(104 days)
No reference devices were used in this submission.
No
The document describes a standard automated blood coagulation analyzer and its associated reagents. There is no mention of AI, ML, or any related technologies in the intended use, device description, or performance studies. The performance studies focus on standard analytical validation methods like method comparison, reproducibility, and linearity.
No
The device is an in vitro diagnostic (IVD) blood coagulation analyzer, not a device used for therapy. Its purpose is to analyze blood samples for diagnostic purposes.
Yes.
The "Intended Use / Indications for Use" section explicitly states, "The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use..." and lists specific diagnostic determinations it performs.
No
The device is described as an "automated blood coagulation instrument" which is a piece of hardware. While it utilizes software for analysis and display, it is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use..."
Furthermore, the description of the associated reagents also includes the phrase "In vitro diagnostic reagent".
These statements clearly indicate that the device and its associated reagents are intended for use in examining specimens derived from the human body to provide information for the diagnosis, prevention, or treatment of disease or impairment, which is the definition of an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.
For determination of:
- Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® .
- . Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
- . Fibrinogen (Fbg) with Dade® Thrombin Reagent
- . Coagulation Factor V with Dade® Innovin®
- . Coagulation Factor VII with Dade® Innovin®
- . Protein C with Protein C Reagent
- . Antithrombin (AT) with INNOVANCE® Antithrombin
- Protein C with Berichrom® Protein C
- D-dimer with INNOVANCE® D-Dimer
Coagulation Factor V Deficient Plasma:
In vitro diagnostic reagent for the determination of the activity of coagulation factor V in human plasma.
Coagulation Factor II, VII and X Deficient Plasmas:
In vitro diagnostic reagents for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods.
Protein C Reagent:
Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma.
Berichrom® Protein C:
For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies.
Product codes (comma separated list FDA assigned to the subject device)
JPA, GGP, GJT
Device Description
The Sysmex® CS-5100 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated
- Reagents
- Controls
- Calibrators
- Consumable materials
The subject of this 510(k) notification are reagent applications which perform the coagulation tests Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent and Protein C with Berichrom® Protein C.
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-5100 Analysis Principles
Reagent, Application, Methodology
Dade® Innovin® with Coagulation Factor V Deficient Plasma, Coagulation Factor V with Dade® Innovin®, Clotting (extrinsic pathway)
Dade® Innovin® with Coagulation Factor VII Deficient Plasma, Coagulation Factor VII with Dade® Innovin®, Clotting (extrinsic pathway)
Protein C Reagent, Protein C with Protein C Reagent, Clotting
Berichrom® Protein C, Protein C with Berichrom® Protein C, Chromogenic
The intended Environment of Use is a clinical central/hospital laboratory.
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
Method comparison (Clinical Testing):
EP09-A3 CLSI Guideline 'Measurement Procedure Comparison and Bias Estimation Using Patient Samples' studies were conducted at four external sites in the United States, 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-5100), in random order to eliminate any inherent bias. Results were compared by Passing-Bablok regression analysis as well as Bland-Altman plots.
Sample sizes for method comparison:
- Coagulation Factor V with Dade® Innovin®: N = 133 (1st Site), N = 151 (2nd Site), N = 148 (3rd Site), N = 177 (4th Site), N = 609 (Sites Combined)
- Coagulation Factor VII with Dade® Innovin®: N = 121 (1st Site), N = 145 (2nd Site), N = 102 (3rd Site), N = 137 (4th Site), N = 505 (Sites Combined)
- Protein C with Protein C Reagent: N = 138 (1st Site), N = 176 (2nd Site), N = 110 (3rd Site), N = 200 (4th Site), N = 624 (Sites Combined)
- Protein C with Berichrom® Protein C: N = 127 (1st Site), N = 149 (2nd Site), N = 130 (3rd Site), N = 125 (4th Site), N = 531 (Sites Combined)
Reproducibility Studies:
Twenty-day precision studies were performed at two external sites in Germany and one external site 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'.
Detection Capability Studies:
Studies were conducted following the CLSI document EP17-A2 'Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures'.
Linearity & Measuring Range Studies:
Studies were conducted as described in CLSI EP6-A 'Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach'.
Reference Interval Studies:
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'.
Sample size for reference interval study: N = 194 for all applications.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method comparison:
- Study type: Method comparison studies designed according to EP09-A3 CLSI Guideline 'Measurement Procedure Comparison and Bias Estimation Using Patient Samples'
- Sample size: N = 609 (Coagulation Factor V), N = 505 (Coagulation Factor VII), N = 624 (Protein C Reagent), N = 531 (Berichrom® Protein C) for sites combined. Individual site sample sizes as listed in the "Description of the test set" section.
