Who is the manufacturer of HbA1c Advanced?

Beckman Coulter Ireland, Inc. filed the 510(k) submission for HbA1c Advanced (K182651).

What is the FDA product code for HbA1c Advanced?

PDJ. It is classified under 21 CFR 862.1373 as a Class 2 device in the Clinical Chemistry panel.

What is the regulatory pathway for HbA1c Advanced?

510(k) clearance (submission type: Traditional).

What are the predicate devices for HbA1c Advanced?

D-100™ HbA1c, D-100™HbA1c Calibrator Pack (K151321).

Who can help prepare an FDA 510(k) submission like HbA1c Advanced?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

HbA1c Advanced

K182651 · Beckman Coulter Ireland, Inc. · PDJ · Jan 16, 2019 · Clinical Chemistry

Device Facts

Record ID	K182651
Device Name	HbA1c Advanced
Applicant	Beckman Coulter Ireland, Inc.
Product Code	PDJ · Clinical Chemistry
Decision Date	Jan 16, 2019
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.1373
Device Class	Class 2

Intended Use

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.

Device Story

HbA1c Advanced assay is an in vitro diagnostic reagent kit for use on the Beckman Coulter DxC700 AU Clinical Chemistry Analyzer. It processes human venous whole blood samples (K2-EDTA, K3-EDTA, Li-Heparin, Na-Heparin). The device uses an automated hemolysis step with tetradecyltrimethylammonium bromide (TTAB) to eliminate leukocyte interference. Total hemoglobin is measured colorimetrically (570/660 nm). HbA1c is measured via a turbidimetric immunoinhibition method (340/700 nm) where HbA1c antibodies form soluble complexes with sample HbA1c, and polyhaptens bind excess antibodies for turbidimetric measurement. The system calculates the HbA1c/Total Hemoglobin ratio, outputting results in mmol/mol (IFCC) or %HbA1c (DCCT/NGSP). Used in clinical laboratories by trained personnel; results assist clinicians in diagnosing diabetes and monitoring long-term glycemic control. The device provides standardized, precise quantification of HbA1c, aiding in patient management and risk assessment.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP05-A3 over 20 days (n=2) across 3 lots and 3 instruments; total precision CVs ranged from 1.14% to 2.09% (NGSP). Linearity confirmed for 4-15% HbA1c (NGSP) and 20-140 mmol/mol (IFCC). Method comparison (n=138) against NGSP Secondary Reference Laboratory (HPLC) showed strong correlation (R=0.998, slope 0.990). Interference studies (CLSI EP07) confirmed no significant interference (recovery within 7%) for endogenous substances, drugs, hemoglobin derivatives, and common variants (HbC, D, E, S, A2). HbF >7% may cause lower results.

Technological Characteristics

Turbidimetric inhibition immunoassay. Reagents: Anti-human HbA1c antibody (sheep), HbA1c polyhapten, TTAB hemolyzing reagent. Analyzed on DxC 700 AU Clinical Chemistry Analyzer. Measures absorbance at 340/700 nm (HbA1c) and 570/660 nm (T-Hb). Standardized to IFCC reference material; NGSP certified. Liquid, ready-to-use format. Automated hemolysis.

Indications for Use

Indicated for quantitative determination of HbA1c in human venous whole blood to aid in diabetes mellitus diagnosis, monitor long-term glucose control in diabetic patients, and identify individuals at risk for developing diabetes.

Regulatory Classification

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.

Special Controls

(b) Classification. Class II (special controls). Hemoglobin A1c test systems must comply with the following special controls: 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%, 6.5%, 8.0% and 12% hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least 3 lots of the device and 3 instruments, as applicable. ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the new device and compare results of the new device to results of the 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%. 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.

*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.

