(192 days)
IMMULITE® Toxoplasma IgM - For in vitro diagnostic use with the IMMULITE® Analyzers - for the presumptive qualitative detection of IgM antibodies to Toxoplasma gondii in human serum, particularly for women of childbearing age. When performed in conjunction with a Toxoplasma IgG assay, the IMMULITE® Toxoplasma IgM can be used as an aid in the presumptive diagnosis of acute, recent or reactive Toxoplasma gondii infection. This product has not been cleared/approved by the FDA for blood/plasma donor screening.
IMMULITE® 2000 Toxoplasma IgM - For in vitro diagnostic use with the IMMULITE® 2000 Analyzers - for the presumptive qualitative detection of IgM antibodies to Toxoplasma gondii in human serum, particularly for women of childbearing age. When performed in conjunction with a Toxoplasma IgG assay, the IMMULITE® 2000 Toxoplasma IgM can be used as an aid in the presumptive diagnosis of acute, recent or reactive Toxoplasma gondii infection. This product has not been cleared/approved by the FDA for blood/plasma donor screening.
IMMULITE and IMMULITE 2000 Toxoplasma IgM are clinical devices for use with their respective IMMULITE and IMMULITE 2000 Automated Immunoassay Analyzers.
IMMULITE Toxoplasma IgM is a solid-phase, two-step chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with partially purified Toxoplasma gondii antigen.
IMMULITE 2000 Toxoplasma IgM is a solid-phase, two-step chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead added to an IMMULITE 2000 Reaction Tube, is coated with partially purified Toxoplasma gondii antigen.
Here's a breakdown of the acceptance criteria and study information for the IMMULITE® and IMMULITE® 2000 Toxoplasma IgM devices, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as quantitative targets (e.g., "sensitivity must be > X%") in the document. Instead, the studies demonstrate "substantial equivalence" to predicate devices (Vidas Toxo IgM and Zeus Scientific Toxo IgM ELISA Test System). The performance is reported as agreement percentages with these predicate devices and with a CDC panel.
| Metric (Acceptance Criteria - Implied by Substantial Equivalence) | IMMULITE Toxoplasma IgM (Reported Performance) | IMMULITE 2000 Toxoplasma IgM (Reported Performance) |
|---|---|---|
| Agreement with Predicate Device (Zeus Scientific Toxo IgM ELISA Test System) | ||
| Positive Agreement (All subjects) | 90.0% (36/40, 95% CI: 76.3% - 97.2%) | 95.0% (38/40, 95% CI: 83.1% - 99.4%) |
| Negative Agreement (All subjects) | 100% (116/116, 95% CI: 96.9% - 100%) | 100% (115/115, 95% CI: 96.8% - 100%) |
| Overall Agreement (All subjects) | 97.4% (152/156, 95% CI: 93.6% - 99.3%) | 98.7% (153/155, 95% CI: 95.4% - 99.8%) |
| Positive Agreement (Pregnant subjects) | 91.7% (22/24, 95% CI: 73.0% - 99.0%) | 95.8% (23/24, 95% CI: 78.9% - 99.9%) |
| Negative Agreement (Pregnant subjects) | 100% (58/58, 95% CI: 93.8% - 100%) | 100% (58/58, 95% CI: 93.8% - 100%) |
| Overall Agreement (Pregnant subjects) | 97.6% (80/82, 95% CI: 91.5% - 99.7%) | 98.8% (81/82, 95% CI: 93.4% - 100%) |
| Agreement with Predicate Device (Vidas Toxo IgM) | (Not tested against Vidas Toxo IgM for IMMULITE 2000) | |
| Positive Agreement (All subjects) | 96.6% (28/29, 95% CI: 82.2% - 99.9%) | N/A |
| Negative Agreement (All subjects) | 95.3% (122/128, 95% CI: 90.1% - 98.3%) | N/A |
| Overall Agreement (All subjects) | 95.5% (150/157, 95% CI: 91.0% - 98.2%) | N/A |
| Positive Agreement (Pregnant subjects) | 100% (16/16, 95% CI: 79.4% - 100%) | N/A |
| Negative Agreement (Pregnant subjects) | 94.1% (64/68, 95% CI: 85.6% - 98.4%) | N/A |
| Overall Agreement (Pregnant subjects) | 95.2% (80/84, 95% CI: 88.3% - 98.7%) | N/A |
| Agreement with CDC Toxoplasma 1998 Human Serum Panel | ||
| Total Agreement | 97.9% | 99.0% |
| Positive Specimens Agreement | 93.8% | 96.9% |
| Negative Specimens Agreement | 100% | 100% |
| Precision (Total CV across sites) | ||
| IMMULITE Toxoplasma IgM Serum Ratio (Example: Sample 1) | 11.1% (Site 1), 6.2% (Site 2), 4.9% (Site 3) | N/A |
| IMMULITE 2000 Toxoplasma IgM Serum Ratio (Example: Sample 1) | N/A | 2.4% (Site 1), 4.3% (Site 2) |
| Cross-Reactivity (vs. various pathogens & RF) | All negative results | All negative results |
| Interference (Bilirubin, Lipemia, Hemoglobin) | No effect observed up to tested concentrations | No effect observed up to tested concentrations |
2. Sample Sizes Used for the Test Set and Data Provenance
- IMMULITE Toxoplasma IgM (vs. Zeus Scientific):
- Sample Size: 172 samples (from apparently healthy male/female subjects, pregnant women, and patients suspected of being toxoplasma IgM positive).
