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K Number
K232027
Device Name
CAPI 3 NEONAT Hb, CAPILLARYS 3 DBS Instrument
Manufacturer
Sebia
Date Cleared
2024-04-04

(272 days)

Product Code
GKA
Regulation Number
864.7415
Type
Traditional
Panel
HE
Reference & Predicate Devices
K091283
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The CAPI 3 NEONAT Hb kit is intended as a qualitative screen for the detection of normal hemoglobins (F and A) and abnormal hemoglobins (S, C, E, D and Bart's) in blood from human new-born collected on filter paper. This analysis is performed by capillary electrophoresis with the CAPILLARYS 3 DBS instrument.

The CAPILLARYS 3 DBS instrument is a capillary electrophoresis based automated analyzer which performs a complete hemoglobin profile for the qualitative analysis of hemoglobins (A, F, S, C, D, E and Bart's). The assay is performed on the hemolysate of whole blood samples previously collected on filter paper.

The test result must be interpreted in conjunction with other biological and clinical findings. In case of abnormal hemoglobin presence, it should be confirmed by additional tests as per local recommendations. The device is intended for professional use only.

For In Vitro Diagnostic Use only.

Device Description

The CAPI 3 NEONAT Hb kit is intended for the detection of normal hemoglobins (F and A) and abnormal hemoglobins (S, C, E, D and Bart's) in blood from human new-born collected on filter paper. The resulting electrophoregrams are automatically evaluated for pattern abnormalities with identification of normal and pathological patterns.

The CAPILLARYS 3 DBS 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 DBS instrument has silica capillaries functioning in parallel allowing 12 simultaneous analyses. 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 wavelength specific to hemoglobins. Before each run. the capillaries are washed with a wash solution and prepared for the next analysis with buffer.

The CAPILLARYS 3 DBS performs all sequences automatically to obtain a complete hemoglobin profile for the qualitative analysis of hemoglobins. The assay is performed on the hemolysate of whole blood samples previously collected on Guthrie filter paper and punched to obtain a paper circle.

By using alkaline pH buffer. normal and abnormal (or variant) hemoglobins are detected in the following order. from cathode to anode: C, A2, E, S, D, F, degraded F, A, degraded A and Bart's. Variants generated by the mutation of the y chain may appear in different zones of the electrophoretic pattern. The carbonic anhydrase is not visualized on the hemoglobin electrophoretic patterns with capillary electrophoresis.

AI/ML Overview

The provided text describes the analytical performance data for the CAPI 3 NEONAT Hb kit using the CAPILLARYS 3 DBS instrument. This device is intended for qualitative screening of normal and abnormal hemoglobins in newborn blood samples.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implicitly demonstrated through its performance in various analytical studies, primarily focusing on 100% identification pattern concordance and high positive/negative percent agreement (PPA/NPA) compared to a reference method.

Acceptance Criterion (Implicit)Reported Device Performance
Precision: Consistent identification of hemoglobin patterns across different capillaries, reagent lots, instruments, and days.Between capillaries, lots, instruments, and days: All tested samples (6 new-born whole blood samples with various patterns and 2 controls) showed 100% identification pattern concordance across all conditions. Total concordance (95% CI):
  • Between capillaries: 100% (96.2%; 100.0%)
  • Between lots: 100% (96.7%; 100.0%)
  • Between instruments: 100% (96.7%; 100.0%)
  • Between days: 100% (98.0%; 100.0%) |
    | Analytical Specificity/Interference: No significant interference from common endogenous substances. | No interference was detected from conjugated bilirubin (up to 40 mg/dL), unconjugated bilirubin (up to 40 mg/dL), and triglycerides (up to 1500 mg/dL). |
    | Qualitative Method Comparison: High agreement with a commercially available capillary electrophoresis reference procedure. | Internal Study:
  • Positive Percent Agreement (PPA): 100% (95% CI: 94.6%; 100.0%)
  • Negative Percent Agreement (NPA): 100.0% (95% CI: 94.9%; 100.0%)
    External Study No. 1 (USA):
  • PPA: 100.0% (95% CI: 98.1%; 100.0%)
  • NPA: 100.0% (95% CI: 98.2%; 100.0%)
    External Study No. 2 (Spain):
  • PPA: 100.0% (95% CI: 96.9%; 100.0%)
  • NPA: 100.0% (95% CI: 96.9%; 100.0%) |

