K Number

Device Name

Sysmex CS-2100i

Manufacturer

Siemens Healthcare Diagnostics Products GmbH

Date Cleared

2016-12-26

(90 days)

Product Code

JPA GGP GJT

Regulation Number

864.5425

Intended Use

For Sysmex® CS-2100i: The Sysmex CS-2100i 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. For Coagulation Factor V Deficient Plasma: In vitro diagnostic reagent for the determination of the activity of coagulation factor V in human plasma. For Coagulation Factor VII Deficient Plasma: 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. For Protein C Reagent: Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma. For 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.

Device Description

The Sysmex® CS-2100i is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated Reagents, Controls, Calibrators, and Consumable materials. The subject of this 510(k) notification are reagent applications which perform the coagulation tests Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent and Protein C with Berichrom® Protein C.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K011235, K993299, K993299, K000649, K001645

Reference Devices

No reference devices were used in this submission.

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes a standard automated blood coagulation analyzer and associated reagents, focusing on analytical performance studies. There is no mention of AI, ML, or related technologies in the intended use, device description, or performance studies.

Therapeutic

No
This device is an in vitro diagnostic analyzer used to measure coagulation factors in blood samples, which aids in diagnosis rather than providing direct therapy.

Diagnostic

Yes

The device, Sysmex CS-2100i, is clearly stated as an "in vitro diagnostic use" device for analyzing various blood coagulation parameters, which are used to determine specific conditions or levels of substances in patient samples to aid in diagnosis.

SaMD (Software as a Medical Device)

The device description explicitly states it is an "automated blood coagulation instrument" and mentions hardware components like an "Information Processing Unit (IPU) screen" and the ability to print on "external printers or transmitted to a host computer." The 510(k) is for reagent applications used with this hardware.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The "Intended Use / Indications for Use" section explicitly states: "The Sysmex CS-2100i is a fully automated blood coagulation analyzer intended for in vitro diagnostic use..."

Furthermore, the descriptions for the associated reagents also state "In vitro diagnostic reagent".

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

For Sysmex® CS-2100i:

The Sysmex CS-2100i 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.

For Coagulation Factor V Deficient Plasma:

Intended Use

In vitro diagnostic reagent for the determination of the activity of coagulation factor V in human plasma.

For Coagulation Factor VII Deficient Plasma:

Intended Use

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.

For Protein C Reagent: Intended Use Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma.

For Berichrom® Protein C:

Intended Use

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

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.

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

The intended Environment of Use is a 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

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-2100i), 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.

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'. 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.

Detection Capability Results

Detection capability studies were measured for the calibrated assays on the Sysmex® CS-2100i: 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.

Linearity & Measuring Range

Linearity studies were performed for the calibrated assays on the Sysmex® CS-2100i: 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'.

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 study population did not include neonate and pediatric sample populations.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Method Comparison:

Passing-Bablok Regression

Factor V with Dade® Innovin®: N=589, Sample range=7.2 - 145.1 (% of norm), r=0.983, Slope=0.990 (0.977, 1.003), Intercept=1.861 (1.025, 2.784)
Factor VII with Dade® Innovin®: N=492, Sample range=6.2 - 148.8 (% of norm), r=0.991, Slope=1.039 (1.028, 1.051), Intercept=0.636 (-0.135, 1.104)
Protein C with Protein C Reagent: N=584, Sample range=10.3 - 129.3 (% of norm), r=0.977, Slope=0.966 (0.952, 0.981), Intercept=-0.372 (-1.207, 0.470)
Protein C with Berichrom® Protein C: N=507, Sample range=11.3 - 134.7 (% of norm), r=0.994, Slope=0.942 (0.934, 0.951), Intercept=-0.292 (-1.037, 0.399)

Reproducibility Summarized Table (%CV)

Within Run:

