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
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.

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, and 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.

AI/ML Overview

Here's an analysis of the acceptance criteria and the studies performed for the Sysmex CS-5100 device, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values for most of the performance metrics within the tables. Instead, it states that "Results from each application met the pre-established acceptance criteria" for method comparison, and "The data for all tested reagents met the pre-determined acceptance criteria" for detection capability. For linearity, it states "All reagents met the pre-determined acceptance criteria."

However, we can infer some implied criteria based on the reported values alongside statements of acceptance, especially for Method Comparison, Reproducibility, Detection Capability, and the D-Dimer PE Exclusion Study. For the D-Dimer study, specific lower bounds for 95% LCL are provided for sensitivity and NPV, which act as de facto acceptance criteria.

Inferred Acceptance Criteria and Reported Performance for Sysmex CS-5100:

Study Category	Performance Metric	Inferred Acceptance Criteria	Reported Device Performance
Method Comparison	*Passing-Bablok Regression (y = ax + b, r)**	Slope (a) close to 1, Intercept (b) close to 0, Correlation coefficient (r) close to 1 (indicating strong agreement with predicate). The document states "Results from each application met the pre-established acceptance criteria."	Prothrombin Time (seconds) with Dade® Innovin®: n=469 (combined), y = 1.000x + 0.100, r = 0.998 Prothrombin Time (INR) with Dade® Innovin®: n=465 (combined), y = 1.047x - 0.047, r = 0.999 Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL: n=466 (combined), y = 1.026x - 1.315, r = 0.996 Fibrinogen quantitation with Dade® Thrombin Reagent: n=368 (combined), y = 1.018x + 4.633, r = 0.995 Antithrombin quantitation with INNOVANCE® Antithrombin: n=381 (combined), y = 0.980x + 0.222, r = 0.996 D-dimer quantitation with INNOVANCE® D-Dimer: n=361 (combined), y = 1.021x - 0.007, r = 0.996
Reproducibility	Within Run %CV, Between Run %CV, Between Day %CV, Site-to-Site %CV, Total CV (Within Site)	%CVs within acceptable limits for laboratory assays (e.g., typically < 10-20% depending on the assay and concentration). The document states "The data is summarized in the following tables." implying compliance with pre-established criteria.	Prothrombin Time (seconds): Total %CV (Within Site, Sites Combined) 0.86 – 2.95 Prothrombin Time (INR): Total %CV (Within Site, Sites Combined) 0.72 – 2.96 APTT: Total %CV (Within Site, Sites Combined) 1.00 – 7.45 Fibrinogen: Total %CV (Within Site, Sites Combined) 2.08 – 4.33 Antithrombin: Total %CV (Within Site, Sites Combined) 1.81 – 5.64 D-dimer: Total %CV (Within Site, Sites Combined) 2.05 – 5.51 (Ranges indicating performance across different sample ranges)
Detection Capability	Measured Limit of Quantitation (LoQ) vs. Lower Limit of Clinical Reportable Range (CRR) and Maximum Total Error (%)	Measured LoQ should be less than or equal to the Lower Limit of CRR. Maximum Total Error (%) within acceptable limits (e.g., often < 30% for LoQ). The document states "Data for all tested reagents met the pre-determined acceptance criteria and support the lower limit of the clinical reportable range claim."	Fibrinogen: CRR = 50 mg/dL, Measured LoQ = 46.1 mg/dL, Max Total Error = 16.66% Antithrombin: CRR = 9.0% of norm, Measured LoQ = 8.783% of norm, Max Total Error = 27.34% D-dimer: CRR = 0.19 mg/L FEU, Measured LoQ = 0.146 mg/L FEU, Max Total Error = 31.76%
Linearity & Measuring Range	Measured Linear Range should encompass or exceed Clinical Reportable Range.	Measured Linear Range should encompass or exceed the Clinical Reportable Range. The document states "All reagents met the pre-determined acceptance criteria and support the clinical reportable range claim."	Fibrinogen: Measured Linear Range = 40.300 to 1124.000 mg/dL, CRR = 50 to 860 mg/dL Antithrombin: Measured Linear Range = 6.280 to 152.300% of norm, CRR = 9.0 to 128.0% of norm D-dimer: Measured Linear Range = 0.149 to 50.862 mg/L FEU, CRR = 0.19 to 35.20 mg/L FEU
D-Dimer PE Exclusion Validation Study (0.50 mg/L FEU cut-off)	Sensitivity % (95% LCL), Negative Predictive Value (NPV) % (95% LCL)	High sensitivity and NPV required for PE exclusion. Specific criteria are implied by the reported 95% LCLs. For combined US and OUS data: Sensitivity 95% LCL > 93.0%; NPV 95% LCL > 99.0% (for non-standardized); NPV* 95% LCL > 97.7% (for standardized to 15% prevalence).	US and OUS Combined Data (n=1467): Sensitivity % = 98.0 (95% LCL= 93.0) Specificity % = 54.5 (95% LCL= 51.9) NPV % = 99.7 (95% LCL= 99.0) NPV % (standardized to 15% prevalence) = 99.4* (95% LCL= 97.7) PPV % = 13.8 (95% LCL= 11.4) PPV % (standardized to 15% prevalence) = 27.6* (95% LCL= 23.5)

