(143 days)
No reference devices were used in this submission.
No
The summary describes a standard automated blood coagulation analyzer and its associated reagents and testing methods. There is no mention of AI, ML, or any advanced computational techniques beyond standard data processing and analysis for clinical laboratory measurements.
No
This device is an in vitro diagnostic device used to analyze blood coagulation parameters for diagnostic purposes, not for direct therapeutic intervention.
Yes
The "Intended Use / Indications for Use" section explicitly states that the Sysmex® Automated Blood Coagulation Analyzer CS-2500 is "intended for in vitro diagnostic use." The functions listed, such as determining Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), and various coagulation factors, are all diagnostic tests.
No
The device description clearly states it is an "automated blood coagulation instrument" and mentions physical components like an "Information Processing Unit (IPU) screen," external printers, and a host computer connection. It also describes the analysis principles used on the instrument, which are physical processes. While software is undoubtedly involved in controlling the instrument and processing data, the device itself is a physical instrument, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states in multiple places that the device and its associated reagents are intended for "in vitro diagnostic use". This is the primary indicator that the device falls under the category of IVDs.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
JPA, GGW, GJT, GIR
Device Description
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 instrument's front view includes: (1) Light shield lid, (2) Sampler, (3) Reagent section lid, (4) Cuvette hopper, (5) Alarm indicator LED, (6) Mechanical stop switch, (7) Start button, and (8) Cuvette trash box.
The Informational Processing Unit (IPU) includes: (1) Touch panel display, (2) IPU Main Unit, (3) Keyboard, and (4) Mouse.
The instrument is capable of measuring in two analysis modes:
(1) Normal mode: Samples for all 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 include:
(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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
The performance of this device has not been established in neonate and pediatric patient populations.
Intended User / Care Setting
clinical laboratory / clinical central/hospital laboratory.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method comparison studies: designed according to EP09-A3 CLSI Guideline 'Measurement Procedure Comparison and Bias Estimation Using Patient Samples'. Conducted at four external sites (3 in the United States, 1 in Germany).
Sample size:
- Factor V Leiden with Factor V Leiden Assay (Ratio): N = 494 (Sites Combined)
- Coagulation Factor VIII with Dade® Actin® FSL (% of norm): N = 408 (Sites Combined)
- Coagulation Factor IX with Dade® Actin® FSL (% of norm): N = 459 (Sites Combined)
- Lupus Anticoagulant with LA 1 Screening Reagent (seconds): N = 402 (Sites Combined)
- Lupus Anticoagulant with LA 2 Confirmation Reagent (seconds): N = 390 (Sites Combined)
- Lupus Anticoagulant with LA1/ LA2 Ratio (Ratio): N = 347 (Sites Combined)
Results were compared by Passing-Bablok regression analysis as well as Bland-Altman plots. Results from each application met the predetermined acceptance criteria. The proposed and predicate devices provide equivalent results when used in a clinical setting.
Reproducibility Studies: Twenty-day precision studies performed at one external site in Germany and two external sites in the United States, following CLSI EP05-A2 'Evaluation of Precision Performance of Quantitative Measurement Methods'.
Testing scheme: two runs per day, with two replicates per run, at each of the three sites. The order of analysis varied to avoid bias. One calibration curve was used for each calibrated application. Within Run, Between Run, Between Day, and Total (within site) were calculated.
Detection Capability Studies: Measured for calibrated assays (Coagulation Factor VIII with Dade® Actin® FSL and Coagulation Factor IX with Dade® Actin® FSL). Studies followed CLSI document EP17-A2 'Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures'.
Key result: Data for all tested reagents met the predetermined acceptance criteria and support the lower limit of the clinically reportable range claim.
- Coagulation Factor VIII with Dade® Actin® FSL: Lower Limit of Clinically Reportable Range = 3.0 % of norm; Measured Limit of Quantitation = 2.52 % of norm; Maximum Total Error = 0.51 % of norm.
- Coagulation Factor IX with Dade® Actin® FSL: Lower Limit of Clinically Reportable Range = 3.0 % of norm; Measured Limit of Quantitation = 2.76 % of norm; Maximum Total Error = 1.01 % of norm.
Linearity & Measuring Range Studies: Performed for calibrated assays (Coagulation Factor VIII with Dade® Actin® FSL and Coagulation Factor IX with Dade® Actin® FSL) following CLSI EP6-A 'Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach'.
