(448 days)
The ADVIA Centaur Toxoplasma M (Toxo M) assay is an IgM antibody capture microparticle direct chemiluminometric in vitro diagnostic immunoassay intended for the qualitative detection of IgM antibodies to Toxoplasma gondii in serum or plasma (EDTA, heparin) using the ADVIA Centaur and ADVIA Centaur XP systems.
The ADVIA Centaur Toxo M assay is used to measure IgM antibody against T. gondii which is presumptive of an acute, recent, or reactivated toxoplasma infection. Any measurement of IgM antibody to T. gondii must be performed in conjunction with the determination of IgG antibody to T. gondii.
The ADVIA Centaur Toxo M assay is an immunoqlobulin class-capture sandwich immunoassay using direct, chemiluminometric technology. The anti-human IgM monoclonal antibody is covalently coupled to paramagnetic particles in the Solid Phase. In the Lite Reagent, the T. gondii antigen is complexed with an anti-p30 monoclonal antibody (F(ab)> fragment) labeled with acridinium ester. Antibody-antigen complexes will form if toxoplasma IgM is present in the sample.
The provided document describes a 510(k) premarket notification for a modified in vitro diagnostic immunoassay, the ADVIA Centaur Toxoplasma M (Toxo M) assay. The purpose of the submission is to demonstrate that the modified device is substantially equivalent to a legally marketed predicate device.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
Acceptance Criteria and Reported Device Performance
The document states that the purpose of the submission is to describe changes to the ADVIA Centaur Toxoplasma M (Toxo M) assay (K010755) and that the performance characteristics of the modified assay (precision, interference, and panel/patient sample testing) were evaluated and found comparable to those established for the previous version of the device (currently-marketed predicate).
The "Performance Characteristics" section in Table 2 (Similarities) lists the following for both the Predicate and Modified Device:
| Type of Performance Characteristic | Acceptance Criteria (from Predicate Device) | Reported Device Performance (Modified Device) |
|---|---|---|
| Positive Percent Agreement | 99.2% | Same (Implied to be 99.2% or comparable) |
| Negative Percent Agreement | 99.2% | Same (Implied to be 99.2% or comparable) |
The overall conclusion states: "The results of performance testing and verification activities demonstrate that the design modifications to the ADVIA Centaur Toxo M assay do not impact its safety or effectiveness and do not alter its performance claims or alter its intended use, as described in the labeling. Based on the results of comparative testing, the modified ADVIA Centaur Toxo M assay is substantially equivalent in principle and performance to the currently-marketed predicate device, ADVIA Centaur Toxo M, cleared under 510(k) K010755."
This implies that the modified device met the same performance metrics as the predicate, which serves as the acceptance criteria.
Study Details and Data Provenance
The document describes "performance testing and verification activities" and "comparative testing" against the predicate device.
1. Sample sizes used for the test set and the data provenance:
- The document does not explicitly state the specific sample sizes used for the test set in the analytical performance and panel/patient sample testing. It mentions "testing with panel samples and patient samples."
- Data Provenance: The document does not specify the country of origin for the data. It also does not explicitly state whether the studies were retrospective or prospective, though "performance testing and verification activities" would typically involve prospective testing with samples.
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not provided in the document. The device is an in vitro diagnostic immunoassay, and its performance is typically assessed against a known standard or reference method, rather than expert clinical interpretation of images. The ground truth for this type of test generally comes from well-characterized reference panels or clinically confirmed diagnoses.
3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Adjudication methods like 2+1 or 3+1 are typically used for subjective assessments, such as image interpretation by radiologists. For an objective immunoassay, an "adjudication method" in this sense is not applicable. The outcome is a quantitative measurement translated into a qualitative result (reactive/nonreactive) based on a defined cutoff.
4. 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 is an in vitro diagnostic immunoassay, not an AI-assisted diagnostic imaging device that involves "human readers." Therefore, an MRMC comparative effectiveness study is not applicable and was not performed.
5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- This is an immunoassay device, which by its nature operates "standalone" in that it provides a result (reactive/nonreactive) based on its chemical and detection processes. While a human operates the instrument and interprets the final qualitative result (Index Value to reactive/nonreactive), the core measurement is a direct output of the algorithm/instrument. The device itself is the "standalone" entity.
6. The type of ground truth used (expert concensus, pathology, outcomes data, etc):
- The document mentions "panel samples" and "patient samples." For an immunoassay detecting antibodies, the ground truth would typically be established by:
- Reference laboratory testing using a gold standard method.
- Clinical diagnosis based on a combination of patient symptoms, additional laboratory tests, and clinical follow-up.
- Well-characterized control panels with known positive and negative status for T. gondii IgM antibodies.
- The document does not explicitly state which specific type/combination was used, but it would not be expert consensus in the sense of subjective interpretation, nor pathology in the tissue sense, but rather definitive lab results or clinical outcomes.
7. The sample size for the training set:
- This is a 510(k) submission for a modified immunoassay, not a machine learning or AI device that typically involves a distinct "training set." The development of the assay's cutoff values and optimization would have involved internal development processes, akin to "training," but the document does not specify a numerical sample size for this developmental phase.
8. How the ground truth for the training set was established:
- Similar to the testing set, the ground truth for the development/optimization of the immunoassay would have been established through well-characterized samples, reference methods, or clinically confirmed cases. As it's not an AI model, the concept of "ground truth for training set" in the context of supervised learning does not directly apply in the same manner. The establishment of reagent formulations and reaction parameters is based on biochemical principles and empirical optimization using characterized samples.
In summary, the provided document focuses on demonstrating substantial equivalence of a modified immunoassay by showing its performance is comparable to the predicate device, especially in terms of positive and negative percent agreement. Many of the questions regarding MRMC studies, expert adjudication, and distinct training/test sets are more relevant to AI/ML or imaging devices than to the described immunoassay.
§ 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).