ABX PENTRA HBA1C WB, CALIBRATOR, CONTROL AND HEMOLYSIS REAGENT
Device Facts
| Record ID | K073309 |
|---|---|
| Device Name | ABX PENTRA HBA1C WB, CALIBRATOR, CONTROL AND HEMOLYSIS REAGENT |
| Applicant | Horiba Abx |
| Product Code | LCP · Hematology |
| Decision Date | Oct 17, 2008 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 864.7470 |
| Device Class | Class 2 |
Indications for Use
ABX Pentra HbA1c WB reagent is intended for use on the ABX PENTRA 400 for the quantitative in-vitro determination of HbA1c using whole blood and hemolysate. The controls, calibrators and additional reagents are intended for use in association with the above reagents.
Device Story
The ABX PENTRA HbA1c WB system is an in vitro diagnostic assay for quantitative determination of Hemoglobin A1c in human whole blood. The device utilizes a turbidimetric and colorimetric test principle on the ABX PENTRA 400 benchtop clinical chemistry analyzer. The system processes whole blood samples, which are lysed using the provided hemolysis reagent. The analyzer performs photometric measurements to determine HbA1c levels. Results are used by clinicians to monitor long-term diabetic control and assess treatment efficacy. The system includes specific calibrators and assayed controls to ensure measurement accuracy and precision. The device is intended for professional use in clinical laboratory settings.
Clinical Evidence
Bench testing only. Precision assessed via CLSI EP05-A2 (n=80 per method); linearity via CLSI EP06-A; interference testing per CLSI guidelines. Method comparison study (n=144) against predicate (Olympus AU400) showed strong correlation (r=0.98) for both manual and automated hemolysis methods. No clinical studies performed.
Technological Characteristics
Turbidimetric and colorimetric assay. Reagents include animal-derived substances, purified human material, and chemical solutions. System is a discrete photometric benchtop clinical chemistry analyzer. Calibrators are liquid chemical solutions; controls are lyophilized human whole blood. Reagents stored at 2-8°C. No specific ASTM standards cited.
Indications for Use
Indicated for quantitative in vitro diagnostic determination of Hemoglobin A1c percentage (%HbA1c) in human whole blood to assess long-term glycemic control in patients with diabetes. Used on the ABX PENTRA 400 Clinical Chemistry Analyzer.
Regulatory Classification
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.
Predicate Devices
Related Devices
- K033674 — MULTIGENT HEMOGLOBIN A1C (REAGENTS), HB A1C CALIBRATORS AND HB A1C CONTROLS · Seradyn, Inc. · Feb 9, 2004
- K120497 — EASYRA HBALC REGENT EASYCAL HBLC CALIBRATOR EASYQC HBALC MATERIAL · Medica Corp. · May 14, 2012
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k073309
B. Purpose for Submission:
New device
C. Measurand:
Hemoglobin A1c (HbA1c)
D. Type of Test:
Quantitative turbidimetric immunoassay
E. Applicant:
Horiba ABX
F. Proprietary and Established Names:
ABX PENTRA HbA1c WB
ABX PENTRA HbA1c WB Cal
ABX PENTRA HbA1c WB Control
ABX PENTRA HbA1c WB Hemolysis Reagent
G. Regulatory Information:
1. Regulation section:
21CFR §864.7470 – Glycosylated hemoglobin Assay
21CFR §862.1150 – Calibrator, multi-analyte mixture
21CFR §862.1660 – Quality control material (assayed and unassayed)
2. Classification:
Class II
Class II
Class I
3. Product code:
LCP - Glycosylated hemoglobin assay
JIX - Calibrator, multi-analyte mixture
JJY - Multi-Analyte Controls (Assayed and Unassayed)
4. Panel:
Hematology (81) and Chemistry (75)
H. Intended Use:
1. Intended use(s):
See indications for use below.
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2. Indication(s) for use:
ABX PENTRA HbA1c WB reagent with associated calibrators and controls are for quantitative in vitro diagnostic determination of Hemoglobin A1c percentage (%HbA1c) in human whole blood based on a colorimetric and turbidimetric assay. It is intended for use on ABX PENTRA 400 Clinical Chemistry Analyzer
Percent HbA1c measurements are used in the clinical management of diabetes to assess the long-term efficacy of diabetic control.
The ABX PENTRA HbA1c WB Cal is a calibrator for use in the calibration of quantitative Horiba ABX PENTRA HbA1c WB method on Horiba ABX clinical chemistry analyzers.
