(114 days)
No
The description focuses on chemical and turbidimetric methods for measurement and does not mention any AI/ML components.
No
The device is for in vitro diagnostic use, intended for the quantitative determination of HbA1c to aid in the diagnosis and monitoring of diabetes mellitus, not for direct treatment of a disease or condition.
Yes
The "Intended Use / Indications for Use" section explicitly states that the determination of HbA1c with this device "is used as an aid in the diagnosis of diabetes mellitus, for the monitoring of long-term glucose control in individuals with diabetes mellitus and identifying patients who may be at risk for developing diabetes mellitus. For in vitro diagnostic use only."
No
The device is a reagent kit and associated calibrator used on a clinical chemistry analyzer. It involves chemical reactions and physical measurements of absorbance and turbidity, indicating it is a hardware-dependent in vitro diagnostic device, not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states in the "Intended Use / Indications for Use" section: "For in vitro diagnostic use only." This is a clear indication that the device is intended for use in examining specimens derived from the human body to provide information for the diagnosis, prevention, or treatment of a disease or condition.
Furthermore, the "Device Description" and "Summary of Performance Studies" sections detail the analysis of human venous whole blood samples to determine HbA1c concentration, which is used as an aid in the diagnosis and monitoring of diabetes mellitus. This aligns with the definition of an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
The HbA 1c (Hemoglobin A 1c) Advanced assay on the Beckman Coulter DxC700 AU Clinical Chemistry Analyzer, is intended for the quantitative determination of mmol/mol HbA1c (DCCT/NGSP) concentration in human venous whole blood. The determination of HbA1c is used as an aid in the diagnosis of diabetes mellitus, for the monitoring of long-term glucose control in individuals with diabetes mellitus and identifying patients who may be at risk for developing diabetes mellitus. For in vitro diagnostic use only.
Product codes (comma separated list FDA assigned to the subject device)
PDJ, LCP
Device Description
The HbA1c Advanced reagent kit is in a liquid format and is ready to use. It contains four reagents HbA1c R1 and HbA1c R2, Total Hemoglobin R1 and Hemolyzing reagent R1. The HbA1c calibrator is supplied with the reagent, in a liquid, ready to use format and contains 5 x 2mL calibrator levels. The sample hemolysis is automated on the DxC700 AU Clinical Chemistry analyzer. Sample handling is performed as follows: 200 uL of hemolyzing reagent is aspirated from the Hemolyzing Reagent R1and dispensed into a cuvette. Tetradecyltrimethylammonium bromide (TTAB) in the hemolyzing reagent eliminates interference from leukocytes. 2 µL of whole blood sample is then aspirated from the patient sample and added to the hemolyzing reagent in the cuvette. This hemolyzed whole blood is then added to the THb assay cuvette and HbA1c assay cuvette as per the assay parameters.
The concentrations of both HbA1c and Total Hemoglobin are determined. The HbA1c/Total Hemoglobin ratio is expressed either as mmol/mol (IFCC) or %HbA1c (DCCT/NGSP).
Total Hemoglobin Reagent is used to measure total hemoglobin concentration by a colorimetric method. Change in absorbance is measured at 570/660 nm.
HbA1c reagent is used to measure hemoglobin A1c concentration by a turbidimetric immunoinhibition method. In the reaction, hemoglobin A1c antibodies combine with HbA1c from the sample to form soluble antigen-antibody complexes. Polyhaptens from the reagent then bind with the excess antibodies and the resulting agglutinated complex is measured turbidimetrically. Change in absorbance is measured at 340/700 nm.
The calibrator is manufactured from human material; therefore should be handled as though capable of transmitting infectious disease. Each donor used in the preparation of this material was tested by the United States Food and Drug Administration (FDA), approved method and found to be negative for the presence of the antibodies for HIV-1/2, HCV, Hepatitis B surface antigen and was determined to not be repeatedly reactive.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
Description of test set, sample size, and data source:
Precision studies were carried out on 3 lots of HbA1c Advanced by testing four levels of HbA1c K2 EDTA human venous whole blood patient samples at HbA1c concentrations of approximately 5.0%, 6.5%, 8.0%, 12% and 14%. The experimental design used duplicate sample analysis, twice daily, over the course of twenty working days.
