(265 days)
The ADAMS A1c HA-8180V system is intended for the quantitative determination of hemoglobin A1c (IFCC mmol/mol and NGSP %) in human whole blood and hemolysate samples using Ion Exchange high performance liquid chromatography (HPLC).
Hemoglobin A1c measurements obtained from the ADAMS A1C HA-8180V are used as an aid in the diagnosis of diabetes mellitus, an aid in the identification of individuals who may be at risk of developing diabetes, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. The ADAMS A1c HA-8180V is intended for Professional Use Only.
The CALIBRATOR 80 is for the calibration of the ADAMS A1c HA-8180V system used for the quantitative determination of hemoglobin A1c in human whole blood and hemolysate samples.
For In Vitro Diagnostic Use Only.
The ADAMS A1c HA-8180V system is a fully automated analyzer that uses ion exchange high performance liquid chromatography (HPLC) technology to separate glycated (labile A1c(L-A1c) and stable A1c (S-A1c)) and non-glycated (HbA0) forms of hemoglobin.
Hemoglobin A1c measurements obtained from the ADAMS A1C HA-8180V are used as an aid in the diagnosis of diabetes mellitus, an aid in the identification of individuals who may be at risk of developing diabetes, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. The subject device consists of the ADAMS A1c HA-8180V test analytical instrument and CALIBRATOR 80, which is used to calibrate the HA-8180V. The ADAMS A1c HA-8180V system is for use in professional clinical laboratory settings.
This method is certified by the National Glycohemoglobin Standardization Program (NGSP).
Hemoglobin test samples are prepared by automated dilution of anticoagulated whole blood in Hemolysis Washing Solution 80H. Alternately, hemolysis samples may be prepared "off-line" by manual dilution of anticoagulated whole blood with Diluent 80. The sample is then injected into the column, which contains a filter to remove sample impurities. The differing polarity and ionic charges of the released hemoglobin fractions bind with variable strength to the negatively charged stationary phase of the column. The mobile phase, consisting of three eluents of increasing ionic strength, is injected into the column. Hemoglobin fractions eluted from the column are identified and quantified using light absorption, and are measured at 420 nm and 500 nm. The dual wavelength colorimetric analysis of the separated peaks is processed by a microcomputer to obtain peak identification and hemoglobin fraction quantitation. All pre-analytical and analytical steps are performed automatically by the ADAMS A1c HA-8180V system. Tests may be ordered in batch or for STAT measurement.
HbA1c and HbF results are reported in the presence of HbC, HbD, HbE, or HbS. A result of the detected HbC or HbS, and a peak resulting from HbD or HbE is also listed in the peak information. When a peak resulting from HbD or HbE is detected, a 'V' is listed in the peak information. HbA1c and HbF results are not reported when the instrument detects other peaks that affect HbA1c measurement value. The identification of any of these variants is not intended for use in diagnosis of hemoglobinopathies.
This document describes the validation study for the ADAMS A1c HA-8180V system, a device for quantitative determination of hemoglobin A1c.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Precision: Performance testing must use blood samples with concentrations near 5.0%, 6.5%, 8.0%, and 12% HbA1c, evaluated over a minimum of 20 days using at least three lots of the device and three instruments. | Precision demonstrated: The study used four donor samples at ~5.0%, ~6.5%, ~8.0%, and ~12.0% HbA1c, plus three quality control materials. It was evaluated using three reagent lots and three HA-8180V systems over 20 days, in duplicate, two runs per instrument per day. The total CV for whole blood samples combined across instruments ranged from 0.5% at 5.2% HbA1c to 1.0% at 11.8% HbA1c. For hemolysate samples combined across instruments, the total CV ranged from 0.4% at 5.2% HbA1c to 0.9% at 11.9% HbA1c. IFCC values also showed similar low CVs. |
| Accuracy (Method Comparison): Performance testing 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. | Accuracy demonstrated: A method comparison study included 143 variant-free whole blood K2-EDTA samples ranging from 4.1% to 17.7% HbA1c. These were compared against a secondary NGSP reference laboratory (Tosoh G8 HPLC method). The weighted Deming regression for whole blood showed a slope of 0.9864 and an R² of 0.998. For hemolysate, the slope was 0.9906 and R² was 0.998. The findings demonstrated little to no bias. |
| Total Error: 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%. | Total Error demonstrated: Total Error (TE) was calculated at 5.0%, 6.5%, 8.0%, and 12.0% HbA1c using bias from method comparison and CV from precision studies. For whole blood, the %TE ranged from 1.5% at 5.0% HbA1c to 2.4% at 12.0% HbA1c. For hemolysate, the %TE ranged from 1.6% at 8.0% HbA1c to 2.1% at 6.5% HbA1c. All reported %TE values were significantly less than the ≤6% acceptance criterion. |
| Interference from Hemoglobin Variants: 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. | Interference demonstrated: A study with 165 samples containing Hb variants (A2, C, D, E, F, S) showed that HbA1c results were accurate with no significant interference for HbA2 (≤16%), HbC (≤39%), HbD (≤36%), HbF (≤30%), HbS (≤40%). Bias results for HbA1c at ~6.5% and ~8.0% were generally within a low percentage range, indicating no significant interference. |
| Standardization Verification: Device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by the FDA. | Standardization verified: The HA-8180V HbA1c assay is NGSP certified, and certification is re-certified annually by ARKRAY. Traceability is established to the IFCC reference calibrators and the DCCT. |
2. Sample sizes used for the test set and data provenance
- Precision Study:
- Sample Size: 4 EDTA whole blood samples from different donors at approximate HbA1c concentrations of ~5.0%, ~6.5%, ~8.0%, and ~12.0%, and 3 quality control materials. Each sample was run in duplicate in two runs per instrument per day for 20 days across three instruments and three reagent lots.
- Data Provenance: The study was conducted at ARKRAY, USA, Edina, MN. It is a prospective study, as samples were "utilized in the study" and data "collected at ARKRAY."
- Method Comparison Study:
- Sample Size: 143 variant-free whole blood K2-EDTA samples.
- Data Provenance: The samples were collected from donors in an unspecified country (likely the US, given the study location in Minneapolis, MN) and were "variant-free." The study is likely prospective, involving the collection and testing of these specific samples.
- Hemoglobin Variant Study:
- Sample Size: 165 samples known to contain Hemoglobin variants A2, C, D, E, F, or S.
- Data Provenance: Not explicitly stated, but implies a collection of samples with known variants, likely from a clinical setting. It's a retrospective analysis of samples or prospective collection of specific variant samples.
3. Number of experts used to establish the ground truth for the test set and their qualifications
Ground truth for the test set was not established by human experts in a subjective manner as it is an in vitro diagnostic device for quantitative measurements.
- Precision Study: The ground truth was based on the device's own measurements of samples at known approximate HbA1c concentrations and quality control materials.
- Method Comparison Study: The ground truth (reference method) was established by a secondary NGSP reference laboratory using a previously cleared HPLC method (Tosoh G8), which is itself standardized and traceable.
- Hemoglobin Variant Study: The ground truth (reference method) was a method "that has been demonstrated to be free from the hemoglobin interference being tested." This implies an established and validated reference method for comparison, not expert consensus.
4. Adjudication method for the test set
Not applicable. This is a quantitative diagnostic device, and ground truth is established by reference methods or material characteristics, not subjective human assessment requiring adjudication.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done
No, an MRMC comparative effectiveness study was not done. This device is an automated in vitro diagnostic (IVD) system, not an imaging or interpretive device that typically involves human readers.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are standalone performance evaluations of the ADAMS A1c HA-8180V system. It is an automated analyzer, so its performance is inherently standalone (algorithm/instrument only) without human-in-the-loop performance affecting the results.
7. The type of ground truth used
- Precision Study: Intrinsic measurement from known samples and quality control materials.
