The AxSYM Toxo IgM assay is a Microparticle Enzyme Immunoassay (MEIA) for the qualitative measurement of IgM antibodies to Toxoplasma gondii in human serum and plasma (EDTA, heparin, or sodium citrate) to aid in the diagnosis of primary infection. The AxSYM Toxo IgM assay is not for use with cord blood or neonatal specimens. This product is not FDA cleared for use in testing blood or plasma donors.

Device Description

The AxSYM Toxo IgM assay is a Microparticle Enzyme Immunoassay (MEIA) for the qualitative measurement of IgM antibodies to Toxoplasma gondii in human serum and plasma (EDTA, heparin, or sodium citrate). It utilizes polystyrene microparticles coated with Toxoplasma gondii antigen and a conjugate containing goat anti-human IgM antibody conjugated to alkaline phosphatase. The assay is performed on an automated instrument and utilizes a rheumatoid neutralization buffer.

AI/ML Overview

Here's an analysis of the provided text, outlining the acceptance criteria and the study used to demonstrate the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criterion	Device Performance (AxSYM Toxo IgM assay)
Relative Sensitivity	96.3%
Relative Specificity	99.8%
Relative Agreement	99.3%
Percent CV (positive panel members/control)	6.0% to 10.1%

Note: The document does not explicitly state pre-defined acceptance criteria values for these metrics. Instead, it presents the device's performance as evidence of substantial equivalence to the predicate device. The implied acceptance is that these performance metrics are comparable or superior to the predicate.

2. Sample Size and Data Provenance

Test Set Sample Size: 1,400 samples
Data Provenance:
- Country of Origin: Two U.S. sites and one European site.
- Retrospective/Prospective: The document does not explicitly state whether the study was retrospective or prospective. Given the comparison to a legally marketed device and sample collection from specific populations (pregnant women, non-pregnant individuals, and individuals positive for IgM antibodies to T. gondii), it is likely a combination or a retrospective analysis of collected samples.

3. Number of Experts and Qualifications for Ground Truth

The document does not specify the number of experts used to establish the ground truth for the primary comparison.
The ground truth for discordant results was established by re-testing with two other legally marketed devices (Platelia Toxo IgM and Abbott IMx Toxo IgM Antibody assay). This implies the "experts" in this context are the established performance and results of these reference assays, rather than human experts directly.

4. Adjudication Method for the Test Set

Discordant Resolution: Discordant results between the AxSYM Toxo IgM assay and the VIDAS Toxo IgM assay were resolved by testing with two additional legally marketed devices: Platelia Toxo IgM (Sanofi) and Abbott IMx Toxo IgM Antibody assay. This is a form of "reference method adjudication" using other commercial assays as the adjudicators.

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

No, an MRMC comparative effectiveness study was not done. This study solely focuses on comparing the performance of the AxSYM Toxo IgM assay to a predicate device (VIDAS Toxo IgM assay). It does not involve human readers or assess the improvement of human readers with or without AI assistance, as it is a diagnostic laboratory assay, not an AI-assisted diagnostic tool for interpretation.

6. Standalone Performance

Yes, a standalone performance study was done. The reported performance metrics (relative sensitivity, specificity, and agreement) are for the AxSYM Toxo IgM assay itself when compared against the predicate device and the reference methods used for discordant resolution. This represents the algorithm's (assay's) performance without human intervention in the result determination beyond running the assay.

7. Type of Ground Truth Used

The primary "ground truth" was established by comparison to a predicate device (bioMerieux VIDAS Toxo-M).
For discordant results, the ground truth was further established by agreement with two other legally marketed reference assays (Platelia Toxo IgM and Abbott IMx Toxo IgM Antibody assay). This can be considered a form of "reference assay consensus" or "established test outcome."

8. Sample Size for the Training Set

The document does not specify a training set sample size. This is common for this type of in vitro diagnostic device (IVD) submission, as it describes a comparative study for substantial equivalence, not the development and training of a novel algorithm in the AI sense. The study focuses on validation of the assay's performance rather than algorithmic training.

9. How Ground Truth for the Training Set Was Established

Since there's no mention of a dedicated "training set" in the context of an AI algorithm, details on how its ground truth was established are not applicable and not provided in this document. The study is a performance validation against a predicate, implying the predicate itself represents the established clinical utility or "ground truth" for the comparison.

Summary

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K954576

AUG 23 1996

ATTACHMENT A

[510(k)] Summary Of Safety And Effectiveness Information Supporting A

Substantially Equivalent Determination

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[510(k)] Summary Of Safety And Effectiveness Information Supporting A Substantially Equivalent Determination

The following information as presented in the [510(k)] notification for the AxSYM Toxo IqM assay constitutes data supporting a substantially equivalent determination:

[510(k)] Summary of Device Performance

The predicate device for determination of substantial equivalence is the bioMerieux VIDAS Toxo-M. The VIDAS Toxo IgM (TXM) assay is intended for use with a VIDAS (Vitek ImmunoDiagnostic Assay System) instrument as an automated enzyme-linked fluorescent immunoassay (ELFA) for the qualitative detection of anti-Toxoplasma gondii IgM antibodies in human serum, as an aid in the diagnosis of toxoplasmosis. It is not intended for use in testing (screening) blood or plasma donors.

