CAPILLARYS Hb A1c
Device Facts
| Record ID | K171861 |
|---|---|
| Device Name | CAPILLARYS Hb A1c |
| Applicant | Sebia |
| Product Code | PDJ · Clinical Chemistry |
| Decision Date | Feb 7, 2018 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1373 |
| Device Class | Class 2 |
Intended Use
The CAPILLARYS Hb A1c kit is intended for separation and quantification of the HbA1c glycated fraction of hemoglobin (in IFCC unit (mmol/mol) and NGSP unit (%)) in venous whole human blood, by capillary electrophoresis in alkaline buffer with the CAPILLARYS 2 FLEX-PIERCING instrument. Measurement of hemoglobin A1c is used as an aid in diagnosis of diabetes, as an 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 CAPILLARYS Hb A1c kit is intended for in vitro Diagnostic Use Only.
Device Story
The CAPILLARYS Hb A1c system uses capillary electrophoresis in an alkaline buffer to separate and quantify the HbA1c glycated fraction of hemoglobin from venous whole blood. The CAPILLARYS 2 FLEX-PIERCING instrument performs 8 simultaneous analyses; samples are diluted, aspirated, and subjected to high-voltage protein separation. Hemoglobins are detected directly at the cathodic end via 415 nm absorbance. The system provides HbA1c concentrations in NGSP (%) and IFCC (mmol/mol) units. Used in clinical laboratories, the device aids physicians in diagnosing diabetes, identifying at-risk patients, and monitoring long-term glucose control. The high-resolution procedure allows quantification in the presence of labile HbA1c, carbamylated/acetylated hemoglobins, and major variants (HbA2, S, C, D, E, F). Results assist clinicians in assessing patient glycemic status and adjusting therapeutic interventions.
Clinical Evidence
Bench testing only. Precision evaluated per CLSI EP5-A3 over 20 days using 3 lots, demonstrating total reproducibility CVs between 1.2% and 3.4%. Linearity confirmed across 4.4%–16.6% (NGSP) range per CLSI EP06-A. Method comparison study (n=150) against a cleared HPLC method showed high correlation (r=0.999) and low bias. Interference studies (CLSI EP07-A2) confirmed no significant interference from common endogenous factors, drugs, or hemoglobin variants (S, C, D, E, A2, F) up to specified concentrations.
Technological Characteristics
Capillary electrophoresis in free solution; alkaline buffer; silica capillaries; 415 nm absorbance detection. Dimensions/form factor: CAPILLARYS 2 FLEX-PIERCING instrument. Connectivity: Standalone. Software: PHORESIS software. Reagents: Buffer, hemolysing solution, wash solution. Standardization: Traceable to IFCC reference calibrators; NGSP certified.
Indications for Use
Indicated for use in venous whole blood samples for the diagnosis of diabetes, identification of patients at risk for diabetes, and monitoring long-term blood glucose control in patients with diabetes mellitus. Contraindicated for point-of-care use, daily glucose monitoring, or as a replacement for home testing. Not for use in pediatric patients, pregnant women, patients with Type 1 diabetes, or patients with conditions affecting red blood cell lifespan (e.g., hemolytic anemia, hemoglobinopathies, severe hepatic/renal disease, recent blood loss/transfusion). Not for diagnosing gestational diabetes.
Regulatory Classification
Identification
A hemoglobin A1c test system is a device used to measure the percentage concentration of hemoglobin A1c in blood. Measurement of hemoglobin A1c is used as an aid in the diagnosis of diabetes mellitus and as an aid in the identification of patients at risk for developing diabetes mellitus.
Special Controls
(b) Classification. Class II (special controls). Hemoglobin A1c test systems must comply with the following special controls: 1) The device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by FDA. 2) The premarket notification submission must include performance testing to evaluate precision, accuracy, linearity and interference, including the following: i) Performance testing of device precision must, at a minimum, use blood samples with concentrations near 5.0%, 6.5%, 8.0% and 12% hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least 3 lots of the device and 3 instruments, as applicable. ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the new device and compare results of the new device to results of the standardized test method. Results must demonstrate little or no bias versus the standardized method. iii) Total error of the new device must be evaluated using single measurements by the new device compared to results of the standardized test method, and this evaluation must demonstrate a total error less than or equal to 6%. iv) Performance testing must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2 and Hemoglobin S. 3) When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all labeling material for these devices describing the interference and any affected populations.
*Classification.* Class II (special controls). The special controls for this device are:(1) The device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by FDA. (2) The premarket notification submission must include performance testing to evaluate precision, accuracy, linearity, and interference, including the following: (i) Performance testing of device precision must, at a minimum, use blood samples with concentrations near 5.0 percent, 6.5 percent, 8.0 percent, and 12 percent hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least three lots of the device and three instruments, as applicable. (ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the device and compare results of the new device to results of a standardized test method. Results must demonstrate little or no bias versus the standardized method. (iii) Total error of the new device must be evaluated using single measurements by the new device compared to results of the standardized test method, and this evaluation must demonstrate a total error less than or equal to 6 percent. (iv) Performance testing must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin S. (3) When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all labeling material for these devices describing the interference and any affected populations.
Predicate Devices
- Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 (k131580)
Related Devices
- K171537 — CAPI 3 Hb A1c · Sebia · Sep 12, 2017
- K122101 — CAPILLARYS HEMOGLOBIN HBA1C CAPILLARYS 2 FLEX PIERCING CAPILLARYS HBA1C CONTROLS CAPILLARYS HBA1C C · Sebia · Dec 6, 2012
- K133344 — MINICAP HB A1C, MINICAP FLEX-PIERCING, HB A1C CAPILLARYS CONTROLS, HBA1C CAPILLARYS CALIBRATORS · Sebia · Mar 28, 2014
Submission Summary (Full Text)
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February 7, 2018
Sebia Karen Anderson Director of Technical and Regulatory 1705 Corporate Drive Suite 400 Norcross, GA 30093
Re: K171861
Trade/Device Name: CAPILLARYS Hb A1c Regulation Number: 21 CFR 862.1373 Regulation Name: Hemoglobin A1c test system Regulatory Class: Class II Product Code: PDJ Dated: December 14, 2017 Received: December 20, 2017
Dear Karen Anderson:
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. Ke
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) k171861
Device Name CAPILLARYS Hb A1c
#### Indications for Use (Describe)
The CAPILLARYS Hb A1c kit is intended for separation and quantification of the HbA1c glycated fraction of hemoglobin (in IFCC unit (mmol/mol) and NGSP unit (%)) in venous whole human blood, by capillary electrophoresis in alkaline buffer with the CAPILLARYS 2 FLEX-PIERCING instrument of hemoglobin A1c is used as an aid in diagnosis of diabetes, as an 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 CAPILLARYS Hb A 1c kit is intended for in vitro Diagnostic Use Only.
