(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.
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| SUBMITTED BY: | Mari A. MeyerRegulatory Affairs SpecialistDiaSorin Inc.1951 Northwestern AvenueP.O. Box 285Stillwater, MN 55082-0285Phone (651) 351-5635Fax (651) 351-5669E-mail: mari.meyer@diasorin.com |
|---|---|
| NAME OF DEVICE: | |
| Trade Name: | DiaSorin LIAISON® TOXO IgM |
| Common Names/Descriptions: | Immunoassay for the detection of IgM antibodiesToxoplasma gondii |
| Classification Names: | Enzyme Linked Immunosorbent Assay, Toxoplasma |
| Product Code: | LGD |
| PREDICATE DEVICES: | DiaSorin Toxoplasma IgM ELISA Kit (K963289) |
6.0 510 (k) SUMMARY
INTENDED USE:
DEVICE DESCRIPTION:
The DiaSorin 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 FDA for blood/plasma screening.
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, neonatal specimens, or infants.
KIT DESCRIPTION:
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.
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PERFORMANCE DATA:
COMPARATIVE CLINICAL TRIALS:
OOM ANVE SENTORE Samples were tested – 613 collected from the U.S and 279 collected from Europe. The U.S. collection included 200 samples from pregnant women. The testing was performed at three sites – a hospital, a physician's laboratory, and at DiaSorin. All samples were tested with the LIAISON® Toxo IgG Assay and an enzyme immunoassay, ELISA. Equivocal results were not repeat tested per the manufacturers' recommendations; these results were not included in the calculations of overall agreement.
U.S. Prospective samples:
| DiaSorin Toxo IgM ELISA Results | ||||
|---|---|---|---|---|
| LIAISON® Toxo IgMResults | Positive | Equivocal | Negative | Total |
| Positive (>= 10.0 AU) | 1 | 0 | 0 | 1 |
| Equivocal (8.0 - 9.9 AU) | 1 | 0 | 1 | 2 |
| Negative (< 8.0 AU) | 1 | 1 | 408 | 410 |
| Total | 3 | 1 | 409 | 413 |
| Percent Agreement | Exact 95% confidence interval | |
|---|---|---|
| Positive | 33.3% (1/3) | 0.8 - 90.6% |
| Negative | 99.8% (408/409) | 98.7 - 99.9% |
| Overall | 99.3% (409/412) | 97.9 - 99.9% |
European Prospective sample:
| LIAISON® Toxo IgMResults | DiaSorin Toxo IgM ELISA Results | |||
|---|---|---|---|---|
| Positive | Equivocal | Negative | Total | |
| Positive (>= 10 AU) | 41 | 0 | 3 | 44 |
| Equivocal (8.0- 9.9 AU) | 3 | 1 | 0 | 4 |
| Negative (< 8.0 AU) | 1 | 7 | 223 | 231 |
| Total | 45 | 8 | 226 | 279 |
| Percent Agreement | Exact 95% confidence interval | |
|---|---|---|
| Positive | 91.1% (41/45) | 78.0 - 97.5% |
| Negative | 98.7% (223/226) | 96.2 - 99.7% |
| Overall | 94.9% (265/279) | 91.7 - 97.3% |
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Prospective samples: Pregnant Women
| LIAISON® Toxo IgMResults | ELISA Results | |||
|---|---|---|---|---|
| Positive | Equivocal | Negative | Total | |
| Positive | 1 | 0 | 1 | 2 |
| Equivocal | 1 | 0 | 0 | 1 |
| Negative | 1 | 2 | 194 | 197 |
| Total | 3 | 2 | 195 | 200 |
| Percent Agreement | Exact 95% confidenceinterval | |||
|---|---|---|---|---|
| Positive: | 33.3% | (1/3) | 0.8 - 90.6% | |
| Negative: | 99.5% | (194/195) | 97.2 - 99.9% | |
| Overall: | 98.5% | (195/198) | 95.6 - 99.7% |
CDC PANEL STUDY:
The CDC (Centers for Disease Control and Prevention) Toxoplasma 1998 Human Serum Panel was tested by LIAISON® Toxo IgM assay. The panel is comprised of 100 frozen blinded specimens: 32 Toxoplasma IgM positive, 3 dilutions of three true Toxoplasma IgM positive, and 65 Toxoplasma IgM negative samples. Of the 6 IgM neqative samples 30 were Toxoplasma IgG negative. The data obtained were submitte to the CDC for analysis. The LIAISON® Toxo IgM Assay correctly detected the 32 out of the 32 IgM positives, 1 out of the three IgM positive dilutions, and 63 out of the 65 IgM negatives. Note: These results are presented as means to convey further information on the performance of this assay with a masked, characterized serum panı This does not imply endorsement of the assay by the CDC.
