(32 days)
The DiaSorin LIAISON® N-TACT® PTH Calibration Verifiers are assayed quality control materials intended for use in the quantitative verification of calibration and reportable range of the LIAISON® N-TACT® PTH Assay when performed on the LIAISON® Analyzer.
The LIAISON® N-TACT® PTH Calibration Verifiers consist of four levels. Each vial contains Iyophilized pooled human plasma spiked with PTH. The calibration verifiers are reconstituted with 2.0 mL of deionized or distilled water, allowed to sit for 10 minutes, and mixed gently before use. The calibration verifier set is provided with targeted PTH concentrations of 20, 150, 350 and 1500 pg/mL. The four levels were chosen to incorporate the range of the LIAISON® N-TACT® PTH Assay and to challenge the decision points of clinical importance for PTH.
The provided document describes a premarket notification for the DiaSorin LIAISON® N-TACT® PTH Calibration Verifiers. This device is an assayed quality control material, not an AI/ML powered device, and therefore the concepts of test sets, ground truth, expert adjudication, MRMC studies, or standalone performance do not apply. The document focuses on demonstrating substantial equivalence to a predicate device for regulatory clearance.
Here's an analysis based on the information provided, reinterpreting the "acceptance criteria" and "study" in the context of a quality control material seeking substantial equivalence:
1. Table of Acceptance Criteria and Reported Device Performance
For this type of device (calibration verifiers/quality control materials), the "acceptance criteria" revolve around demonstrating that the new device performs similarly to or meets the requirements for a quality control material and is substantially equivalent to an existing predicate device. The performance is assessed by comparing its characteristics and intended use to the predicate.
| Acceptance Criteria (Inferred) | Reported Device Performance (LIAISON® N-TACT® PTH Calibration Verifiers) |
|---|---|
| Intended Use Equivalence: Must be intended for similar quality control/calibration verification in a PTH assay. | Assayed quality control samples for use in the quantitative verification of calibration and reportable range of the LIAISON® N-TACT® PTH Assay. (Similar purpose to predicate's "assayed quality control samples to monitor accuracy and precision"). |
| Analyte Equivalence: Must measure the same analyte. | Parathyroid Hormone |
| Matrix Equivalence: Must have a similar biological matrix. | Pooled human plasma with stabilizers and 0.2% Proclin® 300 |
| Format Equivalence: Must have a similar physical form. | Lyophilized |
| Storage Conditions Equivalence: Must have similar storage requirements. | 2 - 8°C before reconstitution, -20°C after reconstitution |
| Handling Equivalence: Must have similar reconstitution and handling procedures. | Reconstitute with 2 mL deionized or distilled H2O, allow to dissolve on bench top for 10 minutes, mix thoroughly to ensure complete reconstitution |
| Volume Equivalence: Must have a similar final volume after reconstitution. | 2.0 mL after reconstitution |
| Required Reagent Equivalence: Must be used with the same main assay. | LIAISON® N-TACT® PTH Assay |
| Processing Equivalence: Must be processed on the same instrument. | LIAISON® Analyzer |
| Appropriate Number of Levels: Must provide adequate levels for its intended use (calibration verification). | Four levels (20, 150, 350, 1500 pg/mL) chosen to incorporate the range of the LIAISON® N-TACT® PTH Assay and challenge decision points. (Predicate had two levels, new device has more, which is an improvement for calibration verification). |
Study Proving Acceptance Criteria:
The "study" in this context is a substantial equivalence comparison to a legally marketed predicate device, the LIAISON® N-TACT® PTH Control Set (K033426). The provided text outlines this comparison, highlighting similarities and differences to demonstrate that the new device is as safe and effective as the predicate.
2. Sample Size Used for the Test Set and Data Provenance
This concept is not applicable to this type of regulatory submission. There is no "test set" in the sense of patient data or algorithm performance evaluation. The "sample" here would refer to the characteristics of the calibration verifiers themselves, such as the different levels provided. The data provenance relates to the formulation of the human plasma, but not its origin in terms of "patient data."
- Sample Size: The device consists of four levels of calibration verifiers.
- Data Provenance: The matrix is "pooled human plasma." No specific country of origin or whether it's retrospective/prospective is detailed for the plasma source, as it's a raw material for a control.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This concept is not applicable. "Ground truth" in the context of AI/ML or diagnostic claim validation refers to an independent, highly accurate determination of a clinical condition. For a quality control material, the "truth" is the target concentration of PTH within the verifier, established during its manufacturing and assay. This is typically done through certified reference materials and established laboratory methods, not by clinical experts adjudicating cases.
4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set
This concept is not applicable. There is no "adjudication" of patient cases or diagnostic outputs for a quality control material.
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 concept is not applicable. This device is a laboratory reagent (calibration verifier), not an AI-powered diagnostic tool used by human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done
This concept is not applicable. This is a reagent, not an algorithm.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The "ground truth" for the LIAISON® N-TACT® PTH Calibration Verifiers would be their assigned target PTH concentrations (20, 150, 350, 1500 pg/mL). These values are established during the manufacturing process using validated analytical methods and reference materials, ensuring the accuracy of the PTH concentration within each level of the verifier. It is not based on expert consensus, pathology, or outcomes data in a clinical sense, but rather on metrological traceability for an in-vitro diagnostic reagent.
8. The Sample Size for the Training Set
This concept is not applicable. There is no "training set" for this type of device.
9. How the Ground Truth for the Training Set Was Established
This concept is not applicable. There is no "training set" or corresponding "ground truth" in the AI/ML sense.
§ 862.1660 Quality control material (assayed and unassayed).
(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.