Predicate Devices

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 its associated reagents. There is no mention of AI, ML, or any related technologies in the device description, intended use, or performance studies. The analysis methods described are traditional laboratory techniques (clotting, chromogenic, immunoassay).

Therapeutic

No
The device is an in vitro diagnostic (IVD) analyzer used to measure coagulation parameters in blood samples, which aids in diagnosis rather than directly treating a condition.

Diagnostic

Yes

The "Intended Use / Indications for Use" explicitly states that the Sysmex CS-2100i is "intended for in vitro diagnostic use" to analyze various coagulation parameters in blood samples, which are used to aid in diagnosis.

SaMD (Software as a Medical Device)

No

The device description explicitly states it is an "automated blood coagulation instrument" and mentions hardware components like the Information Processing Unit (IPU) screen and external printers. The 510(k) is for reagent applications used on this instrument, not the software of the instrument itself as a standalone medical device.

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 using plasma collected from venous blood samples..."

This statement clearly indicates that the device is designed to be used outside of the body to examine specimens (blood plasma in this case) for diagnostic purposes.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

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
Antithrombin (AT) with INNOVANCE® Antithrombin
D-dimer with INNOVANCE® D-Dimer.

The performance of this device has not been established in neonate and pediatric patient populations.

Product codes (comma separated list FDA assigned to the subject device)

JPA

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
Consumable materials

The subject of this 510(k) notification are reagent applications which perform the coagulation tests Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®; Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL; Fibrinogen (Fbg) with Dade® Thrombin Reagent; Antithrombin (AT) with INNOVANCE® Antithrombin; and D-dimer with INNOVANCE® D-Dimer. 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

clinical central/hospital laboratory.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Method comparison studies: designed according to EP09-A3 CLSI Guideline "Measurement Procedure Comparison and Bias Estimation Using Patient Samples" were conducted at three external sites in the United States, all sites using the same protocols. Samples were measured on both the predicate device (Sysmex CA-1500) as well as the new device (Sysmex CS-2100i), in random order as 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 pre-established acceptance criteria. The summary of Passing-Bablok regression showed that the proposed and predicate devices provide equivalent results when used in a clinical setting. Sample sizes per site for different applications ranged from 95 to 215.

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 was varied so as not to add 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) variability were calculated.

Detection Capability Results: Detection capability studies were measured for the calibrated assays on the Sysmex CS-2100i: Fibrinogen with Dade® Thrombin Reagent, Antithrombin with INNOVANCE® Antithrombin, and D-dimer with INNOVANCE® D-Dimer. Studies were conducted following the description in CLSI document EP17-A2 'Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures'. All reagents met the pre-determined acceptance criteria and support the lower limit of the clinical reportable range claim.

Linearity & Measuring Range: Linearity studies were performed for the calibrated assays on the Sysmex CS-2100i: Fibrinogen with Dade® Thrombin Reagent, Antithrombin with INNOVANCE® Antithrombin, and D-dimer with INNOVANCE® D-Dimer. All reagents met the pre-determined acceptance criteria and support the clinical 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.

D-Dimer PE Exclusion Validation Study: The INNOVANCE® D-Dimer assay was evaluated on the Sysmex CS-2100i in a multi-center study to validate the exclusion of Pulmonary Embolism (PE) using frozen specimens collected prospectively from 1930 consecutive outpatients presenting to the emergency or ambulatory department with suspected PE. 96 patients were excluded, resulting in 1834 patients initially considered. Patients with a high PTP score for PE were excluded from enrollment. Patients with no or a positive D-dimer result were evaluated by imaging. Patients with a negative D-dimer result underwent imaging at the physician's discretion. Patients with unobtainable follow-up data were excluded, resulting in n=1467 patients available for final analysis. The overall prevalence of PE in the 1467 patients was 6.9 %. The specimens were tested with the INNOVANCE® D-Dimer assay and results were compared to a cut-off value of 0.50 mg/L FEU. A D-dimer result

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

0

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

January 26, 2016

Siemens Healthcare Diagnostics Products GmbH Mr. Nils Neumann Regulatory Manager, US Affairs Emil-von-Behring-Str. 76 35041 Marburg, Germany

Re: K151259

Trade/Device Name: Sysmex CS-2100i Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: JPA Dated: December 24, 2015 Received: December 28, 2015

Dear Mr. Neumann:

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, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21

1

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 vours.