- Method Comparison Study: The "gold standard" or reference method was the results from a secondary NGSP reference laboratory using a previously cleared HPLC method (Tosoh G8), which is traceable to IFCC and DCCT.
- Hemoglobin Variant Study: A "reference method that has been demonstrated to be free from the hemoglobin interference being tested."
- Linearity/Reportable Range: Theoretical values based on dilution factors of samples with known low and high HbA1c concentrations.
8. The sample size for the training set
This device does not utilize a "training set" in the context of machine learning. It is a chemical analyzer based on ion exchange HPLC technology. Its performance characteristics (precision, accuracy, linearity, interference) are evaluated directly through studies, rather than by training a model on data.
9. How the ground truth for the training set was established
Not applicable, as there is no "training set" in the machine learning sense for this type of IVD device.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
June 29, 2017
ARKRAY, INC. C/O NAVEEN THURAMALLA ARKRAY AMERICA, INC. 5182 WEST 76TH STREET EDINA MN 55439
Re: K162822
Trade/Device Name: ADAMS A1c HA-8180V Regulation Number: 21 CFR 862.1373 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: II Product Code: PDJ, LCP, JIT Dated: May 30, 2017 Received: May 31, 2017
Dear Naveen Thuramalla:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney H. Lias -S
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K162822
Device Name ADAMS A1c HA-8180V
Indications for Use (Describe)
The ADAMS A1c HA-8180V system is intended for the quantitative determination of hemoglobin A1c (IFCC mmol/mol and NGSP %) in human whole blood and hemolysate samples using lon Exchange high performance liquid chromatography (HPLC).
Hemoglobin A1c measurements obtained from the ADAMS A1C HA-8180V are used as an aid in the diagnosis of diabetes mellitus, an aid in the identification of individuals who may be at risk of developing diabetes, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. The ADAMS A1c HA-8180V is intended for Professional Use Only.
The CALIBRATOR 80 is for the calibration of the ADAMS A1c HA-8180V system used for the quantitative determination of hemoglobin A1c in human whole blood and hemolysate samples.
For In Vitro Diagnostic Use Only.
| Type of Use ( Select one or both, as applicable ) | |
|---|---|
| ---------------------------------------------------------- | -- |
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) SUMMARY
Summary of Safety & Effectiveness
K162822
Date Prepared: June 21, 2017
This summary of 510(k) Safety and Effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR § 807.92.
| 1. | Applicant Name: | ARKRAY, INC.Yousuien-Nai, 59 Gansuin-Cho,Kamigyo-Ku Kyoto, JAPAN 602-0008Telephone: +81 75-662-8979; Fax: +81 75-431-1202Establishment Registration # 3002807423 |
|---|---|---|
| 2. | Contact Person: | Naveen ThuramallaVice President, Regulatory AffairsTelephone: 202-738-8303; Fax: 952-646-3230Email: thuramallan@arkrayusa.com |
| 3. | Device Name/Trade Name: | DeviceTrade Name: ADAMS A1c HA-8180VClassification Name: Hemoglobin Alc Test SystemCommon Name: HbA1cProduct Codes: PDJ, LCPClassification Panel: Clinical ChemistryDevice Classification: Class IIC.F.R. Sections: Primary: 21 CFR § 862.1373;Secondary: 21 CFR § 864.7470CalibratorTrade Name: Calibrator 80Classification Name: CalibratorCommon Name: CalibratorProduct Codes: JITClassification Panel: Clinical ChemistryDevice Classification: Class IIC.F.R. Sections: 21 CFR § 862.1150 |
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5. Device Description
The ADAMS A1c HA-8180V system is a fully automated analyzer that uses ion exchange high performance liquid chromatography (HPLC) technology to separate glycated (labile A1c(L-A1c) and stable A1c (S-A1c)) and non-glycated (HbA0) forms of hemoglobin.
Hemoglobin A1c measurements obtained from the ADAMS A1C HA-8180V are used as an aid in the diagnosis of diabetes mellitus, an aid in the identification of individuals who may be at risk of developing diabetes, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. The subject device consists of the ADAMS A1c HA-8180V test analytical instrument and CALIBRATOR 80, which is used to calibrate the HA-8180V. The ADAMS A1c HA-8180V system is for use in professional clinical laboratory settings.
This method is certified by the National Glycohemoglobin Standardization Program (NGSP).
DEVICE:
Hemoglobin test samples are prepared by automated dilution of anticoagulated whole blood in Hemolysis Washing Solution 80H. Alternately, hemolysis samples may be prepared "off-line" by manual dilution of anticoagulated whole blood with Diluent 80. The sample is then injected into the column, which contains a filter to remove sample impurities. The differing polarity and ionic charges of the released hemoglobin fractions bind with variable strength to the negatively charged stationary phase of the column. The mobile phase, consisting of three eluents of increasing ionic strength, is injected into the column. Hemoglobin fractions eluted from the column are identified and quantified using light absorption, and are measured at 420 nm and 500 nm. The dual wavelength colorimetric analysis of the separated peaks is processed by a microcomputer to obtain peak identification and hemoglobin fraction quantitation. All pre-analytical and analytical steps are performed automatically by the ADAMS A1c HA-8180V system. Tests may be ordered in batch or for STAT measurement.
HbA1c and HbF results are reported in the presence of HbC, HbD, HbE, or HbS. A result of the detected HbC or HbS, and a peak resulting from HbD or HbE is also listed in the peak information. When a peak resulting from HbD or HbE is detected, a 'V' is listed in the peak information. HbA1c and HbF results are not reported when the instrument detects other peaks that affect HbA1c measurement value. The identification of any of these variants is not intended for use in diagnosis of hemoglobinopathies.
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CALIBRATOR:
Value assignment for HA-8180V HbA1c Calibrators are traceable to International Federation of Clinical Chemistry (IFCC) reference method and can be transferred to Diabetes Control and Complications Trial (DCCT)/NGSP values by calculation.
The Calibrator 80 consists of two levels of single-use, lyophilized calibrators. Diluent used to reconstitute the calibrators is also included. Three eluent solutions, a washing solution, and a control dilution set (used for sample dilutions and control material preparation) are also provided by ARKRAY for use on the HA-8180V system.
6. Indications for Use: (Prescription Device)
Device Name: ADAMS A1c HA-8180V
The ADAMS A1c HA-8180V system is intended for the quantitative determination of hemoglobin A1c (IFCC mmol/mol and NGSP %) in human whole blood and hemolysate samples using Ion Exchange high performance liquid chromatography (HPLC).
Hemoglobin A1c measurements obtained from the ADAMS A1C HA-8180V are used as an aid in the diagnosis of diabetes mellitus, an aid in the identification of individuals who may be at risk of developing diabetes, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. The ADAMS A1c HA-8180V is intended for Professional Use Only.
The CALIBRATOR 80 is for the calibration of the ADAMS A1c HA-8180V system used for the quantitative determination of hemoglobin A1c in human whole blood and hemolysate samples.
For In Vitro Diagnostic Use Only.
7. Substantial Equivalence Information:
Predicate Device Information
| Predicate Device Name | Predicate Device 510(k) Number |
|---|---|
| Tosoh Bioscience, Inc. Automated GlycohemoglobinAnalyzer HLC-723G8 | K131580 |
| Tosoh Bioscience, Inc. Hemoglobin A1c CalibratorSet | K071132 |
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The ADAMS A1c HA-8180V System (candidate device) utilizes principles of ion-exchange high-performance liquid chromatography (HPLC) similar to the same technology of the Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 (predicate device).