Type of Use (Select one or both, as applicable)
| <div><span style="font-size:16px">☒</span> Prescription Use (Part 21 CFR 801 Subpart D)</div> |
|-----------------------------------------------------------------------------------------------|
| <div><span style="font-size:16px">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C)</div> |
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# k171861
# 510K SUMMARY (Summary of Safety and Effectiveness)
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Submitter Name | Sebia, Inc. |
|------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Address | 1705 Corporate Drive Suite 400<br>Norcross, Georgia 30093, USA |
| Contact | Karen Anderson, Dir of Technical and QA<br>Phone: 1-800-835-6497<br>Fax: 770-446-8511<br>Email: karen.anderson@sebia-usa.com |
| Date Prepared | February 6, 2018 |
| Manufacturing | Sebia<br>Parc Technologique Léonard de Vinci<br>Rue Léonard de Vinci,<br>CP 8010 LISSES, 91008 EVRY Cedex<br>FRANCE<br>Phone: (33) 1 69 89 80 80<br>Fax: (33) 1 69 89 78 78 |
| Product Name | CAPILLARYS Hb A1c |
| Common Name | Whole blood hemoglobin A1c (HbA1c) by capillary<br>electrophoresis |
| Product Regulation No. | 21 CFR 862.1373 |
| Product Codes | PDJ |
| Device classification and Panel Classification | Class II , Clinical Chemistry(75) |
| Establishment Registration No. | 8023024 |
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# 1. DEVICE DESCRIPTION
The CAPILLARYS 2 FLEX-PIERCING instrument uses the principle of capillary electrophoresis in free solution. With this technique, charged molecules are separated by their electrophoretic mobility in an alkaline buffer with a specific pH. Separation occurs according to the electrolyte pH and electroosmotic flow.
The CAPILLARYS 2 FLEX-PIERCING instrument has silica capillaries functioning in parallel allowing 8 simultaneous analyses of HbA1c quantification in a whole blood sample. A sample dilution with hemolysing solution is prepared and injected by aspiration at the anodic end of the capillary. A high voltage protein separation is then performed and direct detection of the hemoglobins is made at the cathodic end of the capillary at 415 nm, which is the absorbance wave length specific to hemoglobins. Before each run, the capillaries are washed with a wash solution and prepared for the next analysis with buffer.
Direct detection provides accurate relative quantification of individual hemoglobin A1c fraction. In addition, the high resolution of CAPILLLARYS Hb A1c procedure allows the quantification of HbA1c even in the presence of labile HbA1c, carbamylated and acetylated hemoglobins, and major hemoglobin variants.
By using an alkaline pH buffer, normal and abnormal (or variant) hemoglobins are detected in the following order, from cathode to anode: A2/C, E, S/D, F, A0, other Hb (including minor Hb A1) and then A1c.
The HbA1c concentrations are standardized and indicated in %HbA1c (DCCT/NGSP) and in mmol/mol (IFCC) units.
# Reagents:
# CAPILLARYS HbA1c KIT
| ITEMS | PN 2015 |
|------------------------------------|----------------------|
| Buffer (ready to use) | 2 vials, 700 mL each |
| Hemolysing solution (ready to use) | 1 vial, 700 mL |
| Wash solution (stock solution) | 1 vial, 75 mL |
| Green dilution segments | 1 pack of 90 |
| Filters | 4 filters |
## Additional reagents not included in the CAPILLARYS Hb A1c KIT
| ITEMS | PN | COMPONENTS |
|-----------|------|---------------|
| CAPICLEAN | 2058 | 1 vial, 25 mL |
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| CAPILLARYS WASH SOLUTION | 2052 | 2 vial, 75mL |
|-------------------------------------------|--------------|-----------------------|
| TUBES AND CAPS FOR CONTROLS | 9202<br>9205 | 20 units<br>500 units |
| Wedge adapters | 9203 | 10 per box |
| PHORESIS software | 1110 | |
| CAPILLARYS 2 FLEX-PIERCING<br>INSTRUMENT | 1227 | |
| Hb A1c CAPILLARY CALIBRATORS | 4755<br>4756 | 1 SET<br>5 SETS |
| MULTI-SYSTEM Hb A1c<br>CAPILLARY CONTROLS | 4767<br>4768 | 10 SETS<br>1 SET |
## 2. INDICATIONS FOR USE
## CAPILLARYS Hb A1c kit:
The CAPILLARYS Hb A1c kit is intended for separation and quantification of the HbA1c glycated fraction of hemoglobin (in IFCC unit (mmol/mol) and NGSP unit (%)) in venous whole human blood, by capillary electrophoresis in alkaline buffer with the CAPILLARYS 2 FLEXPIERCING instrument. Measurement of hemoglobin A1c is used as an aid in diagnosis of diabetes, as an 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 CAPILLARYS Hb A1c kit is intended for in vitro Diagnostic Use Only
## 3. SUBSTANTIAL EQUIVALENCE INFORMATION:
| Predicate Device Name | Predicate Device Product Code Regulation No.<br>510(k) number | | |
|-------------------------------------------------------------|-------------------------------------------------------------------|-----|----------|
| Tosho Automated<br>Glycohemoglobin Analyzer HLC-<br>723G-8 | k131580 | PDJ | 862.1373 |
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## Similarities between the candidate device (CAPILLARYS Hb A1c) and the predicate device (Tosoh HLC-723G8, k131580 (Table A).
| Similarities | | |
|----------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Table A | Sebia CAPILLARYS Candidate Device Hb A1c | Tosoh HLC-723G8 Predicate Device (k131580) |
| Intended use | The CAPILLARYS Hb A1c kit is intended for separation and quantification of the HbA1c glycated fraction of hemoglobin (in IFCC unit (mmol/mol) and NGSP unit (%)) in venous whole human blood, by capillary electrophoresis in alkaline buffer with the CAPILLARYS 2 FLEX-PIERCING instrument. Measurement of hemoglobin A1c is used as an aid in diagnosis of diabetes, as an 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 CAPILLARYS Hb A1c kit is intended for in vitro Diagnostic Use Only | The Tosoh Automated Glycohemoglobin Analyzer HLC723G8 is intended for the 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 of developing diabetes. |
| Specimen Type | Human Whole Blood | Human Whole Blood |
| Standardization | Traceable to the Diabetes Contraol and Complications Trial (DCCT) reference method and IFCC. Certified via the National Glycohemoglobin Standardization Program ( NGSP) | Same |
| Linearity<br>Measuring Range | 4.4 – 16.6% (NGSP)<br>24 – 158 mmol/mol ( IFCC) | 4.0 – 16.9 % |
| Total<br>Errorallowable bias<br>6% | Concentration<br>5.1<br>6.4<br>8.2<br>12.2 | Concentration<br>5.0<br>6.5<br>8.0<br>12.0 |
| | TE%<br>5.9<br>4.1<br>2.8<br>3.1 | TE%<br>5.8<br>2.8<br>3.0<br>3.1 |
| Hemoglobin<br>Variant<br>Interferences | HbA2, HbS, HbC, HbD, does not interfere with this assay | HbA2, HbF, HbS, HbC, HbD, does not interfere with this assay |
Table B. Differences between the predicate device (CAPILLARYS Hb A1c) and the candidate device (Tosoh HLC-723G8, k131580) in (Table B).