- Key results: Results from each application met the predetermined acceptance criteria. The Passing-Bablok regression showed that the proposed and predicate devices provide equivalent results.
Reproducibility Studies:
- Study type: Twenty-day precision studies performed at two external sites in Germany and one external site in the United States, following CLSI EP05-A2 'Evaluation of Precision Performance of Quantitative Measurement Methods'.
- Sample size: Not explicitly stated, but implies multiple samples tested over 20 days, two runs per day, two replicates per run, at three sites.
- Key results:
- Within Run %CV ranges: 1.13 - 9.94%
- Between Run %CV ranges: 0.00 - 5.51%
- Between Day %CV ranges: 0.00 - 2.75%
- Total CV (Within Site) ranges: 1.34 - 9.95%
- Total CV (Sites Combined) ranges: 3.22 - 7.92%
- All data is summarized in tables.
Detection Capability Results:
- Study type: Detection capability studies following CLSI document EP17-A2 'Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures'.
- Key results: Data for all tested reagents met the predetermined acceptance criteria and support the lower limit of the clinically reportable range claim.
- Measured Limit of Quantitation was below the Lower Limit of Clinically Reportable Range for all applications.
Linearity & Measuring Range:
- Study type: Linearity studies as described in CLSI EP6-A 'Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach'.
- Key results: All reagents met the predetermined acceptance criteria and support the clinically reportable range claim. The measured linear range encompassed or exceeded the clinically reportable range for all applications.
Reference Interval:
- Study type: Reference interval studies following CLSI document EP28-A3c 'Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory'.
- Sample size: N = 194
- Key results: 5th Percentile reference intervals were established for each application (Coagulation Factor V, Coagulation Factor VII, Protein C Reagent, Berichrom® Protein C).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found. Values like correlation coefficient (r and r^2) from Passing-Bablok regression and %CV from reproducibility studies are provided.
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.
K011235 (Sysmex® CA-1500)
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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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird-like symbol composed of three overlapping profiles facing to the right. The profiles are arranged in a way that creates a sense of depth and movement. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the symbol.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
December 12, 2016
Siemens Healthcare Diagnostics Products GmbH Petra M. Dissmann, Ph.D. Regulatory Affairs Manager Emil-von-Behring Strasse 76 35041 Marburg, Germany
Re: K162420 Trade/Device Name: Sysmex® CS-5100 Coagulation Factor V Deficient Plasma Coagulation Factor II. VII and X Deficient Plasmas Protein C Reagent Berichrom® Protein C Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: JPA, GGP, GJT Dated: September 12, 2016 Received: September 13, 2016
Dear Dr. Dissmann:
We have reviewed your 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. Isting 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.
1
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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education 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. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 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 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
Leonthena R. Carrington, MS. MBA. MT(ASCP) 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) K162420
Device Name
Sysmex® CS-5100, Coagulation Factor V Deficient Plasma, Coagulation Factor II, VII and X Deficient Plasmas, Protein C Reagent, Berichrom® Protein C
Indications for Use (Describe)
Sysmex® CS-5100:
The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.
For determination of:
- Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® .
- . Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
- . Fibrinogen (Fbg) with Dade® Thrombin Reagent
- . Coagulation Factor V with Dade® Innovin®
- . Coagulation Factor VII with Dade® Innovin®
- . Protein C with Protein C Reagent
- . Antithrombin (AT) with INNOVANCE® Antithrombin
- Protein C with Berichrom® Protein C
- D-dimer with INNOVANCE® D-Dimer
The performance of this device has not been established in neonate and pediatric patient populations.
Coagulation Factor V Deficient Plasma:
In vitro diagnostic reagent for the determination of the activity of coagulation factor V in human plasma.
Coagulation Factor II, VII and X Deficient Plasmas:
In vitro diagnostic reagents for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods.
Protein C Reagent:
Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma.
Berichrom® Protein C:
For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies.
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
510(k) Summary
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of 21 CFR 8807.92 and follows the FDA guidance 'The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]', issued July 28, 2014.
