ACE Hemoglobin A lc (HbA lc) Reagent is intended for the quantitative determination of percent hemoglobin A lc in venous whole blood collected in K2-EDTA tubes using the ACE Axcel® Clinical Chemistry Systems. This test is intended for use in clinical laboratories and physician office laboratories to monitor long term blood glucose control in individuals with diabetes mellitus. For in vitro diagnostic use only.

Device Description

The ACE Hemoglobin A1c (HbA1c) Reagent assay requires a pretreatment step of denaturation of the whole blood samples, which is performed off-line. The red blood cells in the sample are lysed by the Hemoglobin Denaturant and the hemoglobin chains are hydrolyzed. For determination of HbA1c, a latex agglutination inhibition assay is used. In the absence of HbA1c in the sample, the synthetic polymer containing the immunoreactive portion of HbA 1c Agglutinator Reagent will agglutinate with the antibody-coated microparticles in the HbA1c Antibody Reagent. The presence of HbA1c in the blood sample competes for the antibody binding sites and inhibits agglutination. The increase in absorbance, monochromatically at 692 mm, is inversely proportional to the HbA1c present in the sample. For the determination of total hemoglobin, all hemoglobin derivatives in the sample are converted to alkaline hematin. The reaction produces a green colored solution. which is measured bichromatically at 573 nm/692 nm. The intensity of color produced is directly proportional to the total hemoglobin concentration in the sample. The concentrations of both HbA 1 c and total hemoglobin are measured, the ratio is calculated, and the result reported as percent HbA1c.

AI/ML Overview

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the ACE Hemoglobin A1c (HbA1c) Reagent device are implicitly established by demonstrating comparable performance to the predicate device, the DCA 2000+ System for Hemoglobin A1c (K951361), across a range of analytical performance characteristics. While explicit numerical acceptance criteria are not always stated, the study aims to show that the new device's performance aligns with acceptable standards for HbA1c measurement in clinical diagnostics.

Here's a table summarizing the reported device performance:

