(319 days)
The AxSYM Toxo IqG Antibody assay is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative measurement of IgG antibodies to Toxoplasma gondii in human serum or plasma (EDTA, heparin or sodium citrate) to aid in the determination of immune status. This product is not FDA cleared for use in testing blood or plasma donors.
The AxSYM Toxo IgG Antibody assay is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative measurement of IgG antibodies to Toxoplasma gondii in human serum or plasma (EDTA, heparin or sodium citrate). It uses polystyrene microparticles coated with Toxoplasmosis gondii antigen (RH strain derived from HeLa cell cultures) as the solid phase and goat anti-human IgG antibody conjugated to alkaline phosphatase as the conjugate. It uses 4-Methylumbelliferyl Phosphate (MUP) as the enzyme substrate and is performed on an automated instrument.
Here's a breakdown of the acceptance criteria and study details based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the performance of the predicate device (VIDAS Toxo IgG) as well as the observed performance of the AxSYM Toxo IgG. The intent is to demonstrate at least comparable performance.
| Performance Metric | Acceptance Criteria (Implied by Predicate) | Reported Device Performance (AxSYM Toxo IgG) |
|---|---|---|
| Relative Sensitivity | ~96.0% - 98.4% (VIDAS study range) | 99.66% |
| Relative Specificity | ~97.8% - 97.9% (VIDAS study range) | 99.10% |
| Relative Agreement | (Not explicitly stated for predicate) | 99.34% |
| Percent CVs (Positive Panel/Control) | (Not explicitly stated for predicate) | 7.6% to 12.7% |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 1400 specimens
- Data Provenance: From pregnant women and random low-risk individuals. The study was conducted in two U.S. sites and one European site. (Retrospective, as these were "specimens" being tested, not newly collected for the study's primary purpose relative to the device).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The text does not explicitly state the number or qualifications of experts used. However, it indicates that discordant results were resolved using:
- IMx Toxo IgG Antibody assay (legally marketed device)
- Platelia Toxo IgG (legally marketed device)
- Sabin-Feldman dye test (a reference laboratory method, considered the most sensitive and specific for detecting IgG antibodies to toxoplasma, developed in 1948).
While specific "experts" are not mentioned, the use of a reference laboratory method (Sabin-Feldman dye test) implies specialized laboratory personnel with expertise in this established method.
4. Adjudication Method for the Test Set
A form of adjudication was used for discordant results.
- Method: Discordant results between the AxSYM Toxo IgG and the VIDAS Toxo IgG were resolved by testing with two other legally marketed devices (IMx Toxo IgG Antibody assay and Platelia Toxo IgG) and the Sabin-Feldman dye test. This implies a process where disagreements were arbitrated by multiple independent methods, especially the gold standard Sabin-Feldman dye test. This is an indirect adjudication process rather than direct expert consensus of, for example, a single image.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study compares two devices (assays) rather than the performance of human readers with or without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this study represents a standalone performance evaluation of the AxSYM Toxo IgG antibody assay. It assesses the assay's performance characteristics (sensitivity, specificity) directly against a predicate device and reference methods, without involving human interpretation as part of the primary outcome measure.
7. The Type of Ground Truth Used
The ground truth was established by a combination of:
- Reference Laboratory Method: Sabin-Feldman dye test (considered the gold standard for Toxo IgG detection).
- Other Legally Marketed Devices: IMx Toxo IgG Antibody assay and Platelia Toxo IgG.
This represents a composite reference standard where highly regarded established methods are used to determine the true immune status for discordant results.
8. The Sample Size for the Training Set
The document does not mention a separate "training set." The study conducted was primarily a clinical performance evaluation of the final device against a predicate, using the 1400 specimens as a test set. This type of device (an assay) does not typically have a "training set" in the same way an AI/ML algorithm would, as it's not a learned model but rather an enzyme immunoassay.
9. How the Ground Truth for the Training Set Was Established
As no training set is described for this type of device, this question is not applicable. The development and validation of such an assay would involve extensive biochemical and analytical studies, but not a "training set" with ground truth in the context of machine learning.
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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 presented in the [510(k)] notification for the AxSYM Toxo IgG antibody assay constitutes data supporting a substantially equivalent determination:
[510(k) ]Summary of Device Performance
The AxSYM Toxo IqG Antibody assay is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative measurement of IgG antibodies to Toxoplasma gondii in human serum or plasma (EDTA, heparin or sodium citrate) to aid in the determination of immune status. This product is not FDA cleared for use in testing blood or plasma donors.