| Differences | | |
|-----------------|---------------------------------------------|-----------------------------------------------|
| Table B | Sebia CAPILLARYS Hb A1c<br>Candidate Device | Tosoh HLC-723G8<br>Predicate Device (k131580) |
| Assay Principle | Capillary electrophoresis | Ion-exchange HPLC |
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| Hemoglobin<br>Variant<br>Interferences | Hb E no interference | Hb E has known interference, a HbE<br>flag is displayed and no Hb A1c is<br>reported. |
|----------------------------------------|----------------------|---------------------------------------------------------------------------------------|
|----------------------------------------|----------------------|---------------------------------------------------------------------------------------|
4. Performance Data:
## a. Precision / Reproducibility:-
#### Precision
The precision of the CAPILLARYS Hb A1c procedure using the CAPILLARYS 2 FLEX-PIERCING was evaluated in a study based on the Clinical Laboratory Standards Institute (CLSI - USA) EP5A3 guideline "Evaluation of Precision of Quantitative Measurements Procedures; Approved Guideline - Third Edition".
The means, standard deviations (SD) and coefficients of variation (CV %) were calculated for HbA1c concentration (mmol/mol) and percentage (%) for each sample.
Evaluation of Precision of Quantitative Measurement Procedures. Four whole blood samples at the following targeted HbA1c concentration of ~ 5%. ~ 6.5%. ~ 8%, and ~12% were used in the study
Eight (8) different samples were run using the CAPILLARYS Hb A1c procedure on the CAPILLARYS 2 FLEX-PIERCING instrument. The analyzed samples included 4 human blood samples (blood No. 1 to 4), 2 controls and 2 calibrators. Each sample was analyzed in duplicate on two capillaries per run, two runs per day over 20 days per lot of CAPILLARYS Hb A1c kit, using three lots yielding a total of 1440 results per sample over 60 days.
The reproducibility between instruments is summarized in the following tables including withincapillary, between-capillary, between-run, between-lot, between-instrument and total reproducibility precision estimates (SD and %CV) for the HbAre percentages.
| | Mean<br>(mmol/mol) | Within-capillary | | Between-capillary | | Between-run | | Between-day | | Between-lot | | Between-instrument | | Total reproducibility (*) | |
|--------------|--------------------|------------------|------|-------------------|------|-------------|------|-------------|------|-------------|------|--------------------|------|---------------------------|------|
| Sample | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 32 | 0,60 | 1,9% | 0,67 | 2,1% | 0,00 | 0,0% | 0,26 | 0,8% | 0,35 | 1,1% | 0,00 | 0,0% | 0,99 | 3,1% |
| Blood No. 2 | 46 | 0,76 | 1,7% | 0,40 | 0,9% | 0,00 | 0,0% | 0,27 | 0,6% | 0,38 | 0,8% | 0,00 | 0,0% | 0,98 | 2,1% |
| Blood No. 3 | 66 | 0,78 | 1,2% | 0,58 | 0,9% | 0,00 | 0,0% | 0,32 | 0,5% | 0,36 | 0,6% | 0,00 | 0,0% | 1,09 | 1,6% |
| Blood No. 4 | 109 | 0,89 | 0,8% | 0,88 | 0,8% | 0,00 | 0,0% | 0,51 | 0,5% | 1,18 | 1,1% | 0,00 | 0,0% | 1,79 | 1,6% |
| Control 1 | 33 | 0,64 | 2,0% | 0,57 | 1,8% | 0,00 | 0,0% | 0,36 | 1,1% | 0,57 | 1,8% | 0,03 | 0,1% | 1,10 | 3,4% |
| Control 2 | 63 | 0,73 | 1,2% | 0,99 | 1,6% | 0,00 | 0,0% | 0,79 | 1,2% | 0,17 | 0,3% | 0,91 | 1,4% | 1,73 | 2,7% |
| Calibrator 1 | 37 | 0,76 | 2,0% | 0,41 | 1,1% | 0,00 | 0,0% | 0,32 | 0,8% | 0,44 | 1,2% | 0,00 | 0,0% | 1,02 | 2,7% |
| Calibrator 2 | 87 | 0,94 | 1,1% | 0,67 | 0,8% | 0,00 | 0,0% | 0,23 | 0,3% | 0,62 | 0,7% | 0,00 | 0,0% | 1,33 | 1,5% |
(*) Total reproducibility includes: within-capillary, between-capillary, between-run, between-day, between-lot and between-instrument.
| Sample | Mean<br>(%) | Within-capillary | | Between-capillary | | Between-run | | Between-day | | Between-lot | | Between-instrument | | Total reproducibility (*) | |
|--------------|-------------|------------------|------|-------------------|------|-------------|------|-------------|------|-------------|------|--------------------|------|---------------------------|------|
| | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 5,1 | 0,06 | 1,1% | 0,06 | 1,2% | 0,00 | 0,0% | 0,03 | 0,6% | 0,03 | 0,5% | 0,00 | 0,0% | 0,09 | 1,8% |
| Blood No. 2 | 6,4 | 0,07 | 1,1% | 0,04 | 0,6% | 0,00 | 0,0% | 0,03 | 0,4% | 0,04 | 0,6% | 0,00 | 0,0% | 0,09 | 1,4% |
| Blood No. 3 | 8,2 | 0,07 | 0,9% | 0,05 | 0,7% | 0,00 | 0,0% | 0,03 | 0,3% | 0,03 | 0,4% | 0,00 | 0,0% | 0,10 | 1,2% |
| Blood No. 4 | 12,2 | 0,08 | 0,7% | 0,08 | 0,6% | 0,00 | 0,0% | 0,04 | 0,4% | 0,10 | 0,9% | 0,00 | 0,0% | 0,16 | 1,3% |
| Control 1 | 5,1 | 0,06 | 1,1% | 0,05 | 1,1% | 0,00 | 0,0% | 0,03 | 0,7% | 0,05 | 1,0% | 0,01 | 0,3% | 0,10 | 2,0% |
| Control 2 | 8,0 | 0,07 | 0,9% | 0,09 | 1,1% | 0,00 | 0,0% | 0,07 | 0,9% | 0,01 | 0,2% | 0,08 | 1,1% | 0,16 | 2,0% |
| Calibrator 1 | 5,6 | 0,07 | 1,3% | 0,04 | 0,7% | 0,00 | 0,0% | 0,03 | 0,5% | 0,05 | 0,9% | 0,00 | 0,0% | 0,10 | 1,8% |
| Calibrator 2 | 10,1 | 0,08 | 0,8% | 0,06 | 0,6% | 0,00 | 0,0% | 0,02 | 0,2% | 0,07 | 0,7% | 0,00 | 0,0% | 0,13 | 1,3% |
(") Total reproducibility includes : within-capillary, between-run, between-day, between-day, between-lot and betwee
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The reproducibility within the same instrument is summarized in the following tables :
including within-capillary, between-capillary, between-day, between-day, between-lot and total reproducibility precision estimates (SD and %CV) for the HbA% concentrations (in mmol/mol) and percentages for each instrument.