Predicate Devices

D-100™ HbA1c, D-100™HbA1c Calibrator Pack (K151321)

Reference Devices

Trinity Premier Hb9210
Trinity Ultra Primus 2
Menarini HA8180V (k162822)
Tosoh G8

Related Devices

K120199 — GLYCOSYLATED HEMOGLOBIN ASSAY; CLINICAL CHEMISTRY · Beckman Coulter, Inc. · Oct 12, 2012
K173909 — Dimension Hemoglobin A1c Assay · Siemens Healthcare Diagnostics, Inc. · Jul 13, 2018
K121492 — UNICEL DXC SYNCHRON SYSTEMS HEMOGLOBIN ALC-(HBA1C-) REAGENT · Beckman Coulter, Inc. · Sep 11, 2012

Submission Summary (Full Text)

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health and Human Services logo on the left and the FDA logo on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. Food & Drug Administration" in blue. 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) | <div> <div> ☑ Prescription Use (Part 21 CFR 801 Subpart D) </div> </div> | |------------------------------------------------------------------------------------------------------------------------------| | <div> <div> ☐ Over-The-Counter Use (21 CFR 801 Subpart C) </div> </div> | #### CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {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<5.7 NGSP%, <39 IFCC mmol/mol | Same | | Traceability | Traceable to the Diabetes Control and Complications trial (DCCT) reference | Same | | | method and IFCC. Certified via the National Glycohemoglobin Standardization Program (NGSP). | | | Sensitivity | Not stated | Not stated | | Specificity (Interference - Hb Variants) | Significant interference was defined as ≥ 7% change in HbA1c value in the presence of the hemoglobin variant relative to control. | No Significant interference (NSI) is recovery within 7% of the reference value from Hb variants C, S, D, E, A2. | | | HbC, HbD, HbE, HbS HbA2, HbF | Hemoglobin F interference shall be displayed as a disclaimer on package insert. | | | NSI is observed from the following endogenous substances up to the stated concentrations (Significant interference is defined as ≥7% change in HbA1c value of the mean test value relative to mean of the reference samples): | The criteria for NSI is recovery within 7% of the initial value (sample containing no interferent). Similar for: | | Specificity (Interferences - Endogenous) | Conjugated Bilirubin: NSI up to 60 mg/dL Unconjugated Bilirubin: NSI up 60 mg/dL | Conjugated Bilirubin: NSI up to 60 mg/dL Unconjugated Bilirubin: NSI up to 60 mg/dL | | | Glucose: NSI up 2000 mg/dL | Glucose: NSI up to 2000 mg/dL | | | Total Protein: NSI up to 21 g/dL | Total Protein: NSI up to 21 g/dL | | Specificity (Interference - Hb Derivatives and Cross Reactants) | Significant interference defined as % recovery of ±7% change in % HbA1c value from the control Acetylated Hb: up to 50 mg/dL | NSI is recovery within 7% of the initial value (sample containing no interferent). Acetylated Hb: NSI up to 0.5 mg/mL | | Specificity (Interference - Drug) | Significant interference was defined as a ≥7% change in %HbA1c value from the control. Acetylcysteine: 166 mg/dL Ampicillin-Na: 1000 mg/dL Acetylsalicylic Acid: 1000 mg/dL Ascorbic Acid: 300 mg/dL Cefoxitin: 2500 mg/dL Levodopa: 20 mg/dL Methyldopa: 20 mg/dL Metronidazole: 200 mg/dL Doxycyclin: 50 mg/dL Cyclosporine: 5 mg/L Theophylline: 100 mg/L Ibuprofen: 500 mg/L Theophylline: 100mg/L | The criteria for no significant