(149 days)
The MINICAP Hb A1c kit is designed for separation and quantification of the HbA1c glycated fraction of hemoglobin in human whole blood, by capillary electrophoresis in alkaline buffer with the MINICAP FLEX-PIERCING instrument. Measurement of hemoglobin A1c is effective in monitoring long-term glycemic control in individuals with diabetes mellitus. Results are provided in IFCC (mmol/mol) and NGSP (%Hb A1c) units.
The MINICAP Hb A1c kit is designed for Professional Use Only.
For In Vitro Diagnostic Use.
The Hb A1c CAPILLARY Controls are designed for the quality control of human glycated hemoglobin A1c quantification with SEBIA capillary electrophoresis procedures using the MINICAP HbA1c kit with the MINICAP FLEX-PIERCING automated instrument.
The Hb A1c CAPILLARY Controls are designed for Professional Use Only.
For In Vitro Diagnostic Use.
The Hb A1c CAPILLARY Calibrators are designed for the calibration and migration control of human glycated hemoglobin A1c quantification with SEBIA capillary electrophoresis procedures using the MINICAP HbA1c kit with the MINICAP FLEX-PIERCING automated instrument.
The Hb A1c CAPILLARY Calibrators are designed for Professional Use Only.
For In Vitro Diagnostic Use.
The MINICAP FLEX-PIERCING instrument is an automated analyzer which performs a complete hemoglobin profile for the quantitative analysis of HbA1c fraction. The hemoglobins, separated in silica capillaries, are directly detected by their absorbance at 415 nm. The assay is performed on the hemolysate of whole blood samples collected in tubes containing K2EDTA as anticoagulant.
Quantitative determination of hemoglobin A1c is effective in monitoring middle-term blood glucose control in diabetic individuals.
The MINICAP Hb A1c procedure performed with the MINICAP FLEX-PIERCING instrument has been certified by the National Glycohemoglobin Standardization Program (NGSP).
Electrophoresis is a well established technique routinely used in clinical laboratories for measuring components from body fluids, including HbA1c glycated fraction. The MINICAP FLEX-PIERCING instrument has been developed to provide complete automation of this testing with fast separation and good resolution. In many aspects, the methodology can be considered as an intermediary type of technique between classical zone electrophoresis and liquid chromatography.
The MINICAP 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 also occurs according to the electrolyte pH and electroosmotic flow.
The MINICAP FLEX-PIERCING instrument has silica capillaries functioning in parallel allowing 2 simultaneous analyses for HbA1c quantification from 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 analvsis with buffer.
Direct detection provides accurate relative quantification of individual hemoglobin Are fraction. In addition, the high resolution of MINICAP Hb A1c procedure allows the quantification of HbA1c, even in the presence of labile HbArc, carbamylated and acetylated hemoglobins, and major hemoglobin variants such as HbS, HbC, HbD, HbE and HbF and common interfering factors such as Triglycerides, Bilirubin, Ascorbic Acid, Urea, Rheumatoid factor and Glybenclamide as outline in the package insert labeling.
By using 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.
This FDA 510(k) summary (K133344) pertains to the MINICAP Hb A1c kit and associated instruments, calibrators, and controls, which are in vitro diagnostic devices used for the quantification of glycated hemoglobin A1c. The submission aims to demonstrate substantial equivalence to a previously cleared predicate device, not to prove clinical utility through new, independent clinical studies with expert reviewers.
Therefore, many of the requested details regarding acceptance criteria for AI-based systems (e.g., number of experts, adjudication methods, MRMC studies, standalone performance, training set details) are not applicable to this type of device submission and the performance data presented. This document focuses on analytical performance and comparison to a predicate device, which falls under the scope of laboratory testing.
Here's an analysis of the provided information, addressing applicable points and noting those that are not relevant:
1. A table of acceptance criteria and the reported device performance.
The acceptance criteria for this type of in vitro diagnostic device are typically established based on analytical performance targets such as precision, linearity, and interference. The submission demonstrates that the new device meets performance characteristics comparable to or better than the predicate device. While explicit "acceptance criteria" for each test are not listed as a separate table, the study results implicitly define the demonstrated performance that was deemed acceptable for clearance by the FDA.
Here's a summary of the analytical performance:
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (MINICAP Hb A1c) |
|---|---|---|
| Precision/Reproducibility | Based on CLSI Guideline "EP5-A2". Low CV% values indicating good precision. | Between lots and instruments:- HbA1c (%) - CV (%) ranges: Within-run reproducibility: 0.0-2.1%; Total reproducibility: 0.0-2.2%- HbA1c (mmol/mol) - CV (%) ranges: Within-run reproducibility: 0.0-4.0%; Total reproducibility: 0.0-4.0%Within same capillary and between capillaries:- HbA1c (%): Within-run CV% 0.7-1.1%, Within-capillary CV% 0.7-1.5%, Between-run CV% 0.0-0.7%, Between-day CV% 0.0-0.7%, Total CV% 0.8-1.3%- HbA1c (mmol/mol): Within-run CV% 0.8-1.9%, Within-capillary CV% 0.8-2.8%, Between-run CV% 0.0-1.4%, Between-day CV% 0.0-1.3%, Total CV% 0.8-2.3% |
| Linearity/Reportable Range | Based on CLSI EP6-A guideline. Strong linear correlation (high r² and r). | HbA1c (%): Y=0.08982x+4.764, r²=0.998, r=0.999. Linearity range: 4.8 - 13.8% HbA1c.HbA1c (mmol/mol): Y=0.9855x+28.41, r²=0.999, r=0.999. Linearity range: 29 - 127 mmol/mol HbA1c.Linear across 2.5 to 31.1 g/dL total hemoglobin, with HbA1c not affected by total hemoglobin concentration. |
| Detection Limit | Defined by LoB and LoD. | LoB: 0.3%, LoD: 1.1% |
| Analytical Specificity (Interference) | Defined as ≤ 0.3% HbA1c difference for common substances, and ±10% difference vs. NGSP reference for hemoglobin variants. | Common Interfering Substances (no significant interference ≤0.3% HbA1c): Triglycerides (3.07 g/dL), Bilirubin (25.8 mg/dL), Ascorbic acid (60 mg/dL), Urea (291 mg/dL), Rheumatoid factor (2178 IU/mL), Glybenclamide (3 mg/dL).Carbamylated hemoglobin: ≤ 8.7% (no significant interference).Labile HbA1c: ≤ 14.8% (no significant interference).Acetylated hemoglobin: ≤ 3.0% (no significant interference).Hemoglobin Variants (no significant interference ±10% difference vs. NGSP): HbS (≤ 40.5%), HbE (≤ 24.7%), HbD (≤ 41.0%), HbC (≤ 37.0%), HbF (≤ 19.7%). |
| Method Comparison (vs. Predicate Device) | Strong correlation (high correlation coefficient) with predicate device. | Internal Study (N=101):- Percentage (%): Correlation 0.998, y-Intercept 0.165, Slope 0.982- Concentration (mmol/mol): Correlation 0.998, y-Intercept 1.262, Slope 0.985External Study No. 1 (N=126):- Percentage (%): Correlation 0.998, y-Intercept -0.032, Slope 0.997- Concentration (mmol/mol): Correlation 0.998, y-Intercept -0.396, Slope 0.996External Study No. 2 (N=140):- Percentage (%): Correlation 0.998, y-Intercept -0.057, Slope 1.019- Concentration (mmol/mol): Correlation 0.998, y-Intercept -0.316, Slope 1.023 |
| Matrix Comparison (K2 EDTA vs K3 EDTA) | Strong correlation (high correlation coefficient) between matrix types. | N=41:- HbA1c (%): Correlation 0.999, y-intercept 0.039, Slope 0.998- HbA1c (mmol/mol): Correlation 0.999, y-intercept 0.091, Slope 1.001 |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective).