Submitter 1
Siemens Healthcare Diagnostics Products GmbH Emil-von-Behring-Str. 76 35041 Marburg, Germany Contact Person: Dr. Petra M. Dissmann Email: petra.dissmann@siemens.com Phone: + 49 6421 39 2009 Facsimile: + 49 6421 39 4977 Date Prepared: August 29, 2016 2 Device Name of Device: Sysmex® CS-5100 Common or Usual Name: Automated Coagulation Instrument Classification Name: Multipurpose system for in vitro coagulation studies (21 CFR 864.5425) Regulatory Class: Class II 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: Class II 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.
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 | ||||
| Coagulation Factor V | |||||
| with Dade® Innovin® | |||||
| In vitro diagnostic | |||||
| reagent for the | |||||
| determination of the | |||||
| activity of coagulation | |||||
| factor V in human | |||||
| plasma. | K993299 | 864.7290 | Class II | GJT | Hematology |
| Coagulation Factor VII | |||||
| with Dade® Innovin® | |||||
| In vitro diagnostic | |||||
| reagents for the | |||||
| determination of the | |||||
| activity of coagulation | |||||
| factor II (prothrombin), | |||||
| coagulation factor VII | |||||
| and coagulation factor X | |||||
| in human plasma by | |||||
| coagulometric methods. | K993299 | 864.7290 | Class II | GJT | Hematology |
| Protein C with | |||||
| Protein C Reagent | |||||
| Protein C Reagent is a | |||||
| coagulation test for the | |||||
| quantitative | |||||
| determination of protein | |||||
| C activity in human | |||||
| plasma. | K000649 | 864.7290 | Class II | GGP | Hematology |
| Protein C with | |||||
| Berichrom® Protein C | |||||
| For the quantitative | |||||
| determination of | |||||
| functionally active | |||||
| protein C using a | |||||
| chromogenic substrate as | |||||
| an aid in the diagnosis of | |||||
| inherited and acquired | |||||
| deficiencies. | K001645 | 864.7290 | Class II | GGP | Hematology |
6
Device Description / Test Principle 4
The Sysmex® CS-5100 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated
- Reagents ●
- Controls
- Calibrators ●
- Consumable materials ●
The subject of this 510(k) notification are reagent applications which perform the coagulation tests Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent and Protein C with Berichrom® Protein C.
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-5100 Analysis Principles | |||
|---|---|---|---|
| Reagent | Application | Methodology | |
| Dade® Innovin® with | |||
| Coagulation Factor V | |||
| Deficient Plasma | Coagulation Factor V with | ||
| Dade® Innovin® | Clotting | ||
| (extrinsic pathway) | |||
| Dade® Innovin® with | |||
| Coagulation Factor | |||
| VII Deficient Plasma | Coagulation Factor VII with | ||
| Dade® Innovin® | Clotting | ||
| (extrinsic pathway) | |||
| Protein C Reagent | Protein C with | ||
| Protein C Reagent | Clotting | ||
| Berichrom® Protein C | Protein C with | ||
| Berichrom® Protein C | Chromogenic |
The intended Environment of Use is a clinical central/hospital laboratory.
7
Front View of the Instrument
Image /page/7/Figure/2 description: This image is a line drawing of a machine with several components labeled with numbers. The top section of the machine is labeled (1), and below it, a small component is labeled (2). The left cabinet door is labeled (3), while the top right corner features labels (4), (5), and (6). The middle section is labeled (7), and the right cabinet door is labeled (8).
- (1) Light shield lid: Open this cover to set reagents, perform maintenance, etc.
- (2) Power switch: Turns the power ON/OFF.
- (3) Left door: Holds the Pneumatic Unit inside. Open this door to adjust the positive pressure (0.22 MPa).
- (4) Alarm indicator LED: Indicates the instrument status.
- (5) Mechanical stop switch: Press this switch to immediately stop the instrument's mechanical movement.
- (6) Start button: Press this button to immediately start an analysis. This button is the same as the [Start] button on the IPU toolbar.
- (7) Sampler: Automatically transports samples that are set in the sample rack to the aspiration position.
- (8) Right door: Open the door for maintenance or to discard cuvettes.
8
Informational Processing Unit
Image /page/8/Figure/2 description: This image shows a computer setup with four labeled parts. The labels point to the monitor (1), the computer tower (2), the keyboard (3), and the mouse (4). The computer is a desktop model with a separate monitor, keyboard, and mouse.
- (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.
- Keyboard: Used to operate the IPU together with the touch panel. (3)
- (4) Mouse: Used to operate the IPU together with the touch panel.
Options and Accessories
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) Wand barcode reader: Reads barcodes to input sample numbers, rack numbers and reagent IDs.