- Data Provenance: Retrospective, samples were frozen. Collected from a clinical study in the southern United States.
- IMMULITE Toxoplasma IgM (vs. Vidas Toxo IgM):
- Sample Size: 168 samples (from apparently healthy male/female subjects, pregnant women, and patients suspected of being toxoplasma IgM positive).
- Data Provenance: Retrospective, samples were frozen. Collected from a clinical study in the northeastern United States.
- IMMULITE 2000 Toxoplasma IgM (vs. Zeus Scientific):
- Sample Size: 172 samples (from normal male/female subjects, pregnant women, and patients suspected of being toxoplasma IgM positive).
- Data Provenance: Retrospective, samples were frozen. Collected from a clinical study in the southern United States.
- IMMULITE 2000 Toxoplasma IgM (vs. IMMULITE Toxoplasma IgM):
- Sample Size: 291 samples.
- Data Provenance: Conducted at DPC (in-house).
- CDC Toxoplasma 1998 Human Serum Panel:
- Sample Size: 97 samples (32 positive, 65 negative).
- Data Provenance: From the CDC (a characterized, masked serum panel).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the clinical study samples. The primary method for establishing ground truth in these studies was comparison to predicate devices (Zeus Scientific Toxo IgM ELISA Test System and Vidas Toxo IgM), which are themselves diagnostic assays.
For the CDC Toxoplasma 1998 Human Serum Panel, the ground truth was established by the CDC, meaning the samples were already "characterized." The specific number or qualifications of experts involved in the CDC's characterization are not provided in this document.
4. Adjudication Method for the Test Set
The document describes comparisons between the new devices and predicate devices. No formal "adjudication method" involving human expert review to resolve discrepancies is mentioned for the clinical study samples. Instead, indeterminate results were excluded from agreement calculations. For the CDC panel, it was a "masked, characterized serum panel," implying the CDC's own established results were used as truth without further adjudication by the sponsor.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
This document describes the performance of in vitro diagnostic assays (chemiluminescent enzyme immunoassays) for detecting antibodies in serum, not an AI-assisted diagnostic device that would typically involve human readers interpreting images or data. Therefore, an MRMC comparative effectiveness study, and the concept of "human readers improve with AI," is not applicable to this device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
This describes a standalone assay. The IMMULITE and IMMULITE 2000 systems are automated immunoassay analyzers. While they require human operation for sample loading and result interpretation, the measurement of the signal and calculation of the signal/cutoff ratio (the quantitative result of the device) is performed by the instrument itself without human "reading" of the raw immunological reaction. The comparison studies cited are effectively standalone performance studies relative to other standalone diagnostic assays.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The primary type of ground truth used for the clinical performance studies was the results from legally marketed predicate diagnostic devices (Zeus Scientific Toxo IgM ELISA Test System and Vidas Toxo IgM). For the CDC panel, the ground truth was the CDC's characterization of its serum panel. These are essentially reference assay results, not explicitly pathology, expert consensus (beyond the assay's own validation), or patient outcomes data.
8. The Sample Size for the Training Set
The document does not specify a separate training set for the device. This is typical for traditional in vitro diagnostic assays (like immunoassays) which are developed and validated rather than "trained" in the machine learning sense. The "development" of such assays usually involves optimization using various panels, but a distinct "training set" as understood in AI/ML is not a concept explicitly applied or reported here. The performance studies presented are essentially validation/test sets for demonstrating substantial equivalence.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" is mentioned in the context of machine learning, this question is not applicable in the same way it would be for an AI device. The ground truth for the validation/test sets (as described in point 7) was established by comparing the devices' results to predicate devices and a characterized CDC panel.