interference (NSI) is recovery within 7% of the initial value (Sample containing no interferent): Acetylcystein:166 mg/dL Ampicillin-Na: 1000 mg/dL Acetylsalicylic Acid: 1000 mg/dL Ascorbic Acid: 300 mg/dL Cefoxitin: 2500 mg/dL Levodopa: 20 mg/dL Methyldopa: 20 mg/dL Metronidazole: 200 mg/dL Doxycyclin: 50 mg/dL Cyclosporine: 0.5 mg/dL Theophylline: 10 mg/dL Ibuprofen: 50 mg/dL | | Total Allowable Error | ≤6% | ≤6% | # Table 2: Similarities between the Predicate Device and the Proposed Device: {6}------------------------------------------------ {7}------------------------------------------------ {8}------------------------------------------------ # Table 3: Differences between the Predicate Device and the Proposed Device: | Feature | Predicate | Proposed New System | |--------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Proprietary and Established Names | D-100™ HbA1c, D-100™ HbA1c Calibrator Pack | HbA1c Advanced | | Instrument Platform | D-100™ Hemoglobin Testing System | DxC 700 AU Clinical Chemistry Analyzer | | Control | Commercially available Bio- Rad Lyphocheck Diabetes control materials | 2 Levels of control material | | Operating Principle | Ion-exchange Quantitative high performance liquid chromatography (HPLC) | Quantitative turbidimetric inhibition immunoassay | | Sample Types | Capillary blood Acceptable anticoagulants are Potassium Oxalate/ Sodium Fluoride Sodium Citrate | Not Applicable for HbA1c Advanced | | Analytical Range (Linearity) | HbA1c: 3.5 to 20% HbA1c (NGSP) 15 - 195 mmol/mol (IFCC) | HbA1c: 4.0 - 15% HbA1c (NGSP) 20 - 140 mmol/mol (IFCC) | | Specificity (Interferences - Endogenous) | Significant interference defined as a ±7% change in % HbA1c value from the control Lipemia (Intralipid): NSI up to 6000 mg/dL Rheumatoid Factor: NSI up to 750 IU/mL | NSI is recovery within 7% of the initial value (sample containing no interferent). Lipemia: NSI up to 500 mg/dL Rheumatoid Factor (RF): NSI up to 1000 IU/mL | | Specificity (Interference - Hb Derivatives and Cross Reactants) | Significant interference defined as % recovery of ±7% change in % HbA1c value from the control Carbamylated Hb: up to 5% Labile Hb: up to 1200 mg/dL of glucose does not interfere with this assay | NSI is recovery within 7% of the initial value (sample containing no interferent). Carbamylated Hb: NSI up to 1.5 mg/mL Labile Hb; NSI up to 2000 mg/dL Glycated Albumin: NSI up to 5 mg/mL HbA0: NSI up to 12 mg/mL | | | | HbA1a+b: NSI up to 0.16 mg/mL | | Drug Interference | Significant interference was defined as a ±7% change in %HbA1c value from the control. Acetaminophen: 200 mg/L Heparin: 5000 U/L Rifampicin: 64 mg/L Phenylbutazone – 400 mg/L | NSI is recovery within 7% of the initial value (sample containing no interferent): Acetaminophen: 26 mg/dL Heparin: 5500 IU/L Rifampicin: 8 mg/dL Phenylbutazone: 53.5 mg/dL Glyburide: 0.12 mg/dL Salicylic Acid: 4.76 mg/dL Sitagliptin: 0.2 mg/dL Rosiglitazone: 0.33 mg/dL Metformin: 5 mg/dL Calcium Dobsilate: 20mg/dL Acarbose: 0.05 mg/dL | | Specificity (Interference - Hb Variants) | Significant interference was defined as ≥ 7% change in HbA1c value in the presence of the hemoglobin variant relative to control. HbF concentrations up to 30% do not interfere with the test. | No Significant interference is recovery within 7% of the reference value (value assigned