K Number
K173206
Device Name
SEKURE HbA1c Assay
Date Cleared
2018-07-12

(283 days)

Product Code
Regulation Number
862.1373
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
The SEKURE HbA1c assay is used to measure the percent concentration of hemoglobin A1c (NGSP) or the HbA1c fraction mmol/mol (IFCC) in human venous whole blood and hemolysate on the SK500 Clinical Chemistry System. Measurement of HbA 1c is used as an aid in the diagnosis of diabetes mellitus, as an aid in the identification of patients at risk for development of diabetes mellitus, and for the monitoring of long-term blood glucose with diabetes mellitus. For In Vitro Diagnostic Use Only.
Device Description
The SEKURE HbA1c assay is an enzymatic assay for the measurement of the percent hemoglobin A1c concentration. The assay consists of a pre-treatment hemolyzing buffer solution and two working reagents. Testing is performed on the SK500 K103531in conjunction with calibrators and controls which will be provided separately.
More Information

الك130255

No
The document describes a standard enzymatic assay for measuring HbA1c and a clinical chemistry analyzer. There are no mentions of AI, ML, or related concepts in the intended use, device description, or performance studies. The performance studies focus on traditional analytical validation metrics.

No
The device is an in vitro diagnostic assay used to measure HbA1c in human blood, which aids in the diagnosis and monitoring of diabetes, but it does not directly treat or prevent a disease.

Yes

This device is an aid in the diagnosis of diabetes mellitus and for the monitoring of long-term blood glucose with diabetes mellitus, which are diagnostic purposes.

No

The device is an in vitro diagnostic assay consisting of reagents and intended for use on a specific clinical chemistry analyzer (SK500). It is not a software-only device.

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

  • Intended Use: The "Intended Use / Indications for Use" section explicitly states: "For In Vitro Diagnostic Use Only."
  • Measurement of Analytes in Human Specimens: The device is used to measure the concentration of hemoglobin A1c in human venous whole blood and hemolysate. This is a key characteristic of an IVD.
  • Aid in Diagnosis and Monitoring: The intended use describes how the measurement of HbA1c is used as an aid in the diagnosis of diabetes, identification of patients at risk, and monitoring of long-term blood glucose. These are clinical purposes for which IVDs are used.
  • Device Description: The description details the components of the assay (hemolyzing buffer, working reagents) and its use on a clinical chemistry system, which are typical for IVD tests.

N/A

Intended Use / Indications for Use

The SEKURE HbA1c assay is used to measure the percent concentration of hemoglobin A1c (NGSP) or the HbA1c fraction mmol/mol (IFCC) in human venous whole blood and hemolysate on the SK500 Clinical Chemistry System. Measurement of HbA 1c is used as an aid in the diagnosis of diabetes mellitus, as an aid in the identification of patients at risk for development of diabetes mellitus, and for the monitoring of long-term blood glucose with diabetes mellitus.

For In Vitro Diagnostic Use Only.

Product codes (comma separated list FDA assigned to the subject device)

PDJ, LCP

Device Description

The SEKURE HbA1c assay is an enzymatic assay for the measurement of the percent hemoglobin A1c concentration. The assay consists of a pre-treatment hemolyzing buffer solution and two working reagents. Testing is performed on the SK500 K103531in conjunction with calibrators and controls which will be provided separately.

NGSP Manufacturer Certification: Sekisui has obtained NGSP manufacturer certification for the SEKURE HbA1c assay on the SK500. The certification process included a method comparison of 40 patient samples with a Secondary Reference Laboratory and an assessment of the agreement analysis.

SK500 Clinical Chemistry Analyzer: The SK500 Analyzer is manufactured as Clinical Chemistry Analyzer Tokyo Boeki Medisys Inc. Biolis 50i Superior, cleared under K103531. “SK500" is the Sekisui Diagnostics labeled name for the Tokyo Boeki Medisys Inc. Biolis 50i Superior instrument.

Mentions image processing

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Mentions AI, DNN, or ML

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Input Imaging Modality

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Anatomical Site

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Indicated Patient Age Range

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Intended User / Care Setting

Prescription Use

Description of the training set, sample size, data source, and annotation protocol

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Description of the test set, sample size, data source, and annotation protocol

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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Precision:
Testing was conducted using 3 lots of HbA1c Reagents and Calibrators and 3 instruments. Two levels of controls and 4 levels of human whole blood pools were assayed in 2 replicates at 2 separate times per day for 20 different days. Each reagent lot was calibrated fresh daily.
IFCC: The HbA1c assay is designed to have an imprecision of ≤4.5% within laboratory %CV.
NGSP: The HbA1c assay is designed to have an imprecision of ≤2.5% within laboratory %CV.
Data provided in tables for Precision, All Instruments, Whole Blood, NGSP Units (%HbA1c); Precision, All Instruments, Hemolysate, NGSP Units (%HbA1c); Precision, All Instruments, Whole Blood, IFCC Units (mmol/mol); Precision, All Instruments, Hemolysate, IFCC Units (mmol/mol).