Key result: All reagents met predetermined acceptance criteria and support the clinically reportable range claim.
- Coagulation Factor VIII with Dade® Actin® FSL: Measured Linear Range = 2.12 – 246.41 % of Norm; Clinically Reportable Range = 3.0 – 182.0 % of Norm.
- Coagulation Factor IX with Dade® Actin® FSL: Measured Linear Range = 2.38 – 193.79 % of Norm; Clinically Reportable Range = 3.0 – 145.5 % of Norm.
Reference Interval Studies: Conducted at three clinical study sites in the United States following CLSI document EP28-A3c 'Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory'. The study population did not include neonate and pediatric sample populations.
Sample size: N=187 to N=193 depending on the application.
Factor V Leiden Cut-off Study: A cut-off of 1.8 (ratio) was validated on the CS-2500 instrument. Citrated plasma samples from N=381 thrombophilia screening patients (127 from US, others from Germany) were collected, frozen, and measured with the FV Leiden assay. Results were compared to Factor V Leiden genotype.
Key results:
- Positive Agreement % = 100.0% (95.0% Confidence Interval = 98.3 – 100.0%)
- Negative Agreement % = 99.4% (95.0% Confidence Interval= 96.6 – 100.0%)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Positive Agreement % = 100.0%
- Negative Agreement % = 99.4%
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Sysmex® CA-1500 (K011235)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
No reference devices were used in this submission.
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
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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.
1
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
2
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.
3
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4
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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 Analyzer
CS-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
5
| Reagent Applications that are the subject of this 510(k) notification | |||||
|---|---|---|---|---|---|
| Application | |||||
| Intended Use | 510(k) Number | ||||
| related to | |||||
| application on | |||||
| predicate device | Regulation | ||||
| Number | Regulatory | ||||
| Class | Product | ||||
| Code | Panel | ||||
| 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 the | |||||
| Factor V (Leiden) defect. For in | |||||
| vitro diagnostic use. | K992456 | 864.7925 | Class II | GGW | Hematology |
| Coagulation Factor VIII | |||||
| Deficient Plasma | |||||
| In vitro diagnostic reagents for | |||||
| the determination of the activity | |||||
| of coagulation factors VIII, IX, | |||||
| XI and XII in human plasma by | |||||
| coagulometric methods. | K924396 | 864.7290 | Class II | GJT | Hematology |
| Coagulation Factor IX | |||||
| Deficient Plasma | |||||
| In vitro diagnostic reagents for | |||||
| the determination of the activity | |||||
| of coagulation factors VIII, IX, | |||||
| XI and XII in human plasma by | |||||
| coagulometric methods. | K924396 | 864.7290 | Class II | GJT | Hematology |
| LA 1 Screening Reagent / | |||||
| LA 2 Confirmation Reagent, | |||||
| and LA Ratio | |||||
| LA 1 Screening Reagent / LA 2 | |||||
| Confirmation Reagent are | |||||
| simplified DRVVT reagents for | |||||
| detection of Lupus | |||||
| Anticoagulants (LA) in one- | |||||
| stage clotting tests. LA 1 | |||||
| Screening Reagent: Simplified | |||||
| DRVV reagent to screen for the | |||||
| presence of Lupus | |||||
| Anticoagulants. LA 2 | |||||
| Confirmation Reagent: | |||||
| Phospholipid-rich DRVV | |||||
| reagent for the specific | |||||
| correction of Lupus | |||||
| Anticoagulants. | K993299 | 864.8950 | Class I | GIR | Hematology |
6
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 with | |
| Factor V Leiden Assay | Clotting | |
| (extrinsic pathway); | ||
| Calculated | ||
| Coagulation Factor VIII | ||
| Deficient Plasma | Coagulation Factor VIII | |
| with Dade® Actin FSL® | Clotting | |
| (intrinsic pathway) | ||
| Coagulation Factor IX | ||
| Deficient Plasma | Coagulation Factor IX | |
| with Dade® Actin FSL® | Clotting | |
| (intrinsic pathway) | ||
| LA 1 Screening Reagent | Lupus Anticoagulant with | |
| LA 1 Screening Reagent | Clotting | |
| LA 2 Confirmation | ||
| Reagent | Lupus Anticoagulant with | |
| LA 2 Confirmation | ||
| Reagent | Clotting | |
| LA 1 Screening Reagent | ||
| and LA 2 Confirmation | ||
| Reagent | LA Ratio with LA 1 | |
| Screening Reagent / LA 2 | ||
| Confirmation Reagent | Clotting; | |
| Calculated |
Table of Sysmex® CS-2500 Analysis Principles
The intended Environment of Use is a clinical central/hospital laboratory.
