AXSYM HOLO TC REAGENT KIT, MODEL 3L83-20; STANDARD CALIBRATOR KIT, MODEL 3L83-01; CONTROL KIT, MODEL 3L83-10

• K Number: K062467
• Device Name: AXSYM HOLO TC REAGENT KIT, MODEL 3L83-20; STANDARD CALIBRATOR KIT, MODEL 3L83-01; CONTROL KIT, MODEL 3L83-10
• Manufacturer: AXIS-SHIELD DIAGNOSTICS, LTD.
• Date Cleared: 2006-11-22 ( 90 days)
• Product Code: CDD , JIT , JJX
• Regulation Number: 862.1810
• Type: Traditional
• Panel: CH
• Reference & Predicate Devices: N/A

Intended Use

AxSYM HoloTC assay is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative determination of holotranscobalamin (HoloTC) in human scrum and plasma on the AxSYM System. HoloTC is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.

The AxSYM HoloTC Standard Calibrators are for the standard calibration of the AxSYM System when used for the quantitative determination of holotranscobalmin (HoloTC) in human serum and plasma.

The AxSYM HoloTC Controls are for the use in quality control to monitor the accuracy and precision of the HoloTC assay when used for the quantitative determination of holotranscobalamin (HoloTC) in human serum and plasma on the AxSYM System.

For in vitro diagnostic use.

Device Description

AxSYM HoloTC is based on Microparticle Enzyme Immunoassay (MEIA) technology. The AxSYM HoloTC reagents and sample are pipetted in the following sequence:

SAMPLING CENTER

• Sample and all AxSYM HoloTC reagents required for one test are pipetted by the . Sampling Probe into various wells of a Reaction Vessel (RV).
• . A reaction mixture is formed by combining diluted sample and microparticles coated with Anti-HoloTC monoclonal antibody in the sample well of the RV.
• . When human HoloTC antigen is present in the sample, it binds to the coated microparticles, forming antigen-antibody complexes on the microparticles.
• . The Anti-TC Antibody:Alkaline Phosphatase Conjugate is pipetted into a second well of the RV.
• 발 The HoloTC Wash Buffer is pipetted into a third well of the RV.
• 파 The Matrix Cell Wash is pipetted into a fourth well of the RV.

The RV is immediately transferred into the Processing Center. Further pipetting is done in the Processing Center by the Processing Probe.

PROCESSING CENTER

• . An aliquot of the reaction mixture, containing microparticles and bound antigenantibody complex, is transferred to the Matrix Cell. The microparticles bind irreversibly to the glass fiber matrix.
• B The Matrix Cell is washed to remove materials not bound to the microparticles.
• t The Anti-TC Antibody:Alkaline Phosphatase Conjugate is dispensed onto the Matrix Cell and it binds with the antigen-antibody complexes.
• " The Matrix Cell is washed to remove conjugate not bound to the microparticles.
• .. The substrate, 4-Methylumbelliferyl Phosphate, is added to the Matrix Ccll. The alkaline phosphatase-labeled conjugate catalyzes the removal of a phosphate group from the substrate, yielding the fluorescent product, 4-Methylumbelliferone. This fluorescent product is measured by the MEIA optical assembly.

AI/ML Overview

The AxSYM® HoloTC device is a Microparticle Enzyme Immunoassay (MEIA) intended for the quantitative determination of holotranscobalamin (HoloTC) in human serum and plasma to aid in the diagnosis and treatment of vitamin B12 deficiency.

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the AxSYM® HoloTC assay are based on demonstrating substantial equivalence to its legally marketed predicate device, the Axis-Shield HoloTC Radioimmunoassay (K#030655). The key performance metrics evaluated were precision, linearity, interferences, stability, and method comparison, with specific acceptance thresholds for these parameters not explicitly detailed in the provided summary. However, the study concludes that the device successfully met these criteria.

Acceptance Criteria Category	Reported Device Performance (AxSYM® HoloTC vs. Axis-Shield HoloTC RIA)
Precision	Substantially equivalent
Linearity	Substantially equivalent
Interferences	Substantially equivalent
Stability	Substantially equivalent
Method Comparison	Correlation coefficient of 0.90

Study Information:

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

   • The document does not explicitly state the sample size used for the test set.
   • The document implies the use of "human serum and plasma," but the country of origin or whether the data was retrospective or prospective is not specified.

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

   • This information is not provided in the summary. For an in vitro diagnostic device, "ground truth" often refers to a reference method or clinical diagnosis established through various means, not necessarily expert consensus in the same way it would be for an imaging AI.

3. Adjudication Method for the Test Set:

   • This information is not applicable/provided for this type of in vitro diagnostic device study as it's not based on reader interpretation requiring adjudication.

4. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

   • No MRMC comparative effectiveness study was done as this is an in vitro diagnostic assay, not an AI for medical image analysis where human reader performance is typically evaluated.

5. Standalone Performance (Algorithm Only without Human-in-the-Loop Performance):

   • Yes, the performance evaluated in this submission is the standalone performance of the AxSYM® HoloTC assay as an automated laboratory test. There is no human-in-the-loop component being evaluated for its performance.

6. Type of Ground Truth Used:

   • The "ground truth" for this device's performance evaluation is established by comparison to a legally marketed predicate device: the Axis-Shield HoloTC Radioimmunoassay (RIA). The predicate device's results serve as the reference for determining the "substantial equivalence" of the new AxSYM® HoloTC assay. This falls under a form of comparative reference method rather than expert consensus, pathology, or outcomes data directly.

7. Sample Size for the Training Set:

   • This information is not provided and is generally not applicable in the context of traditional in vitro diagnostic assays like MEIA, which do not typically involve machine learning 'training sets' in the same way AI algorithms do. Their 'training' involves optimizing reagents and protocols.

8. How the Ground Truth for the Training Set Was Established:

   • As there is no "training set" in the context of an AI algorithm, this question is not applicable. The "ground truth" for method development and calibration would have been established through a rigorous process of analytical validation, using internal reference materials, spiked samples, and comparison to established methods, though the specifics are not detailed in this summary.

Regulation Number and Section

§ 862.1810 Vitamin B

12 test system.(a)
Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.(b)
Classification. Class II.