Following tables (Table 1 and Table 2) provide the similarities and differences between the HA-8180V system and the predicates (for both the device and calibrator).
| Parameter | ADAMS A1c HA-8180V(Candidate Device) | Tosoh Bioscience, Inc.Automated GlycohemoglobinAnalyzer HLC-723G8K131580(Predicate Device) |
|---|---|---|
| Similarities | ||
| Indications forUse | The ADAMS A1c HA-8180Vsystem is intended for thequantitative determination ofhemoglobin A1c (IFCC mmol/moland NGSP %) in human wholeblood and hemolysate samplesusing Ion Exchange highperformance liquidchromatography (HPLC).Hemoglobin A1c measurementsobtained from the ADAMS A1CHA-8180V are used as an aid inthe diagnosis of diabetes mellitus,an aid in the identification ofindividuals who may be at risk ofdeveloping diabetes, and for themonitoring of long-term bloodglucose control in individuals withdiabetes mellitus. The ADAMSA1c HA-8180V is intended forProfessional Use Only. | The Tosoh AutomatedGlycohemoglobin AnalyzerHLC-723G8 is intended for invitro diagnostic use for themeasurement of % hemoglobinA1c (HbA1c) (DCCT/NGSP)and mmol/mol hemoglobin A1c(IFCC) in whole bloodspecimens. This test is to be usedas an aid in diagnosis of diabetesand identifying patients whomay be at risk for developingdiabetes. |
| Specimen Type | Whole blood, hemolysate sample | Whole blood, diluted blood |
| Assay Principle | Ion exchange HPLC | Ion exchange HPLC |
| Standardization | Traceable to the Diabetes Controland Complications Trial (DCCT)reference method and IFCC.Certified via the NationalGlycohemoglobin StandardizationProgram (NGSP) | Traceable to the DiabetesControl and Complications Trial(DCCT) reference method andIFCC. Certified via the NationalGlycohemoglobinStandardization Program(NGSP) |
| Parameter | ADAMS A1c HA-8180V(Candidate Device) | Tosoh Bioscience, Inc.Automated GlycohemoglobinAnalyzer HLC-723G8K131580(Predicate Device) |
| SystemComponents | Sampling unit, liquid pump,degasser, column, detector,microprocessor, sample loader,operation panel, printer | Sampling unit, liquid pump,degasser, column, detector,microprocessor, sample loader,operation panel, printer |
| DetectionMethod | Dual wavelength (420 nm and500 nm) LED colorimetricdetector | Dual wavelength (415 nm andunknown) LED colorimetricdetector |
| STATCapability | Yes | Yes |
| HbA1cReporting Units | %HbA1c, mmol/mol,chromatogram | %HbA1c, mmol/mol,chromatogram |
| Differences | ||
| MeasurementRange (HbA1c) | 4-15% (NGSP)20 to 140 mmol/mol (IFCC) | 4-16.9% (NGSP)20 to 161 mmol/mol (IFCC) |
| Sample Volume(Consumed) | Whole blood: 14 µLHemolysate: 400 µL | Whole blood: 4 µLDiluted blood: 80 µL |
| Anticoagulant | K2-EDTA and K3-EDTA WholeBlood | K3-EDTA Whole Blood |
| OperatingTemperature | 10 - 30°C | 15 - 30°C |
| Table 2: Calibrator Similarities and Differences | ||
| Parameter | ADAMS A1c HA-8180V(Candidate Device) | Tosoh Bioscience, Inc.Hemoglobin A1c calibratorK071132(Predicate Device) |
| Indications forUse | The CALIBRATOR 80 is for thecalibration of the ADAMS A1cHA-8180V system used for thequantitative determination ofhemoglobin A1c in human wholeblood and hemolysate samples. | The Tosoh A1c Calibrator Set isa reference agent designed forcalibrating Tosoh AutomatedGlycohemoglobin AnalyzerHLC-723G8. |
| CalibratorDescription | Bi-level calibrators (low and high)with human-source material | Bi-level calibrators (low andhigh) with human-sourcematerial |
| Parameter | ADAMS A1c HA-8180V(Candidate Device) | Tosoh Bioscience, Inc.Hemoglobin A1c calibratorK071132(Predicate Device) |
| Concentrations | HbA1c (NGSP Value):Calibrator 80 Low -approximately 5.0-6.0%Calibrator 80 High -approximately 10.0-11.0% | HbA1c (NGSP Value):Calibrator 1 - approximately5.5-6.5%Calibrator 2 - approximately10.5-11.5% |
| Standardization/Traceability | Varies according to lotTraceable to the Diabetes Controland Complications Trial (DCCT)reference method and IFCC.Certified via the NationalGlycohemoglobin StandardizationProgram (NGSP) | Varies according to lotTraceable to the DiabetesControl and Complications Trial(DCCT) reference method andIFCC. Certified via the NationalGlycohemoglobinStandardization Program(NGSP) |
| Matrix | Lyophilized calibrator fromhuman-sourced hemoglobin | Buffered human red blood cells,2 mg/mLHuman hemoglobin |
| Storage &Stability | Shelf life: 18 months at 2 – 8°COpen bottle: 8 hours at 2 – 8°Cafter reconstitution | Shelf life: 2 years at 2 - 8°COpen bottle: One week at 2 -8°C after reconstitution** Based on manufacturer'sInstructions for Use(0T012070/Rev March 2013) |
Table 1: Device Similarities and Differences
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The candidate ADAMS A1c HA-8180V system is similar to the legally marketed predicate Tosoh G8 system in general design and assay principles, technology, performance characteristics and indications for use. The minor differences between the candidate and predicate device do not raise new issues of safety or effectiveness. The same applies to the candidate calibrator to be used with HA-8180V system and the Tosoh's HLC-723G8 system. The performance of the ADAMS A1c HA-8180V system is substantiated in various sections throughout the submission. Therefore, we consider that the ADAMS A1c HA-8180V system is Substantially Equivalent to the predicate.
8. Precision/Reproducibility:
The precision of the ADAMS A1c HA-8180V system was evaluated based on CLSI EP05-A3, Evaluation of Precision Performance of Quantitative Measurement Methods. The study design included three lots and three instruments. All data was collected at ARKRAY, (a Point of Care (POC) claim is not being made), consistent with the FDA recommendations in pre-IDE 1110310. EDTA whole blood samples from four donors at the approximate targeted HbA1c concentrations
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of ~5.0% (Patient 1), ~6.5% (Patient 2), ~8.0% (Patient 3) and ~12.0% (Patient 4) were utilized in the study.
Three quality control materials were also tested. Precision was evaluated using three reagent lots and three HA-8180V HbA1c Testing Systems at one site (ARKRAY USA, Edina, MN). All samples were run in duplicate in two runs per instrument per day for 20 days. National Glycohemoglobin Standardization Program (NGSP) results and International Federation of Clinical Chemistry (IFCC) results are shown in the Table 3 - Table 10.
