FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview

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 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

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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided FDA 510(k) summary:

Device: CAPI 3 HEMOGLOBIN(E) kit used with SEBIA CAPILLARYS 3 TERA instrument.

Intended Use: For the separation of normal hemoglobins (A, A2, F) in human venous blood and for the detection of major hemoglobin variants (S, C, E, D) by capillary electrophoresis. It provides quantitative analysis of fractions A, A2, F and detection of variants S, C, E, D.

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a separate section with specific numerical thresholds for all performance metrics. Instead, it demonstrates performance through various studies and implies that the observed performance (e.g., correlation coefficients close to 1, low CVs for precision) is acceptable for substantial equivalence to a predicate device.

However, based on the provided performance data, we can infer the implied acceptance criteria from the reported excellent results, particularly for method comparison:

Performance Metric	Implicit Acceptance Criteria (Inferred from reported data)	Reported Device Performance
Precision/Reproducibility	Low coefficients of variation (CV%) for all hemoglobin fractions (Hb A, Hb A2, Hb F, Hb S, Hb C, Hb D, Hb E) across within-run, between-run, between-day, between-instrument, and total reproducibility studies.	7-days Reproducibility (3 instruments, 1 lot):

Hb A Total CV: 0.0% - 1.3%
Hb A2 Total CV: 1.3% - 6.5%
Hb F Total CV: 2.5%
Hb S Total CV: 0.6%
Hb C Total CV: 1.4%
Hb D Total CV: 1.4%
Hb E Total CV: 1.6%
20-days Reproducibility (1 instrument, 1 lot):
Hb A Total CV: 0.0% - 0.8%
Hb A2 Total CV: 1.4% - 6.0%
Hb F Total CV: 0.7%
Hb S Total CV: 1.0%
Hb C Total CV: 1.7%
Hb D Total CV: 0.6%
Hb E Total CV: 1.1% |
| Linearity | Demonstrated linearity across the clinically relevant range for all hemoglobin fractions. | 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%) |
| Limit of Blank (LOB) | Very low LOB values. | Hb A, Hb A2, Hb F, Hb S, Hb C, Hb D, Hb E: All 0.1% or 0.2% |
| Limit of Detection (LOD) | Low LOD values indicating sensitivity to detect low concentrations. | Hb A: 1.0%, Hb A2: 0.2%, Hb F: 0.4%, Hb S: 0.9%, Hb C: 0.3%, Hb D: 0.7%, Hb E: 0.3% |
| Limit of Quantitation (LOQ) | Low LOQ values indicating ability to accurately quantify at low concentrations. | Hb A: 1.0%, Hb A2: 0.2%, Hb F: 0.5%, Hb S: 1.1%, Hb C: 0.3%, Hb D: 1.1%, Hb E: 0.3% |
| Analytical Specificity (Interference) | Insignificant interference from common substances like bilirubin and triglycerides at elevated levels. | Interference studies showed that Bilirubin (20.6 mg/dL) and Triglycerides (2.2 g/dL) did not significantly interfere with the analytical performance. (The document states studies were "conducted" and lists maximum concentrations without giving specific results of non-interference, but the conclusion implies acceptability). |
| Method Comparison (Correlation) | Very high correlation coefficients (close to 1.000) for all hemoglobin fractions and variants when compared to a reference method, along with slopes near 1 and y-intercepts near 0 in regression analysis, demonstrating strong agreement. | Site 1:
Hb A: 1.000 (Slope ~1.01, Y-intercept ~-1.0 to -0.7)
Hb A2: 0.998 (Slope ~1.00, Y-intercept ~0.0 to -0.05)
Hb F: 1.000 (Slope ~1.00-1.01, Y-intercept ~-0.008 to 0.05)
Hb S, C, D, E: All 1.000 (Slopes ~1.01-1.02, Y-intercepts close to 0)
Site 2:
Hb A: 1.000 (Slope ~1.01-1.02, Y-intercept ~-1.9 to -1.4)
Hb A2: 0.987 (Slope ~1.00-1.01, Y-intercept ~0.0 to -0.005)
Hb F: 0.999 (Slope ~0.96-1.00, Y-intercept ~-0.12 to 0.0)
Hb S, C, E: All 0.997 - 1.000 (Slopes ~1.00-1.06, Y-intercepts close to 0 or small variations) |
| False Positives (Variant Detection) | No false positives in the detection of abnormal hemoglobin bands or abnormal levels of normal bands. | "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." This statement is made for both Site 1 and Site 2 studies. |

