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The Alinity i Rubella IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of IgG antibodies to rubella virus in human serum, serum separator, and plasma tubes (lithium heparin, lithium heparin separator, and tripotassium EDTA) on the Alinity i system.

The Alinity i Rubella IgG assay is to be used as an aid in the determination of immune status to rubella in individuals including women of child-bearing age.

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

The performance of this device has not been established for cord blood or neonatal samples. Likewise, performance has not been established for populations of immunocompromised or immunosuppressed individuals.

The Alinity i Rubella IgG assay is an automated, two-step immunoassay for the quantitative determination of anti-rubella IgG in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology.

Sample, partially purified rubella virus-coated paramagnetic microparticles, and assay diluent are combined and incubated. The anti-rubella IgG present in the sample bind to the rubella virus coated microparticles. The mixture is washed. Anti-human IgG acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added.

The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a direct relationship between the amount of anti-rubella IgG in the sample and the RLU detected by the system optics.

Here's an analysis of the acceptance criteria and the study proving the device meets those criteria, based on the provided FDA 510(k) clearance letter for the Alinity i Rubella IgG assay.

Overview of the Device and its Purpose:

The Alinity i Rubella IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of IgG antibodies to the rubella virus. It's intended to aid in determining the immune status to rubella, particularly in women of child-bearing age. It is a diagnostic device, not an AI/ML-driven one, so some of the requested points regarding AI/ML studies (like MRMC studies, training set details, expert ground truth establishment for AI) are not applicable.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a diagnostic assay and not an AI/ML device, the acceptance criteria are related to the analytical and clinical performance of the immunoassay itself rather than metrics like AUC, sensitivity/specificity for object detection, or F1 scores inherent to AI. The key performance indicators are Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a composite comparator method.

Acceptance Criteria (Implied by Performance Targets in Context of 510(k) Equivalence):

For a 510(k) substantial equivalence determination, the new device must demonstrate performance that is as safe and effective as a legally marketed predicate device. While explicit numerical acceptance criteria for PPA and NPA are not stated in the summary, typical expectations for diagnostic assays like this are high agreement rates (e.g., >90% or 95%) with the comparator method, especially in categories such as "Reactive" and "Nonreactive." The confidence intervals should also demonstrate a reasonable level of certainty around these agreement rates. The acceptance of the listed performance values below implies that these meet the FDA's criteria for substantial equivalence to the predicate.

Study Description:

The provided document describes several studies to demonstrate the performance of the Alinity i Rubella IgG assay. The most relevant for proving it meets "acceptance criteria" for clinical use are the Clinical Agreement Study and the CDC Panel Agreement Study.

1. Clinical Agreement Study (Comparative Effectiveness):

• Sample Size:
  • Total (including US & OUS): 946 (Routine US) + 457 (Routine OUS) + 435 (Pregnant US) + 52 (Supplemental Negative Pregnant US) + 59 (Supplemental Negative Pregnant OUS) + 135 (Preselected Negative OUS) = 2084 specimens.
• Data Provenance:
  • Country of Origin: Specimens collected from individuals in the US and Outside of the US (OUS).
  • Retrospective/Prospective: Described as "consecutively collected remnant specimens" and "additionally obtained." This mix likely implies a retrospective collection of existing samples, though the "consecutively collected" part could suggest some prospective elements for the routine orders. It's not explicitly stated as purely prospective.
• Number of Experts for Ground Truth: Not applicable in the traditional sense of subjective interpretation (e.g., radiology reads). The ground truth for this diagnostic assay is established by a "composite comparator method" consisting of 3 FDA-cleared anti-rubella IgG assays. This is an objective measurement rather than expert consensus on images.
• Qualifications of Experts: N/A as it's an objective comparator method.
• Adjudication Method: For specimens with initially equivocal results on the primary comparator device (between 5 and <10 IU/mL), the samples were tested with 2 additional FDA-cleared devices, and the final result was a 2 out of 3 consensus. This acts as the adjudication process for discordant or equivocal primary results.
• Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study: No, this is not an MRMC study. MRMC studies are typically performed for imaging devices or AI tools where multiple human readers interpret cases, and the AI's impact on their performance is evaluated. This is a comparison between two assays directly: the investigational assay versus a composite reference method.
  • Effect Size of Human Readers Improvement with AI vs. without AI assistance: Not applicable.
• Standalone (Algorithm only) Performance: Yes, the performance metrics (PPA and NPA) represent the standalone performance of the Alinity i Rubella IgG assay compared to the composite ground truth. There is no human-in-the-loop assistance concept for this type of test.
• Type of Ground Truth Used: Objective measurement by a composite comparator method of 3 FDA-cleared anti-rubella IgG assays, with 2 out of 3 consensus for equivocal initial results. This is considered a highly robust and accepted method for establishing ground truth in serological assays.
• Sample Size for Training Set: Not applicable. This is a diagnostic immunoassay kit, not an AI/ML algorithm that requires a training set in the computational sense. The reagents and assay parameters are developed through laboratory research and optimization, not machine learning on large datasets in the way an AI model is trained.
• How Ground Truth for the Training Set was Established: Not applicable.

2. CDC Panel Agreement Study (External Validation):

• Sample Size: 100 specimens (82 true positive, 18 true negative).
• Data Provenance:
  • Country of Origin: CDC Rubella Reference Sera Panel (collected in 2014), likely representative of a US population.
  • Retrospective/Prospective: Retrospective, using a pre-characterized reference panel.
• Number of Experts for Ground Truth: Not applicable. The "ground truth" here is the established classification by the CDC reference laboratory (which often involves highly characterized, validated methods, potentially including biological principles or reference assays that determine "true" positivity/negativity).
• Qualifications of Experts: N/A.
• Adjudication Method: N/A. The CDC panel has established "true" status.
• MRMC Study: No, not applicable.
• Standalone Performance: Yes, this is a standalone performance test against a known, external standard.
• Type of Ground Truth Used: Reference panel / External standard (CDC Rubella Reference Sera Panel). This is a very strong form of ground truth for diagnostic assays, providing an independent validation.
• Sample Size for Training Set: N/A.
• How Ground Truth for the Training Set was Established: N/A.

Summary of Nonclinical Performance Studies (Analytical Performance):

Beyond the clinical and CDC studies, the filing also details robust nonclinical studies that establish the analytical performance of the device, which also implicitly have their own "acceptance criteria" for a successful product. These include:

• Within-Laboratory Precision (20-Day): Demonstrated low coefficient of variation (%CV) for controls and various panels.
• Reproducibility Study (5-Day): Conducted at 3 US sites to assess consistency.
• Lower Limits of Measurement (LoB, LoD, LoQ): Determined the lowest detectable and quantifiable concentrations.
• Linearity: Confirmed the assay performs reliably across its claimed measuring interval.
• Analytical Specificity / Interference: Tested for the impact of endogenous substances (e.g., bilirubin, hemoglobin) and exogenous substances (e.g., common drugs).
• Potential Cross-Reactivity: Evaluated samples from individuals with other conditions (e.g., other viral infections, autoimmune diseases).
• Matrix Equivalency: Ensured performance is consistent across different blood collection tube types (serum, plasma).

These analytical studies collectively demonstrate that the Alinity i Rubella IgG assay is robust, precise, accurate, and reliably measures rubella IgG antibodies in various clinical settings and sample types, thus fulfilling the necessary technical acceptance criteria for a diagnostic kit.

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