(143 days)
The Sysmex® Automated Blood Coagulation Analyzer CS-2500 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®
- . Coagulation Factor VIII with Dade® Actin® FSL
- . Coagulation Factor IX with Dade® Actin® FSL
- . Lupus Anticoagulant with LA1 Screening / LA2 Confirmation Reagent
- . Factor V Leiden with Factor V Leiden Assay
- . 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.
Intended Use for Factor V Leiden Assay:
The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use.
Intended Use for Coagulation Factor VIII Deficient Plasma:
In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.
Intended Use for Coagulation Factor IX Deficient Plasma:
In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.
Intended Use for LA1 Screening / LA2 Confirmation Reagents:
LA1 Screening Reagent / LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants.
The Sysmex® CS-2500 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 Factor V Leiden with Factor V Leiden Assay, Coagulation Factor VIII with Dade® Actin FSL®, Coagulation Factor IX with Dade® Actin FSL®, Lupus Anticoagulant with LA 1 Screening Reagent / LA 2 Confirmation Reagent. The analysis principles used on the instrument are reflected by the reagent application testing provided in this 510(k) notification and is described in the below table. The instrument is capable of measuring in Normal mode and Micro-sample mode. Options and accessories include a waste tank and a 2D barcode reader.
The provided document describes the 510(k) premarket notification for the Sysmex® Automated Blood Coagulation Analyzer CS-2500. This is a medical device, and the "study that proves the device meets the acceptance criteria" refers to the performance data submitted to demonstrate substantial equivalence to a predicate device.
It's important to note that this document is for an In Vitro Diagnostic (IVD) device, not an AI/ML algorithm for image interpretation. Therefore, many of the typical acceptance criteria and study designs associated with AI/ML (like multi-reader multi-case studies, expert adjudication for ground truth of imaging, or effect size of AI assistance for human readers) do not directly apply in the same way. Instead, the study focuses on analytical performance characteristics compared to a predicate device.
Here's an interpretation based on the provided document:
Acceptance Criteria and Device Performance
The acceptance criteria for this type of IVD device are typically established based on:
- Method Comparison: Showing agreement with a legally marketed predicate device. This is evaluated using statistical methods like Passing-Bablok regression and Bland-Altman plots. Acceptance criteria would involve a high correlation coefficient (r), and a slope close to 1 and intercept close to 0, indicating strong agreement.
- Reproducibility (Precision): Demonstrating the consistency of results when the test is repeated under varying conditions (within-run, between-run, between-day, and total variability). Acceptance criteria are typically expressed as a maximum allowable coefficient of variation (%CV).
- Detection Capability (Limit of Quantitation): Proving the lowest concentration of an analyte that can be reliably measured. Acceptance criteria are usually based on a predefined maximum total error.
- Linearity & Measuring Range: Confirming that the device produces results proportional to the concentration of the analyte across its claimed analytical measuring range. Acceptance criteria mean the measured linear range must encompass the claimed clinically reportable range.
- Reference Interval: Establishing the range of test results expected in a healthy population. Acceptance criteria would be the successful determination of these intervals or confirmation of existing ones.
- Clinical Performance (e.g., Cut-off Study): For specific assays, validating clinical performance characteristics like diagnostic accuracy against a gold standard (e.g., genotype for Factor V Leiden). Acceptance criteria would typically involve achieving high positive and negative percentage agreement.
1. Table of Acceptance Criteria and the Reported Device Performance
The document does not explicitly list the "acceptance criteria" numerical targets. Instead, it states that "Results from each application met the predetermined acceptance criteria." and later, "All reagents met the predetermined acceptance criteria." This implies that Siemens had internal, pre-defined thresholds for these performance metrics, which were successfully met.
Based on the performance data presented, here is a summary table, inferring the intent behind the reported results as meeting acceptance:
| Performance Metric | Specific Test/Application | Reported Device Performance (Summary) | Implied Acceptance Criteria (High-Level) |
|---|---|---|---|
| Method Comparison (Passing-Bablok) | Factor V Leiden Assay | r = 0.902 - 0.995 (across sites), Combined r = 0.978; Slope (y) ~ 0.9-1.0; Intercept (x) ~ 0-0.1 | High correlation (e.g., r > 0.9 or 0.95); Slope close to 1 (e.g., 0.95-1.05); Intercept close to 0 (e.g., within +/- small range), indicating substantial agreement with predicate. |
| Coagulation Factor VIII | r = 0.915 - 0.987 (across sites), Combined r = 0.958; Slope (y) ~ 0.95-1.12; Intercept (x) ~ -7.4 to 1.3 | ||
| Coagulation Factor IX | r = 0.971 - 0.993 (across sites), Combined r = 0.984; Slope (y) ~ 0.99-1.01; Intercept (x) ~ -4.4 to -0.6 | ||
| LA 1 Screening | r = 0.995 - 0.997 (across sites), Combined r = 0.995; Slope (y) ~ 0.92-0.98; Intercept (x) ~ -0.2 to 4.0 | ||
| LA 2 Confirmation | r = 0.982 - 0.995 (across sites), Combined r = 0.988; Slope (y) ~ 0.94-0.96; Intercept (x) ~ 2.0 to 3.1 | ||
| LA 1 / LA 2 Ratio | r = 0.975 - 0.996 (across sites), Combined r = 0.989; Slope (y) ~ 0.90-1.0; Intercept (x) ~ -0.03 to 0.08 | ||
| Reproducibility (Total CV) | Factor V Leiden Assay | 1.47 – 4.68 %CV (Sites Combined) | %CV below pre-defined threshold (e.g., typically < 5-10% depending on assay and concentration), indicating consistent results. |
| Coagulation Factor VIII | 4.16 - 5.96 %CV (Sites Combined) | ||
| Coagulation Factor IX | 5.47 - 10.54 %CV (Sites Combined) | ||
| LA 1 Screening | 1.17 - 3.80 %CV (Sites Combined) | ||
| LA 2 Confirmation | 0.72 - 1.89 %CV (Sites Combined) | ||
| LA 1 / LA 2 Ratio | 1.32 - 3.29 %CV (Sites Combined) | ||
| Detection Capability (LoQ) | Coagulation Factor VIII | Measured LoQ: 2.52% of norm; Max Total Error: 0.51% of norm | Measured LoQ must be less than or equal to the claimed Lower Limit of Clinically Reportable Range, and total error within acceptable limits. This typically means the device can reliably detect activity at or below the lowest claimed clinical range. |
| Coagulation Factor IX | Measured LoQ: 2.76% of norm; Max Total Error: 1.01% of norm | ||
| Linearity & Measuring Range | Coagulation Factor VIII | Measured Linear Range: 2.12 – 246.41% of Norm; Clinically Reportable Range: 3.0 – 182.0% of Norm | Measured linear range must encompass the entire claimed clinically reportable range. |
| Coagulation Factor IX | Measured Linear Range: 2.38 – 193.79% of Norm; Clinically Reportable Range: 3.0 – 145.5% of Norm | ||
| Clinical Performance (Cut-off Study) | Factor V Leiden Assay | Positive Agreement: 100.0% (95% CI: 98.3–100.0%); Negative Agreement: 99.4% (95% CI: 96.6–100.0%) | High positive and negative agreement (e.g., >95% or as per clinical needs) with the gold standard. |
2. Sample sizes used for the test set and the data provenance
- Method Comparison:
- Sample Size (for each application): Varied by site and application, ranging from N=8 to N=173 for individual sites.
