(104 days)
The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.
For determination of:
- Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® .
- . Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
- . Fibrinogen (Fbg) with Dade® Thrombin Reagent
- . Coagulation Factor V with Dade® Innovin®
- . Coagulation Factor VII with Dade® Innovin®
- . Protein C with Protein C Reagent
- . Antithrombin (AT) with INNOVANCE® Antithrombin
- Protein C with Berichrom® Protein C
- D-dimer with INNOVANCE® D-Dimer
The performance of this device has not been established in neonate and pediatric patient populations.
Coagulation Factor V Deficient Plasma:
In vitro diagnostic reagent for the determination of the activity of coagulation factor V in human plasma.
Coagulation Factor II, VII and X Deficient Plasmas:
In vitro diagnostic reagents for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods.
Protein C Reagent:
Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma.
Berichrom® Protein C:
For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies.
The Sysmex® CS-5100 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated Reagents, Controls, Calibrators, and Consumable materials. The subject of this 510(k) notification are reagent applications which perform the coagulation tests Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent and Protein C with Berichrom® Protein C.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Sysmex® CS-5100 device:
The document describes the performance data for the Sysmex® CS-5100 automated blood coagulation analyzer, specifically for the applications: Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent, and Protein C with Berichrom® Protein C. The studies aim to demonstrate substantial equivalence to a predicate device, the Sysmex® CA-1500.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for substantial equivalence are implicitly based on demonstrating comparable performance to the predicate device. The studies aim to show that results from the new device are sufficiently similar to those from the predicate and that the new device's precision, detection capability, and linearity fall within acceptable ranges for clinical laboratory use.
| Study Type | Acceptance Criteria (Implicit from predicate comparison / CLSI guidelines) | Reported Device Performance (Sysmex® CS-5100) |
|---|---|---|
| Method Comparison | Passing-Bablok regression: Slope close to 1, Intercept close to 0, high correlation coefficient (r) with the predicate device. Bland-Altman plots to show agreement. | Coagulation Factor V: y = 1.017x + 0.185 (r=0.984) |
| Coagulation Factor VII: y = 1.051x - 0.241 (r=0.989) | ||
| Protein C (C Reagent): y = 0.988x - 0.413 (r=0.987) | ||
| Protein C (Berichrom): y = 0.950x + 0.375 (r=0.992) | ||
| Conclusion: All applications met predetermined acceptance criteria, showing equivalent results. | ||
| Reproducibility (Within Run) | Coefficients of Variation (CV%) within clinically acceptable limits for precision. | Coagulation Factor V: 2.40 - 3.16% |
| Coagulation Factor VII: 1.33 - 2.00% | ||
| Protein C (C Reagent): 2.53 - 3.22% | ||
| Protein C (Berichrom): 1.48 - 6.85% | ||
| Reproducibility (Between Run) | Coefficients of Variation (CV%) within clinically acceptable limits for precision. | Coagulation Factor V: 3.29 - 4.24% |
| Coagulation Factor VII: 0.65 - 1.29% | ||
| Protein C (C Reagent): 1.73 - 3.86% | ||
| Protein C (Berichrom): 0.00 - 1.04% | ||
| Reproducibility (Between Day) | Coefficients of Variation (CV%) within clinically acceptable limits for precision. | Coagulation Factor V: 0.00 - 0.59% |
| Coagulation Factor VII: 0.94 - 1.97% | ||
| Protein C (C Reagent): 0.00 - 1.01% | ||
| Protein C (Berichrom): 0.39 - 1.16% | ||
| Reproducibility (Total CV) | Coefficients of Variation (CV%) within clinically acceptable limits for precision. | Coagulation Factor V: 4.83 - 6.85% |
| Coagulation Factor VII: 3.39 - 5.03% | ||
| Protein C (C Reagent): 4.54 - 7.15% | ||
| Protein C (Berichrom): 3.22 - 7.92% | ||
| Detection Capability (LoQ) | Measured Limit of Quantitation (LoQ) ≤ Lower Limit of Clinically Reportable Range (CLRR), with Maximum Total Error within acceptance. | Coagulation Factor V: LoQ = 4.80% (CLRR = 6.0%), Max Total Error = 0.74% |
| Coagulation Factor VII: LoQ = 3.39% (CLRR = 6.0%), Max Total Error = 0.27% | ||
| Protein C (C Reagent): LoQ = 9.35% (CLRR = 10.1%), Max Total Error = 2.91% | ||
| Protein C (Berichrom): LoQ = 8.32% (CLRR = 10.0%), Max Total Error = 2.07% | ||
| Conclusion: All data met predetermined acceptance criteria and support the lower limit of the clinically reportable range claim. | ||
| Linearity & Measuring Range | Measured Linear Range ≥ Clinically Reportable Range. | Coagulation Factor V: Linear Range = 3.4 – 180.7% (CLRR = 6.0 – 149.0%) |
| Coagulation Factor VII: Linear Range = 4.3 – 179.5% (CLRR = 6.0 – 149.0%) | ||
| Protein C (C Reagent): Linear Range = 7.0 – 187.7% (CLRR = 10.1 – 131.0%) | ||
| Protein C (Berichrom): Linear Range = 7.1 – 181.3% (CLRR = 10.0 – 138.0%) | ||
| Conclusion: All reagents met the predetermined acceptance criteria and support the clinically reportable range claim. | ||
| Reference Interval | Established reference intervals for healthy populations. | Coagulation Factor V: 80.8% of norm (5th Percentile) |
| Coagulation Factor VII: 67.6% of norm (5th Percentile) | ||
| Protein C (C Reagent): 76.4% of norm (5th Percentile) | ||
| Protein C (Berichrom): 83.0% of norm (5th Percentile) |
2. Sample Sizes Used for the Test Set and Data Provenance
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Method Comparison:
- Coagulation Factor V: N = 609 total samples (133, 151, 148, 177 across 4 sites)
- Coagulation Factor VII: N = 505 total samples (121, 145, 102, 137 across 4 sites)
- Protein C (C Reagent): N = 624 total samples (138, 176, 110, 200 across 4 sites)
- Protein C (Berichrom): N = 531 total samples (127, 149, 130, 125 across 4 sites)
- Data Provenance: Four external sites in the United States. The samples were "patient samples" and seem to be prospective as they were measured on both devices in random order for comparison.
