(266 days)
Not Found
No
The description focuses on the principle of capillary electrophoresis and direct detection based on absorbance, with visual evaluation of electrophoregrams. There is no mention of AI or ML algorithms for analysis or interpretation.
No
The device is described as being for "In Vitro Diagnostic Use" and performs quantitative analysis of hemoglobin, which indicates it's an analytical tool for diagnosis, not a device providing therapy.
Yes
The device is described as an "automated analyzer" that performs "quantitative analysis of the normal hemoglobin fractions ... and for the hemoglobin variants". It is intended for "detection" and "identification" of hemoglobin variants, and A2 hemoglobin quantification may be used with other clinical and laboratory findings for ß thalassemia detection. This indicates its use in providing information for diagnosis. Furthermore, it explicitly states "For In Vitro Diagnostic Use".
No
The device description clearly outlines a physical instrument (CAPILLARYS 3 TERA) that performs capillary electrophoresis on blood samples. This involves hardware components like capillaries, injection mechanisms, detection systems, and washing systems. The software controls this hardware, but the device itself is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states "For In Vitro Diagnostic Use" in the "Intended Use / Indications for Use" section. This is the primary indicator that the device is intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae.
Furthermore, the description of the device and its intended use aligns with the definition of an IVD:
- It is designed to analyze human venous blood samples.
- It performs quantitative analysis of normal hemoglobin fractions and detects major hemoglobin variants.
- The results are intended to be used in conjunction with other laboratory and clinical findings, which is typical for diagnostic tests.
- The performance studies described (Precision, Linearity, LOD, LOQ, Analytical Specificity, Comparison Studies) are standard evaluations for IVD devices.
N/A
Intended Use / Indications for Use
The CAPI 3 HEMOGLOBIN(E) kit is designed for the separation of the normal hemoglobins (A, A2 and F) in human venous blood samples, and for the detection of the major hemoglobin variants (S, C, E and D), by capillary electrophoresis in alkaline buffer (pH 9.4) with the SEBIA CAPILLARYS 3 TERA instrument.
The CAPILLARYS 3 TERA instrument is an automated analyzer which performs a complete hemoglobin profile for the quantitative analysis of the normal hemoglobin fractions A, A2 and F and for the detection of major hemoglobin variants S, C, E and D. The assay is performed on the hemolysate of whole blood samples collected in tubes containing K2EDTA or K3EDTA as anticoagulant. The CAPI 3 HEMOGLOBIN(E) is intended to be used in conjunction with other laboratory and clinical findings.
For In Vitro Diagnostic Use.
Product codes (comma separated list FDA assigned to the subject device)
GKA
Device Description
The CAPILLARYS 3 instrument uses the principle of capillary electrophoresis in free solution which is the most common form of capillary electrophoresis. 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 CAPILLARYS 3 instrument has silica capillaries functioning in parallel allowing 12 simultaneous analyses for hemoglobin 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 fraction, and the resulting electrophoregrams are also evaluated visually for pattern abnormalities. In addition, the high resolution of this procedure should allow the identification of hemoglobin variants, in particular, to differentiate hemoglobins S from D, and E from C. The hemoglobin A2 quantification can also be performed when hemoglobin E is present. A2 hemoglobin quantification may be used with other clinical and laboratory findings for ẞ thalassemia detection.
By using alkaline pH buffer, normal and abnormal (or variant) hemoglobins are detected in the following order, from cathode to anode: δΑ'2 (A2 variant). C. A2, E. S. D. F. and A.
The carbonic anhydrase is not visualized on the hemoglobin electrophoretic patterns by capillary electrophoresis, this permits to identify hemoglobin A2 variants in this migration zone.
NOTE : the name "CAPILLARYS 3" is used for the SEBIA CAPILLARYS 3 TERA automated instrument.
The hemoglobins are reported in % units along with an electrophoresis scan.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
a. Precision / Reproducibility:
- Study Type: 7-days reproducibility study.
- Sample Size: Seven (7) different native blood samples.
- Key Results:
- Within-run CV for Hb A: 0.0%-0.6%, Hb A2: 1.1%-5.2%, Hb F: 0.4%, Hb S: 0.4%, Hb C: 1.1%, Hb D: 0.4%, Hb E: 0.8%.
- Between-run CV for Hb A: 0.0%-0.4%, Hb A2: 0.0%-1.6%, Hb F: 0.2%, Hb S: 0.1%, Hb C: 0.3%, Hb D: 0.3%, Hb E: 0.0%.
- Between-day CV for Hb A: 0.0%-1.3%, Hb A2: 0.0%-3.8%, Hb F: 2.4%, Hb S: 0.2%, Hb C: 0.8%, Hb D: 1.3%, Hb E: 1.4%.