Method comparison studies tested over 120 (duplicates) of venous human frozen whole blood specimens (K2 EDTA anticoagulant type).
No information on annotation protocol.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Precision
Sample Size: Not explicitly stated as one sample size: "four levels of HbA1c K2 EDTA human venous whole blood patient samples at HbA1c concentrations of approximately 5.0%, 6.5%, 8.0%, 12% and 14%. The experimental design used duplicate sample analysis, twice daily, over the course of twenty working days (n=2)".
Key Results: All targets for repeatability and total precision passed.
Study Type: Linearity
Sample Size: N: ≥ 9
Key Results: The results of the study provides data to support the dynamic range/analytical measuring range claim for HbA1c Advanced reagent 4 – 15% (NGSP) HbA1c and 20 – 140 mmol/mol HbA1c (IFCC). Regression parameters for slope, intercept and R value were calculated and passed specifications.
Study Type: Method Comparison (Patient Correlation)
Sample Size: N: ≥ 120 (138 samples tested)
Key Results: Weighted Deming's and Passing-Bablok regression analysis showed that the device passed for Slope, Intercept, and R.
Study Type: Total Error
Sample Size: Not explicitly stated, derived from Method Comparison and Precision studies.
Key Results: Total error was calculated at four concentrations (5.0%, 6.5%, 8.0%, and 12.0%) and passed the acceptance criteria of ≤6% for all levels.
Study Type: Analytical Specificity (Endogenous Interference)
Sample Size: Not explicitly stated, "low level human venous whole blood K2 EDTA sample" and "high level human venous whole blood K2 EDTA sample" for interferents, with "10 replicates tested per level".
Key Results: No Significant Interference (recovery within 7% of the initial value) was observed up to the stated concentrations for Conjugated Bilirubin, Unconjugated Bilirubin, Lipemia, Ascorbic Acid, RF, Total Protein and Glucose.
Study Type: Drug Interference
Sample Size: Not explicitly stated, "low level human venous whole blood EDTA sample" and "high level human venous whole blood EDTA sample" for drugs, with "Ten replicates of each test and reference sample".
Key Results: No Significant Interference (recovery within 7% of the initial value) was observed up to the stated concentrations for various drugs.
Study Type: Hemoglobin Derivative and Cross Reactants
Sample Size: Not explicitly stated, "low level human venous whole blood K2 EDTA sample" and "high level human venous whole blood K2 EDTA sample" for derivatives/reactants, with "10 replicates tested per level".
Key Results: No Significant Interference (recovery within 7% of the initial value) was observed up to the stated concentrations for Labile Hemoglobin, Acetylated Hemoglobin, Carbamylated Hemoglobin, Glycated Albumin, HbA0 and HbA1a+b.
Study Type: Hemoglobin Variants
Sample Size: A minimum of 20 samples were tested for each variant (HbC, HbD, HbE, HbF, HbS and HbA2).
Key Results: The study determined the relative % bias for HbC, HbD, HbE, HbS, and HbA2 at approximately 6.5% and 9.0% HbA1c. Specimens containing high amounts of HbF (> 7%) may yield lower than expected HbA1c Values. No Significant Interference is recovery within 7% of the reference value (value assigned in Secondary Reference Laboratory).
Study Type: Anticoagulants
Sample Size: Not stated.
Key Results: The data supports the use of K2 EDTA, K3 EDTA, Sodium Heparin, and Lithium Heparin blood collection tubes.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not stated
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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§ 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.
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January 16, 2019
Beckman Coulter Ireland Inc. Catriona Hourigan, Regulatory Affairs Specialist Lismeehan O' Callaghan's Mills Co. Clare Ireland V94 PP63
Re: K182651
Trade/Device Name: HbA1c Advanced Regulation Number: 21 CFR 862.1373 Regulation Name: Hemoglobin A1c test system Regulatory Class: Class II Product Code: PDJ, LCP Dated: September 20, 2018 Received: September 24, 2018
Dear Catriona Hourigan:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.
