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The ARCHITECT Cyclosporine assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of cyclosporine in human whole blood on the ARCHITECT i System. The ARCHITECT Cyclosporine assay is used as an aid in the management of heart, liver, and kidney transplant patients receiving cyclosporine therapy.

The ARCHITECT Cyclosporine Calibration are for the ARCHITECT i System when used for the quantitative determination of cyclosporine in human whole blood.

The ARCHITECT Cyclosporine Whole Blood Precipitation Reagent is for the extraction of cyclosporine from samples (human whole blood patient specimens, controls, and ARCHITECT Cyclosporine Calibrators) to be tested on the ARCHITECT i System.

The ARCHITECT Cyclosporine assay is a two-step immunoassay for the quantitative determination of cyclosporine in human whole blood using CMIA technology with flexible assay protocols, referred to as Chemiflex.

Prior to the initiation of the automated ARCHITECT sequence, a manual pretreatment step is performed in which the whole blood sample is lysed with a solubilization reagent, extracted with a precipitation reagent and centrifyged. The supernatant is decanted into a Transplant Pretreatment Tube, which is placed onto the ARCHITECT i System.

In the first step, sample, assay diluent, and anti-cyclosporine coated paramagnetic microparticles are combined to create a reaction mixture. Cyclosprorine present in the sample binds to the anti-cyclosporine coated microparticles. After washing, cyclosporine acridiniumlabeled conjugate is added to create a reaction mixture in the second step. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). An indirect relationship exists between the amount of cyclosporine in the sample and the RLUs detected by the ARCHITECT i System optics.

Here's a breakdown of the acceptance criteria and the studies performed for the ARCHITECT Cyclosporine Assay, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" for precision, linearity, functional sensitivity, or analytical sensitivity in numerical terms (e.g., "Precision must be <= 10% CV"). Instead, it reports the determined performance characteristics. However, for the substantial equivalence study, implicit acceptance is based on strong correlation and a reasonable intercept/slope compared to the predicate and LC/MS/MS.

2. Sample Sizes and Data Provenance

Substantial Equivalence Study:

• Sample Size (Test Set): 227 observations (human whole blood specimens).
• Data Provenance: Human whole blood specimens from heart, renal, and liver transplant patients receiving cyclosporine therapy. This indicates prospective or retrospective clinical samples, primarily from a clinical setting. The country of origin is not specified.

Precision Study:

• Sample Size (Test Set): Not explicitly stated as a single number for a "test set." Instead:
  • 3 levels of Abbott Immunosuppressant-MCC (levels 1, 3, and 4)
  • 2 pooled patient samples
  • 3 human whole blood samples spiked with cyclosporine
• "two lots of reagents, on two instruments, in replicates of two at two separate times per day for 20 days."
• Data Provenance: Clinical samples (pooled patient samples, spiked human whole blood). Country of origin not specified.

Linearity Study:

• Sample Size (Test Set): High concentration cyclosporine whole blood specimens (number not specified) used to create dilutions.
• Data Provenance: Clinical samples (high concentration cyclosporine whole blood specimens). Country of origin not specified.

Functional Sensitivity Study:

• Sample Size (Test Set): Whole blood specimens spiked with cyclosporine (number not specified) "tested in replicates of 10, twice a day, for five days."
• Data Provenance: Spiked whole blood specimens. Country of origin not specified.

Analytical Sensitivity Study:

• Sample Size (Test Set): n=24 runs, 10 replicates for calibrator A, and 4 replicates for calibrator B per run.
• Data Provenance: Calibrator materials. Country of origin not specified.

Interference Study:

• Sample Size (Test Set): Whole blood specimens (number not specified) supplemented with various drugs and potential interfering compounds.
• Data Provenance: Clinical samples (whole blood specimens). Country of origin not specified.

Specificity Study:

• Sample Size (Test Set): 5 whole blood specimens augmented with cyclosporine and spiked with cross-reactant solutions.
• Data Provenance: Clinical samples (whole blood specimens). Country of origin not specified.

3. Number of Experts and Qualifications for Ground Truth

• The document describes analytical performance studies and equivalence to a predicate device and LC/MS/MS, not a diagnostic imaging or pathology study requiring human expert consensus for "ground truth" in the traditional sense.
• For the "ground truth" in the substantial equivalence study: The predicate device (ABBOTT TDx/TDxFLx Cyclosporine Monoclonal Whole Blood) and LC/MS/MS are considered the reference methods. The performance of these reference methods themselves serves as the "ground truth." There is no mention of human experts establishing ground truth for these analytical measurements.

4. Adjudication Method for the Test Set

• Not applicable. This is an in-vitro diagnostic device measuring an analyte concentration, not a study requiring human adjudication of diagnostic findings. The "adjudication" is done by comparing the device's output to the output of established reference methods (predicate device and LC/MS/MS).

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No. An MRMC study is typically for evaluating diagnostic imaging or screening devices where human readers interpret cases. This submission is for an in-vitro diagnostic assay for quantitative measurement of cyclosporine.

6. Standalone Performance Study (Algorithm Only)

• Yes, implicitly. All the performance characteristic studies (precision, linearity, functional sensitivity, analytical sensitivity, interference, specificity) and the substantial equivalence study (comparison to predicate and LC/MS/MS) represent the standalone performance of the ARCHITECT Cyclosporine Assay without human intervention in the measurement process itself, beyond sample preparation and loading onto the automated instrument. The device is intended to be automated.

7. Type of Ground Truth Used

• Substantial Equivalence Study: The ground truth was established by comparison to:

  • Predicate Device: ABBOTT TDx/TDxFLx Cyclosporine Monoclonal Whole Blood assay. This is an existing, legally marketed diagnostic device.
  • Reference Method: LC/MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry). This is a highly accurate and precise analytical technique, often considered a "gold standard" for quantitative measurements of many analytes in clinical chemistry.

• Other Performance Studies (Precision, Linearity, etc.): The ground truth was established by statistical analysis of repeat measurements, dilutions with known concentrations, or spiked samples with known concentrations.

8. Sample Size for the Training Set

• The document does not explicitly mention a "training set" in the context of machine learning. The studies described are performance validation studies for an immunoassay. The device calculates results based on a calibrator curve.
• Calibrator Curve: The assay uses 6 levels of calibrators (0 - 1500 ng/mL) to establish the calibration curve. This is analogous to a very small "training set" for the instrument to learn the relationship between RLU signal and cyclosporine concentration.

9. How the Ground Truth for the Training Set (Calibrator Curve) was Established

• The ground truth for the calibrator curve is established by using pre-defined calibrator materials with known concentrations of cyclosporine. These calibrators are typically manufactured to precise specifications.
• The document states: "The ARCHITECT Cyclosporine Calibrators are for the calibration of the ARCHITECT i System..." and "Calibrators: 6 Levels (0 - 1500 ng/mL)" with a "Processed human whole blood" matrix.
• The known concentrations of these calibrators are used to generate the standard curve against which unknown patient samples are then measured.

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