- (3) 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.
- (4) IPU cart: The IPU (which includes the keyboard, PC and touch panel display), and the tanks for waste, rinse and CA Clean II can be placed on this cart.
- (5) External indicator light: The status of the instrument is indicated with a red, yellow or green light that can be seen when the operator is not directly in front of the instrument.
- (6) IPU holder: This is an optional holder for the IPU which includes the keyboard, PC and touch panel display which can be installed on the right side of the instrument to minimize the instrument footprint.
9
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. In a normal mode, a capped sample tube analysis can be performed. Automatic re-analysis can also be performed.
- (2) Micro-sample mode: Samples set in the sampler or STAT holder are taken into the instrument for each analysis through a secondary dispensing sample probe. When measurements are to be performed in Micro mode, sample tubes must be uncapped. The instrument detects capped tubes automatically and displays an error message. This analysis mode can be performed with less sample volume than normal mode (consult instruction manual for further information). However, automatic re-analysis cannot be performed.
5 Intended Use / Indications for Use
The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.
For determination of:
- Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® ●
- Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL ●
- Fibrinogen (Fbg) with Dade® Thrombin Reagent ●
- Coagulation Factor V with Dade® Innovin® ●
- Coagulation Factor VII with Dade® Innovin® ●
- Protein C with Protein C Reagent
- Antithrombin (AT) with INNOVANCE® Antithrombin ●
- Protein C with Berichrom® Protein C
- D-dimer with INNOVANCE® D-Dimer ●
The performance of this device has not been established in neonate and pediatric patient populations.
6 Comparison of Technological Characteristics with the Predicate Device
Both the subject and predicate instruments employ the same technological characteristics in that they automatically analyze various clotting tests using reagents, calibrators and controls previously cleared for automated coagulation analyzers. The reagents perform at least equally well on both the subject and predicate instruments. At a high level, the devices have the following same technological elements:
10
Similarities between CS-5100 and CA-1500
There are no technological differences between the subject and predicate devices. However the following minor changes exist between the subject and predicate devices:
| Similarities between CS-5100 and CA-1500 | ||
|---|---|---|
| Analyzer Component | Proposed Device | |
| Sysmex® CS-5100 | Predicate Device | |
| Sysmex® CA-1500 | ||
| Regulatory Classification | JPA, Class II | |
| System, Multipurpose for in | ||
| vitro coagulation studies | Same | |
| Intended Use Statement | The Sysmex® CS-5100 is a fully | |
| automated blood coagulation | ||
| analyzer intended for in vitro | ||
| diagnostic use using plasma | ||
| collected from venous blood | ||
| samples in 3.2% sodium citrate | ||
| tubes to analyze clotting, | ||
| chromogenic and immunoassay | ||
| methods in the clinical laboratory. | ||
| For determination of: | ||
| • Prothrombin Time (PT) seconds | ||
| and PT INR with Dade® | ||
| Innovin® | ||
| • Activated Partial Thromboplastin | ||
| Time (APTT) with Dade® | ||
| Actin® FSL | ||
| • Fibrinogen (Fbg) with Dade® | ||
| Thrombin Reagent | ||
| • Coagulation Factor V with | ||
| Dade® Innovin® | ||
| • Coagulation Factor VII with | ||
| Dade® Innovin® | ||
| • Protein C with Protein C Reagent | ||
| • Antithrombin (AT) with | ||