2. Sample Size Used for the Test Set and Data Provenance

Method Comparison:
- Sample Sizes:
  - PT (seconds): n=469 (combined from 3 sites: n=125, n=209, n=135)
  - PT (INR): n=465 (combined from 3 sites: n=122, n=208, n=135)
  - APTT: n=466 (combined from 3 sites: n=126, n=210, n=130)
  - Fibrinogen: n=368 (combined from 3 sites: n=145, n=91, n=132)
  - Antithrombin: n=381 (combined from 3 sites: n=135, n=120, n=126)
  - D-dimer: n=361 (combined from 3 sites: n=137, n=108, n=116)
- Data Provenance: Conducted at three external sites in the United States (US). The samples were patient samples.
Reproducibility Studies:
- Sample Sizes: Not explicitly stated as 'n=' count for each sample tested, but refers to "Sample Range (mean of all sites)" for each application. These studies involved "two runs per day, with two replicates per run, at each of the three sites". Given the "20-day precision studies", this implies a significant number of measurements for each sample type.
- Data Provenance: Two external sites in Germany and one external site in the United States.
Detection Capability Studies:
- Sample Sizes: Not explicitly stated, but performed for specific reagents: Fibrinogen, Antithrombin, and D-dimer.
- Data Provenance: Not explicitly stated, but typically in vitro studies.
Linearity & Measuring Range Studies:
- Sample Sizes: Not explicitly stated, but performed for Fibrinogen, Antithrombin, and D-dimer.
- Data Provenance: Not explicitly stated, but typically in vitro studies.
Reference Interval Studies:
- Sample Sizes: Not explicitly stated as a number, but indicates the study population "did not include neonate and pediatric sample populations".
- Data Provenance: Conducted at three clinical study sites in the United States.
D-Dimer PE Exclusion Validation Study:
- Initial Patients: 1930 consecutive outpatients.
- Excluded Patients: 96.
- Patients for Final Analysis: n=1467 (US: n=1424, OUS: n=43).
- Data Provenance: Multi-center study using frozen specimens collected prospectively from outpatients presenting to emergency or ambulatory departments with suspected PE. Data from both the US and "OUS" (Outside US, specifically European population for prevalence) were included.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts

For Method Comparison, Reproducibility, Detection Capability, Linearity, and Reference Intervals: The ground truth for these analytical performance studies is established by the methods themselves, often comparing the device to a reference method or evaluating inherent precision characteristics against statistical benchmarks. No human experts are described for establishing ground truth in these sections.
For D-Dimer PE Exclusion Validation Study:
- Ground Truth Establishment: The ground truth for PE diagnosis was established through imaging methods (e.g., spiral CT and/or VO scan) and 3-month follow-up for patients with initial negative diagnosis.
- Number/Qualifications of Experts: The document mentions "physician's discretion" for imaging and that "All potentially eligible patients were evaluated using the Wells' rules...". This implies that medical professionals (e.g., emergency physicians, radiologists, other clinicians) were involved in the diagnosis and follow-up, but the specific number and detailed qualifications of these individual experts are not provided.

4. Adjudication Method for the Test Set

For Method Comparison, Reproducibility, Detection Capability, Linearity, and Reference Intervals: No adjudication method as typically understood for human interpretation of data (e.g., 2+1 rule) is described. These are analytical performance studies where results are quantitative values compared against other instruments or statistical metrics.
For D-Dimer PE Exclusion Validation Study: The ground truth involved a combination of imaging and 3-month follow-up. While a final diagnosis would likely involve a consensus among the treating clinicians or specialists (e.g., radiologists, internists), no explicit "adjudication method" (like multiple readers reaching a consensus on an image) is described for the final PE diagnosis. The process relies on standard clinical diagnostic pathways and follow-up.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, an MRMC comparative effectiveness study involving human readers with/without AI assistance was not done. The Sysmex CS-5100 is an automated blood coagulation analyzer, not an AI-powered diagnostic imaging tool that assists human readers. The studies focus on the analytical performance of the instrument itself and its diagnostic utility (e.g., D-dimer for PE exclusion).

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the studies described are standalone performance evaluations of the device (or algorithm if you consider the reagent-instrument combination an 'algorithm') in an automated setting. The device operates automatically, and the performance data (method comparison, reproducibility, detection capability, linearity, D-dimer PE exclusion) reflect its direct analytical output without direct human interpretation influencing the measurement itself at the point of testing. Human input is involved in sample collection, entering patient data, and clinical interpretation of the results, but not in the "reading" of the output in a way that an AI for image analysis would be 'standalone'.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

For Method Comparison: The ground truth is the result from the predicate device (Sysmex CA-1500), which is a legally marketed device for the same intended use.
For D-Dimer PE Exclusion Validation Study: The ground truth for the presence or absence of PE was based on a combination of imaging methods (e.g., spiral CT and/or VO scan) and 3-month clinical outcomes data (follow-up) to confirm the absence of PE in initially negative cases.

8. The sample size for the training set

The document describes premarket notification for a medical device (instrument), not an AI/ML algorithm that typically requires a distinct training set for model development and a test set for performance evaluation. For this type of device, the "training" analogous to an AI model would be the internal development and calibration of the instrument by the manufacturer using their own data, which is not typically detailed in a 510(k) summary in terms of "training set sample size." The studies presented are all performance validations of the final device. Therefore, a specific "training set sample size" is not applicable/provided in this context.

9. How the ground truth for the training set was established

As there is no "training set" described in the context of an AI/ML algorithm development, this question is not applicable to this device submission. The device's internal calibration and development would have used reference materials and established laboratory methods, but these are not referred to as a "training set" with ground truth established in the same manner as for an AI model.

Summary

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

January 11, 2016

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

Re: K150678

Trade/Device Name: Sysmex CS-5100 Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: JPA Dated: December 10, 2015 Received: December 11, 2015

Dear Ms. Noah:

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

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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 yours.

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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Indications for Use

510(k) Number (if known) K150678

Device Name Sysmex CS-5100

Indications for Use (Describe)

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: Donna Noeh Email: donna.noeh@siemens.com Phone: + 49 6421 39 5107 Facsimile: + 49 6421 39 4977 Date Prepared: January 7, 2016 2. Device Sysmex CS-5100 Name of Device: Common or Usual Name: Automated Coagulation Instrument Multipurpose system for in vitro coagulation studies (21 CFR Classification Name: 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 Hematology 510(k) Review Panel

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.