- Between-instrument CV for Hb A: 0.0%-0.2%, Hb A2: 0.0%-0.5%, Hb F: 0.0%, Hb S: 0.4%, Hb C: 0.0%, Hb D: 0.0%, Hb E: 0.0%.
- Total reproducibility CV for Hb A: 0.0%-1.3%, Hb A2: 1.3%-6.5%, Hb F: 2.5%, Hb S: 0.6%, Hb C: 1.4%, Hb D: 1.4%, Hb E: 1.6%.
- Study Type: 20-days reproducibility study.
- Sample Size: Five (5) different samples, analyzed in duplicate on twelve capillaries per run, two runs per day over 20 days yielding a total of 960 results per sample.
- Key Results:
- Within-capillary CV for Hb A: 0.0%-0.5%, Hb A2: 0.8%-3.1%, Hb F: 0.4%, Hb S: 0.4%, Hb C: 0.9%, Hb D: 0.5%, Hb E: 1.0%.
- Between-capillary CV for Hb A: 0.0%-0.4%, Hb A2: 0.9%-4.4%, Hb F: 0.1%, Hb S: 0.5%, Hb C: 0.8%, Hb D: 0.2%, Hb E: 0.1%.
- Between-run CV for Hb A: 0.0%-0.3%, Hb A2: 0.0%-2.4%, Hb F: 0.5%, Hb S: 0.1%, Hb C: 0.4%, Hb D: 0.1%, Hb E: 0.4%.
- Between-day CV for Hb A: 0.0%-0.5%, Hb A2: 0.7%-1.3%, Hb F: 0.2%, Hb S: 0.7%, Hb C: 1.1%, Hb D: 0.3%, Hb E: 0.3%.
- Total reproducibility CV for Hb A: 0.0%-0.8%, Hb A2: 1.4%-6.0%, Hb F: 0.7%, Hb S: 1.0%, Hb C: 1.7%, Hb D: 0.6%, Hb E: 1.1%.
b. Linearity:
- Study Type: Linearity study per CLSI EP06-A.
- Key Results: Determined to be linear within the entire range studied for Hb A (1.0 -97.3%), HbS (1.1-89.7%), Hb A2 (0.2-9.1%), Hb F (0.5-83.1%), Hb C (0.3-82.0%), Hb D (1.1-43.5%), Hb E (0.3-86.9%).
c. Limit of Blank (LOB), Limit of Detection (LOD), Limit of Quantitation (LOQ):
- Study Type: Studies per CLSI EP17-A.
- Sample Size: Five (5) different blood samples.
- Key Results: LOB, LOD, LOQ determined for each hemoglobin fraction.
- Hb A: LOB 0.1%, LOD 1.0%, LOQ 1.0%
- Hb A2: LOB 0.1%, LOD 0.2%, LOQ 0.2%
- Hb F: LOB 0.2%, LOD 0.4%, LOQ 0.5%
- Hb S: LOB 0.1%, LOD 0.9%, LOQ 1.1%
- Hb C: LOB 0.1%, LOD 0.3%, LOQ 0.3%
- Hb D: LOB 0.1%, LOD 0.7%, LOQ 1.1%
- Hb E: LOB 0.1%, LOD 0.3%, LOQ 0.3%
d. Analytical Specificity:
- Study Type: Interference studies per CLSI, EP7-A2.
- Sample Size: Three (3) blood samples.
- Key Results: Maximum concentration of interferents Bilirubin 20.6 mg/dL and Triglycerides 2.2 g/dL.
e. Comparison Studies:
- Study Type: Method comparison studies per CLSI, EP09-A2-IR.
- Sample Size: Total of 304 samples (180 without hemoglobin variant /124 with hemoglobin variant).
- Key Results:
- Site 1 (153 blood samples, 64 with hemoglobin variants): Perfect correlation between the two analysis procedures for Hb A, Hb A2, Hb F, Hb S, Hb C, Hb D and Hb E quantitative determination. Correlation coefficients for all fractions were 0.998 to 1.000. No false positives observed.
- Site 2 (151 blood samples, 60 with hemoglobin variants): Perfect correlation between the two analysis procedures for Hb A, Hb A2, Hb F, Hb S, Hb C and Hb E quantitative determination. Correlation coefficients for all fractions were 0.987 to 1.000. No false positives observed.
- Combined abnormal hemoglobin variants detected: HbS=46, HbC = 24, HbD=9 HbE= 17. All abnormal hemoglobins and abnormal levels of normal hemoglobins detected were in agreement with the comparative system and clinical diagnosis.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 864.7415 Abnormal hemoglobin assay.