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

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K151259

Device Name Sysmex CS-2100i

Indications for Use (Describe)

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
Antithrombin (AT) with INNOVANCE® Antithrombin
· D-dimer with INNOVANCE® D-Dimer.

The performance of this device has not been established in neonate and pediatric patient populations.

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)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

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510(k) Summary

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of 21 CFR §807.92 and follows the FDA guidance "The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]", issued July 28, 2014.

1. Submitter

Siemens Healthcare Diagnostics Products GmbH Emil-von-Behring-Str. 76 35041 Marburg, Germany Contact Person: Nils Neumann Email: neumann.nils@siemens.com Phone: + 49 6421 39 7133 Facsimile: + 49 6421 39 4977 Date Prepared: January 14, 2016 2. Device

Name of Device:	Sysmex CS-2100i
Common or Usual Name:	Automated Coagulation Instrument
Classification Name:	Multipurpose system for in vitro coagulation studies (21 CFR
864.5425)
Regulatory Class:	2
Product Code:	JPA
510(k) Review Panel:	Hematology

3. Predicate Device

Name of Device:	Sysmex CA-1500 (K011235)
Common or Usual Name:	Automated Coagulation Instrument
Classification Name:	Multipurpose system for in vitro coagulation studies (21 CFR
864.5425)
Regulatory Class:	2
Product Code:	JPA
510(k) Review Panel:	Hematology

The predicate has not been subject to a design-related recall for any of the applications associated with this Premarket Notification. No reference devices were used in this submission.

4. Device Description / Test Principle

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:

510(k) Summary K151259 Sysmex CS-2100i

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Reagents I
Controls
트 Calibrators
트 Consumable materials

The subject of this 510(k) notification are reagent applications which perform the coagulation tests Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®; Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL; Fibrinogen (Fbg) with Dade® Thrombin Reagent; Antithrombin (AT) with INNOVANCE® Antithrombin; and D-dimer with INNOVANCE® D-Dimer. 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®	PT, Prothrombin Time (seconds)	Clotting (extrinsic pathway)
Dade® Innovin®	PT, Prothrombin Time (INR)	Clotting, calculated
Dade® Actin® FSL	APTT, Activated Partial Thromboplastin Time	Clotting (intrinsic pathway)
Dade® Thrombin Reagent	Fibrinogen quantitation	Clotting (common pathway)
INNOVANCE® Antithrombin	Antithrombin quantitation	Chromogenic
INNOVANCE® D-Dimer	D-dimer quantitation	Immunochemical

The intended Environment of Use is a clinical central/hospital laboratory.

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Instrument (main unit)

Image /page/6/Figure/2 description: This image is a line drawing of a piece of equipment with multiple labeled parts. The labels are numbers 1 through 9 and point to different parts of the machine. The machine 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.

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Informational Processing Unit (IPU)

Image /page/7/Figure/2 description: The image shows a desktop computer setup with four labeled components. Label (1) points to the computer monitor, which is rectangular and sits atop a stand. Label (2) points to the computer case, which is a rectangular box that sits below the monitor. Label (3) points to the keyboard, which is a standard QWERTY keyboard. Label (4) points to the computer mouse, which is a standard two-button 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.

(3) Keyboard: Used to operate the IPU together with the touch panel.

(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.

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: Sampler or STAT holder are taken into the instrument for each analysis through a secondary dispensing sample probe. When measurements are to be

8

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-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:

I Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®
트 Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
Fibrinogen (Fbq) with Dade® Thrombin Reagent l
Antithrombin (AT) with INNOVANCE® Antithrombin
D-dimer with INNOVANCE® D-Dimer.

The performance of this device has not been established in neonate and pediatric patient populations.