1
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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kellie B. Kelm -S
Courtney H. Lias, Ph.D. for Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K182651
Device Name HbA1c Advanced
Indications for Use (Describe)
The HbA 1c (Hemoglobin A 1c) Advanced assay on the Beckman Coulter DxC700 AU Clinical Chemistry Analyzer, is intended for the quantitative determination of mmol/mol HbA1c (DCCT/NGSP) concentration in human venous whole blood. The determination of HbA1c is used as an aid in the diagnosis of diabetes mellitus, for the monitoring of long-term glucose control in individuals with diabetes mellitus and identifying patients who may be at risk for developing diabetes mellitus. For in vitro diagnostic use only.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(k) Summary
HbA1c Advanced
1.0 Submitted By:
Catriona Hourigan Regulatory Affairs Specialist Beckman Coulter Ireland Inc., Lismeehan, O' Callaghan's Mills, Co. Clare, Ireland. Phone: +353-65-683-1417 FAX: +353-65-683-1122 email: chourigan@beckman.com
2.0 Date Submitted:
15th January 2019
3.0 Device Name(s):
Proprietary Name: HbA1c Advanced K182651
4.0 Predicate Device:
Table 1: Predicate Details
| Candidate(s) | Predicate | Manufacturer | Docket
Number |
|----------------|-------------------------------------------------|-------------------------------|------------------|
| HbA1c Advanced | D-100™ HbA1c,
D-100™HbA1c
Calibrator Pack | Bio-Rad
Laboratories, Inc; | K151321 |
4
5.0 Recommended Reagent Classification: Name: Hemoglobin A1c Test System Requlation: 862.1373 Class: II
Name: Assay Glycosylated Hemoglobin Regulation: 864.7470 Class: II Panel: Hematology Product Code: LCP
Panel: Clinical Chemistry Product Code: PDJ
6.0 Description:
The HbA1c Advanced reagent kit is in a liquid format and is ready to use. It contains four reagents HbA1c R1 and HbA1c R2, Total Hemoglobin R1 and Hemolyzing reagent R1. The HbA1c calibrator is supplied with the reagent, in a liquid, ready to use format and contains 5 x 2mL calibrator levels. The sample hemolysis is automated on the DxC700 AU Clinical Chemistry analyzer. Sample handling is performed as follows: 200 uL of hemolyzing reagent is aspirated from the Hemolyzing Reagent R1and dispensed into a cuvette. Tetradecyltrimethylammonium bromide (TTAB) in the hemolyzing reagent eliminates interference from leukocytes. 2 µL of whole blood sample is then aspirated from the patient sample and added to the hemolyzing reagent in the cuvette. This hemolyzed whole blood is then added to the THb assay cuvette and HbA1c assay cuvette as per the assay parameters.
The concentrations of both HbA1c and Total Hemoglobin are determined. The HbA1c/Total Hemoglobin ratio is expressed either as mmol/mol (IFCC) or %HbA1c (DCCT/NGSP).
Total Hemoglobin Reagent is used to measure total hemoglobin concentration by a colorimetric method. Change in absorbance is measured at 570/660 nm.
HbA1c reagent is used to measure hemoglobin A1c concentration by a turbidimetric immunoinhibition method. In the reaction, hemoglobin A1c antibodies combine with HbA1c from the sample to form soluble antigen-antibody complexes. Polyhaptens from the reagent then bind with the excess antibodies and the resulting agglutinated complex is measured turbidimetrically. Change in absorbance is measured at 340/700 nm.
The calibrator is manufactured from human material; therefore should be handled as though capable of transmitting infectious disease. Each donor used in the preparation of this material was tested by the United States Food and Drug Administration (FDA), approved method and found to be negative for the presence of the antibodies for HIV-1/2, HCV, Hepatitis B surface antigen and was determined to not be repeatedly reactive.
Because no test method can offer complete assurance that HIV-1/2, HCV, hepatitis B virus
5
or other infectious agents are absent from biological materials, this product should be handled at the Biosafety Level 2 as recommended for any infectious human serum or blood specimen in the Centers for Disease Control and Prevention/National Institutes of Health manual, Biosafety in Microbiological and Biomedical Laboratories.
7.0 Intended Use:
HBA1c Advanced
The HbA1c Advanced assay on the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer, is intended for the quantitative determination of mmol/mol HbA1c (IFCC) and % HbA1c (DCCT/NGSP) concentration in human venous whole blood. The determination of HbA1c is used as an aid in diagnosis of diabetes mellitus, for the monitoring of long-term blood glucose control in individuals with diabetes mellitus and identifying patients who may be at risk for developing diabetes mellitus. For In vitro diagnostic use only.
