* | %TE^ | |
|---|---|---|---|---|---|---|---|
| VITROS 5600 | Control | 5.0 | -0.036 | -0.723 | 1.41 | 3.48 | 3.46 |
| Control | 6.5 | -0.030 | -0.467 | 1.40 | 3.21 | 3.19 | |
| Control | 8.0 | -0.024 | -0.306 | 1.27 | 2.80 | 2.79 | |
| Control | 12.0 | -0.009 | -0.075 | 1.76 | 3.52 | 3.52 | |
| Patient | 5.0 | -0.036 | -0.723 | 1.05 | 2.79 | 2.77 | |
| Patient | 6.5 | -0.030 | -0.467 | 1.12 | 2.66 | 2.65 | |
| Patient | 8.0 | -0.024 | -0.306 | 1.28 | 2.81 | 2.80 | |
| Patient | 12.0 | -0.009 | -0.075 | 1.94 | 3.88 | 3.88 |
TE = |Bias| + 1.96SD
^%TE = |%Bias| + 1.96*%CV*(1+%Bias)
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Summary statistics of the Accuracy study are provided.
Summary of Accuracy Study Results
| NGSP Units | HbA1c Sl Units (mmol/mol) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n | Slope | 95% Clof Slope | CorrelationCoefficient | Range ofSampleConc. | Intercept | 95% Cl ofIntercept | Sy.x | Range ofSampleConc. | Intercept | 95% Cl ofIntercept | Sy.x | |
| 5600 vs.comparativemethod | 357 | 1.00 | 0.99 -1.02 | 0.996 | 4.2 - 13.4 | -0.06 | -0.13 - 0.02 | 0.18 | 22 - 123 | -0.4 | -0.9 - 0.2 | 1.9 |
| 4600 vs.comparativemethod | 357 | 1.02 | 1.01 -1.03 | 0.995 | 4.2 - 13.4 | -0.14 | -0.22 - (-0.06) | 0.19 | 22 - 123 | -0.9 | -1.5 - (-0.3) | 2.1 |
| 5,1 FS vs.comparativemethod | 357 | 1.01 | 0.99 -1.02 | 0.996 | 4.2 - 13.4 | -0.08 | -0.16 - 0.01 | 0.18 | 22 - 123 | -0.5 | -1.1 - 0.1 | 1.9 |
| 4600 vs. 5600 | 125 | 1.00 | 0.99 -1.01 | 0.998 | 4.3 - 13.1 | -0.01 | -0.09 - 0.06 | 0.10 | 23 - 120 | -0.1 | -0.7 - 0.4 | 1.1 |
| 5,1 FS vs.5600 | 126 | 0.99 | 0.97 -1.00 | 0.998 | 4.3 - 13.8 | 0.01 | -0.09 - 0.12 | 0.12 | 23 - 127 | -0.2 | -1.0 - 0.6 | 1.3 |
*Secondary Reference Laboratory of the NGSP
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Analysis was performed by Deming Regression and Passing-Bablok for each analyzer type. Plots of the Deming regression are shown for each analyzer type and a Summary table is provided below.
Image /page/15/Figure/1 description: The image is a scatter plot titled "Scatter Plot with Deming Fit". The x-axis is labeled "Hemoglobin A1c (%A1c) - NGSP Reference", and the y-axis is labeled "Hemoglobin A1c (%A1c) - VITROS 5,1 FS". The plot shows a strong positive correlation between the two hemoglobin A1c measurements. A Deming fit line is plotted with the equation (-0.08 + 1.01x), along with an identity line.
Scatter Plot for the Deming regression on the VITROS 5,1 FS for the combined data
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Image /page/16/Figure/0 description: This image is a scatter plot titled "Scatter Plot with Deming Fit". The x-axis is labeled "Hemoglobin A1c (%A1c) - NGSP Reference", and the y-axis is labeled "Hemoglobin A1c (%A1c) - VITROS 4600". The plot shows a strong positive correlation between the two hemoglobin measurements. A Deming fit line is plotted with the equation (-0.14 + 1.02x), along with an identity line.
Scatter Plot for the Deming regression on the VITROS 4600 for the combined data
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Image /page/17/Figure/0 description: The image is a scatter plot with a Deming fit. The x-axis is labeled 'Hemoglobin A1c (%A1c) - NGSP Reference' and ranges from 4 to 14. The y-axis is labeled 'Hemoglobin A1c (%A1c) - VITROS 5600' and ranges from 4 to 14. The plot shows a strong positive correlation between the two variables, with data points clustered tightly around the Deming fit line, which is represented by the equation (-0.06 + 1.00x).