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:

Similarities between Sysmex CS-2100i and Sysmex CA-1500
Analyzer Component	Proposed Device
Sysmex CS-2100i	Predicate Device
Sysmex CA-1500
Regulatory
Classification	JPA Class 2
System, Multipurpose for in vitro
coagulation studies	Same
Sample Type	Human plasma,
3.2% sodium citrate	Same
Applications	Clotting Applications:
Prothrombin Time (PT) with Dade®
Innovin®;
Activated Partial Thromboplastin
Time (APTT) with Dade® Actin®
FSL	Same
Similarities between Sysmex CS-2100i and Sysmex CA-1500
Analyzer Component	Proposed Device
Sysmex CS-2100i	Predicate Device
Sysmex CA-1500
	Fibrinogen (Clauss) with Dade®
Thrombin Reagent
	Chromogenic Application:
Antithrombin with INNOVANCE®
Antithrombin	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	Same
	D-dimer with
INNOVANCE® D-Dimer
0.19 to 35.2 mg/L FEU	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
Sample Volumes in
Normal Mode	PT with Dade® Innovin® 50 μL
APTT with Dade® Actin® FSL 50 μL
Fibrinogen with Dade® Thrombin	Same
Similarities between Sysmex CS-2100i and Sysmex CA-1500
Analyzer Component	Proposed Device
Sysmex CS-2100i	Predicate Device
Sysmex CA-1500
	Reagent 10 μL
	Antithrombin with INNOVANCE®
Antithrombin 10 µL
	D-dimer with INNOVANCE® D-
Dimer 13 µL
	PT with Dade® Innovin® 50 μL
Sample Volumes in
Micro Mode (Plasma)	APTT with Dade® Actin® FSL 50 μL	Same
	Fibrinogen with Dade® Thrombin
Reagent 10 μL
Rinse & Buffer
Solutions
• On-board	• CA-CLEAN I
• CA-CLEAN II
• Dade Owren's Buffer	• Same
• Same
• Same
• External	• Water	• Same
Light Source
Chromogenic	Halogen Lamp	Same
Immuno-chemical	Halogen Lamp	Same
Probes	1 Sample probe;
1 Reagent probe	1 Sample probe;
1 Reagent probe
Wavelengths used in
Analysis	Antithrombin with INNOVANCE®
Antithrombin (405 nm)	Same
Temperature Control	Sample incubation well: 37°C ±
1.0°C	Same
Analyzer Component	Proposed Device
Sysmex CS-2100i	Predicate Device
Sysmex CA-1500
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 Antithrombin (AT) with
INNOVANCE® Antithrombin D-dimer with INNOVANCE® D-
Dimer The performance of this device
has not been established in
neonate and pediatric patient
populations. | 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 Prameters:
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 |
| Differences between Sysmex CS-2100i and Sysmex CA-1500 | | |
| Analyzer Component | Proposed Device
Sysmex CS-2100i | Predicate Device
Sysmex CA-1500 |
| Clinical Reportable
Range | | |
| PT with Dade® Innovin® | 8.7 – 90.0 seconds
0.93 – 8.00 INR | 8.7 to 148.7 seconds
0.80 to13.90 INR |
| APTT with
Dade® Actin® FSL | 20.0 - 139.0 seconds | 17.2 to 153.4 seconds |
| 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. | Rate of change of optical
density 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
applications. | Optical Density at 405, 575, or
800 nm |
| Differences between Sysmex CS-2100i and Sysmex CA-1500 | | |
| Analyzer Component | Proposed Device
Sysmex CS-2100i | 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. | PT (seconds) Dade® Innovin®
(Default = 660 nm; Sub-
Wavelength= 800 nm)

PT (INR) with Dade® Innovin®
(Default = 660 nm; Sub-
Wavelength= 800 nm)

APTT with Dade® Actin® FSL
Activated PTT Reagent (Default =
660 nm; Sub-Wavelength= 800
nm)

Fibrinogen with Dade® Thrombin
Reagent (Default = 405 nm; Sub-
Wavelength= none)

D-dimer with INNOVANCE® D-
Dimer (Default = 660 nm; Sub-
Wavelength= none) | 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=
none)

Fibrinogen with Dade®
Thrombin (Default = 660 nm;
Sub-Wavelength= none)