including the within-lot precision estimates (SD and %CV) for the HbA1ം concentrations (in mmol/mol) and percentages for each lot on each instrument.
| Sample | Mean<br>(mmol/mol) | Within-capillary | | Between-capillary | | Between-run | | Between-day | | Between-lot | | Total reproducibility (*) | |
|--------------------------------------------------------------------------------------------------------------------|--------------------|------------------|------|-------------------|------|-------------|------|-------------|------|-------------|------|---------------------------|------|
| | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 32 | 0,60 | 1,9% | 0,49 | 1,5% | 0,00 | 0,0% | 0,22 | 0,7% | 0,42 | 1,3% | 0,91 | 2,8% |
| Blood No. 2 | 46 | 0,80 | 1,7% | 0,37 | 0,8% | 0,00 | 0,0% | 0,22 | 0,5% | 0,38 | 0,8% | 0,99 | 2,1% |
| Blood No. 3 | 66 | 0,77 | 1,2% | 0,50 | 0,8% | 0,00 | 0,0% | 0,44 | 0,7% | 0,36 | 0,6% | 1,08 | 1,6% |
| Blood No. 4 | 109 | 0,90 | 0,8% | 0,79 | 0,7% | 0,00 | 0,0% | 0,53 | 0,5% | 1,11 | 1,0% | 1,72 | 1,6% |
| Control 1 | 33 | 0,64 | 2,0% | 0,49 | 1,5% | 0,00 | 0,0% | 0,40 | 1,2% | 0,51 | 1,6% | 1,04 | 3,2% |
| Control 2 | 63 | 0,75 | 1,2% | 1.36 | 2,2% | 0,00 | 0,0% | 0,40 | 0,6% | 0,29 | 0,5% | 1,63 | 2,6% |
| Calibrator 1 | 37 | 0,80 | 2,1% | 0,29 | 0,8% | 0,00 | 0,0% | 0,40 | 1,1% | 0,32 | 0,8% | 0,99 | 2,7% |
| Calibrator 2 | 87 | 0,91 | 1,1% | 0,77 | 0,9% | 0,00 | 0,0% | 0,13 | 0,2% | 0,65 | 0,7% | 1,36 | 1,6% |
| (*) Total reproducibility includes : within-capillary, between-capillary, between-run, between-day and between-lot | | | | | | | | | | | | | |
Instrument No. 1
withi Within-lot (*)
| Sample | Mean<br>(mmol/mol) | Lot No. 1 | | Lot No. 2 | | Lot No. 3 | |
|--------------|--------------------|-----------|------|-----------|------|-----------|------|
| | | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 32 | 0,88 | 2,7% | 0,67 | 2,1% | 0,87 | 2,7% |
| Blood No. 2 | 46 | 0,91 | 2,0% | 0,96 | 2,1% | 0,89 | 1,9% |
| Blood No. 3 | 66 | 0,87 | 1,3% | 1,08 | 1,6% | 1,10 | 1,7% |
| Blood No. 4 | 109 | 1,33 | 1,2% | 1,36 | 1,2% | 1,24 | 1,1% |
| Control 1 | 33 | 0,81 | 2,5% | 0,99 | 3,1% | 0,89 | 2,7% |
| Control 2 | 63 | 1,25 | 2,0% | 1,59 | 2,5% | 1,91 | 3,0% |
| Calibrator 1 | 37 | 0,87 | 2,3% | 0,99 | 2,7% | 1,02 | 2,7% |
| Calibrator 2 | 87 | 0,95 | 1,1% | 1,40 | 1,6% | 1,25 | 1,4% |
(*) Within lot reproducibility includes : within-capillary, between-capillary, between-run and between-day
| | Mean | Within-capillary | | Between-capillary | | Between-run | | Between-day | | Between-lot | | Total reproducibility (*) | |
|---------------------------------------------------------------------------------------------------------------------|----------|------------------|------|-------------------|------|-------------|------|-------------|------|-------------|------|---------------------------|------|
| Sample | (%) | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 5,1 | 0,06 | 1,3% | 0,04 | 0,7% | 0,00 | 0,0% | 0,03 | 0,5% | 0,03 | 0,7% | 0,09 | 1,7% |
| Blood No. 2 | 6,4 | 0,07 | 1,1% | 0,04 | 0,5% | 0,00 | 0,0% | 0,03 | 0,4% | 0,03 | 0,5% | 0,09 | 1,4% |
| Blood No. 3 | 8,2 | 0,08 | 0,9% | 0,05 | 0,6% | 0,00 | 0,0% | 0,04 | 0,4% | 0,04 | 0,5% | 0,10 | 1,3% |
| Blood No. 4 | 12,2 | 0,08 | 0,7% | 0,08 | 0,6% | 0,00 | 0,0% | 0,05 | 0,4% | 0,10 | 0,8% | 0,16 | 1,3% |
| Control 1 | 5,1 | 0,06 | 1,2% | 0,04 | 0,7% | 0,00 | 0,0% | 0,04 | 0,7% | 0,04 | 0,8% | 0,09 | 1,8% |
| Control 2 | 8,0 | 0,07 | 0,9% | 0,12 | 1,5% | 0,00 | 0,0% | 0,03 | 0,4% | 0,02 | 0,3% | 0,14 | 1,8% |
| Calibrator 1 | 5,6 | 0,07 | 1,2% | 0,04 | 0,7% | 0,00 | 0,0% | 0,04 | 0,7% | 0,04 | 0,7% | 0,10 | 1,7% |
| Calibrator 2 | 10,1 | 0,09 | 0,9% | 0,07 | 0,7% | 0,00 | 0,0% | 0,02 | 0,2% | 0,07 | 0,7% | 0,14 | 1,3% |
| (*) Total reproducibility includes : within-capillary, between-capillary, between-run, between-day and between-lot. | | | | | | | | | | | | | |
| Sample | Mean (%) | Within-lot (*) | | | | | | | | | | | |
{9}------------------------------------------------
| | | Lot No. 1 | | Lot No. 2 | | Lot No. 3 | |
|--------------|------|-----------|------|-----------|------|-----------|------|
| | | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 5,1 | 0,07 | 1,5% | 0,07 | 1,4% | 0,09 | 1,8% |
| Blood No. 2 | 6,4 | 0,07 | 1,1% | 0,08 | 1,3% | 0,09 | 1,4% |
| Blood No. 3 | 8,2 | 0,08 | 1,0% | 0,10 | 1,2% | 0,10 | 1,2% |
| Blood No. 4 | 12,2 | 0,13 | 1,1% | 0,12 | 1,0% | 0,12 | 0,9% |
| Control 1 | 5,1 | 0,07 | 1,4% | 0,09 | 1,7% | 0,08 | 1,6% |
| Control 2 | 8,0 | 0,11 | 1,4% | 0,13 | 1,6% | 0,17 | 2,2% |
| Calibrator 1 | 5,6 | 0,07 | 1,3% | 0,09 | 1,7% | 0,10 | 1,7% |
| Calibrator 2 | 10,1 | 0,09 | 0,9% | 0,14 | 1,3% | 0,11 | 1,1% |
(1) Within-lot reproducibility includes : within-capillary, between-run and between-run and between-day.