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JAN 1 0 2002
012075 510(k) Summary of Safety and Effectiveness IMMULITE and IMMULITE 2000 Toxoplasma IgM
This summary of safety and effectiveness information has been prepared in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92.
| Name:Address: | Diagnostic Products Corporation5700 West 96th StreetLos Angeles, California 90045-5597 |
|---|---|
| Telephone Number:Facsimile Number: | (310) 645-8200(310) 645-9999 |
| Contact Person: | Edward M. Levine, Ph.D.Director of Clinical Affairs |
| Date of Preparation: | January 8, 2002 |
| Device Name:Trade: | IMMULITE® Toxoplasma IgMIMMULITE® 2000 Toxoplasma IgM |
| Catalog Number: | LKTM1 (100 tests), LKTM2 (200 tests)L2KTM2 (200 tests), L2KTM6 (600 tests) |
| Common: | Reagent system for the detection of IgM antibodies toToxoplasma gondii in human serum |
| Classification: | Class II device, 83-LGD (21CFR 866.3780) |
| Manufacturer: | Diagnostic Products Corporation5700 West 96th StreetLos Angeles, CA 90045(The Quality System of Diagnostic Products Corporation isregistered to ISO 9001:1994) |
| Establishment RegistrationNumber | DPC's Registration Number 2017183 |
| Substantially EquivalentPredicate Device: | Vidas (ELFA) Toxo IgM (K923166)Zeus Scientific Toxo IgM ELISA Test System (K913787) |
| Description of Devices: | IMMULITE and IMMULITE 2000 Toxoplasma IgM areclinical devices for use with their respective IMMULITEand IMMULITE 2000 Automated Immunoassay Analyzers. |
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Intended Use of the Device:
IMMULITE® Toxoplasma IgM is a solid-phase chemiluminescent enzyme immunoassay for in vitro diagnostic use with the IMMULITE® Analyzer - for the presumptive qualitative detection of IgM antibodies to Toxoplasma in human serum or plasma (EDTA or heparinized), particularly for women of childbearing age. When performed in conjunction with a Toxoplasma IgG assay, the IMMULITE® Toxoplasma IgM can be used as an aid in the presumptive diagnosis of acute, recent or reactivated Toxoplasma infection.
IMMULITE® 2000 Toxoplasma IgM is a solid-phase chemiluminescent enzyme immunoassay for in vitro diagnostic use with the IMMULITE® 2000 Analyzer – for the presumptive qualitative detection of IgM antibodies to Toxoplasma in human serum or plasma (EDTA or heparinized), particularly for women of childbearing age. When performed in conjunction with a Toxoplasma IgG assay, the IMMULITE® 2000 Toxoplasma IgM can be used as an aid in the presumptive diagnosis of acute, recent or reactivated Toxoplasma infection.
Performance Equivalence:
Diagnostic Products Corporation (DPC) asserts that IMMULITE Toxoplasma IgM and IMMULITE 2000 Toxoplasma IgM produce substantially equivalent results to other commercially marketed assays, such Vidas (ELFA) Toxo IgM or Zeus Scientific Toxo IgM ELISA Test System.
Technology Comparison:
Provided below is a comparison of DPC's IMMULITE and IMMULITE 2000 Toxoplasma IgM technology vs. the Zeus Scientific Toxo IgM ELISA Test System and Vidas Toxo IgM technology.
IMMULITE Toxoplasma IgM is a solid-phase, two-step chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with partially purified Toxoplasma gondii antigen.
Prediluted patient sample (1-in-21 dilution) and a protein-based buffer are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37℃ with intermittent agitation. During this time. Toxoplasma -specific IgM in the sample binds to the Toxoplasma antigen-coated bead. Unbound serum is then removed by a centrifugal wash.
An alkaline phosphatase-labeled anti-human IgM antibody is introduced, and the Test Unit is incubated for approximately another 30-minute cycle. The unbound enzyme conjugate is removed by a centrifugal wash. Substrate is then added, and the Test Unit is incubated for a further 10 minutes.
The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to vield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving
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precision by providing a window for multiple readings. The bound complex -- and thus also the photon output, as measured by the luminometer -- is related to the presence of Toxoplasma InM in the sample. A result is then obtained by comparing the patient result to the response of the cutoff material (i.e., the adjustor).
IMMULITE 2000 Toxoplasma IgM is a solid-phase, two-step chemiluminescent enzyme immunoassay. The solid phase, a polystyrene bead added to an IMMULITE 2000 Reaction Tube, is coated with partially purified Toxoplasma gondii antigen.
Prediluted patient sample (1-in-20 dilution) and a protein-based buffer are simultaneously introduced into the Reaction Tube, and incubated for approximately 30 minutes at 37℃ with intermittent agitation. During this time. Toxoplasma -specific IgM in the sample binds to the Toxoplasma antigen-coated bead. Unbound serum is then removed by a centrifyigal wash.