-Reagent probe :
37.5 °C ± 0.5 °C | -Detector: 37°C ± 1.0°C

-Reagent incubation probe:
37°C ± 1.0°C |
| Reagent Cooling | 10°C ± 2°C, when ambient
temperature is 20°C - 28°C.
During operation 4°C -15°C,
when ambient temperature is
15°C – 30°C | 15°C ± 2°C, when ambient
temperature is 15°C – 30°C |
| Pipetting Capabilities | Reagent probe:
20 – 200 μL

Sample probe:
4 – 270 μL | Reagent probe:
3 – 200 μL

Sample probe:
5 - 450 μL |

9

10

11

There are no technological differences between the subject and predicate devices. However the following minor changes exist between the subject and predicate devices:

12

13

14

Differences between Sysmex CS-2100i and Sysmex CA-1500
Analyzer Component	Proposed Device
Sysmex CS-2100i	Predicate Device
Sysmex CA-1500
Sample Volumes in
Micro Mode	Antithrombin with INNOVANCE®
Antithrombin 14 µL

D-dimer with INNOVANCE® D-
Dimer 15 µL | Antithrombin with
INNOVANCE® Antithrombin 10 µL

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

Method comparison studies designed according to EP09-A3 CLSI Guideline "Measurement Procedure Comparison and Bias Estimation Using Patient Samples" were conducted at three external sites in the United States, all sites using the same protocols.

Samples were measured on both the predicate device (Sysmex CA-1500) as well as the new device (Sysmex CS-2100i), in random order as 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 pre-established 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.

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Sysmex CS-2100i: Method Comparison Summary Table, Passing-Bablok regression
Application
(Clinical Reportable
Range)	Site 01	Site 02	Site 03	Sites Combined
Prothrombin Time
with Dade®
Innovin®
(8.7 -90.0
seconds)	n=120
y = 1.000x +
0.200
r = 0.997	n=215
y = 1.000x +
0.000
r = 0.999	n=125
y = 0.985x +
0.299
r = 1.000	n=460
y = 1.000x +
0.000
r = 0.999
Prothrombin Time
(INR) with Dade®
Innovin® (0.93 –
8.00 INR)	n=117
y = 1.045x -
0.037
r = 0.996	n=213
y = 1.026 x -
0.037
r = 0.999	n=124
y = 1.040x -
0.030
r = 1.000	n=454
y = 1.047x -
0.052
r = 0.999
Activated Partial
Thromboplastin
Time with Dade®
Actin® FSL
(20.0 - 139.0
seconds)	n=119
y = 1.083x -
2.242
r = 0.994	n=211
y = 1.055x -
1.829
r = 0.996	n=102
y = 1.079x -
2.147
r = 0.998	n=432
y = 1.077x -
2.305
r = 0.996
Fibrinogen
quantitation with
Dade® Thrombin
Reagent
(50 – 860 mg/dL)	n=146
y = 1.053x +
0.112
r = 0.996	n=95
y = 1.064x -
3.587
r = 0.997	n=115
y = 0.984x -
0.520
r = 0.995	n=356
y=1.048x -
4.417
r = 0.994
Antithrombin
quantitation with
INNOVANCE®
Antithrombin
(9.0 - 128.0% of
norm)	n=135
y = 0.978x -
0.196
r = 0.993	n=120
y = 0.972x +
2.517
r = 0.994	n=117
y = 0.975x +
0.843
r = 0.995	n=372
y = 0.970x +
1.321
r = 0.994
D-dimer
quantitation with
INNOVANCE® D-
Dimer (0.19 - 35.20
mg/L FEU¹)	n=129
y = 1.031x +
0.005
r = 0.999	n=112
y = 0.967x -
0.021
r = 0.998	n=108
y = 0.982x +
0.017
r = 0.998	n=349
y = 0.982x +
0.015
r = 0.997

1 D-dimer results are reported in fibrinogen equivalent units (FEU).

16

7.2 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 was varied so as not to add 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) variability were calculated. The data for normal mode are summarized in the following tables.