8.0 Comparison to the Predicate(s):
| Test System | HbA1c Predicate | Proposed New System |
|---|---|---|
| Proprietary and | ||
| Established Names | D-100™ HbA1c, | |
| D-100™ HbA1c Calibrator | ||
| Pack | HbA1c Advanced | |
| Similarities | ||
| Intended use | The D-100™ HbA1c test is | |
| intended for the quantitative | ||
| determination of | ||
| hemoglobin A1c (IFCC | ||
| mmol/mol and NGSP %) in | ||
| human whole blood using | ||
| ion-exchange high | ||
| performance liquid | ||
| chromatography (HPLC) on | ||
| the D-100 Hemoglobin | ||
| testing system. |
Hemoglobin A1c
measurements are used as
an aid in the diagnosis of
diabetes mellitus, as an aid
to identify patients who may
be at risk for developing
diabetes mellitus, and for
the monitoring of long-term | The HbA1c (Hemoglobin A1c)
Advanced assay on the
Beckman Coulter DxC 700 AU
Clinical Chemistry Analyzer, is
intended for the quantitative
determination of mmol/mol
HbA1c (IFCC) or % HbA1c
(DCCT/NGSP) concentration in
human venous whole blood. The
determination of HbA1c is used
as an aid in the diagnosis of
diabetes mellitus, for the
monitoring of long-term blood
glucose control in individuals
with diabetes mellitus and
identifying patients who may be
at risk for developing diabetes
mellitus. For in vitro diagnostic
use only. |
| | blood glucose control in
individuals with diabetes
mellitus.
Calibrators:
The D-100™ HbA1c
Calibrator pack is for the
calibration of the D-100
Hemoglobin Testing System
used for the quantitative
determination of
hemoglobin A1c (HbA1c) in
human whole blood. | |
| Reporting Units | HbA1c results are provided
to the customers using two
different units:
NGSP equivalent units (%)
and IFCC equivalent units
(mmol/mol). | Same |
| Sample Types | Whole blood
K2-EDTA
K3-EDTA
Lithium Heparin
Sodium Heparin | Whole blood
K2-EDTA
K3-EDTA
Li-Heparin
Na-Heparin |
| Reagent Stability | Unopened
2° - 8°C until expiration date | Unopened
2° - 8°C until expiration date |
| Reference Range | Literature reference:
Diabetic ≥6.5 NGSP %, ≥48
IFCC mmol/mol;
Pre-Diabetic
5.7 - 6.4 NGSP%, IFCC 39
- 47 mmol/mol;
Non--Diabetic 9% | 10 | 7.25 | 10 | 7.25 |
| Total Samples | 138 | 100% | 138 | 100% |
Table 13: Sample Distribution
Weighted Deming's and Passing-Bablok regression analysis was performed for the HbA1c Advancedmethod versus an NGSP SRL standardized method, results are summarized below in tables 14 and 15.
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Table 14: Summary of Method Comparison for HbA1c Advanced results and specifications (Weighted Deming analysis) NGSP Units.
| Sample Range: | Specifications | Results
(95%CI Low; High) | Pass
Fail |
|---------------------------------|---------------------------|----------------------------------------|--------------|
| Method X:
4.7 - 14.2 % HbA1c | Slope: 1.0 ± 0.05 | 0.990
(0.978; 1.002) | Pass |
| Method Y:
4.6 – 14.3 % HbA1c | Intercept: ≤ ± 0.5% HbA1c | 0.010 %HbA1c
(-0.070; 0.089) %HbA1c | Pass |
| | R: ≥ 0.975 | 0.998 | Pass |
| | N: ≥ 120 | 138 | Pass |
Table 15: Summary of Method Comparison for HbA1c Advanced results and specifications (Passing-Bablok analysis) NGSP Units.