For analytical performance studies:
- Precision/Reproducibility: 8 different blood samples were used in the multi-instrument/lot study. Each sample was analyzed in duplicate across 60 runs over 10 working days. Another study used 8 different blood samples, analyzed in duplicate, across 40 runs over 20 working days for within-capillary/between-capillary reproducibility. The provenance of the samples (e.g., country of origin, retrospective/prospective) is not specified, but given it's an IVD manufacturer in France, it's likely from their local or collaborating clinical sites.
- Linearity: Two blood samples (normal and elevated HbA1c) mixed in different proportions, analyzed in duplicate. Additionally, 3 characteristic blood samples serially diluted and electrophoresed.
- Detection Limit: Five zero samples (blank) and six low HbA1c samples.
- Analytical Specificity (Interference): Whole blood samples with four different HbA1c concentrations for common substances. Four whole blood patient samples for carbamylated, labile, and acetylated hemoglobin studies (each tested in triplicate or triblicate). Hemoglobin variant studies used samples known to contain specific variants (quantities not specified beyond "samples"). Sixteen whole blood samples for HbF interference.
- Method Comparison:
- Internal Study: 101 whole blood samples.
- External Study No. 1: 126 whole blood samples.
- External Study No. 2: 140 whole blood samples.
- The provenance of these samples (country of origin, retrospective/prospective) is not explicitly stated. However, the term "External study" suggests collaboration with other laboratories. These are typically retrospective samples from clinical labs acquired for method comparison.
- Matrix Comparison: 41 random matched sample pairs (K2 EDTA and K3 EDTA). Data provenance is not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience).
This question is not applicable to this type of IVD device submission. Ground truth for HbA1c measurements in this context is established by highly standardized and certified reference methods (NGSP and IFCC), not by subjective expert review of images or clinical data. The predicate device's measurements also serve as a comparative ground truth.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set.
This is not applicable. As it's an analytical device measuring a biochemical marker, there is no subjective adjudication process for the results.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance.
This is not applicable. This submission is for an in vitro diagnostic assay and instrument, not an AI-assisted diagnostic imaging system that uses human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done.
The device itself (MINICAP Hb A1c kit with MINICAP FLEX-PIERCING instrument) operates as a standalone analytical system. Its performance metrics (precision, linearity, detection limit, analytical specificity) are its "standalone" performance. There is no human interpretation or "human-in-the-loop" aspect to the quantification of HbA1c % or mmol/mol by the instrument, other than standard laboratory procedures for sample handling and quality control.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.).
The "ground truth" or reference for the MINICAP Hb A1c test performance is established against:
- NGSP (National Glycohemoglobin Standardization Program) and IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) requirements/guidelines: The device is standardized according to these globally recognized reference methods for HbA1c measurement. This is the primary "ground truth" for the accuracy of the HbA1c values.
- Predicate Device (CAPILLARYS Hb A1c kit on CAPILLARYS 2 FLEX-PIERCING instrument, K122101): For method comparison studies, the results from the predicate device serve as the comparative standard. Given that the predicate device was also cleared based on NGSP/IFCC standardization, this indirectly links to the same reference standard.
8. The sample size for the training set.
This implies a machine learning or AI context, which is not applicable to this traditional IVD device. The "training" for such a system would be its development and calibration against reference materials and methods, rather than a labeled dataset in the AI sense.
9. How the ground truth for the training set was established.
As the concept of a "training set" in the AI sense is not applicable, this question is also irrelevant. The device's calibration and validation are based on established laboratory standards and reference materials (NGSP/IFCC traceable calibrators and controls).
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K133344
MAR 2 8 2014
510(K) Summary
SEBIA's manufacturing and corporate office is located at:
Parc Technologique Léonard de Vinci, Rue Léonard de Vinci CP 8010 LISSES 91008 EVRY Cedex, FRANCE
Phone: (33) 1 69 89 80 80; Fax: (33) 1 69 89 78 78
In the United States, the product will be distributed by:
SEBIA Inc. Suite 400 - 1705 Corporate drive NORCROSS GA 30093, USA Phone 770 446 - 3707; Fax 770 446 - 8511 Contact person: Karen Anderson Prepared on March 26, 2014
- Product/Device Names: MINICAP Hb A1c (PN 2215), MINICAP FLEX-PIERCING (PN 1232), Hb A1c CAPILLARY Calibrators (PN 4755), Hb A1c CAPILLARY Controls (PN 4774)
Common Name: glycosylated hemoglobin
Product Regulation Name: glycosylated hemoglobin assay
The MINICAP Hb A1c type of devices/assays are classified by FDA as Class II, under Regulation No. 21 CFR 864.7470. SEBIA is seeking clearance to import the assay described above, and by this submission is notifying FDA of its intent to market these products in the United States.
| Product Code | Classification | Regulation Section | Panel |
|---|---|---|---|
| LCP | II | 21 CFR 864.7470Glycosylatedhemoglobin assay | Hematology (81) |
| JIS | II | 21 CFR 862.1150Calibrator | Chemistry (75) |
| JJX | Class I, Reserved | 21 CFR 862.1660Quality controlmaterial (assayedand unassayed) | Chemistry (75) |
Product Nomenclature:
HEMOGLOBINS A1C BY CAPILLARY ELECTROPHORESIS
Establishment Registration Number:
8023024
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STANDARDS: MINICAP Hb A1c test is standardized according to NGSP and IFCC requirements/quidelines.
This submission is limited to the MINICAP Hb A1c kit (PN 2215) using the MINICAP FLEX-PIERCING instrument (PN 1232) and the performance using the Hb A1c CAPILLARY Controls (PN 4774) with the system and Hb A1c CAPILLARY Calibrators (PN 4755)
The SEBIA Hb A1c CAPILLARY Controls (PN 4774) and Hb A1c CAPILLARY Calibrators (PN 4755) were FDA cleared (K122101), December 6, 2012.
Substantial Equivalence to Predicate Devices:
For the separation and quantification of the Hb A1c glycated fraction of hemoglobin in human blood, by capillary electrophoresis in an alkaline buffer using the MINICAP Hb A1c kit with the MINICAP FLEX-PIERCING instrument.
The new device, MINICAP Hb A1c procedure using the MINICAP FLEX-PIERCING instrument, utilizes the previous cleared SEBIA Hb A1c CAPILLARY Calibrators and Hb A1c CAPILLARY Controls (K122101).
The performance of the MINICAP Hb A1c kit using the MINICAP FLEX-PIERCING instrument. Hb A1c CAPILLARY Calibrators and Hb A1c CAPILLARY Controls was compared to the predicate device, CAPILLARYS Hb A1c kit using the CAPILLARYS 2 FLEX-PIERCING instrument, the Hb A1c CAPILLARY Calibrators and the Hb A1c CAPILLARY Controls (K122101).