- Factor V Leiden: Total N = 494 (Combined Sites)
- Coagulation Factor VIII: Total N = 408 (Combined Sites)
- Coagulation Factor IX: Total N = 459 (Combined Sites)
- Lupus Anticoagulant (LA1, LA2, Ratio): Total N = 347-402 (Combined Sites)
- Data Provenance: Conducted at four external sites; 3 in the United States and one in Germany. Samples were patient samples. Retrospective (implied by "patient samples collected," likely frozen/stored retrospectively as this is an analyzer validation, not a live clinical trial for patient outcomes).
- Sample Size (for each application): Varied by site and application, ranging from N=8 to N=173 for individual sites.
- Reproducibility Studies:
- Sample Size: Not explicitly stated as a number of distinct patient samples. The study design followed CLSI EP05-A2, which involves repetitive testing of control materials or pooled patient samples over multiple days/runs. "Twenty-day precision studies" were performed.
- Data Provenance: One external site in Germany and two external sites in the United States.
- Detection Capability, Linearity & Measuring Range:
- Sample Size: Not explicitly stated as a number of distinct patient samples. These studies typically use diluted samples or spiked samples to cover the analytical range.
- Data Provenance: Not specified, but likely conducted at the same or similar labs as the other analytical performance studies.
- Reference Interval:
- Sample Size: Between N=187 and N=193 samples per application.
- Data Provenance: Three clinical study sites in the United States. Study population did not include neonate and pediatric patient populations.
- Factor V Leiden Cut-off Study:
- Sample Size: N = 381 patients (combined from US and OUS sites), with N=127 patients from the US.
- Data Provenance: Three different clinical sites (one site in the US and two sites in Germany). Samples were citrated plasma from patients submitted for thrombophilia screening, collected and then frozen.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable in the context of this IVD device. Ground truth for clinical assays is typically established by:
- Comparison to a legally marketed predicate device: As seen in the method comparison.
- Defined analytical standards: For precision, linearity, and detection limits.
- Clinical gold standard: For the Factor V Leiden cut-off study, genetic testing (Factor V Leiden PCR method) served as the "reference," which is an objective laboratory test, not expert interpretation.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable for an IVD device analytical performance study. Adjudication is relevant for subjective assessments, particularly in imaging or clinical endpoints. This study measures quantitative values from blood samples.
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
Not applicable. This is an IVD device (blood coagulation analyzer), not an AI imaging algorithm. There are no "human readers" interpreting images assisted by AI in this context.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in a way. The device (Sysmex® CS-2500) functions as a standalone instrument to measure coagulation parameters. The performance studies (method comparison, reproducibility, detection capability, linearity, reference interval) evaluate the device's output without direct human "interpretation" of raw signals for diagnosis, but rather human use of the device and its generated numerical reports. The "algorithm" here refers to the instrument's internal measurement and calculation procedures rather than a predictive AI model.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The "ground truth" or reference for this device's performance evaluation was primarily:
- Predicate Device: For method comparison (Sysmex® CA-1500). The predicate itself is a legally marketed device with established performance.
- Analytical Standards/Reference Materials: For studies like reproducibility, detection capability, and linearity.
- External Laboratory Test (PCR): For the Factor V Leiden study, the "Reference (Factor V Leiden PCR method)" served as the objective ground truth for the genetic variant.
8. The sample size for the training set
Not applicable. This document is for the validation of an IVD medical device (a physical instrument and associated reagents), not a machine learning model that requires a "training set" in the conventional sense. The "training" of such a device refers to its design, calibration, and internal programming by the manufacturer, which is distinct from data-driven machine learning.
9. How the ground truth for the training set was established
Not applicable, as there is no "training set" in the context of an AI/ML model. The "ground truth" (or design specifications and analytical performance ranges) for such a device is established through comprehensive engineering, chemical, and biological research and development, following recognized industry standards (e.g., CLSI guidelines).