The ABX PENTRA HbA1c WB Control is for use in quality control by monitoring accuracy and precision for the quantitative ABX PENTRA HbA1c WB method.
The ABX PENTRA HbA1c WB Hemolysis Reagent is an additional reagent for use in combination for the quantitative ABX PENTRA HbA1c WB method.
3. Special conditions for use statement(s):
For prescription use only
HbS or HbC variants significantly interfere with this assay; this method should not be used to test patient samples with these hemoglobin variants.
4. Special instrument requirements:
ABX PENTRA 400 Clinical Chemistry Analyzer
I. Device Description:
The ABX PENTRA HbA1c WB Set contains ready-to-use vials of reagents R1, R2, R3, R4, R5 and Diluent I. R1 contains particles coupled with mouse anti-human HbA1c monoclonal antibody in buffer. R2 contains agglutinator reagent containing covalent polymer-bonding hapten in buffer. R3 contains Hemoglobin denaturant containing porcine pepsin in buffer. R4 contains the total hemoglobin reagent containing sodium hydroxide and surfactant. R5 contains diluent I, a saline solution.
This assay may be used in two formats: a method for automatic hemolysis of blood samples by the ABX PENTRA 400 or a method where hemolysis of blood samples is done manually before analysis by the ABX PENTRA 400. The automated analyzer method uses R1, R2, R3, and R4 while the manual method uses R1, R2, R3, R4, and R5.
The calibrator kit contains ready to use vials of Calibrators 1 - 6. Each vial contains HbA1c and hemoglobin in buffer.
The control kit consists of two vials (Control 1 and Control 2). The vials contain
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lyophilized hemoglobin A1c (hemolysate prepared from packed human erythrocytes) and stabilizers. One control is in the normal range and the other is in the elevated range.
The human whole blood used in the calibrators and controls is nonreactive for HBsAg, HIV-1 Ag or HIV-1 RNA, Anti- HIV-1/HIV-2, and anti-HCV or HCV RNA.
## J. Substantial Equivalence Information:
1. Predicate device name(s):
Bayer Hemoglobin A1c
Olympus America Hemoglobin A1c Test
2. Predicate 510(k) number(s):
k955087 (Bayer) and k031380 (Olympus)
3. Comparison with predicate:
Reagent Similarities:
| | k955087 | k031380 | ABX Pentra HbA1c WB |
| --- | --- | --- | --- |
| Intended Use | Determination of % HbA1c for use in clinical management of diabetes | Determination of % HbA1c for use in clinical management of diabetes | Determination of % HbA1c for use in clinical management of diabetes |
| Method : | Latex-enhanced turbidimetric immunoassay for detection of HbA1c and colorimetric assay for detection of total hemoglobin method.
HbA1c %: determined from the HbA1c/Hb ratio. | Latex agglutination inhibition immunoassay for detection of HbA1c and colorimetric assay for detection of total hemoglobin method.
HbA1c %: determined from the HbA1c/HB ratio. | Latex-enhanced turbidimetric immunoassay for detection of HbA1c and colorimetric assay for detection of total hemoglobin method.
HbA1c %: determined from the HbA1c/HB ratio. |
| Specimen : | Whole blood | Whole blood | Whole blood |
| Format | Liquid | Liquid | Liquid |
Reagent Differences:
| | k955087 | k031380 | ABX Pentra HbA1c WB |
| --- | --- | --- | --- |
| Reference method | Correction by a conversion factor to match a HPLC reference method | Correction by a conversion factor to match a DCCT reference method | Correction by a conversion factor to match a HPLC reference method (NGSP certification) |
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| | k955087 | k031380 | ABX Pentra HbA1c WB |
| --- | --- | --- | --- |
| Measuring range | HbA1c%: 1.8 % – 14.7 % | HbA1c%: 2.6 % – 14.5 % | HbA1c%: 5.0 % – 15.2 % |
| Calibration stability | | 14 days | 3 weeks |
| Open Reagent stability | Open reagent stability : until the expiry date at 2-8°C | Open reagent stability : 30 days | Stability after reconstitution of the latex antibody complex: 2 months |
## Calibrator Comparison:
| | k031380 | ABX Pentra HbA1c WB Cal |
| --- | --- | --- |
| Similarities: | | |
| Method : | Calibration for the determination of HbA1c on OLYMPUS analyzers | Calibration for the determination of:
- HbA1c
- Total Hemoglobin on ABX PENTRA 400 analyzers |
| Component matrices | Liquid chemical solutions with HbA1c hapten | Liquid chemical solutions with HbA1c hapten |
| Format | Liquid – 6 levels | Liquid – 6 levels |
| Differences: | | |
| Calibration values and traceability | - Determined using the methods mentioned in the package insert. Traceable to IFCC reference preparations. | - Determined using HPLC method for HbA1c and the Drabkin method for total hemoglobin. |