Analytical Sensitivity:
Limit of Blank (LoB) and Limit of Detection (LoD): Testing based on CLSI guidance document EP17-A2. 5 blank samples and 5 low concentration samples analyzed in quadruplicate for 3 days (total 60 measurements) using 2 lots of SEKURE HbA1c reagent on two SK500 analyzers. Results: LoB %HbA1c 3.27, LoD %HbA1c 3.32.

Linearity/Assay Reportable Range:
A linearity study was performed based on guidance from the CLSI guidance document EP06-A. The linearity study was performed using two lots of SEKURE HbA1c reagent on one SK500. A dilution series consisting of 11 levels across the assay range were prepared by mixing high and low HbA1c dipotassium EDTA venous whole blood samples. Samples were run in quadruplicate, mean values are presented.
IFCC: The HbA1c assay is linear across the range of 20.02 to 129.34 mmol/mol HbA1c based on an allowable tolerance of within or equal to ±7%.
NGSP: The HbA1c assay is linear across the range of 4.0 to 14.0 %HbA1c based on an allowable tolerance of within or equal to ±7%. The linearity study supports an assay measuring range of 4.0 to 14.0% HbA1c (20.02 to 129.34 mmol/mol IFCC).

Analytical Specificity (Endogenous and Exogenous Interference):
Interference study based on CLSI EP7-A2 guideline. Tested using 2 lots of SEKURE HbA1c reagent. All interferents tested at ~ 6.5 and 8.0% HbA1c concentrations in replicates of ten. Significant interference was identified as a percent difference greater than 5% from control. Conjugated bilirubin and unconjugated bilirubin showed interference at > 18 mg/dL.
Drug interference testing based on CLSI EP7-A2 guideline. All potential drug interferents tested at ~ 6.5 and 8.0% HbA1c concentrations in replicates of ten. Significant interference was identified as a percent difference greater than 5% from control. No significant drug interferences were observed from the tested drugs.

Hemoglobin Variants:
Study performed according to CLSI EP7-A2. Interference effects assessed by comparing HbA1c values to a comparative method for samples containing variants. No significant interference observed for HbA2, HbC, HbD, HbE or HbS. Significant negative interference with fetal hemoglobin (HbF). HbA1c results are not valid for patients with elevated levels of HbF.

Method comparison with Predicate Device:
Method comparison testing based on CLSI EP09-A3 on 2 SK500 analyzers using 2 lots of SEKURE HbA1c reagent. 130 dipotassium EDTA whole blood specimens analyzed over 5 operating days in duplicate. Samples assayed using both online (whole blood) and offline hemolysis (hemolysate). Sample range was 4.3 to 13.8% NGSP.
Designed slope of 1.1 ± 0.10 and correlation coefficient (r) of ≥ 0.95.
Whole Blood: Passing-Bablok r = 0.9977. Deming r = 0.9977.
Hemolysate: Passing-Bablok r = 0.9981. Deming r = 0.9981.
Bias: Designed to have a bias of ≤ 3% at 5.0, 6.5, 8.0 and 12.0 %HbA1c using Passing-Bablok regression. Bias in %HbA1c (NGSP) ranged from -2.40 to -2.50%.
Total Error Near the Cutoff: Calculated using %Bias and %CV. %TE calculated as %Bias + 1.96 * %CV * (1+%Bias/100). Provided for Whole Blood (NGSP) Passing Bablok, Hemolysate (NGSP) Passing Bablok, Whole Blood (NGSP) Deming, and Hemolysate (NGSP) Deming.

Matrix Comparison:
A matrix study performed to determine suitability of various anticoagulants using two lots of reagents, and 41 matched patient specimens analyzed in duplicate. Sample %HbA1c concentrations spanned the assay range.
Dipotassium EDTA (control tube), Sodium Fluoride/Disodium EDTA, and Tripotassium EDTA support the use based on acceptance criteria for %Bias (≤ 5%), Slope (1.0 ± 0.1), and Correlation Coefficient (≥ 0.95).

Clinical studies: Not Applicable.

Expected values/Reference Range:
Verification of Reference Range conducted using two lots of SEKURE HbA1c reagent and fresh blood from 20 clinically healthy patient samples tested in singlicate. Observed Range for SEKURE HbA1c Lot 1 was 4.60 to 5.66, and for SEKURE HbA1c Lot 2 was 4.74 to 5.83. All samples within verification range (4.43 to 6.27).