Sysmex CS-2100i: Reproducibility Summary Table, Within Run
Application
(CRR/ Clotting time
range)	Sample Range
(mean of all
sites)	Site 01
Within
Run (%
CV)	Site 02
Within
Run (%
CV)	Site 03
Within
Run (%
CV)	Sites
Combined
(% CV)
Prothrombin Time
using Dade® Innovin®
(8.7 - 90.0 seconds)	9.23 - 78.94
seconds	0.55 – 2.21	0.63 – 1.94	0.66 - 1.79	0.62 – 1.87
Prothrombin Time
(INR) using Dade®
Innovin® (0.93 – 8.00
INR)	1.016 - 7.658
INR	0.45 – 2.83	0.40 - 1.53	0.60 - 1.57	0.49 – 2.02
Activated Partial
Thromboplastin Time
using Dade® Actin®
FSL
(20.0 - 139.0 seconds)	22.10 - 127.52
seconds	0.81 – 4.51	0.73 - 3.98	0.85 - 2.88	0.87 – 3.99
Fibrinogen
quantitation using
Dade® Thrombin
Reagent
(50 – 860 mg/dL)	55.9 - 738.5
mg/dL	1.19 – 3.99	1.41 - 5.14	1.44 – 4.60	1.44 – 4.60
Antithrombin
quantitation using
INNOVANCE®
Antithrombin
(9.0 – 128.0% of norm)	11.39 - 121.05%
of norm	1.18 – 4.36	1.31 - 4.55	1.44 – 4.63	1.51 – 4.53
D-dimer quantitation
using INNOVANCE®
D-Dimer (0.19 - 35.20
mg/L FEU)	0.258 - 31.767
mg/L FEU	2.00 – 3.51	2.25 – 4.62	2.00 – 5.11	2.15 – 4.06

17

Sysmex CS-2100i: Reproducibility Summary Table, Between Run
Application
(CRR / Clotting
time range)	Sample Range
(mean of all
sites)	Site 01
Between
Run (% CV)	Site 02
Between
Run (% CV)	Site 03
Between
Run (% CV)	Sites
Combined
(% CV)
Prothrombin
Time using Dade®
Innovin®
(8.7 – 90.0 sec)	9.23–78.94
seconds	0.24 - 2.37	0.00 - 2.09	0.00 - 2.46	0.00 - 2.00
Prothrombin
Time (INR) using
Dade® Innovin®
(0.93 – 8.00 INR)	1.016 – 7.658
INR	0.00 - 2.19	0.00 - 1.35	0.54 - 1.75	0.46 - 1.84
Activated Partial
Thromboplastin
Time using Dade®
Actin® FSL
(20.0 – 139.0 sec)	22.10 - 127.52
seconds	0.00 - 3.23	0.00 - 1.47	0.33 - 3.47	0.00 - 3.18
Fibrinogen
quantitation using
Dade® Thrombin
Reagent
(50 – 860 mg/dL)	55.9 - 738.5
mg/dL	0.00 - 0.87	0.00 - 1.60	0.00 - 1.56	0.00 - 0.95
Antithrombin
quantitation using
INNOVANCE®
Antithrombin
(9.0 – 128.0% of
norm)	11.39 - 121.05
% of norm	0.00 - 4.59	0.00 - 3.49	0.00 - 2.80	0.27 - 3.51
D-dimer
quantitation using
INNOVANCE® D-
Dimer (0.19 –
35.20 mg/L FEU)	0.258 – 31.767
mg/L FEU	0.00 - 2.92	0.00 - 1.57	0.00 - 2.81	0.00 - 2.36