| INNOVANCE® Antithrombin | ||
| • Protein C with Berichrom® | ||
| Protein C | ||
| • D-dimer with INNOVANCE® | ||
| D-Dimer | ||
| The performance of this device has | ||
| not been established in neonate and | ||
| pediatric patient populations. | 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 | |
| Analyzer Component | Proposed Device | |
| Sysmex® CS-5100 | 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® | ||
| 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 | |
| Specimen Processing | Automatic Pipetting and Dilution | Same |
| Random Access | Yes | Same |
| Liquid Level Sensing | Yes - reagent and sample | Same |
| Bar Code Reader | Sample + reagent | Same |
| STAT Testing | Yes | Same |
| Sampling Capabilities | Normal and Micro Mode | Same |
| Similarities between CS-5100 and CA-1500 | ||
| Analyzer Component | Proposed Device | |
| Sysmex® CS-5100 | 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) | Same | |
| 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) | ||
| 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 uL) | ||
| Protein C with Berichrom® | ||
| Protein C (15 µL) | Same | |
| Rinse & Buffer Solutions | ||
| On-board | ||
| External | CA-CLEAN I | |
| CA-CLEAN II | ||
| Dade® Owren's Buffer | ||
| Water | ||
| Light Source | ||
| Chromogenic | ||
| Immuno-chemical | Halogen Lamp | |
| Halogen Lamp | ||
| Similarities between CS-5100 and CA-1500 | ||
| Analyzer Component | Proposed Device | |
| Sysmex® CS-5100 | Predicate Device | |
| Sysmex® CA-1500 | ||
| Wavelengths* used in Analysis | ||
| *The default wavelength is | ||
| normally used to generate the | ||
| reported value of the measurement. | ||
| The sub-wavelength is run in | ||
| parallel. If a light intensity error | ||
| occurs by using the default | ||
| wavelength the value from the sub- | ||
| wavelength is used automatically. | Clotting Applications: | |
| Coagulation Factor V with | ||
| Dade® Innovin® | ||
| (Default = 660 nm; | ||
| sub-wavelength = none) | ||
| Coagulation Factor VII with | ||
| Dade® Innovin® | ||
| (Default = 660 nm; | ||
| Sub-wavelength = none) | ||
| Protein C with Protein C Reagent | ||
| (Default = 660 nm; | ||
| Sub-wavelength = none) | ||
| Chromogenic Application: | ||
| Antithrombin with | ||
| INNOVANCE® Antithrombin | ||
| (Default = 405 nm; | ||
| Sub-wavelength = none) | ||
| Protein C with | ||
| Berichrom® Protein C | ||
| (Default = 405 nm; | ||
| Sub-wavelength = none) | Same | |
| Temperature Control | Sample incubation well: | |
| 37 °C ± 1.0 °C | Same | |
| Differences between CS-5100 and CA-1500 | ||
| Analyzer Component | Proposed Device | |
| Sysmex® CS-5100 | Predicate Device | |
| Sysmex® CA-1500 | ||
| Operating Principle | ||
| Clotting | Transmitted Light Detection | |
| (Absorbance) at 340, 405, 575, 660 | ||
| or 800 nm. Wavelengths 340 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 | ||
| Immuno-Chemical | 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 | Transmitted Light Detection | |
| (Absorbance) at 405, 575, or 800 | ||
| nm | ||
| Clotting Applications: | Clotting Applications: | |
| Wavelengths* used in Analysis | ||
| *The default wavelength is normally | ||
| used to generate the reported value | ||
| of the measurement. The | ||
| sub-wavelength is run in parallel. If | ||
| a light intensity error occurs by | ||
| using the default wavelength the | ||
| value from the sub-wavelength is | ||
| used automatically. | PT (seconds) with | |
| Dade® Innovin® | ||
| (Default = 660 nm; | ||
| Sub-Wavelength = 800 nm) | ||
| PT (INR) with Dade® Innovin® | ||
| (Default = 660 nm; | ||
| Sub-Wavelength= 800 nm) | PT (seconds) with | |