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Key metrics for performance:
Precision: ≤4.5% within laboratory %CV (IFCC) and ≤2.5% within laboratory %CV (NGSP).
Linearity: Linear across 4.0 to 14.0 %HbA1c (NGSP) and 20.02 to 129.34 mmol/mol HbA1c (IFCC) with allowable tolerance of within or equal to ±7%.
Bias: ≤ 3% at 5.0, 6.5, 8.0 and 12.0 %HbA1c (NGSP).
Correlation coefficient (r) to NGSP secondary reference laboratory method: ≥ 0.95.
Slope: 1.1 ± 0.10.

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.

K130255

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.

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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

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§ 862.1373 Hemoglobin A1c test system.

(a)
Identification. A hemoglobin A1c test system is a device used to measure the percentage concentration of hemoglobin A1c in blood. Measurement of hemoglobin A1c is used as an aid in the diagnosis of diabetes mellitus and as an aid in the identification of patients at risk for developing diabetes mellitus.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by FDA.
(2) The premarket notification submission must include performance testing to evaluate precision, accuracy, linearity, and interference, including the following:
(i) Performance testing of device precision must, at a minimum, use blood samples with concentrations near 5.0 percent, 6.5 percent, 8.0 percent, and 12 percent hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least three lots of the device and three instruments, as applicable.
(ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the device and compare results of the new device to results of a standardized test method. Results must demonstrate little or no bias versus the standardized method.
(iii) Total error of the new device must be evaluated using single measurements by the new device compared to results of the standardized test method, and this evaluation must demonstrate a total error less than or equal to 6 percent.
(iv) Performance testing must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin S.
(3) When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all labeling material for these devices describing the interference and any affected populations.

0

July 12, 2018

Sekisui Diagnostics PEI Inc. Penny White Regulatory Affairs Manager 70 Watts Ave. Charlottetown, Prince Edward Island C1E 2B9 Canada

Re: K173206

Trade/Device Name: SEKURE HbA1c Assay Regulation Number: 21 CFR 862.1373 Regulation Name: Hemoglobin A1c Test System Regulatory Class: Class II Product Code: PDJ, LCP Dated: May 31, 2018 Received: June 4, 2018

Dear Penny White:

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

1

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 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

2

Indications for Use

510(k) Number (if known) K173206

Device Name SEKURE HbA1c Assay

Indications for Use (Describe)

The SEKURE HbA1c assay is used to measure the percent concentration of hemoglobin A1c (NGSP) or the HbA1c fraction mmol/mol (IFCC) in human venous whole blood and hemolysate on the SK500 Clinical Chemistry System. Measurement of HbA 1c is used as an aid in the diagnosis of diabetes mellitus, as an aid in the identification of patients at risk for development of diabetes mellitus, and for the monitoring of long-term blood glucose with diabetes mellitus.

For In Vitro Diagnostic Use Only.

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

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3

Section 5 510k Summary

This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR §807.92. This is a Traditional 510(k).

The assigned 510(k) number: K173206

5.1. Applicant Information and Date [807.92(a) (1)]

Applicant Name and Address:SEKISUI DIAGNOSTICS P.E.I. INC.
70 Watts Avenue, Charlottetown, PE
Canada, C1E 2B9
Establishment Registration Number: 8020316
Application correspondent:Penny White
Regulatory Affairs Manager
902-628-0934
Penny.white@sekisuidiagnostics.com
Date Summary prepared:06 July 2018

4

Trade NameCommon NameClassification NameRegulationClassificationProduct CodePanel
SEKURE
HbA1c AssayHemoglobin
A1c Test
SystemHemoglobin
A1c Test
System21 CFR
862.1373Class IIPDJClinical
Chemistry
21 CFR
864.7470Class IILCPHematology

5.2. Device Name and Classification [807.92 (a)(2)]

5.3. Identification of Legally Marketed Predicate Devices [807.92(a)(3)]

Trade NamePredicate DevicePredicate 510(k) Number
SEKURE HbA1c AssayArchitect Hemoglobin A1cK130255

5.4. Device Description [807.92 (a)(4)]

Trade NameDevice Description
SEKURE HbA1c
AssayThe SEKURE HbA1c assay is an enzymatic assay for the measurement of the
percent hemoglobin A1c concentration. The assay consists of a pre-treatment
hemolyzing buffer solution and two working reagents. Testing is performed on the
SK500 K103531in conjunction with calibrators and controls which will be
provided separately.
NGSP
Manufacturer
CertificationSekisui has obtained NGSP manufacturer certification for the SEKURE HbA1c
assay on the SK500. The certification process included a method comparison of 40
patient samples with a Secondary Reference Laboratory and an assessment of the
agreement analysis.
SK500 Clinical
Chemistry
AnalyzerThe SK500 Analyzer is manufactured as Clinical Chemistry Analyzer Tokyo
Boeki Medisys Inc. Biolis 50i Superior, cleared under K103531. “SK500" is the
Sekisui Diagnostics labeled name for the Tokyo Boeki Medisys Inc. Biolis 50i
Superior instrument.