Scatter Plot for the Deming regression on the VITROS 5600 for the combined data
| Regression Summary Table Statistics for the combined data for each analyzer family | |||
|---|---|---|---|
| Analyzer | Regression | Slope | 95% CI | Intercept | 95% CI |
|---|---|---|---|---|---|
| 5,1 FS | Passing-Bablok | 0.998 | 0.991 to 1.006 | -0.019 | -0.072 to 0.031 |
| Deming | 1.007 | 0.995 to 1.02 | -0.076 | -0.16 to 0.008 | |
| 4600 | Passing-Bablok | 1.012 | 1.004 to 1.02 | -0.079 | -0.133 to -0.025 |
| Deming | 1.020 | 1.007 to 1.032 | -0.139 | -0.222 to -0.056 | |
| 5600 | Passing-Bablok | 1.004 | 0.996 to 1.011 | -0.056 | -0.107 to -0.005 |
| Deming | 1.004 | 0.992 to 1.015 | -0.056 | -0.132 to 0.021 |
VITROS Chemistry Products HbA1c assay and controls
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b. Precision/Reproducibility:
The precision of the VITROS® Chemistry Products HbA1c assay was evaluated on the VITROS 5,1 FS Chemistry System, VITROS 4600 Chemistry System and VITROS 5600 Integrated System following CLSI EP05-A233. The evaluation was conducted on three of each VITROS systems. Three reagent lots were evaluated on each analyzer system. Data were analyzed by Analysis of Variance (ANOVA). Test samples were targeted at 5.0, 6.5, 8.0, and 12.0 % A1c. Precision was evaluated with quality control materials (hemolysate and whole blood-based) for 20-days. An intermediate precision study using whole blood patient samples spanned 4-days. All acceptance criteria for precision were met.
Within Lab precision (Total) was determined using a three lots of reagents on each platform, using a single calibration per lot. Data is shown in both NGSP units. Results are summarized in the following tables.
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| Single Cal | Repeatability | Between Run | Between Day | Between Lot | BetweenAnalyzer | Total | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fluid | Days | N | Ave | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| VITROS PV1 | 21 | 756 | 5.65 | 0.033 | 0.58% | 0.037 | 0.65% | 0.039 | 0.69% | 0.045 | 0.80% | 0.085 | 1.50% | 0.115 | 2.03% |
| 5% BBI Control | 22 | 792 | 4.96 | 0.026 | 0.52% | 0.032 | 0.64% | 0.029 | 0.58% | 0.043 | 0.87% | 0.063 | 1.27% | 0.091 | 1.83% |
| 6.5% BBI Control | 21 | 756 | 6.38 | 0.048 | 0.75% | 0.052 | 0.82% | 0.050 | 0.78% | 0.057 | 0.89% | 0.084 | 1.32% | 0.133 | 2.09% |
| 8% BBI Control | 22 | 792 | 8.17 | 0.065 | 0.80% | 0.041 | 0.50% | 0.065 | 0.80% | 0.081 | 0.99% | 0.178 | 2.18% | 0.220 | 2.69% |
| 12% BBI Control | 20 | 720 | 11.85 | 0.147 | 1.24% | 0.092 | 0.78% | 0.119 | 1.00% | 0.102 | 0.86% | 0.058 | 0.49% | 0.241 | 2.03% |
| 5% Patient | 4 | 144 | 5.02 | 0.023 | 0.46% | 0.031 | 0.62% | 0.032 | 0.64% | 0.033 | 0.66% | 0.094 | 1.87% | 0.111 | 2.21% |
| 6.5% Patient | 4 | 144 | 6.51 | 0.038 | 0.58% | 0.038 | 0.58% | 0.042 | 0.64% | 0.053 | 0.81% | 0.099 | 1.52% | 0.131 | 2.01% |
| 8% Patient | 4 | 144 | 8.16 | 0.054 | 0.66% | 0.071 | 0.87% | 0.031 | 0.38% | 0.064 | 0.78% | 0.107 | 1.31% | 0.157 | 1.92% |
| 12% Patient | 4 | 144 | 11.93 | 0.171 | 1.43% | 0.173 | 1.45% | 0.090 | 0.75% | 0.114 | 0.96% | 0.100 | 0.84% | 0.301 | 2.52% |
Summary of ANOVA Precision Results for VITROS 5,1 FS Chemistry Systems (%A1c, NGSP)
Summary of ANOVA Precision Results for VITROS 5,1 FS Chemistry Systems (mmol/mol, SI)
| Single Cal | Repeatability | Between Run | Between Day | Between Lot | BetweenAnalyzer | Total | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fluid | Days | N | Ave | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| VITROS PV1 | 21 | 756 | 38.3 | 0.36 | 0.9% | 0.40 | 1.0% | 0.43 | 1.1% | 0.49 | 1.3% | 0.93 | 2.4% | 1.26 | 3.3% |
| 5% BBI Control | 22 | 792 | 30.7 | 0.28 | 0.9% | 0.35 | 1.1% | 0.32 | 1.0% | 0.47 | 1.5% | 0.69 | 2.2% | 0.99 | 3.2% |