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4. Device Description / Test Principle

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.

Table of Sysmex CS-5100 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 PartialThromboplastin Time	Clotting(intrinsic pathway)
Dade® ThrombinReagent	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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Front View of the Instrument

Image /page/6/Figure/2 description: This image shows a diagram of a machine with several parts labeled with numbers. The top part of the machine is labeled (1), and there are buttons labeled (4), (5), and (6). The middle section has a part labeled (7), and the bottom section has parts labeled (3) and (8), with a button labeled (2) on the side.

(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.

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Informational Processing Unit

Image /page/7/Figure/2 description: The image shows a desktop computer with a monitor, CPU, keyboard, and mouse. The monitor is labeled as (1), the CPU is labeled as (2), the keyboard is labeled as (3), and the mouse is labeled as (4). The computer is a desktop model, with the CPU placed under the monitor and the keyboard and mouse connected to the CPU.

(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.
(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.

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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 ●
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 the CS-5100 and CA-1500

Similarities between Sysmex CS-5100 and Sysmex CA-1500
Analyzer Component	Proposed DeviceSysmex CS-5100	Predicate DeviceSysmex CA-1500
Regulatory Classification	JPA, Class 2System, Multipurpose for invitro coagulation studies	Same
Sample Type	Human plasma3.2% sodium citrate	Same
Similarities between Sysmex CS-5100 and Sysmex CA-1500
Analyzer Component	Proposed Device	Predicate Device
	Sysmex CS-5100	Sysmex CA-1500
Application type	Clotting Applications:Prothrombin Time (PT) withDade® Innovin®;Activated Partial ThromboplastinTime (APTT) with Dade® Actin®FSL;Fibrinogen (Clauss) with Dade®Thrombin ReagentChromogenic Application:Antithrombin withINNOVANCE® AntithrombinImmuno-chemical Application:D-dimerwith INNOVANCE® D-Dimer	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 NormalMode (Plasma)	PT with Dade® Innovin® 50 µLAPTT with Dade® Actin® FSL50 µLFibrinogen with Dade®Thrombin Reagent 10 µLAntithrombin withINNOVANCE® Antithrombin10 µLD-dimer with INNOVANCE® D-Dimer	Same
Similarities between Sysmex CS-5100 and Sysmex CA-1500
Analyzer Component	Proposed Device	Predicate Device
	Sysmex CS-5100	Sysmex CA-1500
Sample Volumes in MicroMode (Plasma)	PT with Dade® Innovin® 50 µLAPTT with Dade® Actin® FSL50 µLFibrinogen with Dade®Thrombin Reagent 10 µL	Same
Rinse & Buffer Solutions
On-board	CA-CLEAN I	Same
External	CA-CLEAN II	Same
	Dade Owren's Buffer	Same
	Water	Same
Light Source
Chromogenic	Halogen Lamp	Same
Immuno-chemical	Halogen Lamp	Same
Wavelengths used in Analysis	Antithrombin withINNOVANCE® Antithrombin(405 nm)	Same
Temperature Control	Sample incubation well: 37℃ ±1.0°C	Same

