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Immunoglobulin Isotypes (GAM) for the EXENT Analyser:

The Immunoglobulin Isotypes (GAM) for the EXENT Analyser is a MALDI-TOF mass spectrometry immunoassay that is used in conjunction with the Binding Site Optilite IgG, IgA and IgM assays for the semi-quantitative in vitro measurement of monoclonal IgG, IgA, and IgM as a reflex test in serum for patients with a result suggestive of the presence of monoclonal immunoglobulins by serum protein electrophoresis (gel or capillary zone electrophoresis), or with an abnormal serum free light chain concentration and free light chain ratio result.

The assay is intended for use as an aid in the evaluation of monoclonal gammopathy of undetermined significance (MGUS); and as an aid in the diagnosis of smouldering multiple myeloma (SMM), multiple myeloma (MM), Waldenström's macroglobulinaemia, and AL amyloidosis.

Assay results should be used in conjunction with other laboratory and clinical findings.

EXENT Analyser:

The EXENT Analyser is an automated analyser intended for the qualitative and quantitative in vitro measurement of analytes in human body fluids used in conjunction with the EXENT assays. The device is designed for professional in vitro diagnostic use only and it is not a device for self-testing.

The system consisting of the EXENT® Analyser and the EXENT® assays are intended for the in vitro measurements of analytes in human body fluids. It is designed to provide automation and integration of all the analytical steps (including liquid handling and MALDI-ToF mass spectrometry). The EXENT Analyser is designed to be used solely in combination with EXENT assays to measure a variety of analytes depending on the reagents. The device is designed for professional use only and it is not a device for self-testing.

The EXENT Analyser combines automated immunoassay with readout by MALDI-ToF mass spectrometry. It is a modular analyser, and the major components are described in Table 3 and illustrated schematically in Figure 1.

The EXENT-iP500 component is an automated liquid handler that prepares human body fluids using the EXENT assay specific reagents. The samples are prepared using magnetic beads that are coated with isotype-specific antibodies. Any unbound material is washed away during the sample preparation process. The EXENT-iP500 also manages the transfer of the prepared patient sample to the MALDI plate.

The EXENT-iX500 component is a MALDI-ToF mass spectrometer. Signals are produced by ionizing the compound or biological material under investigation and separating the resulting ions by means of an electrical and magnetic field according to their mass-to-charge ratios. The EXENT-iX500 is used to read samples prepared by the EXENT-iP500.

The EXENT-iQ software integrates sample preparation and MALDI-ToF mass spectrometry and is used for data storage and processing. It is the primary user interface used by the user to review and release results.

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The Kenota 1 Total IgE is an in vitro test system intended for semi-quantitative measurement of total IgE in human capillary whole blood on the Kenota 1 instrument. It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE-mediated allergic disorders in conjunction with other clinical findings, and is to be used in allergist/immunologist offices.

The Kenota 1 Total IgE test system consists of Kenota 1 Total IgE Cartridge (reagent) and other test components, including Kenota 1 Total IgE External Controls (EC), Kenota 1 (instrument), Kenota 1 Sample Collection Kit (SCK), and Kenota 1 Developing Solution.

Here's an analysis of the provided text to extract acceptance criteria and study details for the Kenota 1 Total IgE device:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for semi-quantitative classification are implied by the "Percent in ATE" (Allowable Test Error) within the method comparison study, where ATE means the result is within one category of the comparator. While explicit thresholds for numeric precision are provided, the primary acceptance for classification appears centered around this categorical agreement.

Study Information

1. Sample Size Used for the Test Set and Data Provenance:

   • Method Comparison Study: 357 samples were used for comparison analysis out of 411 eligible subjects (6 to 80 years).
   • Data Provenance: Subjects were "recruited as representative of the intended use population, for patients with eczema or atopy coming in for regular appointments to the allergy specialty care clinics." Data was collected from three CLIA-waived sites in the US (likely prospective, given the recruitment and paired sample collection for the study).
   • Fingerstick Repeatability Study: 355 fresh fingerstick whole blood samples.
   • Data Provenance: Conducted in three CLIA-waived sites in the U.S. (likely prospective).
   • Reference Interval Study: 117 fingerstick samples.
   • Data Provenance: Collected from adult (N=95, 22-79 years) and pediatric (N=22, 8 to <22 years) volunteer donors from populations in North Carolina, Virginia, and Minnesota, USA (likely prospective).

2. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications:
   For the method comparison study, the ground truth was established by a predicate device: "ImmunoCAP Total IgE (K161899)", not by human experts. The predicate device is a quantitative measurement system for total IgE. The text does not mention human experts establishing ground truth for the test set.

3. Adjudication Method for the Test Set:
   Not applicable, as the ground truth was based on a predicate device, not expert consensus requiring adjudication.

4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size:
   No, an MRMC comparative effectiveness study was not done. The study compares the Kenota 1 device's performance against a predicate device, not human readers with and without AI assistance.

5. If a Standalone (Algorithm Only) Performance Was Done:
   Yes, the entire performance section, including analytical studies (precision, linearity, interference, detection limit) and comparison with the predicate device, represents a standalone performance evaluation of the Kenota 1 Total IgE system. It assesses the device's accuracy and reliability as a direct test system.

6. Type of Ground Truth Used:

   • Method Comparison Study: The ground truth was established by the predicate device, ImmunoCAP Total IgE (K161899). This is a legally marketed quantitative test system for total IgE.
   • Analytical Studies (e.g., Precision, Linearity, Detection Limit, Interference): Ground truth was established through spiked samples, pooled samples, or samples with known IgE concentrations measured by validated quantitative laboratory methods or reference materials (e.g., WHO 3rd International Standard Human IgE).

7. Sample Size for the Training Set:
   The document does not provide details on a separate training set for the device itself. The studies described are performance validation studies, usually analogous to a test set for a machine learning model, rather than a training set. For in vitro diagnostic devices like this, calibration (9-level multipoint calibration performed at the manufacturing site) is part of the "training" process. The calibrators used were 0, 2.17, 6.2, 18.6, 37.2, 93, 310, 620, and 930 kU/L.

8. How the Ground Truth for the Training Set Was Established:
   As mentioned above, the device itself is an immunoassay system, not an AI/ML algorithm requiring a distinct "training set" in the conventional sense. Its "training" or calibration involves tying its measurements to a recognized standard.