In two U.S. sites and one European site, the AxSYM Toxo IgM assay was compared to the VIDAS Toxo IgM assay using 1,400 samples from pregnant women, non-pregnant individuals and individuals positive for IgM antibodies to T. gondii. Discordant results were resolved by testing with Platelia Toxo IgM (Sanofi) and Abbott IMx Toxo IgM Antibody assay, both of which are legally marketed devices in the United States. Based on this study, the AxSYM Toxo IgM assay showed relative sensitivity of 96.3%, relative specificity of 99.8% and relative agreement of 99.3%. Specimens giving equivocal results were not included in the calculation of relative agreement, relative sensitivity, or relative specificity. Percent CV's on positive panel members and positive control was 6.0% to 10.1%.

In conclusion, the AxSYM Toxo IgM Assay is substantially equivalent to the VIDAS Toxo IgM assay for the detection of IgM antibodies to T. gondii in human serum and plasma (EDTA, heparin, or sodium citrate) specimens.

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[510(k)] Summary Of Technological Comparison

The AxSYM Toxo IgM Antibody assay and the bioMerieux VIDAS Toxo IgM are substantially equivalent in that:

A. Both are in vitro immunologic test methods.
B. Both are intended for use in the detection of IgM antibody to T. gondii in human serum.
C. Both are based on information of immune complexes between T. gondii antigens and antibody.
D. Both use a polystyrene solid phase.
E. Both are qualitative assays.
F. Both use automated immunoassay analyzers.
G. Both use 4 methylumbelliferyl phosphate (MUP) as the enzyme substrate.

The AxSYM Toxo IgM Antibody assay and the VIDAS Toxo IgM assay differ in that:

A. The solid phase in the AxSYM Toxo IgM assay contains polystyrene microparticles coated with Toxoplasma gondii antigen. The VIDAS Toxo IgM assay is coated with goat anti-u chain antibodies inside of the SPR (solid phase receptacle).
B. The conjugate in the AxSYM Toxo IgM assay contains goat anti-human IgM antibody conjugated to alkaline phosphatase. The conjugate in the VIDAS Toxo IgM assay contains an immune complex of T. gondii antigen and anti-P30 mouse monoclonal antibody conjugated to alkaline phosphatase.
C. Serum and plasma (EDTA, heparin, sodium citrate) specimens may be tested in the AxSYM Toxo IgM assay. The use of plasma specimens has not been validated in the VIDAS Toxo IqM Assay.
D. The AxSYM Toxo IgM assay utilizes a rheumatoid neutralization buffer to remove rheumatoid factor interference antibodies. The VIDAS Toxo IgM assay does not utilize a buffer for rheumatoid factor interference antibodies.

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Comparison Of Methods

Assay Characteristic	AxSYM Toxo IgM Assay	VIDAS Toxo IgM Assay
Assay Type	Qualitative	Qualitative
Antibody Measured	Specific IgM	Specific IgM
Assay Principle	MEIA	EIA (ELFA)
Solid Phase	polystyrene microparticle	polystyrene solid phasereceptacle
Solid Phase Coating	Toxoplasma antigen, RHstrain derived from HeLacell culture	goat anti-μ chain antibodies
Conjugate	goat anti-human IgMantibodies conjugated toalkaline phosphatase	mouse anti-P30 monoclonalantibody conjugated toalkaline phosphatase
Specimen	Human serum and plasma(EDTA, heparin, citrate)	Human serum
Automation	performed on anautomated instrument	performed on anautomated instrument
Relative Specificity	99.8%( European & U.S. )	93.0% - 94.3% ( U.S. )99.4% - 99.6% ( European )
Relative Sensitivity	96.3%( European & U.S. )	87.9% - 99.5% ( U.S. )97.7% - 100.0% ( European )

Regulation Number and Section

§ 866.3780

Toxoplasma gondii serological reagents.(a)
Identification. Toxoplasma gondii serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toToxoplasma gondii in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identifyToxoplasma gondii from clinical specimens. The identification aids in the diagnosis of toxoplasmosis caused by the parasitic protozoanToxoplasma gondii and provides epidemiological information on this disease. Congenital toxoplasmosis is characterized by lesions of the central nervous system, which if undetected and untreated may lead to brain defects, blindness, and death of an unborn fetus. The disease is characterized in children by inflammation of the brain and spinal cord.(b)
Classification. Class II (performance standards).