Alinity i Toxo IgM

• K Number: K233932
• Device Name: Alinity i Toxo IgM
• Manufacturer: Abbott Laboratories
• Date Cleared: 2024-08-30 ( 260 days)
• Product Code: LGD
• Regulation Number: 866.3780
• Type: Traditional
• Panel: MI
• Reference & Predicate Devices: k923166

Intended Use

The Alinity i Toxo IgM assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of IgM antibodies to Toxoplasma gondii in human serum, serum separator, and plasma tubes (lithium heparin, lithium heparin separator, and tripotassium EDTA) on the Alinity i system.

The Alinity i Toxo IgM assay is to be used as an aid in the diagnosis of acute or recent Toxoplasma gondii infection in suspected individuals including women of child-bearing age. It is recommended that the assay be performed in conjunction with a Toxoplasma gondii IgG assay.

The Alinity i Toxo IgM assay has not been cleared for use in screening blood, plasma, or tissue donors.

Device Description

The Alinity i Toxo IgM assay is an automated, two-step immunoassay for the qualitative detection of IgM antibodies to Toxoplasma gondii in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology. The kit includes Reagents (Microparticles and Conjugate), Calibrator, and Controls.

AI/ML Overview

The provided text is a 510(k) Summary for the Abbott Laboratories Alinity i Toxo IgM assay. It details the device's characteristics, intended use, and performance studies to demonstrate substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided document:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly present a "table of acceptance criteria" with predefined thresholds that the device must meet in a comparative format. Instead, it presents various performance studies (precision, analytical specificity, cross-reactivity, matrix equivalency, class specificity, CDC panel agreement, and clinical agreement) and then summarizes the results of these studies. The implicit acceptance criteria are the successful demonstration of performance comparable to a cleared device and FDA guidance documents.

However, we can infer some "acceptance criteria" from the results presented, especially in the CDC Panel Agreement and Clinical Agreement sections. The document highlights the Percentage Positive Agreement (PPA) and Percentage Negative Agreement (NPA) as key metrics.

Here's a table focusing on the performance of the Alinity i Toxo IgM assay as tested against established benchmarks:

Table of Device Performance Metrics

Performance Metric	Acceptance Criteria (Implicit/Inferred)	Reported Device Performance
Precision	Low Coefficient of Variation (CV%) for various panels and controls, demonstrating consistent results within and across runs, days, and lots.	Within-Laboratory (20-Day):

• Negative Control: SD 0.014 (NAc)
• Positive Control: SD 0.104 (3.8% CV)
• High Nonreactive Panel: SD 0.040 (NAc)
• Low Reactive Panel: SD 0.064 (4.7% CV)
• Reactive Panel: SD 0.109 (4.3% CV)

Reproducibility (5-Day, Multi-Site):