Both the new device (MINICAP Hb A1c kit & MINICAP FLEX-PIERCING instrument using the Hb A1c CAPILLARY Calibrators and the Hb A1c CAPILLARY Controls) and the predicate device (CAPILLARYS Hb A1c kit & CAPILLARYS 2 FLEX-PIERCING instrument using the Hb A1c CAPILLARY Calibrators and the Hb A1c CAPILLARY Controls) use capillary electrophoresis technology. The devices compared were found to be substantially equivalent in function, concept, principle, technique, use, safety and effectiveness,
The 510(K) number of the predicate device, CAPILLARYS Hb A1c using CAPILLARYS 2 FLEX-PIERCING instrument, the Hb A1c CAPILLARY Calibrators and the Hb A1c CAPILLARY Controls predicate device, was FDA cleared as K122101 on December 6, 2012.
| 510K Table of Predicate Devices | ||
|---|---|---|
| Predicate Device | 510K | Clearance Date |
| CAPILLARYS Hb A1cCAPILLARYS 2 FLEX PIERCING | K122101 | December 6, 2012 |
| Hb A1c CAPILLARY Controls | K122101 | December 6, 2012 |
| Hb A1c CAPILLARY Calibrators | K122101 | December 6, 2012 |
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DEVICE DESCRIPTION
The MINICAP FLEX-PIERCING instrument is an automated analyzer which performs a complete hemoglobin profile for the quantitative analysis of HbA1c fraction. The hemoglobins, separated in silica capillaries, are directly detected by their absorbance at 415 nm. The assay is performed on the hemolysate of whole blood samples collected in tubes containing K2EDTA as anticoagulant.
Quantitative determination of hemoglobin A1c is effective in monitoring middle-term blood glucose control in diabetic individuals.
The MINICAP Hb A1c procedure performed with the MINICAP FLEX-PIERCING instrument has been certified by the National Glycohemoglobin Standardization Program (NGSP).
Electrophoresis is a well established technique routinely used in clinical laboratories for measuring components from body fluids, including HbA1c glycated fraction. The MINICAP FLEX-PIERCING instrument has been developed to provide complete automation of this testing with fast separation and good resolution. In many aspects, the methodology can be considered as an intermediary type of technique between classical zone electrophoresis and liquid chromatography.
The MINICAP 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 also occurs according to the electrolyte pH and electroosmotic flow.
The MINICAP FLEX-PIERCING instrument has silica capillaries functioning in parallel allowing 2 simultaneous analyses for HbA1c quantification from 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 analvsis with buffer.
Direct detection provides accurate relative quantification of individual hemoglobin Are fraction. In addition, the high resolution of MINICAP Hb A1c procedure allows the quantification of HbA1c, even in the presence of labile HbArc, carbamylated and acetylated hemoglobins, and major hemoglobin variants such as HbS, HbC, HbD, HbE and HbF and common interfering factors such as Triglycerides, Bilirubin, Ascorbic Acid, Urea, Rheumatoid factor and Glybenclamide as outline in the package insert labeling.
By using 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.
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INTENDED USE
The MINICAP Hb A1c kit is designed for separation and quantification of the HbA1c glycated fraction of hemoglobin in human whole blood, by capillary electrophoresis in alkaline buffer with the MINICAP FLEX-PIERCING instrument. Measurement of hemoglobin A1c is effective in monitoring long-term glycemic control in individuals with diabetes mellitus. Results are provided in IFCC (mmol/mol) and NGSP (%Hb A1c) units.
The MINICAP Hb A1c kit is designed for Professional Use Only.
The Hb A1c CAPILLARY Controls are designed for the quality control of human glycated hemoglobin A1c quantification with SEBIA capillary electrophoresis procedures using the MINICAP HbA1c kit with the MINICAP FLEX-PIERCING automated instrument.
The Hb A1c CAPILLARY Controls are designed for Professional Use Only.
The Hb A1c CAPILLARY Calibrators are designed for the calibration and migration control of human glycated hemoglobin A1c quantification with SEBIA capillary electrophoresis procedures using the MINICAP HbA1c kit with the MINICAP FLEX-PIERCING automated instrument.
The Hb A1c CAPILLARY Calibrators are designed for Professional Use Only.
For In Vitro Diagnostic Use.
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PRODUCT DESCRIPTION
1. MINICAP FLEX PIERCING instrument, Part Number 1232
2. Reagent Kit
The MINICAP Hb A1c kits, Hb A1c CAPILLARY Controls and Hb A1c CAPILLARY Calibrators are used with the MINICAP FLEX- PIERCING system.
The configurations of the components are summarized:
- . MINICAP Hb A1c kits in Table I.
- . Hb A1c CAPILLARY Calibrators in Table II.
- Hb A1c CAPILLARY Controls in Table III. .
- Reagents that are required to perform the test but are sold separately in Table IV. .
For additional details, see Package Inserts and instrument operators manual. Each kit, control and calibrators is supplied with a Package Insert which contains instruction for use and all the necessary information on the reagents needed to run the tests. Each Package Insert also contains information on storage conditions, shelf life and signs of deterioration of the components and the reagents sold separately.
| ITEMS | PN 2215 |
|---|---|
| Buffer (ready to use) | 2 vials, 250 mL each |
| Hemolysing solution (ready to use) | 1 vial, 225 mL |
| Wash solution (stock solution) | 1 vial, 25 mL |
| Reagent Cups | 1 pack of 125 |
| Filters | 3 filters |
| Bins for used cups | 4 bins |
| Hemolysing solution bar code labels | 5 sheets of 4 labels |
TABLE I. REAGENTS AND MATERIALS SUPPLIED IN THE MINICAP Hb A1c KIT (PN 2215)
TABLE II. REAGENTS AND MATERIALS SUPPLIED WITH Hb A1c CAPILLARY CALIBRATORS (PN 4755)
| ITEMS | PN 4755 |
|---|---|
| Hb A1c CAPILLARY Calibrator 1 (green cap) | 1 vial of each, 600µL each |
| Hb A1c CAPILLARY Calibrator 2 (red cap) | |
| Barcode label Hb A1c CAPILLARY Calibrator 1 | 1 |
| Barcode label Hb A1c CAPILLARY Calibrator 2 | 1 |
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TABLE III. REAGENTS AND MATERIALS SUPPLIED WITH Hb A1c CAPILLARY CONTROLS (PN 4774)
| ITEMS | PN 4744 |
|---|---|
| Hb A1c CAPILLARY Control 1 ( white cap ) | 1 vial of each, 600µL each |
| Hb A1c CAPILLARY Control 2 ( black cap) | |
| Barcode label HbA1c CAPILLARY Control 1 | 2 |
| Barcode label HbA1c CAPILLARY Control 2 | 2 |
| White dilution segments* | 4 |
| Grey dilution segments* | 4 |
- Not used with the MINICAP FLEX-PIERCING instrument
TABLE IV. REAGENTS AND MATERIALS REQUIRED BUT NOT SUPPLIED IN THE MINICAP HbA1c KIT, Hb A1c CAPILLARY CONTROLS OR Hb A1c CAPILLARY CALIBRATORS
| ITEMS | PN | COMPONENTS |
|---|---|---|
| CAPICLEAN | 2058 | 1 vial, 25 mL |
| CAPILLARYS / MINICAP Wash Solution | 2052 | 2 vials, 75 mL |
| Tubes and caps for controls | 9202, 9205 | 200 per box, 500 per box |
| MINICAP Reagent Cups | 2280 | 250 per box |
| Lids for bins for used reagent cups | 2286 | 12 per box |
| "AUTOMATIC LOW VOLUME" bar code labels | 9208 | 20 per box |
| "MANUAL LOW VOLUME" bar code labels | 9209 | 20 per box |
| MINICAP FLEX-PIERCING centering rings | 1612 | 27 per box |
| PHORESIS software | 1110 | |
| MINICAP | 1232 | |
| FLEX-PIERCING INSTRUMENT | ||
| Update HbA1c kit for MINICAP FLEX-PIERCING | 1238 |
LABELING
Labeling contained in this submission includes:
- A. MINICAP Hb A1c operators manual
- B. MINICAP Hb A1c package insert
- C. Hb A1c CAPILLARY Controls package insert
- D. Hb A1c CAPILLARY Calibrators package insert
and the box labels and the product labels of the MINICAP Hb A1c kit, MINICAP Hb A1c CAPILLARY Controls, Hb A1c CAPILLARY Calibrators and of the reagents and materials required but not supplied.
