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The IDS iSYS 25 VilD assay is intended for the quantitative determination of total 25-hydroxyvitamin D (125(OH)D) in hyman serum or plasma on the IDS iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in an adult population.

The IDS-iSYS 25 VitD Control Set is used for quality control of the IDS-iSYS 25 VitD assay on the IDS-iSYS Multi-Discipline Automated System.

The IDS-iSYS 25 VitDs reagent kit consists of one (1) Immunoassay Cartridge, one (1) vial each of 2 concentration Calibrator levels and a mini-CD containing the Instructions For Use (IFU), CRY files and Certificate of Analysis.

IDS-iSYS 25 VitDS Cartridge, sufficient for 100 tests, consists of reagents provided in individual compartment within a plastic container called the Cartridge. IDS-iSYS 25 VitDS Cartridge contains the following ready to use reagents:

• Magnetic particles coated with streptavidin in a phosphate . buffer containing sodium azide.
• . Sodium hydroxide solution.
• . 25(OH)D labelled with an acridinium ester derivative, in buffer containing bovine serum albumin with sodium azide.
• . Anti-25(OH)D sheep polyclonal antibody labelled with an biotin, in buffer containing bovine, sheep and mouse proteins and sodium azide.
• . Assay buffer containing proprietary displacing compounds, methanol and sodium azide.

The IDS-iSYS 25 VitD® Calibrators are included in the reagent kit. The ready to use calibrators contains human serum buffer matrix with two defined concentrations of 25(OH)D and sodium azide as preservative (<0.1 %), 1 bottle per concentration level.

The IDS-iSYS 25VitDe Control Set contains human serum in a buffer matrix with two defined concentrations of 25(OH)D and sodium azide as a preservative; 3 bottles per concentration level.

The provided document describes the IDS-iSYS 25VitD8 assay, a device for the quantitative determination of total 25-hydroxyvitamin D [25(OH)D] in human serum or plasma. Below is an analysis of its acceptance criteria and the studies performed.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" for all performance characteristics in a single, consolidated table. However, it presents performance data for various analytical characteristics, and in some cases, implicitly defines acceptable ranges or desired outcomes for these studies. For instance, in the specificity study, an acceptance criterion of "<10% bias between the test and control samples" is stated.

Based on the provided information, a table can be constructed to show the reported device performance and implicitly derived or explicitly stated acceptance criteria.

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

• Precision/Reproducibility: Nine serum-based samples at different 25(OH)D concentration levels were used. Each sample was likely tested multiple times over several days and systems (as indicated by the methodology for LoB/LoD/LoQ, which involved 3 batches, multiple runs, and operators, though precision specifics aren't identical).
• Linearity: One high and one low human serum sample were used, along with 9 evenly spaced dilutions created by mixing them. (Total of 11 unique concentrations tested).
• Detection Limits (LoB, LoD, LoQ):
  • LoB: 3 manufacturing batches (MB1, MB2B, MB3). Each batch ran 6 assays over 4-5 days, with 2 duplicates per assay. Total 60 replicates per batch.
  • LoD: 6 very low 25(OH)D samples. Each batch ran 6 assays over 3-5 days, with 2 duplicates per assay. Total 72 replicates for each manufacture batch.
  • LoQ: 10 low 25(OH)D samples. Each batch ran 6 assays over 3-5 days, with 2 duplicates per assay. Total 120 replicates for each manufacture batch (118 for MB1 due to mislabeling).
• Analytical Specificity (Interference): Two serum samples at two different 25(OH)D concentrations for each interferent tested. Each condition tested with 26 replicates (spiked vs. control).
• Analytical Specificity (Cross-reactivity): Samples spiked with relevant cross-reactants. Specific numbers of replicates or distinct samples are not detailed for each cross-reactant. Endogenous cross-reactants were tested with samples having established ID-LC-MS/MS values.
• Method Comparison: A total of 136 human serum samples with a wide range of 25(OH)D concentrations (5.6 to 110 ng/mL).
• Expected Values/Reference Range: 392 apparently healthy donors (200 males, 192 females) from three diverse regions of the United States (North, Central, South), sampled in the winter.
• Matrix Comparison: 57 native samples plus 10 treated (spiked or diluted) samples, covering a range of 4.8 to 108 ng/mL from serum without additives, compared across various tube types.

Data Provenance:

• For the Expected Values/Reference Range study, data was collected from the United States (North, Central, South regions).
• For other studies (Precision, Linearity, Detection Limits, Specificity, Method Comparison, Matrix Comparison), the country of origin is not explicitly stated, but given Immunodiagnostic Systems Limited is based in the UK, it is plausible some studies might have been conducted there or in collaboration with international labs. The method comparison refers to NIST/Ghent ID-LC-MS/MS, suggesting international standards and potentially international lab involvement. Based on the 510(k) submission, the studies were conducted by the manufacturer for the purpose of demonstrating substantial equivalence to a US-marketed device. All data is retrospective as it was collected before the submission for marketing clearance.