REPRODUCIBILITY:
An assay reproducibility study was conducted at two external US laboratories and at DiaSorin. A coded panel comprised of 9 frozen repository serum samples was prepared by DiaSorin and provided to each site for testing by the LIAISON Toxo IgM assay. The panel contained 3 sets of serum samples. The sets were prepared to represent low to mid positive analyte levels. All panel members were divided into aliquots and stored frozen prior to testing. The same coded panel was tested at all three siles, in three replicates per run for ten runs. The results are summarized below.
| ID# | N | mean(AU/mL) | withinrunS.D. | withinrun%CV | betweenrunS.D. | betweenrun%CV | betweensiteS.D. | betweensite%CV | overallsd. | overall%CV |
|---|---|---|---|---|---|---|---|---|---|---|
| TMS1 | 90 | 33.1 | 3.08 | 9.18 | 9.12 | 12.54 | 6.04 | 18.26 | 7.57 | 22.89 |
| TMS2 | 90 | 19.7 | 1.30 | 6.88 | 5.06 | 9.36 | 3.94 | 19.99 | 3.92 | 19.91 |
| TMS3 | 90 | 847 | 47.1 | 5.71 | 187 | 8.52 | 91.9 | 10.87 | 120.3 | 14.21 |
| TM1 | 90 | 24.4 | 1.70 | 6.65 | 7.38 | 10.33 | 6.23 | 25.48 | 6.10 | 24.96 |
| TM2 | 90 | 34.0 | 2.08 | 5.74 | 12.26 | 9.77 | 11.49 | 33.78 | 10.71 | 31.48 |
| TM3 | 90 | 26.7 | 1.95 | 7.17 | 7.55 | 8.20 | 6.03 | 25.57 | 6.04 | 22.63 |
| TM4 | 90 | 25.9 | 1.65 | 6.14 | 8.35 | 8.67 | 7.17 | 27.65 | 6.91 | 26.67 |
| TM5 | 90 | 14.0 | 0.97 | 6.83 | 3.57 | 8.73 | 2.44 | 17.46 | 2.64 | 18.84 |
| TM6 | 90 | 18.8 | 0.88 | 4.52 | 6.00 | 8.62 | 5.16 | 27.41 | 4.95 | 26.31 |
*TMS3 dose was below the reading range of the assay. Precision calculations are based on signal (RLU) for this sample.
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CROSS-REACTIONS:
Cross-reactivity studies for the LIAISON® Toxo IgM assay were designed to evaluate potential interference from IgM immunoglobulins directed against closely-related members of the herpes virus fincherchoo from 18m inntantal that may cause symptoms similar to Toxoplasmosis family (10 v 1, 10 v 1, 10 v 1, 10 virus, hepatitis B virus) and conditions that may result from atypical immune system activity (rheumatoid factor (RF), anti-nuclear antibodies (ANA)). Samples for these studies were selected using commercially available devices.
| Organism/condition | Number of ExpectedNegative Samples | LIAISON®Positive Result |
|---|---|---|
| HAV Total | 9 | (0/9) |
| HBc Total | 21 | (0/21) |
| VZV IgM | 8 | (0/8) |
| Rubella IgM | 7 | (0/7) |
| CMV IgM | 13 | (0/13) |
| VCA IgM | 14 | (0/14) |
| HSV1-2 IgM | 10 | (0/10) |
| ANA | 10 | (0/10) |
| RF | 10 | (0/10) |
| HAMA | 10 | (0/10) |
| Total | 112 | (0/112) |
No positive result was found for the samples when tested by LIAISON® Toxo IgM.