   • Calibration Ground Truth: The working calibrators for the Kenota 1 Total IgE were "traceable to the primary reference material WHO 3rd International Standard Human IgE (11/234)." This international standard serves as the ground truth for establishing the device's measurement scale.

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In-vitro diagnostic reagents for the quantitative determination of immunoglobulins (IgG. IgA and IgM) in human serum, heparinized and EDTA plasma, and IgG in human urine and cerebrospinal fluid (CSF) by means of immunonephelometry on the BN II and BN ProSpec® System. Measurements of IgG aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

The N Antiserum to Human IgG reagent containing animal serum, produced by immunization of rabbits with highly purified human immunoglobulin (< 3.5 g/L). The reagent is a ready-to-use liquid containing preservatives. There are two product variants available. One variant (REF OSAS11) contains 1 x 2 mL vial / box, and the other variant (REF OSAS19) contains 1 x 5 mL vial / box. Proteins contained in human body fluids form immune complexes in an immunochemical reaction with specific antibodies. These complexes scatter a beam of light passed through the sample. The intensity of the scattered light is proportional to the concentration of the relevant protein in the result is evaluated by comparison with a standard of known concentration.

The provided text describes a special 510(k) premarket notification for a modified device, "N Antisera to Human Immunoglobulins (IgG, IgA, and IgM)". The sole modification is the addition of a High Dose Hook (HDH) effect claim for IgG in cerebrospinal fluid (CSF) samples.

Here's a breakdown of the requested information based on the provided document:

1. A table of acceptance criteria and the reported device performance

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Sample Size: The study used a "CSF high sample pool." The exact number of individual patient samples contributing to this pool (if multiple were pooled) is not specified. However, the study involved a dilution scheme with twelve (12) individual dilution levels, including the neat sample.
• Data Provenance: Not explicitly stated. The manufacturer is Siemens Healthcare Diagnostics Products GmbH, located in Marburg, Germany, which suggests the study was likely conducted in Germany or a similar geographic region. It is implicitly a prospective study designed to evaluate the HDH effect for the modified device.

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 section is not applicable as the device is an in-vitro diagnostic reagent for quantitative determination, not an imaging or interpretive device that would typically require expert ground truth establishment in the described manner. The "ground truth" for this type of test is the quantitatively measured concentration of IgG in a sample, established through laboratory methods and comparison to known standards.

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

This section is not applicable. Adjudication methods like 2+1 or 3+1 are typically used for establishing ground truth in interpretive studies (e.g., radiologists reviewing images). For a quantitative in-vitro diagnostic test, the "ground truth" is determined by the analytical method itself against known standards.

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. The device is an in-vitro diagnostic reagent, not an AI-assisted diagnostic tool or an imaging device requiring human reader interpretation. No MRMC study was performed.

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

This refers to the performance of the analytical system (N Antisera reagent on BN II System) without human intervention in the measurement process. The HDH study performed is a standalone performance evaluation of the reagent/instrument system. The acceptance criteria and performance data in the table above demonstrate this standalone performance.

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

For this in-vitro diagnostic device, the "ground truth" for the High Dose Hook study was established by creating known dilutions of a high-concentration CSF sample, which were then measured by the device. The reported concentrations for these dilutions serve as the reference. The ultimate analytical ground truth for the quantitative measurement itself is tied to international standards like ERM-DA470k/IFCC (as stated in the "Traceability/Standardization" section).

8. The sample size for the training set

This document does not describe the development or training of a machine learning model, so there is no training set in the typical sense. The "training" for such a diagnostic test involves method development, optimization, and validation using various samples and controls, but these are not referred to as a "training set" for an algorithm.

9. How the ground truth for the training set was established

As there is no training set for an algorithm, this question is not applicable.

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System reagent for the quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on Beckman Coulter AU/DxC AU analyzers. The measurement of IgG aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

The device consists of two reagents: R1 buffer (Tris buffer pH 7.2, polyethylene glycol 6000) and R2 (goat anti-IgG antiserum). The reagents contain sodium azide as preservative.

When a sample is mixed with R1 buffer and R2 antiserum solution, human IqG reacts specifically with anti-human IgG antibodies to yield insoluble aggregates. Immune complexes formed in solution scatter light in proportion to their size, shape, and concentration. Turbidimeters then measure the reduction of incidence light due to reflection, absorption, or scatter. The decrease in intensity of light transmitted (increase in absorbance) through particles suspended in solution is a result of complexes formed during the antigen-antibody reaction.

The Beckman Coulter Immunoglobulin G (IgG) reagent for quantitative determination of IgG immunoglobulins in human serum, plasma, and cerebrospinal fluid on Beckman Coulter AU/DxC AU analyzers, device K221114, underwent various non-clinical (bench) studies to demonstrate substantial equivalence to its predicate device (K162208).

Here is a summary of the acceptance criteria and reported device performance based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample sizes for the test set and data provenance:

• Method Comparison:
  • Serum: 147 samples
  • CSF: 114 samples
  • Data Provenance: Not explicitly stated regarding country of origin or whether retrospective/prospective. The studies were conducted "using patient correlation studies", suggesting human patient samples were used.
• Linearity/Reportable Range: Each dilution was assayed in quadruplicate on a DxC 500 AU analyzer. High and low pools were prepared and inter-diluted. Number of distinct patient samples used for pooling is not specified.
• Sensitivity (LOB, LOD, LOQ):
  • LOB: 72 blank replicates per reagent lot (4 blank native serum samples 'analyte-depleted' run n=6 for 3 days).
  • LOD and LOQ: 500 replicates per reagent lot for each application (10 low-level samples for IgG run 10-fold for 5 days).
• Precision:
  • 20-day study: Not explicitly stated as a number of distinct samples, but samples were tested over 20 days.
  • 5-day study: Not explicitly stated as a number of distinct samples, but samples were tested over 5 days.
• Interference: All test samples were assayed n=5 at two analyte levels. The number of distinct samples for each interferent type is not specified.
• Reference Interval: "Transference approach" used to validate the original IgG serum reference interval. The specific number of samples for the transference study is not detailed.

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

This device is an in vitro diagnostic (IVD) test for quantitative measurement of immunoglobulins. The "ground truth" in this context is the analytically measured concentration of IgG in samples, determined by laboratory methods. Therefore, expert interpretation or consensus as seen in imaging or clinical diagnosis is not directly applicable. The "ground truth" is established by the analytical method itself, calibrated against known standards, and verified through method comparison with predicate devices and established guidelines.