7
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.
8
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.
9
5 Similarities between Sysmex CS-2500 and Sysmex CA-1500
| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
|---|---|---|
| Analyzer Component | Proposed Device | |
| Sysmex® CS-2500 | Predicate Device | |
| Sysmex® CA-1500 | ||
| Regulatory Classification | JPA, Class 2 | |
| System, Multipurpose for in | ||
| vitro coagulation studies | Same | |
| Intended Use | The Sysmex® 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. | 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; a2- | ||
| Antiplasmin. | ||
| Immunologic Analysis Parameters: | ||
| D-dimer. | ||
| Calculated Parameters: PT Ratio; | ||
| PT INR; PT %; Derived | ||
| Fibrinogen; Factor Assays % | ||
| Activity. | ||
| Sample Type | Human plasma | |
| 3.2% sodium citrate | Same | |
| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
| Analyzer Component | Proposed Device | |
| Sysmex® CS-2500 | Predicate Device | |
| Sysmex® CA-1500 | ||
| Application type | Clotting Applications: | |
| Prothrombin Time (PT) with | ||
| Dade® Innovin®; | ||
| Activated Partial Thromboplastin | ||
| Time (APTT) with | ||
| Dade® Actin® FSL; | ||
| Fibrinogen (Clauss) 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 LA 1 | ||
| Screening / LA 2 Confirmation | ||
| Reagents | ||
| Factor V Leiden with Factor V Leiden | ||
| Assay | ||
| Protein C with Protein C Reagent | Same | |
| Chromogenic Application: | ||
| Antithrombin with | ||
| INNOVANCE® Antithrombin; | ||
| Protein C with | ||
| Berichrom® Protein C | Same | |
| Immuno-Chemical Application: | ||
| D-dimer with | ||
| INNOVANCE® D-Dimer | Same | |
| Calculated Application: | ||
| PT INR with Dade® Innovin® | Same | |
| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
| Analyzer Component | Proposed Device | |
| Sysmex® CS-2500 | Predicate Device | |
| Sysmex® 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 Leiden | ||
| Assay: 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
11
12
| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
|---|---|---|
| Analyzer Component | Proposed Device | |
| Sysmex® CS-2500 | Predicate Device | |
| Sysmex® CA-1500 | ||
| Sample Volumes (Plasma) | PT with Dade® Innovin® (50 µL) | |
| APTT with Dade® Actin® FSL | ||
| (50 µL) | ||
| Fibrinogen with Dade® Thrombin | ||
| Reagent (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 LA1 | ||
| Screening Reagent (100 µL) | ||
| Lupus Anticoagulant with LA2 | ||
| Confirmation Reagent (100 µL) | ||
| Factor V Leiden with Factor V | Same | |
| Similarities between Sysmex CS-2500 and Sysmex CA-1500 | ||
| Analyzer Component | Proposed Device | |
| Sysmex® CS-2500 | Predicate Device | |
| Sysmex® CA-1500 | ||
| Sample Volumes in Micro | ||
| Mode (Plasma) | PT with Dade® Innovin® (50 µL) | |
| APTT with Dade® Actin® FSL | ||
| (50 µL) | ||
| Fibrinogen with Dade® Thrombin | ||
| Reagent (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 LA1 | ||
| Screening Reagent (100 µL) | ||
| Lupus Anticoagulant with LA2 | ||
| Confirmation Reagent (100 µL) | ||
| Factor V Leiden with Factor | ||
| V Leiden Assay (50 µL) | Same | |
| Rinse & Buffer Solutions | ||
| On-board | CA-CLEAN I | |
| CA-CLEAN II | ||
| Dade® 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 Device | |
| Sysmex® CS-2500 | Predicate Device | |
| Sysmex® 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 LA1 | ||
| Screening Reagent | ||
| (Default = 660 nm; Sub-wavelength=none) | ||
| Lupus Anticoagulant with LA2 | ||
| Confirmation Reagent | ||
| (Default = 660 nm; Sub-wavelength=none) | ||
| Factor V Leiden with Factor V Leiden | ||
| Assay (Default = 660 nm; Sub-wavelength=none) | Same | |
| Temperature Control | Sample incubation well: | |
| 37 °C ± 1.0 °C | Same |
13
14
15
Differences between Sysmex CS-2500 and CA-1500 6.