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STUDY SUMMARY
-
- Analytical performance:
- a. Precision/Reproducibility:
The reproducibility studies have been performed according to CLSI Guideline "EPS-A2: Evaluation of Precision Performance of Clinical Chemistry Devices".
Reproducibility between lots and instruments
Eight (8) different blood samples were run using the MINICAP Hb A1c procedure in both capillaries of 3 different MINICAP FLEX-PIERCING instruments and with 3 lots of MINICAP Hb A1c kits. The analyzed blood samples included 3 samples with normal HbA% level (No. 1, 2 and 3), 1 sample with HbArelevel close to the cut-off value (No. 4) and 4 samples with elevated HbAre level (No. 5, 6, 7 and 8). In this study, each blood sample was analyzed on both capillaries from each instrument, including 60 runs over 10 working days (at 2 different times of the day). Within each run, samples were analyzed in duplicate.
The following tables summarize the within-run and total instrument-reagent C.V. % ranges for the HbA1c concentrations (in mmol/mol) and percentages.
| Within-run reproducibility | Total reproducibility | Mean (HbA1cconcentration- mmol/mol) | Within-run reproducibility | Total reproducibility | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean(% HbA1c) | CV min (%) | CV max (%) | Total CV min (%) | Total CV max (%) | CV min (%) | CV max (%) | Total CV min (%) | Total CV max (%) | |||
| Sample No. 1 | 5.2 | 0.9 | 2.0 | 0.9 | 2.2 | Sample No. 1 | 33 | 0.9 | 3.5 | 0.9 | 3.5 |
| Sample No. 2 | 5.4 | 0.9 | 2.1 | 0.9 | 2.1 | Sample No. 2 | 36 | 1.1 | 4.0 | 1.2 | 4.0 |
| Sample No. 3 | 5.5 | 0.5 | 2.0 | 0.7 | 2.1 | Sample No. 3 | 37 | 0.0 | 3.0 | 1.4 | 3.3 |
| Sample No. 4 | 6.4 | 0.5 | 1.9 | 0.8 | 1.9 | Sample No. 4 | 47 | 1.2 | 2.6 | 1.3 | 2.6 |
| Sample No. 5 | 7.9 | 0.7 | 1.4 | 0.8 | 1.6 | Sample No. 5 | 63 | 0.7 | 1.6 | 0.7 | 2.2 |
| Sample No. 6 | 9.1 | 0.0 | 1.1 | 0.0 | 1.1 | Sample No. 6 | 76 | 0.0 | 1.4 | 0.0 | 1.4 |
| Sample No. 7 | 10.1 | 0.6 | 1.1 | 0.6 | 1.2 | Sample No. 7 | 87 | 0.3 | 1.3 | 0.3 | 1.4 |
| Sample No. 8 | 12.3 | 0.4 | 1.2 | 0.6 | 1.8 | Sample No. 8 | 110 | 0.4 | 1.4 | 0.6 | 2.2 |
| CV (%) ranges | 0.0 | 2.1 | 0.0 | 2.2 | CV (%) ranges | 0.0 | 4.0 | 0.0 | 4.0 |
Reproducibility within the same capillary and between capillaries from the same instrument
Eight (8) different blood samples were run using the MINICAP Hb A1c procedure in both capillaries of the same MINICAP FLEX-PIERCING instrument and with 1 lot of MINICAP Hb A1c kit. The analyzed blood samples included 3 samples with normal HbAic level (No. 1, 2 and 3), 1 sample with HbA . level close to the cut-off value (No. 4) and 4 samples with elevated HbA% . level (No. 5, 6, 7 and 8). In this study, each blood sample was analyzed on both capillaries from the same
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instrument, including 40 runs over 20 working days (at 2 different times of the day). Within each run, samples were analyzed in duplicate.
The results for HbAje concentrations (in mmol/mol) and percentages are summarized in the following tables.
For reproducibility within the same capillary, maximal CV's have been calculated for each blood sample from pooled data obtained on each capillary.
| SampleNo. 1 | SampleNo. 2 | SampleNo. 3 | SampleNo. 4 | SampleNo. 5 | SampleNo. 6 | SampleNo. 7 | SampleNo. 8 | |
|---|---|---|---|---|---|---|---|---|
| Mean (% HbA1c) | 5.2 | 5.2 | 5.7 | 6.4 | 7.8 | 9.0 | 10.1 | 11.9 |
| Within-runreproducibility(CV %) | 1.0 | 1.1 | 1.0 | 0.9 | 1.1 | 0.9 | 0.7 | 1.1 |
| Within-capillaryreproducibility(CV %) | 1.4 | 1.4 | 1.5 | 1.1 | 0.7 | 0.8 | 0.8 | 0.9 |
| Between-runreproducibility(CV %) | 0.0 | 0.3 | 0.7 | 0.0 | 0.0 | 0.0 | 0.3 | 0.0 |
| Between-dayreproducibility(CV %) | 0.7 | 0.0 | 0.5 | 0.6 | 0.2 | 0.4 | 0.3 | 0.1 |
| Total (CV%) | 1.2 | 1.1 | 1.3 | 1.1 | 1.1 | 1.0 | 0.8 | 1.1 |
8
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| SampleNo. 1 | SampleNo. 2 | SampleNo. 3 | SampleNo. 4 | SampleNo. 5 | SampleNo. 6 | SampleNo. 7 | SampleNo. 8 | |
|---|---|---|---|---|---|---|---|---|
| Mean (HbA1cconcentration –mmol/mol) | 33 | 34 | 38 | 46 | 62 | 75 | 87 | 106 |
| Within-runreproducibility(CV %) | 1.7 | 1.9 | 1.7 | 1.1 | 0.8 | 1.2 | 0.8 | 1.2 |
| Within-capillaryreproducibility(CV %) | 2.5 | 2.8 | 2.4 | 1.3 | 0.8 | 1.2 | 1.0 | 0.9 |
| Between-runreproducibility(CV %) | 0.0 | 1.4 | 0.3 | 0.5 | 0.0 | 0.0 | 0.4 | 0.0 |
| Between-dayreproducibility(CV %) | 1.3 | 0.0 | 0.6 | 0.5 | 0.0 | 0.6 | 0.3 | 0.2 |
| Total (CV %) | 2.2 | 2.3 | 1.8 | 1.3 | 0.8 | 1.3 | 1.0 | 1.2 |
b. Linearity/assay reportable range:
The linearity of the MINICAP HbA1c procedure was evaluated based on CLSI EP6-A quideline "Evaluation of the Linearity Quantitative Measurement Procedures: A Statistical Approach". Two blood samples, including a normal sample with HbA1c concentration at 4.8% (29 mmol/mo)) and an elevated HbA1c level sample with HbA1c concentration at 13.8% (127 mmol/mol) were mixed within different proportions and the dilutions were electrophoresed with the MINICAP HbA1c assay kit using the MINICAP FLEX-PIERCING instrument. Samples were analyzed in duplicate.