4. Adjudication method for the test set:

Not applicable in the context of quantitative IVD testing. Analytical results are directly compared to predefined acceptance criteria based on industry guidelines (e.g., CLSI).

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:

Not applicable. This is an in vitro diagnostic device, not an AI-assisted diagnostic imaging or clinical decision support tool that involves human readers.

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

The device is an analytical reagent system used on automated analyzers. Its performance is inherently "standalone" in the sense that the instrument and reagent determine the quantitative result without human subjective interpretation of the primary measurement. Human involvement lies in sample preparation, loading, and result interpretation, but not in the analytical measurement itself. The studies described are assessing the performance of this standalone analytical system.

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

The ground truth used for performance evaluation is based on analytical measurements against established standards and comparison to a legally marketed predicate device. For example:

• Method Comparison: Comparison against the predicate device (Beckman Coulter IgG Reagent on DxC 700 AU analyzer) to demonstrate similar quantitative results.
• Linearity/Sensitivity/Precision: Determined by assessing the device's ability to accurately and reproducibly measure known concentrations or concentrations derived from highly characterized samples.
• Reference Interval: Validation of an existing reference interval for the predicate device, implying that the ground truth for this is derived from previously established clinical studies.

8. The sample size for the training set:

Not applicable. This device is a diagnostic reagent, not a machine learning or AI algorithm that requires a "training set" in the conventional sense. The development of the reagent and its methods would involve extensive research and development, but this is distinct from "training data" for an AI model.

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

Not applicable, as there is no "training set" in the context of this IVD device.

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Automated latex enhanced immunoassay for the quantitative in vitro determination of total immunoglobulin E (1gE) in human serum or plasma (EDTA, heparin, citrate) using the ARCHITECT c Systems. The measurement of total IgE is useful in the clinical diagnosis of IgE-mediated allergies, if used in conjunction with other clinical studies.

The Quantia IgE reagent is a suspension of polystyrene latex particles of uniform size coated with mouse anti-human IgE. When a sample containing IgE is mixed with the latex reagent and the reaction buffer included in the kit, agglutination occurs. The degree of agglutination is directly proportional to the concentration of IgE in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates. Methodology: Turbidimetric/Immunoturbidimetric.

The provided document outlines the acceptance criteria and study results for the Quantia IgE assay, a device for quantitatively determining total IgE in human serum or plasma. It's important to note that this document is a 510(k) summary, focusing on demonstrating substantial equivalence to a predicate device after a modification, rather than a comprehensive de novo approval study. Therefore, some information typically found in a de novo clinical trial report (e.g., specific details on training set size, number of experts for training ground truth) might not be explicitly detailed.

Here's an analysis of the provided information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the performance characteristics presented and their comparison to the predicate device or established clinical standards (e.g., CLSI guidelines). The document focuses on demonstrating that the modified device performs as well as the predicate and meets relevant analytical performance metrics.

The table clearly shows that the modified device's performance metrics are either improved (e.g., lower LoD, LoQ, extended stability) or remain comparable to the predicate device, demonstrating that the device meets or exceeds the previous performance. The linearity range was expanded downwards from 25.0 to 20.0 IU/mL. The precision values reported for the subject device are well within the specified acceptance criteria for the predicate.

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

The document provides sample sizes for various analytical validation studies:

• Sample Matrix Comparison:
  • Predicate device: Five sets of 52 paired samples were run (total 260 samples).
  • Subject device: Forty paired samples were run (serum vs. various plasma types).
• Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ):
  • LoB: n ≥ 60 replicates of zero-analyte samples.
  • LoD: n ≥ 60 replicates of low-analyte level samples.
  • LoQ: n ≥ 60 replicates of low-analyte level samples.
• Precision:
  • Control (Level I, Mixture I&II, Level II): 50 replicates each (for predicate data summary).
  • Subject device: 80 replicates for "Panel 50 IU/mL", "Control I", "1:1 Mix Control I and II", "Control II", "Panel 800 IU/mL" (tested in a minimum of 2 replicates, twice per day on 20 days).
  • Additionally, 3 native serum pools (Panel A, B, C) were tested with 48 replicates each (in a minimum of 2 replicates, twice per day on 12 days).

Data Provenance: The document does not explicitly state the country of origin for the data or whether the studies were retrospective or prospective. However, based on the nature of analytical validation studies for an in-vitro diagnostic device, these are typically prospective laboratory studies conducted at the manufacturer's R&D facilities or contracted labs.

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

For an in-vitro diagnostic (IVD) device like Quantia IgE, the ground truth for performance evaluation (e.g., linearity, LoD, LoQ, precision, matrix effects) is established through analytical reference methods and calibrated standards, not human expert review. These studies rely on precise laboratory measurements and established protocols (e.g., CLSI guidelines). Therefore, there are no "experts" in the sense of radiologists reviewing images to establish ground truth.

4. Adjudication Method for the Test Set

Not applicable for analytical performance studies of an IVD. Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies, particularly for diagnostic imaging or subjective assessments, where human agreement on a diagnosis or finding is crucial. Here, the values are quantitative measurements compared to reference values or statistical criteria.

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

Not applicable. This device is an in-vitro diagnostic assay for measuring total IgE levels, not an imaging device or AI-assisted diagnostic tool that would involve human readers interpreting results. Therefore, an MRMC study is irrelevant to its validation.

6. Standalone (Algorithm Only) Performance

This entire submission describes the standalone performance of the Quantia IgE assay, a laboratory test. It is not an "algorithm" in the typical sense of AI, but rather a biochemical assay system. All performance metrics described (linearity, LoD, LoQ, precision, etc.) are characteristics of the assay system itself, without human interpretation beyond standard laboratory procedures and result reporting.

7. Type of Ground Truth Used

The ground truth used for these analytical performance studies is based on:

• Reference Standards/Calibrators: For linearity, LoD, LoQ, and IgE International Standard Recovery, the ground truth is established by using highly characterized, traceable calibrators and reference materials with known concentrations.
• Statistical Definitions/Methodologies: The definitions for LoB, LoD, and LoQ explicitly state how they are determined using a certain number of replicates of zero-analyte or low-analyte samples, and statistical calculations (e.g., 95th percentile, mean + 2 SD).
• Established CLSI Protocols: The studies explicitly state that they were performed based on guidance from CLSI (Clinical and Laboratory Standards Institute) protocols, such as NCCLS EP6-A (now EP06), EP17-A2, EP07-A2, EP37, and EP05-A3. These protocols outline the scientifically accepted methods for establishing analytical performance characteristics.