(a)
Identification. An abnormal hemoglobin assay is a device consisting of the reagents, apparatus, instrumentation, and controls necessary to isolate and identify abnormal genetically determined hemoglobin types.(b)
Classification. Class II (special controls). A control intended for use with an abnormal hemoglobin assay is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
December 14, 2018
Sebia, Inc. Karen Anderson Director of Technical & Regulatory 1705 Corporate Drive, Suite 400 Norcross, Georgia 30093
Re: K180762
Trade/Device Name: CAPI 3 HEMOGLOBIN(E) Regulation Number: 21 CFR 864.7415 Regulation Name: Abnormal hemoglobin assay Regulatory Class: Class II Product Code: GKA Dated: March 23, 2018 Received: March 23, 2018
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 mav, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be avare that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
1
requirements, including, but not limited to: registration and listing (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Leonthena R. Carrington -S
Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K180762
Device Name CAPI 3 HEMOGLOBIN(E)
Indications for Use (Describe)
The CAPI 3 HEMOGLOBIN(E) kit is designed for the separation of the normal hemoglobins (A. A2 and F) in human venous blood samples, and for the detection of the major hemoglobin variants (S, C, E and D), by capillary electrophoresis in alkaline buffer (pH 9.4) with the SEBIA CAPILLARYS 3 TERA instrument.
The CAPILLARYS 3 TERA instrument is an automated analyzer which performs a complete for the quantitative analysis of the normal hemoglobin fractions A. A2 and F and for themoglobin variants S. C. E and D. The assay is performed on the hemolysate of whole blood samples collected in tubes containing K2EDTA or K3EDTA as anticoagulant. The CAPI 3 HEMOGLOBIN(E) is intended to be used in conjunction with other laboratory and clinical findings.
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)
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3
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 | |
| Norcross, Georgia 30093, USA | ||
| Contact | Karen Anderson, Dir of Technical and Regulatory | |
| Phone: 1-800-835-6497, 3704 | ||
| Fax: 770-446-8511 | ||
| Email: karen.anderson@sebia-usa.com | ||
| Matthew C. Wagner, Ph.D. Scientific | ||
| Affairs Specialist | ||
| Phone: 1-800-835-6497 | ||
| Email: matthew.wagner@sebia-usa.com | ||
| Date Prepared | December 13, 2018 | |
| Manufacturing | Sebia | |
| 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 | ||
| Product Name | CAPI 3 HEMOGLOBIN(E) | |
| Common Name | Hemoglobin by capillary electrophoresis | |
| Product Regulation No. | 21 CFR 864.7415 | |
| Product Codes , Device | ||
| classification and Panel | ||
| Classification | GKA, Class II , Hematology (81) | |
| Establishment Registration No. | 8023024 |
4
1. DEVICE DESCRIPTION
The CAPILLARYS 3 instrument uses the principle of capillary electrophoresis in free solution which is the most common form of capillary electrophoresis. 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 CAPILLARYS 3 instrument has silica capillaries functioning in parallel allowing 12 simultaneous analyses for hemoglobin 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 fraction, and the resulting electrophoregrams are also evaluated visually for pattern abnormalities. In addition, the high resolution of this procedure should allow the identification of hemoglobin variants, in particular, to differentiate hemoglobins S from D, and E from C. The hemoglobin A2 quantification can also be performed when hemoglobin E is present. A2 hemoglobin quantification may be used with other clinical and laboratory findings for ß thalassemia detection.
By using alkaline pH buffer, normal and abnormal (or variant) hemoglobins are detected in the following order, from cathode to anode: δΑ'2 (A2 variant). C. A2, E. S. D. F. and A.
The carbonic anhydrase is not visualized on the hemoglobin electrophoretic patterns by capillary electrophoresis, this permits to identify hemoglobin A2 variants in this migration zone.
NOTE : the name "CAPILLARYS 3" is used for the SEBIA CAPILLARYS 3 TERA automated instrument.
The hemoglobins are reported in % units along with an electrophoresis scan.