| Mean%HbA1c | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient1,5.2% | 0.01 | 0.3% | 0.00 | 0.0% | 0.00 | 0.0% | 0.00 | 0.0% | 0.01 | 0.3% |
| Patient 2,6.4% | 0.02 | 0.3% | 0.01 | 0.2% | 0.00 | 0.0% | 0.05 | 0.8% | 0.05 | 0.8% |
| Patient 3,7.9% | 0.03 | 0.4% | 0.03 | 0.4% | 0.01 | 0.2% | 0.06 | 0.7% | 0.07 | 0.9% |
| Patient 4,11.8% | 0.03 | 0.3% | 0.02 | 0.1% | 0.04 | 0.3% | 0.07 | 0.6% | 0.08 | 0.7% |
| Control 1,5.2% | 0.03 | 0.7% | 0.03 | 0.7% | 0.02 | 0.3% | 0.02 | 0.4% | 0.05 | 1.1% |
| Control 2,9.0% | 0.03 | 0.3% | 0.03 | 0.3% | 0.01 | 0.2% | 0.01 | 0.1% | 0.04 | 0.5% |
| Control 3,13.4% | 0.02 | 0.2% | 0.04 | 0.3% | 0.03 | 0.2% | 0.02 | 0.1% | 0.06 | 0.4% |
Table 3: Instrument 1 Whole Blood Samples (NGSP):
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| Mean% HbA1c | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,5.2% | 0.02 | 0.4% | 0.01 | 0.2% | 0.00 | 0.0% | 0.01 | 0.2% | 0.03 | 0.5% |
| Patient 2,6.4% | 0.01 | 0.1% | 0.00 | 0.0% | 0.00 | 0.0% | 0.06 | 0.9% | 0.06 | 0.9% |
| Patient 3,7.9% | 0.03 | 0.4% | 0.02 | 0.3% | 0.01 | 0.1% | 0.08 | 1.0% | 0.09 | 1.1% |
| Patient 4,11.8% | 0.05 | 0.4% | 0.01 | 0.1% | 0.03 | 0.2% | 0.10 | 0.9% | 0.12 | 1.0% |
| Control 1,5.2% | 0.02 | 0.4% | 0.03 | 0.5% | 0.01 | 0.3% | 0.04 | 0.9% | 0.06 | 1.1% |
| Control 2,9.0% | 0.02 | 0.2% | 0.03 | 0.4% | 0.01 | 0.2% | 0.04 | 0.5% | 0.06 | 0.6% |
| Control 3,13.4% | 0.03 | 0.2% | 0.03 | 0.3% | 0.04 | 0.3% | 0.05 | 0.4% | 0.08 | 0.6% |
Table 4: Instrument 2 Whole Blood Samples (NGSP):
Table 5: Instrument 3 Whole Blood Samples (NGSP):
| Mean% HbA1c | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,5.2% | 0.02 | 0.4% | 0.02 | 0.4% | 0.00 | 0.0% | 0.01 | 0.2% | 0.03 | 0.6% |
| Patient 2,6.4% | 0.02 | 0.4% | 0.01 | 0.2% | 0.00 | 0.0% | 0.06 | 0.9% | 0.06 | 1.0% |
| Patient 3,7.9% | 0.03 | 0.4% | 0.02 | 0.2% | 0.02 | 0.3% | 0.05 | 0.7% | 0.07 | 0.9% |
| Patient 4,11.8% | 0.02 | 0.2% | 0.03 | 0.2% | 0.02 | 0.2% | 0.11 | 1.0% | 0.12 | 1.0% |
| Control 1,5.2% | 0.02 | 0.5% | 0.02 | 0.3% | 0.01 | 0.2% | 0.02 | 0.4% | 0.04 | 0.8% |
| Control 2,9.1% | 0.03 | 0.4% | 0.03 | 0.3% | 0.03 | 0.3% | 0.05 | 0.5% | 0.07 | 0.8% |
| Control 3,13.4% | 0.03 | 0.2% | 0.04 | 0.3% | 0.04 | 0.3% | 0.08 | 0.6% | 0.10 | 0.7% |
{11}------------------------------------------------
| Mean%HbA1c | Repeatability | BetweenRun | Between Day | Between Lot | BetweenInstrument | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,5.2% | 0.02 | 0.4% | 0.01 | 0.2% | 0.00 | 0.1% | 0.01 | 0.1% | 0.01 | 0.1% | 0.03 | 0.5% |
| Patient 2,6.4% | 0.02 | 0.3% | 0.01 | 0.2% | 0.00 | 0.0% | 0.05 | 0.9% | 0.00 | 0.0% | 0.06 | 0.9% |
| Patient 3,7.9% | 0.03 | 0.4% | 0.02 | 0.3% | 0.02 | 0.3% | 0.06 | 0.8% | 0.02 | 0.3% | 0.08 | 1.0% |
| Patient 4,11.8% | 0.04 | 0.3% | 0.02 | 0.2% | 0.04 | 0.3% | 0.09 | 0.8% | 0.03 | 0.3% | 0.11 | 1.0% |
| Control 1,5.2% | 0.03 | 0.5% | 0.03 | 0.5% | 0.02 | 0.4% | 0.03 | 0.5% | 0.02 | 0.4% | 0.05 | 1.1% |
| Control 2,9.0% | 0.03 | 0.3% | 0.03 | 0.3% | 0.02 | 0.3% | 0.03 | 0.4% | 0.02 | 0.2% | 0.06 | 0.7% |
| Control 3,13.4% | 0.03 | 0.2% | 0.04 | 0.3% | 0.04 | 0.3% | 0.05 | 0.4% | 0.03 | 0.2% | 0.08 | 0.6% |
Table 6: Instruments Combined Whole Blood Samples (NGSP):
Table 7: Instrument 1 Whole Blood Samples (IFCC):
| Meanmmol/mol | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,33 | 0.2 | 0.7% | 0.2 | 0.7% | 0.0 | 0.0% | 0.3 | 0.9% | 0.4 | 1.4% |
| Patient 2,47 | 0.3 | 0.6% | 0.2 | 0.5% | 0.1 | 0.2% | 0.4 | 0.9% | 0.5 | 1.2% |
| Patient 3,62 | 0.3 | 0.5% | 0.1 | 0.2% | 0.1 | 0.1% | 0.6 | 1.0% | 0.7 | 1.1% |
| Patient 4,105 | 0.3 | 0.3% | 0.2 | 0.2% | 0.2 | 0.2% | 0.7 | 0.7% | 0.8 | 0.8% |
| Control 1,33 | 0.2 | 0.7% | 0.2 | 0.7% | 0.1 | 0.2% | 0.2 | 0.5% | 0.4 | 1.1% |
| Control 2,75 | 0.3 | 0.4% | 0.3 | 0.3% | 0.2 | 0.2% | 0.0 | 0.0% | 0.4 | 0.6% |
| Control 3,123 | 0.2 | 0.2% | 0.4 | 0.3% | 0.2 | 0.2% | 0.2 | 0.2% | 0.6 | 0.5% |
{12}------------------------------------------------
| Meanmmol/mol | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,33 | 0.2 | 0.7% | 0.1 | 0.3% | 0.0 | 0.0% | 0.5 | 1.4% | 0.5 | 1.6% |
| Patient 2,47 | 0.3 | 0.7% | 0.0 | 0.0% | 0.2 | 0.5% | 0.5 | 1.1% | 0.7 | 1.4% |
| Patient 3,63 | 0.4 | 0.6% | 0.2 | 0.4% | 0.2 | 0.3% | 0.8 | 1.2% | 0.9 | 1.4% |
| Patient 4,106 | 0.5 | 0.5% | 0.3 | 0.3% | 0.2 | 0.2% | 1.1 | 1.0% | 1.2 | 1.2% |
| Control 1,33 | 0.2 | 0.7% | 0.3 | 0.8% | 0.1 | 0.4% | 0.1 | 0.5% | 0.4 | 1.2% |
| Control 2,75 | 0.3 | 0.3% | 0.4 | 0.5% | 0.0 | 0.0% | 0.5 | 0.7% | 0.7 | 0.9% |
| Control 3,123 | 0.3 | 0.3% | 0.3 | 0.3% | 0.3 | 0.3% | 0.6 | 0.5% | 0.8 | 0.7% |
Table 8: Instrument 2 Whole Blood Samples (IFCC):
Table 9: Instrument 3 Whole Blood Samples (IFCC):
| Meanmmol/mol | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,33 | 0.2 | 0.6% | 0.2 | 0.5% | 0.0 | 0.0% | 0.5 | 1.6% | 0.6 | 1.8% |
| Patient 2,47 | 0.3 | 0.7% | 0.2 | 0.3% | 0.2 | 0.4% | 0.3 | 0.7% | 0.5 | 1.1% |
| Patient 3,63 | 0.3 | 0.5% | 0.2 | 0.4% | 0.3 | 0.4% | 0.6 | 1.0% | 0.8 | 1.3% |
| Patient 4,106 | 0.3 | 0.3% | 0.3 | 0.3% | 0.3 | 0.2% | 1.3 | 1.2% | 1.4 | 1.3% |
| Control 1,33 | 0.2 | 0.6% | 0.2 | 0.5% | 0.2 | 0.6% | 0.1 | 0.4% | 0.4 | 1.1% |
| Control 2,75 | 0.3 | 0.4% | 0.3 | 0.4% | 0.3 | 0.4% | 0.5 | 0.6% | 0.7 | 0.9% |
| Control 3,123 | 0.3 | 0.2% | 0.4 | 0.3% | 0.4 | 0.3% | 0.9 | 0.7% | 1.1 | 0.9% |
Table 10: Instruments Combined Whole Blood Samples (IFCC):
| Repeatability | Between Run | Between Day | Between Lot | Between Instrument | Total | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Meanmmol/mol | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Patient 1, 33 | 0.22 | 0.7% | 0.17 | 0.5% | 0.06 | 0.2% | 0.44 | 1.3% | 0.07 | 0.2% | 0.53 | 1.6% |
{13}------------------------------------------------
| Patient 2, | 0. | 0.7% | 0.14 | 0.3% | 0.27 | 0.6% | 0.35 | 0.7% | 0.27 | 0.6% | 0.61 | 1.3% |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 47 | 31 | |||||||||||
| Patient 3, | 0. | 0.5% | 0.20 | 0.3% | 0.24 | 0.4% | 0.64 | 1.0% | 0.21 | 0.3% | 0.81 | 1.3% |
| 63 | 32 | |||||||||||
| Patient 4, | 0. | 0.4% | 0.29 | 0.3% | 0.33 | 0.3% | 1.00 | 0.9% | 0.31 | 0.3% | 1.20 | 1.1% |
| 106 | 39 | |||||||||||
| Control 1, | 0. | 0.7% | 0.22 | 0.7% | 0.14 | 0.4% | 0.14 | 0.4% | 0.13 | 0.4% | 0.39 | 1.2% |
| 33 | 22 | |||||||||||
| Control 2, | 0. | 0.4% | 0.31 | 0.4% | 0.27 | 0.4% | 0.32 | 0.4% | 0.23 | 0.3% | 0.63 | 0.8% |
| 75 | 28 | |||||||||||
| Control 3, | 0. | 0.2% | 0.40 | 0.3% | 0.43 | 0.4% | 0.53 | 0.4% | 0.34 | 0.3% | 0.90 | 0.7% |
| 123 | 28 |
NGSP results and IFCC results for Hemolyzed Samples are shown in Table 11 – Table 18.