Instrument No. 2
| Sample | Mean<br>(mmol/mol) | Within-capillary | | Between-capillary | | Between-run | | Between-day | | Between-lot | | Total reproducibility (*) | |
|--------------|--------------------|------------------|------|-------------------|------|-------------|------|-------------|------|-------------|------|---------------------------|------|
| | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 32 | 0,60 | 1,9% | 0,25 | 0,8% | 0,00 | 0,0% | 0,23 | 0,7% | 0,23 | 0,7% | 0,73 | 2,3% |
| Blood No. 2 | 46 | 0,68 | 1,5% | 0,36 | 0,8% | 0,00 | 0,0% | 0,35 | 0,8% | 0,48 | 1,0% | 0,97 | 2,1% |
| Blood No. 3 | 66 | 0,72 | 1,1% | 0,32 | 0,5% | 0,21 | 0,3% | 0,26 | 0,4% | 0,52 | 0,8% | 1,00 | 1,5% |
| Blood No. 4 | 109 | 0,85 | 0.8% | 0,72 | 0,7% | 0,00 | 0,0% | 0,44 | 0,4% | 1,40 | 1,3% | 1,84 | 1,7% |
| Control 1 | 33 | 0,62 | 1,9% | 0,48 | 1,4% | 0,00 | 0,0% | 0,26 | 0,8% | 0,63 | 1,9% | 1,04 | 3,2% |
| Control 2 | 63 | 0,60 | 0,9% | 0,92 | 1,4% | 0,00 | 0,0% | 0,63 | 1,0% | 0,25 | 0,4% | 1,30 | 2,0% |
| Calibrator 1 | 37 | 0,69 | 1,8% | 0,31 | 0,8% | 0,00 | 0,0% | 0,28 | 0,7% | 0,55 | 1,5% | 0,97 | 2,6% |
| Calibrator 2 | 87 | 0,89 | 1,0% | 0,46 | 0,5% | 0,30 | 0,3% | 0,32 | 0,4% | 0,74 | 0,9% | 1,32 | 1,5% |
| (*) Total reproducibility includes : within-capillary, between-capillary, between-run, between-day and between-lot. | | | | | | | |
|---------------------------------------------------------------------------------------------------------------------|--------------------|-----------|------|-----------|------|-----------|------|
| Sample | Mean<br>(mmol/mol) | Lot No. 1 | | Lot No. 2 | | Lot No. 3 | |
| | | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 32 | 0,67 | 2,0% | 0,63 | 2,0% | 0,81 | 2,5% |
| Blood No. 2 | 46 | 0,83 | 1,8% | 0,89 | 1,9% | 0,85 | 1,8% |
| Blood No. 3 | 66 | 0,82 | 1,2% | 0,85 | 1,3% | 0,91 | 1,4% |
| Blood No. 4 | 109 | 1,08 | 1,0% | 1,19 | 1,1% | 1,30 | 1,2% |
| Control 1 | 33 | 0,88 | 2,6% | 0,79 | 2,4% | 0,81 | 2,4% |
| Control 2 | 63 | 1,39 | 2,2% | 1,04 | 1,6% | 1,36 | 2,1% |
| Calibrator 1 | 37 | 0,87 | 2,3% | 0,77 | 2,1% | 0,81 | 2,2% |
| Calibrator 2 | 87 | 0,92 | 1,1% | 1,14 | 1,3% | 1,18 | 1,4% |
| (*) Within lot reproducibility includes : within-capillary, between-capillary, between-run and between-day. | | | | | | | |
| Sample | Mean<br>(%) | Within-capillary | | Between-capillary | | Between-run | | Between-day | | Between-lot | | Total reproducibility (*) | |
|--------------|-------------|------------------|------|-------------------|------|-------------|------|-------------|------|-------------|------|---------------------------|------|
| | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 5,1 | 0,05 | 1,0% | 0,02 | 0,4% | 0,00 | 0,0% | 0,02 | 0,5% | 0,01 | 0,2% | 0,06 | 1,2% |
| Blood No. 2 | 6,4 | 0,07 | 1,1% | 0,04 | 0,6% | 0,00 | 0,0% | 0,03 | 0,4% | 0,05 | 0,8% | 0,10 | 1,5% |
| Blood No. 3 | 8,2 | 0,07 | 0,8% | 0,02 | 0,3% | 0,02 | 0,2% | 0,03 | 0,3% | 0,05 | 0,6% | 0,09 | 1,1% |
| Blood No. 4 | 12,2 | 0,08 | 0,7% | 0,06 | 0,5% | 0,00 | 0,0% | 0,03 | 0,3% | 0,12 | 1,0% | 0,16 | 1,3% |
| Control 1 | 5,1 | 0,05 | 1,1% | 0,05 | 1,0% | 0,00 | 0,0% | 0,03 | 0,5% | 0,06 | 1,1% | 0,10 | 1,9% |
| Control 2 | 8,0 | 0,05 | 0,7% | 0,09 | 1,1% | 0,00 | 0,0% | 0,06 | 0,7% | 0,02 | 0,3% | 0,12 | 1,5% |
| Calibrator 1 | 5,6 | 0,07 | 1,3% | 0,03 | 0,6% | 0,00 | 0,0% | 0,02 | 0,4% | 0,06 | 1,1% | 0,10 | 1,8% |
| Calibrator 2 | 10,1 | 0,08 | 0,8% | 0,05 | 0,5% | 0,03 | 0,3% | 0,02 | 0,2% | 0,08 | 0,7% | 0,12 | 1,2% |
(*) Total reproducibility includes : within-capillary, between-run, between-run, between-day and between-lot.
{10}------------------------------------------------
| | | Within-lot (*) | | | | | |
|--------------|-------------|----------------|------|-----------|------|-----------|------|
| Sample | Mean<br>(%) | Lot No. 1 | | Lot No. 2 | | Lot No. 3 | |
| | | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 5,1 | 0,05 | 1,1% | 0,06 | 1,2% | 0,07 | 1,3% |
| Blood No. 2 | 6,4 | 0,08 | 1,2% | 0,08 | 1,3% | 0,08 | 1,3% |
| Blood No. 3 | 8,2 | 0,07 | 0,9% | 0,08 | 0,9% | 0,08 | 1,0% |
| Blood No. 4 | 12,2 | 0,09 | 0,7% | 0,11 | 0,9% | 0,12 | 1,0% |
| Control 1 | 5,1 | 0,08 | 1,6% | 0,09 | 1,7% | 0,08 | 1,5% |
| Control 2 | 8,0 | 0,13 | 1,6% | 0,10 | 1,3% | 0,12 | 1,4% |
| Calibrator 1 | 5,6 | 0,08 | 1,4% | 0,08 | 1,4% | 0,09 | 1,6% |
| Calibrator 2 | 10,1 | 0,08 | 0,8% | 0,11 | 1,1% | 0,10 | 1,0% |
(*) Within-lot reproducibility includes : within-capillary, between-run and between-run and between-day.