5
Reagents:
CAPI 3 HEMOGLOBIN(E) KIT
| ITEMS | PN 2507 |
|---|---|
| Buffer (ready to use) | 2 vials, 700 mL each |
| Hemolysing solution (ready to use) | 1 vial, 700 mL |
| Filters | 4 filters |
Additional reagents and accessories not included in the CAPI 3 HEMOGLOBIN(E) KIT
| ITEMS | PN | COMPONENTS |
|---|---|---|
| CAPICLEAN CAPILLARYS 3 | 2060 | 1 vial, 25 mL |
| CAPILLARYS 3 WASH SOLUTION | 2062 | 1 vial, 75mL |
| CAPI 3 REAGENT CUPS | 2582 | 24 X 14 packs of reagent cups |
| TEST TUBES | 9214 | 200 of 100 mm-tubes |
| CAPI 3 BINS | 2581 | 5 units |
| TUBES AND CAPS FOR | 9202 | 20 units |
| CONTROLS | 9205 | 500 units |
| CAPILLARYS 3 & MC SWITCH | ||
| RACK FOR HEMOGLOBIN(E) | 1373 | 1 unit |
| CAPILLARYS 3 & MC LOW | ||
| VOLUME RACKS | 1364 | 5 units |
| SEBIA CAPILLARYS 3 | 1246 | 1 unit |
2. INDICATIONS FOR USE
CAPI 3 HEMOGLOBIN(E) kit:
The CAPI 3 HEMOGLOBIN(E) kit is designed for the separation of the normal hemoglobins (A, A2 and F) in human venous blood samples, and for the detection of the major hemoglobin variants (S. C. E and D), by capillary electrophoresis in alkaline buffer (pH 9.4) with the SEBIA CAPILLARYS 3 TERA instrument.
The CAPILLARYS 3 TERA instrument is an automated analyzer which performs a complete hemoglobin profile for the quantitative analysis of the normal hemoglobin fractions A, A2 and F and for the detection of major hemoglobin variants S, C, E and D. The assay is performed on the hemolysate of whole blood samples collected in tubes
6
containing K₂EDTA or K₃EDTA as anticoagulant. The CAPI 3 HEMOGLOBIN(E) is intended to be used in conjunction with other laboratory and clinical findings.
For In Vitro Diagnostic Use.
3. TECHNOLOGICAL CHARACTERISTICS
The CAPILLARYS 3 instrument in combination with the CAPI3 HEMOGLOBIN(E) kit uses the principle of capillary electrophoresis in free solution which is the most common form of capillary electrophoresis. 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 CAPILLARYS 3 instrument has silica capillaries functioning in parallel allowing 12 simultaneous analyses for hemoglobin 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 fraction, and the resulting electrophoregrams are also evaluated visually for pattern abnormalities. In addition, the high resolution of this procedure should allow the identification of hemoglobin variants, in particular, to differentiate hemoglobins S from D, and E from C. The hemoglobin A2 quantification can also be performed when hemoglobin E is present. A2 hemoglobin quantification may be used with other clinical and laboratory findings for ß thalassemia detection.. By using alkaline pH buffer, normal and abnormal (or variant) hemoglobins are detected in the following order, from cathode to anode: δΑ΄2 (A2 variant), C, A2, E, S, D, F and A. The carbonic anhydrase is not visualized on the hemoglobin electrophoretic patterns by capillary electrophoresis, this permits to identify hemoglobin A2 variants in this migration zone.
4. SUBSTANTIAL EQUIVALENCE INFORMATION:
| Predicate Device Name | Predicate Device 510(k) number | Product Code | Regulation No. |
|---|---|---|---|
| CAPILLARYS HEMOGLOBIN(E) using the | |||
| CAPILLARYS 2 FLEX-PIERCING | |||
| instrument, | K112550 | GKA | 864.7415 |
7
Similarities between the candidate device (CAPI 3 HEMOGLOBIN(E)) and the predicate device (CAPILLARYS HEMOGLOBIN(E)), K112550 (Table A).