Coagulation Factor V with Dade® Innovin® (6.0 - 149.0% of norm): 1st Site=4.07 – 7.40, 2nd Site=2.07 - 3.34, 3rd Site=2.70 - 6.09, Sites Combined=3.16 - 5.01
Coagulation Factor VII with Dade® Innovin® (6.0 - 149.0% of norm): 1st Site=1.74 - 2.38, 2nd Site=1.71 – 2.87, 3rd Site=1.99 - 2.59, Sites Combined=1.85 - 2.63
Protein C with Protein C Reagent (10.1 - 131.0% of norm): 1st Site=2.26 - 3.75, 2nd Site=2.08 - 2.68, 3rd Site=2.43 - 7.02, Sites Combined=2.46 - 4.78
Protein C with Berichrom® Protein C (10.0 - 138.0% of norm): 1st Site=1.02 - 5.34, 2nd Site=1.00 - 4.56, 3rd Site=1.20 - 5.26, Sites Combined=1.15 - 4.63

Between Run:

Coagulation Factor V with Dade® Innovin® (6.0 - 149.0% of norm): 1st Site=0.00 - 2.80, 2nd Site=0.00 - 3.87, 3rd Site=0.00 - 3.36, Sites Combined=1.76 - 2.55
Coagulation Factor VII with Dade® Innovin® (6.0 - 149.0% of norm): 1st Site=0.65 - 1.41, 2nd Site=0.00 - 1.35, 3rd Site=0.00 - 2.32, Sites Combined=0.00 - 1.72
Protein C with Protein C Reagent (10.1 - 131.0% of norm): 1st Site=0.00 - 1.65, 2nd Site=0.85 - 2.70, 3rd Site=0.00 - 2.50, Sites Combined=0.56 - 1.95
Protein C with Berichrom® Protein C (10.0 - 138.0% of norm): 1st Site=0.54 - 2.51, 2nd Site=0.32 - 2.23, 3rd Site=0.00 - 1.20, Sites Combined=0.84 - 1.66

Between Day:

Coagulation Factor V with Dade® Innovin® (6.0 - 149.0% of norm): 1st Site=0.00 - 1.55, 2nd Site=0.00 - 2.56, 3rd Site=0.00 - 2.81, Sites Combined=0.00 - 1.64
Coagulation Factor VII with Dade® Innovin® (6.0 - 149.0% of norm): 1st Site=0.00 - 1.02, 2nd Site=1.48 – 2.68, 3rd Site=0.00 - 1.92, Sites Combined=0.89 - 1.67
Protein C with Protein C Reagent (10.1 - 131.0% of norm): 1st Site=0.00 - 2.41, 2nd Site=0.00 - 1.20, 3rd Site=0.00 - 2.60, Sites Combined=0.00 - 2.17
Protein C with Berichrom® Protein C (10.0 - 138.0% of norm): 1st Site=0.00 - 0.57, 2nd Site=0.00 - 1.02, 3rd Site=0.00 - 2.36, Sites Combined=0.00 - 1.40

Total CV (Within Site and Sites Combined):

Coagulation Factor V with Dade® Innovin® (6.0 - 149.0% of norm): 1st Site Total CV=4.64 - 7.40, 2nd Site Total CV=3.37 - 5.12, 3rd Site Total CV=3.85 - 6.95, Sites Combined Total CV=4.78 - 10.43
Coagulation Factor VII with Dade® Innovin® (6.0 - 149.0% of norm): 1st Site Total CV=2.01 - 2.81, 2nd Site Total CV=2.58 – 3.56, 3rd Site Total CV=2.23 - 3.31, Sites Combined Total CV=2.57 - 3.59
Protein C with Protein C Reagent (10.1 - 131.0% of norm): 1st Site Total CV=2.78 - 4.55, 2nd Site Total CV=2.36 - 3.83, 3rd Site Total CV=3.47 - 7.49, Sites Combined Total CV=3.47 - 5.85
Protein C with Berichrom® Protein C (10.0 - 138.0% of norm): 1st Site Total CV=1.40 - 5.91, 2nd Site Total CV=1.40 - 5.18, 3rd Site Total CV=1.70 - 5.26, Sites Combined Total CV=2.19 - 5.69

