(98 days)
The Emit® 2000 Cyclosporine Specific Assay is for in vitro quantitative analysis of cyclosporine (CsA) in human whole blood as an aid in the management of cyclosporine therapy in kidney, heart and liver transplant patients.
The Emit® 2000 Cyclosporine Specific Assay employs a homogeneous enzyme immunoassay technique used for the analysis of cyclosporine in whole blood. The assay contains mouse monoclonal antibodies with a high specificity for cyclosporine. The Emit® 2000 Cyclosporine Specific Assay is based on competition for cyclosporine antibody binding sites. Cyclosporine in the sample competes with cyclosporine in Enzyme Reagent B that is labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH). Active (unbound) enzyme converts the oxidized nicotinamide adenine dinucleotide (NAD) in Antibody Reagent A to NADH, resulting in a kinetic absorbance change that can be measured spectrophotometrically. Enzyme activity decreases upon binding to the antibody, allowing the cyclosporine concentration in the sample to be measured in terms of enzyme activity. Endogenous serum G6PDH does not interfere because the coenzyme NAD functions only with the bacterial (Leuconostoc mesenteroides) enzyme employed in the assay.
The provided text describes the 510(k) submission for the Emit® 2000 Cyclosporine Specific Assay. It outlines the device's intended use and presents comparative method studies to demonstrate its performance against predicate devices and a reference method.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the results of the comparative method studies demonstrating substantial equivalence to the predicate devices and an established reference method (LC/MS). The performance is presented in terms of linear regression analysis (slope, intercept, and correlation coefficient 'r').
| Comparison Method | Acceptance Criteria (Implicit from Predicate & LC/MS) | Reported Device Performance (Emit® 2000 vs. Comparative Method) |
|---|---|---|
| LC/MS (Reference Method) | ||
| All samples | High correlation (r close to 1), slope close to 1, small intercept | Slope: 1.01, Intercept: 36.07, r: 0.971 (n=138) |
| Heart | High correlation, slope close to 1, small intercept | Slope: 1.04, Intercept: 19.00, r: 0.989 (n=33) |
| Liver | High correlation, slope close to 1, small intercept | Slope: 1.00, Intercept: 42.11, r: 0.971 (n=40) |
| Kidney | High correlation, slope close to 1, small intercept | Slope: 1.14, Intercept: -49.0, r: 0.951 (n=59) |
| Abbott TDx®/TDxFLx® CSA Monoclonal Whole Blood Assay (Predicate Device) | ||
| All samples | High correlation (r close to 1), slope close to 1, small intercept | Slope: 1.13, Intercept: -92.4, r: 0.969 (n=134) |
| Heart | High correlation, slope close to 1, small intercept | Slope: 1.12, Intercept: -86.6, r: 0.976 (n=33) |
| Liver | High correlation, slope close to 1, small intercept | Slope: 1.14, Intercept: -102, r: 0.982 (n=40) |
| Kidney | High correlation, slope close to 1, small intercept | Slope: 1.15, Intercept: -114, r: 0.950 (n=59) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Sizes for Test Set:
- LC/MS Comparison: 138 samples (33 Heart, 40 Liver, 59 Kidney)
- Abbott TDx®/TDxFLx® Comparison: 134 samples (33 Heart, 40 Liver, 59 Kidney)
- Data Provenance: Banked retrospective samples from 3 transplant patient groups (heart, liver, and kidney). The studies were conducted at two external sites, but the country of origin is not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not applicable to this type of device and study. The "ground truth" for this assay is established by quantitative measurement methods (LC/MS and predicate immunoassays), not by expert interpretation of images or clinical cases.
4. Adjudication Method for the Test Set
This information is not applicable to this type of device and study. Adjudication methods (like 2+1, 3+1) are typically used for establishing ground truth in studies involving expert review of qualitative data (e.g., medical images). Here, the comparison is against established quantitative measurement methods.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This is not a diagnostic imaging device or an AI-assisted interpretation tool. It is a quantitative assay, and therefore, an MRMC comparative effectiveness study involving human readers with and without AI assistance is not relevant or performed for this device.
6. Standalone Performance Study
Yes, a standalone performance was essentially done. The "Comparative Method" studies analyze the Emit® 2000 Cyclosporine Specific Assay's measurements directly against the reference (LC/MS) and predicate immunoassay results. This demonstrates the algorithm's (assay's) performance in generating quantitative values for cyclosporine in whole blood.
7. Type of Ground Truth Used
The ground truth used consisted of:
- A "gold standard" quantitative measurement: Liquid Chromatography / Mass Spectrometry (LC/MS) for cyclosporine concentration.
- A legally marketed predicate device: Abbott TDx®/TDxFLx® Cyclosporine Monoclonal Whole Blood Assay. This serves as a comparative benchmark to demonstrate substantial equivalence.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" or its sample size. This assay is a chemical immunoassay, not a machine learning model that typically requires a distinct training phase with labeled data. The development of the assay reagents and protocols would involve internal validation and optimization, but not in the same sense as a machine learning training set.
9. How the Ground Truth for the Training Set Was Established
As there is no explicit "training set" in the context of a machine learning model, this question is not strictly applicable. The "ground truth" (reference measurements) for the assay's development and validation would have been established through a combination of methods, including the use of known concentration standards, spiked samples, and potentially comparisons to existing reference methods during assay development. However, the document does not detail these developmental stages, focusing instead on the performance evaluation for regulatory submission.
§ 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.