(148 days)
The LIAISON® Toxo IgG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer for the the qualitative determination of specific IgG antibodies to Toxoplasma gondii in human serum. The results of this assay can be used as an aid in the assessment of the patient's serological status to infection with Toxoplasma gondii and in the determination of immune status of individuals including pregnant women.
This assay has not been cleared/approved by the F.D.A for blood/plasma donor screening.
The LIAISON® Toxo IgM assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer for the presumptive qualitative determination of IgM antibodies to Toxoplasma gondii in human serum. The LIAISON® Toxo IgM can be used as an aid in the presumptive diagnosis of acute or recent Toxoplasma gondii infection. It is recommended that the LIAISON® Toxo IgM assay be performed in conjunction with a Toxoplasma gondii IgG assay.
This assay has not been cleared/approved by the F.D.A for blood/plasma donor screening.
The method for qualitative determination of IgM antibodies to Toxoplasma gondii (anti-Toxo IgM) is an anthody capture chemiluminescence immunoassay (CLIA). All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the components of the test are magnetic particles (solid phase) coated with igG to human IgM (mouse, monoclonal), Toxoplasma gondii antigen, and a conjugate of mouse monoclonal antibodies to Toxoplasma gondii linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, IgM antibodies present in diluted calibrators, samples or controls bind to the solid phase. During the second incubation, the mouse monoclonal antibody conjugate reacts with Toxoplasma gondii antigen previously added and the immune complex thus formed reacts with IgM already bound to the solid phase. After each incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and therefore the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of anti-Toxo IgM in calibrators, samples or controls.
The method for qualitative determination of IgG antibodies to Toxoplasma gondii (anti-Toxo IgG) is an indirect chemiluminescence immunoassay (CLIA). All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the LIAISON® Analyzer. The principal components of the test are magnetic particles (solid phase) coated with Toxoplasma gondii and a conjugate of mouse monoclonal antibodies to human IgG linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, Toxoplasma gondii antibodies present in diluted calibrators, samples or controls bind to the solid phase. During the second incubation, the monoclonal antibody conjugate reacts with anti-Toxo IgG that is already bound to the solid phase. After each incubation, unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal and therefore, the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of anti-Toxo IgG in calibrators, samples or controls.
The provided text describes two devices, DiaSorin LIAISON® TOXO IgM and DiaSorin LIAISON® TOXO IgG. They are both immunoassays for detecting antibodies to Toxoplasma gondii.
Here's an analysis of the acceptance criteria and supporting studies for each device:
DiaSorin LIAISON® TOXO IgM
Intended Use: Presumptive qualitative determination of IgM antibodies to Toxoplasma gondii in human serum as an aid in the presumptive diagnosis of acute or recent Toxoplasma gondii infection. Recommended for use with a Toxoplasma gondii IgG assay.
1. Table of Acceptance Criteria and Reported Device Performance:
The document does not explicitly state pre-defined acceptance criteria in terms of specific percentage agreements. However, the performance is reported as percent agreement with a predicate ELISA assay, and implicitly, the FDA's clearance indicates these results met their review standards. Given the context of a 510(k) summary, the "acceptance criteria" are the performance levels deemed "substantially equivalent" to the predicate device.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (U.S. Prospective) | Reported Device Performance (European Prospective) | Reported Device Performance (Pregnant Women) |
|---|---|---|---|---|
| Positive Agreement | Sufficiently high to show substantial equivalence to predicate | 33.3% (1/3) CI: 0.8-90.6% | 91.1% (41/45) CI: 78.0-97.5% | 33.3% (1/3) CI: 0.8-90.6% |
| Negative Agreement | Sufficiently high to show substantial equivalence to predicate | 99.8% (408/409) CI: 98.7-99.9% | 98.7% (223/226) CI: 96.2-99.7% | 99.5% (194/195) CI: 97.2-99.9% |
| Overall Agreement | Sufficiently high to show substantial equivalence to predicate | 99.3% (409/412) CI: 97.9-99.9% | 94.9% (265/279) CI: 91.7-97.3% | 98.5% (195/198) CI: 95.6-99.7% |
| CDC Panel Positive Detection | Correctly detect positive samples | 32/32 (1/3 positive dilutions detected) | N/A | N/A |
| CDC Panel Negative Detection | Correctly detect negative samples | 63/65 | N/A | N/A |
| Cross-Reactivity | No positive results with specified interfering substances | 0/112 positive (for HAV, HBc, VZV, Rubella, CMV, VCA, HSV1-2 IgM, ANA, RF, HAMA) | N/A | N/A |
| Interfering Substances | Performance not affected by specified substances | Not affected by hemolysis (1000 mg/dL Hb), lipemia (3000 mg/dL TG), icterus (20 mg/dL bilirubin) | N/A | N/A |
Note on Acceptance Criteria: The provided document does not explicitly state numerical acceptance criteria for the agreement percentages (e.g., "must be >90%"). The FDA determines "substantial equivalence" based on the presented data compared to the predicate device. The varied performance in positive agreement across different sample sets (particularly the low number of positive U.S. and pregnant women samples) suggests that for a relatively uncommon condition like acute toxoplasmosis, good negative agreement might be highly valued, especially when an IgG assay is recommended in conjunction.
