(265 days)
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No
The description focuses on standard HPLC technology and a microcomputer for processing, with no mention of AI or ML algorithms for analysis or interpretation.
No.
This device is an in vitro diagnostic (IVD) device used for the quantitative determination of hemoglobin A1c to aid in the diagnosis and monitoring of diabetes. It does not provide treatment or directly interact with the patient for therapeutic purposes.
Yes
The device aids in the diagnosis of diabetes mellitus and identifies individuals at risk, which are diagnostic purposes.
No
The device description clearly states it is a "fully automated analyzer that uses ion exchange high performance liquid chromatography (HPLC) technology" and includes an "analytical instrument" and "CALIBRATOR 80". This indicates significant hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The document explicitly states "For In Vitro Diagnostic Use Only" in the "Intended Use / Indications for Use" section.
- Intended Use: The device is intended for the quantitative determination of hemoglobin A1c in human whole blood and hemolysate samples. This is a test performed on biological samples taken from the body, which is a key characteristic of an IVD.
- Clinical Purpose: The results are used as an aid in the diagnosis of diabetes mellitus, identification of individuals at risk, and monitoring of long-term blood glucose control. These are clinical applications for the test results.
- Professional Use: The device is intended for "Professional Use Only" and for use in "professional clinical laboratory settings," indicating it's used by trained personnel in a healthcare environment for diagnostic purposes.
- Device Description: The description details the analytical method (HPLC) used to analyze the biological sample (whole blood/hemolysate) to obtain a quantitative result for a specific analyte (HbA1c).
- Performance Studies: The document describes performance studies like precision, linearity, analytical specificity (interferences and variants), and method comparison, which are standard evaluations for IVD devices to demonstrate their analytical performance and clinical utility.
- Calibrator: The system includes a calibrator (CALIBRATOR 80) which is also explicitly stated as being "For In Vitro Diagnostic Use Only." Calibrators are essential components of many IVD systems.
All these factors strongly indicate that the ADAMS A1c HA-8180V system is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
PDJ, LCP, JIT
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.
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
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Intended User / Care Setting
Professional Use Only.
professional clinical laboratory settings.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision/Reproducibility:
Study type: Evaluation of Precision Performance of Quantitative Measurement Methods (CLSI EP05-A3)
Sample size: EDTA whole blood samples from four donors at approximate targeted HbA1c concentrations of ~5.0%, ~6.5%, ~8.0% and ~12.0%. Three quality control materials were also tested.
Data source: ARKRAY, (a Point of Care (POC) claim is not being made).
Key results: Reproducibility data for both NGSP and IFCC units were provided across three instruments and combined. Total Coefficient of Variation (CV) for NGSP units ranged from 0.5% to 1.1% for patient samples and 0.7% to 1.1% for controls. For IFCC units, Total CV ranged from 1.0% to 1.6% for patient samples and 0.8% to 2.7% for controls.
Linearity/Reportable Range:
Study type: Evaluation of the Linearity of Quantitative Measuring Procedures; A Statistical Approach (CLSI EP06-A)
Sample size: Controlled samples ranging from low (3% HbA1c) to high (19% HbA1c) EDTA whole blood patient samples, mixed in varying ratios.
Key results: 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. This supports the claimed measurement range of 4.0 to 15.0% (NGSP) / 20 to 140 mmol/mol (IFCC) HbA1c. R2 values for NGSP and IFCC were both 0.9999.
Analytical Specificity (Interferences Study):
Study type: Interference Testing in Clinical Chemistry (CLSI EP07-A2)
Sample size: Whole blood samples with HbA1c values of ~6.5% and ~8.0% spiked with various exogenous and endogenous substances. Ten replicates of each drug were analyzed.
Key results: No significant interference (defined as > ±7.0% change in %HbA1c value from control) was observed at therapeutic levels up to the stated highest concentrations for tested exogenous substances (e.g., Acetaminophen, Ibuprofen, Metformin) and endogenous substances (e.g., Acetylated Hb, Albumin, Bilirubin).
Analytical Specificity (Hemoglobin Variant Study):
Sample size: 165 samples known to contain Hemoglobin variants A2, C, D, E, F, or S. At least 10 samples were tested around HbA1c concentrations of ~6.5% and ~8.0%.
