(121 days)
The SIRO method is an in vitro diagnostic test for the quantitative measurement of Sirolimus in human whole blood on the Dimension® clinical chemistry system. Measurements of Sirolimus are used as an aid in the management of sirolimus therapy in renal transplant patients.
The Sirolimus Calibrator is an in vitro diagnostic product for the calibration of Sirolimus (SIRO) on the Dimension® clinical chemistry system.
The automated Dimension® SIRO method uses an immunoassay technique in which free and sirolimus-bound antibody-enzyme conjugates are separated using magnetic particles. The assay is performed using a method specific Flex® reagent cartridge. The Flex® cartridge contains a pretreatment reagent, antibody-B-galactosidase conjugate, sirolimus immobilized on chromium dioxide particles, chlorophenol red ß-d-galactopyranoside (CPRG) substrate, and diluent to hydrate the tablets.
To perform the SIRO assay, a sample cup (or SSC) containing the whole blood sample to be analyzed and a SIRO Flex® reagent cartridge are placed appropriately on the Dimension® system. The Dimension® system mixes and lyses the whole blood sample. The lysed sample is then mixed with the antibody enzyme conjugate. The sirolimus present in the sample is bound by the sirolimus antibody conjugate reagent. Magnetic particles coated with sirolimus are added to bind free (unbound) antibody-enzyme conjugate. The reaction mixture is then separated magnetically. Following separation, the supernatant containing the sirolimus-antibody-enzyme complex is transferred to another cuvette and mixed with the substrate. B-galactosidase catalyzes the hydrolysis of CPRG (chlorophenol red ß-d-galactopyranoside) to produce CPR (chlorophenol red) that absorbs light maximally at 577 nm. The change in absorbance at 577 nm due to the formation of CPR is directly proportional to the amount of sirolimus in the patient's sample and is measured using a bichromatic (577, 700 nm) rate technique.
The Dimension® Sirolimus Calibrator (DC306) is an in-vitro diagnostic product intended to be used to calibrate the Dimension® Sirolimus method. It is a frozon liquid product packaged as a single vial for each of five levels. The matrix is human whole blood hemolysate with preservatives. Levels 2, 3, 4, and 5 contain sirolimus drug at target values of 5, 10, 20, and 31.5 ng/mL, respectively. Level 1 is a human whole blood hemolysate that does not contain sirolimus drug.
Here's a summary of the acceptance criteria and study details for the Dimension SIRO Flex® reagent cartridge, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary focuses on demonstrating substantial equivalence to a predicate device (Abbott IMx Sirolimus) and uses specific performance characteristics as evidence. While explicit "acceptance criteria" for each performance metric are not strictly defined as numerical thresholds in the provided text beyond the predicate device's performance, the goal is to show comparable or improved performance.
| Performance Metric | Predicate Device (Abbott IMx Sirolimus) | Acceptance Criteria (Implied by Substantial Equivalence to Predicate) | Reported Device Performance (Dimension SIRO) |
|---|---|---|---|
| Intended Use | Quantitative determination of sirolimus in human whole blood, aid in management of renal transplant patients. | Same intended use as predicate. | Quantitative measurement of Sirolimus in human whole blood, aid in management of sirolimus therapy in renal transplant patients. (Matches predicate) |
| Assay Technology | Enzyme immunoassay (Microparticle) | Comparable immunoassay technology. | Enzyme immunoassay (Affinity chrome mediated) |
| Sample Type | EDTA whole blood | Same sample type. | EDTA whole blood (Matches predicate) |
| Sample Pretreatment | Required | Improved/Comparable (Ideally none) | Not required (Improved over predicate) |
| Reportable Range | 0 to 30 ng/mL | Comparable or wider range. | 1.5 to 30 ng/mL (Slightly different lower limit, but overall comparable) |
| Functional Sensitivity | 0.95 and clinically acceptable slope/intercept. | Slope: 1.2, Intercept: -0.7 ng/mL, Correlation Coefficient: 0.95 | |
| Reproducibility (%CV) | (Not explicitly stated in table for predicate, but generally low %CV is desirable) | Low %CV for repeatability and within-lab variability, demonstrating consistency across different concentrations. | Repeatability: |
| Level 1: 8.0% | |||
| Level 2: 5.73% | |||
| Level 3: 6.67% | |||
| QC Level 1: 12.98% | |||
| QC Level 2: 5.48% | |||
| Within Lab: | |||
| Level 1: 8.61% | |||
| Level 2: 5.77% | |||
| Level 3: 7.07% | |||
| QC Level 1: 14.52% | |||
| QC Level 2: 5.75% |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison (Test Set for demonstrating agreement with reference method):
- Sample Size: n = 119 patient samples.
