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The Dimension Tacrolimus Flex® Reagent Cartridge (TAC) is an in vitro diagnostic test for the quantitative measurement of tacrolimus in human whole blood on the Dimension® clinical chemistry system. Measurements of tacrolimus are used as an aid in the management of tacrolimus therapy in renal and hepatic transplant patients.

The Dimension Tacrolimus Callbrator (TAC CAL) is an in vitro diagnostic product for the Tacrolimus (TAC) method on the Dimension® clinical chemistry system.

The automated Dimension® TAC method uses an immunoassay technique in which free and tacrolimus-bound antibody-enzyme conjugate is separated using magnetic particles. The assay is performed using a method specific Flex® reagent cartridge. The Flex® cartridge contains a pretreatment reagent, antibody-ß-galactosidase conjugate, tacrolimus immobilized on chromium dioxide particles, chlorophenol red ß-d-galactopyranoside (CPRG) substrate, and diluent to hydrate the tablets.

Dimension® Tacrolimus (TAC) Calibrator is five level frozen liquid, whole blood hemolysate containing purified tacrolimus. The provided in 4.0 mL vials, 2 vials per level. There are five calibrator levels per kit which span the assay range for the Dimension® Tacrolimus (TAC) assay. Calibrators are filled with 1.0 mL per vial except for Level 1 calibrator which contains 2.0 mL per vial.

Here's a summary of the acceptance criteria and study information for the Dimension Tacrolimus Flex® Reagent Cartridge (TAC) and Dimension Tacrolimus Calibrator (TAC CAL), based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in a quantitative format for most categories. Instead, it describes the type of testing performed and then indicates whether the device met certain expectations (e.g., "All samples met the acceptance criterion of ≤ 10% mean bias in recovery"). Where specific quantitative performance is given, it is included.

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

• Precision: No specific sample size for a single "test set" is provided, but reproducibility testing was conducted using different levels (1.8 to 27.4 ng/mL).

• Linearity: No specific sample size mentioned, but the study was performed by mixing a sample with a known high tacrolimus concentration (40.3 ng/mL) with a normal patient pool with no tacrolimus in various ratios.

• Specificity: No specific sample size mentioned for the interference or cross-reactivity studies, beyond stating "compounds tested" and "major tacrolimus metabolite... as well as minor metabolites."

• Recovery: No specific sample size mentioned, but "samples spiked with USP tacrolimus" were used.

• Method Comparison:

  • Versus LC-MS/MS: n = 315 patient samples.
  • Versus ARCHITECT Tacrolimus Assay: n = 308 patient samples.
  • Versus Dimension Tacrolimus (TACR) method: n = 213 patient samples.

• Data Provenance: The document states that method comparison studies, and some precision testing, were performed at two external evaluation sites in addition to internal testing. Patient samples for method comparison included a "nearly equal distribution of liver and kidney transplant patients." The country of origin is not specified but is implied to be within the scope of Siemens Healthcare Diagnostics operations, likely in the US given the FDA submission. The studies were retrospective in the sense that existing patient samples (whole blood) were used, though the testing itself was prospective for the device evaluation.

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

The concept of "experts" for ground truth (e.g., radiologists) is not applicable here as this is an in vitro diagnostic (IVD) assay. The ground truth for the method comparison studies was established using:

• LC-MS/MS reference method: This is an analytical "gold standard" for measuring tacrolimus concentrations.
• Predicate devices: ARCHITECT Tacrolimus Assay (K070820) and Dimension Tacrolimus (TACR) method (K060502), which are already legally marketed and accepted methods.

The experts involved would be the laboratory personnel performing these high-complexity reference and predicate assays, who are implicitly qualified to conduct such tests according to established laboratory practices. No specific number or qualifications (e.g., "10 years of experience") are provided for these individuals.

4. Adjudication Method for the Test Set

Not applicable. This is an IVD assay where quantitative measurements are obtained. Adjudication typically refers to resolving discrepancies between multiple human readers in image-based diagnostics. Here, the "truth" is established by a reference method or comparison to established predicate devices.

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

Not applicable. This is an in vitro diagnostic (IVD) assay and does not involve human readers interpreting images, nor does it involve AI assistance in the context of imaging diagnostics. The comparison is between the new device's analytical performance and established reference/predicate methods.

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

Yes, the studies reported are essentially standalone performance evaluations of the Dimension Tacrolimus Flex® Reagent Cartridge (TAC) system. The described testing (precision, linearity, specificity, recovery, method comparison) evaluates the analytical performance of the automated assay system itself. Human intervention is limited to standard laboratory procedures like sample preparation, loading, and result interpretation, not in an "AI-assisted reader" capacity.

7. The Type of Ground Truth Used

• Analytical Measuring Range (Linearity) & Recovery: "USP tacrolimus" (United States Pharmacopeia tacrolimus), which refers to highly pure, standardized tacrolimus used to spike samples to known concentrations.
• Method Comparison:
  • LC-MS/MS Assay for Tacrolimus: This is considered the analytical "reference method" and serves as a highly accurate ground truth.
  • Predicate Devices: ARCHITECT Tacrolimus Assay and Dimension Tacrolimus (TACR) method. While not a "ground truth" in the strictest sense of an absolute standard, they serve as the established clinical "truth" for comparison, demonstrating substantial equivalence.

8. The Sample Size for the Training Set

No explicit "training set" or sample size for it is mentioned. This is a chemical assay, not a machine learning algorithm in the typical sense that requires a separate training set for model development. The development of the assay reagents and protocols would involve internal optimization, but this is not typically referred to as a "training set" in the context of regulatory submissions for IVD devices.

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

Since there is no explicit "training set" or machine learning model, this question is not directly applicable. The development and optimization of the assay would rely on:

• Understanding of tacrolimus chemistry and pharmacology: To design reagents that specifically target tacrolimus.
• Standards and reference materials: Such as purified tacrolimus (used for calibrators and recovery studies) to ensure accurate concentration measurements.
• Internal validation and optimization studies: To fine-tune reagent concentrations, reaction conditions, and instrument parameters to achieve desired analytical performance characteristics.

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