| 6.5% BBI Control | 21 | 756 | 46.2 | 0.52 | 1.1% | 0.57 | 1.2% | 0.55 | 1.2% | 0.62 | 1.3% | 0.92 | 2.0% | 1.45 | 3.1% |
| 8% BBI Control | 22 | 792 | 65.7 | 0.71 | 1.1% | 0.45 | 0.7% | 0.71 | 1.1% | 0.89 | 1.4% | 1.95 | 3.0% | 2.40 | 3.7% |
| 12% BBI Control | 20 | 720 | 106.0 | 1.61 | 1.5% | 1.01 | 1.0% | 1.30 | 1.2% | 1.11 | 1.0% | 0.63 | 0.6% | 2.63 | 2.5% |
| 5% Patient | 4 | 144 | 31.3 | 0.25 | 0.8% | 0.34 | 1.1% | 0.35 | 1.1% | 0.36 | 1.2% | 1.03 | 3.3% | 1.21 | 3.9% |
| 6.5% Patient | 4 | 144 | 47.7 | 0.42 | 0.9% | 0.42 | 0.9% | 0.46 | 1.0% | 0.58 | 1.2% | 1.08 | 2.3% | 1.43 | 3.0% |
| 8% Patient | 4 | 144 | 65.6 | 0.59 | 0.9% | 0.78 | 1.2% | 0.34 | 0.5% | 0.70 | 1.1% | 1.17 | 1.8% | 1.72 | 2.6% |
| 12% Patient | 4 | 144 | 106.9 | 1.87 | 1.7% | 1.89 | 1.8% | 0.98 | 0.9% | 1.25 | 1.2% | 1.09 | 1.0% | 3.29 | 3.1% |
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| Single Cal | Repeatability | Between Run | Between Day | Between Lot | BetweenAnalyzer | Total | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fluid | Days | N | Ave | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| VITROS PV1 | 21 | 756 | 5.63 | 0.035 | 0.62% | 0.021 | 0.37% | 0.029 | 0.52% | 0.033 | 0.59% | 0.043 | 0.76% | 0.074 | 1.32% |
| 5% BBI Control | 22 | 792 | 4.94 | 0.028 | 0.57% | 0.017 | 0.34% | 0.024 | 0.49% | 0.033 | 0.67% | 0.028 | 0.57% | 0.059 | 1.19% |
| 6.5% BBI Control | 21 | 756 | 6.35 | 0.050 | 0.79% | 0.045 | 0.71% | 0.034 | 0.54% | 0.055 | 0.87% | 0.044 | 0.69% | 0.103 | 1.62% |
| 8% BBI Control | 22 | 792 | 8.07 | 0.071 | 0.88% | 0.037 | 0.46% | 0.046 | 0.57% | 0.043 | 0.53% | 0.054 | 0.67% | 0.115 | 1.43% |
| 12% BBI Control | 20 | 720 | 11.89 | 0.177 | 1.49% | 0.069 | 0.58% | 0.109 | 0.92% | 0.095 | 0.80% | 0.000 | 0.00% | 0.239 | 2.01% |
| 5% Patient | 4 | 144 | 4.98 | 0.027 | 0.54% | 0.025 | 0.50% | 0.016 | 0.32% | 0.012 | 0.24% | 0.036 | 0.72% | 0.055 | 1.10% |
| 6.5% Patient | 4 | 144 | 6.47 | 0.049 | 0.76% | 0.019 | 0.29% | 0.020 | 0.31% | 0.034 | 0.53% | 0.040 | 0.62% | 0.077 | 1.19% |
| 8% Patient | 4 | 144 | 8.06 | 0.090 | 1.12% | 0.064 | 0.79% | 0.032 | 0.40% | 0.052 | 0.65% | 0.044 | 0.55% | 0.134 | 1.66% |
| 12% Patient | 4 | 144 | 11.96 | 0.157 | 1.31% | 0.142 | 1.19% | 0.117 | 0.98% | 0.064 | 0.54% | 0.000 | 0.00% | 0.250 | 2.09% |
Summary of ANOVA Precision Results for VITROS 4600 Chemistry Systems (%A1c, NGSP)
Summary of ANOVA Precision Results for VITROS 4600 Chemistry Systems (mmol/mol, SI)
| Single Cal | Repeatability | Between Run | Between Day | Between Lot | BetweenAnalyzer | Total | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fluid | Days | N | Ave | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| VITROS PV1 | 21 | 756 | 38.0 | 0.38 | 1.0% | 0.23 | 0.6% | 0.32 | 0.8% | 0.36 | 0.9% | 0.47 | 1.2% | 0.81 | 2.1% |
| 5% BBI Control | 22 | 792 | 30.5 | 0.31 | 1.0% | 0.19 | 0.6% | 0.26 | 0.9% | 0.36 | 1.2% | 0.31 | 1.0% | 0.64 | 2.1% |
| 6.5% BBI Control | 21 | 756 | 45.9 | 0.55 | 1.2% | 0.49 | 1.1% | 0.37 | 0.8% | 0.60 | 1.3% | 0.48 | 1.0% | 1.13 | 2.5% |
| 8% BBI Control | 22 | 792 | 64.7 | 0.78 | 1.2% | 0.40 | 0.6% | 0.50 | 0.8% | 0.47 | 0.7% | 0.59 | 0.9% | 1.26 | 1.9% |
| 12% BBI Control | 20 | 720 | 106.5 | 1.93 | 1.8% | 0.75 | 0.7% | 1.19 | 1.1% | 1.04 | 1.0% | 0.00 | 0.0% | 2.61 | 2.5% |
| 5% Patient | 4 | 144 | 30.9 | 0.30 | 1.0% | 0.27 | 0.9% | 0.17 | 0.6% | 0.13 | 0.4% | 0.39 | 1.3% | 0.60 | 1.9% |
| 6.5% Patient | 4 | 144 | 47.1 | 0.54 | 1.1% | 0.21 | 0.4% | 0.22 | 0.5% | 0.37 | 0.8% | 0.44 | 0.9% | 0.84 | 1.8% |
| 8% Patient | 4 | 144 | 64.6 | 0.98 | 1.5% | 0.70 | 1.1% | 0.35 | 0.5% | 0.57 | 0.9% | 0.48 | 0.7% | 1.46 | 2.3% |
| 12% Patient | 4 | 144 | 107.2 | 1.72 | 1.6% | 1.55 | 1.4% | 1.28 | 1.2% | 0.70 | 0.7% | 0.00 | 0.0% | 2.73 | 2.5% |