| Mean% HbA1c | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,5.2% | 0.02 | 0.4% | 0.03 | 0.5% | 0.01 | 0.2% | 0.00 | 0.1% | 0.04 | 0.7% |
| Patient 2,6.4% | 0.01 | 0.2% | 0.02 | 0.3% | 0.02 | 0.3% | 0.05 | 0.8% | 0.06 | 0.9% |
| Patient 3,7.9% | 0.03 | 0.4% | 0.02 | 0.2% | 0.02 | 0.3% | 0.04 | 0.6% | 0.06 | 0.8% |
| Patient 4,11.9% | 0.03 | 0.3% | 0.03 | 0.3% | 0.02 | 0.2% | 0.07 | 0.6% | 0.08 | 0.7% |
| Control 1,5.2% | 0.03 | 0.5% | 0.07 | 1.3% | 0.06 | 1.2% | 0.05 | 0.9% | 0.11 | 2.1% |
| Control 2,9.1% | 0.03 | 0.3% | 0.02 | 0.2% | 0.04 | 0.4% | 0.01 | 0.2% | 0.05 | 0.6% |
| Control 3,13.5% | 0.03 | 0.2% | 0.05 | 0.4% | 0.04 | 0.3% | 0.03 | 0.3% | 0.08 | 0.6% |
Table 11: Instrument 1 Hemolysate Samples (NGSP):
Table 12: Instrument 2 Hemolysate Samples (NGSP):
| Mean% HbA1c | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,5.2% | 0.01 | 0.2% | 0.02 | 0.4% | 0.02 | 0.3% | 0.01 | 0.2% | 0.03 | 0.6% |
| Patient 2,6.4% | 0.02 | 0.3% | 0.01 | 0.1% | 0.02 | 0.3% | 0.05 | 0.8% | 0.06 | 0.9% |
| Patient 3,7.9% | 0.02 | 0.2% | 0.02 | 0.3% | 0.01 | 0.1% | 0.06 | 0.8% | 0.07 | 0.9% |
| Patient 4, | 0.03 | 0.3% | 0.02 | 0.2% | 0.03 | 0.3% | 0.10 | 0.8% | 0.11 | 0.9% |
{14}------------------------------------------------
| 11.9% | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Control 1,5.2% | 0.03 | 0.5% | 0.05 | 1.0% | 0.05 | 1.0% | 0.04 | 0.8% | 0.09 | 1.7% |
| Control 2,9.1% | 0.02 | 0.3% | 0.05 | 0.5% | 0.05 | 0.5% | 0.03 | 0.4% | 0.08 | 0.8% |
| Control 3,13.6% | 0.03 | 0.2% | 0.05 | 0.4% | 0.05 | 0.4% | 0.06 | 0.4% | 0.10 | 0.7% |
Table 13: Instrument 3 Hemolysate Samples (NGSP):
| Mean% HbA1c | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,5.2% | 0.02 | 0.3% | 0.00 | 0.0% | 0.01 | 0.3% | 0.00 | 0.1% | 0.02 | 0.4% |
| Patient 2,6.5% | 0.03 | 0.5% | 0.02 | 0.4% | 0.00 | 0.0% | 0.03 | 0.5% | 0.05 | 0.8% |
| Patient 3,7.9% | 0.01 | 0.1% | 0.01 | 0.1% | 0.00 | 0.0% | 0.06 | 0.7% | 0.06 | 0.8% |
| Patient 4,11.9% | 0.03 | 0.2% | 0.03 | 0.2% | 0.02 | 0.2% | 0.10 | 0.9% | 0.11 | 0.9% |
| Control 1,5.2% | 0.02 | 0.4% | 0.04 | 0.7% | 0.04 | 0.8% | 0.03 | 0.5% | 0.07 | 1.2% |
| Control 2,9.1% | 0.03 | 0.3% | 0.04 | 0.4% | 0.03 | 0.4% | 0.04 | 0.5% | 0.07 | 0.8% |
| Control 3,13.6% | 0.04 | 0.3% | 0.05 | 0.4% | 0.04 | 0.3% | 0.08 | 0.6% | 0.11 | 0.8% |
Table 14: Instruments Combined Hemolysate Samples (NGSP):
| Mean %HbA1c | Repeatability | Between Run | Between Day | Between Lot | Between Instrument | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,5.2% | 0.02 | 0.3% | 0.02 | 0.4% | 0.01 | 0.3% | 0.01 | 0.1% | 0.00 | 0.0% | 0.03 | 0.6% |
| Patient 2,6.5% | 0.02 | 0.4% | 0.02 | 0.3% | 0.02 | 0.3% | 0.04 | 0.7% | 0.02 | 0.2% | 0.06 | 0.9% |
| Patient 3,7.9% | 0.02 | 0.2% | 0.02 | 0.2% | 0.02 | 0.2% | 0.05 | 0.7% | 0.01 | 0.1% | 0.06 | 0.8% |
| Patient 4,11.9% | 0.03 | 0.3% | 0.03 | 0.2% | 0.03 | 0.3% | 0.09 | 0.7% | 0.03 | 0.3% | 0.11 | 0.9% |
| Control 1,5.2% | 0.02 | 0.5% | 0.05 | 1.1% | 0.05 | 1.0% | 0.04 | 0.7% | 0.01 | 0.3% | 0.09 | 1.7% |
{15}------------------------------------------------
| Control2,9.1% | 0.03 | 0.3% | 0.04 | 0.4% | 0.04 | 0.5% | 0.03 | 0.3% | 0.02 | 0.2% | 0.07 | 0.8% |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Control3, | 0.03 | 0.2% | 0.05 | 0.4% | 0.05 | 0.4% | 0.05 | 0.4% | 0.03 | 0.3% | 0.10 | 0.8% |
Table 15: Instrument 1 Hemolysate Samples (IFCC):
| Meanmmol/mol | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,33 | 0.3 | 0.8% | 0.3 | 0.8% | 0.2 | 0.7% | 0.4 | 1.1% | 0.6 | 1.7% |
| Patient 2,47 | 0.3 | 0.6% | 0.2 | 0.3% | 0.2 | 0.4% | 0.2 | 0.5% | 0.4 | 0.9% |
| Patient 3,63 | 0.3 | 0.5% | 0.3 | 0.5% | 0.2 | 0.3% | 0.5 | 0.8% | 0.7 | 1.2% |
| Patient 4,106 | 0.3 | 0.3% | 0.3 | 0.2% | 0.2 | 0.2% | 0.7 | 0.6% | 0.8 | 0.8% |
| Control 1,33 | 0.2 | 0.6% | 0.7 | 2.0% | 0.7 | 2.0% | 0.3 | 1.0% | 1.0 | 3.0% |
| Control 2,76 | 0.3 | 0.4% | 0.3 | 0.4% | 0.4 | 0.5% | 0.2 | 0.2% | 0.6 | 0.8% |
| Control 3,125 | 0.3 | 0.3% | 0.6 | 0.5% | 0.5 | 0.4% | 0.4 | 0.3% | 0.9 | 0.7% |
| Table 16: Instrument 2 Hemolysate Samples (IFCC): | |||||
|---|---|---|---|---|---|
| --------------------------------------------------- | -- | -- | -- | -- | -- |
| Meanmmol/mol | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,33 | 0.2 | 0.7% | 0.2 | 0.5% | 0.2 | 0.5% | 0.4 | 1.1% | 0.5 | 1.5% |
| Patient 2,47 | 0.3 | 0.5% | 0.2 | 0.5% | 0.2 | 0.4% | 0.3 | 0.7% | 0.5 | 1.1% |