8. Sample Size for the Training Set

This document describes a "Special 510(k)" for a modification to an existing device (Quantia IgE) to demonstrate substantial equivalence. For IVD analytical performance studies, there isn't a "training set" in the machine learning sense alongside a "test set." The studies performed are the analytical validation studies on actual samples or controls covering the relevant range. The sample sizes for these studies are provided above (e.g., 40 paired samples for matrix comparison, ≥60 replicates for LoD/LoQ, 80 replicates for precision controls, 48 for native serum panels).

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

As explained under points 3 and 7, the concept of a "training set" and "ground truth established by experts" for this type of device and study is not directly applicable. The "training" for such an IVD device happens during its development and optimization phases, where various reagent formulations and assay parameters are tested against known concentration panels to achieve optimal performance. The "ground truth" during this development is based on the known concentrations of calibrators and reference materials, and the adherence to established analytical performance standards. The studies detailed in this 510(k) summary are the formal validation (test set) of the modified device's performance.

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The IgE assay is intended for use in the quantitative determination of Total Immunoglobulin E (lgE) concentration in human serum and plasma (lithium heparin, K2-EDTA, K3-EDTA, K3-EDTA) on Beckman Coulter AU/DxC AU clinical chemistry analyzers. The determination aids in the diagnosis of IgEmediated allergic disorders in conjunction with other clinical findings. For in vitro diagnostic use only.

The Total Immunoglobulin E (IgE) reagent kit is in a liquid ready-to-use format designed for optimal performance on Beckman Coulter's AU/DxC AU clinical chemistry analyzers. Each reagent kit contains one buffer reagent (R1), one antibody reagent (R2), and a six-level lot matched calibrator set. The IgE reagent test system utilizes a turbidimetric immunoassay methodology. The AU analyzer measures the change in absorbance at 800 nm to calculate and express the concentration of immunoglobulin E in the test sample based on a stored calibration curve. The IgE assay is traceable to the World Health Organization (WHO) 3rd International Standard 11/234.

The provided document is a 510(k) Premarket Notification for the Beckman Coulter Total Immunoglobulin E (IgE) assay. It describes the device's performance characteristics and how they meet established acceptance criteria, demonstrating substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and study data based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document presents several tables detailing acceptance criteria and study results for different performance parameters.

Table 1: Method Comparison Summary (from Table 9.1.1)

This table compares the Beckman Coulter IgE Assay (candidate device) against the Roche Elecsys IgE II Assay (predicate device).

Table 2: Precision Performance Summary (from Table 9.2.1)

Note: For Pool 1, the document states criteria of "≤5.0 IU/mL" for repeatability and "≤7.0 IU/mL" for total precision. The reported results are 2.1 IU/mL (repeatability) and 2.3 IU/mL (total precision), which meet these criteria.

Table 3: Analytical Range (Linearity) Study Summary (from Table 9.3.1)

Further breakdown of linearity criteria for individual points in Table 9.3.2 shows "Bias Spec" of 10.0 for values ≤100 IU/mL and "%Bias Spec" of 10.0 for values > 100 IU/mL. All individual points "Pass".

Table 4: Detection Limit Study Summary (LoB, LoD & LoQ) (from Table 9.4.1)

Table 5: Anticoagulant Study Results Summary (from Table 9.7.1)

Table 6: In-Use Stability Study Summary (from Table 9.8.1)

Note: For the stability studies, the acceptance criteria are implicitly met if the "Pass" status is indicated after testing beyond the claimed duration, implying that the mean IgE recovery criteria (within 10 IU/mL or 10% of Day 0 mean) were met.

2. Sample sizes used for the test set and the data provenance

• Method Comparison: 136 fresh serum samples spanning the analytical measuring range. Provenance not explicitly stated.
• Precision: Three lots of IgE reagent, tested using two levels of human serum-based quality control material and three patient pools. The experimental design used duplicate sample analysis twice daily over twenty working days (N=80 results for each control/pool). Provenance not explicitly stated.
• Linearity: 15-level linearity test set of inter-diluted patient pools. Provenance not explicitly stated.
• Sensitivity (LoB, LoD, LoQ): LoB evaluated four unique lots of Immunoglobulin (Ig)-depleted human serum. LoD and LoQ used native patient pools diluted with Ig-depleted serum. Provenance not explicitly stated.
• Analytical Specificity (Interference): Test samples containing various interferents (Hemoglobin, Bilirubin, Lipemia, RF, 21 common drugs and concentrations). Specific sample sizes per interferent are not given but are implied by tables (e.g., "Level Tested"). Provenance not explicitly stated.
• Anticoagulant Studies: Freshly drawn serum and plasma from apparently healthy adult volunteer donors. Five specimen tubes were drawn from each donor: one serum tube and one tube of each type of anticoagulant. Sample sizes listed for each anticoagulant type: Na Heparin (N=55), Li Heparin (N=55), K2 EDTA (N=55), K3 EDTA (N=53). Provenance not explicitly stated.
• In-Use Stability: Three levels of quality control material were evaluated. Specific N is not detailed, but implied by the "classical design for sampling, storage, and testing." Provenance not explicitly stated.

Generally, the data provenance (e.g., country of origin, retrospective/prospective) is not explicitly mentioned for any of the studies in the provided document. The studies appear to be prospective analytical performance studies designed to evaluate the device's technical specifications.

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

This device is an in vitro diagnostic (IVD) quantitative assay for Total IgE. The "ground truth" for such devices is typically established through:

• Traceability to International Standards: The IgE assay is stated to be traceable to the World Health Organization (WHO) 3rd International Standard 11/234. This is a primary method of establishing "ground truth" for quantitative lab tests, where the standard itself defines the "true" concentration.
• Reference Methods: The method comparison study uses a legally marketed predicate device (Roche Elecsys IgE II Assay) as the comparative "truth" or reference standard for patient samples. The predicate device itself would have undergone similar rigorous validation, likely traceable to international standards.

Therefore, for this type of device, the concept of "experts" in the sense of clinicians or radiologists establishing a diagnostic "ground truth" for individual cases (like in an imaging study) is not directly applicable. The "ground truth" for the test set is inherent in the certified international standard and the established performance of the predicate device.