18

Sysmex CS-2100i: Reproducibility Summary Table, Between Day
Application
(CRR / Clotting
time range)	Sample Range
(mean of all
sites)	Site 01
Between
Day (% CV)	Site 02
Between
Day (% CV)	Site 03
Between
Day (% CV)	Sites
Combined
(% CV)
Prothrombin
Time using Dade®
Innovin®
(8.7 – 90.0 sec)	9.23– 78.94
seconds	0.00 – 1.59	0.00 – 1.91	0.00 – 2.93	0.32 – 1.87
Prothrombin
Time (INR) using
Dade® Innovin®
(0.93 – 8.00 INR)	1.016 – 7.658
INR	0.00 – 2.41	0.00 – 2.24	0.30 – 2.85	0.17 – 1.77
Activated Partial
Thromboplastin
Time using Dade®
Actin® FSL
(20.0 – 139.0 sec)	22.10 – 127.52
seconds	0.15 – 3.53	0.03 – 2.25	0.00 – 2.05	0.32 – 1.54
Fibrinogen
quantitation using
Dade® Thrombin
Reagent
(50 – 860 mg/dL)	55.9 – 738.5
mg/dL	1.10 – 2.39	0.00 – 0.71	0.00 – 0.99	0.00 – 1.44
Antithrombin
quantitation using
INNOVANCE®
Antithrombin
(9.0 – 128.0% of
norm)	11.39 –
121.05% of
norm	0.00 – 1.58	0.00 – 0.77	0.00 – 1.54	0.00 – 1.06
D-dimer
quantitation using
INNOVANCE® D-
Dimer (0.19 –
35.20 mg/L FEU)	0.258 – 31.767
mg/L FEU	0.00 – 4.63	0.00 – 2.16	0.00 – 4.39	0.62 – 3.22

19

Sysmex CS-2100i: Reproducibility Summary Table, Total CV (Within Site)
Application
(CRR / Clotting
time range)	Sample Range
(mean of all
sites)	Site 01
(% CV)	Site 02
(% CV)	Site 03
(% CV)	Sites
Combined
(% CV)
Prothrombin Time
using Dade®
Innovin®
(8.7 – 90.0 sec)	9.23 – 78.94
seconds	0.92 – 3.30	0.71 – 2.74	0.96 – 3.33	1.01 – 2.95
Prothrombin Time
(INR) using Dade®
Innovin® (0.93 –
8.00 INR)	1.016 – 7.658
INR	0.78 – 4.05	0.42 – 2.71	0.87 – 3.24	0.76 – 2.98
Activated Partial
Thromboplastin
Time using Dade®
Actin® FSL
(20.0 – 139.0 sec)	22.10 – 127.52
seconds	1.01 – 6.57	0.78 – 4.80	0.98 – 4.51	0.96 – 6.58
Fibrinogen
quantitation using
Dade® Thrombin
Reagent
(50 – 860 mg/dL)	55.9 – 738.5
mg/dL	2.05 – 4.14	1.55 – 5.23	1.47 – 4.86	1.98 – 4.62
Antithrombin
quantitation using
INNOVANCE®
Antithrombin
(9.0 – 128.0% of
norm)	11.39 – 121.05 %
of norm	1.34 – 6.33	1.54 – 5.74	1.95 – 5.38	2.79 – 7.24
D-dimer
quantitation using
INNOVANCE® D-
Dimer (0.19 – 35.20
mg/L FEU)	0.258 – 31.767
mg/L FEU	2.78 – 6.50	2.66 – 5.10	3.02 – 5.95	2.90 – 6.55

20

Sysmex CS-2100i: Reproducibility Summary Table, Site-to-Site
Application
(CRR / Clotting time range)	Sample Range
(mean of all sites)	Between
Sites (%CV)
Prothrombin Time using
Dade® Innovin®
(8.7 – 90.0 sec)	9.23–78.94
seconds	0.00 - 0.70
Prothrombin Time (INR) using
Dade® Innovin® (0.93 – 8.00
INR)	1.02 – 7.66
INR	0.00 - 0.88
Activated Partial
Thromboplastin Time using
Dade® Actin® FSL
(20.0 - 139.0 sec)	22.10 - 127.52
seconds	0.11 - 3.86
Fibrinogen quantitation using
Dade® Thrombin Reagent
(50 - 860 mg/dL)	55.9 - 738.5 mg/dL	0.00 - 2.05
Antithrombin quantitation
using INNOVANCE®
Antithrombin
(9.0- 128.0% of norm)	11.39 - 121.05%
of norm	2.00 - 4.43
D-dimer quantitation using
INNOVANCE® D-Dimer (0.19 –
35.20 mg/L FEU)	0.26 – 31.77 mg/L
FEU	0.00 - 3.99

7.3 Detection Capability Results

Detection capability studies were measured for the calibrated assays on the Sysmex CS-2100i: Fibrinogen with Dade® Thrombin Reagent, Antithrombin with INNOVANCE® Antithrombin, and Ddimer with INNOVANCE® D-Dimer. Studies were conducted following the description in CLSI document EP17-A2 'Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures'. All reagents met the pre-determined acceptance criteria and support the lower limit of the clinical reportable range claim.