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

Differences between Sysmex CS-5100 and Sysmex CA-1500
Analyzer Component	Proposed Device	Predicate Device
	Sysmex CS-5100	Sysmex CA-1500
Intended Use Statement	The Sysmex CS-5100 is a fullyautomated blood coagulation analyzerintended for in vitro diagnostic useusing plasma collected from venousblood samples in 3.2% sodium citratetubes to analyze clotting, chromogenicand immunoassay methods in theclinical laboratory.For determination of:• Prothrombin Time (PT) seconds andPT INR with Dade® Innovin®• Activated Partial ThromboplastinTime (APTT) with Dade®Actin® FSL• Fibrinogen (Fbg) with Dade®Thrombin Reagent• Antithrombin (AT) withINNOVANCE® Antithrombin• D-dimer with INNOVANCE® D-DimerThe performance of this device has notbeen established in neonate andpediatric patient populations.	The intended use of the Sysmex CA-1500 is as a fully automated,computerized blood plasmacoagulation analyzer for in vitrodiagnostic use in clinicallaboratories.The instrument uses citratedhuman plasma to perform thefollowing parameters andcalculated parameters:Clotting Analysis Prameters:Prothrombin Time (PT); ActivatedPartial Thromboplastin Time(APTT); Fibrinogen (Clauss);Batroxobin Time; Extrinsic Factors(II, V, VII, X); Intrinsic Factors(VIII, IX, XI, XII); Protein C.Chromogenic AnalysisParameters: Antithrombin III;Factor VIII; Plasminogen;Heparin; Protein C; α2-Antiplasmin.Immunologic Analysis Parameters:D-dimer.Calculated Parameters: PT Ratio;PT INR; PT %; Derived Fibrinogen;Factor Assays % Activity
Differences between Sysmex CS-5100 and Sysmex CA-1500
	Proposed Device	Predicate Device
Analyzer Component	Sysmex CS-5100	Sysmex CA-1500
Operating Principle
Clotting	Transmitted Light Detection(Absorbance) at 340, 405, 575, 660 or800 nm. Wavelengths 340 and 575 aretechnically available but not validated incombination with the intendedapplications.	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 notvalidated in combination with theintended applications.	Transmitted Light Detection(Absorbance) at 405, 575, 800 nm
Immuno-chemical	Transmitted Light Detection(Absorbance) at 340, 405, 575, 660 or800 nm. Wavelengths 340, 405, 575,and 800 are technically available but notvalidated in combination with theintended applications.	Transmitted Light Detection(Absorbance) at 405, 575, or 800 nm
Wavelengths* used in Analysis*The default wavelength is normallyused to generate the reported value ofthe measurement. The sub-wavelength	Clotting Applications: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® FSLActivated PTT Reagent (Default =660 nm; Sub-Wavelength= 800 nm)	Clotting Applications: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® FSLActivated PTT Reagent (Default= 660 nm; Sub-Wavelength=none)
is run in parallel. If a light intensityerror occurs by using the defaultwavelength the value from the sub-wavelength is used automatically.	Fibrinogen with Dade® ThrombinReagent (Default = 405 nm; Sub-Wavelength= none)Immuno-chemical Application:D-dimer with INNOVANCE®D-Dimer (Default = 660 nm; Sub-Wavelength= none)	Fibrinogen with Dade® Thrombin(Default = 660 nm;Sub-Wavelength= none)Immuno-chemical Application:D-dimer with INNOVANCE® D-Dimer (Default = 800 nm; Sub-Wavelength= none)
Differences between Sysmex CS-5100 and Sysmex CA-1500
Analyzer Component	Proposed DeviceSysmex CS-5100	Predicate DeviceSysmex CA-1500
Light SourceClotting	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 °C ± 0.5 °C-Reagent probe : 37.5 °C ± 0.5 °C	-Detector: 37°C ± 1.0°C- Reagent 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 μLSample probe:4 – 270 μL	Reagent probe:3 – 200 μLSample probe:5 – 450 μL
Sample Volumes in MicroMode (Plasma)	Antithrombin with INNOVANCE® Antithrombin 14 μLD-dimer with INNOVANCE® D-Dimer 15 µL	Antithrombin with INNOVANCE® Antithrombin 10 μLD-dimer with INNOVANCE® D-Dimer 13 µL
Bidirectional Interfacecommunication protocols	CA-, ASTM-, CS- Protocol	CA-, ASTM-Protocol

Differences between CS-5100 and CA-1500

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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 protocol.

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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 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.