Performance Characteristic	Acceptance Criteria (Implied by Predicate & Clinical Relevance)	Reported Device Performance (ACE Alera & ACE Axcel)
Limit of Quantitation (LoQ)	Clinically relevant lower limit for HbA1c measurement.	ACE Alera: 2.5% HbA1c ACE Axcel: 2.5% HbA1c
Linearity (HbA1c)	Strong correlation (r² close to 1) and a regression equation with a slope near 1 and y-intercept near 0 across the measuring range, indicating accurate and proportional measurement of HbA1c.	ACE Alera (Range 2.7%-13.0% HbA1c): y = 0.987x + 0.3, r² = 0.9948 ACE Axcel (Range 2.4%-13.1% HbA1c): y = 0.954x + 0.3, r² = 0.9936
Linearity (Total Hemoglobin)	Strong correlation (r² close to 1) and a regression equation with a slope near 1 and y-intercept near 0 across the measuring range of total hemoglobin.	ACE Alera (Range 1.4-22.2 g/dL): y = 1.006x + 0.10, r² = 0.9978 ACE Axcel (Range 1.2-21.8 g/dL): y = 0.997x + 0.20, r² = 0.9964
Precision (Within-Run %CV)	Low %CV for different HbA1c levels, indicating consistent results within a single analytical run. Typically, <5% for routine assays.	ACE Alera (In-house): Range from 1.3% to 2.8% ACE Axcel (In-house): Range from 1.6% to 2.4% ACE Alera (POLs): Range from 0.9% to 2.7% ACE Axcel (POLs): Range from 1.1% to 2.2%
Precision (Total %CV)	Low total %CV, indicating good reproducibility over time and across different runs. Typically, <5% for routine assays.	ACE Alera (In-house): Range from 2.4% to 3.1% ACE Axcel (In-house): Range from 2.4% to 2.9% ACE Alera (POLs): Range from 1.6% to 3.1% ACE Axcel (POLs): Range from 1.8% to 4.3%
Comparative Analysis (In-house vs. Predicate)	Strong correlation (correlation coefficient > 0.97) and regression parameters (slope near 1, intercept near 0) indicating agreement with the predicate device. Confidence intervals for slope should include 1 and for intercept should include 0.	ACE Alera (n=101, Range 3.2-12.8% HbA1c): y = 0.979x + 0.05, Correlation = 0.9839, SE = 0.32, CI slope (0.944-1.015), CI intercept (-0.21-0.31) ACE Axcel (n=102, Range 2.5-12.8% HbA1c): y = 0.983x - 0.03, Correlation = 0.9832, SE = 0.34, CI slope (0.948-1.019), CI intercept (-0.29-0.24)
Comparative Analysis (POLs vs. Predicate)	Similar strong correlation and regression parameters to in-house comparative analysis, demonstrating robust performance in typical clinical laboratory settings.	ACE Alera (POLs): Correlation range 0.9892 to 0.9945. Slopes generally close to 1 (e.g., 0.967, 0.984, 0.981). Intercepts generally close to 0 (e.g., 0.34, -0.02, -0.09). ACE Axcel (POLs): Correlation range 0.9885 to 0.9960. Slopes generally close to 1 (e.g., 1.000, 0.993, 0.980). Intercepts generally close to 0 (e.g., -0.28, -0.12, 0.02).
Analytical Specificity	No significant interference from common endogenous substances or therapeutic compounds within specified concentrations.	Interferents: Bilirubin (≤ 53 mg/dL), Triglycerides (≤ 1100 mg/dL), Ascorbic Acid (≤ 6 mg/dL), Sodium Fluoride (≤ 1200 mg/dL), Acetaldehyde (≤ 100 mg/dL) showed no significant interference.
Cross-Reactivity	No significant interference from common hemoglobin variants or modified hemoglobins.	Non-Interfering: Acetylated Hb (2000 mg/dL), Carbamylated Hb (2000 mg/dL), Labile A1c (1440 mg/dL), Non-glycated Hb (HbA0) (1725 mg/dL), HbA1a+b fraction (100 mg/dL) showed no significant interference. Known Interferences (within certain concentrations): HbD (≤ 36.3%), HbE (≤ 22.5%) showed no significant interference. High HbF (> 10.1%), High HbC (> 14.0%), and High HbS (> 17.1%) will result in inaccurate HbA1c results. These interferences are acknowledged and will be included in labeling.
Measuring Range	Consistent with or broader than the predicate device to coverclinically relevant HbA1c values.	Candidate Device: 2.7 – 13.0% HbA1c Predicate Device: 2.5 – 14.0% HbA1c (The candidate device's range is slightly narrower at the upper end but still covers the critical clinical range).

Study Details:

2. Sample Size and Data Provenance for Test Set:

Linearity: 11 samples were used for both HbA1c and Total Hemoglobin linearity studies, run in 4 replicates each, for both the ACE Alera and ACE Axcel systems.
Precision (In-house): 4 samples (A, B, C, D) were tested, but the number of runs/replicates to calculate SD and %CV is not explicitly stated in the table. Typically, precision studies involve multiple replicates over several days.
Precision (Physician Office Labs - POLs): 4 samples were tested across 3 POLs for each instrument (ACE Alera and ACE Axcel). Similar to in-house, the specific number of runs/replicates per POL for SD and %CV calculation is not detailed.
Comparative Analysis (In-house): 101 samples for ACE Alera and 102 samples for ACE Axcel were compared against the predicate device (DCA 2000+).
Comparative Analysis (POLs): 50 samples per POL for a total of 150 samples for ACE Alera, and 52 samples for one POL and 50 samples for the other two POLs (total 152 samples) for ACE Axcel were compared against the predicate device (DCA 2000+).
Analytical Specificity/Cross-Reactivity: The number of samples for these studies is not explicitly stated, but typically involves spiking known concentrations of interferents into samples and measuring the effect.
Data Provenance: The studies were conducted in-house by Alfa Wassermann Diagnostic Technologies, LLC, and in external Physician Office Laboratories (POLs). Given the nature of performance validation for a diagnostic device, these studies are prospective, as samples are analyzed using the new device and compared against a reference method or predicate. The "country of origin of the data" is implicitly the United States, where the manufacturer and the POLs are located.

3. Number of Experts and their Qualifications for Ground Truth:

The document does not mention the use of "experts" in the traditional sense (e.g., radiologists, pathologists) to establish ground truth for the test set. For an in vitro diagnostic device measuring a quantitative analyte like HbA1c, the ground truth is typically established by:

Reference Methods: Highly accurate and precise analytical methods, often traceable to international standards (e.g., NGSP, IFCC), which are considered the "gold standard" for measuring the analyte.
Predicate Devices: Comparison to a legally marketed device that has already established its safety and effectiveness.