| Sample Range: | Specifications | Results
(95% CI Low; High) | Pass / Fail |
|---------------------------------|--------------------------------------------------------|---------------------------------------------------------|----------------------|
| Method X:
4.7 - 14.2 % HbA1c | Slope: 1.0 ± 0.5 | 0.980
(0.964;0.992) | Pass |
| Method Y:
4.6 - 14.3 % HbA1c | Intercept: ≤ ± 0.5
%HbA1c
R: ≥ 0.975
N: ≥ 120 | 0.090 %HbA1c
(-0.006; 0.187) % HbA1c
0.998
138 | Pass
Pass
Pass |
Total Error
Total error was evaluated using the results of the bias estimation (%Bias) from single measurements conducted of the new device compared to results of the standardised test method (method comparison) and precision estimates from the precision study. Total Error (TE) at four concentrations (5.0%, 6.5%, 8.0%, and 12.0%) was calculated as follows: "%TE = |(%Bias)] + 1.96*%CV*(1+%Bias/100)". The results are presented in Table 5.
Table 16: Total Error Estimation
| %HbA1c
Decision Level | % Bias | %CV | %TE | Acceptance
Criteria:
≤6% |
|--------------------------|--------|------|-----|--------------------------------|
| 5.0 | -0.80 | 1.78 | 4.3 | Pass |
| 6.5 | -0.85 | 1.69 | 4.2 | Pass |
| 8.0 | -0.88 | 1.74 | 4.3 | Pass |
| 12.0 | -0.92 | 1.22 | 3.3 | Pass |
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Analytical Specificity
Interference (Analytical Specificity) studies were designed based on CLSI Guideline EP07 Third Edition: "Interference Testing in Clinical Chemistry; Approved Guideline" and used to assess common or known substances which could interfere with the HbA1c Advanced assay.
Endogenous Interference
The interfering substances analyzed were tested at two % HbA1c concentrations; approximately 6.5% HbA1c (low level human venous whole blood K2 EDTA sample) and approximately 8.0% HbA1c (high level human venous whole blood K2 EDTA sample) using one lot of reagent on one DxC700 AU analyzer. Low and high pools were prepared by interdiluting human whole blood samples.
The whole blood samples were tested at a minimum of 5 levels for each interferent (Conjugated Bilirubin, Unconjugated Bilirubin, Lipemia, Ascorbic Acid, RF, Total Protein and Glucose) with 10 replicates tested per level on the DxC700 AU Analyzer to determine the magnitude of the interference.
No Significant Interference is recovery within 7% of the initial value (sample containing no interferent). Results in Table 1 show no significant interference up to the stated concentrations.
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| Potential Interfering
| Substance | Interference pool details | Interferent Level |
|---|---|---|
| Conjugated Bilirubin | Whole Blood Pools spiked with | |
| Conjugated Bilirubin Stock Solution | 60 mg/dL | |
| Unconjugated Bilirubin | Whole Blood Pools spiked with | |
| unconjugated Bilirubin Stock | ||
| Solution | 60 mg/dL | |
| Lipemia | Whole Blood Pools spiked with | |
| 20% w/v Intralipid | 500 mg/dL | |
| Ascorbic Acid | Whole Blood Pools spiked with | |
| Ascorbate | 300 mg/dL | |
| RF | Whole Blood Pools spiked with RF | |
| positive plasma | 1000 IU/ml | |
| Total Protein | Whole Blood Pools spiked with | |
| Human Serum Albumin | 21 g/dL | |
| Glucose | Whole Blood Pools spiked with | |
| Anhydrous Glucose | 2000 mg/dL | |
| Potential Interfering | ||
| Substance | Interference pool details | Interferent Level |
| Glyburide | Whole Blood Pools spiked | |
| with Glyburide Stock | ||
| Solution | 0.12 mg/dL | |
| Salicylic Acid | Whole Blood Pools spiked | |
| with Salicylic Acid Stock | ||
| Solution | 4.76 mg/dL | |
| Sitagliptin | Whole Blood Pools spiked | |
| with Sitagliptin Phosphate | ||
| stock solution | 0.2 mg/dL | |
| Rosiglitazone | Whole Blood Pools spiked | |
| with Rosiglitazone maleate | ||
| stock solution | 0.33 mg/dL | |
| Metformin | Whole Blood Pools spiked | |
| with Metformin | ||
| Hydrochloride stock | ||
| solution | 5 mg/dL | |