Detection Capability Results:

Limit of Quantitation Studies

Coagulation Factor V with Dade® Innovin®: Lower Limit of Clinically Reportable Range=6.0 (% of norm), Measured Limit of Quantitation=4.80 (% of norm), Maximum Total Error=2.04 (% of norm)
Coagulation Factor VII with Dade® Innovin®: Lower Limit of Clinically Reportable Range=6.0 (% of norm), Measured Limit of Quantitation=3.39 (% of norm), Maximum Total Error=0.21 (% of norm)
Protein C with Protein C Reagent: Lower Limit of Clinically Reportable Range=10.1 (% of norm), Measured Limit of Quantitation=9.35 (% of norm), Maximum Total Error=3.62 (% of norm)
Protein C with Berichrom® Protein C: Lower Limit of Clinically Reportable Range=10.0 (% of norm), Measured Limit of Quantitation=8.32 (% of norm), Maximum Total Error=2.07 (% of norm)

Linearity & Measuring Range:

Coagulation Factor V with Dade® Innovin®: Measured Linear Range=3.4 – 180.7% of norm, Clinically Reportable Range=6.0 – 149.0% of norm
Coagulation Factor VII with Dade® Innovin®: Measured Linear Range=4.3 – 179.5% of norm, Clinically Reportable Range=6.0 – 149.0% of norm
Protein C with Protein C Reagent: Measured Linear Range=7.0 – 187.7% of norm, Clinically Reportable Range=10.1 – 131.0% of norm
Protein C with Berichrom® Protein C: Measured Linear Range=7.1 – 181.3% of norm, Clinically Reportable Range=10.0 – 138.0% of norm

Reference Interval Summary Table:

Coagulation Factor V with Dade® Innovin®: N=193, Sysmex® CS-2100i Reference Interval=79.8% (5th Percentile of norm)
Coagulation Factor VII with Dade® Innovin®: N=193, Sysmex® CS-2100i Reference Interval=65.6% (5th Percentile of norm)
Protein C with Protein C Reagent: N=193, Sysmex® CS-2100i Reference Interval=75.6% (5th Percentile of norm)
Protein C with Berichrom® Protein C: N=191, Sysmex® CS-2100i Reference Interval=84.9% (5th Percentile of norm)

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® Automated Blood Coagulation Analyzer CA-1500 (K011235), Factor V with Dade® Innovin® K993299, Factor VII with Dade® Innovin® K993299, Protein C with Protein C Reagent K000649, Protein C with Berichrom® Protein C K001645

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

Regulation Number and Section

§ 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.

Summary

Image /page/0/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. In the center of the seal is a stylized image of a caduceus, a symbol often associated with healthcare. The caduceus is composed of three intertwined snakes and a staff.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 26, 2016

Siemens Healthcare Diagnostics Products GmbH Ms. Donna Noeh Regulatory Affairs Manager Emil-von-Behring Strasse 76 35041 Marburg, Germany

Re: K162688 Trade/Device Name: Sysmex® CS-2100i 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 26, 2016 Received: September 27, 2016

Dear Ms. Noeh:

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.

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/Resourcesfor You/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

Indications for Use

510(k) Number (if known) K162688

Device Name

Sysmex® CS-2100i, Coagulation Factor V Deficient Plasma, Coagulation Factor II, VII, and X Deficient Plasmas, Protein C Reagent, Berichrom® Protein C

Indications for Use (Describe)

For Sysmex® CS-2100i:

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.

For Coagulation Factor V Deficient Plasma:

Intended Use

In vitro diagnostic reagent for the determination of the activity of coagulation factor V in human plasma.

For Coagulation Factor VII Deficient Plasma:

Intended Use

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.

For Protein C Reagent: Intended Use Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma.

For Berichrom® Protein C:

Intended Use

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)

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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.