In this case, the ground truth for the comparative studies was derived from the predicate device (DCA 2000+ System for Hemoglobin A1c), which is itself NGSP Certified and traceable to IFCC reference materials.

4. Adjudication Method for the Test Set:

Not applicable. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies involving interpretation of medical images or complex diagnostic assessments by human readers, where discrepancies between readers need to be resolved. For a quantitative in vitro diagnostic device, the ground truth is established analytically through reference methods or predicate comparison, not through expert consensus requiring adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

Not applicable. MRMC studies are generally performed for image-based diagnostic aids or other devices where human interpretation plays a significant role in the diagnostic outcome. This document describes the analytical performance validation of an in vitro diagnostic reagent, which is a quantitative measurement, not an interpretative task for human readers in the context of an MRMC study. Therefore, no effect size of human readers improving with AI vs. without AI assistance is relevant or reported.

6. Standalone (Algorithm Only) Performance Study:

Yes, this entire submission focuses on the standalone performance of the ACE Hemoglobin A1c (HbA1c) Reagent when used with the ACE Alera® and ACE Axcel® Clinical Chemistry Systems. The studies presented (linearity, precision, comparative analysis, specificity, cross-reactivity) all evaluate the direct analytical performance of the device itself, without human intervention for interpretation beyond standard laboratory procedures for operating the instrument and processing samples.

7. Type of Ground Truth Used:

The ground truth used for the comparative analysis studies was the predicate device, the DCA 2000+ System for Hemoglobin A1c. The document explicitly states that the DCA Hemoglobin A1c test method is National Glycohemoglobin Standardization Program (NGSP) Certified and is traceable to International Federation of Clinical Chemistry (IFCC) reference materials and test methods. This indicates that the predicate device serves as a highly standardized and accepted reference for HbA1c measurement.

8. Sample Size for the Training Set:

The document does not explicitly mention a "training set" in the context of machine learning or AI models. This device is a diagnostic reagent kit for a clinical chemistry system, not a software algorithm that requires a separate training phase with a distinct dataset. The performance data presented are for the validation of the finalized device.

9. How the Ground Truth for the Training Set Was Established:

As there is no "training set" in the context of this device being a reagent for a clinical chemistry system, this question is not applicable. The device's design and formulation would have been developed through internal R&D, likely using internal validation and optimization experiments, but these are not typically referred to as a "training set" with established ground truth in the same way as for AI/ML models. The ground truth for the validation of the device's performance (as described above) was established by comparison to the NGSP/IFCC-traceable predicate device.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

February 27, 2018

Barbara Phillips Vice President, Reagent Technologies Alfa Wassermann Diagnostic Technologies, LLC 4 Henderson Drive West Caldwell, NJ 07006

Re: K170623

Trade/Device Name: ACE Hemoglobin A1c (HbA1c) Reagent Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP Dated: January 25, 2018 Received: January 29, 2018

Dear Barbara Phillips:

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 Part 801 and Part 809); medical device 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

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Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Kellie B. Kelm -S

for 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) K170623

Device Name ACE Hemoglobin A1c (HbA1c) Reagent

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	□ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(K) SUMMARY - K170623

I. Applicant/Submitter Contact Information

Applicant:	Alfa Wassermann Diagnostic Technologies, LLC
Address:	4 Henderson DriveWest Caldwell, NJ 07006
Contact Person:Alternate Contact:Phone Number:Fax Number:	Barbara Phillips, MT (ASCP)Hyman Katz, Ph.D.(973) 852 - 0112(973) 852 - 0237
Date of Preparation:	02/21/2018

II. Device

Trade Name:	ACE Hemoglobin A1c (HbA1c) Reagent
Regulatory Information:	21 C.F.R. § 864.7470
Regulation Numbers:	Assay, Glycosylated Hemoglobin
Regulation Names:	Class 2
Regulatory Class:	LCP
Product Codes:

III. Predicate Devices

K951361 DCA 2000+ System for Hemoglobin A1c

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IV. Device Description

V. Intended Use

Indication for use:

ACE Hemoglobin Alc (HbA1c) Reagent is intended for the quantitative determination of percent hemoglobin A1c in venous whole blood collected in K2-EDTA tubes, using the ACE Alera® and ACE Axcel® Clinical Chemistry Systems. This test is intended for use in clinical laboratories and physician office laboratories to monitor long term blood glucose control in individuals with diabetes mellitus. For in vitro diagnostic use only.