Study Details Proving Acceptance Criteria

  1. Sample sizes used for the test set and the data provenance:

    • Precision Studies:

      • Identification Pattern Concordance: 8 different samples (6 newborn whole blood samples with FA, FAS, FAC, FAD, FAE, FA Bart's patterns, and 2 controls with AF, AFSC patterns).
        • Between capillaries: 12 analyses per sample (total 96 analyses).
        • Between lots: 6 analyses per sample (total 114 analyses).
        • Between instruments: 6 analyses per sample (total 114 analyses).
        • Between days: 10 analyses per sample (total 190 analyses).
      • Precision using controls (CLSI EP05-A3): 2 control samples (AF and AFSC patterns).
        • Within-laboratory: 480 analyses per control (total 960).
        • Between-lots: 90 analyses per control (total 180).
        • Between-instruments: 90 analyses per control (total 180).
      • Data Provenance: Not explicitly stated for precision samples' geographic origin, but samples include "new-born whole blood samples" and controls. The CLSI guidelines are international standards.

    • Analytical Specificity/Interference: Not explicitly stated how many samples were used, but the study evaluated common interfering factors at specified concentrations.

    • Qualitative Method Comparison:

      • Internal Study: 138 different newborn whole blood samples (71 normal and 67 pathological with variants S, C, D, E, and Bart's).
        • Data Provenance: Samples provided by 5 laboratories in France, Thailand, and Panama. This study was likely retrospective, using banked samples.
      • External Study No. 1: 411 different newborn whole blood samples (210 normal samples and 201 pathological samples with variants S, C, D, E, and Bart's).
        • Data Provenance: Samples analyzed in a laboratory based in the United States of America. This study was likely retrospective.
      • External Study No. 2: 240 different newborn whole blood samples (120 normal samples and 120 pathological samples with variants S, C, D, E, and Bart's).
        • Data Provenance: Samples analyzed in a laboratory based in Spain. This study was likely retrospective.

  2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

    • The document implies that the ground truth for the test set (qualitative method comparison) was established by a "commercially available capillary electrophoresis procedure for hemoglobin analysis (reference)." It does not mention the use of human experts for ground truth establishment. This suggests the reference method itself serves as the "gold standard" for comparison, not human interpretation in this context.

  3. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

    • No human adjudication method is described. The comparison is directly between the candidate device and the "reference procedure."

  4. 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:

    • No MRMC or human-in-the-loop study involving human reader improvement with AI assistance was performed or reported. This device is an in vitro diagnostic (IVD) instrument that provides qualitative results directly, not an AI-assisted diagnostic imaging tool requiring human interpretation improvement studies.

  5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

    • Yes, the performance data presented (precision, analytical specificity, method comparison) reflects the standalone performance of the CAPI 3 NEONAT Hb kit and CAPILLARYS 3 DBS instrument, as it is an automated IVD device. The results are automatically evaluated for pattern abnormalities with identification of normal and pathological patterns.

  6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

    • The ground truth for the qualitative method comparison studies was established by a "commercially available capillary electrophoresis procedure for hemoglobin analysis (reference)." This is an established laboratory method serving as the analytical gold standard.

  7. The sample size for the training set:

    • This document describes analytical performance studies of a medical device, not a machine learning or AI algorithm development. Therefore, there is no mention of a "training set" in the context of machine learning. The device's underlying technology is capillary electrophoresis, and its performance is validated through traditional IVD analytical studies, not typically through machine learning training and testing paradigms that would involve a distinct "training set."

  8. How the ground truth for the training set was established:

    • As this is not an AI/ML device in the sense of requiring a "training set" for model development, this question is not applicable to the information provided.

§ 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.