Submitter 1

Siemens Healthcare Diagnostics Products GmbH

Emil-von-Behring-Str. 76

35041 Marburg, Germany

Contact Person:	Donna Noeh
Email:	donna.noeh@siemens.com
Phone:	+ (49) 6421 39 5107
Facsimile:	+ (49) 6421 39 4977
Date Prepared:	November 18, 2016

2 Device

Name of Device:	Sysmex® Automated Blood Coagulation Analyzer CS-2100
Common or Usual Name:	Sysmex® CS-2100i; CS-2100i
Classification Name:	Multipurpose system for in vitro coagulation studies
(21 CFR 864.5425)
Regulatory Class:	II
Product Code:	JPA
510(k) Review Panel	Hematology
Predicate Device
Name of Device:	Sysmex® Automated Blood Coagulation Analyzer CA-1500
(K011235)
Common or Usual Name:	Sysmex® CA-1500
Classification Name:	Multipurpose system for in vitro coagulation studies
(21 CFR 864.5425)
Regulatory 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.

| Reagent Name | K number | Regulation
Number | Regulatory
Class | Product Code | Panel |
|-------------------------------------------|----------|----------------------|---------------------|--------------|------------|
| Factor V with
Dade®
Innovin® | K993299 | 864.7290 | 2 | GJT | Hematology |
| Factor VII with
Dade®
Innovin® | K993299 | 864.7290 | 2 | GJT | Hematology |
| Protein C with
Protein C
Reagent | K000649 | 864.7290 | 2 | GGP | Hematology |
| Protein C with
Berichrom®
Protein C | K001645 | 864.7290 | 2 | GGP | Hematology |

Reagent Applications that are the subject of this 510(k) notification:

Device Description / Test Principle 4

Reagents
Controls
Calibrators ●
Consumable materials ●

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-2100i 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.

Instrument (main unit)

Front View of the Sysmex CS-2100i (main unit) Figure 1:

Image /page/7/Figure/3 description: This image is a line drawing of a piece of equipment with multiple labeled parts. The parts are labeled with the numbers 1 through 9. The equipment has a boxy shape with multiple compartments and openings.

(1) Power connector: Connected to the power cable.

(2) Power Switch: Turns the power ON and OFF.
(3) Light shield lid: Open this cover to set reagents and perform maintenance.
(4) Alarm indicator LED: This displays alarms affecting the instrument.
(5) Cuvette hopper: Holds cuvettes and automatically supplies them to the instrument.
(6) Start button: This is the same as the Start button on the IPU screen.

(7) Mechanical stop switch: Press this switch to immediately stop the instrument's mechanical movement.

(8) Cuvette trash tray: Used cuvettes are discarded here.

(9) Sampler: The sampler automatically transports samples that are set in the sample rack to the aspiration position.

Figure 2: Informational Processing Unit (IPU) Sysmex CS-2100i

Image /page/8/Figure/2 description: The 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 monitor is placed on top of the computer tower, and the keyboard is in front of the tower. The mouse is located to the right of the keyboard.

(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.

5 Intended Use / Indications for Use

The Sysmex® CS-2100i 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 with Dade® Innovin®

In vitro diagnostic reagent for the determination of the activity of factor V in human plasma.

Coagulation Factor VII with Dade® Innovin® Plasma

In vitro diagnostic reagent for the determination of the activity of coagulation factor VII (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods.

Protein C with Protein C Reagent

Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma.

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.

Comparison of Technological Characteristics with the Predicate Device 6

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:

Similarities between CS-2100i and CA-1500
Analyzer Component	Proposed Device
Sysmex® CS-2100i	Predicate Device
Sysmex® CA-1500
Regulatory Classification	JPA, Class II
System, Multipurpose for in
vitro coagulation studies	Same
Intended Use Statement	The Sysmex® CS-2100i 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; α2-
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 CS-2100i and CA-1500
Analyzer Component	Proposed Device
Sysmex® CS-2100i	Predicate Device
Sysmex® CA-1500
Application type	Clotting Applications:	Same
	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
	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
Clinical Reportable Range	Fibrinogen with Dade® Thrombin
Reagent 50 to 860 mg/dL;	Same
	Antithrombin with INNOVANCE®
Antithrombin 9.0 to 128% of norm;
	D-dimer with INNOVANCE® D-
dimer 0.19 to 35.2 mg/L FEU;
	Coagulation Factor V with Dade®
Innovin® 6.0 to 149.0% of norm;
	Coagulation Factor VII with Dade®
Innovin® 6.0 to 149.0% of norm;
	Protein C with Protein C Reagent
10.1 to 131.0% of norm
Specimen Processing	Automatic Pipetting and Dilution	Same
Similarities between CS-2100i and CA-1500
Analyzer Component	Proposed Device
Sysmex® CS-2100i	Predicate Device
Sysmex® CA-1500
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
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 (5 µL)	Same
Similarities between CS-2100i and CA-1500
Analyzer Component	Proposed Device
Sysmex® CS-2100i	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)	Same
Rinse & Buffer Solutions
On-board
External	CA-CLEAN I
CA-CLEAN II
Dade® Owren's Buffer
Water	Same
Light Source
Chromogenic
Immuno-chemical	Halogen Lamp
Halogen Lamp	Same
Same
Probes	1 Sample probe;
1 Reagent probe	Same
Wavelengths used in Analysis	Antithrombin with
INNOVANCE® Antithrombin
(405 nm)
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=	Same
Similarities between CS-2100i and CA-1500
Analyzer Component	Proposed Device
Sysmex® CS-2100i	Predicate Device
Sysmex® CA-1500
	none)
Protein C with
Berichrom® Protein C
(Default = 405 nm; Sub-wavelength=
none)
Temperature Control	Sample incubation well:
37 °C ± 1.0 °C	Same
Differences between CS-2100i and CA-1500
Analyzer Component	Proposed Device
Sysmex® CS-2100i	Predicate Device
Sysmex® CA-1500
Clinical Reportable Range	Protein C with Berichrom® Protein C
10.0 to 138% of norm	5.0 to 138% of norm
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
	Wavelengths* used in Analysis
*The default wavelength is
normally used to generate the
reported value of the measurement.
The sub-wavelength is run in	PT (seconds) Dade® Innovin®
(Default = 660 nm; Sub- Wavelength=
800 nm)	PT (seconds) with Dade®
Innovin® Default = 660 nm; Sub-
Wavelength= none)
parallel. If a light intensity error
occurs by using the default
wavelength the value from the sub-
wavelength is used automatically.	PT (INR) with Dade® Innovin®
(Default = 660 nm; Sub-Wavelength=
800 nm)	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)
Differences between CS-2100i and CA-1500
Analyzer Component	Proposed Device
Sysmex® CS-2100i	Predicate Device
Sysmex® CA-1500
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:
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)

Similarities between CS-2100i and CA-1500

Differences between Sysmex® CS-2100i and Sysmex® CA-1500

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.

7.1 Method comparison

Samples were measured on both the predicate device (Sysmex® CA-1500) as well as the new device (Sysmex® CS-2100i), 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 from the multi-center study shows that the proposed and predicate devices provide equivalent results when used in a clinical setting.

| Application | N | Sample range
(% of norm) | r | Slope
(95% CI) | Intercept
(95% CI) |
|-------------------------------------|-----|-----------------------------|-------|-------------------------|---------------------------|
| Factor V with Dade® Innovin® | 589 | 7.2 - 145.1 | 0.983 | 0.990
(0.977, 1.003) | 1.861
(1.025, 2.784) |
| Factor VII with Dade® Innovin® | 492 | 6.2 - 148.8 | 0.991 | 1.039
(1.028, 1.051) | 0.636
(-0.135, 1.104) |
| Protein C with Protein C Reagent | 584 | 10.3 - 129.3 | 0.977 | 0.966
(0.952, 0.981) | -0.372
(-1.207, 0.470) |
| Protein C with Berichrom® Protein C | 507 | 11.3 - 134.7 | 0.994 | 0.942
(0.934, 0.951) | -0.292
(-1.037, 0.399) |