WARNING: Assay interference due to circulating antibodies against HIV and Hepatitis C virus has not been evaluated. The user is responsible for establishing cross-reactivity performance with these infectious agents.
INTERFERING SUBSTANCES:
Controlled studies of potentially interfering substances showed that the assay performance was not affected by hemolysis (at 1000 mg/dL hemoglobin), lipemia (at 3000 mg/dL triglycerides), icterus (at 20 mg/dL bilirubin).
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| SUBMITTED BY: | Mari A. MeyerRegulatory Affairs SpecialistDiaSorin Inc.1951 Northwestern AvenueP.O. Box 285Stillwater, MN 55082-0285Phone (651) 351-5635Fax (651) 351-5669E-mail: mari.meyer@diasorin.com |
|---|---|
| NAME OF DEVICE:Trade Name: | DiaSorin LIAISON® TOXO IgG |
| Common Names/Descriptions: | Immunoassay for the detection of IgG antibodies toToxoplasma gondii |
| Classification Names: | Enzyme Linked Immunosorbent Assay, Toxoplasma |
| Product Code: | LGD |
| PREDICATE DEVICES: | Diamedix Is-Toxoplasma IgG ELISA Kit (K981498) |
| DEVICE DESCRIPTION: |
6.0 510 (k) SUMMARY
INTENDED USE:
The LIAISON® Toxo IgG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer (Catolog number 15970) 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.
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, neonatal specimens, or infants.
KIT DESCRIPTION: 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.
{5}------------------------------------------------
PERFORMANCE DATA:
COMPARATIVE CLINICAL TRIALS:
A total of 887 prospectively collected samples were tested – 613 collected from the U.S. and 274 collected in A lotal of oor prospouroly oollooted camples from pregnant women. In addition, 200 archived iron Larope: The G.O. onliedion modaod 200 can processed. The testing was performed at four sites. All samples were tested with the LIAISON® Toxo IgG Assay and an enzyme immunoassay ELISA or Sabin Feldman Dye test.
reluivocal results were not repeat tested per the manufacturers' recommendations; these results were not included in the calculations of overall agreement.
U.S. Prospective samples:
| LIAISON® Toxo IgGResults | ELISA Results | Percent Agreement | Exact 95% confidenceinterval | |||||
|---|---|---|---|---|---|---|---|---|
| Positive | Equivocal | Negative | Total | Positive | 91.8% | (78/85) | 83.8 – 96.6% | |
| Positive | 78 | 1 | 8 | 87 | Negative | 95.3% | (304/319) | 92.4 - 97.3% |
| Equivocal | 3 | 4 | 7 | 13 | Overall | 93.5% | (386/413) | 90.6 - 95.6% |
| Negative | 4 | 4 | 304 | 313 | ||||
| Total | 85 | 9 | 319 | 413 |
European Prospective samples:
| LIAISON® Toxo IgGResults | ELISA Results | |||
|---|---|---|---|---|
| Results | Positive | Equivocal | Negative | Total |
| Positive | 139 | 3 | 7 | 149 |
| Equivocal | 2 | 0 | 4 | 6 |
| Negative | 0 | 3 | 116 | 119 |
| Total | 141 | 6 | 127 | 274 |
| Percent Agreement | Exact 95% confidenceinterval | ||
|---|---|---|---|
| Positive | 98.6% | (139/141) | 94.9 - 99.8% |
| Negative | 91.3% | (116/127) | 85.0 - 95.6% |
| Overall | 94.5% | (255/268) | 91.9 - 97.4% |
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Prospective samples: Pregnant Women
| LIAISON® Toxo IgGResults | ELISA ResultsPositive | Equivocal | Negative | Total |
|---|---|---|---|---|
| Positive | 48 | 2 | 3 | 53 |
| Equivocal | 1 | 0 | 1 | 2 |
| Negative | 1 | 1 | 143 | 145 |
| Total | 50 | 3 | 147 | 200 |
