(253 days)
The QMS® Tacrolimus Immunoassay is intended for the quantitative determination of tacrolimus in human whole blood on automated clinical chemistry analyzers. The results obtained are used as an aid in the management of kidney, liver, and heart transplant patients receiving tacrolimus therapy. This in vitro diagnostic device is intended for clinical laboratory use only.
The QMS® Tacrolimus Calibrator set is intended for use in calibration of the QMS® Tacrolimus Immunoassay.
The QMS® Tacrolimus Immunoassay consists of separately packaged reagents (Reagent 1, Reagent 2 and Extraction Reagent) and calibrators (Calibrator A, B, C, D, E, and F).
Reagent 1 (Antibody Reagent):
Here's an analysis of the acceptance criteria and study information for the QMS® Tacrolimus Immunoassay, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied/Contextual) | Reported Device Performance |
|---|---|---|
| Functional Sensitivity (LOQ) | Lowest concentration with ≤20% inter-assay CV over extended period | 0.9 ng/mL |
| Precision (Total-Run) | ≤7.3% CV | ≤7.3% CV (at various levels across the assay range) |
| Dilution Recovery (Linearity) | Demonstrates linearity throughout the assay range | Linear from 0.8 to 29.9 ng/mL |
| Spike Recovery | ≤10% error | ≤10% error (for all samples) |
| Method Comparison (vs. LC-MS/MS) | High correlation (R value close to 1, slope close to 1, intercept close to 0) | y = 1.111x + 0.53, R = 0.972 |
| Method Comparison (vs. Predicate Device) | High correlation (R value close to 1, slope close to 1, intercept close to 0) | y = 1.126x - 0.03, R = 0.937 |
| Specificity (Major Metabolites) | Acceptable level of cross-reactivity | Partial cross-reactivity |
| Specificity (Co-administered/OTC Drugs) | Minimal to no cross-reactivity | Minimal to no cross-reactivity |
| Interfering Substances | ≤10% error | ≤10% error (at concentrations tested) |
| Reagent Stability (Accelerated) | Stable for acceptable duration | Up to 13 months at 2-8°C |
| Reagent On-board Stability | Stable for acceptable duration | Up to 35 days on Beckman AU680® clinical analyzer |
| Calibrator Stability (Accelerated) | Stable for acceptable duration | Up to 15 months at -20°C |
| Calibrator Open Vial Stability | Stable for acceptable duration while capped | 42 days at 2-8°C |
Note: The document implies acceptance criteria based on standard laboratory practices for in vitro diagnostics. Specific numerical thresholds for "high correlation" or "acceptable level" for parameters like comparison studies and specificity are not explicitly stated as acceptance criteria but are inferred from the reported results being presented as evidence of performance.
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the specific number of samples used for the "test set" for each performance study. It mentions "samples were tested" implying internal validation.
- Functional Sensitivity (LOQ): Not specified.
- Precision: Not specified.
- Dilution Recovery: Not specified.
- Spike Recovery: Not specified.
- Method Comparison: Not specified. It indicates "samples were tested" and compared to LC-MS/MS and the predicate device.
- Specificity: Not specified. Indicated "studies were conducted for available major metabolites... medications routinely co-administered... and other over-the-counter drugs."
- Interfering Substances: Not specified. Indicated "endogenous substances... were tested."
- Reagent Stability: Not specified.
- Calibrator Stability: Not specified.
Data Provenance: The studies appear to be internal validation studies conducted by Thermo Fisher Scientific. The document does not specify country of origin for the data, nor does it explicitly state whether the data was retrospective or prospective, though it's typically prospective for performance validation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not applicable to this type of device (immunoassay). The "ground truth" for an immunoassay is established by reference methods or known concentrations, not by expert interpretation of images or other subjective data. For example:
- Method Comparison: The "ground truth" is provided by the LC-MS/MS method (a gold standard analytical technique for tacrolimus quantification). The predicate device also serves as a comparison.
- Dilution Recovery and Spike Recovery: The "ground truth" is the known concentration of tacrolimus added to the samples.
- Specificity: The "ground truth" for cross-reactivity is the known chemical structure and concentration of the potential interfering substances.
4. Adjudication Method for the Test Set
This is not applicable to this type of device. Adjudication methods (like 2+1, 3+1) are typically used in studies where multiple human readers independently assess data (e.g., medical images) and a consensus is needed to establish ground truth or resolve discrepancies. For this immunoassay, results
are quantitative measurements, not subjective interpretations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study assesses how human readers' performance changes with an AI aid. The QMS® Tacrolimus Immunoassay is an in vitro diagnostic device that quantifies a substance in whole blood through an automated process, not an AI system that assists human interpretation of complex medical cases.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the performance studies detailed in the summary (Functional Sensitivity, Precision, Dilution Recovery, Spike Recovery, Method Comparison, Specificity, Interfering Substances, and Stability) represent the standalone performance of the QMS® Tacrolimus Immunoassay. This device operates as an automated system to quantify tacrolimus, without direct human intervention in the interpretative process during testing. The results are generated by the algorithm/device itself.
7. The Type of Ground Truth Used
The ground truth used for validating the QMS® Tacrolimus Immunoassay stems from:
- Reference Method: For method comparison, the LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) method served as the primary reference standard. This is considered a highly sensitive and specific analytical technique for drug quantification.
- Known Concentrations: For studies like Functional Sensitivity, Dilution Recovery, Spike Recovery, Specificity, and Interfering Substances, the ground truth was based on samples with known, precisely prepared concentrations of tacrolimus, its metabolites, co-administered drugs, or endogenous interfering substances.
- Predicate Device Comparison: The previously cleared Abbott ARCHITECT® Tacrolimus Assay served as a comparative reference method for demonstrating substantial equivalence.
8. The Sample Size for the Training Set
The document does not specify a training set sample size. For an immunoassay, the concept of a "training set" in the context of machine learning (where algorithms learn from data) is not directly applicable in the same way. The immunoassays are developed and optimized through iterative processes using various reagents, controls, and calibration materials, rather than "training" an algorithm on a distinct dataset.
9. How the Ground Truth for the Training Set Was Established
As noted above, a traditional "training set" with ground truth in the sense of machine learning is not described or applicable here. The development and optimization of an immunoassay rely on established chemical and biological principles, precise formulation of reagents, and validation against reference methods and known standards to ensure accuracy and reliability. The ground truth for such development is built upon fundamental analytical chemistry and knowledge of the analyte (tacrolimus).
§ 862.1678 Tacrolimus test system.
(a)
Identification. A tacrolimus test system is a device intended to quantitatively determine tacrolimus concentrations as an aid in the management of transplant patients receiving therapy with this drug. This generic type of device includes immunoassays and chromatographic assays for tacrolimus.(b)
Classification. Class II (special controls). The special control is “Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA.” See § 862.1(d) for the availability of this guidance document.