7.2 Reproducibility Studies

Sysmex® CS-2100i: 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)	4.07 – 7.40	2.07 - 3.34	2.70 - 6.09	3.16 - 5.01
Coagulation Factor VII with
Dade® Innovin®
(6.0 - 149.0% of norm)	1.74 - 2.38	1.71 – 2.87	1.99 - 2.59	1.85 - 2.63
Protein C with
Protein C Reagent
(10.1 - 131.0% of norm)	2.26 - 3.75	2.08 - 2.68	2.43 - 7.02	2.46 - 4.78
Protein C with
Berichrom® Protein C
(10.0 - 138.0% of norm)	1.02 - 5.34	1.00 - 4.56	1.20 - 5.26	1.15 - 4.63

Sysmex® CS-2100i: 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)	0.00 - 2.80	0.00 - 3.87	0.00 - 3.36	1.76 - 2.55
Coagulation Factor VII with
Dade® Innovin®
(6.0 - 149.0% of norm)	0.65 - 1.41	0.00 - 1.35	0.00 - 2.32	0.00 - 1.72
Protein C with
Protein C Reagent
(10.1 - 131.0% of norm)	0.00 - 1.65	0.85 - 2.70	0.00 - 2.50	0.56 - 1.95
Protein C with
Berichrom® Protein C
(10.0 - 138.0% of norm)	0.54 - 2.51	0.32 - 2.23	0.00 - 1.20	0.84 - 1.66

Sysmex® CS-2100i: 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 - 1.55	0.00 - 2.56	0.00 - 2.81	0.00 - 1.64
Coagulation Factor VII with
Dade® Innovin®
(6.0 - 149.0% of norm)	0.00 - 1.02	1.48 – 2.68	0.00 - 1.92	0.89 - 1.67
Protein C with
Protein C Reagent
(10.1 - 131.0% of norm)	0.00 - 2.41	0.00 - 1.20	0.00 - 2.60	0.00 - 2.17
Protein C with
Berichrom® Protein C
(10.0 - 138.0% of norm)	0.00 - 0.57	0.00 - 1.02	0.00 - 2.36	0.00 - 1.40

CS-2100i: 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)	4.64 - 7.40	3.37 - 5.12	3.85 - 6.95	4.78 - 10.43
Coagulation Factor VII with
Dade® Innovin®
(6.0 - 149.0% of norm)	2.01 - 2.81	2.58 – 3.56	2.23 - 3.31	2.57 - 3.59
Protein C with
Protein C Reagent
(10.1 - 131.0% of norm)	2.78 - 4.55	2.36 - 3.83	3.47 - 7.49	3.47 - 5.85
Protein C with
Berichrom® Protein C
(10.0 - 138.0% of norm)	1.40 - 5.91	1.40 - 5.18	1.70 - 5.26	2.19 - 5.69

Detection Capability Results 7.3

Sysmex® CS-2100i: Summary of Limit of Quantitation Studies
Application	Lower Limit of
Clinically
Reportable
Range
(% of norm)	Measured Limit
of Quantitation
based on
predicate
(% of norm)	Maximum
Total Error
(% of norm)
Coagulation Factor V with Dade®
Innovin®	6.0	4.80	2.04
Coagulation Factor VII with
Dade® Innovin®	6.0	3.39	0.21
Protein C with
Protein C Reagent	10.1	9.35	3.62
Protein C with
Berichrom® Protein C	10.0	8.32	2.07

Linearity & Measuring Range 7.4

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-2100i: Reference Interval Summary Table
Application	N	Sysmex® CS-2100i Reference Interval
(5th Percentile of norm)
Coagulation Factor V with
Dade® Innovin®	193	79.8%
Coagulation Factor VII with
Dade® Innovin®	193	65.6%
Protein C with
Protein C Reagent	193	75.6%
Protein C with
Berichrom® Protein C	191	84.9%

8 Conclusions

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-2100i 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.