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December 18, 2017
Siemens Healthcare Diagnostic Products GmbH Nils Neumann Regulatory Affairs Manager Emil-von-Behring Strasse 76 35041 Marburg, Germany
Re: K172286
Trade/Device Name: Sysmex® Automated Blood Coagulation Analyzer CS-2500 Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: JPA, GGW, GJT, GIR Dated: December 8, 2017 Received: December 12, 2017
Dear Nils Neumann:
We have reviewed vour Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulation (21 CFR Part 809), please contact the Division of Industry and Consumer Education (DICE) at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education (DICE) at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely,
Leonthena R. Carrington -S
Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K172286
Device Name
Sysmex® Automated Blood Coagulation Analyzer CS-2500, Factor V Leiden Assay, Coagulation Factor VIII, IX, XI and XII Deficient Plasmas, LA1 Screening / LA2 Confirmation Reagents
Indications for Use (Describe)
The Sysmex® Automated Blood Coagulation Analyzer CS-2500 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®
- . Coagulation Factor VIII with Dade® Actin® FSL
- . Coagulation Factor IX with Dade® Actin® FSL
- . Lupus Anticoagulant with LA1 Screening / LA2 Confirmation Reagent
- . Factor V Leiden with Factor V Leiden Assay
- . 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.
Intended Use for Factor V Leiden Assay:
The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use.
Intended Use for Coagulation Factor VIII Deficient Plasma:
In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.
Intended Use for Coagulation Factor IX Deficient Plasma:
In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.
Intended Use for LA1 Screening / LA2 Confirmation Reagents:
LA1 Screening Reagent / LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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510(k) Summary
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of 21 CFR §807.92 and follows the FDA guidance 'The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]', issued July 28, 2014.
1 Submitter
Siemens Healthcare Diagnostics Products GmbH
Emil-von-Behring-Str. 76
35041 Marburg, Germany
| Contact Person: | Nils Neumann |
|---|---|
| Email: | neumann.nils@siemens-healthineers.com |
| Phone: | + (49) 6421 39 7133 |
| Facsimile: | + (49) 6421 39 4977 |
| Date Prepared: | December 12, 2017 |
2 Device
| Name of Device: | Sysmex® Automated Blood Coagulation AnalyzerCS-2500 |
|---|---|
| Common or Usual Name: | Automated Coagulation Instrument |
| Classification Name: | Multipurpose system for in vitro coagulation studies(21 CFR 864.5425) |
| Regulatory Class: | 2 |
| Product Code: | JPA |
| 510(k) Review Panel | Hematology |
3 Predicate Device
| Name of Device: | Sysmex® CA-1500 (K011235) |
|---|---|
| Common or Usual Name: | Automated Coagulation Instrument |
| Classification Name: | Multipurpose system for in vitro coagulation studies(21 CFR 864.5425) |
| Regulatory Class: | 2 |
| Product Code: | JPA |
| 510(k) Review Panel | Hematology |
The predicate has not been subject to a design-related recall for any of the applications associated with this premarket notification. No reference devices were used in this submission. Siemens Healthcare Diagnostics Products, GmbH Page 1 of 22
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| Reagent Applications that are the subject of this 510(k) notification | |||||
|---|---|---|---|---|---|
| ApplicationIntended Use | 510(k) Numberrelated toapplication onpredicate device | RegulationNumber | RegulatoryClass | ProductCode | Panel |
| Factor V Leiden AssayThe Siemens HealthcareDiagnostics Factor V LeidenAssay is a simple functionalclotting test system intended forscreening of resistance toActivated Protein C (APC) inplasma from individuals with theFactor V (Leiden) defect. For invitro diagnostic use. | K992456 | 864.7925 | Class II | GGW | Hematology |
| Coagulation Factor VIIIDeficient PlasmaIn vitro diagnostic reagents forthe determination of the activityof coagulation factors VIII, IX,XI and XII in human plasma bycoagulometric methods. | K924396 | 864.7290 | Class II | GJT | Hematology |
| Coagulation Factor IXDeficient PlasmaIn vitro diagnostic reagents forthe determination of the activityof coagulation factors VIII, IX,XI and XII in human plasma bycoagulometric methods. | K924396 | 864.7290 | Class II | GJT | Hematology |
| LA 1 Screening Reagent /LA 2 Confirmation Reagent,and LA RatioLA 1 Screening Reagent / LA 2Confirmation Reagent aresimplified DRVVT reagents fordetection of LupusAnticoagulants (LA) in one-stage clotting tests. LA 1Screening Reagent: SimplifiedDRVV reagent to screen for thepresence of LupusAnticoagulants. LA 2Confirmation Reagent:Phospholipid-rich DRVVreagent for the specificcorrection of LupusAnticoagulants. | K993299 | 864.8950 | Class I | GIR | Hematology |
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Device Description / Test Principle 4
The Sysmex® CS-2500 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 ●
- Consumable materials ●
The subject of this 510(k) notification are reagent applications which perform the coagulation tests Factor V Leiden with Factor V Leiden Assay, Coagulation Factor VIII with Dade® Actin FSL®, Coagulation Factor IX with Dade® Actin FSL®, Lupus Anticoagulant with LA 1 Screening Reagent / LA 2 Confirmation Reagent.
The analysis principles used on the instrument are reflected by the reagent application testing provided in this 510(k) notification and is described in the below table.
| Table of Sysmex® CS-2500 Analysis Principles | ||
|---|---|---|
| Reagent | Application | Methodology |
| Factor V Leiden Assay | Factor V Leiden withFactor V Leiden Assay | Clotting(extrinsic pathway);Calculated |
| Coagulation Factor VIIIDeficient Plasma | Coagulation Factor VIIIwith Dade® Actin FSL® | Clotting(intrinsic pathway) |
| Coagulation Factor IXDeficient Plasma | Coagulation Factor IXwith Dade® Actin FSL® | Clotting(intrinsic pathway) |
| LA 1 Screening Reagent | Lupus Anticoagulant withLA 1 Screening Reagent | Clotting |
| LA 2 ConfirmationReagent | Lupus Anticoagulant withLA 2 ConfirmationReagent | Clotting |
| LA 1 Screening Reagentand LA 2 ConfirmationReagent | LA Ratio with LA 1Screening Reagent / LA 2Confirmation Reagent | Clotting;Calculated |
Table of Sysmex® CS-2500 Analysis Principles
The intended Environment of Use is a clinical central/hospital laboratory.
