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Elecsys Anti-SARS-CoV-2 is an immunoassay intended for the in vitro qualitative detection of total antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in human serum and Li-heparin, K2-EDTA and K3-EDTA plasma collected on or after 15 days post-symptom onset. The test is intended as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e 601 immunoassay analyzer.

Elecsys Anti-SARS-CoV-2 is a qualitative, serological, double-antigen sandwich principle immunoassay to be used on the cobas e 601 analyzer with an 18-minute test time. Results are determined automatically by the software by comparing the electrochemiluminescence signal obtained from the reaction product of the sample with the signal of the cutoff value previously obtained by calibration. The Elecsys Anti‑SARS‑CoV-2 assay uses a recombinant protein representing the nucleocapsid (N) antigen for the determination of antibodies against SARS‑CoV‑2.

The reagent working solutions include: rackpack (kit placed on the analyzer)

• M Streptavidin-coated microparticles (transparent cap), 1 bottle, 12 mL: Streptavidin-coated microparticles 0.72 mg/mL; preservative.
• R1 SARS-CoV-2-Ag~biotin, (gray cap), 1 bottle, 16 mL: Biotinylated SARS‑CoV‑2‑specific recombinant antigen (E. coli)

The provided FDA 510(k) clearance letter and summary describe the acceptance criteria and the study that proves the device, Elecsys Anti-SARS-CoV-2, meets those criteria.

Here's the breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as clear numerical targets for PPA and NPA prior to presenting the results. However, implied acceptance criteria for qualitative serology tests typically involve a high percentage of agreement. Based on the reported performance, we can infer the acceptance criteria were met by these results.

Additional Non-Clinical Acceptance Criteria (Met for all):

• Precision: Standard Deviation (SD) and Coefficient of Variance (CV) values within predetermined limits for repeatability, between-run, between-day, between-lot, and between-site precision.
• Hook Effect: No hook effect observed.
• Potential Interference (Endogenous Substances): Biotin tolerance $\le$ 1200 ng/mL; no interference within specification for Intralipid, Bilirubin, Hemoglobin, Rheumatoid Factor, IgG, IgM, IgA, human serum albumin, ANA, cholesterol, and triglycerides.
• Analytical Cutoff Sensitivity: Cutoff of 1.00 COI corresponds to 1.137 BAU/mL (demonstrated alignment with international standard).
• Analytical Specificity- Potential Cross-Reactivity: False positive rate for cross-reacting antibodies within acceptable limits (2 false positives out of 7 MERS-CoV glycoprotein samples observed, overall 1836 samples tested).
• Exogenous Interference: Results within specification for 17 common drugs and 18 special drugs (with the exception of Ritonavir, which was within specification at 1x daily dose).
• Matrix Comparison: Matrix equivalency demonstrated for serum, Li-Heparin, K2-EDTA, K3-EDTA plasma, and separation gel tubes.
• Reagent, Calibrator, and Control Stability: Met stated storage times and conditions (e.g., 28 days on-board reagent, 10 hours on-board PreciControl, 30 days refrigerator after first opening, 28 days after first opening for PreciControl, 25 days lot calibration stability, 7 days on-board calibration stability).
• Specimen Stability: Met stated storage times and conditions (e.g., 7 days at 15-25°C, 14 days at 2-8°C, 28 days at -20°C, 3 freeze-thaw cycles).
• Fresh/Frozen Study: All results within specification for fresh vs. frozen samples.

2. Sample Sizes Used for the Test Set and the Data Provenance

• Negative Percent Agreement (NPA):
  • Sample Size: 9007 pre-pandemic specimens.
  • Data Provenance: Not explicitly stated (e.g., country of origin), but implicitly "pre-pandemic" suggests samples collected before December 2019. This is retrospective data.
• Positive Percent Agreement (PPA) - Traditional Clinical Study:
  • Sample Size: 254 specimens collected $\ge$ 15 days post symptom onset (DPSO), excluding COVID-19 vaccinated individuals and immunocompromised subjects.
  • Data Provenance: Not explicitly stated (e.g., country of origin), but described as collected under "routine laboratory conditions." This is retrospective or potentially a mix of retrospective and prospective, reflecting real clinical samples.
• PPA - Real-World Data:
  • Sample Size: 285 samples from non-immunocompromised subjects who did not receive the COVID-19 vaccine, collected $\ge$ 15 DPSO.
  • Data Provenance: Collaborating institution in the United States, collected from March 2020 – March 2021. This is retrospective data.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

For this serology test, the ground truth is established through laboratory methods, not by human expert readers in the way an imaging AI would be adjudicated.

• NPA: Ground truth was "presumed to be negative for anti-SARS-CoV-2 antibodies" based on collection before December 2019, prior to the widespread circulation of SARS-CoV-2.
• PPA (Traditional Clinical Study): Ground truth was established by a composite comparator method comprised of 3 SARS-CoV-2 serology assays (including the predicate assay). Seropositivity was determined by majority rule ($\ge$ 2 out of 3). Additionally, these individuals had a history of SARS-CoV-2 infection confirmed by a prior FDA authorized RT-PCR test.
• PPA (Real-World Data): Ground truth was established by PCR as the comparator. Data was collected from electronic medical records and laboratory information systems.

Qualifications of Experts: Not applicable in the context of serology ground truth determination as it relies on other laboratory assays.

4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set

• NPA: No adjudication method as samples were "presumed negative" based on collection date.
• PPA (Traditional Clinical Study): A form of "majority rule" for the composite comparator method was used: $\ge$ 2 out of 3 serology assays. This is akin to a 2/3 agreement rule, but applied to the reference method rather than human readers adjudicating an AI's output. The confirmatory RT-PCR also served as a strong initial ground truth.
• PPA (Real-World Data): PCR was the direct comparator, so no explicit adjudication method beyond the result of the PCR test itself.

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 is a clinical laboratory immunoassay (serology test), not an AI software intended for medical image interpretation or human-in-the-loop assistance. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

The device itself is a standalone immunoassay system (Elecsys Anti-SARS-CoV-2 on the cobas e 601 analyzer) that provides a qualitative result (positive/negative) automatically. The entire clinical performance evaluation section describes the standalone performance of this device against established ground truths. Thus, a standalone performance evaluation was indeed done.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

• NPA: Pre-pandemic sample collection date (before December 2019), implying presumed negative status. This serves as a strong epidemiological ground truth for SARS-CoV-2 negativity.
• PPA (Traditional Clinical Study):
  • Composite Comparator Method: Majority rule ($\ge$ 2 out of 3) of other FDA-de novo and EUA-authorized Anti-SARS-CoV-2 serology assays.
  • Confirmatory RT-PCR: Individuals had a history of SARS-CoV-2 infection confirmed by a prior FDA authorized RT-PCR test.
• PPA (Real-World Data): FDA authorized RT-PCR test results from electronic medical records and laboratory information systems.

In summary, the ground truth primarily relies on a combination of other FDA-authorized laboratory tests (serology and RT-PCR) and epidemiological/temporal evidence.

8. The Sample Size for the Training Set

This document describes the validation of a serology immunoassay, not a machine learning or AI model. Therefore, there is no "training set" in the context of AI model development. The "training" for such an assay would typically involve analytical development and optimization of reagents and protocols, not a data-driven training set in the AI sense.

9. How the Ground Truth for the Training Set Was Established

As there is no AI training set described or applicable for this type of device, this question is not relevant to the provided information. The ground truth for performance evaluation was established as described in point 7.

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