(22 days)
The CSAE method is an in vitro diagnostic test for the quantitative measurement of cyclosporine A (CSA) in human whole blood on the Dimension Vista® system. Measurements of CSA are used as an aid in the management of heart, liver and kidney transplant patients.
The Dimension Vista® CSAE Flex® reagent cartridge is a pre-packaged in-vitro diagnostic test method (assay) that is specifically designed to be used on the Dimension Vista® Integrated system, a floor model, fully automated microprocessor-controlled, integrated instrument system. The Dimension Vista® system was previously cleared with seven associated test methods (K051087). This Special 510(k) is submitted for a packaging modification to the Dimension® Cyclosporine Extended Range (CSAE) Flex® reagent cartridge (K052017), an in-vitro diagnostic device that has been cleared under the 510(k) process for use on Dimension® clinical chemistry systems. The packaging change is to allow use on the Dimension Vista® system. The modifications also include a change in method parameters (sample size and reagent volume) but the final concentration of sample/reagent ratio in test milieu remains the same.
The reagents contained in the Dimension Vista® CSAE Flex® reagent cartridges are the same as those contained in the Dimension® CSAE Flex® reagent cartridges manyfactured for the Dimension® clinical chemistry systems, another family of Siemens analyzers. The packaging modification does not affect the intended use of the devices, nor does it alter the fundamental scientific technology of the device.
The CSAE method uses an immunoassay technique in which free and CSA bound antibody-enzyme species are separated using magnetic particles. The CSAE Flex® reagent cartridge contains a pretreatment reagent, B-galactosidase-CSA antibody conjugate, CSA immobilized on chromium dioxide particles, chlorophenol red B-dgalactopyranoside (CPRG) substrate, and diluent to hydrate the tablets. To perform the CSAE assay, a sample cup containing the whole blood sample to be analyzed and a CSAE Flex® reagent cartridge are placed appropriately on the Dimension Vista® system. The Dimension Vista® system mixes and lyses the whole blood sample. The lysed sample is then mixed with the antibody conjugate reagent. The CSA present in the sample is bound by the CSA antibody conjugate reagent. Magnetic particles coated with cyclosporine A are added to bind free (unbound) antibody-enzyme conjugate. The reaction mixture is then separated magnetically. Following separation, the supernatant containing the CSA antibody-enzyme complex is transferred to a cuvette and mixed with the substrate. B-galactosidase catalyzes the hydrolysis of CPRG (chlorophenol red B-dgalactopyranoside) to produce CPR (chlorophenol red) that absorbs light maximally at 577mm. The change in absorbance at 577nm due to the formation of CPR is directly proportional to the amount of CSA in the patient's sample and is measured using a bichromatic (577, 700nm) rate technique.
Here's a breakdown of the acceptance criteria and study information for the Dimension Vista® CSAE Flex® reagent cartridge, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document defines acceptance criteria implicitly through the demonstration of "substantial equivalence" to a predicate device. The primary performance metric presented is the method comparison study results.
| Acceptance Criteria Category | Specific Acceptance Criterion (Implicit) | Reported Device Performance (Dimension Vista® CSAE Flex®) |
|---|---|---|
| Method Comparison | Slope of linear regression (vs. predicate device) close to 1.0 | 0.92 |
| Intercept of linear regression (vs. predicate device) close to 0 ng/mL | 37.9 ng/mL | |
| Correlation coefficient (r) close to 1.0 | 0.990 | |
| Intended Use | Must match predicate device's intended use | Matches predicate: Quantitative measurement of CSA in human whole blood on the Dimension Vista® system; aid in management of heart, liver, and kidney transplant patients. |
| Technological Characteristics | Must demonstrate substantially equivalent characteristics to predicate (e.g., reagent form, sample type, range) | Various characteristics shown to be substantially equivalent or improved (e.g., number of tests per cartridge). |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 116 transplant samples.
- Data Provenance: Not explicitly stated, but the samples were human "transplant samples." No information on country of origin or whether they were retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
- Not Applicable. This study is a method comparison between two in-vitro diagnostic devices, not a study evaluating human interpretation against a ground truth established by experts. The "ground truth" for comparison is the measurement obtained from the predicate device.
4. Adjudication Method for the Test Set
- None. This was a quantitative method comparison study between two instruments. Adjudication is typically used when human interpretation or subjective assessments are involved.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No. This study is a technical comparison of an in-vitro diagnostic assay on a new instrument platform against an established assay on an older platform. It does not involve human readers or assess the effectiveness of AI assistance.
6. Standalone (Algorithm Only) Performance Study
- Yes, in essence. The entire evaluation is a standalone performance assessment of the Dimension Vista® CSAE Flex® reagent cartridge's ability to quantitatively measure Cyclosporine A. There is no human-in-the-loop component for the measurement process itself, as it's an automated in-vitro diagnostic method. The algorithm here refers to the instrument's measurement and calculation process.
7. Type of Ground Truth Used
- Comparison to a Legally Marketed Predicate Device. The "ground truth" for this study is the analytical measurement obtained from the Dimension® CSAE Flex® reagent cartridge (K052017), which is the legally marketed predicate device. The study aims to show that the new device's measurements are substantially equivalent to the predicate.
8. Sample Size for the Training Set
- Not applicable / Not explicitly stated. This document describes a Special 510(k) for a packaging and platform modification, not the development of a novel algorithm that requires a "training set" in the machine learning sense. The assay chemistry and fundamental technology are consistent with the predicate device. If there was any internal development or optimization, the details of a "training set" are not provided in this regulatory summary.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. As a Special 510(k) for a modified existing device, there isn't a "training set" in the context of a new algorithm development. The core methodology and reagents are the same as the predicate device, which would have undergone its own qualification and validation studies when it was initially cleared.
§ 862.1235 Cyclosporine test system.
(a)
Identification. A cyclosporine test system is a device intended to quantitatively determine cyclosporine 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 cyclosporine.(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.