| Similarities | ||
|---|---|---|
| Table A | Sebia CAPI 3 HEMOGLOBIN(E) | |
| Candidate Device | Sebia CAPILLARYS | |
| HEMOGLOBIN(E) | ||
| Predicate Device (K112550) | ||
| Intended use | The CAPI 3 HEMOGLOBIN(E) kit is | |
| designed for the separation of the normal | ||
| hemoglobins (A, A2 and F) in human venous | ||
| blood samples, and for the detection of the | ||
| major hemoglobin variants (S, C, E and D), by | ||
| capillary electrophoresis in alkaline buffer (pH | ||
| 9.4) with the SEBIA CAPILLARYS 3 TERA | ||
| instrument. | ||
| The CAPILLARYS 3 TERA instrument is an | ||
| automated analyzer which performs a | ||
| complete hemoglobin profile for the | ||
| quantitative analysis of the normal | ||
| hemoglobin fractions A, A2 and F and for the | ||
| detection of major hemoglobin variants S, C, | ||
| E and D. The assay is performed on the | ||
| hemolysate of whole blood samples collected | ||
| in tubes containing K2EDTA or K3EDTA as | ||
| anticoagulant. The CAPI 3 HEMOGLOBIN(E) | ||
| is intended to be used in conjunction with | ||
| other laboratory and clinical findings. | ||
| For In Vitro Diagnostic Use. | The CAPILLARYS HEMOGLOBIN(E) | |
| kit is designed for the separation of | ||
| the normal hemoglobins (A, A2 and F) | ||
| in human blood samples, and for the | ||
| detection of the major hemoglobin | ||
| variants (S, C, E and D), by capillary | ||
| electrophoresis in alkaline buffer (pH | ||
| 9.4) with the SEBIA CAPILLARYS 2 | ||
| FLEX-PIERCING instrument. | ||
| The CAPILLARYS 2 FLEXPIERCING | ||
| instrument is an automated analyzer | ||
| which performs a complete | ||
| hemoglobin profile for the quantitative | ||
| analysis of the normal hemoglobin | ||
| fractions A, A2 and F and for the | ||
| detection of major hemoglobin | ||
| variants S, C, E and D. The assay is | ||
| performed on the hemolysate of whole | ||
| blood samples collected in tubes | ||
| containing K2EDTA or K3EDTA as | ||
| anticoagulant. | ||
| For In Vitro Diagnostic Use. | ||
| Specimen Type | Venous Human Whole Blood | Same |
| Technology | CAPILLARYS ELECTROPHORESIS | Same |
| DETECTION | ||
| Absorbance | ||
| Wavelength | 415 nm | Same |
| Software | PHORESIS | Same |
| Barcode | ||
| Identification of | ||
| Same | On-board | Same |
| Controls for | ||
| migration | Sebia Normal A2 Control ( sold separately) | Same |
| Buffer and | ||
| Composition | CAPILLARYS HEMOGLOBIN(E) | Same |
| Use of Buffer | ||
| Solution | On-Board | Same |
| Wash Solution | ||
| and Composition | Same | Same |
| Use of the Wash | ||
| Solution | On-Board | Same |
| Hemolysing | ||
| Solution and | ||
| Composition | On-Board | Same |
| Use of | ||
| Hemolysing | ||
| Solution | On-Board | Same |
| Reference Range | Hb A 96.7-97.8% | |
| HbF ≤ 0.5 % | ||
| Hb A2 2.2-3.2 % | Same | |
| Hb variants library | ||
| (on-board) | Yes, displayed by the software and indicated | |
| in the package insert) | Same |
8
Table B. Differences between the candidate device (CAPI 3 HEMOGLOBIN(E)) and the predicate device (CAPILLARYS HEMOGLOBIN(E), K112550 in (Table B).
| Differences | ||
|---|---|---|
| Table B | Sebia CAPI 3 HEMOGLOBIN(E) | |
| Candidate Device | Sebia CAPILLARYS HEMOGLOBIN(E) | |
| Predicate Device (K112550) | ||
| Number of Separation | ||
| units ( Capillaries) | 12 | 8 |
| Bottle for reagents | RFID tag | None |
| Reagent Cups | Supplied separate packaging | Supplied in the kit |
| Wash Solution | Supplied separate packaging | Supplied in the kit |
5. Performance Data:
a. Precision / Reproducibility:-
The precision of the CAPI 3 HEMOGLOBIN(E) procedure was evaluated in studies based on the Clinical and Laboratory Standards Institute (CLSI - USA) EP5-A3 guideline "Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition". The means, standard deviations (SD) and coefficients of variation (CV %) were calculated for percentage (%) of hemoglobin fractions for each sample.
9
7-days reproducibility study with three instruments and one lot of kit
Seven (7) different native blood samples were run using the CAPI 3 HEMOGLOBIN(E) procedure performed with three CAPILLARYS 3 TERA instruments.
The 7-days reproducibility performed with three CAPILLARYS 3 instrument and one lot of CAPI 3 HEMOGLOBIN(E) kit is summarized in the following within-run, between-run, between-day, between-instrument and total reproducibility precision estimates (SD and % CV ranges) for the percentages (%) of each hemoglobin fraction from all samples.