| Differences between Sysmex CS-2500 and Sysmex CA-1500 | ||
|---|---|---|
| Analyzer Component | Proposed Device | |
| Sysmex® CS-2500 | Predicate Device | |
| Sysmex® CA-1500 | ||
| Operating Principle | Clotting: | |
| Transmitted Light Detection | ||
| (Absorbance) at 340, 405, 575, 660 or | ||
| 800 nm. Wavelengths 340, 405 and | ||
| 575 are technically available but not | ||
| validated in combination with the | ||
| intended applications. | Scattered Light Detection at 660 | |
| nm | ||
| Chromogenic: | ||
| Transmitted Light Detection | ||
| (Absorbance) at 340, 405, 575, 660, | ||
| 800 nm. Wavelengths 340, 575, 660, | ||
| and 800 are technically available but not | ||
| validated in combination with the | ||
| intended applications. | Transmitted Light Detection | |
| (Absorbance) at 405, 575, 800 nm | ||
| Immunochemical: | ||
| Transmitted Light Detection | ||
| (Absorbance) at 340, 405, 575, 660 or | ||
| 800 nm. Wavelengths 340, 405, 575, | ||
| and 800 are technically available but not | ||
| validated in combination with the | ||
| intended applications. | Transmitted Light Detection | |
| (Absorbance) at 405, 575, or 800 | ||
| nm | ||
| Light Source | ||
| Clotting | 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 °C | |
| Reagent probe: 37.5 ± 0.5 °C | Detector: 37 ± 1.0 °C Reagent | |
| probe: 37 ± 1.0 °C | ||
| Reagent Cooling | 10 ± 2 °C, when ambient | |
| temperature is 20 – 28 °C. | ||
| During operation 4 – 15 °C, when | ||
| ambient temperature is 15 - 30 °C | 15 ± 2 °C, when ambient | |
| temperature is 15 - 30 | ||
| °C | ||
| Pipetting Capabilities | Reagent probe: | |
| 20 – 200 μL | ||
| Sample probe: | ||
| 4 – 270 μL | Reagent probe: | |
| 4 – 200 μL | ||
| Sample probe: | ||
| 5 - 450 μL | ||
| Clinical Reportable Range | LA2 with LA 2 Confirmation | |
| Reagent: 32.2 – 80.0 sec.; | ||
| LA Ratio with LA 1 / LA 2 reagent : | ||
| 0.71 - 2.60 ratio | LA2 with LA 2 Confirmation | |
| Reagent: 32.2 – 111.2 sec.; | ||
| LA Ratio with LA 1 / LA 2 | ||
| reagent : 0.71 - 2.98 ratio | ||
| Analyzer Component | Proposed Device | |
| Sysmex® CS-2500 | Predicate Device | |
| Sysmex® CA-1500 | ||
| Sample Volumes (Plasma) | Antithrombin with | |
| INNOVANCE® Antithrombin | ||
| (14 μL) | Antithrombin with | |
| INNOVANCE® | ||
| Antithrombin (10 μL) | ||
| D-dimer with INNOVANCE® | ||
| D-Dimer (15 μL) | D-dimer with | |
| INNOVANCE® D-Dimer (13 | ||
| μL) |
16
The above described differences do not raise new questions as to safety and effectiveness of the new device.