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

Not applicable. Adjudication methods like 2+1 or 3+1 consensus are typically used in studies involving subjective interpretation (e.g., imaging reads) to establish a consensus ground truth. For quantitative in vitro diagnostic assays, the "truth" is determined by reference methods, international standards, and analytical evaluation against defined statistical criteria, not by human consensus or adjudication of individual 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

Not applicable. This is an in vitro diagnostic (IVD) assay, not an AI-powered diagnostic imaging device or an AI-assisted interpretation tool for human readers. Therefore, MRMC studies and the concept of "human readers improving with AI assistance" do not apply.

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

Yes, the studies presented are all "standalone" in the sense that they evaluate the performance of the analytical instrument and reagent system itself (the "algorithm only" in a broader sense of the measurement process) without direct human intervention in the result generation or interpretation step for the purpose of the performance evaluation. The device provides a quantitative result (IgE concentration), which is then used by clinicians in conjunction with other clinical findings. The performance data (e.g., precision, linearity, sensitivity, method comparison) directly reflects the device's inherent analytical capabilities.

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

The ground truth for this IgE assay is established primarily through:

• International Standards: The assay's traceability to the WHO 3rd International Standard 11/234 is explicitly stated and serves as the ultimate reference for IgE concentration.
• Reference Measurement Procedures/Predicate Device: For method comparison, the Roche Elecsys IgE II Assay serves as the comparative "reference" for patient samples. This predicate device itself is assumed to be traceable to international standards and validated.
• A priori defined analytical specifications: For precision, linearity, and detection limits, the "ground truth" or acceptance criteria are statistically derived technical specifications (e.g., CV limits, bias limits) that the device must meet to be considered analytically robust.

8. The sample size for the training set

The document does not describe a "training set" in the context of machine learning or AI models because this is not an AI/ML-based device. It is a traditional in vitro diagnostic immunoassay. The performance studies detailed are validation studies for the cleared device.

9. How the ground truth for the training set was established

Not applicable, as there is no "training set" in the AI/ML sense for this traditional IVD product. If "training set" broadly refers to materials used during the development and calibration of the assay, the document indicates that the assay is traceable to the WHO 3rd International Standard 11/234, and a six-level lot-matched calibrator set is included, which would be used to establish the calibration curve for the assay.

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The HYDRASHIFT 2/4 isatuximab kit is intended for the qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis. The HYDRASHIFT 2/4 isatuximab kit is to be used in conjunction with the HYDRAGEL IF kit and the semi-automated HYDRASYS 2 electrophoresis apparatus. The electropherograms are evaluated visually for the presence of specific reactions with the suspect monoclonal proteins. The HYDRASHIFT 2/4 isatuximab kit removes isatuximab IgG kappa interference and enables the visual evaluation of the presence of monoclonal proteins on HYDRAGEL IF kits in patients who have received isatuximab therapy.

For In Vitro Diagnostic use. For Prescription Use Only.

HYDRASYS 2 is a semi-automated multi-parameter system for start-to finish agarose gel electrophoresis: application of samples, migration, drying, staining, destaining and final-stage drying.

Abnormal bands in serum protein electrophoregrams, primarily those in the beta globulin and gamma globulin zones, are always suspected to be monoclonal proteins (M-proteins, paraproteins, monoclonal immunoqlobulins) and therefore, an indication of performing an Immunofixation technique to type and confirm the monoclonal gammopathies.

lsatuximab is a human therapeutic IgG kappa monoclonal antibody and as such, during the clinical monitoring of patients treated with isatuximab, this antibody simulates a band detected by serum protein electrophoresis and immunofixation in the gamma region. It can simulate an endogenous IgG kappa paraprotein.

The HYDRASHIFT isatuximab immunofixation procedure, performed on the HYDRAGEL IF 2/4 gel, is based on the creation of an isatuximab / anti-isatuximab antibody complex and shifting it outside the gammaglobulins zone. With the HYDRASHIFT isatuximab procedure, the isatuximab / anti-isatuximab antibody complex is visualized in alpha-1 zone on IgG and Kappa immunofixation tracks and then the interference is removed from the gamma zone.

The provided text describes the performance data for the HYDRASHIFT 2/4 isatuximab kit, which is intended for the qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis, specifically by removing isatuximab IgG kappa interference.

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

Acceptance Criteria and Reported Device Performance

The core acceptance criterion for this device, based on the performance data presented, is 100% concordance in visual evaluation of the presence or absence of monoclonal proteins, particularly after the removal of isatuximab interference.

Study Details Proving Device Meets Acceptance Criteria

1. A table of acceptance criteria and the reported device performance:
(See table above)

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

• Repeatability Study: 10 different serum samples (2 controls, 8 spiked with monoclonal components). 4 runs per sample within the same gel.
• Reproducibility Study: 8 different serum samples with monoclonal components + Normal Control Serum + Isatuximab Control. Each sample analyzed on 9 runs (1 analysis per gel, over 3 working days) on 3 HYDRASYS 2 instruments with 3 lots of HYDRASHIFT 2/4 isatuximab kit.
• Comparative Studies:
  • Internal Study: 53 serum samples (26 normal, 27 pathological).
  • External Study No. 1: 204 serum samples.
  • External Study No. 2: 203 serum samples. (Note: "The same serum samples were analyzed in both external studies with exception of one sample included in external study 1." suggesting ~204 unique samples across external studies.)

Data Provenance:

• Internal Study: Conducted by Sebia (manufacturer).
• External Studies: Performed in the USA.
• Retrospective/Prospective: Not explicitly stated, but the description of "serum samples" and "analyzed with" suggests they were existing or collected samples, making it likely retrospective for the comparative studies. The repeatability and reproducibility studies appear to be prospective experimental designs.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document does not specify the number or qualifications of experts used to establish the ground truth. The results are described as "100% concordant" based on detection and characterization of monoclonal proteins, which implies a pre-established or expert-verified classification for each sample. However, the exact process or personnel involved in this ground truth establishment are not detailed. Given it's an in vitro diagnostic (IVD) device for lab use, the "ground truth" would likely be the result of a reference method interpretation by qualified lab personnel.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
The document does not specify any adjudication method. The outcome measures are presented as "100% concordant results," which suggests a clear, unambiguous read for each test, or that any discrepancies were resolved, though the process for resolution is not described.