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| Single Cal | Repeatability | Between Run | Between Day | Between Lot | BetweenAnalyzer | Total | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fluid | Days | N | Ave | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| VITROS PV1 | 21 | 756 | 5.66 | 0.036 | 0.64% | 0.013 | 0.23% | 0.020 | 0.35% | 0.031 | 0.55% | 0.041 | 0.72% | 0.067 | 1.18% |
| 5% BBI Control | 22 | 792 | 4.98 | 0.034 | 0.68% | 0.011 | 0.22% | 0.017 | 0.34% | 0.058 | 1.17% | 0.000 | 0.00% | 0.070 | 1.41% |
| 6.5% BBI Control | 21 | 756 | 6.37 | 0.057 | 0.90% | 0.029 | 0.46% | 0.034 | 0.53% | 0.033 | 0.52% | 0.041 | 0.64% | 0.089 | 1.40% |
| 8% BBI Control | 22 | 792 | 8.10 | 0.072 | 0.89% | 0.017 | 0.21% | 0.030 | 0.37% | 0.054 | 0.67% | 0.037 | 0.46% | 0.103 | 1.27% |
| 12% BBI Control | 20 | 720 | 11.89 | 0.178 | 1.50% | 0.055 | 0.46% | 0.067 | 0.56% | 0.018 | 0.15% | 0.066 | 0.56% | 0.209 | 1.76% |
| 5% Patient | 4 | 144 | 5.04 | 0.027 | 0.54% | 0.013 | 0.26% | 0.021 | 0.42% | 0.032 | 0.64% | 0.020 | 0.40% | 0.053 | 1.05% |
| 6.5% Patient | 4 | 144 | 6.53 | 0.042 | 0.64% | 0.026 | 0.40% | 0.019 | 0.29% | 0.038 | 0.58% | 0.032 | 0.49% | 0.073 | 1.12% |
| 8% Patient | 4 | 144 | 8.14 | 0.062 | 0.76% | 0.062 | 0.76% | 0.000 | 0.00% | 0.044 | 0.54% | 0.032 | 0.39% | 0.104 | 1.28% |
| 12% Patient | 4 | 144 | 12.04 | 0.173 | 1.44% | 0.089 | 0.74% | 0.088 | 0.73% | 0.064 | 0.53% | 0.070 | 0.58% | 0.234 | 1.94% |
Summary of ANOVA Precision Results for VITROS 5600 Integrated Systems (%A1c, NGSP)
Summary of ANOVA Precision Results for VITROS 5600 Integrated Systems (mmol/mol, SI)
| Single Cal | Repeatability | Between Run | Between Day | Between Lot | BetweenAnalyzer | Total | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fluid | Days | N | Ave | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| VITROS PV1 | 21 | 756 | 38.4 | 0.39 | 1.0% | 0.14 | 0.4% | 0.22 | 0.6% | 0.34 | 0.9% | 0.45 | 1.2% | 0.73 | 1.9% |
| 5% BBI Control | 22 | 792 | 30.9 | 0.37 | 1.2% | 0.12 | 0.4% | 0.19 | 0.6% | 0.63 | 2.0% | 0.00 | 0.0% | 0.77 | 2.5% |
| 6.5% BBI Control | 21 | 756 | 46.1 | 0.62 | 1.3% | 0.32 | 0.7% | 0.37 | 0.8% | 0.36 | 0.8% | 0.45 | 1.0% | 0.97 | 2.1% |
| 8% BBI Control | 22 | 792 | 65.0 | 0.79 | 1.2% | 0.19 | 0.3% | 0.33 | 0.5% | 0.59 | 0.9% | 0.40 | 0.6% | 1.13 | 1.7% |
| 12% BBI Control | 20 | 720 | 106.4 | 1.95 | 1.8% | 0.60 | 0.6% | 0.73 | 0.7% | 0.20 | 0.2% | 0.72 | 0.7% | 2.28 | 2.1% |
| 5% Patient | 4 | 144 | 31.5 | 0.30 | 1.0% | 0.14 | 0.4% | 0.23 | 0.7% | 0.35 | 1.1% | 0.22 | 0.7% | 0.58 | 1.8% |
| 6.5% Patient | 4 | 144 | 47.8 | 0.46 | 1.0% | 0.28 | 0.6% | 0.21 | 0.4% | 0.42 | 0.9% | 0.35 | 0.7% | 0.80 | 1.7% |
| 8% Patient | 4 | 144 | 65.4 | 0.68 | 1.0% | 0.68 | 1.0% | 0.00 | 0.0% | 0.48 | 0.7% | 0.35 | 0.5% | 1.14 | 1.7% |
| 12% Patient | 4 | 144 | 108.1 | 1.89 | 1.7% | 0.97 | 0.9% | 0.96 | 0.9% | 0.70 | 0.6% | 0.77 | 0.7% | 2.56 | 2.4% |
{22}------------------------------------------------
- c. Linearity/assay measuring range:
Evaluation of the linearity of the VITROS® Chemistry Products HbA1c assay was performed based on CLSI EP06-A14. For each assay component (Hb, HbA1c, %A1c), a low pool and a high pool were prepared with the assay component near the extremes of the calibration range. The low and high concentration pools were mixed to give 16 further pools of intermediate concentrations. The VITROS HbA1c assay was tested using each VITROS System. The VITROS HbA1c assay is linear through the following ranges:
Linear range for Hb: 4.972 - 30.318 g/dL (component) Linear range for HbA1c: 0.080 - 2.530 g/dL (component) Linear range for % A 1 c: 3.034-15.444% (NGSP derived test) Linear range for HbA1c: 9.6-145.3 mmol/mol (SI derived test)
For each test component, the linearity passes the Acceptance Criteria and presents acceptable performance.
