(29 days)
The CEDIA Cyclosporine Plus Assay is for the quantitative determination of cyclosporine in human whole blood using automated clinical chemistry analyzers as an aid in the management of therapy in kidney, liver, and heart transplants. The CEDIA Cyclosporine Calibrators are used to calibrate the CEDIA Cyclosporine Plus Assay in human whole blood.
The CEDIA Cyclosporine Plus Assay is a two-reagent set intended to be used with automated clinical chemistry analyzers. The assay uses recombinant DNA technology (US Patent No. 4708929) to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ß galactosidase, which has been genetically engineered into two inactive fragments, termed Enzyme Acceptor (EA) and Enzyme Donor (ED) spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, to generate a color change that can be measured spectrophotometrically.
In the CEDIA Cyclosporine Plus Assay, drug in the sample competes with drug conjugated to ED for antibody binding sites. If drug is present in the sample, it binds to antibody, leaving the EDdrug conjugate free to reassociate with EA to form active ß-galactosidase. If no drug is present in the sample, antibody binds to the ED-cyclosporine conjugate, inhibiting the reassociation of inactive B-galactosidase fragments, and thus reducing the amount of active enzyme formed. The amount of active enzyme formed, and resulting absorbance change, is proportional to the amount of CEDIA Cyclosporine Plus Assay present in the sample.
The provided 510(k) summary for the CEDIA® Cyclosporine Plus Assay details the device's technical specifications and a comparison to a predicate device, but does not describe an acceptance criteria table, a study explicitly proving the device meets said criteria, or several of the specific points requested (e.g., sample size for test set, number of experts, adjudication method, MRMC study, training set details).
The document focuses on demonstrating substantial equivalence to the EMIT 2000 Cyclosporine Specific Assay (P920031) through a comparison of their intended use, method principle, components, risk to patient, and clinical performance.
However, based on the information provided under "Clinical Performance," we can infer the performance metrics reported for the device, which serve as the basis for demonstrating its suitability.
Here's an attempt to answer the questions based on the available information:
Acceptance Criteria and Reported Device Performance
1. Table of acceptance criteria and the reported device performance
Since explicit "acceptance criteria" are not listed in the document, we infer them from the reported performance of the predicate device and the new device. The predicate device's performance often sets the benchmark for the new device to demonstrate substantial equivalence.
| Performance Metric | Acceptance Criteria (Inferred from Predicate/General Standards) | CEDIA® Cyclosporine Plus Assay (Reported Performance) |
|---|---|---|
| Accuracy (Low Range) | Comparable to predicate (y = 1.05x + 12; r = 0.96, S.E.E. = 25.33 for one site) | y = 0.99x + 8; r = 0.93, S.E.E. = 25.79 |
| Accuracy (High Range) | Not explicitly given for predicate, but expected to be good. | y = 0.97x + 98; r = 0.970, S.E.E. = 80.65 |
| Assay Range (Low) | 0 to 500 ng/mL (Predicate) | 25 to 450 ng/mL (New Device) |
| Assay Range (High) | Not explicitly given for predicate, but expected to be good. | 450 to 2000 ng/mL (New Device) |
| Within Run Imprecision | Percent CVs between 3.0% and 5.0% (Predicate, across 3 levels) | Percent CVs between 3.0% and 8.0% (across 5 levels) |
| Total Imprecision | Percent CVs between 4.5% and 10.5% (Predicate, across 3 levels) | Percent CVs between 4.5% and 9.6% OR S.D=7.4 for a control at 46 ng/mL (across 5 levels) |
Note: The acceptance criteria are inferred based on the direct comparison with the predicate device's reported performance, indicating that the new device should perform equivalently or within acceptable clinical limits. Specific numeric acceptance thresholds are not explicitly stated as "acceptance criteria" in this document.
Study Details
2. Sample size used for the test set and the data provenance
- Sample Size for Test Set: Not specified in the provided document. The "Clinical Performance" section mentions "Method comparison of all transplant types to an HPLC reference method" but does not give a specific number of samples.
- Data Provenance: Not specified (e.g., country of origin). The studies appear to be clinical performance evaluations, but whether they are retrospective or prospective is not explicitly stated. The predicate device's data specifically mentions "studies at four separate sites," implying multi-center data, but this level of detail is not provided for the new device.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- This information is not applicable to this type of device (a quantitative assay). Ground truth for these assays is established by a reference method, not expert consensus.
4. Adjudication method for the test set
- Not applicable as the ground truth is established by an analytical reference method (HPLC), not human expert review.
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 is not an AI/imaging device. Therefore, an MRMC study is not applicable.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, the performance reported for the CEDIA® Cyclosporine Plus Assay is "standalone" in nature, meaning it represents the algorithm's direct measurement output compared to a reference method, without human intervention in the result determination process. The assay produces a quantitative value.
7. The type of ground truth used
- The ground truth for accuracy validation was established using a High-Performance Liquid Chromatography (HPLC) reference method. This is explicitly stated: "Method comparison of all transplant types to an HPLC reference method yielded the following results."
8. The sample size for the training set
- This information is not provided. For this type of immunoassay, while calibration and optimization are performed, explicit "training set" sizes in the context of machine learning are not typically defined or reported in this manner.
9. How the ground truth for the training set was established
- Ground truth for assay calibration (analogous to a training set for machine learning) would be established using known concentrations of cyclosporine, likely prepared gravimetrically or against certified reference materials, and then analyzed by the assay to establish the calibration curve. Specific details are not provided in this document.
§ 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.