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

There were no experts used to establish ground truth in the traditional sense for these studies. This device is an in vitro diagnostic (IVD) for quantitative measurement. The "ground truth" for the test set was established by:

• Reference Methods: The primary ground truth for the Method Comparison study was the NIST/Ghent ID-LC-MS/MS 25(OH) Vitamin D Reference Method Procedure. This is a highly accurate and standardized analytical method, not a human expert.
• Known Concentrations/Spiked Samples: For studies like linearity, detection limits, analytical specificity, and cross-reactivity, ground truth was based on:
  • Known concentrations of analytes (e.g., purified 25(OH)D, interferents, cross-reactants) used to spike samples.
  • Samples with established values from other validated methods, like ID-LC-MS/MS for endogenous cross-reactants.
• Population Studies: For Expected Values/Reference Range, the "ground truth" are the measured values from a characterized "apparently healthy" donor population, with outliers and specific exclusions defined.

4. Adjudication Method for the Test Set

There was no adjudication method for these studies in the context of expert review, as the ground truth was based on analytical reference methods or predefined sample concentrations, not subjective interpretations requiring consensus from multiple human readers.

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 MRMC comparative effectiveness study was done. This device is an automated in vitro diagnostic (IVD) assay designed for quantitative measurement of a biomarker (25(OH)D). It does not involve human readers interpreting images or data that would be assisted by AI. The device directly yields a numerical result. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.

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

This device operates as a standalone algorithm (assay) in the sense that it performs the measurement without human intervention influencing the result of that specific measurement. The IDS-iSYS Multi-Discipline Automated System performs the assay automatically. The results are then used by clinicians in conjunction with other data, but the measurement itself is automated. The performance characteristics described (precision, linearity, detection limits, specificity, method comparison, matrix comparison) are all "standalone" performance metrics of the assay system itself.

7. The Type of Ground Truth Used

The ground truth used was primarily:

• Reference Method Data: Specifically, the isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-MS/MS) 25(OH)D Reference Method Procedure (RMP), particularly for method comparison and traceability. This RMP is itself traceable to the National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 2972.
• Known/Assigned Concentrations: For stability, calibrator, and control value assignments, internal stock solutions, secondary standards (Internal Reference Calibrators, IRs), and manufactured kit calibrators/controls had values assigned back to the CDC VDSP aligned secondary standards or by using validated kit combinations over multiple instruments and runs.
• Spiked Samples: For linearity, analytical specificity (interference and cross-reactivity) studies, samples were spiked with known concentrations of analytes, interferents, or cross-reactants.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" in the context of machine learning or AI development. This device is an immunoassay, not a machine learning model. The various studies described (precision, linearity, specificity, method comparison, etc.) are validation studies performed on the final assay formulation and instrument system.

However, the closest analogous concepts would be:

• Calibrator and Control Value Assignment: This involves multiple runs (minimum 20 assay runs for calibrators, minimum 21 assay runs for controls) and systems to establish and verify values. These essentially "train" the system by defining its response curve and quality control ranges.
• Assay Development: During the initial development of the assay, numerous samples and experiments would have been conducted to optimize reagents, conditions, and performance characteristics. This "development data" would serve a similar purpose to a training set but is not explicitly detailed as such in this 510(k) summary, which focuses on validation of the final device.

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

As noted above, there's no explicit "training set" in the AI sense. For the closest analogous processes:

• Calibrator and Control Value Assignment:
  • Traceability: The assay is traceable to the ID-LC-MS/MS 25(OH)D Reference Method Procedure (RMP), which was used to assign target values for the Vitamin D Standardization Program (VDSP) samples. This RMP is further traceable to the NIST SRM 2972.
  • Internal Standards: An internal stock solution ("Top Dose") of 25-hydroxyvitamin D3 had its concentration assigned by performing dilutions and testing in approved, previously QC-released kits.
  • Secondary Standards (IRs): These were manufactured and value-assigned using the CDC VDSP aligned secondary standards.
  • Kit Calibrators: Tested as unknowns in a minimum of 20 assay runs on one IDS-iSYS instrument, using these secondary standards (IRs) to establish their values through Excel data reduction and Prism for curve parameters. Values were then verified over 3 assays.
  • Kit Controls: Tested as unknowns in a minimum of 21 assay runs using multiple systems and approved kit combinations, with values calculated using the IDS-iSYS instrument's on-board software. Values were then verified in a single assay.

Essentially, the "ground truth" for the calibrators and controls used to define the assay's operating curve and quality parameters is established through a hierarchical traceability chain leading back to NIST-traceable reference methods.

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