A polynomial regression analysis was performed, it allows to conclude on the linearity of MINICAP Hb A1c procedure performed with the MINICAP FLEX-PIERCING instrument for HbA1c fraction within the entire range studied.
HbA1c (%) The 1st order linear regression generated is: Y=0.08982x+4.764, r2=0.998, r=0.999 The linearity range is 4.8 - 13.8% HbA1c
HbA1c (mmol/mol)
The 1st order linear regression generated is:
Y=0.9855x+28.41. r2=0.999. r=0.999
The linearity range is 29 - 127 mmol/mol HbA1c
In addition, 3 different characteristic blood samples, including a normal sample with HbA1c concentration at 5.0 % HbA1c (31 mmol/mol), a sample with HbA1c level close to the cut-off value at 6.3 % HbA1c (46 mmol/mol) and an elevated HbA1c level sample with HbA1c concentration at
{9}------------------------------------------------
9.3 % HbA1c (79 mmol/mol), were all serially diluted in hemolysing solution and electrophoresed with the MINICAP Hb A1c procedure. The tests were determined to be linear within the entire ranges studied from 2.5 to 31.1 g/dL total hemoglobin and HbA1c fraction concentration and percentage were not affected by the hemoglobin concentration of the samples.
c. Detection limit:
The Limit of Blank (LoB) and Limit of Detection (LoD) were determined by assaying a five zero samples (blank) and six low HbA1c samples according to CLSI quideline EP17-A . The results are as follows:
LoB= 0.3%, LoD = 1.1%
The claimed measuring range, 4.8- 13.8% (29 - 127 mmol/mol), is based on linearity.
d. Analytical specificity:
The interference studies have been performed according to the CLSI Guideline "EPT-A2: Interference Testing in Clinical Chemistry".
i) Studies were performed to assess common or known substances that could interfere with the MINICAP HbA1c assay kit. The interfering substances were evaluated in whole blood samples that contained four different concentrations of A1c (~5.0%. ~8.8% and ~11.9%). Samples containing various concentrations of potential interferents were tested and the results compared to those obtained from control samples containing no potential interfering substances. The definition of non-significant interference is ≤ 0,3% HbA1c between the tested and the control samples. The results are as follows:
| Potential interfering substance | Concentration at which no significantinterference (≤0.3%) was observed |
|---|---|
| Triglycerides | 3.07 g/dL (35.1 mM) |
| Bilirubin | 25.8 mg/dL (442 μM) |
| Ascorbic acid | 60 mg/dL (3.41 mM) |
| Urea | 291 mg/dL (48.5 mM) |
| Rheumatoid factor | 2178 IU/mL |
| Glybenclamide | 3 mg/dL |
ii) To study interference from Carbamlyated hemoglobin, four whole blood patient samples with A1c concentrations at ~5.7%, ~6.9% and ~12.4% were split into two aliguots. One aliguot, at each A1c level, was spiked with 8.11 mg/dL (1 mmol/L) of Potassium Cyanate and incubated for 3 hours at 37°C. Another aliquot, at each A1c level, was incubated for 3 hours at 37°C. Samples were then analyzed on the MINICAP FLEX-PIERCING instrument using the MINICAP HbA1c assay kit, Samples were analyzed in triblicate. The definition of non-significant interference is ≤ 0.3 HbA1c% between the tested and the control samples.
To conclude Carbamylated hemoglobin (≤ 8.7 %) does not interfere with this assay.
iii) To study interference from Labile HbA1c, four whole blood patient samples with A1c concentrations at ~4.7%, ~6.8%, ~8.8% and ~12.7% were split into two aliguots. One aliguot. at each A1c level, was spiked with 1800 mg/dL (0,5 mol/L) of glucose and incubated for 3 hours at 37°C. Another aliquot, at each A1c level, was incubated for 3 hours at 37°C. Samples were then analyzed on the MINICAP FLEX-PIERCING instrument using the MINICAP HbA1c assay kit. Samples were analyzed in triplicate. The definition of non-significant interference is ≤ 0.3 HbA1c% between the tested and the control samples.
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To conclude Labile Hb A1c (≤ 14.8 %) does not interfere with this assay.
iv) To study interference from Labile HbA1c, four whole blood patient samples with A1c concentrations at ~5.2%, ~6.6%, ~9.4% and ~11.7% were split into two aliguots. One aliguot, at each A1c level, was spiked with 180 mg/dL (10 mmol/L) of acetylsalicylic and incubated for 4 hours at 37°C. Another aliquot, at each A1c level, was incubated for 4 hours at 37°C. Samples were then analyzed on the MINICAP FLEX-PIERCING instrument using the MINICAP HbA1c assay kit, Samples were analyzed in triplicate. The definition of non-significant interference is ≤ 0.3 HbA1c% between the tested and the control samples.
To conclude Acetylated hemoglobin (≤ 3.0 %) does not interfere with this assay.
v) A hemoglobin variant interference study was carried out using samples known to contain Hemoglobin variants S, E, D and C. These variant samples were tested on the MINICAP FLEX-PIERCING instrument using the MINICAP HbA1c assay kit. The definition of non-significant interference is ±10% difference between the candidate method and a NGSP reference method (performed in a NGSP laboratory).
The testing results show there is no significant interference for HbS (≤ 40.5%), HbE (≤ 24.7%), HbD (≤ 41.0%) and HbC (≤ 37.0%).
vi) An additional variant interference study was carried out to study the variant interference from Hemoglobin F. 16 whole blood samples with HbA1c concentrations of ~5.3% and ~11.6% contained various concentrations of HbF (2.3 to 19.7%) were tested on the MINICAP FLEX-PIERCING instrument using the MINICAP HbA1c assay kit. The definition of non-significant interference is ±10% difference between the candidate method and a NGSP reference method (performed in a NGSP laboratory).
The testing results show there is no significant interference for HbF ≤ 19.7%.
-
- Comparison studies:
- a. Method comparison with predicate device:
The correlation studies have been performed according to CLSI Guideline "EP9-A2: Method Comparison and Bias Estimation Using Patient Samples".