| Percent Agreement | Exact 95% confidenceinterval | |||
| Positive: | 96.0% | (48/50) | 86.3 – 99.5% | |
| Negative: | 97.3% | (143/147) | 91.2 - 99.2% | |
| Overall: | 96.5% | (190/197) | 92.8 - 98.6% |
Retrospective Samples:
| LIAISON® ToxoIgG Results | Sabin Feldman Dye test Results | Positive | Equivocal | Negative | Total |
|---|---|---|---|---|---|
| Positive | 149 | 0 | 0 | 149 | |
| Equivocal | 1 | 0 | 0 | 1 | |
| Negative | 0 | 0 | 50 | 50 | |
| Total | 150 | 0 | 50 | 200 | |
| Percent Agreement | |||||
| Positive | 99.3%(149/150) | 96.3 - 99.9% | |||
| Negative | 100.0%(0/0) | 92.0 - 100.0 | |||
| Overall | 99.5%(49/50) | 97.2 - 99.9% | |||
| Exact 95% confidence interval |
CDC PANEL STUDY:
The CDC (Centers for Disease Control and Prevention) Toxoplasma 1998 Human Serum Panel was tested by LIAISON® Toxo IgG assay. The panel is comprised of 100 frozen blinded specimens, 70 Toxoplasma positive samples and 30 toxoplasma negative samples. The data obtained were submitted to the CDC for analysis. The LIAISON® Toxo IgG Assay correctly detected the 70 positive and the 30 negative specimens. Note: These results are presented as a means to convey further information on the negative ope of this assay with a masked, characterized serum panel. This does not imply endorsement of the assay by the CDC.
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REPRODUCIBILITY:
REEKODUCIDIDIDIDIDIDIDIDIDIDIDIA
An assay reproducibility study was conducted at two external US laboratories and at pitch site An assay reproducibility Study Was ochaded at was prepared by DiaSorin and provided to each site for parier comprised of o Trezon ropotition of the panel contained samples prepared to represent low to mid positive analyte levels. All panel members were divided into aliquots and stored frozen prior to testing. positive analyte levels. All panel mombers works in three replicates per run for ten runs. The results are summarized below.
| ID# | N | mean(IU/mL) | withinrunS.D. | withinrun%CV | betweenrunS.D. | betweenrun%CV | betweensiteS.D. | betweensite%CV | overallsd. | overall%CV |
|---|---|---|---|---|---|---|---|---|---|---|
| TGS1 | 90 | 16.4 | 0.38 | 2.31 | 3.23 | 7.02 | 0.59 | 3.62 | 1.35 | 8.26 |
| TGS2 | 89 | 33.4 | 0.18 | 2.88 | 1.46 | 5.07 | 0.81 | 2.42 | 0.46 | 5.94 |
| TGS3 | 90 | 12.9 | 0.16 | 1.57 | 1.33 | 4.95 | 0.82 | 6.38 | 0.36 | 7.22 |
| TG1 | 90 | 7.6 | 0.96 | 2.38 | 6.37 | 4.96 | 0.28 | 3.68 | 1.99 | 6.05 |
| TG2 | 90 | 8.1 | 0.18 | 2.18 | 1.54 | 4.25 | 0.30 | 3.69 | 0.45 | 5.58 |
| TG3 | 90 | 11.1 | 0.19 | 1.92 | 1.72 | 5.27 | 0.29 | 2.61 | 0.47 | 6.22 |
| TG4 | 90 | 7.1 | 0.20 | 2.22 | 2.50 | 4.08 | 0.20 | 2.89 | 0.93 | 5.07 |
| TG5 | 90 | 9.1 | 0.21 | 2.07 | 2.13 | 3.50 | 0.32 | 3.45 | 0.69 | 5.17 |
| TG6 | 90 | 10.4 | 0.21 | 2.02 | 1.99 | 4.78 | 0.35 | 3.34 | 0.60 | 5.79 |
CROSS-REACTIONS:
Cross-reactivity studies for the LIAISON® Toxo IgG assay were designed to evaluate potential interference from IgG immunoglobulins directed against closely-related members of the herpes virus finans/USV-1, HSV-2, VZV, CMV), other organisms that may cause symptoms similar to Toxoplasmosis (i.e., EBV, rubella virus, hepatitis A virus, hepatitis B virus) and conditions that may result from atypical immune system activity [rheumatoid factor (RF), anti-nuclear antibodies (ANA)]. Samples for these studies were selected using commercially available devices.