| Ranges of % tested | Within-run | Between-run | Between-day | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fraction | Min Value | Max Value | SD min | SD max | CV min | CV max | SD min | SD max | CV min | CV max | SD min | SD max | CV min | CV max |
| Hb A | 56,5 | 97,5 | 0,03 | 0,39 | 0,0% | 0,6% | 0,00 | 0,22 | 0,0% | 0,4% | 0,00 | 0,73 | 0,0% | 1,3% |
| Hb A2 | 1,9 | 4,8 | 0,03 | 0,14 | 1,1% | 5,2% | 0,00 | 0,05 | 0,0% | 1,6% | 0,00 | 0,11 | 0,0% | 3,8% |
| Hb F | 34,9 | 0,15 | 0,4% | 0,08 | 0,2% | 0,84 | 2,4% | |||||||
| Hb S | 40,1 | 0,14 | 0,4% | 0,06 | 0,1% | 0,10 | 0,2% | |||||||
| Hb C | 34,3 | 0,36 | 1,1% | 0,11 | 0,3% | 0,28 | 0,8% | |||||||
| Hb D | 38,6 | 0,15 | 0,4% | 0,11 | 0,3% | 0,50 | 1,3% | |||||||
| Hb E | 23,5 | 0,18 | 0,8% | 0,00 | 0,0% | 0,32 | 1,4% |
CAPI 3 HEMOGLOBIN(E) & CAPILLARYS 3 TERA : Reproducibility study on native whole blood samples (2018/10)
| Ranges of % tested | Between-instrument | Total reproducibility(*) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Fraction | Min Value | Max Value | SD min | SD max | CV min | CV max | SD min | SD max | CV min | CV max |
| Hb A | 56,5 | 97,5 | 0,00 | 0,14 | 0,0% | 0,2% | 0,03 | 0,84 | 0,0% | 1,3% |
| Hb A2 | 1,9 | 4,8 | 0,00 | 0,03 | 0,0% | 0,5% | 0,03 | 0,17 | 1,3% | 6,5% |
| Hb F | 34,9 | 0,00 | 0,0% | 0,86 | 2,5% | |||||
| Hb S | 40,1 | 0,16 | 0,4% | 0,24 | 0,6% | |||||
| Hb C | 34,3 | 0,00 | 0,0% | 0,47 | 1,4% | |||||
| Hb D | 38,6 | 0,00 | 0,0% | 0,54 | 1,4% | |||||
| Hb E | 23,5 | 0,00 | 0,0% | 0,37 | 1,6% |
(*) Total reproducibility includes : within-run, between-run, between-day and between-instrument.
20-days reproducibility study with one instrument and one lot of kit
Five (5) different samples were run using the CAPI 3 HEMOGLOBIN(E) procedure performed with one CAPILLARYS 3 instrument and one lot on CAPI 3 HEMOGLOBIN(E) kit. Each sample was analyzed in duplicate on twelve capillaries per run, two runs per day over 20 days yielding a total of 960 results per sample.
The 20-days reproducibility performed with one CAPILLARYS 3 instrument and one lot of CAPI 3 HEMOGLOBIN(E) kit is summarized in the following tables including within-capillary, betweencapillary, between-run, between-day and total reproducibility precision estimates (SD and % CV ranges) for the percentages (%) of each hemoglobin fraction from all samples
| Fraction | Ranges of % tested | Within-capillary | Between-capillary | Between-run | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Min Value | Max Value | SD min | SD max | CV min | CV max | SD min | SD max | CV min | CV max | SD min | SD max | CV min | CV max | |
| Hb A | 44,2 | 97,3 | 0,04 | 0,31 | 0,0% | 0,5% | 0,01 | 0,16 | 0,0% | 0,4% | 0,00 | 0,14 | 0,0% | 0,3% |
| Hb A2 | 2,6 | 6,5 | 0,04 | 0,09 | 0,8% | 3,1% | 0,02 | 0,12 | 0,9% | 4,4% | 0,00 | 0,06 | 0,0% | 2,4% |
| Hb F | 26,8 | 0,12 | 0,4% | 0,02 | 0,1% | 0,14 | 0,5% | |||||||
| Hb S | 17,5 | 0,06 | 0,4% | 0,08 | 0,5% | 0,02 | 0,1% | |||||||
| Hb C | 8,9 | 0,08 | 0,9% | 0,07 | 0,8% | 0,04 | 0,4% | |||||||
| Hb D | 40,6 | 0,19 | 0,5% | 0,06 | 0,2% | 0,05 | 0,1% | |||||||
| Hb E | 22,6 | 0,23 | 1,0% | 0,02 | 0,1% | 0,09 | 0,4% |
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| Fraction | Ranges of % tested | Between-day | Total reproducibility(*) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Min Value | Max Value | SD min | SD max | CV min | CV max | SD min | SD max | CV min | CV max | |
| Hb A | 44,2 | 97,3 | 0,02 | 0,22 | 0,0% | 0,5% | 0,05 | 0,40 | 0,0% | 0,8% |
| Hb A2 | 2,6 | 6,5 | 0,02 | 0,05 | 0,7% | 1,3% | 0,05 | 0,16 | 1,4% | 6,0% |
| Hb F | 26,8 | 0,07 | 0,2% | 0,19 | 0,7% | |||||
| Hb S | 17,5 | 0,13 | 0,7% | 0,17 | 1,0% | |||||
| Hb C | 8,9 | 0,10 | 1,1% | 0,15 | 1,7% | |||||
| Hb D | 40,6 | 0,12 | 0,3% | 0,24 | 0,6% | |||||
| Hb E | 22,6 | 0,06 | 0,3% | 0,26 | 1,1% |
(*) Total reproducibility includes : within-capillary, between-capillary, between-run and between
b. Linearity
A linearity study was performed per CLSI EP06-A: Evaluation of Quantitative Measuring Procedures; A Statistical Approach. The results for percentage (%) of hemoglobin fractions were analyzed using statistical tools recommended by CLSI.