The linearity results support a measuring range of the VITROS HbA1c assay from 4% to 14% (alternate units: 20-130 mmole/mol).
Regression Statistics for the Linearity Assessment
%HbA1c. NGSP
| Analyzer | Intercept | Slope | r2 | Concentration RangeTested |
|---|---|---|---|---|
| VITROS5,1 FS | 0.005 | 0.9995 | 0.999 | 2.39 to 17.35 %HbA1c |
| VITROS4600 | 0.030 | 0.9957 | 0.997 | 3.03 to 15.44 %HbA1c |
| VITROS5600 | 0.012 | 0.9988 | 0.999 | 2.89 to 15.79 %HbA1c |
mmol/mol, SI
| Analyzer | Intercept | Slope | r2 | Concentration RangeTested |
|---|---|---|---|---|
| VITROS5,1 FS | 0.044 | 0.9995 | 0.999 | 2.6 to 166.1 mmol/mol |
| VITROS4600 | 0.223 | 0.9957 | 0.997 | 9.6 to 145.3 mmol/mol |
| VITROS5600 | 0.099 | 0.9988 | 0.999 | 8.1 to 149.1 mmol/mol |
d. Detection limit: Limit of Blank, Limit of Detection, Limit of Quantitation
Limits of Detection and Ouantitation were evaluated following CLSI document EP17-A213. The VITROS® Chemistry Products HbA1c assay was tested using eachVITROS System. Separate evaluations were performed for Hb, HbA1c and the derived test % A1c.
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The Limit of Blank, Limit of Detection and Limits of Quantitation were conservatively selected as the Lot/Analyzer yielding the highest values and are summarized in the following tables.
| Limit of Blank, Limit of Detection and Limit of Quantitation – Hb | ||
|---|---|---|
| LoB | LoD* | LoQ |
| LoB | LoD* | LoQ | |||
|---|---|---|---|---|---|
| g/dL | g/L | g/dL | g/L | g/dL | g/L |
| 0.186 | 1.86 | 0.312 | 3.12 | 2.117 | 21.17 |
*Proportions of false positives (α) and false negatives (β) were less than 5%; based on 500 determinations, with 5 low-level samples.
Limit of Blank, Limit of Detection and Limit of Quantitation - HbA1c
| LoB | LoD* | LoQ | |||
|---|---|---|---|---|---|
| g/dL | g/L | g/dL | g/L | g/dL | g/L |
| 0.042 | 0.42 | 0.072 | 0.72 | 0.133 | 1.33 |
*Proportions of false positives (α) and false negatives (β) were less than 5%; based on 500 determinations, with 5 low-level samples.
Limit of Blank, Limit of Detection and Limit of Quantitation - %A1c
| LoB | LoD* | LoQ | |||
|---|---|---|---|---|---|
| NGSP | SI (mmol/mol) | NGSP | SI (mmol/mol) | NGSP | SI (mmol/mol) |
| 2.396 | 2.67 | 2.580 | 4.68 | 2.580 | 4.68 |
*Proportions of false positives (α) and false negatives (β) were less than 5%; based on 500 determinations, with 5 low-level samples.
In all cases (Hb component, HbA1c component and %A1c derived test), the determined LoO met the acceptance criteria and supports a LoO claim of 2.580% NGSP.
-
e. Dilution Study:
On-Analyzer dilution is not supported. -
f. Traceability
Traceability of the Calibration: The values assigned to the VITROS® Chemistry Products Calibrator Kit 31 for %A1c are traceable to the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) Reference Method . The derived result (%A1c) is calculated from the individual quantitative results for hemoglobin (Hb) and glycated hemoglobin (HbA1c). NGSP results are derived from the International Federation of Clinical Chemistry (IFCC) HbA1c
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(mmol/mol) SI units using the Master Equation; %NGSP = (0.09148 x IFCC) + 2.152.
Analytical specificity: g.