| Organism/condition | Number of ExpectedNegative Samples | LIAISON®Positive Result |
|---|---|---|
| HAV Total | 12 | (0/12) |
| HBc Total | 17 | (0/17) |
| VZV IgG | 8 | (0/8) |
| Rubella IgG | 5 | (0/5) |
| CMV IgG | 10 | (0/10) |
| VCA IgG | 12 | (0/12) |
| HSV1-2 IgG | 2 | (0/2) |
| ANA | 7 | (0/7) |
| RF | 8 | (0/8) |
| HAMA | 7 | (0/7) |
| Total | 88 | (0/88) |
No positive result was found for the samples when tested by LIAISON® Toxoplasma IgG.
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WARNING: Assay interference due to circulating antibodies against HIV and Hepatitis C virus has withing. The user is responsible for establishing cross-reactivity performance with these infectious agents.
INTERFERING SUBSTANCES:
Controlled studies of potentially interfering substances showed that the assay performance was not ഗ്ഗന്തം അവലംബം mg/dL bilirubin).
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its wing and body. The eagle faces to the right. Encircling the eagle is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA".
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
2006 FEB 8
Ms. Mari Meyer Regulatory Affairs Specialist DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285
K052499 Re:
Trade/Device Name: LIAISON® Toxo IgG LIAISON® Toxo IgM Regulation Number: 21 CFR 866.3780 Regulation Name: Toxoplasma gondii Serological Reagents Regulatory Class: Class II Product Code: LGD Dated: January 5, 2006 Received: January 6, 2006
Dear Ms. Meyer:
We have reviewed your Section 510(k) premarket notification of intent to market the indication We have reviewed your Section > ro(x) premained issubstantially equivalent (for the indications referenced and nave decembled the actering and arrased predicate devices marketed in interstant for use stated in the encrosule) to regally mancted producal Device Americal Device Ameradments, or to commerce prior to May 28, 1770, the enactinent and early of the Federal Food. Drug, devices that have been recuire approval of a premarket approval application (PMA).
and Cosmetic Act (Act) that do not require approval of a premarket approval application (PM and Cosment Act (Act) that do not require approvide of the general controls provisions of the Act. The You may, therefore, market the device, bacycer to tirements for annual registration, listing of
general controls provisions of the Act include requirements for annual registe general controls provisions of the received required of childrens against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), , If your device is classified (SCC above) into e. Existing major regulations affecting your device it may be subject to such additional controlial Childring and 800 to 895. In addition, FDA can be found in Thic 21, Code of Peachar regard resgure in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean Please be advised that TDA s Issualities with other requirements of the Act
that FDA has made a determination that your device complies with other must that FDA has made a decemination may your in the Journer Federal agencies. You must light and light or any Federal statutes and regulations administered of registration and listing (21 comply with an the Ace 3 requirements, on and 809); and good manufacturing practice
CFR Part 807); labeling (21 CFR Parts 801 and 809); and good (21 CFR Part 820) CFK Part 807), labeling (21 CFR Patts 60 Parts (QS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) I ins leter will anow you to oogin manisting of substantial equivalence of your device to a legally premarket notification: "The sults in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your devire, If you desire specific infortion and advertising of your device, please contact the Office of In of quostions on the promise Evaluation and Safety at (240)276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the I va may odain other general ers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html
Sincerely yours,
Sale, a ton
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known):
KOS 2499
LIAISON® Toxo IgG Device Name:
The LIAISON® Toxo IgG assay uses chemiluminescent Indications For Use: 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.
Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Sall alany
Division Sign-Off
Page 1 of 1
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K052499
Volume l
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Indications for Use
Kos 24999 510(k) Number (if known):
LIAISON® Toxo IgM Device Name:
- The LIAISON® Toxo IgM assay uses Indications For Use: 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.
Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use_ (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
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Office of In Vitro Diagnostic Device Evaluation and Safety
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§ 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).