in Secondary Reference Laboratory). Samples containing ≥7% HbF may result in lower than expected HbA1c results | {9}------------------------------------------------ {10}------------------------------------------------ {11}------------------------------------------------ # 9.0 Performance Characteristics – Analytical Performance: # Precision Precision of the HbA1c Advanced reagent on the DxC 700 AU was evaluated based on CLSI guideline EP05-A3: "Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Third Edition". 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 (n=2) in random order. NGSP results are shown in Tables 4 - 7. IFCC results are shown in Tables 8 - 11. {12}------------------------------------------------ | Sample/ Control details | Mean % HbA1c | Repeatability (Within-run) | | Specification | Between- Run | | Between- Day | | Between-Lot | | Total Precision | | Specification | |-----------------------------|-----------------|-------------------------------|------|-------------------------------|-----------------|------|-----------------|------|-------------|------|--------------------|------|---------------------------------| | | Concentration | % CV | SD | CV ≤1.5% or SD ≤0.1% HbA1c | % CV | SD | % CV | SD | % CV | SD | % CV | SD | CV <2% or SD ≤0.13% HbA1c | | Human Whole Blood 1 | 5.06 | 0.88 | 0.04 | Pass | 0.80 | 0.04 | 0.64 | 0.03 | 0.92 | 0.05 | 1.63 | 0.08 | Pass | | Human Whole Blood 2 | 6.72 | 1.01 | 0.07 | Pass | 0.60 | 0.04 | 0.65 | 0.04 | 0.93 | 0.06 | 1.64 | 0.11 | Pass | | Human Whole Blood 3 | 8.06 | 0.77 | 0.06 | Pass | 0.47 | 0.04 | 0.73 | 0.06 | 1.06 | 0.09 | 1.57 | 0.13 | Pass | | Human Whole Blood 4 | 11.70 | 0.79 | 0.09 | Pass | 0.48 | 0.06 | 0.84 | 0.10 | 0.19 | 0.02 | 1.26 | 0.15 | Pass | | Spiked Human Whole Blood | 14.02 | 0.74 | 0.10 | Pass | 0.49 | 0.07 | 0.72 | 0.10 | 0.32 | 0.04 | 1.19 | 0.17 | Pass | | Whole Blood Control 1 | 5.32 | 1.19 | 0.06 | Pass | 0.84 | 0.04 | 0.66 | 0.03 | 1.34 | 0.07 | 2.08 | 0.11 | Pass | | Whole Blood Control 2 | 9.88 | 0.77 | 0.08 | Pass | 0.48 | 0.05 | 0.65 | 0.06 | 1.07 | 0.11 | 1.54 | 0.15 | Pass | Table 4: DxC 700 AU: Instrument 1: NGSP units: Summary of 20 Day Precision Performance #### Table 5: DxC 700 AU Instrument 2: NGSP units: Summary of 20 Day Precision Performance | Sample/ Control details | Mean % HbA1c Concentration | Repeatability (Within-run) | | Specification | Between-Run | | Between-Day | | Between-Lot | | Total Precision | | Specification | |-----------------------------|----------------------------------|-------------------------------|------|---------------|-------------|------|-------------|------|-------------|------|--------------------|------|---------------| | | | % CV | SD | | % CV | SD | % CV | SD | % CV | SD | % CV | SD | | | Human Whole Blood 1 | 5.03 | 1.15 | 0.06 | Pass | 0.37 | 0.02 | 0.57 | 0.03 | 1.02 | 0.05 | 1.68 | 0.08 | Pass | | Human Whole Blood 2 | 6.69 | 1.14 | 0.08 | Pass | 0.20 | 0.01 | 0.50 | 0.03 | 0.83 | 0.06 | 1.51 | 0.10 | Pass | | Human Whole Blood 3 | 8.05 | 0.86 | 0.07 | Pass | 0.48 | 0.04 | 0.49 | 0.04 | 0.70 | 0.06 | 1.31 | 0.11 | Pass | | Human Whole Blood 4 | 11.69 | 0.71 | 0.08 | Pass | 0.33 | 0.04 | 0.61 | 0.07 | 0.56 | 0.07 | 1.14 | 0.13 | Pass | | Spiked Human Whole Blood | 14.04 | 0.75 | 0.11 | Pass | 0.58 | 0.08 | 0.34 | 0.05 | 0.69 | 0.10 | 1.22 | 