| Patient 3,63 | 0.2 | 0.4% | 0.3 | 0.4% | 0.2 | 0.3% | 0.6 | 1.0% | 0.7 | 1.2% |
| Patient 4,107 | 0.4 | 0.3% | 0.4 | 0.4% | 0.2 | 0.2% | 1.0 | 0.9% | 1.2 | 1.1% |
| Control 1,33 | 0.2 | 0.6% | 0.6 | 1.7% | 0.7 | 2.0% | 0.2 | 0.6% | 0.9 | 2.7% |
| Control 2,76 | 0.3 | 0.4% | 0.6 | 0.8% | 0.5 | 0.7% | 0.4 | 0.6% | 0.9 | 1.2% |
| Control 3,125 | 0.3 | 0.3% | 0.5 | 0.4% | 0.6 | 0.5% | 0.7 | 0.5% | 1.1 | 0.9% |
{16}------------------------------------------------
| Meanmmol/mol | Repeatability | Between Run | Between Day | Between Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Patient 1,33 | 0.2 | 0.7% | 0.2 | 0.7% | 0.1 | 0.4% | 0.4 | 1.2% | 0.5 | 1.6% |
| Patient 2,47 | 0.2 | 0.4% | 0.2 | 0.3% | 0.1 | 0.3% | 0.4 | 0.8% | 0.5 | 1.0% |
| Patient 3,63 | 0.2 | 0.3% | 0.2 | 0.3% | 0.0 | 0.0% | 0.6 | 1.0% | 0.7 | 1.0% |
| Patient 4,107 | 0.4 | 0.4% | 0.3 | 0.3% | 0.2 | 0.2% | 1.2 | 1.1% | 1.3 | 1.2% |
| Control 1,33 | 0.2 | 0.7% | 0.5 | 1.5% | 0.4 | 1.2% | 0.2 | 0.7% | 0.7 | 2.2% |
| Control 2,76 | 0.3 | 0.4% | 0.4 | 0.5% | 0.4 | 0.5% | 0.5 | 0.6% | 0.8 | 1.0% |
| Control 3,125 | 0.4 | 0.3% | 0.5 | 0.4% | 0.5 | 0.4% | 0.9 | 0.7% | 1.2 | 0.9% |
| Table 18: Instruments Combined Hemolysate Samples (IFCC): |
|---|
| ----------------------------------------------------------- |
| Meanmmol/mol | Repeatability | Between Run | Between Day | Between Lot | Between Instrument | Total | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||
| Patient1, 33 | 0.25 | 0.7% | 0.22 | 0.7% | 0.18 | 0.5% | 0.38 | 1.2% | 0.06 | 0.2% | 0.54 | 1.6% | |
| Patient2, 47 | 0.24 | 0.5% | 0.19 | 0.4% | 0.21 | 0.4% | 0.29 | 0.6% | 0.13 | 0.3% | 0.49 | 1.0% | |
| Patient3, 63 | 0.27 | 0.4% | 0.26 | 0.4% | 0.18 | 0.3% | 0.57 | 0.9% | 0.15 | 0.2% | 0.72 | 1.1% | |
| Patient4, 107 | 0.36 | 0.3% | 0.32 | 0.3% | 0.30 | 0.3% | 0.96 | 0.9% | 0.30 | 0.3% | 1.15 | 1.1% | |
| Control1, 33 | 0.21 | 0.6% | 0.57 | 1.7% | 0.57 | 1.7% | 0.28 | 0.9% | 0.00 | 0.0% | 0.88 | 2.7% | |
| Control2, 76 | 0.28 | 0.4% | 0.44 | 0.6% | 0.44 | 0.6% | 0.36 | 0.5% | 0.23 | 0.3% | 0.81 | 1.1% |
{17}------------------------------------------------
| Control3,125 | 0.35 | 0.3% | 0.53 | 0.4% | 0.58 | 0.5% | 0.62 | 0.5% | 0.34 | 0.3% | 1.12 | 0.9% |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ---------------------- | ------ | ------ | ------ | ------ | ------ | ------ | ------ | ------ | ------ | ------ | ------ | ------ |
9. Linearity/Reportable Range
A linearity study was performed per CLSI EP06-A: Evaluation of the Linearity of Quantitative Measuring Procedures; A Statistical Approach. Linearity across the reportable range was performed using controlled samples ranging from low (3% HbA1c) to high (19% HbA1c) EDTA whole blood patient samples. These samples were mixed together in varying ratios. The measured values were compared to the theoretical values based upon the dilution factor. Acceptance criteria was no more than ±0.15% bias (NGSP% units, not actual percentage) from the theoretical value.
The study demonstrated linearity of ADAMS A1c HA-8180V system over 3.0 to 19.0% (NGSP) and 9 to 184 mmol/mol (IFCC) with a maximum measured difference of -0.10% and -1.09mmol/mol respectively, between the theoretical and measured value. Maximum difference between the predicted 1st order was ±0.08% (NGSP) and ±0.92 mmol/mol (IFCC). This supports the claimed measurement range of 4.0 to 140 mmol/mol) HbA1c.
| Table 19. Linearity Regression Parameters | |||
|---|---|---|---|
| Units | Slope | Intercept | R2 |
| NGSP | 0.9958 | 0.0064 | 0.9999 |
| IFCC | 0.9958 | -0.0275 | 0.9999 |
Table 19. Linearity Regression Parameters
Detection Limit
The claimed measurement range is 4.0 to 15.0 % HbA1c based on the results from the linearity study.
10. Traceability, Stability, Expected Value (Calibrators)
A. Traceability:
The ADAMS A1c HA-8180V test standardization is traceable to the International Federation of Clinical Chemistry (IFCC) reference calibrators. The HA-8180V HbA1c assay is also NGSP certified. The NGSP certification is re-certified by ARKRAY on an annual basis.
The derived results of (%) from the NGSP correlation are calculated from the individual quantitative results for Hemoglobin A1c (HbA1c). The IFCC units of mmol/mol are calculated using the Master Equation:
{18}------------------------------------------------
NGSP (%) = 0.0915 x IFCC (mmol/mol) + 2.15.
