(186 days)
The ARCHITECT Sirolimus assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sirolimus in human whole blood on the ARCHITECT i System. The ARCHITECT Sirolimus assay is to be used as an aid in the management of renal transplant patients receiving sirolimus therapy.
The ARCHITECT Sirolimus Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of sirolimus in human whole blood.
The ARCHITECT Sirolimus Whole Blood Precipitation Reagent is for the extraction of sirolimus from samples (human whole blood patient specimens, controls, and ARCHITECT Sirolimus Calibrators) to be tested on the ARCHITECT i System.
The ARCHITECT Sirolimus assay is a delayed one-step immunoassay for the quantitative determination of sirolimus 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 extracted with a precipitation reagent, heated, and centrifuged. The supernatant is decanted into a Transplant Pretreatment Tube, which is placedonto the ARCHITECT i System.
Sample, assay diluent, and anti-sirolimus coated paramagnetic microparticles are combined to create a reaction mixture. Sirolimus present in the sample binds to the anti-sirolimus coated microparticles. After a delay, sirolimus acridinium-labeled conjugate is added to the reaction mixture. The sirolimus acridinium-labeled conjucate competes for the available binding sites on the anti-sirolimus coated paramagnetic microparticles. Following an incubation, the microparticles are washed, and 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 sirolimus in the RLUs detected by the ARCHITECT i System optics.
The provided document describes the ARCHITECT Sirolimus Assay and its performance characteristics, primarily focusing on demonstrating substantial equivalence to a predicate device (ABBOTT IMx® Sirolimus Microparticle Enzyme Immunoassay) and LC/MS/MS as a reference method.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state numerical acceptance criteria in a dedicated section with pre-defined thresholds. Instead, it presents the results of equivalence studies against a predicate device and a reference method, implying that the observed performance was deemed acceptable for demonstrating substantial equivalence. For performance characteristics like precision, linearity, and sensitivity, the results are presented, and implicit acceptance is given by stating the achieved values (e.g., "less than or equal to 10%").
Here's a table summarizing the reported device performance from the provided text:
| Performance Metric | Acceptance Criteria (Implicit from context) | Reported Device Performance (ARCHITECT Sirolimus Assay) |
|---|---|---|
| Equivalence to IMx Sirolimus (Predicate) | Correlation/Agreement with predicate | Intercept: 0.12 (-0.38 to 0.47) |
| Slope: 1.05 (1.00 to 1.11) | ||
| Correlation Coefficient: 0.94 | ||
| Equivalence to LC/MS/MS (Reference Method) | Correlation/Agreement with reference | Intercept: -0.37 (-0.89 to 0.12) |
| Slope: 1.18 (1.11 to 1.27) | ||
| Correlation Coefficient: 0.91 | ||
| Precision (Total %CV) | No explicit numerical criterion, but generally low %CV is desired. | ≤ 10% |
| Linearity (Mean % Recovery) | No explicit numerical criterion, but generally close to 100% is desired. | Within 10% of the expected result for diluted samples. |
| Functional Sensitivity | Reportable range is 2-30 ng/mL. Lower functional sensitivity desired. | 0.7 ng/mL (at 20% CV, upper 95% CI) |
| Analytical Sensitivity (Limit of Detection) | Reportable range is 2-30 ng/mL. Lower LOD desired. | 0.3 ng/mL (at 2 SD above Calibrator A) |
| Interference (Average Recovery) | Generally, recovery close to 100% (e.g., 90-110%) is desired. | 95 to 106% (for various interfering compounds) |
| Specificity (Cross-Reactivity) | Low cross-reactivity desired for related metabolites. | F2: 8.7% |
| F3: 7.6% | ||
| F4: 36.8% | ||
| F5: 20.3% |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size for Equivalence Studies:
- ARCHITECT Sirolimus vs. IMx Sirolimus: 168 observations (specimens).
- ARCHITECT Sirolimus vs. LC/MS/MS: 167 observations (specimens).
- Data Provenance: "human whole blood specimens from renal transplant patients receiving sirolimus therapy." The country of origin is not specified, but the context of an FDA 510(k) submission typically implies US-based or internationally accepted clinical study protocols. The data is retrospective in the sense that the patients were already receiving therapy and specimens were collected. It's not explicitly stated if it was a prospective collection for this specific study, but it's patient data.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
This information is not provided in the document. For an immunoassay device like this, ground truth is typically established by comparing against a reference method (like LC/MS/MS) or a previously validated predicate device. Human expert interpretation of results is not usually the primary ground truth for quantitative laboratory assays.
4. Adjudication Method for the Test Set:
This information is not applicable and therefore not provided in the document. Adjudication methods (like 2+1, 3+1) are typically used in studies involving subjective human interpretation of images or clinical events, where multiple readers' assessments need to be reconciled to form a ground truth. For quantitative assays like the Sirolimus assay, the ground truth is based on the chemical measurement itself, often against a gold standard method.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study focuses on the impact of a device on human readers' performance (e.g., radiologists interpreting images using an AI tool). The ARCHITECT Sirolimus Assay is a standalone, quantitative in vitro diagnostic device, not one that assists human readers in making interpretations.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:
Yes, the studies presented are standalone performance studies. The ARCHITECT Sirolimus Assay, as an immunoassay, works as an "algorithm only" (the automated measurement process produces a quantitative result) without human input during the core measurement process. The results reported (equivalence, precision, linearity, sensitivity, interference, specificity) directly reflect the performance of the device itself.
7. Type of Ground Truth Used:
- Predicate Device Comparison: The ABBOTT IMx® Sirolimus Microparticle Enzyme Immunoassay (K042411) was used as a reference for comparison. While not a "ground truth" in the strictest sense, it's a legally marketed and accepted assay that served as a benchmark for substantial equivalence.
- Reference Method Comparison: LC/MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) was used as a more definitive "ground truth" or reference method for validating the assay's accuracy against a highly sensitive and specific analytical technique.
8. Sample Size for the Training Set:
The document does not provide specific information on the sample size used for the training set. Immunoassays are often developed and optimized using a variety of samples and reagents during the R&D phase, but a distinct "training set" in the machine learning sense is not typically explicitly defined or reported for this type of device in a 510(k) summary. The development process would involve iterative testing and refinement.
9. How the Ground Truth for the Training Set was Established:
As the document doesn't detail a specific "training set" or its ground truth, this information is not provided. For immunoassay development, ground truth for initial optimization would similarly be based on established reference methods (like LC/MS/MS) or careful spiking/dilution experiments with known concentrations of the analyte.
§ 862.3840 Sirolimus test system.
(a)
Identification. A sirolimus test system is a device intended to quantitatively determine sirolimus concentrations in whole blood. Measurements are used as an aid in management of transplant patients receiving therapy with sirolimus.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Sirolimus Test Systems.” See § 862.1(d) for the availability of this guidance document.