Internal Study :
101 whole blood samples with HbA1c ranging from 4.8% (29 mmol/mol) to 13.3% (122 mmol/mol) were analyzed in singlicate using the MINICAP HbA1c assay kit on the MINICAP FLEX-PIERCING instrument (candidate device) and on the CAPILLARYS Hb A1c assay on the CAPILLARYS 2 FLEX-PIERCING instrument. The linear regression correlation was calculated as follows:
| HbA1c | Correlation coefficient | y-Intercept | Slope | Range of valuesMINICAP Hb A1c |
|---|---|---|---|---|
| Percentage(%) | 0.998 | 0.165 | 0.982 | 4.8 - 13.3 |
| Concentration(mmol/mol) | 0.998 | 1.262 | 0.985 | 29 - 122 |
External study No.1
126 whole blood samples with HbA1c ranaing from 4.8% (29 mmol/mol) to 13.6% (125 mmo//mol) were analyzed in singlicate using the MINICAP HbA1c assay kit on the MINICAP FLEX-PIERCING
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instrument (candidate device) and on the CAPILLARYS Hb A1c assay on the CAPILLARYS 2 FLEX-PIERCING instrument. The linear regression correlation was calculated as follows:
| HbA1c | Correlation coefficient | y-Intercept | Slope | Range of valuesMINICAP Hb A1c |
|---|---|---|---|---|
| Percentage(%) | 0.998 | - 0.032 | 0.997 | 4.8 - 13.6 |
| Concentration(mmol/mol) | 0.998 | - 0.396 | 0.996 | 29 - 125 |
External study No. 2
140 whole blood samples with HbA1c ranging from 4.8% (29 mmol/mol) to 13.1% (119 mmol/mol) were analyzed in singlicate using the MINICAP HbA1c assay kit on the MINICAP FLEX-PIERCING instrument (candidate device) and on the CAPILLARYS Hb A1c assay on the CAPILLARYS 2 FLEX-PIERCING instrument. The linear regression correlation was calculated as follows:
| HbA₁c | Correlation coefficient | y-Intercept | Slope | Range of valuesMINICAP Hb A1c |
|---|---|---|---|---|
| Percentage(%) | 0.998 | - 0.057 | 1.019 | 4.8 - 13.1 |
| Concentration(mmol/mol) | 0.998 | - 0.316 | 1.023 | 29 - 119 |
b. Matrix comparison:
A total of 41 random matched sample pairs (K2 EDTA and K3 EDTA) were tested on the MINICAP FLEX-PIERCING instrument using the MINICAP HbA1c assay kit. The linear regression is presented in the table below:
| Fraction | Number ofsamples | Correlationcoefficient | y-intercept | Slope | Range ofHbA1cfractions(test) |
|---|---|---|---|---|---|
| HbA1c (%) | 41 | 0,999 | 0,039 | 0,998 | 4,9 - 13,3 |
| HbA1c(mmol/mol) | 41 | 0,999 | 0,091 | 1,001 | 30 - 122 |
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SUBSTANTIAL EQUIVALENCE
The performance and comparative studies of the MINICAP Hb A1c test with the MINICAP FLEX-PIERCING instrument were performed using SEBIA's commercially available materials and standard procedures.
In the comparative studies, commercially available materials and standard procedures were used with the predicate device: CAPILLARYS Hb A1c using the CAPILLARYS 2 FLEX-PIERCING instrument (K122101).
Both the new device MINICAP Hb A1c with the MINICAP FLEX-PIERCING and the predicate method, CAPILLARYS Hb A1c with the CAPILLARYS 2 FLEX-PIERCING instrument use the same technology of capillary electrophoresis of blood samples for Hb A1c analysis. The MINICAP HbA1c kit using the MINICAP FLEX-PIERCING instrument and the predicate device the CAPILLARYS Hb A1c kit used with the CAPILLARYS 2 FLEX-PIERCING instrument utilize EDTA collection tubes of (K2 and K3).
The SEBIA MINICAP Hb A1c procedure, performed with the MINICAP FLEX-PIERCING system was found to be substantially equivalent in function, use, safety, effectiveness and the performance to predicate devices described above.
The following tables A, B, C and D present the similarities and the differences.
Table A : SEBIA MINICAP Hb A1c kit used with the MINICAP FLEX PIERCING instrument as compared to the predicate CAP!LLARYS Hb A1c kit used with the CAPILLARYS 2 FLEX-PIERCING instrument
Table B: SEBIA Hb A1c CAPILLARY Calibrators used with the MINICAP Hb A1C kit and MINICAP FLEX-PIERCING Instrument to the predicate CAPILLARYS Hb A1c kit used with the CAPILLARYS 2 FLEX-PIERCING instrument.
Table C: SEBIA Hb A1c CAPILLARY Controls used with the MINICAP Hb A1c kit and MINICAP FLEX-PIERCING instrument as compared to the predicate devices CAPILLARYS Hb A1c kit used with the CAPILLARYS 2 FLEX-PIERCING instrument.
Table D: SEBIA MINICAP FLEX-PIERCING Instrument to the predicate the CAPILLARYS 2 FLEX-PIERCING instrument.
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Table A
SEBIA MINICAP Hb A1c kit used with the MINICAP FLEX PIERCING instrument as compared to the predicate CAPILLARYS Hb A1c kit used with the CAPILLARYS 2 FLEX-PIERCING instrument.
| SEBIA CAPILLARYS Hb A1c technique withCAPILLARYS 2 FLEX-PIERCING instrument | SEBIA MINICAP Hb A1c technique with MINICAPFLEX-PIERCING instrument | |
|---|---|---|
| Intended Use | The CAPILLARYS Hb A1c kit is designed forseparation and quantification of the HbA1c glycatedfraction of hemoglobin in human blood, by capillaryelectrophoresis in alkaline buffer (pH 9.4) with theCAPILLARYS 2 FLEX-PIERCING instrument.Measurement of hemoglobin A1c is effective inmonitoring long-term glycemic control in individualswith diabetes mellitus. The CAPILLARYS Hb A1c kitis designed for Professional Use Only.For In Vitro Diagnostic Use. | The MINICAP Hb A1c kit is designed for separationand quantification of the HbA1c glycated fraction ofhemoglobin in human blood, by capillaryelectrophoresis in alkaline buffer (pH 9.4) with theMINICAP FLEX-PIERCING instrument.Measurement of hemoglobin A1c is effective inmonitoring long-term glycemic control in individualswith diabetes mellitus. The MINICAP Hb A1c kit isdesigned for Professional Use Only.For In Vitro Diagnostic Use. |
| Separationsystem | Free solution capillary electrophoresis (FSCE):protein separation in an alkaline buffer (pH 9.4)according to their charge, to the electrolyte pH andelectroosmotic flow.Fast separation and good resolution.Electrophoregrams show separated fractionsaccording to their charge. | Same |
| Instrument | SEBIA CAPILLARYS 2 FLEX-PIERCING instrument,PN 1227 | SEBIA MINICAP FLEX-PIERCING instrument, PN1232 |
| Picture | Image: SEBIA CAPILLARYS 2 FLEX-PIERCING instrument | Image: SEBIA MINICAP FLEX-PIERCING instrument |
| Interface | PC interface | Same |
| Absorbance wavelength | 415 nm | Same |
| Software | SEBIA PHORESIS™ software | Same |
| Number ofseparation units | 8 parallel capillaries | 2 parallel capillaries |
| Calibration | Yes | Yes |
| Sample type | Whole blood in capped tube | Same |
| Samplesidentification | Yes (Bar code reading on both sample racks andtubes) | Yes (Bar code reading on sample tubes) |
| Hemolysis | Performed automatically by the instrument | Same |
| Introduction ofthe samples intothe automaticsystem | Continuous loading using sample racks | Continuous loading on the rotating sampler |
| Analysisthroughput | 40 analyses / hour | 7.6 analyses / hour |
| Collection tubes | Tubes with K2EDTA or K3EDTA anticoagulant | Same |
| SEBIA CAPILLARYS Hb A1c technique withCAPILLARYS 2 FLEX-PIERCING instrument | SEBIA MINICAP Hb A1c technique with MINICAPFLEX-PIERCING instrument | |
| Reagent | CAPILLARYS Hb A1c Kit (PN 2015) : | MINICAP Hb A1c Kit (PN 2215) : |
| Buffer | Buffer | |
| Hemolyzing solution | Hemolyzing solution | |