The final reportable range is traceable to both the IFCC and the Diabetes Control and Complications Trial (DCCT). HbA1c results are provided to the customers using two different units: NGSP equivalent units (%) and IFCC equivalent units (mmol/mol).
B. Calibrator Materials:
Value assignment for ADAMS A1c HA-8180V Calibrators are traceable to IFCC reference method and can be transferred to DCCT/NGSP values by calculation.
Using an ADAMS A1c HA-8180V instrument calibrated using standard material JCCRM-411 (provided by ReCCS, a primary (APRL) as well as a secondary (ASRL) reference laboratory within the NGSP Network), CALIBRATOR 80 was measured (n=9) over 3 days (total of n=27) to assign values. The mean generated over the 3 days is set as the reference value. Values are given in IFCC value system and converted to NGSP using the master equation.
C. Stability/Shelf Life Claims:
C.1. Shelf life claims: Shelf life studies were performed with three lots of Calibrator 80 as per CLSI EP 25, Evaluation of Stability of In Vitro Diagnostic Reagents. Based on the NGSP certification standards, acceptance criteria was defined as: relative bias in HbA1c (%) from 0 month result should be within ± 6% bias at 18 months, when the un-opened calibrators were stored between 2-8ºC.
The study results confirmed that the acceptance criteria was met. This supports the recommendation that un-opened calibrators can be stored at 2-8°C until expiration date or for 18 months.
C.2 Open-Vial Stability: The open-vial stability studies were performed with two lots of Calibrator 80 as per CLSI EP 25, Evaluation of Stability of In Vitro Diagnostic Reagents. Based on the NGSP certification standards, acceptance criteria was defined as: relative bias in HbA1c (%) should be within ± 6% for measurement at 0 and 8 hours.
The study resultsconfirmed that the acceptance criteria was met. This supports the recommended open vial stability claim of 8 hours when stored at 2-8℃. On-board stability for the Calibrator 80 pack is not evaluated as the calibrators are intended for single use only.
11. Analytical Specificity:
A. Interferences Study
An Interference study was performed per CLSI EP07-A2 Interference Testing in Clinical Chemistry. The study assessed common or known endogenous substances, drugs and hemoglobin derivatives that could interfere with ADAMS A1c HA-8180V system. Whole blood samples with HbA1c values of ~6.5% and ~8.0% were analyzed by spiking the interfering substance into each
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of the two whole blood samples as shown in Table 29. Ten replicates of each drug prepared with the test and control samples were analyzed using ADAMS A1c HA-8180V system.
Significant interference was defined as a more than ±7.0% change in %HbA1c value from the control. No significant interference was observed at therapeutic levels up the stated highest concentrations as summarized below.
| Interferent | Highest ConcentrationWithout Interference |
|---|---|
| Acetaminophen | 20 mg/dL |
| Acetylcysteine | 330 mg/dL |
| Acetylsalicylic Acid (Aspirin) | 65 mg/dL |
| Ampicillin-Na | 1,000 mg/dL |
| Ascorbic Acid | 200 mg/dL |
| Cefoxitin-Na | 2,500 mg/dL |
| Cyclosporine | 0.67 mg/dL |
| Doxycyclin | 50 mg/dL |
| Ibuprofen | 50 mg/dL |
| Levodopa | 20 mg/dL |
| Metformin | 5 mg/dL |
| Methyldopa | 30 mg/dL |
| Metronidazole | 200 mg/dL |
| Rifampicin | 6.4 mg/dL |
| Salicylic Acid | 60 mg/dL |
| Theophylline | 10 mg/dL |
| Table 28: Exogenous Substances | |
|---|---|
Table 29: Endogenous Substances
| Interferent | Highest ConcentrationWithout Interference |
|---|---|
| Acetylated Hb | 50 mg/dL |
| Albumin (human) | 20,000 mg/dL |
| Bilirubin (conj.) | 100 mg/dL |
| Bilirubin (unconj.) | 100 mg/dL |
| Carbamylated Hb | 25 mg/dL |
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| Labile Hb(Glucose) | 2,000 mg/dL |
|---|---|
| Rheumatoid Factor | 750 IU/mL |
| Triglycerides | 2,000 mg/dL |
B. Hemoglobin Variant Study:
A hemoglobin variant interference study was performed using a total of 165 samples known to contain Hemoglobin variants A2, C, D, E, F, or S. At least, 10 samples were tested around each of the two HbA1c concentrations of ~6.5% and ~8.0%. Testing of the samples containing the Hemoglobin variants A2, C, D, E, F, or S was performed at least in duplicate. Testing was performed on the HA-8180V system and compared to results obtained by a reference method that has been demonstrated to be free from the hemoglobin interference being tested. Table 20 shows the samples that were measured.
| Variant | n | Variant Range (%) | Range in % HbA1cConcentration |
|---|---|---|---|
| HbA2 | 30 | 1.9 - 25.4% | 4.8 - 8.9% |
| HbC | 26 | 26.9 - 39.0% | 4.6 - 9.2% |
| HbD | 22 | 31.6 - 35.9% | 5.7 - 10.3% |
| HbE | 22 | 18.0 - 30.0% | 4.9 - 9.7% |
| HbF | 24 | 1.0 - 30.3% | 4.7 - 11.7% |
| HbS | 41 | 12.9 - 42.1% | 4.5 - 11.6% |
Table 20: Hemoglobin Variant Study Samples
As shown in Table 21, HbA1c results are accurate (with no significant interference) in samples containing HbA2 (≤16%), HbC (≤39%), HbD (≤36%), HbF (≤30%), HbF (≤30%), HbS (≤40%),
| Table 21: Hemoglobin Variant Study Bias Results | ||
|---|---|---|
| Relative % Bias [Range of % Bias] Observedto Reference Method | ||
|---|---|---|
| Hemoglobin Variant | HbA1c ~6.5% A1c | HbA1c ~8.0% A1c |
| HbA2 | -1.6% [-6.7% to 1.5%] | 1.2% [-1.3% to 3.4%] |
| HbC | 0.1% [-5.6% to 4.6%] | -0.5% [-4.7% to 5.7%] |
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| HbD | -1.7% [-6.8% to 1.7%] | -2.6% [-5.7% to 1.2%] |
|---|---|---|
| HbE | -0.1% [-3.0% to 4.8%] | -1.1% [-2.8% to 3.5%] |
| HbF | -0.3% [-6.5% to 4.0%] | 0.5% [-2.7% to 6.9%] |
| HbS | 0.1% [-8.8% to 5.7%] | -0.4% [-4.7% to 5.5%] |
12. Comparison Studies:
A. Method Comparison with Predicate Device
A Method comparison study was performed per CLSI EP09-A2-IR, Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline - Second Edition. 143 variant-free whole blood K2-EDTA samples ranging from 4.1% to 17.7% HbA1c were evaluated using the candidate ADAMS A1c HA-8180V system. The results were compared to testing performed at a secondary NGSP reference laboratory using a previously cleared HPLC method (Tosoh G8).
The distribution of samples spanned the measuring interval are listed in Table 22 and Table 23.
| A1c Level (%) | n | % of Total Samples |
|---|---|---|
| <5.0% | 5 | 3% |
| 5.0 – 6.0% | 19 | 13% |
| 6.0 – 6.5% | 40 | 28% |
| 6.5 – 7.0% | 36 | 25% |
| 7.0 – 8.0% | 21 | 15% |
| 8.0 – 9.0% | 10 | 7% |
| ≥9.0% | 12 | 8% |
| Total | 143 | 100% |
Table 22: Distribution of Samples (Whole Blood)
| A1c Level (%) | n | % of Total Samples |
|---|---|---|
| <5.0% | 5 | 3% |
| 5.0 - 6.0% | 19 | 13% |
| 6.0 - 6.5% | 40 | 28% |
| 6.5 - 7.0% | 36 | 25% |
| 7.0 - 8.0% | 21 | 15% |
| 8.0 - 9.0% | 10 | 7% |
| ≥9.0% | 12 | 8% |
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Image /page/22/Picture/0 description: The image shows the Arkray logo, followed by the text "510(k) Summary ADAMS A1c HA-8180V". Below this is a table with two columns. The left column contains the word "Total", and the right column contains the numbers "143" and "100%".