2. Sample Size Used for the Test Set and Data Provenance:
- Comparative Clinical Trials (Test Set 1 - U.S. Prospective): 413 samples collected from the U.S. (including 200 from pregnant women). Prospective.
- Comparative Clinical Trials (Test Set 2 - European Prospective): 279 samples collected from Europe. Prospective.
- Comparative Clinical Trials (Test Set 3 - Pregnant Women): 200 samples (subset of U.S. prospective data). Prospective, from the U.S.
- CDC Panel Study (Test Set 4): 100 frozen blinded specimens (32 IgM positive, 3 dilutions of three true IgM positive, 65 IgM negative (30 IgG negative)). Origin: CDC (presumably U.S.).
- Reproducibility Study: 9 frozen repository serum samples in a coded panel.
3. Number of Experts and Qualifications for Ground Truth:
The document refers to a "DiaSorin Toxo IgM ELISA Results" and "ELISA Results" as the comparator (ground truth proxy) for the clinical trials. For the CDC Panel Study, the samples were "characterized serum panel" and "Toxoplasma IgM positive" or "negative" as determined by the CDC. The document does not specify the number of experts or their qualifications for establishing the ground truth for these comparator assays or the CDC panel.
4. Adjudication Method for the Test Set:
Not explicitly stated. The comparison is made against the results of a predicate ELISA assay or CDC-characterized panel. "Equivocal results were not repeat tested per the manufacturers' recommendations; these results were not included in the calculations of overall agreement." This implies that equivocal results from either the LIAISON® Toxo IgM or the predicate ELISA were excluded from the agreement calculations.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not mentioned. This device is an immunoassay, not an AI-assisted diagnostic imaging tool, so such a study would not be applicable.
6. Standalone Performance:
Yes, the study presents the standalone performance of the LIAISON® Toxo IgM assay by comparing its results directly to a predicate ELISA or a characterized CDC panel. There is no human-in-the-loop component for the device's output itself.
7. Type of Ground Truth Used:
- For Comparative Clinical Trials: Another immunoassay (DiaSorin Toxo IgM ELISA) used as a predicate/comparator. This serves as a "surrogate ground truth" based on an established method.
- For CDC Panel Study: Characterized serum panel from the CDC, indicating expert determination of positive/negative status, likely based on a combination of reference methods.
8. Sample Size for the Training Set:
Not applicable in the context of an immunoassay. Immunoassays are "trained" during their development and optimization phases, which involve reagent formulation, antibody selection, and protocol tuning, typically not referred to as "training sets" in the same way as machine learning models. The document describes a "reproducibility study" which evaluates the consistency of the assay itself, not as a training set for an algorithm.
9. How the Ground Truth for the Training Set was Established:
Not applicable for the reason stated above.
DiaSorin LIAISON® TOXO IgG
Intended Use: Qualitative determination of specific IgG antibodies to Toxoplasma gondii in human serum as an aid in the assessment of the patient's serological status and immune status, including pregnant women.