VI. Comparison of Technological Characteristics with the predicate device

Both candidate and predicate devices are used for the measurement of the same analyte, have the same intended use, utilize whole blood samples, and are read on an automated instrument.

The candidate device utilizes a different reaction type and different reading wavelengths.

The candidate device requires an off-board pretreatment of the whole blood sample prior to analyzing the sample.

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Technological Similarities and Differences

	Candidate Device	Predicate Device
510(k)#	K170623	K951361
Name	ACE Hemoglobin A1c (HbA1c) Reagent	Siemens Healthcare Diagnostics
	(Off-board pretreatment)	Hemoglobin A1c Reagent Kit
IntendedUse/Indicationsfor Use	ACE Hemoglobin A1c (HbA1c) Reagent isintended for the quantitative determinationof percent hemoglobin A1c in venous wholeblood collected in K2-EDTA tubes, usingthe ACE Alera® and ACE Axcel® ClinicalChemistry Systems. This test is intended foruse in clinical laboratories and physicianoffice laboratories to monitor long termblood glucose control in individuals withdiabetes mellitus. For in vitro diagnostic useonly.	This assay provides a convenient,quantitative method for measuring thepercent concentration of hemoglobin A1c inblood. The measurement of hemoglobin A1cconcentration is recommended formonitoring the long-term care of personswith diabetes. The Diabetes Control andComplications Trial (DCCT) showed theimportance of improved glycemic control inreducing the risk and progression of thecomplications of diabetes. Glycemic controlwas determined by the measurement ofhemoglobin A1c. The American DiabetesAssociation (ADA) recommendsmeasurement of hemoglobin A1c levels twoto four times per year, less frequently inpatients with stable control. This assay isbased on a latex immunoagglutinationinhibition methodology. After loading thereagent test cartridge into the DCATMAnalyzer, the test result is displayed in sixminutes. The DCA Hemoglobin A1c assay isfor use in laboratories such as physicianoffice laboratories, clinics, and hospitals.
Conditions forUse	The g/dL HbA1c and total hemoglobinvalues generated are intended for use in thecalculation of the HbA1c/THb ratio andcannot be used individually for diagnosticpurposes.	No contraindications
InstrumentPlatforms	ACE Alera and ACE Axcel ClinicalChemistry Systems	DCA 2000+ Analyzer
AnalytesMeasured	Same	%HbA1c (ratio of HbA1c to totalhemoglobin)
	Candidate Device	Predicate Device
510(k)#	K170623	K951361
Name	ACE Hemoglobin A1c (HbA1c) Reagent	Siemens Healthcare Diagnostics
	(Off-board pretreatment)	Hemoglobin A1c Reagent Kit
Calibration	6 point calibration for HbA1c,1 point calibration for Total Hemoglobin	Calibrated by the manufacturer. Before reagent cartridges are released by the manufacturer, each lot of reagent cartridges undergoes a thorough analysis and characterization. Values of calibration parameters based on a DCCT reference method are determined that provide for optimal reagent performance. The DCA HbA1c test method is National Glycohemoglobin Standardization Program (NGSP) Certified and is traceable to International Federation of Clinical Chemistry (IFCC) reference materials and test methods. The values for the calibration parameters are encoded onto the calibration card provided with each lot of reagent cartridges.
MethodTraceability orStandardization	Same	NGSP Standardization
Basic Principle	Same	Photometric
Methodology	Same	Antibody-coated latex agglutinationinhibition
ReactiveIngredients	Porcine pepsinSodium hydroxideHbA1c hapten polymerBovine serum albuminHbA1c antibody (mouse) coupled particlesBuffer	HbA1c-specific mouse monoclonalantibodyadsorbed onto latex particlesGlycine BufferHbA1c hapten polymerSodium Citrate BufferBovine serum albuminBuffer
Non-reactiveIngredients	Surfactants, preservatives	Surfactants, preservatives
Dimensions	Bottles with total volumes of 12 and 30 mLcontaining the reagents	Single test cartridges
AnalysisTemperature	Same	37°C
Reaction Type	HbA1c: DeltaTotal Hb: Final Point	Endpoint
MeasurementType	Same	Quantitative ratio of HbA1c to totalhemoglobin, expressed as percent
	Candidate Device	Predicate Device
510(k)#	K170623	K951361
Name	ACE Hemoglobin A1c (HbA1c) Reagent(Off-board pretreatment)	Siemens Healthcare DiagnosticsHemoglobin A1c Reagent Kit
Sample Type	K2-EDTA Whole Blood	Capillary whole bloodVenous whole blood collected in EDTA,heparin, fluoride/oxalate, citrateanticoagulants
MeasuringRange	2.7 – 13.0% HbA1c	2.5 – 14.0% HbA1c
ExpectedValues	Glycemic recommendation for many non-pregnant adults with diabetes:A1c < 7.0%	4.2% HbA1c to 6.5% HbA1c95% CI (4.3% to 5.7%)Risk classifications:3% – 6% in non-diabetics6% – 8% in controlled diabetics
TestingEnvironment	Clinical laboratories or physician officelaboratories	Laboratories such as physician officelaboratories, clinics, and hospitals.