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:
No MRMC study was performed or described. This device is an in vitro diagnostic (IVD) kit for immunofixation electrophoresis, not an AI-assisted diagnostic imaging device for human readers. It automates a lab procedure and provides an electropherogram for visual evaluation. The "visual evaluation" mentioned refers to lab personnel interpreting the results of the gel electrophoresis.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, effectively. This device is an IVD kit. Its performance is evaluated on its ability to process serum samples and produce an electropherogram that then is visually evaluated. The "performance data" sections (repeatability, reproducibility, comparative studies) essentially describe the standalone performance of the kit itself in consistently producing the expected analytical result (i.e., shifting the isatuximab band and allowing for accurate detection/characterization of monoclonal proteins). While the final "reading" is visual, the kit's function is mechanistic/chemical, not algorithmic interpretation requiring human oversight in the AI sense.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth appears to be based on the presence and characterization of monoclonal proteins in serum samples, determined by standard laboratory methods and potentially confirmed by expert consensus in a clinical laboratory setting. For the comparative studies, samples were characterized as "normal" or "abnormal with monoclonal components," implying a reference standard or pre-established truth for each sample type. The "native" samples and "spiked" samples with isatuximab served as a form of ground truth for evaluating the device's ability to differentiate between intrinsic monoclonal proteins and isatuximab interference.

8. The sample size for the training set:
Not applicable/Not specified. This is an in vitro diagnostic (IVD) kit, not a machine learning or AI-based device that typically requires a separate "training set" for model development. The development process for such a kit involves chemical and biochemical optimization rather than data-driven learning.

9. How the ground truth for the training set was established:
As above, not applicable. The device is a wet-lab kit, not an AI algorithm.

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Yumizen C1200 Immunoglobulin A reagent is intended for the quantitative in vitro diagnostic determination of Immunoglobulin A (IgA) in serum and lithium heparin plasma by immunoturbidimetry on Yumizen analyzers.Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. This test should be used in conjunction with other findings,

Yumizen C1200 Immunoglobulin G reagent is intended for the quantitative in vitro diagnostic determination of Immunoglobulin G (IgG) in serum and lithium heparin plasma by immunoturbidimetry on Yumizen analyzers.Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. This test should be used in conjunction with other findings.

Yumizen C1200 Immunoglobulin M reagent is intended for the quantitative in vitro diagnostic determination of Immunoglobulin M (IgM) in serum and lithium heparin plasma by immunoturbidimetry on Yumizen analyzers. Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

This test should be used in conjunction with other laboratory and clinical findings.

This submission consists in the Yumizen C1200 Immunoglobulin A (1300023881), Yumizen C1200 Immunoglobulin G (1300023883) and Yumizen C1200 Immunoglobulin M (1300023884) reagent for serum and plasma testing for Yumizen C1200 reagent.

The Yumizen C1200 Level 1 Protein Control (1300023944) and Yumizen C1200 Level 2 Protein Control (1300023945) for use on Yumizen C1200 Analyzer and the Yumizen C1200 Protein Cal (1300023893) for use on Yumizen C1200 Analyzer are sold separately.

This document describes the analytical performance characteristics of the Yumizen C1200 Immunoglobulin A, G, and M reagents, intended for quantitative in vitro diagnostic determination of immunoglobulins in serum and lithium heparin plasma. The study aims to demonstrate that the device meets acceptance criteria for various analytical parameters, ensuring its safety and effectiveness.

1. Table of Acceptance Criteria and Reported Device Performance

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

• Measuring Range (Linearity):
  • IgA, IgG, IgM: Samples were "spiked" to create different concentrations, then serially diluted. The exact number of initial samples for spiking is not specified, but dilutions were "assayed in quadruplicate within a single run."
• Precision (Total Precision: analyzer variability - 20x2x2 study):
  • IgA, IgG, IgM: 5 human sera samples and 2 levels of Yumizen C1200 Protein Control. Tested with "two replicates per run, two runs per day for 20 days on each of three analyzers" (n=240 per sample).
• Precision (Lot to Lot variability study: 3x5x2x3):
  • IgA, IgG, IgM: 5 human sera samples and 2 levels of Yumizen C1200 Protein Control. Tested in "triplicates per run, two runs per day for five days on each of three lots" (n=90 per sample).
• Interferences: The exact sample size is not stated, but the study implies testing samples with varying concentrations of interfering substances to determine acceptable bias.
• Matrix Comparison:
  • IgA: 62 paired samples (serum and heparinized plasma) from single donors.
  • IgG: 45 paired samples (serum and heparinized plasma) from single donors. Of these, 43 were used for correlation analysis.
  • IgM: 43 paired samples (serum and heparinized plasma) from single donors.
• Method Comparison:
  • IgA: 190 "native samples" from human serum.
  • IgG: 214 "native samples" from human serum.
  • IgM: 153 "native samples" from human serum.

Data Provenance: The human serum samples used for precision, matrix comparison, and method comparison studies were "anonymous remnants of human serum specimens collected from blood bank." "Spiked" samples were used for linearity studies, and "normal samples" from a blood bank were used for reference range verification. The document does not explicitly state the country of origin, but the manufacturer is based in France. The studies appear to be prospective analytical performance evaluations.

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

No external experts are mentioned for establishing ground truth in these analytical performance studies. The studies rely on established CLSI guidelines for evaluation and comparison with a legally marketed predicate device. The ground truth for quantitative measurements is the direct measurement by the devices themselves and comparison against predicate devices or known spiked concentrations.

4. Adjudication Method for the Test Set

Not applicable. These are analytical performance studies for an in vitro diagnostic device, not studies involving human interpretation or adjudication.

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

No. This document describes the analytical performance of an in vitro diagnostic reagent and analyzer system, not a device requiring human interpretation for diagnostic purposes where MRMC studies would typically be conducted.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, this can be considered a standalone performance study. The Yumizen C1200 system (reagents and analyzer) performs the quantitative determination of immunoglobulins. The studies evaluate the analytical capabilities of the system itself, such as accuracy (via method comparison, linearity), precision, interference, and stability, without direct human intervention in the result generation or diagnostic interpretation loop. The intent is to demonstrate the device's ability to accurately measure predefined analytes.