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Instrument (main unit)
Image /page/7/Figure/2 description: This image shows a diagram of a machine with labels pointing to different parts. The labels include numbers 1 through 8, each pointing to a specific component of the machine. The diagram appears to be a technical illustration, possibly from a user manual or product guide, intended to identify and explain the various parts of the machine.
Front View of the Sysmex CS-2500 (main unit) Figure 1:
- (1) Light shield lid: Open this cover to set reagents, perform maintenance, etc.
- (2) Sampler: Automatically transports samples that are set in the sample rack to the aspiration position.
- (3) Reagent section lid: Open this cover to set reagents.
- (4) Cuvette hopper: Cuvettes placed here are automatically supplied to the interior of the instrument.
- (5) Alarm indicator LED: Indicates the instrument status.
- (6) Mechanical stop switch:
- (7) Start button: This button is the same as the [Start] button on the IPU toolbar.
- (8) Cuvette trash box: Used cuvettes are discarded here.
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Figure 2: Informational Processing Unit (IPU) Sysmex CS-2500
Image /page/8/Figure/2 description: The image shows a desktop computer setup with four labeled components. The monitor, labeled (1), sits atop the computer case, labeled (2). Below the case is the keyboard, labeled (3), and to the right of the keyboard is the mouse, labeled (4). The image is a black and white line drawing.
- (1) Touch panel display: Displays the IPU screen. It can also be used as a touch panel.
- (2) IPU Main Unit: This is the Main Unit of IPU.
- (3) Keyboard: Used to operate the IPU together with the touch panel.
- (4) Mouse: Used to operate the IPU together with the touch panel.
The instrument is capable of measuring in the following analysis modes:
(1) Normal mode: Samples for all the analyses including re-analyses are taken into the instrument at the same time and analyzed. Automatic re-analysis can also be performed.
(2) Micro-sample mode: The sample volume from samples set in the sampler or STAT holder is taken into the instrument for each analysis through dispensing sample probe and analyzed. This analysis mode can also be performed with less sample volume than normal mode; however, automatic re-analysis cannot be performed.
Options and accessories that can be used for this instrument are as follows:
(1) Waste tank (with float switch for waste tank): Waste fluids discharged from the Main Unit enter this tank.
(2) 2D barcode reader: Reads barcodes to input calibrator's or reagent's assay sheet values, normal values and ISI values, and control's targets/limits. It also reads barcodes to input sample numbers, rack numbers and reagent IDs.
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5 Similarities between Sysmex CS-2500 and Sysmex CA-1500
| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
|---|---|---|
| Analyzer Component | Proposed DeviceSysmex® CS-2500 | Predicate DeviceSysmex® CA-1500 |
| Regulatory Classification | JPA, Class 2System, Multipurpose for invitro coagulation studies | Same |
| Intended Use | The Sysmex® CS-2500 is a fullyautomated blood coagulation analyzerintended for in vitro diagnostic use usingplasma collected from venous bloodsamples in 3.2% sodium citrate tubes toanalyze clotting, chromogenic andimmunoassay methods in the clinicallaboratory.For determination of:• Prothrombin Time (PT) seconds andPT 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®• Coagulation Factor VIII with Dade®Actin® FSL• Coagulation Factor IX with Dade®Actin® FSL• Lupus Anticoagulant with LA1Screening / LA2 Confirmation Reagent• Factor V Leiden with Factor V LeidenAssay• Protein C with Protein C Reagent• Antithrombin (AT) withINNOVANCE® Antithrombin• Protein C with Berichrom® Protein C• D-dimer with INNOVANCE® D-DimerThe performance of this device has notbeen established in neonate andpediatric patient populations. | The intended use of the Sysmex®CA-1500 is as a fully automated,computerized blood plasmacoagulation analyzer for in vitrodiagnostic use in clinicallaboratories.The instrument uses citratedhuman plasma to perform thefollowing parameters andcalculated parameters:Clotting Analysis Parameters:Prothrombin Time (PT); ActivatedPartial Thromboplastin Time(APTT); Fibrinogen (Clauss);Batroxobin Time; Extrinsic Factors(II, V, VII, X); Intrinsic Factors(VIII, IX, XI, XII); Protein C.Chromogenic AnalysisParameters: Antithrombin III;Factor VIII; Plasminogen;Heparin; Protein C; a2-Antiplasmin.Immunologic Analysis Parameters:D-dimer.Calculated Parameters: PT Ratio;PT INR; PT %; DerivedFibrinogen; Factor Assays %Activity. |
| Sample Type | Human plasma3.2% sodium citrate | Same |
| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
| Analyzer Component | Proposed DeviceSysmex® CS-2500 | Predicate DeviceSysmex® CA-1500 |
| Application type | Clotting Applications:Prothrombin Time (PT) withDade® Innovin®;Activated Partial ThromboplastinTime (APTT) withDade® Actin® FSL;Fibrinogen (Clauss) withDade® Thrombin Reagent;Coagulation Factor V withDade® Innovin®Coagulation Factor VII withDade® Innovin®Coagulation Factor VIII with Dade®Actin® FSLCoagulation Factor IX with Dade®Actin® FSLLupus Anticoagulant with LA 1Screening / LA 2 ConfirmationReagentsFactor V Leiden with Factor V LeidenAssayProtein C with Protein C Reagent | Same |
| Chromogenic Application:Antithrombin withINNOVANCE® Antithrombin;Protein C withBerichrom® Protein C | Same | |
| Immuno-Chemical Application:D-dimer withINNOVANCE® D-Dimer | Same | |