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VII. Performance Data

The following performance data were provided in support of the substantial equivalence determination.

Performance Data Detection Limit and Limit of Quantitation:

Because HbA1c is present to some extent in all samples (without homozygous hemoglobin variants), there is no need to determine the detection limit (LoD) of this assay.

	ACE Alera ClinicalChemistry System	ACE Axcel ClinicalChemistry System
LoQ (%)	2.5	2.5

Linearity:

%HbA1c	ACE Alera	ACE Axcel
No. of Samples	11	11
No. of Reps/Sample	4	4
Range Tested	2.7% – 13.0% HbA1c	2.4% - 13.1% HbA1c
Regression Equation	y=0.987x + 0.3	y=0.954x + 0.3
Coefficient of Determination (r²)	0.9948	0.9936

Total Hemoglobin	ACE Alera	ACE Axcel
No. of Samples	11	11
No. of Reps/Sample	4	4
Range Tested	1.4 – 22.2 g/dL	1.2 – 21.8 g/dL
Regression Equation	y=1.006x + 0.10	y=0.997x + 0.20
Coefficient of Determination (r²)	0.9978	0.9964

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Precision: In-house

ACE Alera		Within run		Total
Sample	Mean	SD	%CV	SD	%CV
A	5.1	0.07	1.4	0.13	2.5
B	6.8	0.14	2.1	0.18	2.6
C	8.2	0.10	1.3	0.20	2.4
D	11.2	0.32	2.8	0.34	3.1

ACE Axcel		Within run		Total
Sample	Mean	SD	%CV	SD	%CV
A	5.0	0.08	1.6	0.12	2.4
B	6.8	0.14	2.0	0.17	2.6
C	8.2	0.13	1.6	0.21	2.6
D	11.1	0.27	2.4	0.32	2.9

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Precision: Physician office labs

ACE Alera		Within-Run			Total
Lab	Sample	Mean	SD	%CV	SD	%CV
POL 1	1	5.3	0.09	1.6	0.09	1.6
POL 2		5.2	0.11	2.1	0.12	2.4
POL 3		4.6	0.08	1.8	0.13	2.9
POL 1	2	6.8	0.12	1.7	0.12	1.7
POL 2		6.7	0.08	1.2	0.14	2.1
POL 3		6.0	0.07	1.1	0.14	2.3
POL 1	3	8.8	0.24	2.7	0.27	3.1
POL 2		8.5	0.11	1.3	0.18	2.1
POL 3		7.9	0.07	0.9	0.25	3.1
POL 1	4	12.5	0.29	2.4	0.32	2.5
POL 2		12.5	0.36	2.9	0.36	2.9
POL 3		11.5	0.13	1.1	0.27	2.3