An alkaline phosphatase-labeled anti-human IgM antibody is introduced, and the Reaction Tube is incubated for approximately another 30-minute cycle. The unbound enzyme conjugate is removed by a centrifugal wash. Substrate is then added, and the Reaction Tube is incubated for a further 5 minutes.
The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex -- and thus also the photon output, as measured by the luminometer -- is related to the presence of Toxoplasma IgM in the sample. A result is then obtained by comparing the patient result to the response of the cutoff material (i.e., the adjustor)
Zeus Scientific Toxo IgM ELISA Test System is an enzyme-linked immunosorbent assay (ELISA) designed to detect IgM class antibodies to T. gondii antigen. Patient serum samples to be assayed for antibody are first diluted and incubated in microwells coated with T. gondii antigen. Any antigen specific IgM antibody in the sample will bind to the immobilized antigen. The plate is washed to remove unbound antibody and other serum components.
Peroxidase conjugated goat anti-human IgM is added to the wells and the plate is incubated. The conjugate will react with IgM antibody immobilized on the solid phase in step 2. The wells are washed to remove unreacted conjugate.
The microtiter wells containing immobilized peroxidase conjugate are incubated with peroxidase substrate solution. Hydrolysis of the substrate by peroxidase produces a color change. After a period of time, the reaction is stopped and the color intensity of the solution is measured photometrically. The color intensity of the solution is directly related to the antibody concentration in the test sample.
Vidas Toxo IgM is an enzyme-linked fluorescent immunoassay (ELFA) performed in an automated Vidas instrument. All assay steps and assay temperature are controlled by the instrument. A pipette tip-like disposable device, the Solid Phase Receptacle (SPR) serves as the solid phase as well as the pipettor for the assay. The SPR is coated with goat anti-u chain
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antibodies. The Vidas TXM assay configuration prevents nonspecific reactions with the SPR. Reagents for the assay are in the sealed TXM Reagent Strips.
After a sample dilution step, the sample is cycled in and out of the SPR for a specific length of time. IgM antibodies present in the specimen will bind to the anti-u chain antibodies coating the interior of the SPR. Unbound sample components are washed away. An Immunocomplex of T. gondii antigen and mouse monoclonal anti-P30 antibodies conjugated with alkaline phosphatase is cycled in and out of the SPR and will attach to the human anti-T. gondii IgM bound to the SPR wall. A final wash step removes unbound conjugate.
A fluorescent substrate is introduced into the SPR. Enzyme remaining on the wall of the SPR will catalyze the conversion of the substrate to the fluorescent product. The intensity of the fluorescence is measured by the optical scanner in the instrument.
Expected Values
Individuals infected with the Toxoplasma organism will typically exhibit detectable levels of IgM antibody immediately before or soon after the onset of symptoms.2 IgM titers normally decline within four to six months, but may persist at low levels up to a year. 4 Patients with active toxoplasma chorioretinitis usually have undetectable levels of IgM.
The prevalence of Toxoplasma infection can vary depending on a number of factors such as age, gender, geographical location, socio-economic status, race, type of test used, specimen collection and handling procedures, and clinical and epidemiological history of individual patients. There are approximately 3000 cases of congenital toxoplasmosis reported per year, with an average of 0.6 cases per 1000 pregnancies in the United States.
IMMULITE Toxoplasma IgM
Studies with presumed healthy, asymptomatic subjects and individuals suspected of acute toxoplasma viral infection were conducted at two clinical sites in the southern and northeastern United States. The study in the southern United States consisted of 172 specimens from 93 pregnant women and 79 individuals with various conditions. IMMULITE Toxoplasma IgM tests on these samples vielded the following results:
| Subjects | Totaln | Positive | Negative | Indeterminate | |||
|---|---|---|---|---|---|---|---|
| n | % | n | % | n | % | ||
| Pregnant | 93 | 22 | 24% | 64 | 69% | 7 | 8% |
| Various | 79 | 14 | 18% | 62 | 78% | 3 | 4% |
| All | 172 | 36 | 21% | 126 | 73% | 10 | 6% |
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Image /page/4/Figure/0 description: The image is a bar graph showing frequency on the y-axis and ratio on the x-axis. The frequency ranges from 0 to 70, while the ratio ranges from 0.0 to 5.0. The bar graph shows that the frequency is highest at a ratio of 0.0, with a frequency of around 60, and then decreases as the ratio increases.