The effect of potential interferents on the performance of the VITROS Chemistry Products HbA1c assay was assessed using methods based on the guidelines from CLSI EP7-A216. Potential interferents were evaluated on each of the VITROS Systems.
For each substance tested the control pool and the test substance pool replicates were tested with the VITROS HbA1c assay and results compared.
For HbA0, HbA1a, HbA1b, HbC, HbD, HbE, HbF and HbS, patient samples were tested with the VITROS HbA1c assay. The patient samples were also analyzed by a reference method.
Specificity
Substances That Do Not Interfere
- Samples containing hemoglobin variants HbS up to 41%. HbC up to 38%. . HbD up to 38% and HbE up to 26% of the total hemoglobin concentration do not interfere.
- . The anti-HbA1c antibodies used in this kit do not cross-react with HbA0 up to 90%, HbA1a up to 1.5%, HbA1b up to 4% of the total hemoglobin concentration.
- This method is unaffected by the presence of acetylated hemoglobin, carbamylated hemoglobin, and labile glycated hemoglobin when samples were treated with 50 mg/dL Acetaldehyde, 150 mg/dL Urea, and 1500 mg/dL Glucose for four hours at 37° C, respectively.
- . The substances listed in this table were tested with the VITROS Chemistry Products HbA1c assay at %A1c values of approximately 6.5% and 8.5% (48 and 69 HbA1c (mmol/mol)), using protocols based on CLSI Protocol EP7-6 and found not to interfere, bias ≤ 0.5 % A 1c and ≤ 0.6 % A 1c (≤ 5 and ≤ 7 HbA1c (mmol/mol)), at the concentration shown.
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| Summary of Interferent testing | |||
|---|---|---|---|
| -- | -- | -------------------------------- | -- |
| Substance* | Concentration | |
|---|---|---|
| Acetaminophen | 20 mg/dL | 1.32 mmol/L |
| Acetylsalicylic acid | 100 mg/dL | 5.55 mmol/L |
| Ampicillin | 100 mg/dL | 2.86 mmol/L |
| Ascorbic acid | 80 mg/dL | 4.54 mmol/L |
| Bilirubin | 50 mg/dL | 0.86 mmol/L |
| Ca-dobesilate | 20 mg/dL | 0.48 mmol/L |
| Cefoxitin sodium | 250 mg/dL | 5.56 mmol/L |
| Cholesterol | 350 mg/dL | 9.1 mmol/L |
| Cyclosporin | 0.5 mg/dL | 4.16 µmol/L |
| Doxycyclin hyclate | 5 mg/dL | 0.10 mmol/L |
| Glucose | 1000 mg/dL | 55.5 mmol/L |
| Glycated Albumin | 500 mg/dL | 0.07 mmol/L |
| Ibuprofen | 50 mg/dL | 2.42 mmol/L |
| Insulin | 592.8 µIU/mL | 3926 pmol/L |
| Intralipid | 500 mg/dL | Not Applicable |
| Levodopa | 2 mg/dL | 0.10 mmol/L |
| Metformin | 4 mg/dL | 0.31 mmol/L |
| Methyldopa | 2 mg/dL | 94.7 µmol/L |
| Metronidazole | 20 mg/dL | 1.17 mmol/L |
| N-Acetylcysteine | 166.3 mg/dL | 10.2 mmol/L |
| Phenylbutazone | 40 mg/dL | 1.30 mmol/L |
| Rheumatoid Factor | 750 IU/mL | 750 kIU/L |
| Rifampicin | 6 mg/dL | 72.9 µmol/L |
| Rosiglitazone maleate | 0.8 mg/dL | 16.9 µmol/L |
| Theophylline | 10 mg/dL | 0.56 mmol/L |
| Total Protein | 5 g/dL | 50 g/L |
| Total Protein | 9 g/dL | 90 g/L |
| Triglyceride | 500 mg/dL | 5.7 mmol/L |
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| 5,1 FS Analyzer | |||||||
|---|---|---|---|---|---|---|---|
| # | Variant | Range of | Relative % Difference from Reference Concentration at Lowand High HbA1c Concentrations | ||||
| HemoglobinVariant | samplestested | ConcentrationRange (%) | %A1cConcentration | ~ 6.0 %HbA1c | ~ 9.0 %HbA1c | ||
| Relative% Bias | Range % Bias | Relative% Bias | Range % Bias | ||||
| HbA0 | 49.3 – 90.4 | ||||||
| HbA1a | 70 | 0.1 – 1.5 | 5.8 – 13.4 | -1.11 | -6.15% to 2.91% | -0.90 | -1.93% to 2.04% |
| HbA1b | 1.3 – 4.1 | ||||||
| HbA2 | 22* | 4.9 – 6.1 | 5.7 – 9.0 | -1.80 | -7.25% to 0.68% | -2.67 | -5.08% to -2.13% |
| HbC | 31^ | 24.5–38.4 | 5.1 – 9.8 | -2.56 | -7.13% to 3.24% | -2.85 | -4.00% to 0.30% |
| HbD | 21 | 29.0–38.0 | 5.2 – 11.3 | -1.52 | -7.65% to 2.86% | -2.95 | -4.34% to 0.05% |
| HbE | 30* | 14.3–26.3 | 5.4 – 9.1 | -0.37 | -6.45% to 3.95% | -1.00 | -1.26% to 6.01% |
| HbS | 40 | 28.2–41.6 | 4.6 – 12.7 | 0.76 | -4.72% to 5.95% | 0.70 | -1.60% to 7.86% |
| HbF | 43 | 0.2 – 34.8 | 5.5 – 12.8 | -5.31 | -29.17% to 2.65% | -2.58 | -24.47% to 1.85% |
Hb Variant Test Concentration Ranges, %A1c Concentration Range and %A1c Bias - VITROS 5,1 FS
*All twenty-two HbA2 patient samples were spiked.