Key results: HbA1c results are accurate (with no significant interference) in samples containing HbA2 (≤16%), HbC (≤39%), HbD (≤36%), HbF (≤30%), HbS (≤40%). Bias results for HbA1c ~6.5% ranged from -1.7% to 0.1% and for HbA1c ~8.0% ranged from -2.6% to 1.2%.
Comparison Studies (Method Comparison with Predicate Device):
Study type: Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline - Second Edition (CLSI EP09-A2-IR)
Sample size: 143 variant-free whole blood K2-EDTA samples.
Data source: Testing performed at a secondary NGSP reference laboratory using a previously cleared HPLC method (Tosoh G8) as the comparison.
Key results: Deming (weighted) analysis performed for the HA-8180V system versus the NGSP SRL reference method (Tosoh G8).
- Whole Blood Samples: Slope 0.9864 (95% CI 0.9626 - 1.010), y-intercept 0.09585 (95% CI -0.06895 - 0.2607), R2 0.998.
- Hemolysate Samples: Slope 0.9906 (95% CI 0.9670 - 1.014), y-intercept 0.08047 (95% CI -0.08251 - 0.2434), R2 0.998.
Bias estimation across HbA1c levels (5.0%, 6.5%, 8.0%, 12.0%) showed values ranging from 0.028% to -0.067% for whole blood, and 0.033% to -0.032% for hemolysate.
Total Error (TE) Near the Cutoff: Total Error was calculated as %TE = |%bias| + 1.96 * %CV. For whole blood, %TE ranged from 1.5% to 2.4%. For hemolysate, %TE ranged from 1.6% to 2.1%. All calculated Total Error values were ≤6%, which met the acceptance criteria.
Comparison Studies (Matrix Comparison):
Sample size: 40 different donors.
Key results: K2-EDTA and K3-EDTA anticoagulants were determined to be suitable. Regression result for K2-EDTA whole blood vs K3-EDTA: y = 1.005x - 0.047; R2 = 1.000.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
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Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with lines extending above them.
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
1
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 602-0008
Telephone: +81 75-662-8979; Fax: +81 75-431-1202
Establishment Registration # 3002807423 |
|----|-------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 2. | Contact Person: | Naveen Thuramalla
Vice President, Regulatory Affairs
Telephone: 202-738-8303; Fax: 952-646-3230
Email: thuramallan@arkrayusa.com |
| 3. | Device Name/Trade Name: | Device
Trade Name: ADAMS A1c HA-8180V
Classification Name: Hemoglobin Alc Test System
Common Name: HbA1c
Product Codes: PDJ, LCP
Classification Panel: Clinical Chemistry
Device Classification: Class II
C.F.R. Sections: Primary: 21 CFR § 862.1373;
Secondary: 21 CFR § 864.7470
Calibrator
Trade Name: Calibrator 80
Classification Name: Calibrator
Common Name: Calibrator
Product Codes: JIT
Classification Panel: Clinical Chemistry
Device Classification: Class II
C.F.R. Sections: 21 CFR § 862.1150 |
4
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.
5
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 Glycohemoglobin | |
Analyzer HLC-723G8 | K131580 |
Tosoh Bioscience, Inc. Hemoglobin A1c Calibrator | |
Set | 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 Glycohemoglobin
Analyzer HLC-723G8
K131580
(Predicate Device) |
|--------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Similarities | | |
| Indications for
Use | 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 Tosoh Automated
Glycohemoglobin Analyzer
HLC-723G8 is intended for in
vitro diagnostic use for the
measurement of % hemoglobin
A1c (HbA1c) (DCCT/NGSP)
and mmol/mol hemoglobin A1c
(IFCC) in whole blood
specimens. This test is to be used
as an aid in diagnosis of diabetes
and identifying patients who
may be at risk for developing
diabetes. |
| Specimen Type | Whole blood, hemolysate sample | Whole blood, diluted blood |
| Assay Principle | Ion exchange HPLC | Ion exchange HPLC |
| Standardization | Traceable to the Diabetes Control
and Complications Trial (DCCT)
reference method and IFCC.