Observed signal/cutoff ratios for all samples
The study in the northeastern United States consisted of 168 specimens from 91 pregnant women and 77 individuals with various conditions. IMMULITE Toxoplasma IgM tests on these samples yielded the following results:
| Subjects | Totaln | Positive | Negative | Indeterminate | |||
|---|---|---|---|---|---|---|---|
| n | % | n | % | n | % | ||
| Pregnant | 91 | 20 | 22% | 65 | 71% | 6 | 7% |
| Various | 77 | 14 | 18% | 60 | 78% | 3 | 4% |
| All | 168 | 34 | 20% | 125 | 74% | 9 | 5% |
Observed signal/cutoff ratios for all samples
Image /page/4/Figure/5 description: This image is a bar graph that shows frequency on the y-axis and ratio on the x-axis. The x-axis ranges from 0.0 to 5.0, and the y-axis ranges from 0 to 90. The bar at ratio 0.0 has a frequency of approximately 84, while the bar at ratio 1.0 has a frequency of approximately 21.
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IMMULITE 2000 Toxoplasma IgM
ININGEFFE 2000 renthy, asymptomatic subjects and individuals suspected of acute toxoplasma viral infection were conducted at one clinical sites in the southern United States. The study consisted of 172 specimens from 93 pregnant women and 79 individuals with various study consisted or 172 proplasma IgM tests on these samples yielded the following results:
| Subjects | Totaln | Positive | Negative | Indeterminate | |||
|---|---|---|---|---|---|---|---|
| n | % | n | % | n | % | ||
| Pregnant | 93 | 23 | 25% | 61 | 66% | 9 | 10% |
| Various | 79 | 16 | 20% | 59 | 75% | 4 | 5% |
| All | 172 | 39 | 23% | 120 | 70% | 13 | 8% |
80 70 60 ૨૦ requenc 40 30 20 10 0 5.0 0.0 1.0
Observed signal/cutoff ratios for all samples
Performance Characteristics
Clinical Performance
In a clinical study in the southern United States, a total of 172 frozen samples from apparently healthy male and female subjects, pregnant women and patients suspected of being toxoplasma IgM positive were tested by IMMULITE Toxoplasma IgM and by a commercially available enzyme immunoassay (Kit A- Zeus Scientific Toxo IgM ELISA Test System). These samples were also tested for Toxoplasma IgG. The IMMULITE Toxoplasma IgM results were compared to the results of Kit A.
Comparison for all subjects
| Kit A | Positive | Indeterm | Negative |
|---|---|---|---|
| Positive | 36 | 9 | 4 |
| Indeterm | 0 | 1 | 6 |
| Negative | 0 | 0 | 116 |
| Positive Agreement: 90.0% (36/40, 95% CI: 76.3% - 97.2%) | |||
| Negative Agreement: 100% (116/116, 95% CI: 96.9% - 100%) | |||
| Agreement: 97.4% (152/156, 95% CI: 93.6% - 99.3%) |
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Comparison for pregnant subjects
| Kit A | Pos | Ind | Neg |
|---|---|---|---|
| Pos | 22 | 7 | 2 |
| Ind | 0 | 0 | 4 |
| Neg | 0 | 0 | 58 |
| Positive Agreement: 91.7% (22/24, 95% CI: 73.0% - 99.0%) | |||
| Negative Agreement: 100% (58/58, 95% CI: 93.8% - 100%) | |||
| Agreement: 97.6% (80/82, 95% CI: 91.5% - 99.7%) |
In another clinical study in the northeastern United States, a total of 168 frozen samples from apparently healthy male and female subjects, pregnant women and patients suspected of being toxoplasma IgM positive were tested by IMMULITE Toxoplasma IgM and another commercially available enzyme immunoassay (Kit B - Vidas Toxo IgM). These samples were also tested for Toxoplasma IgG. The IMMULITE Toxoplasma IgM results were compared to the results of Kit B.
Comparison for all subjects
| Kit B | Positive | Indeterm | Negative |
|---|---|---|---|
| Positive | 28 | 4 | 1 |
| Indeterm | 0 | 0 | 2 |
| Negative | 6 | 5 | 122 |
| Positive Agreement: 96.6% (28/29, 95% CI: 82.2% - 99.9%) | |||
| Negative Agreement: 95.3% (122/128, 95% CI: 90.1% - 98.3%) | |||
| Agreement: 95.5% (150/157, 95% CI: 91.0% - 98.2%) |
Comparison for pregnant subjects
| Pos | Ind | Neg | |
|---|---|---|---|
| Pos | 16 | 4 | 0 |
| Ind | 0 | 0 | 1 |
| Neg | 4 | 2 | 64 |
| Positive Agreement: 100% (16/16, 95% CI: 79.4% - 100%) | |||
| Negative Agreement: 94.1% (64/68, 95% CI: 85.6% - 98.4%) | |||
| Agreement: 95.2% (80/84, 95% CI: 88.3% - 98.7%) |
In a clinical study in the southern United States, a total of 172 frozen samples from normal male and female subjects, pregnant women and patients suspected of being toxoplasma IgM positive were tested by IMMULITE 2000 toxoplasma IgM, and by a commercially available enzyme immunoassays (Kit A- Zeus Scientific Toxo IgM ELISA Test System). These samples were also tested for Toxoplasma IgG. The IMMULITE 2000 Toxoplasma IgM results were compared to the results of Kit A.