-
Reproducibility Studies:
- The sample types used for reproducibility studies are not specified as patient samples, but rather analytical samples (possibly controls or pooled plasma). The N for actual samples per run is not explicitly given, but the study design involved "two runs per day, with two replicates per run, at each of the three sites."
- Data Provenance: Two external sites in Germany and one external site in the United States. These are prospective studies performed over 20 days.
-
Detection Capability (LoQ) and Linearity Studies:
- Sample sizes are not explicitly stated for these studies, but they involve different concentrations or dilutions to determine the limits.
- Data Provenance: Not specified, but likely from laboratory settings where the devices were tested.
-
Reference Interval Studies:
- Coagulation Factor V, VII, Protein C (C Reagent), Protein C (Berichrom): N = 194 for each.
- Data Provenance: Three clinical study sites in the United States. This is a prospective study of a "study population."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- No human "experts" established ground truth for the test set. This device is an automated in vitro diagnostic analyzer. The ground truth, in this context, is the accurately measured value of the coagulation factors and protein C using the predicate device (Sysmex® CA-1500) or established clinical analytical methods, which the new device (Sysmex® CS-5100) is compared against. Clinical laboratory standards (CLSI guidelines) are followed to ensure the validity of these reference measurements.
4. Adjudication Method
- Not applicable as this is an automated analytical device rather than a diagnostic imaging or classification system involving human interpretation. The "ground truth" or reference values are obtained through the predicate device or validated laboratory methods, not through human adjudication of ambiguous cases.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done. This type of study is relevant for diagnostic systems where human readers interpret output (e.g., medical images). The Sysmex® CS-5100 is an automated analyzer, and its performance is evaluated by comparing its quantitative results against a predicate device's results, not by comparing human reader performance with and without AI assistance.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- Yes, this is a standalone study. The Sysmex® CS-5100 is an automated instrument with an algorithm (its internal measurement and calculation processes) that generates results without real-time human intervention in the measurement process itself. The performance data presented (method comparison, reproducibility, detection capability, linearity) describe the intrinsic performance of the device's analytical capabilities. While human technicians operate and maintain the device, the core measurement is "algorithm only."
7. Type of Ground Truth Used
- Predicate Device/Method comparison: For the method comparison studies, the "ground truth" for demonstrating substantial equivalence was the measurements obtained from the predicate device (Sysmex® CA-1500).
- Established analytical methods/standards: For reproducibility, detection capability, and linearity studies, the "ground truth" refers to the expected statistical performance (e.g., target CVs, expected linear range) according to CLSI guidelines and accepted laboratory practice for quantitative measurement methods.
- Reference Intervals: For reference interval studies, the "ground truth" is derived from the measurements in a healthy population to establish the normal range, as per CLSI guidelines EP28-A3c.
8. Sample Size for the Training Set
- The document does not explicitly mention a "training set" in the context of machine learning or AI algorithm development. This device is an automated analyzer, and its operational parameters and internal algorithms would typically be developed and validated by the manufacturer using extensive internal testing and calibration with known standards and samples, rather than a distinct "training set" in the AI sense. The studies described are for validation and verification of the final product.
9. How the Ground Truth for the Training Set Was Established
- Given that a "training set" in the AI sense is not explicitly described or applicable in the provided context for this type of IVD device, this question is not directly answerable from the document. The development of such an analyzer involves engineering design, physical and chemical principles, and calibration with reference materials, rather than training an algorithm on a 'ground truth' dataset in the same way an AI for image classification would be trained.
§ 864.5425 Multipurpose system for in vitro coagulation studies.
(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.