| Calculated Application:PT INR with Dade® Innovin® | Same | |
| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
| Analyzer Component | Proposed DeviceSysmex® CS-2500 | Predicate DeviceSysmex® CA-1500 |
| Clinical Reportable Range | Coagulation Factor VIII with Dade®Actin® FSL: 3.0 – 182.0% of norm;Coagulation Factor IX with Dade®Actin® FSL: 3.0 – 145.5%;Factor V Leiden with Factor V LeidenAssay: 0.72 – 5.91 ratio;LA 1 with LA 1 Screening Reagent:24.9 – 158.8 sec. | Same |
| Specimen Processing | Automatic Pipetting and Dilution | Same |
| Random Access | Yes | Same |
| Liquid Level Sensing | Yes - reagent and sample | Same |
| Bar Code Reader | Sample and reagent | Same |
| STAT Testing | Yes | Same |
| Sampling Capabilities | Normal and Micro Mode | Same |
{10}------------------------------------------------
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| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
|---|---|---|
| Analyzer Component | Proposed DeviceSysmex® CS-2500 | Predicate DeviceSysmex® CA-1500 |
| Sample Volumes (Plasma) | PT with Dade® Innovin® (50 µL)APTT with Dade® Actin® FSL(50 µL)Fibrinogen with Dade® ThrombinReagent (10 µL)Coagulation Factor V with Dade®Innovin® (5 µL)Coagulation Factor VII with Dade®Innovin® (5 µL)Protein C with Protein C Reagent(5 µL)Protein C with Berichrom® Protein C(15 µL)Coagulation Factor VIII with Dade®Actin FSL® (2 µL)Coagulation Factor IX with Dade®Actin FSL® (2 µL)Lupus Anticoagulant with LA1Screening Reagent (100 µL)Lupus Anticoagulant with LA2Confirmation Reagent (100 µL)Factor V Leiden with Factor V | Same |
| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
| Analyzer Component | Proposed DeviceSysmex® CS-2500 | Predicate DeviceSysmex® CA-1500 |
| Sample Volumes in MicroMode (Plasma) | PT with Dade® Innovin® (50 µL)APTT with Dade® Actin® FSL(50 µL)Fibrinogen with Dade® ThrombinReagent (10 µL)Coagulation Factor V with Dade®Innovin® (5 µL)Coagulation Factor VII with Dade®Innovin® (5 µL)Protein C with Protein C Reagent(5 µL)Protein C with Berichrom®Protein C (15 µL)Coagulation Factor VIII with Dade®Actin FSL® (2 µL)Coagulation Factor IX with Dade®Actin FSL® (2 µL)Lupus Anticoagulant with LA1Screening Reagent (100 µL)Lupus Anticoagulant with LA2Confirmation Reagent (100 µL)Factor V Leiden with FactorV Leiden Assay (50 µL) | Same |
| Rinse & Buffer SolutionsOn-board | CA-CLEAN ICA-CLEAN IIDade® Owren's Buffer | Same |
| External | Water | |
| Light Source | ||
| Chromogenic | Halogen Lamp | Same |
| Immuno-chemical | Halogen Lamp | Same |
| Probes | 1 Sample probe;1 Reagent probe | Same |
| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
| Analyzer Component | Proposed DeviceSysmex® CS-2500 | Predicate DeviceSysmex® CA-1500 |
| Wavelengths used in Analysis | Coagulation Factor VIII with Dade®Actin FSL®(Default = 660 nm; Sub-wavelength=none)Coagulation Factor IX with Dade®Actin FSL®(Default = 660 nm; Sub-wavelength=none)Lupus Anticoagulant with LA1Screening Reagent(Default = 660 nm; Sub-wavelength=none)Lupus Anticoagulant with LA2Confirmation Reagent(Default = 660 nm; Sub-wavelength=none)Factor V Leiden with Factor V LeidenAssay (Default = 660 nm; Sub-wavelength=none) | Same |
| Temperature Control | Sample incubation well:37 °C ± 1.0 °C | Same |
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Differences between Sysmex CS-2500 and CA-1500 6.
| Differences between Sysmex CS-2500 and Sysmex CA-1500 | ||
|---|---|---|
| Analyzer Component | Proposed DeviceSysmex® CS-2500 | Predicate DeviceSysmex® CA-1500 |
| Operating Principle | Clotting:Transmitted Light Detection(Absorbance) at 340, 405, 575, 660 or800 nm. Wavelengths 340, 405 and575 are technically available but notvalidated in combination with theintended applications. | Scattered Light Detection at 660nm |
| Chromogenic:Transmitted Light Detection(Absorbance) at 340, 405, 575, 660,800 nm. Wavelengths 340, 575, 660,and 800 are technically available but notvalidated in combination with theintended applications. | Transmitted Light Detection(Absorbance) at 405, 575, 800 nm | |
| Immunochemical:Transmitted Light Detection(Absorbance) at 340, 405, 575, 660 or800 nm. Wavelengths 340, 405, 575,and 800 are technically available but notvalidated in combination with theintended applications. | Transmitted Light Detection(Absorbance) at 405, 575, or 800nm | |
| Light SourceClotting | Halogen Lamp | Light Emitting Diode |
| Cap Piercing | Cap Piercer only | Both Cap Piercer model and Non-Cap Piercer models are available |
| Temperature Control | Detector: 37 ± 0.5 °CReagent probe: 37.5 ± 0.5 °C | Detector: 37 ± 1.0 °C Reagentprobe: 37 ± 1.0 °C |
| Reagent Cooling | 10 ± 2 °C, when ambienttemperature is 20 – 28 °C.During operation 4 – 15 °C, whenambient temperature is 15 - 30 °C | 15 ± 2 °C, when ambienttemperature is 15 - 30°C |
| Pipetting Capabilities | Reagent probe:20 – 200 μLSample probe:4 – 270 μL | Reagent probe:4 – 200 μLSample probe:5 - 450 μL |
| Clinical Reportable Range | LA2 with LA 2 ConfirmationReagent: 32.2 – 80.0 sec.;LA Ratio with LA 1 / LA 2 reagent :0.71 - 2.60 ratio | LA2 with LA 2 ConfirmationReagent: 32.2 – 111.2 sec.;LA Ratio with LA 1 / LA 2reagent : 0.71 - 2.98 ratio |
| Analyzer Component | Proposed DeviceSysmex® CS-2500 | Predicate DeviceSysmex® CA-1500 |
| Sample Volumes (Plasma) | Antithrombin withINNOVANCE® Antithrombin(14 μL) | Antithrombin withINNOVANCE®Antithrombin (10 μL) |
| D-dimer with INNOVANCE®D-Dimer (15 μL) | D-dimer withINNOVANCE® D-Dimer (13μL) |
{16}------------------------------------------------
The above described differences do not raise new questions as to safety and effectiveness of the new device.