0.17 | Pass | | Whole Blood Control 1 | 5.28 | 1.23 | 0.06 | Pass | 0.41 | 0.02 | 0.75 | 0.04 | 1.32 | 0.07 | 1.99 | 0.11 | Pass | | Whole Blood Control 2 | 9.88 | 0.77 | 0.08 | Pass | 0.42 | 0.04 | 0.54 | 0.05 | 0.95 | 0.09 | 1.40 | 0.14 | Pass | {13}------------------------------------------------ | Sample/ Control details | | Repeatability (Within-run) | | Specification | Between-Run | | Between-Day | | Between-Lot | | Total Precision | | Specification | |-----------------------------|----------------------------------|-------------------------------|------|----------------------------------|-------------|------|-------------|------|-------------|------|--------------------|------|------------------------------| | | Mean % HbA1c Concentration | % CV | SD | CV <1.5% or SD <0.1% HbA1c | % CV | SD | % CV | SD | % CV | SD | % CV | SD | CV <2% or SD <0.13% HbA1c | | Human Whole Blood 1 | 5.03 | 0.83 | 0.04 | Pass | 0.45 | 0.02 | 0.70 | 0.04 | 1.02 | 0.05 | 1.55 | 0.08 | Pass | | Human Whole Blood 2 | 6.66 | 0.82 | 0.06 | Pass | 0.31 | 0.02 | 0.48 | 0.03 | 1.31 | 0.09 | 1.65 | 0.11 | Pass | | Human whole Blood 3 | 7.98 | 0.73 | 0.06 | Pass | 0.58 | 0.05 | 0.47 | 0.04 | 1.68 | 0.14 | 1.98 | 0.16 | Pass | | Human Whole Blood 4 | 11.68 | 0.71 | 0.08 | Pass | 0.21 | 0.03 | 0.67 | 0.08 | 0.54 | 0.06 | 1.14 | 0.13 | Pass | | Spiked Human Whole Blood | 13.99 | 0.66 | 0.09 | Pass | 0.44 | 0.06 | 0.56 | 0.08 | 0.66 | 0.09 | 1.18 | 0.17 | Pass | | Whole Blood Control 1 | 5.25 | 0.93 | 0.05 | Pass | 0.97 | 0.05 | 0.60 | 0.03 | 1.37 | 0.07 | 2.01 | 0.11 | Pass | | Whole Blood Control 2 | 9.72 | 0.65 | 0.06 | Pass | 0.36 | 0.03 | 0.65 | 0.06 | 1.45 | 0.14 | 1.75 | 0.17 | Pass | Table 6: DxC 700 AU Instrument 3: NGSP units: Summary of 20 Day Precision Performance {14}------------------------------------------------ | Sample/ Control details | Mean % HbA1c Concentration | Repeatability (Within-run) | | Specification | Between- Run | | Between- Day | | Between- Lot | | Between Instrument | | Total Precision | | Specification | |-----------------------------|----------------------------------|-------------------------------|------|------------------------------------|-----------------|------|-----------------|------|-----------------|------|-----------------------|------|--------------------|------|-----------------------------------| | | | % CV | SD | CV <=1.5% or SD <=0.1% HbA1c | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | CV <=2% or SD <=0.13% HbA1c | | Human Whole Blood 1 | 5.07 | 0.96 | 0.05 | Pass | 0.57 | 0.03 | 0.64 | 0.03 | 0.99 | 0.05 | 0.74 | 0.04 | 1.78 | 0.09 | Pass | | Human Whole Blood 2 | 6.72 | 1.00 | 0.07 | Pass | 0.41 | 0.03 | 0.55 | 0.04 | 1.05 | 0.07 | 0.56 | 0.04 | 1.69 | 0.11 | Pass | | Human Whole Blood 3 | 8.07 | 0.79 | 0.06 | Pass | 0.51 | 0.04 | 0.58 | 0.05 | 1.22 | 0.10 | 0.57 | 0.05 | 1.74 | 0.14 | Pass | | Human Whole Blood 4 | 11.71 | 0.74 | 0.09 | Pass | 0.36 | 0.04 | 0.71 | 0.08 | 0.46 | 0.05 | 0.32 | 0.04 | 1.22 | 0.14 | Pass | | Spiked Human Whole Blood | 14.03 | 0.72 | 0.10 | Pass | 0.51 | 0.07 | 0.56 | 0.08 | 0.58 | 0.08 | 0.12 | 0.02 | 1.20 | 0.17 | Pass | | Whole Blood Control 1 | 5.29 | 1.12 | 0.06 | Pass | 0.78 | 0.04 | 0.67 | 0.04 | 1.34 | 0.07 | 0.50 | 0.03 | 2.09 | 0.11 | Pass | | Whole Blood Control 2 | 9.84 | 0.73 | 0.07 | Pass | 0.43 | 0.04 | 0.61 | 0.06 | 1.17 | 0.12 | 0.70 | 0.07 | 1.72 | 0.17 | Pass | Table 7: Instruments Combined (Instrument 1, 2, 3): NGSP units: Summary of 20 Day Precision Performance {15}------------------------------------------------ | Sample/ Control details | Mean (mmol/mol) | Repeatability (Within-run) | | Specification | Between- Run | | Between- Day | | Between-Lot | | Total Precision | | Specification | |-----------------------------|------------------------|-------------------------------|------|---------------------------------|-----------------|------|-----------------|------|-------------|------|--------------------|------|---------------------------------| | | HbA1c Concentration | % CV | SD | CV <2.3% or SD <1.1 mmol/mol | % CV | SD | % CV | SD | % CV | SD | % CV | SD | CV ≤2.9% or SD <1.4 mmol/mol | | Human Whole Blood 1 | 31.84 | 1.51 | 0.48 | Pass | 1.43 | 0.46 | 1.08 | 0.34 | 1.60 | 0.51 | 2.84 | 0.90 | Pass | | Human Whole Blood 2 | 49.92 | 1.49 | 0.75 | Pass | 0.90 | 0.45 | 0.97 | 0.48 | 1.36 | 0.68 | 2.41 | 1.21 | Pass | | Human Whole Blood 3 | 64.65 | 1.06 | 0.68 | Pass | 0.61 | 0.40 | 1.01 | 0.65 | 1.43 | 0.93 | 2.14 | 1.38 | Pass | | Human Whole Blood 4 | 104.38 | 1.31 | 1.37 | Pass | 0.00 | 0.00 | 1.03 | 1.07 | 0.23 | 0.24 | 1.68 | 1.76 | Pass | | Spiked Human Whole Blood | 129.76 | 0.87 | 1.13 | Pass | 0.57 | 0.74 | 0.86 | 1.11 | 0.37 | 0.49 | 1.40 | 1.82 | Pass | | Whole Blood Control 1 | 34.65 | 2.01 | 0.70 | Pass | 1.28 | 0.44 | 1.18 | 0.41 | 2.22 | 0.77 | 3.46 | 1.20 | Pass | | Whole Blood Control 2 | 84.53 | 0.98 | 0.83 | Pass | 0.61 | 0.51 | 0.82 | 0.69 | 1.36 | 1.15 | 1.96 | 1.66 | Pass | # Table 8: DxC 700 AU Instrument 1: IFCC units: Summary of 20 Day Precision Performance {16}------------------------------------------------ | Sample/ Control details | Mean (mmol/mol) HbA1c Concentration | Repeatability (Within-run) | | Specification | Between- Run | | Between-Day | | Between- Lot | | Total Precision | | Specification | |-----------------------------|----------------------------------------------|-------------------------------|------|------------------------------------|-----------------|------|-------------|------|-----------------|------|--------------------|------|------------------------------------| | | | % CV | SD | CV ≤2.3% or SD ≤1.1 mmol/mol | % CV | SD | % CV | SD | % CV | SD | % CV | SD | CV ≤2.9% or SD ≤1.4 mmol/mol | | Human Whole Blood 1 | 31.51 | 2.01 | 0.63 | Pass | 1.19 | 0.37 | 0.77 | 0.24 | 1.81 | 0.57 | 3.05 | 0.96 | Pass | | Human Whole Blood 2 | 49.59 | 1.63 | 0.81 | Pass | 0.42 | 0.21 | 0.74 | 0.37 | 1.18 | 0.59 | 2.18 | 1.08 | Pass | | Human Whole Blood 3 | 64.48 | 1.18 | 0.76 | Pass | 0.66 | 0.43 | 0.67 | 0.43 | 0.96 | 0.62 | 1.79 | 1.15 | Pass | | Human Whole Blood 4 | 104.29 | 0.88 | 0.91 | Pass | 0.38 | 0.40 | 0.75 | 0.78 | 0.70 | 0.73 | 1.40 | 1.46 | Pass | | Spiked Human Whole Blood | 129.92 | 0.88 | 1.15 | Pass | 0.66 | 0.85 | 0.43 | 0.56 | 0.82 | 1.06 | 1.44 | 1.87 | Pass | | Whole Blood Control 1 | 34.24 | 2.09 | 0.72 | Pass | 0.74 | 0.25 | 1.23 | 0.42 | 2.23 | 0.76 | 3.38 | 1.16 | Pass | | Whole Blood Control 2 | 84.52 | 0.98 | 0.83 | Pass | 0.54 | 0.46 | 0.69 | 0.58 | 1.22 | 1.03 | 1.80 | 1.52 | Pass | # Table 9: DxC 700 AU Instrument 2: IFCC units: Summary of 20 Day Precision Performance {17}------------------------------------------------ | Sample/ Control details | Mean (mmol/mol) | Repeatability (Within-run) | | Specification | Between-Run | | Between-Day | | Between-Lot | | Total Precision | | Specifications | |-----------------------------|----------------------------|-------------------------------|------|------------------------------------|-------------|------|-------------|------|-------------|------|--------------------|------|------------------------------------| | | HbA1c Concentrati on | % CV | SD | CV <2.3% or SD <1.1 mmol/mol | % CV | SD | % CV | SD | % CV | SD | % CV | SD | CV ≤2.9% or SD <1.4 mmol/mol | | Human Whole Blood 1 | 31.46 | 1.41 | 0.46 | Pass | 1.18 | 0.38 | 1.31 | 0.42 | 1.78 | 0.58 | 2.88 | 0.93 | Pass | | Human Whole Blood 2 | 49.27 | 1.21 | 0.61 | Pass | 0.46 | 0.23 | 0.70 | 0.35 | 1.93 | 0.97 | 2.42 | 1.22 | Pass | | Human Whole Blood 3 | 63.68 | 1.00 | 0.65 | Pass | 0.79 | 0.52 | 0.63 | 0.41 | 2.29 | 1.49 | 2.69 | 1.75 | Pass | | Human Whole Blood 4 | 104.18 | 0.87 | 0.92 | Pass | 0.25 | 0.26 | 0.81 | 0.85 | 0.66 | 0.70 | 1.39 | 1.46 | Pass | | Spiked Human Whole Blood | 129.37 | 0.79 | 1.02 | Pass | 0.52 | 0.67 | 0.66 | 0.86 | 0.87 | 1.01 | 1.39 | 1.81 | Pass | | Whole Blood Control 1 | 33.83 | 1.58 | 0.54 | Pass | 1.61 | 0.55 | 1.02 | 0.35 | 2.32 | 0.79 | 3.40 | 1.16 | Pass | | Whole Blood Control 2 | 82.77 | 0.83 | 0.69 | Pass | 0.46 | 0.38 | 0.83 | 0.69 | 1.86 | 1.55 | 2.24 | 1.87 | Pass | # Table 10: DxC 700 AU Instrument 3: IFCC units: Summary of 20 Day Precision Performance {18}------------------------------------------------ | Sample/ Control details | Mean (mmol/mol) HbA1c Concen- tration | Repeatability (Within-run) | | Specification | Between- Run | | Between- Day | | Between- Lot | | Between Instrument | | Total Precision | | Specification | |-----------------------------|---------------------------------------------------|-------------------------------|------|---------------------------------------|-----------------|------|-----------------|------|-----------------|------|-----------------------|------|--------------------|------|------------------------------------| | | | % CV | SD | CV ≤2.3% or SD ≤1.1 mmol/mol | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | CV ≤2.9% or SD ≤1.4 mmol/mol | | Human Whole Blood 1 | 31.91 | 1.66 | 0.53 | Pass | 1.27 | 0.41 | 1.08 | 0.34 | 1.73 | 0.55 | 1.31 | 0.42 | 3.20 | 1.02 | Pass | | Human Whole Blood 2 | 49.95 | 1.45 | 0.72 | Pass | 0.63 | 0.31 | 0.81 | 0.41 | 1.53 | 0.76 | 0.82 | 0.41 | 2.49 | 1.24 | Pass | | Human Whole Blood 3 | 64.75 | 1.08 | 0.70 | Pass | 0.69 | 0.45 | 0.79 | 0.51 | 1.66 | 1.07 | 0.77 | 0.50 | 2.37 | 1.53 | Pass | | Human Whole Blood 4 | 104.51 | 1.04 | 1.09 | Pass | 0.23 | 0.24 | 0.87 | 0.91 | 0.57 | 0.60 | 0.40 | 0.42 | 1.54 | 1.61 | Pass | | Spiked Human Whole Blood | 129.84 | 0.85 | 1.10 | Pass | 0.58 | 0.76 | 0.67 | 0.87 | 0.69 | 0.89 | 0.14 | 0.19 | 1.42 | 1.84 | Pass | | Whole Blood Control 1 | 34.32 | 1.91 | 0.66 | Pass | 1.26 | 0.43 | 1.15 | 0.39 | 2.26 | 0.78 | 0.87 | 0.30 | 3.52 | 1.21 | Pass | | Whole Blood Control 2 | 84.10 | 0.93 | 0.78 | Pass | 0.54 | 0.46 | 0.78 | 0.66 | 1.50 | 1.26 | 0.90 | 0.76 | 2.20 | 1.85 | Pass | # Table 10: Instruments Combined (Instrument 1, 2, 3): IFCC units: Summary of 20 Day Precision Performance {19}------------------------------------------------ # Linearity: Dynamic Range/ Analytical Measuring Range studies were designed using CLSI Guideline EP06-A: "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline". High and low pools were prepared as per Table 1. A linearity series was prepared by inter-diluting the high and low pools to achieve a % HbA1c concentration spanning the required analytical range. The samples were mixed together in varying ratios. Data was analyzed using Polynomial regression analysis (for first, second and third order polynomials) to determine the statistical significance of non-linearity. Where data generated was non-linear, the best fitting polynomial was applied to the data and difference between this best fitting, non-linear polynomial and the linear polynomial was calculated. Regression parameters for slope, intercept and R value were calculated. 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). | Reagent | Acceptance Criteria | Results | Pass/ Fail | Acceptance Criteria | Pass/Fail | | |-------------------|------------------------|-------------------|--------------------|------------------------|-------------------------------------------------------------------------|------| | | Linear Range | Linear From | Linear To | | Regression Parameters | | | HbA1c Advanced | 4-15% HbA1c | 3.94% HbA1c | 15.37% HbA1c | Pass | Slope: 1.0 ± 0.05 Intercept: ≤ ± 0.5 % HbA1c R: ≥ 0.990 N: ≥ 9 | Pass | | HbA1c Advanced | 20 – 140 mmol/mol | 19.51 mmol/mol | 144.49 mmol/mol | Pass | Slope: 1.0 ± 0.05 Intercept: ≤ ± 5.5 mmol/L R: ≥ 0.990 N: ≥ 9 | Pass | # Table 12: Linearity Results Summary {20}------------------------------------------------ # Method Comparison Method comparison and bias estimation experiments were designed using CLSI Guideline EP09-A3; "Measurement Procedure Comparison and Bias Estimation using Patient Samples; Approved Guideline." The patient correlation studies were performed using a standardized test method in an NGSP Secondary Reference Laboratory (SRL) using a test system (method X - HA8180V HPLC) with an analytical measuring range of 4-15% HbA1c (NGSP) and the proposed new Beckman Coulter HbA1c test system (method Y - HbA1c Advanced, 1 lot) with a proposed measuring range of 4-15 % HbA1c (NGSP) on a DxC 700 AU analyzer. Over a 120 (duplicates) of venous human frozen whole blood specimens (K2 EDTA anticoagulant type) with HbA1c concentrations were tested using on the DxC 700 AU Analyzer. | Hemoglobin A1c Level | No. of Samples (SRL) | % Samples tested (SRL) | No. of Samples tested (Beckman) | % Samples tested (Beckman) | |-------------------------|----------------------------|---------------------------|------------------------------------|-------------------------------| | ≤5% | 6 | 4.35 | 6 | 4.35 | | 5 – 6% | 18 | 13.04 | 22 | 15.94 | | 6 – 6.5% | 32 | 23.19 | 32 | 23.19 | | 6.5 – 7% | 35 | 25.36 | 35 | 25.36 | | 7 – 8% | 25 | 18.12 | 23 | 16.67 | | 8 – 9% | 12 | 8.7 | 10 | 7.25 | | > 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. {21}------------------------------------------------ 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 | {22}------------------------------------------------ # 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. {23}------------------------------------------------ | 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…

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