| Wash solution | Wash solution | |
| Dilution segments | Reagent cups | |
| Filters | Filters | |
| Bins for used cups | ||
| Hemolysing solution bar code labels | ||
| CAPILLARY Hb A1c CALIBRATORS (PN 4755) : | CAPILLARY Hb A1c CALIBRATORS (PN 4755) : | |
| CAPILLARY Hb A1c Calibrator 1 | CAPILLARY Hb A1c Calibrator 1 | |
| CAPILLARY Hb A1c Calibrator 2 | CAPILLARY Hb A1c Calibrator 2 | |
| CAPILLARY Hb A1c CONTROLS (PN 4774) : | CAPILLARY Hb A1c CONTROLS (PN 4774) : | |
| CAPILLARY Hb A1c Control 1 | CAPILLARY Hb A1c Control 1 | |
| CAPILLARY Hb A1c Control 2 | CAPILLARY Hb A1c Control 2 | |
| Standardization | NGSP | NGSP |
| IFCC | IFCC | |
| SEBIAHbA1c CAPILLARY CALIBRATORSK122101 | SEBIAHbA1c CAPILLARY CALIBRATORS | |
| Intended Use | The Hb A1c CAPILLARY Calibrators aredesigned for the calibration and migrationcontrol of human glycated hemoglobinA1c quantification with SEBIACAPILLARYS Hb A1c electrophoresisprocedure performed with theCAPILLARYS 2 FLEX-PIERCINGautomated instrument for capillaryelectrophoresis.The Hb A1c CAPILLARY Calibrators aredesigned for professional Use Only.For In Vitro Diagnostic Use. | The Hb A1c CAPILLARY Calibrators aredesigned for the calibration and migrationcontrol of human glycated hemoglobinA1c quantification with SEBIA capillaryelectrophoresis procedures:- CAPILLARYS Hb A1c performedwith the CAPILLARYS 2 FLEX-PIERCINGautomated instrument and,- MINICAP Hb A1c performed withthe MINICAP FLEX-PIERCINGautomated instrument.The Hb A1c CAPILLARY Calibrators aredesigned for Professional Use Only.For In Vitro Diagnostic Use |
| Product Number | 4755 | 4755 |
| Format | 2 levels1 vial (0.6 mL) per level | Same |
| Preparation | Reconstitute each lyophilized calibratorvial with 0.6 mL of distilled or deionizedwater. | Same |
| Storagetemperature | Before reconstitution, the lyophilizedcalibrators must be stored between - 30oC and - 18 oC. They are stable until theexpiration date indicated on the viallabels. | Same |
| In use storage | After reconstitution, store the calibratorsat 2 - 8 oC in a closed conical tube forcontrol blood and use them within the day(for 8 hours maximum). After use, theymust be stored without any delay between- 18 oC and - 22 oC due to the risk ofmicrobial contamination and denaturation.They are stable for 6 months maximumbetween - 18 oC and - 22 oC.Do not freeze and thaw the reconstitutedcalibrators more than 3 times. | CAPILLARYS 2 FLEX-PIERCING:After reconstitution, store the calibratorsat 2 - 8 oC in a closed conical tube forcontrol blood and use them within the day(for 8 hours maximum). After use, theymust be stored without any delay between- 18 oC and - 22 oC due to the risk ofmicrobial contamination and denaturation.They are stable for 22 months maximumbetween - 18 oC and - 22 oC.Do not freeze and thaw the reconstitutedcalibrators more than 3 times.MINICAP FLEX-PIERCING:After reconstitution, prepare 2 aliquotswith equivalent volumes (≈ 0.4 mL) of thewhole amount of each calibrator in conicaltubes for control blood, for use and / orstorage. Store the aliquoted calibrators at2 - 8 oC in a closed conical tube forcontrol blood and use them within the day(for 8 hours maximum). After use, theymust be stored without any delay between- 18 oC and - 22 oC due to the risk ofmicrobial contamination and denaturation.They are stable for 22 months maximumbetween - 18 oC and - 22 oC.Do not freeze and thaw the reconstitutedcalibrators more than 5 times. |
| Traceability | The assigned values are traceable toIFCC. | Same |
| Instrument | SEBIA CAPILLARYS 2 FLEX-PIERCING | SEBIA CAPILLARYS 2 FLEX-PIERCING |
| SEBIAHbA1c CAPILLARY CONTROLSK122101 | SEBIAHbA1c CAPILLARY CONTROLS | |
| Intended Use | The Hb A1c CAPILLARY Controls aredesigned for the quality control of humanglycated hemoglobin A1c quantificationwith CAPILLARYS Hb A1celectrophoresis procedure performed withthe CAPILLARYS 2 FLEX-PIERCINGautomated instrument for capillaryelectrophoresis.They should be used like any biologicalsamples.The values obtained must fall within therange determined for each batch.For In Vitro Diagnostic Use. | The Hb A1c CAPILLARY Controls aredesigned for the quality control of humanglycated hemoglobin A1c quantificationwith SEBIA capillary electrophoresisprocedures:- CAPILLARYS Hb A1c performedwith the CAPILLARYS 2 FLEX-PIERCINGautomated instrument and,- MINICAP Hb A1c performed withthe MINICAP FLEX-PIERCING automatedinstrument.The Hb A1c CAPILLARY Controls aredesigned for Professional Use Only.For In Vitro Diagnostic Use. |
| Product Number | 4774 | 4774 |
| Format | 2 levels1 vial (0.6 mL) per level | Same |
| Preparation | Reconstitute each lyophilized control vialwith 0.6 mL of distilled or deionizedwater. | Same |
| Storagetemperature | Before reconstitution, the lyophilizedcontrols must be stored refrigerated (2 to8 °C). They are stable until the expirationdate indicated on the vial labels. | Same |
| In use storage | After reconstitution, store the controls at 2- 8 °C in a closed conical tube for controlblood and use them within the day (for 8hours maximum). After use, they must bestored without any delay between - 18 °Cand - 22 °C due to the risk of microbialcontamination and denaturation. They arestable for 6 months maximum between- 18 °C and - 22 °C.Do not freeze and thaw the reconstitutedcontrols more than 30 times.After hemolysis with the CAPILLARYS 2FLEX-PIERCING instrument, store thedilution segments with controls at 2-8°Cand use them within the day (for 8 hoursmaximum). They may be stored, withoutany delay, between - 18 °C and - 22 °Cfor 1 month maximum. Do not freeze andthaw a dilution segment with hemolyzedcontrol more than three times. | CAPILLARYS 2 FLEX-PIERCING :After reconstitution, store the controls at 2- 8 °C in a closed conical tube for controlblood and use them within the day (for 8hours maximum). After use, they must bestored without any delay between - 18 °Cand - 22 °C due to the risk of microbialcontamination and denaturation. They arestable for 6 months maximum between- 18 °C and - 22 °C.Do not freeze and thaw the reconstitutedcontrols more than 30 times.After hemolysis with the CAPILLARYS 2FLEX-PIERCING instrument, store thedilution segments with controls at 2-8 °Cand use them within the day (for 8 hoursmaximum). They may be stored, withoutany delay, between - 18 °C and - 22 °C for1 month maximum. Do not freeze andthaw a dilution segment with hemolyzedcontrol more than three times.MINICAP FLEX-PIERCING :After reconstitution, store the controls at 2- 8 °C in a closed conical tube for controlblood and use them within the day (for 8hours maximum). After use, they must bestored without any delay between - 18 °Cand - 22 °C due to the risk of microbialcontamination and denaturation. They arestable for 6 months maximum between- 18 °C and - 22 °C.Do not freeze and thaw the reconstitutedcontrols more than 30 times. |
| Instrument | SEBIAHbA1c CAPILLARY CONTROLSK122101SEBIA CAPILLARYS 2 FLEX-PIERCING | SEBIAHbA1c CAPILLARY CONTROLSSEBIA CAPILLARYS 2 FLEX-PIERCING |
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and the control of the country
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:
.