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7 Performance Data
The following performance data were provided in support of the substantial equivalence determination.
Method comparison
Method comparison studies designed according to EP09-A3 CLSI Guideline 'Measurement Procedure Comparison and Bias Estimation Using Patient Samples' were conducted at four external sites; 3 in the United States and one in Germany, all sites using the same protocol.
Samples were measured on both the predicate device (Sysmex® CA-1500) as well as the new device (Sysmex® CS-2500), in random order to eliminate any inherent bias. Results were compared by Passing-Bablok regression analysis as well as Bland-Altman plots. Results from each application met the predetermined acceptance criteria. The following summary of Passing-Bablok regression shows that the proposed and predicate devices provide equivalent results when used in a clinical setting.
| Sysmex® CS-2500: Method Comparison Summary Table, Passing-Bablok regression | |||||
|---|---|---|---|---|---|
| Application | 1st Site | 2nd Site | 3rd Site | 4th Site | SitesCombined |
| Factor V | N = 84 | N = 173 | N = 94 | N = 143 | N = 494 |
| Leiden with | y = 0.928 x + | y = 0.897 x + | y = 0.939 x + | y = 1.018 x - | y = 0.919 x + |
| Factor V | 0.127 | 0.106 | 0.118 | 0.072 | 0.098 |
| Leiden Assay | r = 0.991 | r = 0.995 | r = 0.982 | r = 0.902 | r = 0.978 |
| (Ratio) | (r2 = 0.981) | (r2 = 0.991) | (r2 = 0.965) | (r2 = 0.814) | (r2 = 0.957) |
| Coagulation | N = 80 | N = 153 | N = 77 | N = 98 | N = 408 |
| Factor VIII | y = 0.952 x - | y = 1.042 x - | y = 1.011 x + | y = 1.120 x - | y = 1.037 x - |
| with Dade® | 1.144 | 1.041 | 1.321 | 7.446 | 1.051 |
| Actin® FSL | r = 0.915 | r = 0.987 | r = 0.949 | r = 0.958 | r = 0.958 |
| (% of norm) | (r2 = 0.838) | (r2 = 0.975) | (r2 = 0.901) | (r2 = 0.917) | (r2 = 0.918) |
| Coagulation | N = 86 | N = 145 | N = 78 | N = 150 | N = 459 |
| Factor IX with | y = 0.989 x - | y = 0.991 x - | y = 0.992 x - | y = 1.013 x - | y = 1.000 x - |
| Dade® Actin® | 4.465 | 0.692 | 1.353 | 0.882 | 1.200 |
| FSL | r = 0.971 | r = 0.993 | r = 0.975 | r = 0.989 | r = 0.984 |
| (% of norm) | (r2 = 0.943) | (r2 = 0.985) | (r2 = 0.950) | (r2 = 0.978) | (r2 = 0.969) |
| LupusAnticoagulantwith LA 1ScreeningReagent(seconds) | N = 14y = N/Ar = N/A(r2 = N/A) | N = 110y = 0.943 x +4.024r = 0.997(r2 = 0.994) | N = 115y = 0.986 x -0.218r = 0.995(r2 = 0.989) | N = 163y = 0.928 x +2.965r = 0.996(r2 = 0.992) | N = 402y = 0.961 x +1.767r = 0.995(r2 = 0.990) |
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| Sysmex® CS-2500: Method Comparison Summary Table, Passing-Bablok regression | |||||
|---|---|---|---|---|---|
| Application | 1st Site | 2nd Site | 3rd Site | 4th Site | SitesCombined |
| LupusAnticoagulantwith LA 2ConfirmationReagent(seconds) | N = 13y = N/Ar = N/A(r2 = N/A) | N = 115y = 0.969 x +3.115r = 0.992(r2 = 0.984) | N = 111y = 0.946 x +2.765r = 0.995(r2 = 0.991) | N = 151y = 0.941 x +2.377r = 0.991(r2 = 0.982) | N = 390y = 0.962 x +2.044r = 0.988(r2 = 0.977) |
| LupusAnticoagulantwith LA1/ LA2Ratio(Ratio) | N = 8y = N/Ar = N/A(r2 = N/A) | N = 104y = 0.909 x +0.089r = 0.988(r2 = 0.977) | N = 103y = 1.000 x -0.030r = 0.975(r2 = 0.951) | N = 132y = 0.944 x +0.053r = 0.996(r2 = 0.992) | N = 347y = 0.956 x +0.035r = 0.989(r2 = 0.978) |
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Reproducibility Studies
Twenty-day precision studies were performed at one external site in Germany and two external sites in the United States. Testing followed the scheme of two runs per day, with two replicates per run, at each of the three sites according to CLSI EP05-A2 'Evaluation of Precision Performance of Quantitative Measurement Methods'. The order of the analysis of parameter, samples and quality control samples for each run and day varied to avoid an inherent bias to the study. One calibration curve of each calibrated application was used in the study. Within Run, Between Run, Between Day, and Total (within site) were calculated. The data is summarized in the following tables.