## Control Comparison:
| | k031380 | ABX Pentra HbA1c WB Control |
| --- | --- | --- |
| Intended Use | Quality control by monitoring accuracy and precision for the determination of HbA1c% | Quality control by monitoring the performances for the determination of HbA1c% |
| Format | 2 levels – normal and high. Lyophilized | 2 levels– normal and high. Lyophilized |
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| | k031380 | ABX Pentra HbA1c WB Control |
| --- | --- | --- |
| **Traceability** | Traceable to calibrators which are traceable to IFCC reference preparation | Determined using HPLC method for HbA1c and the Drabkin method for total hemoglobin. |
K. Standard/Guidance Document Referenced (if applicable):
CLSI EP05-A2: Evaluation of Precision performance of Quantitative Measurement Methods, Approved Guideline- Second Edition
CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures, A Statistical Approach; Approved Guideline
CLSI EP09-A2: Method Comparison and Bias Estimation Using Patient Samples, Approved Guideline-Second Edition
CLSI EP17-A: Protocols for the Determination of Limits of Detection and Limits of Quantitation, Approved Guideline
L. Test Principle:
HbA1c/Total Hemoglobin ratio is expressed as percentage HbA1c (units %HbA1c) after the concentrations of both HbA1c and Total Hemoglobin are determined individually. Whole blood samples are pre-treated with the Hemolysis Reagent to lyse the red cells and hydrolyze the hemoglobin chain. Total Hemoglobin is converted into alkaline haematin in the alkaline solution of a non-ionic detergent. Addition of the pre-treated blood sample to the Total Hb reagent results in a green solution, which is measured at 600 nm. HbA1c is measured from the hemolysate by a latex enhanced turbidimetric immunoassay. In the absence of HbA1c in the sample, the antibody-coated micro-particles in the HbA1c R1 and the agglutinator in R2 will agglutinate. This leads to an increase in the absorbance of the suspension. The presence of HbA1c in the sample results in a decrease in the rate of agglutination. The increase in absorbance is therefore inversely proportional to the concentration of HbA1c in the sample. The increase in absorbance is measured at 700 nm.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Precision was assessed using two control samples (normal and high) and three human samples (normal, slightly elevated, and high). Within-run precision samples were prepared according to test protocol and tested 20 times in a single run on an ABX PENTRA 400 instrument. Total precision was assessed using the same samples prepared according to test protocol tested in duplicate twice a day for 20 days following the method in CLSI EP-5A (n = 80).
Results for the manual method for preparing the hemolysate and the automated method are shown in the tables below:
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Precision: Pentra HbA1c WB Assay – Manual Method
| | Within-Run | | | Total Precision | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean | Std Dev | CV | Mean | Std Dev | CV |
| | ng/mL | ng/mL | % | ng/mL | ng/mL | % |
| Control N | 5.20 | 0.10 | 1.87 | 5.27 | 0.07 | 1.41 |
| Control P | 9.70 | 0.26 | 2.72 | 10.11 | 0.24 | 2.42 |
| Normal Sample | 4.95 | 0.07 | 1.51 | 5.27 | 0.11 | 2.18 |
| Elevated Sample | 7.77 | 0.12 | 1.60 | 8.52 | 0.19 | 2.21 |
| High Sample | 10.57 | 0.15 | 1.44 | 12.22 | 0.30 | 2.46 |
Precision: Pentra HbA1c WB Assay – Automated Method
| | Within-Run | | | Total Precision | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean | Std Dev | CV | Mean | Std Dev | CV |
| | ng/mL | ng/mL | % | ng/mL | ng/mL | % |
| Control N | 4.39 | 0.12 | 2.83 | 5.36 | 0.07 | 1.29 |
| Control P | 10.45 | 0.20 | 1.96 | 11.14 | 0.22 | 1.99 |
| Normal Sample | 3.65 | 0.10 | 2.84 | 5.21 | 0.13 | 2.49 |
| Elevated Sample | 7.93 | 0.24 | 2.98 | 8.10 | 0.30 | 3.71 |
| High Sample | 11.23 | 0.40 | 3.57 | 11.76 | 0.31 | 2.63 |
b. Linearity/assay reportable range:
The linear range of the automatic and the manual hemolysate methods were evaluated using a high HbA1c sample diluted with a low HbA1c sample. (Samples prepared as directed for each method.) The dilutions were made as recommended in the CLSI guideline EP6-A and an analysis was carried out in accordance with the guideline by performing 1st, 2nd and 3rd order least squares regressions. The results demonstrated linearity for both datasets. In addition, the observed values were within $\pm 10\%$ of the expected values for all samples tested. The results submitted demonstrated linearity across the claimed measuring range of $5.0\%$ to $15.2\%$ HbA1c.