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Comparison for all subjects
| Kit A | Positive | Indeterm | Negative |
|---|---|---|---|
| Positive | 38 | 9 | 2 |
| Indeterm | 1 | 3 | 3 |
| Negative | 0 | 1 | 115 |
| Positive Agreement: 95.0% (38/40, 95% CI: 83.1% - 99.4%) | |||
| Negative Agreement: 100% (115/115, 95% CI: 96.8% - 100%) | |||
| Agreement: 98.7% (153/155, 95% CI: 95.4% - 99.8%) |
Comparison for pregnant subjects:
| IMMULITE 2000 Toxoplasma IgM | |||||
|---|---|---|---|---|---|
| Kit A | Pos | Ind | Neg | ||
| Pos | 23 | 7 | 1 | ||
| Ind | 0 | 2 | 2 | ||
| Neg | 0 | 0 | 58 | ||
| Positive Agreement: 95.8% (23/24, 95% CI: 78.9% - 99.9%) | |||||
| Negative Agreement: 100% (58/58, 95% CI: 93.8% - 100%) | |||||
| Agreement: | 98.8% (81/82, 95% CI: 93.4% - 100%) |
In a study at DPC, IMMULITE 2000 Toxoplasma IgM was compared to IMMULITE Toxoplasma IgM on 291 samples:
| Positive | Indeterm | Negative | |
|---|---|---|---|
| Positive | 15 | 0 | 0 |
| Indeterm | 3 | 0 | 0 |
| Negative | 0 | 5 | 268 |
| Positive Agreement: 100% (15/15, 95% CI: 78.2% - 100%) | |||
| Negative Agreement: 100% (268/268, 95% CI: 98.6% - 100%) | |||
| Agreement: 100% (283/283, 95% CI: 98.7% - 100%) |
Indeterminate results were excluded from calculations.
Performance Data
Precision (Serum): Precision studies for IMMULITE Toxoplasma IgM assay were conducted at three different sites: in-house at DPC (Site 1) and at two sites in the southern and northeasten United States (Sites 2 and 3). At Site 1, samples were assayed in duplicate over the course of 20 days, two runs per day, for a total of 40 runs and 80 replicates. (See "Site 1" table). At Sites 2 and 3, samples were assayed in triplicate over the course of 5 days, one run per day, for a total of 5 runs and 15 replicates. (See "Site 2" and "Site 3" tables). The means, within-run and total CVs were calculated by the Analysis of Variance. Results are expressed as a signal-to-cutoff ratio. Precision statistics are summarized below.
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| Within-Run | Total | ||||
|---|---|---|---|---|---|
| Mean | SD | CV | SD | CV | |
| 1 | 3.03 | 0.241 | 8.0% | 0.337 | 11.1% |
| 2 | 1.42 | 0.110 | 7.8% | 0.155 | 10.9% |
| 3 | 0.928 | 0.055 | 5.9% | 0.089 | 9.5% |
| 4 | 0.579 | 0.033 | 5.7% | 0.055 | 9.4% |
| 5 | 0.25* |
IMMULITE Toxoplasma IgM Precision - Serum (ratio): Site 1
- Consistently at a very low ratio
IMMULITE Toxoplasma IgM Precision - Serum (ratio): Site 2
| Mean | Within-Run | Total | |||
|---|---|---|---|---|---|
| SD | CV | SD | CV | ||
| 1 | 3.30 | 0.184 | 5.6% | 0.203 | 6.2% |
| 2 | 1.56 | 0.113 | 7.2% | 0.110 | 7.1% |
| 3 | 0.980 | 0.068 | 6.9% | 0.063 | 6.4% |
| 4 | 0.650 | 0.032 | 4.9% | 0.030 | 4.6% |
| 5 | 0.284* |
- Consistently at a very low ratio
IMMULITE Toxoplasma IgM Precision - Serum (ratio): Site 3
| Within-Run | Total | ||||
|---|---|---|---|---|---|
| Mean | SD | CV | SD | CV | |
| 1 | 3.10 | 0.110 | 3.5% | 0.152 | 4.9% |
| 2 | 1.38 | 0.099 | 7.2% | 0.097 | 7.0% |
| 3 | 0.910 | 0.029 | 3.2% | 0.056 | 6.2% |
| 4 | 0.600 | 0.022 | 3.7% | 0.030 | 5.0% |
| 5 | 0.266* | - | - | - | - |
- Consistently at a very low ratio
Precision (Serum): Precision studies for IMMULITE 2000 Toxoplasma IgM assay were conducted at two different sites: in-house at DPC (Site 1) and in the southern United States (Site 2). At both sites, samples were assayed in triplicate over the course of 5 days, one run per day, for a total of 5 runs and 15 replicates. (See "Site 1" and "Site 2" tables). The means, within-run and total CVs were calculated by the Analysis of Variance. Results are expressed as a signal-tocutoff ratio.