| Cyclosporine | Whole Blood Pools spiked | |
| with Cyclosporine stock | ||
| solution | 0.5 mg/dL | |
| Heparin | Whole Blood Pools spiked | |
| with Sodium Heparin stock | ||
| solution | 5500 IU/L | |
| Calcium Dobesilate | Whole Blood Pools spiked | |
| with Calcium Dobsilate | ||
| stock solution | 20 mg/dL | |
| Metronidazole | Whole Blood Pools spiked | |
| with Metronidazole stock | ||
| solution | 200 mg/dL | |
| Levodopa | Whole Blood Pools spiked | |
| with Levodopa Stock | ||
| solution | 20 mg/dL | |
| Acetylsalicyclic acid | Whole Blood spiked with | |
| Acetylsalicyclic acid Stock | ||
| Solution | 1000 mg/dL | |
| Acarbose | Whole blood spiked with | |
| Ascarbose Stock Solution | 0.05 mg/dL | |
| Acetaminophen | Whole blood spiked with | |
| Acetaminophen Stock | ||
| Solution | 26 mg/dL | |
| Acetylcystein | Whole blood spiked with | |
| Acetylcystein Stock | ||
| Solution | 166 mg/dL | |
| Ampicillin-Na | Whole blood spiked with | |
| Ampicillin-Na Stock | ||
| Solution | 1000 mg/dL | |
| Cefoxitin | Whole blood spiked with | |
| Cefoxin Stock Solution | 2500 mg/dL | |
| Doxycyclin | Whole blood spiked with | |
| Doxycyclin Stock Solution | 50 mg/dL | |
| Ibuprofen | Whole blood spiked with | |
| Ibuprofen Stock Solution | 50 mg/dL | |
| Methyldopa | Whole blood spiked with | |
| Methyldopa Stock Solution | 20 mg/dL | |
| Phenylbutazone | Whole blood spiked with | |
| Phenylbutazone Stock | ||
| Solution | 53.5 mg/dL | |
| Rifampicin | Whole blood spiked with | |
| Rifampicin Stock Solution | 8 mg/dL | |
| Theophylline | Whole blood spiked with | |
| Theophylline Stock | ||
| Solution | 10 mg/dL |
Table 17: Specifications and Summary of Endogenous Interference data
Drug Interference
Potential drug interfering substances were analyzed to determine their effect on HbA1c Advanced reagent . All drug interferences were tested at two % HbA1c concentrations, approximately 6.5% HbA1c (low level human venous whole blood EDTA sample) and approximately 8.0% HbA1c (high level human venous whole blood EDTA sample). Testing was completed using one lot of reagent on DxC 700 AU Analyzer.
Low and high pools were prepared by inter-diluting human whole blood samples. The two whole blood sample pools were spiked with each potential interfering drug to create test samples. Ten replicates of each test and reference sample containing no potential interferent) were tested on the DxC 700 AU to determine the magnitude of the interference. Each drug was tested to at least 5 times the highest drug concentration under therapeutic treatment.
No Significant Interference is recovery within 7% of the initial value (sample containing no interferent). Results outlined below showed no significant interference up to the stated concentrations.
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Table 18: Specifications and Summary of Drug Interference data
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Hemoglobin Derivative and Cross Reactants
Hemoglobin derivatives and potential interfering cross reactants were tested at two % HbA1c concentrations; approximately 6.5% HbA1c (low level human venous whole blood K2 EDTA sample) and approximately 8.0% HbA1c (high level human venous whole blood K2 EDTA sample) using one lot of reagent on one DxC700 AU analyzer. Low and high pools were prepared by interdiluting human whole blood samples.
Hemoglobin derivatives and potentially interfering cross reactants were tested at a minimum of 5 levels for: Labile Hemoglobin, Acetylated Hemoglobin, Carbamylated Hemoglobin, Glycated Albumin, HbA0 and HbA1a+b with 10 replicates tested per level on the DxC 700 AU analyzer to determine the magnitude of any interference effect.
No Significant Interference is recovery within 7% of the initial value (sample containing no interferent). Results in Table 19 showed no significant interference up to the stated concentrations.