ACE Axcel			Within-Run		Total
Lab	Sample	Mean	SD	%CV	SD	%CV
POL 1	1	5.4	0.12	2.2	0.24	4.3
POL 2		4.6	0.09	2.0	0.11	2.3
POL 3		4.8	0.10	2.1	0.10	2.2
POL 1	2	6.8	0.08	1.1	0.13	1.9
POL 2		6.1	0.13	2.2	0.16	2.7
POL 3		6.3	0.11	1.7	0.12	1.8
POL 1	3	8.8	0.12	1.3	0.20	2.2
POL 2		8.8	0.16	1.8	0.24	2.8
POL 3		9.1	0.15	1.7	0.27	2.9
POL 1	4	11.9	0.19	1.6	0.29	2.5
POL 2		11.8	0.34	2.9	0.42	3.5
POL 3		12.2	0.15	1.2	0.35	2.9

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	ACE Alera	ACE Axcel
n	101	102
Range (x-method)	3.2% - 12.8%HbA1c	2.5% - 12.8%HbA1c
Regression Equation	y=0.979x + 0.05	y=0.983x - 0.03
Correlation Coefficient	0.9839	0.9832
Standard Error	0.32	0.34
Confidence Interval – slope	0.944 to 1.015	0.948 to 1.019
Confidence Interval - intercept	-0.21 to 0.31	-0.29 to 0.24

Comparative Analysis Regression Evaluation: In-house vs. DCA 2000+

Comparative Analysis Regression Evaluation: Physician office labs vs. DCA 2000+

ACE Alera

Lab	n	Range(x-method)% HbA1c	RegressionEquation	CorrelationCoefficient	StandardError	ConfidenceInterval Slope	ConfidenceIntervalIntercept
POL 1	50	3.2 - 13.4	y=0.967x+0.34	0.9892	0.35	0.925 to 1.008	0.04 to 0.65
POL 2	50	3.1 - 12.9	y=0.984x-0.02	0.9945	0.21	0.955 to 1.014	-0.23 to 0.18
POL 3	50	3.2 - 12.4	y=0.981x-0.09	0.9939	0.21	0.950 to 1.013	-0.30 to 0.12

ACE Axcel

Lab	n	Range(x-method)% HbA1c	RegressionEquation	CorrelationCoefficient	StandardError	ConfidenceInterval Slope	ConfidenceIntervalIntercept
POL 1	52	3.2 - 12.9	y=1.000x-0.28	0.9885	0.33	0.957 to 1.043	-0.59 to 0.03
POL 2	50	3.4 - 12.8	y=0.993x-0.12	0.9932	0.25	0.960 to 1.027	-0.37 to 0.13
POL 3	50	3.5 - 12.9	y=0.980x+0.02	0.9960	0.22	0.955 to 1.006	-0.16 to 0.20

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Expected Values:

Glycemic recommendation for many non-pregnant adults with diabetes:
A1c	<7.0%/*

*More or less stringent glycemic goals may be appropriate for individual patients. Goals should be individualized based on duration of diabetes, age/life expectancy, comorbid conditions, known CVD or advanced microvascular complications, hypoglycemia unawareness, and individual patient considerations.

Source: American Diabetes Association. Glycemic Targets: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018 Jan; 41 (Supplement 1): S55-S64.

Analytical Specificity

Interferent	No significantinterference ≤
Bilirubin	53 mg/dL
Triglycerides	1100 mg/dL
Ascorbic Acid	6 mg/dL
Sodium Fluoride	1200 mg/dL
Acetaldehyde	100 mg/dL

Cross Reactivity:

Acetylated Hb showed no significant interference at 2000 mg/dL. Carbamylated Hb showed no significant interference at 2000 mg/dL. Labile A1c showed no significant interference at 1440 mg/dL. Non-glycated Hb (HbA0) showed no significant interference at 1725 mg/dL. HbA1a+b fraction showed no significant interference at 100 mg/dL.