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| Mean | Within-Run | Total | |||
|---|---|---|---|---|---|
| SD | CV | SD | CV | ||
| 1 | 3.90 | 0.081 | 2.1% | 0.094 | 2.4% |
| 2 | 2.07 | 0.150 | 7.2% | 0.149 | 7.2% |
| 3 | 1.34 | 0.074 | 5.5% | 0.071 | 5.3% |
| 4 | 0.810 | 0.092 | 11.4% | 0.082 | 10.1% |
| 5 | 0.262* | – | – | – | – |
IMMULITE 2000 Toxoplasma IgM Precision - Serum (ratio): Site 1
*Consistently at a very low ratio
IMMULITE 2000 Toxoplasma IgM Precision - Serum (ratio): Site 2
| Within-Run | Total | |||||
|---|---|---|---|---|---|---|
| Mean | SD | CV | SD | CV | ||
| 1 | 3.20 | 0.130 | 4.1% | 0.138 | 4.3% | |
| 2 | 1.72 | 0.109 | 6.3% | 0.113 | 6.6% | |
| 3 | 1.18 | 0.044 | 3.7% | 0.078 | 6.6% | |
| 4 | 0.720 | 0.031 | 4.3% | 0.104 | 14.4% | |
| 5 | 0.300* |
*Consistently at a very low ratio
Precision (Plasma): Precision studies for IMMULITE Toxoplasma IgM and IMMULITE 2000 Toxoplasma IgM assays on plasma samples (EDTA and heparin) were conducted at DPC by testing samples in triplicate over the course of 3 days, two runs per day, for a total of 6 runs and 18 replicates. The means, within-run and total CVs were calculated by the Analysis of Variance. Results are expressed as a signal-to-cutoff ratio. Precision statistics are summarized below.
IMMULITE Toxoplasma IgM Precision - EDTA (ratio):
| Within-Run | Total | ||||
|---|---|---|---|---|---|
| Mean | SD | CV | SD | CV | |
| 1 | 0.262 | 0.023 | 8.8% | 0.033 | 12.6% |
| 2 | 1.11 | 0.052 | 4.7% | 0.069 | 6.2% |
| 3 | 1.33 | 0.075 | 5.6% | 0.077 | 5.8% |
| 4 | 1.66 | 0.087 | 5.2% | 0.083 | 5.0% |
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| Mean | Within-Run | Total | |||
|---|---|---|---|---|---|
| SD | CV | SD | CV | ||
| 1 | 0.259 | 0.0191 | 7.4% | 0.0183 | 7.1% |
| 2 | 1.00 | 0.06 | 6.0% | 0.052 | 5.2% |
| 3 | 1.21 | 0.097 | 8.0% | 0.084 | 6.9% |
| 4 | 1.51 | 0.084 | 5.6% | 0.073 | 4.8% |
IMMULITE 2000 Toxoplasma IgM Precision - EDTA (ratio):
IMMULITE Toxoplasma IgM Precision - Heparin (ratio):
| Within-Run | Total | ||||
|---|---|---|---|---|---|
| Mean | SD | CV | SD | CV | |
| 1 | 0.67 | 0.077 | 11.5% | 0.081 | 12.1% |
| 2 | 1.18 | 0.089 | 7.5% | 0.123 | 10.4% |
| 3 | 1.42 | 0.112 | 7.9% | 0.136 | 9.6% |
| 4 | 1.71 | 0.137 | 8.0 | 0.161 | 9.4% |
IMMULITE 2000 Toxoplasma IgM Precision - Heparin (ratio):
| Mean | Within-Run | Total | ||||
|---|---|---|---|---|---|---|
| SD | CV | SD | CV | |||
| 1 | 0.65 | 0.068 | 10.5% | 0.07 | 10.8% | |
| 2 | 1.2 | 0.061 | 5.1% | 0.057 | 4.8% | |
| 3 | 1.32 | 0.073 | 5.5% | 0.071 | 5.4% | |
| 4 | 1.54 | 0.084 | 5.5% | 0.078 | 5.1% |
Crossreactivity: Crossreactivity: A study was conducted to evaluate whether the measurement of Toxoplasma IgM antibody is affected by closely related microorganisms. Ninety-three seronegative sera containing antibodies to Varicella Zoster Virus (n=3), Measles (n=10), Cytomegalovirus (CMV) (n=10), Herpes Simplex Virus (n=10), Toxoplasma (n=10), mvcloplasma pneumoniae (n=10), Epstein-Barr Virus (n=10), Syphilis (n=10) and Parvovirus (n=10) and rheumatoid factor (n=10) were tested by IMMULITE and IMMULITE 2000 Toxoplasma IgM and all yielded negative results.