Instrument No. 3
| Sample | Mean<br>(mmol/mol) | Within-capillary | | Between-capillary | | Between-run | | Between-day | | Between-lot | | Total reproducibility (*) | |
|--------------|--------------------|------------------|------|-------------------|------|-------------|------|-------------|------|-------------|------|---------------------------|------|
| | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 32 | 0,60 | 1,9% | 1,01 | 3,2% | 0,00 | 0,0% | 0,31 | 1,0% | 0,36 | 1,1% | 1,27 | 3,9% |
| Blood No. 2 | 46 | 0,81 | 1,7% | 0,45 | 1,0% | 0,14 | 0,3% | 0,21 | 0,5% | 0,24 | 0,5% | 0,99 | 2,1% |
| Blood No. 3 | 66 | 0,85 | 1,3% | 0,82 | 1,2% | 0,00 | 0,0% | 0,22 | 0,3% | 0,00 | 0,0% | 1,20 | 1,8% |
| Blood No. 4 | 109 | 0,92 | 0,8% | 1,08 | 1,0% | 0,00 | 0,0% | 0,54 | 0,5% | 0,98 | 0,9% | 1,81 | 1,7% |
| Control 1 | 33 | 0,66 | 2,1% | 0,72 | 2,2% | 0,00 | 0,0% | 0,41 | 1,3% | 0,56 | 1,7% | 1,20 | 3,7% |
| Control 2 | 63 | 0,83 | 1,3% | 0,49 | 0,8% | 0,00 | 0,0% | 1,13 | 1,8% | 0,00 | 0,0% | 1,49 | 2,4% |
| Calibrator 1 | 37 | 0,78 | 2,1% | 0,57 | 1,5% | 0,00 | 0,0% | 0,25 | 0,7% | 0,41 | 1,1% | 1,08 | 2,9% |
| Calibrator 2 | 87 | 1,02 | 1,2% | 0,73 | 0,8% | 0,00 | 0,0% | 0,19 | 0,2% | 0,43 | 0,5% | 1,34 | 1,5% |
(*) Total reproducibility includes : within-capillary, between-run, between-day and between-lot. .
| Sample | Mean (mmol/mol) | Within-lot (*) | | | | | |
|--------------|-----------------|----------------|------|-----------|------|-----------|------|
| | | Lot No. 1 | | Lot No. 2 | | Lot No. 3 | |
| | | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 32 | 0,90 | 2,8% | 1,24 | 3,9% | 1,44 | 4,4% |
| Blood No. 2 | 46 | 0,76 | 1,6% | 0,94 | 2,0% | 1,16 | 2,5% |
| Blood No. 3 | 66 | 1,19 | 1,8% | 1,12 | 1,7% | 1,39 | 2,1% |
| Blood No. 4 | 109 | 1,45 | 1,3% | 1,26 | 1,1% | 1,80 | 1,7% |
| Control 1 | 33 | 0,92 | 2,8% | 0,99 | 3,1% | 1,25 | 3,8% |
| Control 2 | 63 | 1,50 | 2,4% | 1,42 | 2,3% | 1,53 | 2,4% |
| Calibrator 1 | 37 | 1,10 | 2,9% | 0,91 | 2,5% | 1,09 | 2,9% |
| Calibrator 2 | 87 | 1,18 | 1,4% | 1,21 | 1,4% | 1,42 | 1,6% |
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------. (*) Within lot reproducibility includes : within-capillary, between-capillary, between-run and betwe en-day.
| | | Within-capillary | | Between-capillary | | Between-run | | Between-day | | Between-lot | | Total reproducibility (*) | |
|--------------|-------------|------------------|------|-------------------|------|-------------|------|-------------|------|-------------|------|---------------------------|------|
| Sample | Mean<br>(%) | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 5,1 | 0,06 | 1,1% | 0,10 | 1,9% | 0,00 | 0,0% | 0,04 | 0,7% | 0,03 | 0,6% | 0,12 | 2,4% |
| Blood No. 2 | 6,4 | 0,07 | 1,2% | 0,04 | 0,6% | 0,00 | 0,0% | 0,02 | 0,3% | 0,02 | 0,3% | 0,09 | 1,4% |
| Blood No. 3 | 8,2 | 0,08 | 0,9% | 0,08 | 0,9% | 0,00 | 0,0% | 0,02 | 0,2% | 0,00 | 0,0% | 0,11 | 1,3% |
| Blood No. 4 | 12,2 | 0,08 | 0,7% | 0,09 | 0,8% | 0,00 | 0,0% | 0,05 | 0,4% | 0,09 | 0,7% | 0,16 | 1,3% |
| Control 1 | 5,1 | 0,06 | 1,2% | 0,07 | 1,3% | 0,00 | 0,0% | 0,04 | 0,7% | 0,05 | 1,0% | 0,11 | 2,1% |
| Control 2 | 8,0 | 0,08 | 1,0% | 0,05 | 0,6% | 0,00 | 0,0% | 0,10 | 1,3% | 0,00 | 0,0% | 0,13 | 1,7% |
| Calibrator 1 | 5,6 | 0,08 | 1,4% | 0,05 | 0,9% | 0,00 | 0,0% | 0,03 | 0,5% | 0,05 | 0,9% | 0,11 | 1,9% |
| Calibrator 2 | 10,1 | 0,09 | 0,9% | 0,07 | 0,7% | 0,00 | 0,0% | 0,02 | 0,2% | 0,05 | 0,5% | 0,13 | 1,2% |
(*) Total reproducibility includes : within-capillary, between-run, between-run, between-day and between-lot.
{11}------------------------------------------------
| | | Within-lot (*) | | | | | |
|--------------|-------------|----------------|------|-----------|------|-----------|------|
| Sample | Mean<br>(%) | Lot No. 1 | | Lot No. 2 | | Lot No. 3 | |
| | | SD | CV | SD | CV | SD | CV |
| Blood No. 1 | 5,1 | 0,09 | 1,8% | 0,12 | 2,3% | 0,14 | 2,7% |
| Blood No. 2 | 6,4 | 0,07 | 1,1% | 0,09 | 1,4% | 0,10 | 1,6% |
| Blood No. 3 | 8,2 | 0,10 | 1,3% | 0,10 | 1,2% | 0,13 | 1,6% |
| Blood No. 4 | 12,2 | 0,12 | 1,0% | 0,11 | 0,9% | 0,16 | 1,3% |
| Control 1 | 5,1 | 0,09 | 1,7% | 0,09 | 1,8% | 0,11 | 2,2% |
| Control 2 | 8,0 | 0,13 | 1,7% | 0,12 | 1,6% | 0,14 | 1,8% |
| Calibrator 1 | 5,6 | 0,10 | 1,8% | 0,09 | 1,6% | 0,11 | 2,0% |
| Calibrator 2 | 10,1 | 0,11 | 1,1% | 0,12 | 1,1% | 0,12 | 1,2% |
#### b. Linearity / assay reportable range
A linearity study was performed per CLSI EP06-A: Evaluation of Quantitative Measuring Procedures; A Statistical Approach. Linearity across the reportable range was performed using low 4.4% Hb A1c (24 mmol/mol) and high 16.7% (159 mmol/mol).