5

5.5. Intended Use [807.92 (a)(5)]

Trade NameIntended Use
SEKURE HbA1c AssayThe SEKURE HbA1c assay is used to measure the percent concentration of
hemoglobin A1c (NGSP) or the HbA1c fraction mmol/mol (IFCC) in
human venous whole blood and hemolysate on the SK500 Clinical
Chemistry System.
Measurement of HbA1c is used as an aid in the diagnosis of diabetes
mellitus, as an aid in the identification of patients at risk for development
of diabetes mellitus, and for the monitoring of long-term blood glucose
control in individuals with diabetes mellitus.
For In Vitro Diagnostic Use Only

5.6. Technological Similarities and Differences to the Predicate [807.92 (a)(6)]

The SEKURE HbA1c Assay included in the submission each have a predicate device, as described in the tables below.

Predicate DeviceNew Device
CharacteristicHemoglobin A1c
Abbott
LaboratoriesSEKURE HbA1c Assay
Intended UseThe HbA1c assay is used in clinical
laboratories for the quantitative in
vitro measurement of hemoglobin
A1c or HbA1c fraction mmol/mol
(IFCC) in human whole blood and
hemolysate on the ARCHITECT c
8000 System.

HbA1c measurement is used as an
aid in the diagnosis of diabetes
mellitus and as and aid to identify
patients who may be at risk for
developing diabetes mellitus, and for
the monitoring of long-term blood
glucose control in individuals with
diabetes mellitus. | The SEKURE HbA1c assay is used to
measure the percent concentration of
HbA1c (NGSP) or the HbA1c fraction
mmol/mol (IFCC) in human venous
whole blood and hemolysate on the
SK500 Clinical Chemistry System.

Measurement of hemoglobin A1c is used
as an aid in the diagnosis of diabetes
mellitus, as an aid in the identification of
patients who may be at risk for
development of diabetes mellitus, and for
the monitoring of long-term blood
glucose control in individuals with
diabetes mellitus.

For In Vitro Diagnostic Use Only. |

5.6.1 SEKURE HbA1c Assay

6

Predicate DeviceNew Device
CharacteristicHemoglobin A1c
Abbott
LaboratoriesSEKURE HbA1c Assay
PlatformARCHITECT c 8000 (Clinical
Chemistry Analyzer)SK500 (K103531) (Clinical Chemistry
Analyzer)
MethodologyEnzymaticSAME
Specimen typeWhole blood and hemolysate
Dipotassium EDTA
Lithium Heparin
Sodium Heparin
Sodium fluoride/disodium EDTA
Tripotassium EDTAWhole blood and Hemolysate
Dipotassium EDTA
Sodium fluoride/disodium EDTA
Tripotassium EDTA
Measuring interval4.0 to 14.0% HbA1c (DCCT/NGSP)
20.22-129.51 mmol/mol HbA1c
(IFCC)4.0 to 14.0% HbA1c (DCCT/NGSP)
20.02 to 129.34 mmol/mol HbA1c

5.7. Summary of Non-Clinical Performance Data [807.92 (b)(1)]

5.7.1 SEKURE HbA1c Assay

Precision

Testing was conducted using 3 lots of HbA1c Reagents and Calibrators and 3 instruments. Two levels of controls and 4 levels of human whole blood pools were assayed in 2 replicates at 2 separate times per day for 20 different days. Each reagent lot was calibrated fresh daily.

IFCC

The HbA1c assay is designed to have an imprecision of ≤4.5% within laboratory %CV.

NGSP

The HbA1c assay is designed to have an imprecision of ≤2.5% within laboratory %CV.

RepeatabilityBetween RunBetween DayBetween InstrumentsBetween LotTotal Precision
SampleMeanSDCVSDCVSDCVSDCVSDCVSDCV
QC 15.230.0551.10.0280.50.0561.10.0531.00.0090.20.0831.6
QC 29.770.0640.70.0370.40.0610.60.0410.40.0040.00.0961.0
Patient 15.010.0440.90.0340.70.0410.80.0561.10.0070.10.0691.4
Patient 26.330.0450.70.0370.60.0470.70.0590.90.0110.20.0741.2
Patient 37.790.0370.50.0440.60.0450.60.0590.80.0150.20.0740.9
Patient 412.070.0360.30.0490.40.0670.60.0610.50.0210.20.0910.8

Precision, All Instruments, Whole Blood, NGSP Units (%HbA1c)