| Dade® Innovin® | ||
| (Default = 660 nm; | ||
| Sub-Wavelength = none) | ||
| PT (INR) with Dade® Innovin® | ||
| (Default = 660 nm; | ||
| Sub-Wavelength = none) | ||
| APTT with Dade® Actin® FSL | ||
| Activated PTT Reagent | ||
| (Default = 660 nm; | ||
| Sub-Wavelength= 800 nm) | APTT with Dade® Actin® FSL | |
| Activated PTT Reagent | ||
| (Default = 660 nm; | ||
| Sub-Wavelength= none) | ||
| Fibrinogen with | ||
| Dade® Thrombin Reagent | ||
| (Default = 405 nm; | ||
| Sub-Wavelength = none) | Fibrinogen with | |
| Dade® Thrombin Reagent | ||
| (Default = 660 nm; | ||
| Sub-Wavelength = none) | ||
| Differences between CS-5100 and CA-1500 | ||
| Analyzer Component | Proposed Device | |
| Sysmex® CS-5100 | Predicate Device | |
| Sysmex® CA-1500 | ||
| Wavelengths* used in Analysis | ||
| *The default wavelength is normally | ||
| used to generate the reported value | ||
| of the measurement. The | ||
| sub-wavelength is run in parallel. If | ||
| a light intensity error occurs by | ||
| using the default wavelength the | ||
| value from the sub-wavelength is | ||
| used automatically. | Immuno-chemical Application: | |
| D-dimer with | ||
| INNOVANCE® D-Dimer | ||
| (Default = 660 nm; | ||
| Sub-Wavelength = none) | Immuno-chemical Application: | |
| D-dimer with | ||
| INNOVANCE® D-Dimer | ||
| (Default = 800 nm; | ||
| Sub-Wavelength = none) | ||
| Light Source | ||
| Clotting | Halogen Lamp | Light Emitting Diode |
| Probes | 2 Sample probes; | |
| 3 Reagent probes | 1 Sample probe; | |
| 1 Reagent probe | ||
| Cap Piercing | Cap Piercer only | Both options available: |
| Cap Piercer and Non-Cap Piercer | ||
| 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: | |
| 3 – 200 μL | ||
| Sample probe: | ||
| 5 - 450 μL | ||
| Sample Volumes (Plasma) | Antithrombin with | |
| INNOVANCE® Antithrombin | ||
| (14 μL) | ||
| D-dimer with INNOVANCE® | ||
| D-Dimer (15 μL) | Antithrombin with | |
| INNOVANCE® Antithrombin | ||
| (10 μL) | ||
| D-dimer with INNOVANCE® | ||
| D-Dimer (13 μL) | ||
| Bidirectional Interface | ||
| communication protocols | CA-, ASTM-, CS- Protocol | CA-, ASTM-Protocol |
11
12
13
14
Differences between CS-5100 and CA-1500
15
The above described differences do not raise new questions as to safety and effectiveness of the new device.
7 Performance Data
The following performance data were provided in support of the substantial equivalence determination.
16
Method comparison 7.1
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 in the United States, 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-5100), 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-5100: Method Comparison Summary Table, Passing-Bablok regression | |||||
|---|---|---|---|---|---|
| Application | |||||
| (measuring | |||||
| interval) | 1st Site | 2nd Site | 3rd Site | 4th Site | Sites |
| Combined | |||||
| Coagulation | |||||
| Factor V | |||||
| with Dade® | |||||
| Innovin® | |||||
| (6.0 - 149.0 | |||||
| % of norm) | N = 133 | ||||
| y = 1.013 x - | |||||
| 0.205 | |||||
| r = 0.991 | |||||
| (r² = 0.983) | N = 151 | ||||
| y = 1.048 x - | |||||
| 1.431 | |||||
| r = 0.992 | |||||
| (r² = 0.983) | N = 148 | ||||
| y = 0.974 x + | |||||
| 0.853 | |||||
| r = 0.988 | |||||
| (r² = 0.975) | N = 177 | ||||
| y = 1.036 x + | |||||
| 1.319 | |||||
| r = 0.974 | |||||
| (r² = 0.950) | N = 609 | ||||
| y = 1.017 x + | |||||
| 0.185 | |||||
| r = 0.984 | |||||
| (r² = 0.969) | |||||
| Coagulation | |||||
| Factor VII | |||||
| with Dade® | |||||
| Innovin(B) | |||||
| (6.0 - 149.0 | |||||
| % of norm) | N = 121 | ||||
| y = 1.040 x - | |||||
| 1.567 | |||||
| r = 0.993 | |||||
| (r² = 0.986) | N = 145 | ||||
| y = 1.017 x - | |||||
