Sysmex Automated Blood Coagulation Analyzer CS-5100

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ## A. 510(k) Number: K161317 ## B. Purpose for Submission: The purpose of this premarket notification is to extend the deep vein thrombosis (DVT) exclusion claim with the cleared INNOVANCE® D-dimer (K093626) to the Sysmex® CS-5100. In addition to D-dimer, the Sysmex® CS-5100 also performs the following assays: prothrombin time and internationalized ratio (PT/INR), activated partial thromboplastin time (APTT), fibrinogen, and antithrombin. The performance for the abovementioned assays in combination with the Sysmex® CS-5100 was evaluated in premarket notification K150678. In the same premarket notification K150678, the use of INNOVANCE® D-dimer (K093626) for the exclusion of pulmonary embolism (PE) was extended to the Sysmex® CS-5100. ## C. Manufacturer and Instrument Name: Sysmex Corporation, Sysmex® CS-5100 ## D. Type of Test or Tests Performed: Quantitative D-dimer assay ## E. System Descriptions: 1. **Device (Instrument) Description:** The Sysmex® CS-5100 is a standalone automated blood coagulation analyzer which analyzes citrated venous plasma collected in 3.2% sodium citrate anticoagulant. Results are displayed on the Information Processing Unit (IPU) screen and can be printed on external printers or transmitted to a host computer. 2. **Principles of Operation:** The Sysmex® CS-5100 uses mechanical, hydraulic, and electrical systems to perform analysis. The basic flow of analysis begins with sample presentation in the normal mode or micro-sample mode. The instrument warms a specified quantity of sample for a defined time period prior to the addition of reagents. The instrument utilizes the clotting, chromogenic, and immunoassay methods of analysis. The clotting method determines {1} the clotting time using the percentage detection method for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. The chromogenic and immunoassay methods determine the change in light absorbance per minute (doD/min). The instrument determines antithrombin using the chromogenic method whereas D-dimer is quantitated using the immunoassay method. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ☐ X ☐ or No ☐ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ☐ or No ☐ X ☐ 4. Specimen Identification: Manual entry and barcode reader 5. Specimen Sampling and Handling: The CS-5100 supports two different analysis modes; normal mode for capped (closed) and uncapped (open) sampling from collection tubes, and the micro-sample mode for open (uncapped) sampling. In the normal mode, capped and uncapped samples may be loaded into the same sample rack for analysis. Automatic reanalysis is also an exclusive function of the normal mode. In the micro-sample mode, uncapped samples may be loaded in the sampler or STAT holder. 6. Calibration: Calibration is an automated function of the Sysmex® CS-5100 coagulation analyzer and was performed for the D-dimer assay using the INNOVANCE® D-dimer calibrator, a component of the INNOVANCE® D-dimer kit. 7. Quality Control: Quality control was performed using INNOVANCE® D-dimer CONTROL 1 and CONTROL 2 (K081732). The analyzer has two types of control assessment methods: X-Bar and Levy-Jennings. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for 2 {2} this line of product types: Yes ☐ X ☐ or No ☐ The Hazard Analysis and Software Development processes were reviewed in premarket notification K150678. The technological characteristics cleared in K150678 remain unchanged; therefore, additional software analysis was not required to support substantial equivalence in this premarket notification. F. Regulatory Information: 1. Regulation section: 21 CFR 864.5425 2. Classification: Class II 3. Product code: JPA, System, Multipurpose for in vitro coagulation studies 4. Panel: Hematology (81) G. Intended Use: 1. Indication(s) for Use: 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 - Antithrombin (AT) with INNOVANCE® Antithrombin - D-dimer with INNOVANCE® D-Dimer The performance of this device has not been established in neonate and pediatric patient populations. 