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Test Set (Method Comparison): A total of 304 samples were used across two sites.
- Site 1: 153 samples (64 with hemoglobin variants)
- Site 2: 151 samples (60 with hemoglobin variants)
Data Provenance: The samples were "provided by hospitals and laboratories international and United States." The study design is implied to be retrospective, as samples were collected and then analyzed by both the candidate and reference methods.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The document does not explicitly state the number of experts used to establish ground truth or their specific qualifications (e.g., "radiologist with 10 years of experience").
The "reference procedure" used for comparison is described as "a commercially available capillary electrophoresis technique for hemoglobin analysis." This implies that the ground truth for quantitative values and variant identification was established by a previously validated and accepted clinical laboratory method. For abnormal hemoglobin detection, the agreement with "clinical diagnosis" is also mentioned, suggesting that expert clinical assessment contributed to the overall understanding of the ground truth.

4. Adjudication Method (for the test set)

The document does not explicitly describe an adjudication method (e.g., 2+1, 3+1).
The comparison studies directly compare the quantitative results and variant detection of the candidate device against a "reference procedure." Any discrepancies would typically be investigated, but the method for their resolution is not detailed. The statement of "no observed false positives" implies a direct agreement determination.

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

No, an MRMC comparative effectiveness study was not done.
This device is an in-vitro diagnostic (IVD) for laboratory use that provides quantitative measurements and detects specific analytes. It does not involve human readers interpreting images or data for diagnosis in a way that would typically warrant an MRMC study to assess AI-assisted human performance improvement. The performance is assessed by comparison to a reference laboratory method.

6. Standalone Performance Study (algorithm only without human-in-the-loop performance)

Yes, the provided performance data primarily represents the standalone performance of the device.
The CAPI 3 HEMOGLOBIN(E) kit processes samples and provides quantitative results and variant detection via the automated CAPILLARYS 3 TERA instrument. The precision, linearity, LOB/LOD/LOQ, and analytical specificity studies, as well as the method comparison studies, evaluate the device's inherent analytical performance without direct human intervention in the result generation or interpretation (beyond standard laboratory procedures for running the instrument and reviewing results, which is inherent to any IVD). The measurements and variant identifications are generated by the instrument's software.

7. Type of Ground Truth Used

The ground truth for the test set was established primarily through:

Reference Procedure/Comparative System: A "commercially available capillary electrophoresis technique for hemoglobin analysis" (predicate device or similar accepted method). This acts as the gold standard for quantitative values and identification of hemoglobin fractions and variants.
Clinical Diagnosis: For the detection of abnormal hemoglobins, agreement with "clinical diagnosis" is also mentioned, suggesting that patient medical records and expert clinical assessment contributed to confirming the presence or absence of variants.

8. Sample Size for the Training Set

The document does not explicitly state the sample size for the training set.
As this is a 510(k) submission for an IVD kit and instrument, it's likely that extensive internal development and validation data would have been generated during the device's creation (which can be likened to a training/development phase), but this specific information is not typically required in the 510(k) summary provided. The focus of the 510(k) is often on the clinical validation/test set performance.

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

The document does not explicitly describe how the ground truth for a training set was established.
Given that this is an analytical device, the "training" (development) process would involve optimizing reagents, instrument parameters, and algorithms to accurately measure hemoglobin fractions and identify variants. This would typically involve using well-characterized control materials, spiked samples, and patient samples with known hemoglobin profiles (established by reference methods, genetic testing, or clinical diagnosis) to calibrate and refine the system, but the specifics are not detailed in this summary.