#### Mixture of 2 different blood samples:
This linearity study of the CAPILLARYS Hb A1c procedure was evaluated in a study based on the Clinical Laboratory Standards Institute (CLSI - USA) EP6-A guideline "Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach: Approved Guideline". The results for HbA . concentration (mmol/mol) and percentage (%) were analyzed using statistical tools recommended by CLSI.
2 characteristic blood samples, including a normal sample and an elevated HbAre level sample were mixed within different proportions and the mixtures were electrophoresed with the CAPILLARYS Hb A1c procedure. For each mixture, samples were analyzed in triplicate. The tests were determined to be linear within the entire range studied for HbAit hemoglobin fraction. The stated measuring range is 24 mmol/mol to 158 mmol/mol HbAre (4.4 % to 16.6 % HbA«¿).
#### c. Traceability, Stability (controls, calibrators, or methods)
The CAPILLARYS Hb A1c test standardization is traceable to the International Federation of Clinical Chemistry (IFCC) reference calibrators.
The CAPILLARYS Hb A1c assay is NGSP certified. The NGSP certification expires in one year. See the NGSP website for current certification at http://www.ngsp.org
Hb A1c results are provided in two different units: NGSP equivalent units (%) and IFCC equivalent units (mmol/mol).
{12}------------------------------------------------
## d. Calibrators and Controls
The Hb A1c CAPILLARY CALIBRATORS are required for use with this device. Value assignment and stability protocol and acceptance criteria were previously reviewed and cleared in k122101.
Sebia MULTI-SYSTEM Hb A1c CAPILLARYS CONTROLS are required for use with this device and cleared in submission k162281.
#### e. Comparison Studies
A method comparison study of 150 variant-free whole blood samples covering the measuring range were evaluated using the CAPILLARYS Hb A1c kit and the CAPILLARYS 2 FLEXPIERCING instrument. The results were compared to the testing performed at a NGSP reference laboratory using the cleared HPLC HbA1c method (Automated Glycohemoglobin Analyzer HLC-712G8).
To support the diagnostic claim for HbA1c the samples spanned around the decision points as follows:
| HbA1c level | Number of samples | % of samples |
|-----------------------|-------------------|--------------|
| HbA1c ≤ 5,0 % | 7 | 5 |
| 5,0 % < HbA1c ≤ 6,0 % | 19 | 13 |
| 6,0 % < HbA1c ≤ 6,5 % | 35 | 23 |
| 6,5 % < HbA1c ≤ 7,0 % | 36 | 24 |
| 7,0 % < HbA1c ≤ 8,0 % | 23 | 15 |
| 8,0 % < HbA1c ≤ 9,0 % | 13 | 9 |
| HbA1c > 9,0 % | 17 | 11 |
| Total | 150 | 100 |
#### Samples distribution
{13}------------------------------------------------
#### HbA1c results given as a NGSP unit (%)
| Fraction | Regression Analysis | Correlation coefficient | y-intercept | Slope | Range of HbA1c % value CAPILLARYS Hb A1c |
|----------|---------------------|-------------------------|-------------|-------|------------------------------------------|
| HbA1c | Ordinary linear fit | 0.999 | -0.265 | 1.027 | 4.4 - 16.6 |
150 samples
HbA1c results given as a NGSP unit (%)
| | Regression Analysis (HbA1c fraction) | | | | |
|------------------------------|----------------------------------------------------|---------------------------|---------------------------|--|--|
| | Ordinary linear fit | Weighed Deming | Passing Bablok | | |
| | 95 % Confidence Intervals are shown in parentheses | | | | |
| Points (Plotted/Total) | 150/150 | | | | |
| Results Ranges | 4,4 to 16,6 | | | | |
| Normal range | < 6.5 | | | | |
| Correlation coefficient (r) | 0,999 | | | | |
| Slope | 1,027 (1,019 to 1,035) | 1,023 (1,012 to 1,034) | 1,000 (1,000 to 1,026) | | |
| vintercept | -0,265 (-0,325 to -0,204) | -0,235 (-0,312 to -0,158) | -0,100 (-0,248 to -0,039) | | |
| Average bias (all samples) | | -0,07 (-0,08 to -0,05) | | | |
| Bias at normal range (6,5 %) | -0.09 (-0.11 to -0.07) | -0,09 (-0,10 to -0,07) | -0,10 (-0,10 to -0,04) | | |
| | | | | | |
The unit of the bias is the same of the result provided (%)
## f. Total Error Calculations
Total error (TE) is calculated for 4 concentrations, corresponding to the concentrations of the samples used in the reproducibility study, (5.1 %, 6.4 %, 8.2 % and 12.2 %) using the results of bias estimation (%Bias) and coefficients of variation (CV).
Total Error is calculated as follows: Total Error is calculated as follows: %TE= (%Bias)+ 1.96 x %CV×(1+%Bias/100)
The results are presented in the following table for the CAPILLARYS Hb A1c using the CAPILLARYS 2 FLEX-PIERCING instrument:
HbA1c results given as a NGSP unit (%)
| Linear equation<br>regression | Target (%) | y from linear<br>equation | Deviation from<br>target | %Bias | CV (%) | TE (%) | Specification |
|-------------------------------|------------|---------------------------|--------------------------|-------|--------|--------|---------------|
| y = 1,027 x -0,265 | 5,1 | 5,0 | -0,1 | -2,47 | 1,8 | 5,9 | ≤ 6,0% |
| | 6,4 | 6,3 | -0,1 | -1,42 | 1,4 | 4,1 | |
| | 8,2 | 8,2 | 0,0 | -0,51 | 1,2 | 2,8 | |
| | 12,2 | 12,3 | 0,1 | 0,55 | 1,3 | 3,1 | |
Total Error is calculated as follows: %TE= 1%Bias + 1.96 x %CV×(1+%Bias/100)
#### g. Interferences
Interference studies were performed per CLSI EP07-A2, Interference Testing in Clinical Chemistry. Each study was performed using 2 different whole blood samples: a blood sample close to the cut-off value and a blood sample with elevated HbA1c level. Ten replicates were analyzed using the CAPILLARYS Hb A1c on the CAPILLARYS 2 FLEX-PIERCING testing system.