| 0.914 | |||||
| r = 0.993 | |||||
| (r² = 0.986) | N = 102 | ||||
| y = 1.081 x + | |||||
| 0.724 | |||||
| r = 0.995 | |||||
| (r² = 0.991) | N = 137 | ||||
| y = 1.117 x + | |||||
| 0.261 | |||||
| r = 0.987 | |||||
| (r² = 0.974) | N = 505 | ||||
| y = 1.051 x - | |||||
| 0.241 | |||||
| r = 0.989 | |||||
| (r² = 0.978) | |||||
| Protein C | |||||
| with Protein | |||||
| C Reagent | |||||
| (10.1 - 131.0 | |||||
| % of norm) | N = 138 | ||||
| y = 1.005 x - | |||||
| 1.892 | |||||
| r = 0.996 | |||||
| (r² = 0.993) | N = 176 | ||||
| y = 1.006 x + | |||||
| 1.483 | |||||
| r = 0.994 | |||||
| (r² = 0.988) | N = 110 | ||||
| y = 0.891 x + | |||||
| 0.714 | |||||
| r = 0.993 | |||||
| (r² = 0.986) | N = 200 | ||||
| y = 0.973 x + | |||||
| 0.644 | |||||
| r = 0.984 | |||||
| (r² = 0.968) | N = 624 | ||||
| y = 0.988 x - | |||||
| 0.413 | |||||
| r = 0.987 | |||||
| (r² = 0.974) | |||||
| Protein C | |||||
| with | |||||
| Berichrom® | |||||
| Protein C | |||||
| (10.0 - 138.0 | |||||
| % of norm) | N = 127 | ||||
| y = 0.963 x - | |||||
| 0.922 | |||||
| r = 0.995 | |||||
| (r² = 0.991) | N = 149 | ||||
| y = 0.935 x - | |||||
| 1.805 | |||||
| r = 0.992 | |||||
| (r² = 0.984) | N = 130 | ||||
| y = 0.923 x + | |||||
| 2.610 | |||||
| r = 0.995 | |||||
| (r² = 0.990) | N = 125 | ||||
| y = 0.985 x - | |||||
| 0.302 | |||||
| r = 0.994 | |||||
| (r² = 0.987) | N = 531 | ||||
| y = 0.950 x + | |||||
| 0.375 | |||||
| r = 0.992 | |||||
| (r² = 0.984) |
17
Reproducibility Studies 7.2
Twenty-day precision studies were performed at two external sites in Germany and one external site 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-5100: Reproducibility Summary Table, Within Run | ||||
|---|---|---|---|---|
| Application | ||||
| (measuring interval) | 1st Site | |||
| Within Run | ||||
| (%CV) | 2nd Site | |||
| Within Run | ||||
| (%CV) | 3rd Site | |||
| Within Run | ||||
| (%CV) | Sites Combined | |||
| (%CV) | ||||
| Coagulation Factor V with | ||||
| Dade® Innovin® | ||||
| (6.0 - 149.0% of norm) | 2.43 - 3.52 | 1.94 - 2.96 | 2.38 - 3.42 | 2.40 - 3.16 |
| Coagulation Factor VII with | ||||
| Dade® Innovin® | ||||
| (6.0 - 149.0% of norm) | 1.50 - 2.18 | 1.13 - 1.92 | 1.36 - 1.97 | 1.33 - 2.00 |
| Protein C with | ||||
| Protein C Reagent | ||||
| (10.1 - 131.0% of norm) | 3.00 - 3.83 | 2.11 - 2.94 | 1.80 - 2.47 | 2.53 - 3.22 |
| Protein C with | ||||
| Berichrom® Protein C | ||||
| (10.0 - 138.0% of norm) | 1.24 - 5.59 | 1.43 – 3.62 | 1.71 - 9.94 | 1.48 - 6.85 |
18
| Sysmex® CS-5100: Reproducibility Summary Table, Between Run | ||||
|---|---|---|---|---|
| Application | ||||
| (measuring interval) | 1st Site | |||
| Between | ||||
| Run | ||||
| (%CV) | 2nd Site | |||
| Between | ||||
| Run | ||||
| (%CV) | 3rd Site | |||
| Between | ||||
| Run | ||||
| (%CV) | Sites Combined | |||
| (%CV) | ||||
| Coagulation Factor V with | ||||
| Dade® Innovin® | ||||
| (6.0 - 149.0% of norm) | 4.08 - 5.33 | 2.22 - 3.72 | 2.55 - 4.21 | 3.29 - 4.24 |
| Coagulation Factor VII with | ||||
| Dade® Innovin® | ||||
| (6.0 - 149.0% of norm) | 0.39 - 1.80 | 0.00 - 0.93 | 0.64 - 1.09 | 0.65 - 1.29 |
| Protein C with | ||||
| Protein C Reagent | ||||
| (10.1 - 131.0% of norm) | 2.51 - 3.96 | 0.00 - 1.68 | 1.48 - 5.51 | 1.73 — 3.86 |
| Protein C with | ||||
| Berichrom® Protein C | ||||
| (10.0 - 138.0% of norm) | 0.00 - 2.56 | 0.00 - 1.44 | 0.00 - 1.14 | 0.00 - 1.04 |
| Sysmex® CS-5100: Reproducibility Summary Table, Between Day | ||||
|---|---|---|---|---|
| Application | ||||
| (measuring interval) | 1st Site | |||
| Between | ||||
| Day | ||||
| (%CV) | 2nd Site | |||
| Between | ||||
| Day | ||||
| (%CV) | 3rd Site | |||
| Between | ||||
| Day | ||||