7

RepeatabilityBetween RunBetween DayBetween InstrumentsBetween LotTotal Precision
SampleMeanSDCVSDCVSDCVSDCVSDCVSDCV
QC 14.990.0481.00.0320.60.0350.70.0150.30.0090.20.0671.4
QC 29.610.0370.40.0460.50.0360.40.0210.20.0090.10.0690.7
Patient 15.000.0330.70.0320.60.0370.70.0591.20.0080.20.0601.2
Patient 26.340.0360.60.0360.60.0410.60.0570.90.0110.20.0661.0
Patient 37.810.0290.40.0550.70.0370.50.0570.70.0170.20.0730.9
Patient 412.050.0480.40.470.40.0540.50.0580.50.0210.20.0860.7

Precision, All Instruments, Hemolysate, NGSP Units (%HbA1c)

Precision, All Instruments, Whole Blood, IFCC Units (mmol/mol)

RepeatabilityBetween RunBetween DayBetween InstrumentsBetween LotTotal Precision
SampleMeanSDCVSDCVSDCVSDCVSDCVSDCV
QC 133.600.6001.80.3020.90.6171.80.5761.70.1010.30.9122.7
QC 283.330.6980.80.4070.50.6670.80.4510.50.0480.11.0471.3
Patient 131.190.4821.50.741.20.4521.40.6122.00.0810.30.7592.4
Patient 245.640.4881.10.4060.90.5091.10.6431.40.1180.30.8141.8
Patient 361.660.4060.70.4860.80.4950.80.6501.10.1660.30.8041.3
Patient 4108.430.3940.40.5390.50.7310.70.6690.60.2270.20.9900.9

Precision, All Instruments, Hemolysate, IFCC Units (mmol/mol)

RepeatabilityBetween RunBetween DayBetween InstrumentsBetween LotTotal Precision
SampleMeanSDCVSDCVSDCVSDCVSDCVSDCV
QC 131.020.5241.70.3511.10.3801.20.1660.50.1040.30.7362.4
QC 281.570.4020.50.5000.60.3950.50.2260.30.1000.10.7540.9
Patient 131.130.3661.20.3541.10.4091.30.6502.10.0920.30.6532.1
Patient 245.740.3980.90.3970.90.4491.00.6291.40.1170.30.7191.6
Patient 361.800.3140.50.6041.00.4080.70.6241.00.1820.30.7941.3
Patient 4108.200.5280.50.5100.50.5930.50.6320.60.2340.20.9440.9

Analytical Sensitivity

Limit of Blank (LoB) and Limit of Detection (LoD):

Limit of Blank and Limit of Detection testing was based on guidance from the CLSI guidance document EP17-A2. Testing was completed by analyzing 5 blank samples and 5 low concentration samples in quadruplicate for 3 days producing a total of 60 measurements of each level using 2 lots of SEKURE HbA1c reagent on two SK500 analyzers. Low concentration samples were dilutions of dipotassium EDTA venous whole blood.

Limit%HbA1cumol/L A1cumol/L THb
Limit of Blank (LoB)3.270.660.2
Limit of Detection (LoD)3.320.750.5

8

Linearity/Assay Reportable Range:

A linearity study was performed based on guidance from the CLSI guidance document EP06-A. The linearity study was performed using two lots of SEKURE HbA1c reagent on one SK500. A dilution series consisting of 11 levels across the assay range were prepared by mixing high and low HbA lc dipotassium EDTA venous whole blood samples. Samples were run in quadruplicate, mean values are presented.

IFCC

The HbA1c assay is linear across the range of 20.02 to 129.34 mmol/mol HbA1c based on an allowable tolerance of within or equal to ±7%.

NGSP

The HbA1c assay is linear across the range of 4.0 to 14.0 %HbA1c based on an allowable tolerance of within or equal to ±7%.

The linearity study supports an assay measuring range of 4.0 to 14.0% HbA1c (20.02 to 129.34 mmol/mol IFCC).

Traceability, Stability, Expected Values (controls calibrators or methods):

Traceability:

The SEKURE HbA1c Assay standardization is traceable to the International Federation of Clinical Chemistry (IFCC) reference calibrators. The SEKURE HbA1c Assay is NGSP certified. The NGSP certification expires in one year. The derived result of (%) from the NGSP correlation is calculated from the individual quantitative results for the total hemoglobin A1c (HbA1c). The IFCC units of mmol/mol are calculated using the equation IFCC = (NGSP-2.152) / 0.09148. Two different units are provided to users: NGSP equivalent units (%) and IFCC equivalent units (mmol/mol).