| Sysmex® CS-2500: Reproducibility Summary Table, Within Run | ||||
|---|---|---|---|---|
| Application | 1st SiteWithin Run(%CV) | 2nd SiteWithin Run(%CV) | 3rd SiteWithin Run(%CV) | Sites Combined(%CV) |
| Factor V Leiden with Factor VLeiden Assay | 1.16 - 5.37 | 0.73 - 1.64 | 0.83 - 1.71 | 0.93 - 3.30 |
| Coagulation Factor VIII withDade® Actin® FSL | 3.81 - 6.15 | 3.35 - 5.41 | 3.06 - 4.64 | 3.42 - 5.09 |
| Coagulation Factor IX withDade® Actin® FSL | 3.16 - 6.98 | 3.58 - 6.25 | 2.45 - 6.62 | 3.39 - 6.61 |
| Lupus Anticoagulant with LA 1Screening Reagent (seconds) | 0.56 - 4.82 | 0.65 - 2.13 | 0.36 - 2.53 | 0.59 - 3.38 |
| Lupus Anticoagulant with LA 2Confirmation Reagent(seconds) | 0.33 - 1.82 | 0.36 - 1.28 | 0.32 - 1.13 | 0.32 - 1.38 |
| Lupus Anticoagulant with LA1/LA2 Ratio(Ratio) | 0.71 - 1.15 | 0.55 - 1.32 | 0.55 - 1.27 | 0.65 - 1.15 |
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| Sysmex® CS-2500: Reproducibility Summary Table, Between Run | ||||
|---|---|---|---|---|
| Application | 1st SiteBetweenRun (%CV) | 2nd SiteBetweenRun (%CV) | 3rd SiteBetweenRun (%CV) | Sites Combined(%CV) |
| Factor V Leiden with Factor VLeiden Assay | 0.73 - 3.05 | 0.67 - 1.85 | 0.53 - 1.41 | 0.71 - 2.19 |
| Coagulation Factor VIII withDade® Actin® FSL | 0.00 - 4.89 | 0.00 - 2.94 | 1.98 – 3.77 | 1.80 - 3.62 |
| Coagulation Factor IX withDade® Actin® FSL | 4.16 - 8.39 | 1.31 - 3.46 | 1.51 - 7.07 | 2.77 - 6.21 |
| Lupus Anticoagulant with LA 1Screening Reagent (seconds) | 0.00 - 1.86 | 0.00 - 1.28 | 0.54 - 1.43 | 0.49 - 1.54 |
| Lupus Anticoagulant with LA 2Confirmation Reagent(seconds) | 0.00 - 1.06 | 0.00 - 0.69 | 0.00 - 0.50 | 0.00 - 0.41 |
| Lupus Anticoagulant with LA1/LA2 Ratio(Ratio) | 0.60 - 1.86 | 0.51 - 1.39 | 0.54 - 1.70 | 0.71 - 1.66 |
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| Sysmex® CS-2500: Reproducibility Summary Table, Between Day | |||||
|---|---|---|---|---|---|
| Application | 1st SiteBetweenDay(%CV) | 2nd SiteBetweenDay(%CV) | 3rd SiteBetweenDay(%CV) | Sites Combined(%CV) | |
| Factor V Leiden with Factor VLeiden Assay | 0.00 – 0.98 | 0.00 – 0.50 | 0.38 – 1.39 | 0.00 – 1.03 | |
| Coagulation Factor VIII withDade® Actin® FSL | 0.00 – 1.58 | 0.61 – 2.82 | 0.00 – 1.81 | 0.00 – 1.61 | |
| Coagulation Factor IX withDade® Actin® FSL | 0.00 – 0.00 | 0.00 – 0.81 | 0.00 – 3.43 | 0.00 – 0.00 | |
| Lupus Anticoagulant with LA 1Screening Reagent (seconds) | 0.00 – 2.24 | 0.00 – 2.51 | 0.37 – 1.68 | 0.47 – 1.59 | |
| Lupus Anticoagulant with LA 2Confirmation Reagent(seconds) | 0.00 – 0.53 | 0.00 – 0.43 | 0.00 – 0.46 | 0.00 – 0.41 | |
| Lupus Anticoagulant with LA1/LA2 Ratio(Ratio) | 0.00 – 2.11 | 0.15 – 3.44 | 0.36 – 1.65 | 0.47 – 2.36 |
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| Sysmex® CS-2500: Reproducibility Summary Table, Total CV(Within Site and Sites Combined) | ||||
|---|---|---|---|---|
| Application | 1st SiteTotal CVWithin Site(%CV) | 2nd SiteTotal CVWithin Site(%CV) | 3rd SiteTotal CVWithin Site(%CV) | Total CVSites Combined(%CV) |
| Factor V Leiden with Factor VLeiden Assay | 1.45 - 6.18 | 1.14 - 2.32 | 1.21 - 2.41 | 1.47 – 4.68 |
| Coagulation Factor VIII withDade® Actin® FSL | 4.23 - 6.85 | 3.91 - 6.00 | 3.94 - 5.81 | 4.16 - 5.96 |
| Coagulation Factor IX withDade® Actin® FSL | 5.22 - 10.92 | 3.92 - 6.46 | 3.23 - 10.28 | 5.47 - 10.54 |
| Lupus Anticoagulant with LA 1Screening Reagent (seconds) | 1.18 - 5.32 | 1.06 - 3.32 | 1.09 – 2.86 | 1.17 - 3.80 |
| Lupus Anticoagulant with LA 2Confirmation Reagent(seconds) | 0.50 - 2.11 | 0.60 - 1.30 | 0.53 - 1.28 | 0.72 - 1.89 |
| Lupus Anticoagulant with LA1/LA2 Ratio(Ratio) | 1.43 - 2.54 | 0.99 - 3.68 | 1.34 - 2.37 | 1.32 - 3.29 |
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Detection Capability Results
Detection capability studies were measured for the calibrated assays on the Sysmex® CS-2500: Coagulation Factor VIII with Dade® Actin® FSL and Coagulation Factor IX with Dade® Actin® FSL. Studies were conducted following the CLSI document EP17-A2 'Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures'. Data for all tested reagents met the predetermined acceptance criteria and support the lower limit of the clinically reportable range claim.