3 {3} 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: Sysmex® CA-1500; K011235 2. Comparison with Predicate Device: | Similarities | | | | --- | --- | --- | | Item | Device Sysmex® CS-5100 | Predicate Sysmex® CA-1500 | | Intended use | 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 • Antithrombin (AT) with INNOVANCE® Antithrombin • D-dimer with INNOVANCE® D-Dimer The performance of this device | The intended use of the Sysmex® CA-1500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform the following parameters and calculated parameters: Clotting Analysis Parameters: Prothrombin Time (PT); Activated Partial Thromboplastin Time (APTT); Fibrinogen (Clauss); Batroxobin Time; Extrinsic Factors (II, V, VII, X); Intrinsic Factors (VIII, IX, XI, XII); Protein C. Chromogenic Analysis Parameters: Antithrombin III; Factor VIII; Plasminogen; Heparin; Protein C; α2-Antiplasmin. Immunologic Analysis Parameters: D-dimer. Calculated Parameters: PT Ratio; PT INR; PT %; Derived | 4 {4} | Similarities | | | | --- | --- | --- | | Item | Device Sysmex® CS-5100 | Predicate Sysmex® CA-1500 | | | has not been established in neonate and pediatric patient populations. | Fibrinogen; Factor Assays % Activity | | Assay methodology | Immunoassay | Same | | Light source for immunoassay method | Halogen lamp | Same | | Sample type | 3.2% sodium citrate plasma, venous collection | Same | | Clinical reportable range | 0.19 to 35.2 mg/L FEU | Same | | Sample volume in normal mode | 13 μL | Same | | Specimen sampling | Normal and micro-sample mode | Same | | Specimen processing | Automatic pipetting and dilution | Same | | STAT testing | Yes | Same | | Temperature control | Sample incubator: 37°C ± 1.0°C | Same | | Differences | | | | --- | --- | --- | | Item | Device Sysmex® CS-5100 | Predicate Sysmex® CA-1500 | | Detection wavelength for D-dimer | 660 nm | 800 nm | | Temperature control | Detector: 37°C ± 0.5°C Reagent probe: 37°C ± 0.5°C | Detector: 37°C ± 1.0°C Reagent probe: 37°C ± 1.0°C | | Incubator | 36 wells | 14 wells | | Detector | 20 wells | 8 wells: scattered light detection 4 wells: transmitted light detection | | Installation | Standalone analyzer | Tabletop analyzer | I. Special Control/Guidance Document Referenced (if applicable): CLSI H59-A, Quantitative D-Dimer for the Exclusion of Venous Thromboembolic Disease; Approved Guideline J. Performance Characteristics: {5} 6 1. Analytical Performance: In premarket notification K150678 the following studies were performed with the INNOVANCE® D-Dimer assay in combination with the Sysmex® CS-5100: method comparison to the Sysmex® CA-1500, precision/reproducibility, linearity, carryover, and interference studies. The established performance and technological characteristics cleared in K150678 remain unchanged; therefore, additional performance studies were not required to support substantial equivalence in this premarket notification. 2. Other Supportive Instrument Performance Data Not Covered Above: a. Clinical Studies: The objective of this premarket notification is to extend the DVT exclusion claim for the cleared INNOVANCE® D-Dimer assay (K093626) to the Sysmex® CS-5100. In K093626, the clinical cut-off for DVT was established using INNOVANCE® D-Dimer in combination with the BCS® and BCS® XP Systems. Therefore, a clinical cut-off study was performed to validate the clinical cut-off for the exclusion of DVT using the INNOVANCE® D-Dimer assay in combination with the Sysmex® CS-5100. The INNOVANCE® D-Dimer assay was evaluated on the Sysmex® CS-5100 System in a multi-center study to validate exclusion of a