.
:
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Table B
SEBIA Hb A1c CAPILLARY Calibrators used with the MINICAP Hb A1c kit and MINICAP FLEX-PIERCING Instrument to the predicate CAPILLARYS Hb A1c kit used with the CAPILLARYS 2 FLEX-PIERCING instrument.
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Table C
SEBIA Hb A1c CAPILLARY Controls used with the MINICAP Hb A1c kit and MINICAP FLEX-PIERCING instrument as compared to the predicate devices CAPILLARYS Hb A1c kit used with the CAPILLARYS 2 FLEX-PIERCING instrument.
·
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TABLE D
SEBIA MINICAP FLEX-PIERCING Instrument to the predicate the CAPILLARYS 2 FLEX-PIERCING instrument.
| SEBIA CAPILLARYS 2 FLEX-PIERCINGinstrument | SEBIA MINICAP FLEX-PIERCING instrument | |
|---|---|---|
| Intended Use | The CAPILLARYS 2 FLEX-PIERCING instrument isdesigned and intended for the human protein andhemoglobin separation by capillary electrophoresison 8 parallel capillaries. The analysis is performedusing uncapped tubes or capped tubes with a cappiercing function according to the procedure. TheCAPILLARYS 2 FLEX-PIERCING instrument isintended to be used with the SEBIA CAPILLARYSreagent kits.The CAPILLARYS 2 FLEX-PIERCING instrument isdesigned for Professional Use Only.For In Vitro Use. | The MINICAP FLEX-PIERCING instrument isdesigned and intended for the human protein andhemoglobin separation by capillary electrophoresison 2 parallel capillaries. The analysis is performedusing uncapped tubes or capped tubes with a cappiercing function according to the procedure. TheMINICAP FLEX-PIERCING instrument is intended tobe used with the SEBIA MINICAP reagent kits.The MINICAP FLEX-PIERCING instrument isdesigned for Professional Use Only.For In Vitro Use. |
| Separation | Free solution capillary electrophoresis (FSCE):protein separation in an alkaline buffer according totheir charge, to the electrolyte pH and electroosmoticflow.Fast separation and good resolution.Electrophoregrams show separated fractionsaccording to their charge. | Same |
| system | ||
| Product Number | PN 1227 | PN 1232 |
| Picture | Image: SEBIA CAPILLARYS 2 FLEX-PIERCING instrument | Image: SEBIA MINICAP FLEX-PIERCING instrument |
| Interface | PC interface | Same |
| Detection system | Deuterium lamp | Deuterium lamp and LED |
| Software | SEBIA PHORESIS™ software | Same |
| Number of | 8 parallel capillaries | 2 parallel capillaries |
| separation units | ||
| Samples tubes | uncapped tubes or capped tubes depending on theprocedure | Same |
| Samplesidentification | Yes (Bar code reading on both sample racks andtubes) | Yes (Bar code reading on sample tubes) |
| Introduction ofthe samples intothe automaticsystem | Continuous loading using sample racks | Continuous loading on the rotating sampler |
| Dimensions | L. 95 cm x H. 39 cm x D. 63 cm | L. 44 cm x H. 41.5 cm x D. 58 cm |
| Weight | 50 kg | 32 kg |
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Image /page/18/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular pattern around the symbol. The caduceus is a common symbol associated with healthcare and medicine. The logo is black and white.
DEPARTMENT OF HEALTH & IIUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
March 28, 2014
SEBIA C/O KAREN ANDERSON DIRECTOR OF TECHNICAL AND QUALITY ASSURANCE 1705 CORPORATE DRIVE SUITE 400 NORCROSS GA 30093
Re: K133344
Trade/Device Name: Minicap HbA Ic kit, Hb Alc Capillary Controls, Hb Alc Capillary Calibrators Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: II Product Code: LCP, JIS. JJX Dated: February 18, 2014 Received: February 20, 2014
Dear Ms. 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 upproval 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 docs 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{19}------------------------------------------------
Page 2-Ms. Anderson
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/Cl)RHOffices/ucm | 15809.html for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Ruth A. Chesler -S
for
Courtney H. Lias 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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.
510(k) Number (if known) K133344
Device Name
9
Hb A Ic CAPILLARY Calibrators using the MINICAP FLEX-PIERCING instrument
Indications for Use (Describe)
The Ho AIc CAPILLARY Calibrators are designed for the calibration control of human glycated hemoglobin Alc quantification with SEBIA capillary electrophoresis procedures using the MINICAP Hb A 1c kit with the MINICAP FLEX-PIERCING automated instrument.
The Hb Alc CAPILLARY Calibrators are designed for Professional Use Only. For In Vitro Diagnostic Use.
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)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
FORM FDA 3881 (1/14)
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This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.
510(k) Number (if known) K133344
Device Name
Hb Alc CAPILLARY Controls using the MINICAP FLEX-PIERCING instrument
Indications for Use (Describe)
The Hb AIc CAPILLARY Controls are designed for the quality control of human glycated hemoglobin AIc quantification with SEBIA capillary electrophoresis procedures using the MINICAP Hb A1c kit with the MINICAP FLEX-PIERCING automated instrument.
The Hb Alc CAPILLARY Controls are designed for Professional Use Only. For In Vitro Diagnostic Use.
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)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
arraster for the more of the Form FDA USE ONLY - FOR FDA USE ONLY - FOR FOR FOR SEASE - LE - FOR FOR FOR SEASE - LE -Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
{23}------------------------------------------------
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{24}------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K133344
Device Name MINICAP Hb Alc kit
Indications for Use (Describe)
The MINICAP Hb A 1c kit is designed for separation and quantification of the HbA 1c glycated fraction of hemoglobin in human whole blood, by capillary electrophoresis in alkaline buffer with the MINICAP FLEX-PIERCING instrument. Measurement of hemoglobin Alc is effective in monitoring long-term glycemic control in individuals with diabetes mellitus. Results are provided in IFCC (mmol/mol) and NGSP (%Hb A Ic) units.
The MINICAP Hb Alc kit is designed for Professional Use Only. For In Vitro Use.
Type of Use (Select one or both, as applicable)
2 Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 -
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
FORM FDA 3881 (1/14)
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.
PSC Publishing Services (30)) 443-6740
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This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
§ 864.7470 Glycosylated hemoglobin assay.
(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).