Value Assignment:

The SEKURE HbA 1c calibrators are aligned to IFCC reference calibrators through internal value assignment in which the calibrator values must meet the pre-determined acceptance criteria within a set specification. Each lot of calibrators is value-assigned. The concentration of glycated hemoglobin (HbA1c) and total hemoglobin (THb) is provided for each lot. Calibrators are prepared gravimetrically, lyophilized and then value assigned using secondary calibrators that are traceable to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference method.

The value assigned HbA1c concentration falls within the following HbA1c ranges:

Calibrator 1: 4.59% to 6.02% HbA1c

Calibrator 2: 10.52% to 13.37% HbA1c

The SEKURE HbA1c Controls are value assigned using the secondary calibrators. The values obtained must meet the pre-determined acceptance criteria.

9

The value-assigned HbA1c Control values are within the following HbA1c ranges: Control L: 4.59% to 6.02% HbA1c Control H: 9.42% to 11.07 % HbA1c

Stability:

Shelf-life claims: Current testing supports a shelf life of 11 months for un-opened calibrators and controls stored at 2-8 °C. Testing is ongoing to extend the shelf life further.

Onboard Stability for the SK500 was established by real time studies on the SK500 analyzer and demonstrated on-board reagent stability of 28 days. Current testing supports a stability of 11 months for un-opened SEKURE HbA1c Assay. Testing is ongoing to extend the shelf life further.

Analytical Specificity (Endogenous and Exogenous Interference)

An interference study was performed based on the CLSI EP7-A2 guideline to assess common or known substances that could interfere with the HbA1c Assay. Interference testing was conducted using 2 lots of SEKURE HbA1c reagent. All interferents were tested at % HbA1c concentrations of ~ 6.5 and 8.0% in replicates of ten. Significant interference was identified as a percent difference greater than 5% from control.

Highest Tested Concentration at which no significant
Potential Interferentinterference (>5%) was observed
Conventional UnitsSI Units
Conjugated Bilirubin18 mg/dL216 umol/L
Unconjugated Bilirubin18 mg/dL307.8 umol/L
Total Protein22 g/dL220 g/L
Triglycerides3000 mg/dL33.9 mmol/L
Rheumatoid Factor200 IU/mL200 IU/mL
Ascorbic Acid3.0 mg/dL0.15 mmol/L
Glucose1000 mg/dL55.5 mmol/L
Urea667 mg/dL111.06 mmol/L
Vitamin E8.6 mg/dL200 umol/L

The interference study results are summarized in the following table:

The HbA1c assay is susceptible to interference effects from conjugated bilirubin at > 18 mg/dL (216 umol/L) and unconjugated bilirubin at > 18 mg/dL (307.8 umol/L). The bias at 18 mg/dL conjugated bilirubin is -4.2% and the bias at 18 mg/dL unconjugated bilirubin is -4.5%.

Potential drug interference testing was performed based on the CLSI EP7-A2 guideline to assess common or known drugs that could interfere with the HbA1c Assay. All potential drug interferents were tested at % HbA1c concentrations of ~ 6.5 and 8.0% in replicates of ten. Significant interference was identified as a percent difference greater than 5% from control.

The drug interference study results are summarized in the following table:

10

| Potential Drug Interferent | Highest Tested Concentration at which no significant
interference (>5%) was observed | | |
|----------------------------|-----------------------------------------------------------------------------------------|---------------|--|
| | Conventional Units | SI Units | |
| Acarbose | 50 mg/dL | 0.77 mmol/L | |
| Acetaminophen | 20 mg/dL | 1324 umol/L | |
| Acetylsalicylate | 50.8 mg/dL | 2.82 mmol/L | |
| Atorvastatin | 0.06mg/dL | 600 µg Eq/L | |
| Captopril | 0.5 mg/dL | 23 umol/L | |
| Chlorpropamide | 74.7 mg/dL | 2.7 mmol/L | |
| Cyanate | 65 mg/dL | 10 mmol/L | |
| Furosemide | 6.0 mg/dL | 181 umol/L | |
| Gemfibrozil | 7.5 mg/dL | 300 umol/L | |
| Ibuprofen | 50 mg/dL | 2425 umol/L | |
| Insulin | 450 uUlmL | 450 µUlmL | |
| Losartan | 5 mg/dL | 0.11 mmol/L | |
| Metformin | 5.1 mg/dL | 310 µmol/L | |
| Nicotinic Acid | 61 mg/dL | 4.95 mmol/L | |
| Propranolol | 0.2 mg/dL | 7.71 umol/L | |
| Repaglinide | 0.006 mg/dL | 132.57 nmol/L | |