Mixtures of two different blood samples were mixed at different proportions and tested in triplicate and analyzed using the CAPI 3 HEMOGLOBIN(E) procedure on the CAPILLARYS 3 instrument. The tests were determined to be linear within the entire range studied for each of the following hemoglobins fractions:
Hb A ( 1.0 -97.3%), HbS (1.1-89.7%), Hb A2 (0.2-9.1%), Hb F (0.5-83.1%), Hb C (0.3-82.0%), Hb D (1.1-43.5%), Hb E (0.3-86.9%).
c. Limit of Blank (LOB), Limit of Detection (LOD), Limit of Quantitation (LOQ)
Per CLSI guidelines , EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantitation , studies were conducted using the CAPI 3 HEMOGLOBIN(E) procedure using the CAPILLARYS 3 for each hemoglobin fraction using five (5) different blood samples. Results are as follows:
| Fraction | LOB % | LOD % | LOQ % |
|---|---|---|---|
| Hb A | 0,1 | 1,0 | 1,0 |
| Hb A2 | 0,1 | 0,2 | 0,2 |
| Hb F | 0,2 | 0,4 | 0,5 |
| Hb S | 0,1 | 0,9 | 1,1 |
| Hb C | 0,1 | 0,3 | 0,3 |
| Hb D | 0,1 | 0,7 | 1,1 |
| Hb E | 0,1 | 0,3 | 0,3 |
d. Analytical Specificity
Interference studies were conducted following CLSI, EP7-A2, Interference Testing in Clinical Chemistry. Three (3) blood samples (one blood sample with normal Hb A2 level, one blood sample with increased Hb A2 level and one blood sample with Hb S). Each sample was analyzed 3 times for reproducibility using CAPI 3 HEMOGLOBIN(E) procedure and CAPILLARYS 3 TERA instrument :
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| Interferents | Maximum Concentration |
|---|---|
| Bilirubin | 20.6 mg/dL , or 352 µmol/L |
| Triglycerides | 2.2 g/dL , or 25.1 mmol/L |
e. Comparison Studies
Method comparison studies were preformed using CAPI 3 HEMOGLOBIN(E) assay using the CAPILLARYS 3 TERA instrument. The studies were conducted following CLSI, EP09-A2-IR, Method Comparison and Bias Estimation Using Patient Samples-200 edition.
The samples were provided by hospitals and laboratories international and United States. A total of 304 samples (180 without hemoglobin variant /124 with hemoglobin variant) were analyzed.
The measured values of hemoglobin fractions from both procedures were analyzed by three regression statistical procedures. The results of regression analysis are tabulated below:
Site 1:
The levels of hemoglobin fractions were measured in 153 blood samples, including 64 samples with hemoqlobin variants, both by electrophoretic separations obtained with the CAPI 3 HEMOGLOBIN(E) procedure performed with the CAPILLARYS 3 instrument and a commercially available capillary electrophoresis technique for hemoglobin analysis (reference).