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Bias between Candidate and NGSP methods:
Deming (weighted) analysis was performed for the HA-8180V system versus the NGSP SRL reference method. Summary of the results are shown in Table 25, and Figure 1 and Figure 2.
Table 24: Method Comparison Study Results Summary (Whole Blood)
| Regression Type | Slope [95% CI] | y-Intercept [95% CI] | R2 |
|---|---|---|---|
| WeightedDeming | 0.9864[0.9626 - 1.010] | 0.09585[-0.06895 - 0.2607] | 0.998 |
Table 25: Method Comparison Study Results Summary (Hemolysate)
| Regression Type | Slope [95% CI] | y-Intercept [95% CI] | R2 |
|---|---|---|---|
| WeightedDeming | 0.9906[0.9670 - 1.014] | 0.08047[-0.08251 - 0.2434] | 0.998 |
Image /page/23/Figure/8 description: The image is a scatter plot comparing two methods, HA-8180V and Tosoh G8. The x-axis represents Tosoh G8, while the y-axis represents HA-8180V, with values ranging from 2 to 18 on both axes. A red line represents the weighted Deming fit, with the equation y = 0.09585 + 0.9864x, and gray dashed lines indicate the allowable difference of ±0.5 or ±10%.
Figure 1: Scatter Plot using Weighted Deming Fit, %HbA1c, Reference Method vs ADAMS A1c HA-8180V (Whole Blood Samples)
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Image /page/24/Figure/2 description: The figure is a scatter plot comparing two different methods, HA-8180V and Tosoh G8. The x-axis represents Tosoh G8, and the y-axis represents HA-8180V, with values ranging from 2 to 18. The plot includes a red line representing the weighted Deming fit, with the equation y = 0.08047 + 0.9906x, and dashed lines indicating the allowable difference of ±0.5 or ±10%.
Figure 2: Scatter Plot using Weighted Deming Fit, %HbA1c, Reference Method vs HA-8180V (Hemolysates Samples)
Note: Scatter plots included in the manual will only show up to 15% to be consistent with the ADAMS A1c HA-8180V claimed HbA1c level.
Bias Estimation
Table 26 and Table 27 show the following biases between the candidate HA-8180V system and the reference NGSP SRL (Tosoh G8) system.
| HbA1c Level (%) | Bias | % Bias |
|---|---|---|
| 5.0 | 0.028 | 0.56% |
| 6.5 | 0.007 | 0.11% |
| 8.0 | -0.013 | -0.16% |
| 12.0 | -0.067 | -0.56% |
Table 26: Bias Estimation (Whole Blood)
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| HbA1c Level (%) | Bias | % Bias |
|---|---|---|
| 5.0 | 0.033 | 0.67% |
| 6.5 | 0.019 | 0.30% |
| 8.0 | 0.005 | 0.07% |
| 12.0 | -0.032 | -0.27% |
Table 27: Bias Estimation (Hemolysate)
Total Error Near the Cutoff
Using the results of bias estimation (%Bias) in the method comparison study and precision estimated in the reproducibility study, Total Error (TE) at four concentrations (5.0%, 6.5%, 8.0% and 12.0%) were calculated as follows: %TE = |%bias| + 1.96 * %CV * (1 + %000). The study results, as summarized in Table 28 and Table 29 demonstrated that the Total Error was ≤6%.
| Alc Level (%) | % Bias | % CV | % TE |
|---|---|---|---|
| 5.0 | 0.56% | 0.5% | 1.5% |
| 6.5 | 0.11% | 0.9% | 1.9% |
| 8.0 | -0.16% | 1.0% | 2.1% |
| 12.0 | -0.56% | 1.0% | 2.4% |
Table 28: Results Summary (Whole Blood)
Table 29: Results Summary (Hemolysate)
| A1c Level (%) | % Bias | % CV | % TE |
|---|---|---|---|
| 5.0 | 0.67% | 0.6% | 1.8% |
| 6.5 | 0.31% | 0.9% | 2.1% |
| 8.0 | 0.07% | 0.8% | 1.6% |
| 12.0 | -0.27% | 0.9% | 2.0% |
B. Matrix Comparison:
A matrix study was performed to determine the suitability of K2-EDTA and K3-EDTA, anticoagulants used with fresh whole blood for use with the ADAMS A1c HA8180V system. Specimens with concentration values spanning 4.7 to 15.7% HbA1c were collected from a total of 40 different donors.
K2 EDTA was the reference anticoagulant and K3 EDTA was the test anticoagulant. Following regression results were obtained:
K2-EDTA whole blood vs K3-EDTA: y = 1.005x - 0.047; R2 = 1.000
The labeling lists K2-EDTA and K3-EDTA as the acceptable anticoagulants.
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13. Expected Values/Reference Range
Hemoglobin A1c expected values reference range cited below is from the American Diabetes Association (ADA), "Diagnosis and Classification of Diabetes Mellitus" Diabetes Care; 39 (Supplement 1): S13-S22; 2016.
| Suggested Diagnosis | HbA1c (%) | HbA1c (mmol/mol) |
|---|---|---|
| Diabetic | $\ge$ 6.5 | $\ge$ 48 |
| Prediabetes | 5.7 – 6.4 | 39 - 47 |
| Normal | < 5.7 | < 39 |
14. Special Control Requirements Checklist for Diabetes Diagnosis Claim
ADAMS A1c HA-8180V System performance substantiates that the device meets the FDA's "Special Controls" requirements to support a diagnostic claim as set forth in the Federal Register, "Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of Hemoglobin A1c Test System: FDA, Final Order", 79 FR 164 (25 Aug 2014), pp. 50549-50551.
| RequirementMet? | Requirement |
|---|---|
| Yes | Device must have initial and annual standardization verification by acertifying glycohemoglobin standardization organization deemedacceptable by the FDA. |
| Yes | Device must meet the following performance testing requirements:Performance testing of device precision must, at a minimum, use bloodsamples with concentrations near 5.0 percent, 6.5 percent, 8.0 percent, and12 percent hemoglobin A1c. This testing must evaluate precision over aminimum of 20 days using at least three lots of the device and threeinstruments, as applicable. |
| Yes | Performance testing of device accuracy must include a minimum of 120blood samples that span the measuring interval of the device and compareresults of the new device to results of a standardized test method. Resultsmust demonstrate little or no bias versus the standardized method |
| Yes | Total error of the new device must be evaluated using single measurementsby the new device compared to results of the standardized test method, andthis evaluation must demonstrate a total error less than or equal to 6 percent |
| Yes | Performance testing must demonstrate that there is little to no interferencefrom common hemoglobin variants, including Hemoglobin C, HemoglobinD, Hemoglobin E, Hemoglobin A2, and Hemoglobin S. |
| Not Applicable | When assay interference from Hemoglobin F or interference with otherhemoglobin variants with low frequency in the population is observed, awarning statement must be placed in a black box and must appear in all |
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| labeling material for these devices describing the interference and any |
|---|
| affected populations. |
CONCLUSION:
The information and data in this 510(k) notification demonstrates that the ADAMS A1c HA-8180V System is an accurate, reliable, precise test that correlates well with currently cleared methods and NGSP standardized testing for the quantitation of HbA1c.
The contents of this notification demonstrate that the ADAMS A1c HA-8180V System performance is substantially equivalent to its predicate device. The performance criteria as stipulated by the Special Controls requirements for HbA1c systems that diagnose diabetes have been met.
§ 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.