Hemoglobin Variants

The hemoglobin variant study was performed according to guidance from the CLSI EP7-A2. The interference effects of the hemoglobin variants were assessed by comparing the HbA1c values to a comparative method for samples containing potentially interfering hemoglobin variants. The number and concentrations hemoglobin variants tested, and the range of % HbA1c concentrations in which they were tested are shown below:

| Hemoglobin Variant | n | Range in % Abnormal Variant | Range in % HbA1c
Concentration |
|--------------------|----|-----------------------------|-----------------------------------|
| HbA2 | 36 | 4.1 - 6.2 | 4.06 - 10.0 |
| HbC | 14 | 27.4 - 38.4 | 4.81 - 10.46 |
| HbD | 25 | 19.6 - 40.0 | 4.79 - 12.62 |
| HbE | 22 | 24.0 - 28.0 | 5.2 - 10.0 |
| HbF | 25 | 4.4 - 29.3 | 5.1 - 12.8 |
| HbS | 15 | 28.2 - 37.5 | 4.45 - 12.31 |

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| Hemoglobin
Variant | Relative % Difference from Reference Concentration at Low and High
Concentrations | | | |
|-----------------------|--------------------------------------------------------------------------------------|-----------------|--------------------------------------|-----------------|
| | ~ 6.0 % HbA1c
(5.5 to 6.5 %HbA1c) | | ~9.0 %HbA1c
(7.5 to 10.5 %HbA1c)* | |
| | Relative %
Difference | Range | Relative %
Difference | Range |
| HbA2 | -2.28 | -5.56 to 5.08 | -1.28 | -2.30 to -0.14 |
| HbC | -1.64 | -3.30 to 1.90 | -0.97 | -1.72 to -0.38 |
| HbD | 0.10 | -5.69 to 2.91 | -1.14 | -2.83 to 0.67 |
| HbE | 3.41 | 1.85 to 5.42 | 3.50 | -0.50 to 6.34 |
| HbF | -15.42 | -23.06 to -6.25 | -15.33 | -21.73 to -4.81 |
| | HbF interferes with this assay | | | |
| HbS | 1.83 | 0.51 to 2.40 | 0.41 | -0.94 to 1.73 |

The results for the hemoglobin variant study are summarized below:

*The HbA2 results at ~9.0 %HbA1c consisted of samples between 7.2 – 10.0% HbA1c

There was no significant (Relative % Difference >5%) interference observed for HbA2, HbC, HbD, HbE or HbS at the concentrations tested above. There was significant negative interference with fetal hemoglobin (HbF). HbA1c results are not valid for patients with elevated levels of HbF, including those with known Hereditary Persistence of Fetal Hemoglobin. A warning to this effect will be included in product labeling.

Summary of Method Comparison 5.8

Method comparison with Predicate Device:

Method comparison testing was conducted based on CLSI EP09-A3 on 2 SK500 analyzers using 2 lots of SEKURE HbA1c reagent. Testing was completed on 130 dipotassium EDTA whole blood specimens over 5 operating days in duplicate. Samples were assayed using both online (whole blood) and offline hemolysis (hemolysate) using the SEKURE HbA1c assay on the SK500.

The sample range tested was 4.3 to 13.8% NGSP. The distribution of samples spanned the measuring interval with a concentration of samples around the clinical decision points as demonstrated in the table below.

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Method Comparison Sample Range Summary

Hemoglobin A1c leveln% Samples tested
7%4635.3
Total samples130100

First replicate analysis is summarized below. The Hemoglobin A1c assay is designed to have a slope of 1.1 ± 0.10 and a correlation coefficient (r) of ≥ 0.95 for specimens across the measuring interval when compared to an NGSP secondary reference laboratory method.

A correlation study was performed using CLSI protocol EP09-A3 with Passing-Bablok regression and Deming analysis. Human venous whole blood specimen results from the SEKURE Hemoglobin A 1 c assay were compared with those from an NGSP secondary reference laboratory method.

The data are summarized in the following tables:

Whole blood: Passing-Bablok Regression

UnitsComparison Assay (x)NrRegression EquationSample Range
NGSPNGSP Reference Method1300.9977$y = 0.974x + 0.007$4.30 to 13.80
IFCCNGSP Reference Method1300.9977$y = 0.974x - 0.671$23.48 to 127.33

Hemolysate: Passing-Bablok Regression

UnitsComparison Assay (x)NrRegression EquationSample Range
NGSPNGSP Reference Method1300.9981$y = 0.969x + 0.101$4.30 to 13.80
IFCCNGSP Reference Method1300.9981$y = 0.969x + 0.185$23.48 to 127.33

Whole blood: Deming Regression

UnitsComparison Assay (x)NrRegression EquationSample Range
NGSPNGSP Reference Method1300.9977$y = 0.987x - 0.087$4.30 to 13.80
IFCCNGSP Reference Method1300.9977$y = 0.987x - 1.442$23.48 to 127.33

Hemolysate: Deming Regression

Units Comparison Assay (x)NrRegression EquationSample Range
NGSP NGSP Reference Method1300.9981y=0.984x-0.0124.30 to 13.80
IFCCNGSP Reference Method130 0.9981ッ=0.984x - 0.70623.48 to 127.33

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Bias (NGSP)

The HbA1c assay is designed to have a bias of ≤ 3% at 5.0, 6.5, 8.0 and 12.0 %HbA1c using Passing- Bablok regression.