| Fraction | Number of samples | Correlation coefficient | Ordinary linear regression | | Weighted Deming regression | | Passing-Bablok regression | | Range of Hb % values
CAPI 3 HEMOGLOBIN(E) |
|----------|-------------------|-------------------------|----------------------------|-------|----------------------------|-------|---------------------------|-------|----------------------------------------------|
| | | | y-intercept | Slope | y-intercept | Slope | y-intercept | Slope | |
| Hb A | 150 | 1.000 | -0.993 | 1.010 | -0.703 | 1.007 | -0.994 | 1.010 | 16.9 - 98.7 |
| Hb A2 | 148 | 0.998 | 0.005 | 0.986 | -0.032 | 1.000 | -0.050 | 1.000 | 0.5 - 9.2 |
| Hb F | 22 | 1.000 | -0.008 | 1.009 | 0.049 | 0.999 | 0.027 | 1.009 | 0.8 - 83.1 |
| Fraction | Number of samples | Correlation coefficient | Ordinary linear regression | | Weighted Deming regression | | Passing-Bablok regression | | Range of Hb % values
CAPI 3 HEMOGLOBIN(E) |
| | | | y-intercept | Slope | y-intercept | Slope | y-intercept | Slope | |
| Hb S | 13 | 1,000 | -0,025 | 1,010 | -0,127 | 1,013 | -0,122 | 1,013 | 1,8 - 89,7 |
| Hb C | 13 | 1,000 | 0,099 | 1,008 | 0,009 | 1,009 | -0,163 | 1,018 | 2,0 - 89,5 |
| Hb D | 9 | 1,000 | -0,068 | 1,015 | 0,063 | 1,008 | -0,032 | 1,015 | 3,3 - 43,7 |
| Hb E | 13 | 1,000 | 0,183 | 1,001 | -0,054 | 1,015 | -0,080 | 1,020 | 5,0 - 86,9 |
Normal hemoglobins
This study demonstrated a perfect correlation between the 2 analysis procedures for the Hb A, Hb A2, Hb F, Hb S, Hb C, Hb D and Hb E quantitative determination.
All abnormal hemoglobins or abnormal levels of normal hemoglobins detected with the CAPI 3 HEMOGLOBIN(E) procedure performed with the CAPILLARYS 3 instrument were in agreement with the reference procedure. There was no case observed of false positive, i.e., detection of an abnormal band or abnormal level of a normal band where no such abnormality existed.
12
Site 2
The levels of hemoglobin fractions were measured in 151 blood samples, including 60 samples with hemoglobin variants, both by electrophoretic separations obtained with the CAPI 3 HEMOGLOBIN(E) procedure performed with the CAPILLARYS 3 instrument and a commercially available capillary electrophoresis technique for hemoglobin analysis (reference).
The measured values of hemoglobin fractions from both procedures were analyzed by three regression statistical procedures.
Normal hemoglobins
| Fraction | Number of
samples | Correlation
coefficient | Ordinary linear
regression | | Weighted Deming
regression | | Passing-Bablok
regression | | Range of Hb % values
CAPI 3 HEMOGLOBIN(E) |
|----------|----------------------|----------------------------|-------------------------------|-------|-------------------------------|-------|------------------------------|-------|----------------------------------------------|
| Hb A | 148 | 1,000 | -1,928 | 1,020 | -1,553 | 1,015 | -1,379 | 1,014 | 15,7 - 98,3 |
| Hb A2 | 151 | 0,987 | -0,005 | 1,017 | 0,004 | 1,012 | 0,000 | 1,000 | 0,9 - 6,1 |
| Hb F | 30 | 0,999 | -0,127 | 1,009 | -0,021 | 0,965 | 0,000 | 1,000 | 0,5 - 34,3 |
Hemoglobin variants
| Fraction | Number of
samples | Correlation
coefficient | Ordinary linear
regression | | Weighted Deming
regression | | Passing-Bablok
regression | | Range of Hb % values
CAPI 3 HEMOGLOBIN(E) |
|----------|----------------------|----------------------------|-------------------------------|-------|-------------------------------|-------|------------------------------|-------|----------------------------------------------|
| Hb S | 33 | 0,999 | 0,475 | 1,006 | 0,105 | 1,015 | 0,272 | 1,011 | 25,8 - 78,3 |
| Hb C | 11 | 0,997 | -1,431 | 1,069 | -1,332 | 1,066 | -1,480 | 1,067 | 25,2 - 37,3 |
| Hb E | 4 | 1,000 | 0,625 | 1,002 | 0,630 | 1,002 | 0,660 | 1,001 | 22,1 - 91,9 |
This study demonstrated a perfect correlation between the 2 analysis procedures for the Hb A, Hb A2, Hb F, Hb S, Hb C and Hb E quantitative determination.
All abnormal hemoglobins or abnormal levels of normal hemoglobins detected with the CAPI 3 HEMOGLOBIN(E) procedure performed with the CAPILLARYS 3 instrument were in agreement with the reference procedure. There was no case observed of false positive. i.e., detection of an abnormal band or abnormal level of a normal band where no such abnormality existed
The combined number of abnormal hemoglobin variants detected in the combined comparison studies is as follows: HbS=46, HbC = 24, HbD=9 HbE= 17
All abnormal hemoglobins and abnormal levels of normal hemoglobins detected were in agreement with the comparative system and clinical diagnosis. There were no observed false positives (i.e. detection of an abnormal band or abnormal level of a normal band where no such abnormal existed).
6. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.