first deep vein thrombosis (DVT) event. The specimens were prospectively collected from 1,907 consecutive outpatients presenting to the emergency or ambulatory department with suspected DVT. Overall, samples were collected from a total of 23 sites; 17 in the United States and 6 in Germany. The Wells' score clinical pre-test probability (PTP) assessment model was used to categorize patients as likely or unlikely for suspicion of DVT; or alternatively as high, intermediate or at low PTP for suspected DVT. Patients with a high or likely PTP score were excluded from the study. Samples collected from patients with a low, intermediate or unlikely score were tested with the INNOVANCE® D-Dimer assay and the results were compared to an established cutoff value of 0.50 mg/L FEU. A D-dimer result ≥ 0.50 mg/L FEU was considered positive; whereas a < 0.50 mg/L FEU D-dimer result was considered negative. Patients with a positive D-dimer result were evaluated by imaging methods, e.g. ultrasound. Of the 1,907 patients, 368 were excluded from analysis; of which 213 had a reported history of chronic DVT, and 155 were excluded on the basis of the defined exclusion criteria (e.g. oral anticoagulation therapy, inpatient status, and pre- or post-analytical variables). 222 patients with unobtainable follow-up data were excluded from the study, for a total of 1,317 patients included in the data analysis. The instrument-specific sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) with the lower bound of two-sided 95% confidence intervals (LCL) were obtained with the INNOVANCE® D-Dimer clinical cut-off of {6} 0.50 mg/L FEU. The overall prevalence of DVT in the 1,317 patients was 6.1% (80 of 1,317) with 7.0% (56 of 803) in the US population and 4.7% (24 of 514) in the European population. | US Sites | Imaging and 3-month follow-up | | | Predictive Value (Lower confidence limit) | | | --- | --- | --- | --- | --- | --- | | | | | | | | | INNOVANCE® D-dimer on Sysmex® CS-5100 | Positive | Negative | Total | NPV | 99.7% (LCL: 98.1%) | | Positive | 55 | 457 | 512 | PPV | 10.7% (LCL: 8.3%) | | Negative | 1 | 290 | 291 | Sensitivity | 98.2% (LCL: 90.4%) | | Total | 56 | 747 | 803 | Specificity | 38.8% (LCL: 35.3%) | *The NPV and PPV shown in the table above (US sites) were standardized to a prevalence of 15% within the intended use population. The standardized NPV and PPV are 99.2% (LCL: 95.6%) and 22.1% (LCL: 17.7%), respectively. | Non-US Sites | Imaging and 3-month follow-up | | | Predictive Value (Lower confidence limit) | | | --- | --- | --- | --- | --- | --- | | INNOVANCE® D-dimer on Sysmex® CS-5100 | Positive | Negative | Total | NPV | 99.6% (LCL: 97.9%) | | Positive | 23 | 222 | 245 | PPV | 9.4% (LCL: 6.3%) | | Negative | 1 | 268 | 269 | Sensitivity | 95.8% (LCL: 78.9%) | | Total | 24 | 490 | 514 | Specificity | 54.7% (LCL: 50.2%) | *The NPV and PPV shown in the table above (non-US sites) were standardized to a prevalence of 15% within the intended use population. The standardized NPV and PPV are 98.7% (LCL: 92.9%) and 27.2% (LCL: 19.6%), respectively. | Combined Sites | Imaging and 3-month follow-up | | | Predictive Value (Lower confidence limit) | | | --- | --- | --- | --- | --- | --- | | INNOVANCE® D-dimer on Sysmex® CS-5100 | Positive | Negative | Total | NPV | 99.6% (LCL: 98.7%) | | Positive | 78 | 679 | 757 | PPV | 10.3% (LCL: 8.3%) | | Negative | 2 | 558 | 560 | Sensitivity | 97.5% (LCL: 91.3%) | | Total | 80 | 1237 | 1317 | Specificity | 45.1% (LCL: 42.3%) | *The NPV and PPV shown in the table above (combined sites) were standardized to a prevalence of 15% within the intended use population. The standardized NPV and PPV {7} are 99.0% (LCL: 96.5%) and 23.9% (LCL: 19.9%), respectively. ## K. Proposed Labeling: The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10. ## L. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 8