{14}------------------------------------------------
No interference with the CAPILLARYS Hb A1c procedure was detected due to the blood sample's high concentration of the following interfering factors tested at levels equal to the concentrations listed below:
| Endogenous interfering<br>factor | Concentration |
|----------------------------------|---------------------|
| Conjugated bilirubin | 60 mg/dL |
| Unconjugated bilirubin | 60 mg/dL |
| D-glucose | 1000 mg/dL (55 mM) |
| Rheumatoid factor | 1076 IU/mL |
| Total Protein | 149,5 g/L |
| Triglycerides | 2,89 g/dL (33,1 mM) |
| Urea | 265 mg/dL (44,2 mM) |
| Drug | Concentration |
|----------------------|-----------------------|
| Acetaminophen | 200 mg/L (1325 μΜ) |
| Acetylcysteine | 200 mg/dL (12,3 mM) |
| Acetylsalicilyc acid | 1000 mg/dL (55,56 mM) |
| Ampicillin-Na | 1000 mg/dL (28653 μΜ) |
| Ascorbic acid | 300 mg/dL (17045 μΜ) |
| Cefoxitin | 2500 mg/dL (58548 μΜ) |
| Cyclosporine | 5 mg/L |
| Doxycycline | 50 mg/dL (1123,6 μΜ) |
| Glybenclamide | 3 mg/dL |
| Heparin | 5000 U/L |
| Ibuprofen | 500 mg/L (2427 μΜ) |
| Levodopa | 40 mg/dL |
| Metformin | 5 mg/dL (387 μΜ) |
| Methyldopa | 40 mg/dL (1896 μΜ) |
| Metronidazole | 200 mg/dL (11696 μΜ) |
| Phenylbutazone | 400 mg/L |
| Rifampicin | 70 mg/L (85,1 μΜ) |
| Theophylline | 100 mg/L (556 μΜ) |
| Hemoglobin Derivatives and<br>cross reactants | Concentrations |
|-----------------------------------------------|----------------|
| Carbamylated Hemoglobin | ≤ 8.1 mg/mL |
| HbA1a+b | ≤ 0.20 mg/mL |
| Labile HbA1c | ≤ 19.7 mg/mL |
| Acetylated hemoglobin | ≤ 4.2 mg/mL |
{15}------------------------------------------------
| Glycated Albumin | ≤ 2.2 mg/mL |
|------------------|-------------|
|------------------|-------------|
Hemoglobin Variant Study was performed using specific samples known to contain hemoglobin variants S. C. E. D. A2 and F. The samples were analyzed with a reference method performed in a NGSP laboratory (reference) and with CAPILLARYS Hb A1c procedure on CAPILLARYS 2 FLEX-PIERCING instrument (test): percentages of HbA1c fraction. The relative deviation (%) between the reference procedure and the test procedure has been calculated for each sample (see the following tables).
| Hemoglobin<br>Variants | No.of<br>Samples | Ranges in %<br>Variant | Range of % HbA1c<br>Concentration |
|------------------------|------------------|------------------------|-----------------------------------|
| Hb A2 | 20 | 4.0-7.7 | 4.5-11.0 |
| Hb F | 20 | 1.5-31.4 | 4.9-15.1 |
| Hb S | 20 | 33.0-40.8 | 4.9-14.0 |
| Hb C | 20 | 28.0-37.2 | 4.6-13.1 |
| Hb D | 21 | 35.5-41.3 | 5.2-11.8 |
| Hb E | 22 | 21.3-37.0 | 4.8-9.8 |
| Hemoglobin fraction | Mean relative % Bias (Range of relative % Bias) | |
|---------------------|-------------------------------------------------|---------------------|
| | ~ 6,5 % Hb A1c | ~ 9,0 % Hb A1c |
| Hb S | 0,8 (0,0 to 1,6) | 0,4 (-3,1 to 3,2) |
| Hb C | 0,0 (0,0 to 0,0) | 3,3 (1,0 to 5,7) |
| Hb D | 0,5 (-1,4 to 1,6) | -1,9 (-2,4 to -1,2) |
| Hb E | -0,4 (-3,3 to 1,5) | -0,3 (-3,7 to 2,1) |
| Hb A2 | -3,4 (-4,5 to -1,4) | -0,8 (-2,0 to 0,0) |
| Hb F | -3,3 (-4,8 to -1,6) | -2,0 (-5,0 to 0,0) |
- Levels of Hb F up to 23 % in the blood sample do not interfere with HbA1c fraction quantification, a result is reported by the software when the Hb F level is higher than 23 % along with a warning message "Atypical profile – Possible quantitative interference if Hb F or variant > 23 %". It is recommended to analyze the sample with CAPILLARYS HEMOGLOBIN(E) procedure to verity the Hb F percentage and to study the patient's clinical data.
- Levels of Hb A2 up to 7.7 % in the blood sample do not interfere with HbA1c fraction quantification.
- No interference has been observed with HbA1c fraction quantification due to the presence of major abnormal hemoglobins Hb S (≤ 40.8 %), Hb C (≤ 37.2 %), Hb D (≤ 41.3 %) and Hb E (≤ 37.0 %).
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# h. Expected Values/ Reference Range
Hemoglobin A1c expected value range was cited from the American Diabetes Association (Standards of Medical Care in Diabetes 2016, 39 (Suppl 1)
The American Diabetes Association's (ADA) most recent Clinical Practice are:
| Category | HbA1c Range (IFCC) | HbA1c Range (NGSP/DCCT) |
|----------------------------------------------|---------------------------|-------------------------|
| Normal | < 39 mmol/mol | < 5.7 % |
| Prediabetes (increased risk for<br>diabetes) | 39 mmol/mol - 47 mmol/mol | 5.7 % - 6.4 % |
| Diabetes | ≥ 48 mmol/mol | ≥ 6.5 % |
The expected HbA1c range for non-diabetic adults is 20 - 42 mmol/mol or 4.0 - 6.0 %. However, each laboratory should establish its reference range and HbA1c goal following state and federal regulations and taking into account sex, age, ethnicity and individual patient situation.
| YES OR NO | Requirement |
|-----------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| YES | Device must have initial and annual standardization verification by<br>certifying glycohemoglobin standardization organization deemed<br>acceptable by FDA |
| YES | Performance testing of device precision must, at a minimum use blood<br>samples with concentrations near 5.0%, 6.5%, 8.0% and 12 %<br>hemoglobin A1c. Testing must evaluate precision over a minimum of<br>20 days using at least 3 lots of the device and instruments, as<br>applicable |
| YES | Performance testing of accuracy must include a minimum of 120<br>blood samples that span the measuring interval of the new device<br>and compare results of the new device to results of the standardized<br>method. Results must demonstrate little or no bias versus the<br>standardized method. |
| YES | Total error of the new device must be evaluated using single<br>measurements by the new device compared to the results of the<br>standardized test method, and this evaluation must demonstrate a<br>total error of less than or equal to 6% |
| YES | Performance testing must demonstrate that there is little to no<br>interference from common hemoglobin variants, including<br>Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2 and<br>Hemoglobin S. |
| NA | When assay interference from Hemoglobin F or interference with other<br>hemoglobin variants with low frequency in the population is observed,<br>a warning statement must be placed in a black box and must appear<br>in all the labeling material for these devices describing the interference<br>and any affected population. |
#### 5. Requirements for Diabetes Diagnosis Claim
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# 6. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