7. Type of Ground Truth Used

The ground truth for these analytical performance studies is established through:

• Known concentrations: For linearity studies, spiked samples with known concentrations were used.
• Predicate device measurements: For method comparison, results from the candidate device were compared against measurements obtained from legally marketed predicate devices (Beckman Coulter's Olympus IgA, IgG, IgM reagents on AU analyzers).
• CLSI guidelines and established methodologies: The studies adhere to CLSI guidelines (e.g., EP05-A3 for precision, EP17-A2 for detection capability, EP06-A for linearity, EP25-A for stability, C28-A3 for reference intervals, EP-9A3 for method comparison) which define accepted methods for evaluating analytical performance and establishing performance characteristics.
• Literature-established reference ranges: For reference range verification, the device's measurements on "normal" samples were compared against ranges cited in scientific literature (e.g., Dati et al., 1996).

8. Sample Size for the Training Set

The document does not explicitly delineate a "training set" in the context of machine learning or AI models. This device is an in vitro diagnostic reagent and analyzer system, not an AI/ML-based diagnostic algorithm that typically undergoes a distinct training phase with a dedicated dataset. The performance studies described here are for analytical validation rather than algorithm training.

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

Not applicable, as there is no mention of a "training set" in the context of an AI/ML model for this in vitro diagnostic device. The analytical evaluations described involve testing the reagent and instrument system, not training a learning algorithm.

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For in vitro diagnostic use in the quantitative determination of total IgE in serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur®, ADVIA Centaur XP, and ADVIA Centaur XPT systems.

The ADVIA Centaur Total IgE (tlgE) assay is a two-site sandwich immunoassay using direct chemiluminometric technology, which uses constant amounts of two antibodies to IqE. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve with the reagent bar code. The ADVIA Centaur Total IgE (tlgE) assay is intended for use on the ADVIA Centaur family of analyzers. The ADVIA Centaur Calibrator 80 is a set of 2 level calibrators for the assay. Siemens Healthcare Diagnostics recommends the use of commercially available quality control materials with at least 2 levels (low and high).

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

Device: ADVIA Centaur Total IgE (tIgE) Assay

Purpose of Submission: Addition of plasma (EDTA and lithium heparin) sample claim and updating the detection capability claim.

1. Table of Acceptance Criteria and Reported Device Performance

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

• Specimen Equivalence by Method Comparison:

  • Sample Size: N = 73 for both Dipotassium EDTA Plasma vs. Serum and Lithium Heparin vs. Serum.
  • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, given it's for an in vitro diagnostic device and involves method comparison, it typically involves collected patient samples.

• Detection Capability (LoB, LoD, LoQ) and Interferences:

  • Sample Size: Not explicitly stated how many individual samples were used to determine LoB, LoD, LoQ, or for interference testing. These typically involve a series of measurements on spiked or known concentration samples rather than a large set of patient samples like method comparison.
  • Data Provenance: Not explicitly stated.

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

This submission document primarily focuses on analytical performance of an in vitro diagnostic (IVD) assay and does not involve human expert interpretation of results to establish ground truth in the way a medical imaging AI would. Therefore, this section is not applicable in the traditional sense for this type of device. The "ground truth" for this device's performance is established by the known concentrations of analytes in controls, calibrators, and spiked samples, and comparison to a reference method (in the case of method comparison studies).

4. Adjudication Method for the Test Set

Not applicable. As noted above, this is an analytical performance study for an IVD assay, not a study involving human reader interpretation requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. A MRMC study is typically performed for AI-assisted diagnostic imaging devices to evaluate the impact of AI on human reader performance. This submission is for an in vitro diagnostic assay, which does not involve human interpretation of images in this context.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This device is a standalone device in terms of its operation. It's an automated immunoassay system (ADVIA Centaur family of analyzers) that quantitatively determines total IgE. Its performance characteristics (detection capability, specimen equivalence, interference) are evaluated as the algorithm/system running independently on samples. There isn't a human-in-the-loop interacting with the direct measurement as there would be with an AI assisting image interpretation.

7. The Type of Ground Truth Used

• Detection Capability (LoB, LoD, LoQ): Established using statistical methods defined by CLSI EP17-A2, relying on repeated measurements of blank samples and samples with known low concentrations of the analyte.
• Specimen Equivalence by Method Comparison: The "ground truth" for the comparison (serum) is considered the established method against which the alternative sample types (EDTA plasma, lithium heparin plasma) are being evaluated. This relies on the accuracy of the serum measurement itself.
• Interferences: Established by spiking known interfering substances at specified concentrations into samples with known IgE concentrations and measuring the resulting bias.

8. The Sample Size for the Training Set

Not applicable. This is an analytical performance study for a chemical assay. There is no "training set" in the machine learning sense for this device. The assay's parameters and calibration are established through laboratory procedures, calibrators, and master curves, not through a data-driven training process in the way an AI algorithm is trained.

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

Not applicable. As there is no "training set" in the AI sense for this device, there is no ground truth established for it. The assay relies on known chemical reactions, calibrated reagents, and master curves set during the assay's development and manufacturing.

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The CAPI 3 IMMUNOTYPING kit is designed for the qualitative detection and the characterization of monoclonal proteins (immunotyping) in human urine and serum with the CAPILLARYS 3 TERA instrument, SEBIA, for capillary electrophoresis. It is used in conjunction with the CAPI 3 PROTEIN(E) 6 kit, SEBIA, designed for proteins separation into 6 major fractions in alkaline buffer (pH 9.9).

The CAPILLARYS 3 TERA instrument performs all procedural sequences automatically to obtain a profile for qualitative analysis. Each urine or serum sample is mixed with individual antisera that are specific against gamma (Ig G). alpha (Ig A) and mu (Ig M) heavy chains, and kappa (free and bound) light chains and lambda (free and bound) light chains, respectively.

The proteins, separated in silica capillaries, are directly detected by their absorbance at 200 nm.

The electrophoregrams are evaluated visually to detect the presence of specific reactions with the suspect monoclonal proteins.

For In Vitro Diagnostic Use.

The capillary electrophoresis provides complete automation with fast separation and good resolution. This electrokinetic separation technique is carried out in a silica glass tube (i.e., capillary) with internal diameter lower than 100 um filled with a buffer composed of electrolytes.

The CAPILLARYS 3 TERA instrument uses the principle of capillary electrophoresis in free solution. With this technique, charged molecules are separated by their electrophoretic mobility in an alkaline buffer with a specific pH. Separation occurs according to the electrolyte pH and electroosmotic flow. The CAPILLARYS 3 TERA instrument has silica capillaries functioning in parallel allowing 12 simultaneous analyses.