• Negative Control: SD 0.018 (NAc)
• Positive Control: SD 0.132 (5.1% CV)
• High Nonreactive Panel: SD 0.041 (NAc)
• Low Reactive Panel: SD 0.067 (5.1% CV)
• Reactive Panel: SD 0.136 (5.5% CV)
  (Overall low CVs demonstrate good precision.) |
  | Analytical Specificity (Interfering Substances) | No significant interference from common endogenous substances, other conditions, or drugs at specified concentrations. | Endogenous Substances: No significant interference observed for Unconjugated Bilirubin (40 mg/dL), Conjugated Bilirubin (40 mg/dL), Hemoglobin (1000 mg/dL), Total Protein (15 g/dL), Triglycerides (3000 mg/dL).
  Other Conditions: No significant interference observed for HAMA (800 ng/mL), RF (200 IU/mL).
  Drugs: No significant interference observed for Ascorbic Acid (300 mg/L), Atovaquone (120 mg/L), Beta Carotene (6 mg/L), Biotin (4250 ng/mL), Clindamycin (5.1 mg/dL), Folic Acid (100 nmol/L), Pyrimethamine (15 mg/L), Spiramycine (4.2 mg/L), Sulfadiazine (25.5 mg/dL), Sulfamethoxazole (210 mg/dL), Trimethoprim (4.2 mg/dL). |
  | Cross-Reactivity | Minimal false reactive results from individuals with other medical conditions and high titer Toxoplasmosis IgG. | Out of 177 specimens from individuals with various unrelated conditions (e.g., CMV, EBV, HSV, Flu vaccine recipients, Syphilis, etc.) and high titer Toxoplasmosis IgG, only 1 out of 10 RF (Rheumatoid Factor) specimens resulted in a false reactive result. |
  | Matrix Equivalency | Acceptable performance across different blood collection tube types (serum, serum separator, lithium heparin plasma, lithium heparin plasma separator, and tripotassium EDTA plasma). | All tested blood collection tube types were found acceptable for use with the Alinity i Toxo IgM assay. |
  | Class Specificity | Reactivity only to human anti-Toxoplasma IgM and no reactivity to human anti-Toxoplasma IgG. | Demonstrated reactivity only to human anti-Toxoplasma IgM, with no reactivity to human anti-Toxoplasma IgG. |
  | CDC Panel Agreement | High positive and negative percent agreement with the CDC Toxoplasma 1998 Human Serum Panel. | PPA: 100.00% (32/32) with 95% CI (89.28%, 100.00%)
  NPA: 100.00% (65/65) with 95% CI (94.42%, 100.00%) |
  | Clinical Agreement | High positive and negative percent agreement with an FDA-cleared predicate assay. | Population 1 (n=897):
• PPA: 94.94% (150/158) with 95% CI (90.33%, 97.41%)
• NPA: 94.44% (697/738) with 95% CI (92.55%, 95.88%)
  Population 2 (pregnant women, n=234):
• PPA: 94.74% (18/19) with 95% CI (75.36%, 99.06%)
• NPA: 100.00% (215/215) with 95% CI (98.24%, 100.00%) |

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Cutoff Establishment (Internal Validation): 1219 samples (1053 nonreactive, 166 reactive). Data provenance not specified (likely internal laboratory samples, retrospective).
• Within-Laboratory Precision (20-Day): Not directly a "test set" sample size for diagnostic accuracy, but involves 2 controls and 4 plasma panels tested multiple times (360-360 replicates per control/panel).
• Analytical Specificity (Interference): Samples with target ranges of anti-Toxo IgM (0.60 to 0.99 S/CO and 1.00 to 2.00 S/CO) spiked with interferents. Specific number of samples per substance/condition not given, but refers to CLSI guidance.
• Cross-Reactivity: 177 serum specimens from individuals with other medical conditions and high titer Toxoplasmosis IgG. Data provenance not specified (likely retrospective or collected for study).
• Matrix Equivalency: 43 donors (20 reactive, 23 nonreactive). Samples collected in 5 different tube types. Data provenance not specified.
• Class Specificity: Not specified as a separate sample set size, likely inferred from internal controls or prepared samples.
• CDC Panel Agreement: 97 specimens (32 true positive, 65 true negative) from the CDC Toxoplasma 1998 Human Serum Panel. This is a retrospective, well-characterized panel.
• Reproducibility (5-Day, Multi-Site): Same sample panels as within-laboratory precision (controls and 4 plasma panels) tested across 3 US sites. 360 replicates per sample.
• Clinical Agreement:
  • Population 1: 897 consecutively collected remnant specimens. 169 from the US and 710 from outside the US. This implies a mixture of retrospective and potentially prospective collection depending on "consecutively collected remnant specimens."
  • Population 2: 207 consecutively collected remnant specimens from pregnant women in the US. This implies a mixture of retrospective and potentially prospective collection.
  • Total US specimens in the clinical study: 376 (169 from Pop 1 + 207 from Pop 2).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

• The document does not mention the use of experts (e.g., radiologists) for establishing ground truth, as this is an in vitro diagnostic (IVD) device for serological testing.
• Ground Truth for IVDs: For IVDs like this, "ground truth" is typically established by:
  • Reference Method/Predicate Device: The clinical agreement study uses an "FDA-cleared, commercially available anti-Toxo IgM assay" (the bioMérieux VIDAS TOXO IgM assay) as the comparator, which serves as the reference standard for clinical performance.
  • Well-Characterized Panels: The CDC Toxoplasma 1998 Human Serum Panel is used, where the "true positive" and "true negative" status of specimens are established by the CDC through their own rigorous characterization processes.
  • Internal Characterization: For studies like cutoff determination, samples are "characterized with a commercially available anti-Toxo IgM assay," implying the use of an existing reference method.