Sysmex CS-5100: Method Comparison Summary Table, Passing-Bablok regression
Application(measuring interval)	Site 01	Site 02	Site 03	Sites Combined
ProthrombinTime usingDade® Innovin®(8.7 - 90.0seconds)	n=125$y = 1.000x + 0.400$r = 0.997	n=209$y = 1.000x + 0.000$r = 0.999	n=135$y = 0.987x +0.374$r = 0.999	n=469$y = 1.000x + 0.100$r = 0.998
ProthrombinTime (INR) usingDade® Innovin®(0.93 - 8.00 INR)	n=122$y = 1.044x - 0.037$r = 0.997	n=208$y = 1.030x-0.038$r = 0.999	n=135$y = 1.039x - 0.019$r = 0.999	n=465$y = 1.047x-0.047$r = 0.999
Activated PartialThromboplastinTime usingDade® Actin®FSL(20.0 - 139.0seconds)	n=126$y = 1.029x - 1.112$r = 0.994	n=210$y = 1.017x-1.203$r = 0.998	n=130$y = 1.027x - 1.225$r = 0.994	n=466$y = 1.026x - 1.315$r = 0.996
Fibrinogenquantitationusing Dade®Thrombin Reagent(50 - 860 mg/dL)	n=145$y = 1.052x -4.466$r = 0.994	n=91$y = 1.028x + 5.491$r = 0.996	n=132$y = 0.982x + 9.889$r = 0.998	n=368$y = 1.018x + 4.633$r = 0.995
AntithrombinquantitationusingINNOVANCE®Antithrombin(9.0 - 128.0% ofnorm)	n=135$y = 0.990x-0.413$r = 0.996	n=120$y = 0.957x + 1.825$r = 0.994	n=126$y = 0.985x - 0.359$r = 0.997	n=381$y = 0.980x + 0.222$r = 0.996

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Sysmex CS-5100: Method Comparison Summary Table, Passing-Bablok regression
D-dimerquantitationusingINNOVANCE®D-Dimer (0.19 –35.20 mg/L FEU¹)	n=137	n= 108	n=116	n=361
	$y = 1.058x-0.013$r = 0.997	$y = 1.000x - 0.035$r = 0.997	$y = 1.000x + 0.000$r = 0.998	$y = 1.021x - 0.007$r = 0.996

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 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 With-in Site was calculated. The data is summarized in the following tables.

Sysmex CS-5100: Reproducibility Summary Table, Within Run
Application(CRR/Clotting time range)	SampleRange (meanof all sites)	Site 01Within Run(%CV)	Site 02Within Run(%CV)	Site 03Within Run(%CV)	SitesCombined(%CV)
Prothrombin Timeusing Dade® Innovin®(8.7 - 90.0 seconds)	9.27 - 79.67seconds	0.64 – 1.85	0.47 – 0.98	0.51 - 3.61	0.59 — 2.35
Prothrombin Time(INR) using Dade®Innovin® (0.93 - 8.00INR)	1.02 - 7.76INR	0.62 - 2.21	0.45 - 0.92	0.44 - 1.31	0.51 - 1.50
Activated PartialThromboplastin Timeusing Dade® Actin®FSL(20.0 - 139.0 seconds)	22.02 -123.25seconds	0.71 - 5.51	0.51 - 3.05	0.56 - 2.67	0.76 - 3.93
Fibrinogenquantitation usingDade® ThrombinReagent(50 - 860 mg/dL)	56.2 - 752.6mg/dL	1.14 - 6.18	0.99 - 3.27	1.41 - 2.72	1.20 - 4.20

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

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Sysmex CS-5100: Reproducibility Summary Table, Within Run
Antithrombinquantitation usingINNOVANCE®Antithrombin(9.0 - 128.0% of norm)	10.17 -119.41% ofnorm	0.71 - 2.66	0.81 - 3.45	0.97 - 3.13	0.92 - 3.11
D-dimer quantitationusing INNOVANCE®D-Dimer (0.19 - 35.20mg/L FEU)	0.25 - 33.81mg/L FEU	0.91 - 2.15	0.80 - 1.56	1.27 – 2.51	1.08 – 2.07