In capillary electrophoresis, abnormal fractions detected in serum or urine protein electrophoregrams, primarily those in the beta globulin and gamma globulin zones, are always suspect of being monoclonal proteins (M-proteins, paraproteins, monoclonal immunoglobulins). With the CAPI 3 IMMUNOTYPING procedure, the immunotyping procedure uses specific antibodies to identify these abnormal fractions.

In immunotyping a sample dilution is prepared and injected at the anodic end of six capillaries. The reference pattern (ELP pattern), which is a complete electrophoretic pattern of the sample's proteins, is obtained by mixing the sample with the ELP solution and injection into the 1st capillary. The antisera patterns are obtained by sample aspiration into the 5 subsequent capillaries. Previously diluted samples are mixed with specific antisera against gamma (Ig G), alpha (lg A), mu (lg M) heavy chains, and free and bound Kappa and Lambda light chains. Protein separation is performed in a high voltage electrical field. The separated proteins are detected using absorbance at 200 nm at the cathodic end of the capillary. After the analysis, the capillaries are immediately washed with a wash solution and filled with buffer which prepares the capillaries for the next analysis.

The immunotyping is performed in four automated steps:

1. Dilution of serum or urine samples with a specific diluent in the pre-dilution well of the reagent cup. This dilution is made according to the sample's immunoglobulin concentration.
2. Mixing diluted serum sample with specific antisera. The antigen - antibody complex is formed rapidly in liquid medium without the need for extra incubation step or removal of the immune complexes.
3. Injection of the prepared samples with simultaneous aspiration into 6 capillaries at the anodic end. Protein separation occurs when a high voltage field is applied to the alkaline buffer. The separated proteins are detected using absorbance at 200 nm at the cathodic end of the capillary.
4. Overlay of the ELP pattern on the antisera patterns (Ig G, Ig A, Ig M, Kappa and Lambda) allows characterization of suspected monoclonal component.

Here's an analysis of the acceptance criteria and study data for the CAPI 3 IMMUNOTYPING device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The FDA 510(k) summary does not explicitly list predefined quantitative acceptance criteria with specific numerical thresholds for all performance metrics (e.g., repeatability, reproducibility, accuracy). Instead, for qualitative assessments, the acceptance criterion appears to be "concordant results" or "100% agreement." For sensitivity, the acceptance criterion is implicitly shown by the reported detection limits.

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

• Repeatability: 4 different urine samples with monoclonal proteins (including Bence Jones proteins).
• Reproducibility: 3 different urine samples with monoclonal proteins (including Bence Jones proteins).
• Sensitivity: 3 pathological urine samples, serially diluted in normal urine.
• Sample Stability (2-8 °C): 10 urine samples (normal and pathological).
• Sample Stability (-70/-80 °C): 10 urine samples (normal and pathological).
• Accuracy/Concordance: 52 urine samples (8 without monoclonal component, 44 with monoclonal component including Bence Jones proteins).

Data Provenance: The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. Given that it's a 510(k) submission from Sebia (manufacturing in France, submitter in USA), and refers to "urine samples," these are likely clinical samples, but details on their origin are not provided. The phrase "analyzed at the beginning of the study (reference) and after X storage (test)" suggests a prospective element for the stability studies on stored samples.

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

The document states: "All electrophoregrams were evaluated visually for the qualitative results." However, it does not specify the number of experts used for ground truth establishment or their qualifications (e.g., "radiologist with 10 years of experience"). This is a significant omission from the perspective of external validation of the ground truth. It is implied that visual evaluation by trained personnel (likely laboratory professionals or experts in electrophoresis interpretation) was the method, but no further details are provided.

4. Adjudication Method for the Test Set

The document does not detail an adjudication method (such as 2+1 or 3+1 consensus) for the visual evaluation of electrophoregrams. It simply states they were "evaluated visually." This implies a single evaluator, or an internal process where disagreement (if any) was resolved, but the process is not described.

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

No multi-reader multi-case (MRMC) comparative effectiveness study was described. The accuracy/concordance study compares the new device's visual interpretation results to an existing, cleared device's visual interpretation results, which is a comparison of two methods, not an assessment of human readers with and without AI assistance. The device itself is a qualitative detection and characterization system, and the evaluation stated is "electrophoregrams were evaluated visually," indicating human interpretation is still involved in the final result.

6. Standalone Performance Study

The studies described (repeatability, reproducibility, sensitivity, stability, accuracy/concordance) evaluate the performance of the integrated system (CAPI 3 IMMUNOTYPING kit on CAPILLARYS 3 TERA instrument). The "electrophoregrams are evaluated visually" suggests human-in-the-loop performance, rather than a purely standalone algorithm. The device produces a "protein profile for qualitative analysis," which is then visually interpreted. Therefore, a standalone (algorithm only) performance study, in the sense of an AI algorithm making a definitive diagnosis without human oversight, does not appear to have been performed or is not directly applicable to the described use case which involves visual evaluation.

7. Type of Ground Truth Used

The ground truth for the test sets (e.g., for accuracy, repeatability, reproducibility studies) appears to be established by the visual evaluation of electrophoregrams performed by an expert or experts using a "reference technique" or the device itself.

• For the accuracy/concordance study, the "reference technique" (CAPILLARYS IMMUNOTYPING URINE procedure performed with the CAPILLARYS 2 instrument) served as the comparator for establishing ground truth, assuming the predicate device's results are considered the established truth.
• For other studies like repeatability and reproducibility, the "ground truth" seems to implicitly be the correct identification of presence/absence and type of monoclonal protein based on the expected outcome for the known pathological samples, assessed by visual evaluation.
• No mention of pathology, outcomes data, or independent gold standard beyond another electrophoretic method is provided.

8. Sample Size for the Training Set

The document does not mention a "training set" or explicitly describe the development of an algorithm that learns from data. This device is an immunodiagnostic test system based on capillary electrophoresis and specific antisera, producing profiles that are then visually interpreted. It is not presented as an AI/ML-driven device requiring a training set in the conventional sense. The "training" for such a system would typically involve its chemical and mechanical design, calibration, and validation against a standard.

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

As no training set is described for an AI/ML algorithm, this question is not applicable. The assay's "truth" is inherent in its biochemical principle (antigen-antibody reaction, electrophoretic separation) and the expertise of interpreting the resulting electrophoregrams.

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