Therefore, the "experts" in this context are the established reference methods and panels from organizations like the CDC, rather than individual human interpretative experts for modalities like radiology.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

• Adjudication methods like 2+1 or 3+1 are typically used in imaging studies where multiple human readers interpret images, and discrepancies are resolved by an expert panel.
• For an IVD assay like this, the "adjudication" is inherent in the comparison to a predefined reference standard (the predicate device or the CDC panel's established status) or by the assay's internal cutoff determination process.
• The document does not describe any specific human "adjudication" process for the result of the Alinity i Toxo IgM assay beyond its comparison to the comparator assay or CDC panel.

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

• No, an MRMC comparative effectiveness study was not done.
• MRMC studies are specific to AI/CADe (Computer-Assisted Detection) or CADx (Computer-Assisted Diagnosis) devices that assist human readers in interpreting medical images.
• The Alinity i Toxo IgM assay is an in vitro diagnostic (IVD) device that performs a laboratory test for antibodies; it does not involve human readers interpreting images or AI assistance for such interpretation.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

• Yes, this device inherently performs as a standalone "algorithm" in the sense that it is an automated laboratory assay. The results (S/CO values) are generated by the instrument based on its chemical reactions and detection system, and then interpreted against predefined cutoffs.
• While a human operator loads samples and manages the instrument, the diagnostic detection (CMIA technology for Toxo IgM antibodies) is fully automated by the device itself, without human interpretation of the primary result (RLU or S/CO). The physician then interprets the qualitative result (Reactive, Grayzone, Nonreactive) in the context of the patient's clinical picture.
• The performance metrics (precision, analytical specificity, cross-reactivity, CDC panel agreement, clinical agreement) are all measures of this standalone analytical performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for this device was established primarily through:

• Reference Standard/Predicate Assay: For the clinical agreement study, the Alinity i Toxo IgM assay results were compared against an FDA-cleared, commercially available anti-Toxo IgM assay (the bioMérieux VIDAS TOXO IgM assay). This predicate device serves as the clinical "ground truth" or reference.
• Well-Characterized Panel: For the CDC Panel Agreement study, the ground truth was the established status of samples within the CDC Toxoplasma 1998 Human Serum Panel (i.e., known true positive or true negative Toxoplasma specimens). This panel's characterization is highly reliable.
• Internal Characterization/Comparator Assay: For cutoff establishment, samples were characterized using a "commercially available anti-Toxo IgM assay."

8. The sample size for the training set

• The document does not explicitly describe a separate "training set" in the context of machine learning or AI model development.
• For IVD devices, a "training set" might loosely refer to the samples used during assay development and optimization (e.g., for reagent formulation, instrument parameters, and initial cutoff setting), but this data is not typically reported as a formalized "training set" size in the same way as for AI.
• The closest description of data used for internal calibration/optimization is the 1219 samples used for assay cutoff establishment (1053 anti-Toxo IgM nonreactive samples and 166 anti-Toxo IgM reactive samples). This dataset could be considered analogous to a development/training set for establishing the assay's interpretation rules, although it's crucial to understand this isn't an AI/ML context.

9. How the ground truth for the training set was established

• As mentioned above, there isn't a traditional "training set" for an AI model.
• For the 1219 samples used to establish the assay cutoff, the ground truth (reactive/nonreactive) was established by characterizing these samples with a "commercially available anti-Toxo IgM assay." This means the existing, established methods of Toxo IgM detection were used to classify these samples, allowing the Alinity i assay to be "trained" (or its cutoff optimized) to align with those established classifications.

Regulation Number and Section

§ 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).