21

Sysmex CS-2100i: Summary of Limit of Quantitation
Reagent	Lower Limit of
Clinical Reportable
Range	Measured Limit
of Quantitation	Maximum Total
Error (%)
Result
Fibrinogen quantitation
with Dade® Thrombin
Reagent	50.0 mg/dL	46.1 mg/dL	14.83%
Antithrombin quantitation
with INNOVANCE®
Antithrombin	9.0% of norm	8.78% of norm	26.17%
D-dimer quantitation with
INNOVANCE® D-Dimer	0.19 mg/L FEU	0.15 mg/L FEU	40.40%

The Sysmex CS-2100i performs tests with three non-calibrated test applications: PT seconds with Dade® Innovin®, PT INR with Dade® Innovin®, and APTT with Dade® Actin® FSL Activated PTT Reagent. There is no detection limit for these reagents and the measuring interval is set at the lower end of the measurement interval by a software setting.

7.4 Linearity & Measuring Range

Linearity studies were performed for the following calibrated assays on the Sysmex CS-2100i: Fibrinogen with Dade® Thrombin Reagent, Antithrombin with INNOVANCE® Antithrombin, and D-dimer with INNOVANCE® D-Dimer. All reagents met the pre-determined acceptance criteria and support the clinical reportable range claim. The Sysmex CS-2100i performs tests with three non-calibrated test applications: PT seconds with Dade® Innovin®, PT INR with Dade® Innovin®, and APTT with Dade® Actin® FSL. Linearity testing is not applicable to non-calibrated assays. Studies were conducted as described in CLSI EP6-A "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach".

22

Sysmex CS-2100i: Summary of Linearity and Measuring Range
Reagent	Measured Linear Range	Clinical Reportable Range
Prothrombin Time
(seconds) with Dade®
Innovin®	Not applicable	8.7 to 90.0 seconds
Prothrombin Time (INR)
with Dade® Innovin®	Not applicable	0.93 to 8.00 INR
Activated Partial
Thromboplastin Time
(seconds) with Dade®
Actin® FSL	Not applicable	20.0 to 139.0 seconds
Fibrinogen quantitation
(mg/dL) with Dade®
Thrombin Reagent	40.3 to 1124.0 mg/dL	50 to 860 mg/dL
Antithrombin quantitation
(% of norm) with
INNOVANCE® Antithrombin	6.28 to 152.30% of norm	9.0 to 128.0% of norm
D-dimer quantitation (mg/L
FEU) with INNOVANCE® D-
Dimer	0.15 to 50.86 mg/L FEU	0.19 to 35.20 mg/L FEU

7.5 Reference Interval

Reference interval studies were conducted at three clinical study sites in the United States. The summary is provided below.

| Application | Sysmex CS-2100i Reference
Interval |
|---------------------------------------------------------------------------|---------------------------------------|
| Prothrombin Time (seconds) using Dade®
Innovin® | 2.5th – 97.5th perc.
9.5 – 12.1 |
| Prothrombin Time (INR) using Dade®
Innovin® | 2.5th – 97.5th perc.
0.93 – 1.15 |
| Activated Partial Thromboplastin Time
(seconds) using Dade® Actin® FSL | 2.5th – 97.5th perc.
23.9 – 30.7 |

23

| Application | Sysmex CS-2100i Reference
Interval |
|------------------------------------------------------------------------|---------------------------------------|
| Fibrinogen quantitation using Dade®
Thrombin Reagent (mg/dL) | 2.5th – 97.5th perc.
187 – 446 |
| Antithrombin quantitation using
INNOVANCE® Antithrombin (% of norm) | 2.5th – 97.5th perc.
79.2 – 125.3 |
| D-dimer quantitation using INNOVANCE®
D-Dimer (mg/L FEU) | 2.5th – 97.5th perc.