1. Table of Acceptance Criteria and Reported Device Performance:
Similar to the IgM assay, explicit numerical acceptance criteria are not stated for percent agreement, but the reported performance met the FDA's criteria for substantial equivalence to the predicate device.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (U.S. Prospective) | Reported Device Performance (European Prospective) | Reported Device Performance (Pregnant Women) | Reported Device Performance (Retrospective) |
|---|---|---|---|---|
| Positive Agreement | Sufficiently high to show substantial equivalence to predicate | 91.8% (78/85) CI: 83.8–96.6% | 98.6% (139/141) CI: 94.9–99.8% | 96.0% (48/50) CI: 86.3–99.5% | 99.3% (149/150) CI: 96.3-99.9% |
| Negative Agreement | Sufficiently high to show substantial equivalence to predicate | 95.3% (304/319) CI: 92.4–97.3% | 91.3% (116/127) CI: 85.0–95.6% | 97.3% (143/147) CI: 91.2–99.2% | 100.0% (50/50) (Note: "0/0" for agreement calculations listed for 0 positive retrospective) CI: 92.0-100.0% |
| Overall Agreement | Sufficiently high to show substantial equivalence to predicate | 93.5% (386/413) CI: 90.6–95.6% | 94.5% (255/268) CI: 91.9–97.4% | 96.5% (190/197) CI: 92.8–98.6% | 99.5% (199/200) (Note: "49/50" listed) CI: 97.2-99.9% |
| CDC Panel Positive Detection | Correctly detect positive samples | 70/70 | N/A | N/A | N/A |
| CDC Panel Negative Detection | Correctly detect negative samples | 30/30 | N/A | N/A | N/A |
| Cross-Reactivity | No positive results with specified interfering substances | 0/88 positive (for HAV, HBc, VZV, Rubella, CMV, VCA, HSV1-2 IgG, ANA, RF, HAMA) | N/A | N/A | N/A |
| Interfering Substances | Performance not affected by specified substances | Not affected by hemolysis (1000 mg/dL Hb), lipemia (3000 mg/dL TG), icterus (20 mg/dL bilirubin) | N/A | N/A | N/A |
2. Sample Size Used for the Test Set and Data Provenance:
- Comparative Clinical Trials (Test Set 1 - U.S. Prospective): 413 samples collected from the U.S. Prospective.
- Comparative Clinical Trials (Test Set 2 - European Prospective): 274 samples collected from Europe. Prospective.
- Comparative Clinical Trials (Test Set 3 - Pregnant Women): 200 samples (subset of U.S. prospective data). Prospective, from the U.S.
- Comparative Clinical Trials (Test Set 4 - Retrospective Samples): 200 archived samples. Provenance not specified, but likely from a diverse source given the "archived" nature, possibly U.S.
- CDC Panel Study (Test Set 5): 100 frozen blinded specimens (70 Toxoplasma positive, 30 Toxoplasma negative). Origin: CDC (presumably U.S.).
- Reproducibility Study: 9 frozen repository serum samples in a coded panel.
3. Number of Experts and Qualifications for Ground Truth:
The document refers to "ELISA Results" or "Diamedix Is-Toxoplasma IgG ELISA Kit" (for the clinical trials) and "Sabin Feldman Dye test" (for retrospective samples) as the comparator (ground truth proxy). For the CDC Panel Study, the samples were "Toxoplasma positive" or "negative" as determined by the CDC. The document does not specify the number of experts or their qualifications for establishing the ground truth for these comparator assays or the CDC panel.
4. Adjudication Method for the Test Set:
Not explicitly stated. The comparison is made against the results of a predicate ELISA assay, Sabin Feldman Dye test, or CDC-characterized panel. "Equivocal results were not repeat tested per the manufacturers' recommendations; these results were not included in the calculations of overall agreement." This implies that equivocal results from either the LIAISON® Toxo IgG or the predicate assay were excluded from the agreement calculations.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not mentioned. This device is an immunoassay, not an AI-assisted diagnostic imaging tool, so such a study would not be applicable.
6. Standalone Performance:
Yes, the study presents the standalone performance of the LIAISON® Toxo IgG assay by comparing its results directly to a predicate ELISA, Sabin Feldman Dye test, or a characterized CDC panel. There is no human-in-the-loop component for the device's output itself.
7. Type of Ground Truth Used:
- For Comparative Clinical Trials (Prospective): Another immunoassay (ELISA) used as a predicate/comparator. This serves as a "surrogate ground truth" based on an established method.
- For Comparative Clinical Trials (Retrospective): Sabin Feldman Dye test, a classic reference method for Toxoplasma serology, considered a "gold standard" or high-accuracy reference method.
- For CDC Panel Study: Characterized serum panel from the CDC, indicating expert determination of positive/negative status, likely based on a combination of reference methods.
8. Sample Size for the Training Set:
Not applicable in the context of an immunoassay. As with the IgM assay, immunoassays are developed and optimized through reagent formulation and protocol tuning, not typically described with "training sets" in the machine learning sense. The document describes a "reproducibility study" which evaluates the consistency of the assay itself.
9. How the Ground Truth for the Training Set was Established:
Not applicable for the reason stated above.
§ 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).