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Table 19: Specification and Summary of Hemoglobin Derivative and Cross Reactant Interferences
| Potential Interfering
| Substance | Interference Pool details | Interferent Level |
|---|---|---|
| Labile Hemoglobin | Whole Blood Pools spiked with | |
| Glucose Stock Solution | 2000 | |
| mg/dL | ||
| Acetylated | ||
| Hemoglobin | Whole Blood Pools spiked with | |
| Acetylsalicylic acid Stock Solution | 0.5 mg/mL | |
| Carbamylated | ||
| Hemoglobin | Whole Blood Pools spiked with | |
| Potassium Cyanate Stock | ||
| Solution | 1.5 mg/mL | |
| Glycated Albumin | Whole Blood Pools spiked with | |
| Human Glycated Albumin Stock | ||
| Solution | 5mg/mL | |
| HbA0 | Whole Blood Pools spiked with | |
| HbA0 Stock Solution | 12 mg/mL | |
| HbA1a + 1b | Whole Blood Pools spiked with | |
| HbA1a +1b Stock Solution | 0.16 mg/mL |
Hemoglobin Variants
A hemoglobin variant study was performed to determine the presence of significant hemoglobin variant interference with major hemoglobin variants in the HbA1c Advanced assay. Results from singlicate measurements of samples were compared to results from a reference method, demonstrated to be free from hemoglobin interference; Trinity Biotech Hb9210 and Ultra2, Menarini HA8181V and TOSOH G8.
A minimum of 20 samples were tested for each variant (HbC, HbD, HbE, HbF, HbS and HbA2) on the DxC 700 AU Analyzer.
The following tables outline the number of samples of each variant, the range of % variant concentrations, %HbA1c concentrations and the relative % bias at 6.5% and 9.0% HbA1c.
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Table 20: Hemoglobin Variant Sample Ranges
| Hemoglobin
Variant | Number of
Samples | Range in %Variant
Concentration | Range in %HbA1c
Concentration |
|-----------------------|----------------------|------------------------------------|----------------------------------|
| HbC | 28 | 28.5 - 38.2 | 4.8 - 14.7 |
| HbD | 23 | 31.1 - 42.0 | 5.0 - 10.6 |
| HbE | 24 | 20.1 - 36.1 | 5.4 - 10.8 |
| HbF | 22 | 3.2 - 34.0 | 4.9 - 12.8 |
| HbS | 29 | 31.0 - 42.0 | 5.0 - 12.7 |
| HbA2 | 28 | 3.3 - 6.2 | 5.4 - 7.5 |
Table 21: Relative Bias Summary
| Hb Variant | Relative % bias (Range of % bias) observed relative to
Reference method | |
|------------|--------------------------------------------------------------------------------------------|--------------------------|
| | HbA1c6.5% HbA1c | HbA1c9.0% HbA1c |
| HbC | -2.57 (-4.30% to -1.80%) | -3.19 (-6.48% to 0.41%) |
| HbD | -0.77 (-4.81% to 2.99%) | -1.22 (-6.30% to -0.22%) |
| HbE | -1.12 (-9.16% to 2.48%) | 0.47 (-1.76% to 4.21%) |
| HbS | -1.18 (-2.17% to 3.04%) | -1.04 (-3.33% to 4.41%) |
| HbA2 | 0.48 (-1.92% to 5.60%) | 2.49 (-0.98% to 3.60%) |
| HbF | Specimens containing high amounts of HbF (> 7%) may yield lower than expected HbA1c Values | |
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Anticoaqulants
The data supports the use of the following blood collection tubes with the HbA1c Advanced reagent .
- K2 EDTA ●
- K3 EDTA ●
- Sodium Heparin ●
- Lithium Heparin .
Expected Values/Reference Interval
Beckman Coulter used evidence recommended by the American Diabetes Association Standards of (ADA), which may be used as an aid in the diagnosis of diabetes mellitus:
Table 1: HbA1c ranges recommended by the ADA as an aid in the diagnosis of diabetes mellitus 1,2,3
| HbA1c Advanced | ||
|---|---|---|
| NGSP % | IFCC mmol/mol | Suggested |
| Diagnosis | ||
| ≥ 6.5 | ≥48 | Diabetic |
| 5.7 – 6.4 | 39 - 47 | Pre-Diabetic |