| Sysmex® CS-2500: Summary of Limit of Quantitation Studies | |||
|---|---|---|---|
| Application | Lower Limit ofClinicallyReportableRange(% of norm) | Measured Limitof Quantitationbased onpredicate device(% of norm) | Maximum TotalError(% of norm) |
| Coagulation Factor VIII withDade® Actin® FSL | 3.0 | 2.52 | 0.51 |
| Coagulation Factor IX withDade® Actin® FSL | 3.0 | 2.76 | 1.01 |
Linearity & Measuring Range
Linearity studies were performed for the calibrated assays on the Sysmex® CS-2500: Coagulation Factor VIII with Dade® Actin® FSL and Coagulation Factor IX with Dade® Actin® FSL. All reagents met the predetermined acceptance criteria and support the clinically reportable range claim. Studies were conducted as described in CLSI EP6-A 'Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach'.
| Sysmex® CS-2500: Linearity and Measuring Range Summary | ||
|---|---|---|
| Application | Measured Linear Range(% of Norm) | Clinically Reportable Range(% of Norm) |
| Coagulation Factor VIII withDade® Actin® FSL | 2.12 – 246.41 | 3.0 – 182.0 |
| Coagulation Factor IX withDade® Actin® FSL | 2.38 – 193.79 | 3.0 – 145.5 |
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Reference Interval
Reference interval studies were conducted at three clinical study sites in the United States following the guidance of CLSI document EP28-A3c 'Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory'. The summary is provided below. The study population did not include neonate and pediatric sample populations.
| Sysmex® CS-2500: Reference Interval Summary Table | ||
|---|---|---|
| Application | N | Sysmex® CS-2500 Reference Interval |
| Factor V Leiden with Factor V LeidenAssay | 187 | 1.38 Ratio (2.5th Percentile) |
| Coagulation Factor VIII with Dade®Actin® FSL | 191 | 83.5% of norm (2.5th Percentile) |
| Coagulation Factor IX with Dade®Actin® FSL | 190 | 78.7% of norm (2.5th Percentile) |
| Lupus Anticoagulant with LA 1Screening Reagent (fresh samples) | 192 | 32.7 seconds (2.5th Percentile) |
| Lupus Anticoagulant with LA 1Screening Reagent (frozen samples) | 193 | 33.4 seconds (2.5th Percentile) |
| Lupus Anticoagulant with LA 2Confirmation Reagent (fresh samples) | 192 | 35.8 seconds (2.5th Percentile) |
| Lupus Anticoagulant with LA 2Confirmation Reagent (frozen samples) | 193 | 36.3 seconds (2.5th Percentile) |
| Lupus Anticoagulant with LA1/ LA2Ratio (fresh samples) | 192 | 0.88 Ratio (2.5th Percentile) |
| Lupus Anticoagulant with LA1/ LA2Ratio (frozen samples) | 193 | 0.90 Ratio (2.5th Percentile) |
{25}------------------------------------------------
Factor V Leiden Cut-off Study
A cut-off of 1.8 (ratio) was validated on the CS-2500 instrument in a performance evaluation study. Citrated plasma samples from patients submitted for thrombophilia screening were collected by three different clinical sites (one site in the US and two sites in Germany). The samples were frozen and measured with the FV Leiden assay on the CS-2500 instrument. The FV Leiden assay results were classified using the cut-off of 1.8: a ratio ≤1.8 is suggestive for FV Leiden variant (single point mutation G1691A) and a ratio >1.8 is considered as negative for the FV Leiden variant. The FV Leiden assay results were subsequently compared to the Factor V Leiden genotype to calculate the positive and negative percentage agreement. In total, n=381 patients of which n=127 patients came from the US were included. The results are shown in the tables below.
| All sites combined (US and OUS) | Reference (Factor V Leiden PCR method) | |||
|---|---|---|---|---|
| Negative | Positive | Total | ||
| Factor V Leiden assayon Sysmex® CS-2500System | Negative | 160 | 0 | 160 |
| Positive | 1 | 220 | 221 | |
| Total | 161 | 220 | 381 | |
| Positive Agreement % = | 100.0% | 95.0% Confidence Interval = 98.3 – 100.0% | ||
| Negative Agreement %t = | 99.4% | 95.0% Confidence Interval= 96.6 – 100.0% |
8 Conclusion
The predicate device was cleared based in part on the results of clinical studies; therefore clinical testing was required to support substantial equivalence.
The non-clinical and clinical data support the safety of the device.
The clinical data demonstrate that the Sysmex® CS-2500 performs comparably to the predicate device that is currently marketed for the same intended use.
The data submitted for this premarket notification demonstrates that the device raises no new concerns as to safety and effectiveness when compared to the predicate device, and is substantially equivalent to the predicate device.
§ 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.