17
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 | Sites |
| Combined | |||||
| 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) |
| Lupus | |||||
| Anticoagulant | |||||
| with LA 1 | |||||
| Screening | |||||
| Reagent | |||||
| (seconds) | N = 14 | ||||
| y = N/A | |||||
| r = N/A | |||||
| (r2 = N/A) | N = 110 | ||||
| y = 0.943 x + | |||||
| 4.024 | |||||
| r = 0.997 | |||||
| (r2 = 0.994) | N = 115 | ||||
| y = 0.986 x - | |||||
| 0.218 | |||||
| r = 0.995 | |||||
| (r2 = 0.989) | N = 163 | ||||
| y = 0.928 x + | |||||
| 2.965 | |||||
| r = 0.996 | |||||
| (r2 = 0.992) | N = 402 | ||||
| y = 0.961 x + | |||||
| 1.767 | |||||
| r = 0.995 | |||||
| (r2 = 0.990) |
18
| Sysmex® CS-2500: Method Comparison Summary Table, Passing-Bablok regression | |||||
|---|---|---|---|---|---|
| Application | 1st Site | 2nd Site | 3rd Site | 4th Site | Sites |
| Combined | |||||
| Lupus | |||||
| Anticoagulant | |||||
| with LA 2 | |||||
| Confirmation | |||||
| Reagent | |||||
| (seconds) | N = 13 | ||||
| y = N/A | |||||
| r = N/A | |||||
| (r2 = N/A) | N = 115 | ||||
| y = 0.969 x + | |||||
| 3.115 | |||||
| r = 0.992 | |||||
| (r2 = 0.984) | N = 111 | ||||
| y = 0.946 x + | |||||
| 2.765 | |||||
| r = 0.995 | |||||
| (r2 = 0.991) | N = 151 | ||||
| y = 0.941 x + | |||||
| 2.377 | |||||
| r = 0.991 | |||||
| (r2 = 0.982) | N = 390 | ||||
| y = 0.962 x + | |||||
| 2.044 | |||||
| r = 0.988 | |||||
| (r2 = 0.977) | |||||
| Lupus | |||||
| Anticoagulant | |||||
| with LA1/ LA2 | |||||
| Ratio | |||||
| (Ratio) | N = 8 | ||||
| y = N/A | |||||
| r = N/A | |||||
| (r2 = N/A) | N = 104 | ||||
| y = 0.909 x + | |||||
| 0.089 | |||||
| r = 0.988 | |||||
| (r2 = 0.977) | N = 103 | ||||
| y = 1.000 x - | |||||
| 0.030 | |||||
| r = 0.975 | |||||
| (r2 = 0.951) | N = 132 | ||||
| y = 0.944 x + | |||||
| 0.053 | |||||
| r = 0.996 | |||||
| (r2 = 0.992) | N = 347 | ||||
| y = 0.956 x + | |||||
| 0.035 | |||||
| r = 0.989 | |||||
| (r2 = 0.978) |
19
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 Site | |||
| Within Run | ||||
| (%CV) | 2nd Site | |||
| Within Run | ||||
| (%CV) | 3rd Site | |||
| Within Run | ||||
| (%CV) | Sites Combined | |||
| (%CV) | ||||
| Factor V Leiden with Factor V | ||||
| Leiden Assay | 1.16 - 5.37 | 0.73 - 1.64 | 0.83 - 1.71 | 0.93 - 3.30 |
| Coagulation Factor VIII with | ||||
| Dade® Actin® FSL | 3.81 - 6.15 | 3.35 - 5.41 | 3.06 - 4.64 | 3.42 - 5.09 |
| Coagulation Factor IX with | ||||
| Dade® Actin® FSL | 3.16 - 6.98 | 3.58 - 6.25 | 2.45 - 6.62 | 3.39 - 6.61 |
| Lupus Anticoagulant with LA 1 | ||||
| Screening Reagent (seconds) | 0.56 - 4.82 | 0.65 - 2.13 | 0.36 - 2.53 | 0.59 - 3.38 |
| Lupus Anticoagulant with LA 2 | ||||
| Confirmation 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 |
20
| Sysmex® CS-2500: Reproducibility Summary Table, Between Run | ||||
|---|---|---|---|---|
| Application | 1st Site | |||
| Between | ||||
| Run (%CV) | 2nd Site | |||
| Between | ||||
| Run (%CV) | 3rd Site | |||
| Between | ||||
| Run (%CV) | Sites Combined | |||
| (%CV) | ||||
| Factor V Leiden with Factor V | ||||
| Leiden Assay | 0.73 - 3.05 | 0.67 - 1.85 | 0.53 - 1.41 | 0.71 - 2.19 |
| Coagulation Factor VIII with | ||||
| Dade® Actin® FSL | 0.00 - 4.89 | 0.00 - 2.94 | 1.98 – 3.77 | 1.80 - 3.62 |
| Coagulation Factor IX with | ||||
| Dade® Actin® FSL | 4.16 - 8.39 | 1.31 - 3.46 | 1.51 - 7.07 | 2.77 - 6.21 |
| Lupus Anticoagulant with LA 1 | ||||
| Screening Reagent (seconds) | 0.00 - 1.86 | 0.00 - 1.28 | 0.54 - 1.43 | 0.49 - 1.54 |