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Instrument Used:	Axcel			Instrument Used:	Alera
Variant:	HbD			Variant:	HbD
% Variant	36.3%	34.0%	17.3%	% Variant	36.3%	34.0%	17.3%
Reference Value	5.2%	9.4%	12.0%	Reference Value	5.2%	9.4%	12.0%
Mean	5.1%	8.9%	12.0%	Mean	5.1%	9.0%	12.7%
% Recovery	98.6	94.4	99.8	% Recovery	98.1	95.2	105.6
Instrument Used:	Axcel			Instrument Used:	Alera
Variant:	HbE			Variant:	HbE
% Variant	22.5%	14.3%	20.7%	% Variant	22.5%	14.3%	20.7%
Reference Value	4.7%	7.8%	10.8%	Reference Value	4.7%	7.8%	10.8%
Mean	5.1%	7.7%	10.8%	Mean	5.1%	7.9%	10.9%
% Recovery	108.0	98.4	99.5	% Recovery	108.5	101.6	100.9
Instrument Used:	Axcel			Instrument Used:	Alera
Variant:	HbF			Variant:	HbF
% Variant	10.1%	16.8%	29.5%	% Variant	10.1%	16.8%	29.5%
Reference Value	5.1%	7.6%	9.3%	Reference Value	5.1%	7.6%	9.3%
Mean	5.2%	6.6%	6.7%	Mean	5.2%	6.4%	6.7%

% Variant	0.0%	7.0%	14.0%	21.0%	28.0%
Reference Value (Abnormal)	7.9%	7.9%	7.9%	7.9%	7.9%
Mean	7.9%	8.0%	8.6%	9.4%	10.8%
% Recovery	100.0	101.9	109.6	119.1	137.3

Instrument Used:	Alera
Variant:	HbC
% Variant	0.0%	8.8%	17.5%	26.3%	35.0%
Reference Value (Normal)	4.7%	4.7%	4.7%	4.7%	4.7%
Mean	4.7%	4.7%	4.8%	5.5%	6.5%
% Recovery	100.0	100.4	103.1	117.0	139.4

Instrument Used:	Alera
Variant:	HbC
% Variant	0.0%	7.0%	14.0%	21.0%	28.0%
Reference Value (Abnormal)	7.4%	7.4%	7.4%	7.4%	7.4%
Mean	7.4%	7.4%	7.8%	9.0%	10.3%
% Recovery	100.0	98.9	105.0	120.5	138.0

{14}------------------------------------------------

Instrument Used:	Axcel
Variant:	HbS
% Variant	0.0%	9.0%	17.9%	26.9%	35.8%
Reference Value (Normal)	4.8%	4.8%	4.8%	4.8%	4.8%
Mean	4.8%	5.1%	5.3%	5.7%	5.9%
% Recovery	100.0	104.6	109.7	118.0	122.7
Instrument Used:	Axcel
Variant:	HbS
% Variant	0.0%	8.6%	17.1%	25.7%	34.2%
Reference Value (Abnormal)	8.0%	8.0%	8.0%	8.0%	8.0%
Mean	8.0%	8.3%	8.5%	9.5%	10.0%
% Recovery	100.0	103.8	106.9	119.8	125.5

Instrument Used:	Alera
Variant:	HbS
% Variant	0.0%	9.0%	17.9%	26.9%	35.8%
Reference Value (Normal)	5.0%	5.0%	5.0%	5.0%	5.0%
Mean	5.0%	5.3%	5.4%	5.8%	5.9%
% Recovery	100.0	106.1	108.6	117.7	119.2
Instrument Used:	Alera
Variant:	HbS
% Variant	0.0%	8.6%	17.1%	25.7%	34.2%
Reference Value (Abnormal)	7.8%	7.8%	7.8%	7.8%	7.8%
Mean	7.8%	8.1%	8.5%	9.2%	9.7%
% Recovery	100.0	103.9	109.7	118.7	125.5

High Hemoglobin F (> 10.1%), Hemoglobin C (> 14.0%) and Hemoglobin S (> 17.1%) will result in inaccurate HbA1c results. Therefore, a statement will be included in the labeling as follows:

Hemoglobinopathies may interfere with glycated hemoglobin analysis. The results from both ACE Alera and ACE Axcel Clinical Chemistry Systems show that there is no significant interference for Hemoglobin D (≤ 36.3%) and Hemoglobin E (≤ 22.5%). High Hemoglobin F (> 10.1%) will result in lower than expected HbA1c values. High Hemoglobin C (> 14.0%) and high Hemoglobin S (> 17.1%) will result in higher than expected HbA1c values.

VIII. Conclusions

Based on the foregoing data, the device is safe and effective. These data also establish substantial equivalence to the predicate device.

Regulation Number and Section

§ 864.7470 Glycosylated hemoglobin assay.

(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).