The predicate device for determination of substantial equivalence is the bioMerieux VIDAS Toxo IgG assav.
The VIDAS Toxo IgG (TXG) assay is intended for use with a VIDAS (Vitek_ ImmunoDiagnostic Assay System) instrument as a semi-quantitative automated enzyme-linked fluorescent immunoassay (ELFA). It is intended for use in determination of Toxoplasma gondii immunological experience from a single serum sample, or as an aid in the diagnosis of T. gondii recent infection or reactivation through evaluation of paired sera for a significant increase in T. aondii-specific lgG. 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 IgG Antibody assay was compared to the VIDAS Toxo IgG Antibody assay using 1400 specimens from pregnant women and random low risk individuals. Discordant results were resolved by testing with IMx Toxo IgG Antibody assay and Platelia Toxo IgG, both of which are legally marketed devices. Discordant results were also resolved by the Sabin-Feldman dye test, a reference laboratory method for the determination of antibody to Toxoplasma gondii in human serum. This method was first developed in 1948 and is still considered the most sensitive and specific method for the detection of IgG antibodies to toxoplasma. Based on this study, the AxSYM Toxo IqG showed relative sensitivity of 99.66%. relative specificity of 99.10% and relative agreement of 99.34%. 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 were 7.6% to 12 7%.
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In conclusion, the AxSYM Toxo IgG antibody assay is substantially equivalent to the bioMerieux VIDAS Toxo IgG antibody assay for the detection of IgG antibodies to toxoplasmosis in human serum and plasma (EDTA, heparin, or sodium citrate) samples.
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[510(k)] Summary Of Technological Comparison
The AxSYM Toxo IgG Antibody Assay and the VIDAS Toxo IgG Antibody assay are substantially equivalent in that:
- A. Both are in vitro immunologic test methods.
- B. Both are intended for use in the detection of IgG antibody to Toxoplasmosis qondii in human serum.
- C. Both are based on the formation of immune complexes between Toxoplasmosis qondii antigens and antibody.
- D. Both are quantitative assays.
- E. Both use automated immunoassay analyzers.
- F. Both use a polystyrene solid phase.
- G. Both use an anti-human IgG antibody conjugated to alkaline phosphatase.
- H. Both use 4-Methylumbelliferyl Phosphate (MUP) as the enzyme substrate.
The AxSYM Toxo IgG Antibody Assay and VIDAS Toxo IgG Antibody assay ** differ in that:
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- The solid phase in the AxSYM Toxo IgG assay is polystyrene microparticles coated with Toxoplasmosis gondii antigen (RH strain derived from HeLa cell cultures). The solid phase for the VIDAS Toxo IgG assay consists of Toxoplasmosis gondii antigen coated to the inside of the SPR (solid phase receptacle).
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- The conjugate in the AxSYM Toxo IgG assay uses goat anti-human IgG antibody. The conjugate in the VIDAS Toxo IgG assay uses mouse monoclonal anti-human IgG antibody.
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- Plasma (EDTA, heparin, sodium citrate) specimens may be tested in the AxSYM Toxo IgG assay. The use of plasma specimens has not been validated in the VIDAS Toxo IgG assay
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Comparison of Methods
| Assay CharacteristicsAssay Type | AXSYM Toxo IgGQuantitative | VIDAS Toxo IgGQuantitative |
|---|---|---|
| Antibody Measured | Specific IgG | Specific IgG |
| Assay Principle | MEIA | EIA(ELFA) |
| Solid Phase | polystyrene microparticles | polystyrene solid phasereceptacle |
| Solid Phase Coating | Toxo antigen, RH strainderived from HeLa cellcultures | Toxo antigen, RH strain |
| Conjugate | goat anti-human IgGconjugated toalkaline phosphatase | mouse monoclonalanti-human IgGconjugated toalkaline phosphatase |
| Specimen | Human serum andplasma (EDTA,heparin, sodium citrate) | Human serum |
| Automation | Performed on anautomated instrument | Performed on anautomated instrument |
| Relative Specificity | 99.1%(European & US) | 97.8% (European study)97.9% (U.S. study) |
| Relative Sensitivity(final interpretation) | 99.6%(European & US) | 98.4% (European study)96.0% (U.S. study) |
§ 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).