^Nineteen native HbC patient samples and 12 spiked patient samples
*Eighteen native HbE patient samples and 12 spiked patient samples
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| 4600 Analyzer | |||||||
|---|---|---|---|---|---|---|---|
| HemoglobinVariant | #samplestested | VariantConcentrationRange (%) | Range of%A1cConcentration | Relative % Difference from Reference Concentration at Lowand High HbA1c Concentrations | |||
| ~ 6.0 %HbA1c | ~ 9.0 %HbA1c | ||||||
| Relative%Bias | Range % Bias | Relative%Bias | Range % Bias | ||||
| HbA0 | 49.3 – 90.4 | ||||||
| HbA1a | 70 | 0.1 – 1.5 | 5.8 – 13.4 | -0.91 | -6.91% to 4.53% | -0.58 | -0.52% to 3.07% |
| HbA1b | 1.3 – 4.1 | ||||||
| HbA2 | 22* | 4.9 – 6.1 | 5.7 – 9.0 | -1.78 | -7.07% to 1.60% | -1.81 | -4.52% to -1.40% |
| HbC | 31^ | 24.5–38.4 | 5.1 – 9.8 | -1.92 | -6.44% to 2.68% | -2.67 | -2.58% to -0.26% |
| HbD | 21 | 29.0–38.0 | 5.2 – 11.3 | -1.33 | -6.09% to 1.25% | -3.74 | -4.61% to -2.58% |
| HbE | 30* | 14.3–26.3 | 5.4 – 9.1 | 2.38 | -3.41% to 7.92% | -0.69 | -5.13% to 1.46% |
| HbS | 40 | 28.2–41.6 | 4.6 – 12.7 | -0.84 | -4.07% to 4.29% | 0.30 | -1.05% to 7.85% |
| HbF | 43 | 0.2 – 34.8 | 5.5 – 12.8 | -4.88 | -28.65% to 4.29% | -2.63 | -23.35% to 2.14% |
Hb Variant Test Concentration Ranges, %A1c Concentration Range and %A1c Bias - VITROS 4600
*All twenty-two HbA2 patient samples were spiked.
^Nineteen native HbC patient samples and 12 spiked patient samples
*Eighteen native HbE patient samples and 12 spiked patient samples
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| 5600 Analyzer | |||||||
|---|---|---|---|---|---|---|---|
| HemoglobinVariant | #samplestested | VariantConcentrationRange (%) | Range of%A1cConcentration | Relative % Difference from Reference Concentration at Lowand High HbA1c Concentrations | |||
| ~ 6.0 %HbA1cRelative% Bias | ~ 6.0 %HbA1cRange % Bias | ~ 9.0 %HbA1cRelative% Bias | ~ 9.0 %HbA1cRange % Bias | ||||
| HbA0 | 49.3 – 90.4 | ||||||
| HbA1a | 70 | 0.1 - 1.5 | 5.8 - 13.4 | 0.06 | -5.83% to 4.53% | 0.03 | 0.03% to 2.79% |
| HbA1b | 1.3 - 4.1 | ||||||
| HbA2 | 22* | 4.9 - 6.1 | 5.7 – 9.0 | -3.25 | -8.12% to 1.33% | -4.12 | -8.03% to -1.66% |
| HbC | 31^ | 24.5-38.4 | 5.1 - 9.8 | -2.86 | -6.46% to 1.18% | -3.52 | -4.05% to -1.26% |
| HbD | 21 | 29.0-38.0 | 5.2 – 11.3 | -2.71 | -7.18% to 0.45% | -5.37 | -6.65% to -4.98% |
| HbE | 30* | 14.3-26.3 | 5.4 - 9.1 | -0.49 | -6.15% to 3.94% | -2.39 | -7.11% to -0.62% |
| HbS | 40 | 28.2-41.6 | 4.6 – 12.7 | -0.74 | -7.40% to 4.24% | -1.87 | -1.83% to 4.21% |
| HbF | 43 | 0.2 - 34.8 | 5.5 - 12.8 | -4.30 | -30.03% to 4.24% | -2.03 | -25.67% to 2.06% |
Hb Variant Test Concentration Ranges, %A1c Concentration Range and %A1c Bias - VITROS 5600
*All twenty-two HbA2 patient samples were spiked.
^Nineteen native HbC patient samples and 12 spiked patient samples
*Eighteen native HbE patient samples and 12 spiked patient samples
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The hemoglobin variants HbA0, HbA1a, HbA1b, C, D, E and S tested over the variant concentration ranges shown do not interfere in this assay.