- Data Provenance: The text states "A split patient sample (EDTA whole blood) method comparison." It does not explicitly state the country of origin or if it was retrospective or prospective, but "split patient sample" implies prospective collection from a patient population specifically for this comparison.
- Reproducibility (Test Set for precision):
- Sample Size: Not explicitly stated as a single "test set" size. However, for each test level (3 whole blood pools and 2 QC levels), a single test from two independent cups was analyzed twice per day over an unspecified number of days/runs. This is repeated across one internal and two external locations.
- Data Provenance: Not explicitly stated, though the mention of "one internal and two external locations" suggests it likely involved multiple sites, potentially geographically diverse (though specific countries are not mentioned). It's a prospective study designed to assess precision.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- For Method Comparison:
- The ground truth was established by HPLC/MS (High-Performance Liquid Chromatography/Mass Spectrometry), which is referred to as "the reference method." This is an analytical laboratory technique, not an expert human assessment.
- For Reproducibility:
- The "ground truth" here is the expected value of the control materials (e.g., "Level 1 Whole Blood Pool" mean 4.41 ng/mL). These values are typically established through extensive testing by the manufacturer using validated methods, not by a panel of experts.
4. Adjudication Method for the Test Set
- For Method Comparison: No adjudication method involving human experts is applicable as the comparison is against an instrumental reference method (HPLC/MS).
- For Reproducibility: No adjudication method is applicable. The data is statistical analysis of repeated measurements of control materials.
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 device is an in-vitro diagnostic (IVD) test for measuring a drug concentration (Sirolimus) in whole blood. It is an automated clinical chemistry system.
- Therefore, an MRMC comparative effectiveness study where human "readers" (e.g., clinicians interpreting images or patient data) improve with "AI assistance" is not applicable to this type of device. There is no human interpretation of complex data that the device is intended to assist. The device provides a quantitative numerical result.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, this is a standalone device. The performance data (method comparison, reproducibility) directly reflects the algorithm (the immunoassay technique and automated system) without human intervention in the result generation process. The device performs the measurement and outputs a quantitative value. Clinical interpretation of that value by a physician occurs after the device provides its result, but the device's performance itself is standalone.
7. The Type of Ground Truth Used
- For Method Comparison: Analytical reference method (HPLC/MS).
- For Reproducibility: Established mean values of control materials (whole blood pools and QC materials) through internal validation processes.
8. The Sample Size for the Training Set
- The 510(k) summary does not provide details on a separate "training set" sample size. For IVD devices like this, the development process involves extensive internal testing and optimization of reagents and methods which could be considered "training data" in a broad sense, but it is not typically disclosed with sample sizes in the same way as machine learning models. The data presented here are for the validation of the final device.
9. How the Ground Truth for the Training Set Was Established
- As mentioned above, specific "training set" details are not provided. However, generally, for the development of such an immunoassay, the "ground truth" during development would be established similarly to the validation:
- Reference methods (like HPLC/MS) for accurate quantification of sirolimus.
- Known concentrations of sirolimus in prepared samples.
- Patient samples with clinically relevant sirolimus levels.
- The goal during development (training) would be to optimize reagent concentrations, reaction conditions, and calibration algorithms to achieve accurate and precise measurements against these known or reference values.
§ 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.