Certified via the National
Glycohemoglobin Standardization
Program (NGSP) | Traceable to the Diabetes
Control and Complications Trial
(DCCT) reference method and
IFCC. Certified via the National
Glycohemoglobin
Standardization Program
(NGSP) |
| Parameter | ADAMS A1c HA-8180V
(Candidate Device) | Tosoh Bioscience, Inc.
Automated Glycohemoglobin
Analyzer HLC-723G8
K131580
(Predicate Device) |
| System
Components | 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 |
| Detection
Method | Dual wavelength (420 nm and
500 nm) LED colorimetric
detector | Dual wavelength (415 nm and
unknown) LED colorimetric
detector |
| STAT
Capability | Yes | Yes |
| HbA1c
Reporting Units | %HbA1c, mmol/mol,
chromatogram | %HbA1c, mmol/mol,
chromatogram |
| Differences | | |
| Measurement
Range (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 µL
Hemolysate: 400 µL | Whole blood: 4 µL
Diluted blood: 80 µL |
| Anticoagulant | K2-EDTA and K3-EDTA Whole
Blood | K3-EDTA Whole Blood |
| Operating
Temperature | 10 - 30°C | 15 - 30°C |
| Table 2: Calibrator Similarities and Differences | | |
| Parameter | ADAMS A1c HA-8180V
(Candidate Device) | Tosoh Bioscience, Inc.
Hemoglobin A1c calibrator
K071132
(Predicate Device) |
| Indications for
Use | 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. | The Tosoh A1c Calibrator Set is
a reference agent designed for
calibrating Tosoh Automated
Glycohemoglobin Analyzer
HLC-723G8. |
| Calibrator
Description | Bi-level calibrators (low and high)
with human-source material | Bi-level calibrators (low and
high) with human-source
material |
| Parameter | ADAMS A1c HA-8180V
(Candidate Device) | Tosoh Bioscience, Inc.
Hemoglobin A1c calibrator
K071132
(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 - approximately
5.5-6.5%
Calibrator 2 - approximately
10.5-11.5% |
| Standardization/
Traceability | Varies according to lot
Traceable to the Diabetes Control
and Complications Trial (DCCT)
reference method and IFCC.
Certified via the National
Glycohemoglobin Standardization
Program (NGSP) | Varies according to lot
Traceable to the Diabetes
Control and Complications Trial
(DCCT) reference method and
IFCC. Certified via the National
Glycohemoglobin
Standardization Program
(NGSP) |
| Matrix | Lyophilized calibrator from
human-sourced hemoglobin | Buffered human red blood cells,
2 mg/mL
Human hemoglobin |
| Storage &
Stability | Shelf life: 18 months at 2 – 8°C
Open bottle: 8 hours at 2 – 8°C
after reconstitution | Shelf life: 2 years at 2 - 8°C
Open bottle: One week at 2 -
8°C after reconstitution*
- Based on manufacturer's
Instructions for Use
(0T012070/Rev March 2013) |
Table 1: Device Similarities and Differences
7
8
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
9
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):
10
| 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 | | 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 | 0.4% | 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):
| Mean
mmol/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
| Mean
mmol/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):
| Mean
mmol/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 | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean | ||||||||||||
mmol/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
| Control
2,
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% |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Control | ||||||||||||
3, | 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):
| Mean
mmol/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): | |||||
---|---|---|---|---|---|
--------------------------------------------------- | -- | -- | -- | -- | -- |
| Mean
mmol/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
| Mean
mmol/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): |
---|
----------------------------------------------------------- |
| Mean
mmol/mol | Repeatability | Between Run | Between Day | Between Lot | Between Instrument | Total | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||
Patient | |||||||||||||
1, 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% | |
Patient | |||||||||||||
2, 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% | |
Patient | |||||||||||||
3, 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% | |
Patient | |||||||||||||
4, 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% | |
Control | |||||||||||||
1, 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% | |
Control | |||||||||||||
2, 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% |
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| Control
3,
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
19
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 Concentration
Without 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 Concentration
Without 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 |
20
| 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 % HbA1c
Concentration |
|---------|----|-------------------|-----------------------------------|
| 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] Observed
to 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%] |
21
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 |
---|---|---|