c. Traceability, Stability, Expected values (controls, calibrators, or methods): The sponsor has documented traceability to the NGSP's recommended accuracy base for Hbg A1c by performing a direct comparison with a Secondary Reference Laboratory (SRL) using 40 fresh human specimens. NGSP certifications expire after one year. Current certifications are posted on the NGSP website at: http://www.ngsp.org/prog/index.html
A HPLC method for measuring HbA1c concentration and the Drabkin method for measuring total hemoglobin are used to assign calibrator values. Control
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values are assigned from the median of 90 measurements for each level (nine measurements per day for five days on two instruments). The stated interval is $\pm 20\%$ of the median.
Assay Component Stability (storage at $2 - 8^{\circ}\mathrm{C}$):
| | Closed | Open | Reconstituted |
| --- | --- | --- | --- |
| Reagent | 24 months | | 2 months |
| Calibrator | 24 months | until the expiry date | N/A |
| Control | 36 months | 3 months | N/A |
| Hemolysis Reagent | 18 months | until the expiry date | N/A |
d. Detection limit:
See linearity studies above.
e. Analytical specificity:
Interference from endogenous substances was tested by analysis of whole blood samples spiked with up to $612\mathrm{mg / dL}$ triglycerides, $1400\mathrm{mg / dL}$ glucose, $29\mathrm{mg / dL}$ total bilirubin or $29\mathrm{mg / dL}$ direct bilirubin. The results showed $< \pm 0.5\%$ (absolute) interference for each substance at the levels tested. The labeling refers the user to Young et al. for a list of drugs and preanalytical variables known to affect this methodology.
The effect of different concentrations of total hemoglobin on the assay was tested. There was less than $10\%$ difference between the test value and the expected HbA1c concentration (not $\% \mathrm{HbA1c}$) from 3.83 to $22.60~\mathrm{g / dL}$ (14.6 to $85.7~{\mu \mathrm{mol}} / \mathrm{L}$) of total hemoglobin.
Interferences from Hemoglobin C, S, and F as well as interferences from carbamylated and acetylated hemoglobins were assessed for this assay. Carbamylated and acetylated hemoglobins did not interfere with the assay while HbF showed no interference up to $15\%$ HbF. Samples containing HbS or HbC showed significant interference; this information is in the limitations section of the labeling. At the time of this decision, NGSP has a list assays used to measure HbA1C and whether the method is affected by either HbS or HbC or HbE: http://www.ngsp.org/prog/index.html.
f. Assay cut-off:
Not applicable.
2. Comparison studies:
a. Method comparison with predicate device:
A method comparison study using 144 remnant whole blood samples compared the ABX Pentra 400 instrument and the predicate method (Olympus AU400).
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Manual method for preparing the hemolysate:
Whole blood samples were prepared as directed. Samples ranged from 4.9%*-12.2% HbA1c. Passing-Bablock regression analysis of the results yielded the following: y = 0.97x + 0.36, r = 0.98
Automatic method for preparing the hemolysate:
Samples ranged from 4.9%*-12.4% HbA1c. Passing-Bablock regression analysis of the results yielded the following: y = 0.98x + 0.41, r = 0.98
* = predicate device
b. Matrix comparison:
Not applicable: EDTA whole blood is the only claimed specimen.
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable.
b. Clinical specificity:
Not applicable.
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable.
4. Clinical cut-off:
Not applicable.
5. Expected values/Reference range:
The expected %HbA1c value for patients with diabetes will depend on physician discretion. In the labeling the sponsor cites the American Diabetes Association’s (ADA) most recent Clinical Practice Recommendation of diabetes specifies a treatment goal of 7% or less. This recommendation also suggests additional action when the HbA1c level is above 8%.
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