| (%CV) | Sites Combined | |||
| (%CV) | ||||
| Coagulation Factor V with | ||||
| Dade® Innovin® | ||||
| (6.0 - 149.0% of norm) | 0.00 - 0.00 | 0.88 - 2.61 | 0.00 - 2.72 | 0.00 - 0.59 |
| Coagulation Factor VII with | ||||
| Dade® Innovin® | ||||
| (6.0 - 149.0% of norm) | 0.00 - 1.64 | 1.49 — 2.66 | 0.95 - 2.05 | 0.94 - 1.97 |
| Protein C with | ||||
| Protein C Reagent | ||||
| (10.1 - 131.0% of norm) | 0.00 - 1.57 | 0.00 - 2.31 | 0.00 - 0.52 | 0.00 - 1.01 |
| Protein C with | ||||
| Berichrom® Protein C | ||||
| (10.0 - 138.0% of norm) | 0.00 - 1.33 | 0.00 - 0.90 | 0.46 - 2.75 | 0.39 - 1.16 |
19
| CS-5100: Reproducibility Summary Table, Total CV (Within Site and Sites Combined) | ||||
|---|---|---|---|---|
| Application | ||||
| (measuring interval) | 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) | ||||
| Coagulation Factor V with | ||||
| Dade® Innovin® | ||||
| (6.0 - 149.0% of norm) | 4.85 - 6.06 | 3.75 - 5.06 | 3.54 - 5.30 | 4.83 - 6.85 |
| Coagulation Factor VII with | ||||
| Dade® Innovin® | ||||
| (6.0 - 149.0% of norm) | 1.87 - 2.82 | 1.83 - 2.96 | 2.15 - 2.87 | 3.39 - 5.03 |
| Protein C with | ||||
| Protein C Reagent | ||||
| (10.1 - 131.0% of norm) | 4.25 - 5.51 | 2.45 - 4.10 | 2.49 - 6.04 | 4.54 - 7.15 |
| Protein C with | ||||
| Berichrom® Protein C | ||||
| (10.0 - 138.0% of norm) | 1.34 - 6.15 | 1.65 - 3.88 | 2.27 - 9.95 | 3.22 - 7.92 |
20
Detection Capability Results 7.3
Detection capability studies were measured for the calibrated assays on the Sysmex® CS-5100: Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent, and Protein C with Berichrom® Protein C. 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-5100: 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 V with | |||
| Dade® Innovin® | 6.0 | 4.80 | 0.74 |
| Coagulation Factor VII with | |||
| Dade® Innovin® | 6.0 | 3.39 | 0.27 |
| Protein C with | |||
| Protein C Reagent | 10.1 | 9.35 | 2.91 |
| Protein C with | |||
| Berichrom® Protein C | 10.0 | 8.32 | 2.07 |
21
Linearity & Measuring Range 7.4
Linearity studies were performed for the calibrated assays on the Sysmex® CS-5100: Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent, and Protein C with Berichrom® Protein C. 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-5100: Linearity and Measuring Range Summary | ||
|---|---|---|
| Application | Measured Linear Range | Clinically Reportable Range |
| Coagulation Factor V with | ||
| Dade® Innovin® | 3.4 – 180.7% of norm | 6.0 – 149.0% of norm |
| Coagulation Factor VII with | ||
| Dade® Innovin® | 4.3 – 179.5% of norm | 6.0 – 149.0% of norm |
| Protein C with | ||
| Protein C Reagent | 7.0 – 187.7% of norm | 10.1 – 131.0% of norm |
| Protein C with | ||
| Berichrom® Protein C | 7.1 – 181.3% of norm | 10.0 – 138.0% of norm |
7.5 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-5100: Reference Interval Summary Table | ||
|---|---|---|
| Application | N | Sysmex® CS-5100 Reference Interval |
| Coagulation Factor V with | ||
| Dade® Innovin® | 194 | 80.8% of norm (5th Percentile) |
| Coagulation Factor VII with | ||
| Dade® Innovin® | 194 | 67.6% of norm (5th Percentile) |
| Protein C with | ||
| Protein C Reagent | 194 | 76.4% of norm (5th Percentile) |
| Protein C with | ||
| Berichrom® Protein C | 194 | 83.0% of norm (5th Percentile) |
22
Conclusions 8
Because the predicate device was cleared based in part on the results of clinical studies, and because clinical settings are required for a well-validated device, clinical testing was required to support substantial equivalence.
The non-clinical data support the safety of the device.
The clinical data demonstrate that the Sysmex® CS-5100 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.