The bias in %HbA1c (NGSP) ranged from -2.40 to -2.50%.

Total Error Near the Cutoff

12.0

Using the results of bias estimation (%Bias) in the method comparison study and precision estimates in the reproducibility study, the Total Error (TE) at the following concentrations (5%, 6.5%, 8% and 12%) was calculated as follows: %TE =%Bias| + 1.96 * %CV * (1+%Bias/100). The results are presented in the tables below.

0.8

4.03

70 Total Effor Summary – Whole Blood (NGSP) Passing Dablok
% Alc - Decision Level% Bias% CV% TE
5.0-2.401.45.08
6.5-2.461.24.75
8.0-2.500.94.22

-2.50

al Error Summery - Whole Rlood (NGSP) Peccing Reblok

% Total Error Summary – Hemolysate (NGSP) Passing Bablok

% A1c - Decision Level% Bias% CV% TE
5.0-1.201.23.52
6.5-1.541.03.47
8.0-1.880.93.61
12.0-2.330.73.67

% Total Error Summary - Whole Blood (NGSP) Deming

% Alc - Decision Level% Bias% CV% TE
5.0-3.041.45.70
6.5-2.641.24.93
8.0-2.390.94.11
12.0-2.030.83.56

% Total Error Summary - Hemolysate (NGSP) Deming

% A1c - Decision Level% Bias% CV% TE
5.0-1.841.24.15
6.5-1.781.03.71
8.0-1.750.93.48
12.0-1.700.73.05

14

Matrix Comparison:

A matrix study was performed to determine the suitability of various anticoagulants for use with the SEKURE HbA1c Assay. The evaluation of different anticoagulants was completed using two lots of reagents, and 41 matched patient specimens analyzed in duplicate. Sample %HbA1c concentrations s panned the range of the assay.

The first replicate Passing-Bablok regression analysis data is summarized in the following table:

| Specification | Acceptance
Criteria | Tripotassium EDTA | | Sodium Fluoride/Disodium EDTA | |
|----------------------------|------------------------|-------------------|--------|-------------------------------|--------|
| | | Lot 1 | Lot 2 | Lot 1 | Lot 2 |
| %Bias | 5% | 0.72 | 0.80 | -0.51 | -0.42 |
| Slope | $1.0 \pm 0.1$ | 1.015 | 0.998 | 1.006 | 0.995 |
| Intercept | N/A | -0.043 | 0.062 | -0.084 | -0.021 |
| Correlation
Coefficient | $\geq 0.95$ | 0.9992 | 0.9992 | 0.9994 | 0.9994 |
| | Pass/Fail | Pass | Pass | Pass | Pass |

Control Tube - Dipotassium EDTA

The data supports the use of the following blood collection tubes with the SEKURE HbA lc assay:

  • . Dipotassium EDTA (control tube)
  • Sodium Fluoride/Disodium EDTA
  • Tripotassium EDTA ●

Clinical studies:

(clinical sensitivity, clinical specificity, other clinical supportive data) Not Applicable

Expected values/Reference Range:

HbA1c values above 6.5 %HbA1c (48 mmol/mol) meet the criteria for diagnosis of diabetes mellitus. Patients with HbA1c values in the range of 5.7 - 6.4 %HbA1c (39 - 47 mmol/mol) are at an increased risk for diabetes (pre-diabetes). HbA1c levels below 5.7 %HbA1c (39 mmol/mol) are considered normal.

    1. American Diabetes Association Position Statement: Standards of medical care in diabetes 2018. In: Diabetes Care 2018; 41 (Suppl 1): S13-S64.

15

Verification of the Reference Range was conducted using two lots of SEKURE HbA1c reagent and fresh blood from 20 clinically healthy patient samples tested in singlicate.

The data in %HbA1c are summarized in the following table:

SEKURE HbA1c Lot 1SEKURE HbA1c Lot 2
Reference Range*4.8 – 5.9%4.8 to 5.9%
Observed Range4.60 to 5.664.74 to 5.83
Verification Range
x – 1/3(y-x) to y +1/3(y-x)
where x = smallest value
y = largest value4.43 to 6.274.43 to 6.27
Samples within verification
range20/2020/20
Pass/FailPassPass

*Source: ROCHE - Reference Ranges for Adults, Pre-Analytical Considerations - 2008

5.8 Proposed Labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10

5.9. Conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.