Conjugated or unconjugated bilirubin: no effect up to 20 mg/dL Interference: Lipemia: no effect of triglycerides up to 3000 mg/dL Hemoglobin: no effect up to 539 mg/dL
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Anti-coagulants: Twenty-eight blood samples drawn into plain, heparinized and EDTA vacutainer tubes were assayed by the IMMULITE 2000 Toxoplasma IgM assay. Results (in S/CO ratio) from the anticoagulant tubes were compared with those from the serum tubes in regression analyses:
| Regressions: | Heparin = $0.96 \times (Serum) + 0.05$EDTA = $0.93 \times (Serum) + 0.04$ | r = 0.991r = 0.992 |
|---|---|---|
| Means (S/CO ratio): | Serum = 0.80Heparin = 0.82EDTA= 0.79 |
Gel Barrier: Twenty-eight blood samples drawn into plain and SST vacutainer tubes were assayed by the IMMULITE 2000 Toxoplasma IgM assay. Results (in S/CO ratio) from the SST tubes were compared with those from the serum tubes in a regression analysis:
| Regressions: $SST = 0.97 \times (Serum) + 0.08$ | $r = 0.994$ |
|---|---|
| Means (S/CO ratio): Serum = 0.80 | |
| SST = 0.85 |
CDC Toxoplasma 1998 Human Serum Panel
The following information is from a serum panel obtained from the CDC and tested by DPC. The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC.
The panel consists of 32 positive and 65 negative samples. IMMULITE Toxoplasma IgM demonstrated 97.9% total agreement with the CDC results. There was 93.8% agreement with the positive specimens and 100% agreement with the negative specimens. IMMULITE 2000 Toxoplasma IgM demonstrated 99.0% total agreement with the CDC results. There was 96.9% agreement with the positive specimens and 100% agreement with the negative specimens.
Conclusion:
The data presented in this summary of safety and effectiveness is the data that the Food and Drug Administration used in granting DPC substantial equivalence for the IMMULITE Toxoplasma IgM and IMMULITE 2000 Toxoplasma IgM assays.
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Image /page/12/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three wavy lines representing its body and wings. The eagle is enclosed in a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. The text is written in a sans-serif font and is evenly spaced around the circle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JAN 1 0 2002
Edward M. Levine, Ph.D. Director of Clinical Affairs Diagnostic Products Corporation 5700 West 96th Street Los Angeles, CA 90045-5597
Re: K012075
Trade/Device Name: IMMULITE® and IMMULITE® 2000 Toxoplasma IgM Regulation Number: 21 CFR 866.3780 Regulation Name: Toxoplasma gondii serological reagents Regulatory Class: Class II Product Code: LGD Dated: November 30, 2001 Received: December 3, 2001
Dear Dr. Levine:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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Page 2 -
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 1 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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/dsma/dsmamain.html".
Sincerely yours,
Steven Sutman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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510(k) Number: Kolao 75 IMMULITE® Toxoplasma IgM and Device Name: IMMULITE® 2000 Toxoplasma IgM
Indications For Use:
IMMULITE® Toxoplasma IgM - For in vitro diagnostic use with the IMMULITE® Analyzers - for the presumptive qualitative detection of IgM antibodies to Toxoplasma gondii in human serum, particularly for women of childbearing age. When performed in conjunction with a Toxoplasma IgG assay, the IMMULITE® Toxoplasma IgM can be used as an aid in the presumptive diagnosis of acute, recent or reactive Toxoplasma gondii infection. This product has not been cleared/approved by the FDA for blood/plasma donor screening.
IMMULITE® 2000 Toxoplasma IgM - For in vitro diagnostic use with the IMMULITE® 2000 Analyzers - for the presumptive qualitative detection of IgM antibodies to Toxoplasma gondii in human serum, particularly for women of childbearing age. When performed in conjunction with a Toxoplasma IgG assay, the IMMULITE® 2000 Toxoplasma IgM can be used as an aid in the presumptive diagnosis of acute, recent or reactive Toxoplasma gondii infection. This product has not been cleared/approved by the FDA for blood/plasma donor screening.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Woody Dubois
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K012075
$\checkmark$
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use
(Optional Format 1-2-96)
§ 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).