| Lupus Anticoagulant with LA 2 | ||||
| Confirmation 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 |
21
| Sysmex® CS-2500: Reproducibility Summary Table, Between Day | |||||
|---|---|---|---|---|---|
| Application | 1st Site | ||||
| Between | |||||
| Day | |||||
| (%CV) | 2nd Site | ||||
| Between | |||||
| Day | |||||
| (%CV) | 3rd Site | ||||
| Between | |||||
| Day | |||||
| (%CV) | Sites Combined | ||||
| (%CV) | |||||
| Factor V Leiden with Factor V | |||||
| Leiden Assay | 0.00 – 0.98 | 0.00 – 0.50 | 0.38 – 1.39 | 0.00 – 1.03 | |
| Coagulation Factor VIII with | |||||
| Dade® Actin® FSL | 0.00 – 1.58 | 0.61 – 2.82 | 0.00 – 1.81 | 0.00 – 1.61 | |
| Coagulation Factor IX with | |||||
| Dade® Actin® FSL | 0.00 – 0.00 | 0.00 – 0.81 | 0.00 – 3.43 | 0.00 – 0.00 | |
| Lupus Anticoagulant with LA 1 | |||||
| Screening Reagent (seconds) | 0.00 – 2.24 | 0.00 – 2.51 | 0.37 – 1.68 | 0.47 – 1.59 | |
| Lupus Anticoagulant with LA 2 | |||||
| Confirmation 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 |
22
| Sysmex® CS-2500: Reproducibility Summary Table, Total CV
| (Within Site and Sites Combined) | ||||
|---|---|---|---|---|
| Application | 1st Site | |||
| Total CV | ||||
| Within Site | ||||
| (%CV) | 2nd Site | |||
| Total CV | ||||
| Within Site | ||||
| (%CV) | 3rd Site | |||
| Total CV | ||||
| Within Site | ||||
| (%CV) | Total CV | |||
| Sites Combined | ||||
| (%CV) | ||||
| Factor V Leiden with Factor V | ||||
| Leiden Assay | 1.45 - 6.18 | 1.14 - 2.32 | 1.21 - 2.41 | 1.47 – 4.68 |
| Coagulation Factor VIII with | ||||
| Dade® Actin® FSL | 4.23 - 6.85 | 3.91 - 6.00 | 3.94 - 5.81 | 4.16 - 5.96 |
| Coagulation Factor IX with | ||||
| Dade® Actin® FSL | 5.22 - 10.92 | 3.92 - 6.46 | 3.23 - 10.28 | 5.47 - 10.54 |
| Lupus Anticoagulant with LA 1 | ||||
| Screening Reagent (seconds) | 1.18 - 5.32 | 1.06 - 3.32 | 1.09 – 2.86 | 1.17 - 3.80 |
| Lupus Anticoagulant with LA 2 | ||||
| Confirmation 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 |
23
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 of | ||
| Clinically | |||
| Reportable | |||
| Range | |||
| (% of norm) | Measured Limit | ||
| of Quantitation | |||
| based on | |||
| predicate device | |||
| (% of norm) | Maximum Total | ||
| Error | |||
| (% of norm) | |||
| Coagulation Factor VIII with | |||
| Dade® Actin® FSL | 3.0 | 2.52 | 0.51 |
| Coagulation Factor IX with | |||
| Dade® 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 with | ||
| Dade® Actin® FSL | 2.12 – 246.41 | 3.0 – 182.0 |
| Coagulation Factor IX with | ||
| Dade® Actin® FSL | 2.38 – 193.79 | 3.0 – 145.5 |
24
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 Leiden | ||
| Assay | 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 1 | ||
| Screening Reagent (fresh samples) | 192 | 32.7 seconds (2.5th Percentile) |
| Lupus Anticoagulant with LA 1 | ||
| Screening Reagent (frozen samples) | 193 | 33.4 seconds (2.5th Percentile) |
| Lupus Anticoagulant with LA 2 | ||
| Confirmation Reagent (fresh samples) | 192 | 35.8 seconds (2.5th Percentile) |
| Lupus Anticoagulant with LA 2 | ||
| Confirmation Reagent (frozen samples) | 193 | 36.3 seconds (2.5th Percentile) |
| Lupus Anticoagulant with LA1/ LA2 | ||
| Ratio (fresh samples) | 192 | 0.88 Ratio (2.5th Percentile) |
| Lupus Anticoagulant with LA1/ LA2 | ||
| Ratio (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 assay | ||||
| on Sysmex® CS-2500 | ||||
| System | 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.