Known Interferenents:
Glycated HbF is not detected as it does not contain the glycated B-chain that characterizes %A1c. However, HbF is measured in the total Hb assay and as a consequence, specimens containing high amounts of HbF (>7%) may result in lower than expected mmol/mol HbA1c values (IFCC) and %A1c values (NGSP).
- Reference interval h.
The expected normal HbA1c range in adults is 4.0-6.0% (NGSP) or 20-42 mmol/mol (IFCC units) . Each laboratory should confirm the validity of these intervals for the population it serves. The Standards of Medical Care in Diabetes - 2015 recommend to diagnose diabetes using a HbA1c method that is NGSPcertified and standardized to the DCCT assay and a cut point of HbA1c ≥ 6.5%.23
| Current* | IFCC traceablemethods | |
|---|---|---|
| Reference interval (non-diabetics) | 4–6% | 20–42 mmol/mol |
Refer to methods aligned to the US National Glycohemoglobin Standardization Program.
To provide clinical decision guidance for laboratories reporting results in %A1c (NGSP units), the NGSP interval was published by the National Glycohemoglobin Standardization Program (NGSP) 2. The reference interval is applicable to methods traceable to the Diabetes Control and Complications Trial (DCCT).4
| %A1c (NGSP) | Interpretation |
|---|---|
| $\u2265$ 6.5 | Action Suggested |
To provide clinical decision guidance for laboratories reporting results in HbA1c mmol/mol (SI units), the following values were calculated from the NGSP % A1c cut point using the Master Equation 56. The HbA1c cut point is ≥ 48 mmol/mol (SI Units).
| Calculated HbA1c(mmol/mol) SI Units | Interpretation |
|---|---|
| > 48 | Action Suggested |
References for updated section h - Reference Interval
-
- Implementation of haemoglobin A 1c results traceable to the IFCC reference system: the way forward; Clin Chem Lab Med 2007; 45(8):942-944.
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-
- Standards of Medical Care in Diabetes 2015. Diabetes Care; 38 (Supplement 1): S8-S16, 2015.
-
- International Expert Committee Report on the Role of the A1c Assay in the Diagnosis of Diabetes. Diabetes Care, 32(7) 1327 - 1345, 2009.
-
- The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetics on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med329:977-86; 1993.
-
- Hanas R, John G., on behalf of the International HbA1c Consensus Committee. 2010 Consensus Statement on the Worldwide Standardization of the Hemoglobin A1c Measurement. Clin. Chem., 56: 1362 - 1364, 2010.
-
- Hoelzel W, Weykamp C, Jeppsson J, Miedema K, Barr JR, Goodall I, Hoshino T, John G, Kobold U, Little R, Mosca A, Mauri P, Paroni R, Susanto F, Takei I, Thienpont L, Umemoto M, Wiedmeyer H. IFCC Working Group on HbA1c Standardization, IFCC Reference System for Measurement of Hemoglobin A1c in Human Blood and the National Standardization Schemes in the United States, Japan and Sweden: A Method Comparison Study, Clin Chem: 50 (1):166-174. 2004
- i. Antigen Excess.
The potential effect of antigen excess was assessed using fluids that were created from a commercial hemolysate fluid with concentrations through and beyond the assay measuring range for the Hb and the HbA1c components. Samples of each fluid were measured on each VITROS System. No effect from antigen excess was observed for the Hb component for concentrations up to 313.3 g/dL or for the HbA1c component for concentrations up to 21.8 g/dL.
- NGSP Certification j.
In accordance with the Special Controls, NGSP certification was received for the VITROS HbA1c assay on the VITROS 5,1 FS Chemistry System, VITROS 4600 Chemistry System and the VITROS 5600 Integrated System.
9. Conclusions
The data presented in the premarket notification provide a reasonable assurance that the VITROS® Chemistry Products HbA1c Reagent Kit. VITROS® Chemistry Products Calibrator Kit 31 and the VITROS® Chemistry Products % A1c Performance Verifiers I and II are safe and effective for the stated intended uses and are substantially equivalent to the cleared predicate devices. Performance was demonstrated with patient samples.
§ 862.1373 Hemoglobin A1c test system.
(a)
Identification. A hemoglobin A1c test system is a device used to measure the percentage concentration of hemoglobin A1c in blood. Measurement of hemoglobin A1c is used as an aid in the diagnosis of diabetes mellitus and as an aid in the identification of patients at risk for developing diabetes mellitus.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by FDA.
(2) The premarket notification submission must include performance testing to evaluate precision, accuracy, linearity, and interference, including the following:
(i) Performance testing of device precision must, at a minimum, use blood samples with concentrations near 5.0 percent, 6.5 percent, 8.0 percent, and 12 percent hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least three lots of the device and three instruments, as applicable.
(ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the device and compare results of the new device to results of a standardized test method. Results must demonstrate little or no bias versus the standardized method.
(iii) Total error of the new device must be evaluated using single measurements by the new device compared to results of the standardized test method, and this evaluation must demonstrate a total error less than or equal to 6 percent.
(iv) Performance testing must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin S.
(3) When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all labeling material for these devices describing the interference and any affected populations.