Sysmex CS-5100: Reproducibility Summary Table, Between Run
Application(CRR/Clotting time range)	Sample Range(mean of allsites)	Site 01Between Run(%CV)	Site 02Between Run(%CV)	Site 03Between Run(%CV)	SitesCombined(%CV)
Prothrombin Timeusing Dade®Innovin®(8.7 - 90.0 sec)	9.27 - 79.67seconds	0.12 - 1.73	0.00 - 1.15	0.00 - 1.45	0.35 - 1.42
Prothrombin Time(INR) using Dade®Innovin® (0.93 –8.00 INR)	1.02 – 7.76INR	0.00 - 2.05	0.00 - 1.12	0.53 - 1.30	0.25 - 1.37
Activated PartialThromboplastinTime using Dade®Actin® FSL(20.0 - 139.0 sec)	22.02 - 123.25seconds	0.00 - 0.97	0.00 - 2.50	0.29 - 2.66	0.34 - 2.40
Fibrinogenquantitation usingDade® ThrombinReagent(50 - 860 mg/dL)	56.2 - 752.6mg/dL	0.00 - 1.25	0.00 - 1.07	0.00 - 1.26	0.00 - 0.88
Antithrombinquantitation usingINNOVANCE®Antithrombin(9.0 - 128.0% ofnorm)	10.17 -119.41% ofnorm	0.42 - 1.40	0.00 - 4.33	0.94 - 4.45	0.78 - 3.73

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Sysmex CS-5100: Reproducibility Summary Table, Between Run
D-dimerquantitation usingINNOVANCE® D-Dimer (0.19 – 35.20mg/L FEU)	0.25 - 33.81mg/L FEU	0.33 - 1.18	0.00 - 1.50	0.00 - 2.12	0.30 - 1.61

Sysmex CS-5100: Reproducibility Summary Table, Between Day
Application(CRR/Clotting timerange)	Sample Range(mean of allsites)	Site 01Between Day(%CV)	Site 02Between Day(%CV)	Site 03Between Day(%CV)	SitesCombined(%CV)
Prothrombin Timeusing Dade®Innovin®(8.7 - 90.0 sec)	9.27 - 79.67seconds	0.00 - 0.97	0.00 - 0.57	0.00 - 2.45	0.17 - 1.45
Prothrombin Time(INR) using Dade®Innovin® (0.93 –8.00 INR)	1.02 - 7.76INR	0.00 - 2.81	0.00 - 0.60	0.44 - 2.38	0.26 - 1.78
Activated PartialThromboplastinTime using Dade®Actin® FSL(20.0 - 139.0 sec)	22.02 - 123.25seconds	0.00 - 3.84	0.00 - 1.94	0.00 - 3.82	0.11 - 2.77
Fibrinogenquantitation usingDade® ThrombinReagent(50 - 860 mg/dL)	56.2 - 752.6mg/dL	0.00 - 1.11	0.00 - 1.02	0.00 - 1.11	0.00 - 0.74
Antithrombinquantitation usingINNOVANCE®Antithrombin(9.0 - 128.0% ofnorm)	10.17 -119.41% ofnorm	0.00 - 1.84	0.00 - 1.62	0.00 - 1.18	0.00 - 1.22
D-dimerquantitation usingINNOVANCE® D-Dimer (0.19 - 35.20mg/L FEU)	0.25 - 33.81mg/L FEU	1.49 - 5.95	0.00 - 1.56	0.85 - 3.19	1.14 - 3.86

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Sysmex CS-5100: Reproducibility Summary Table, Site-to-Site
Application(CRR/Clotting time range)	Sample Range (mean of allsites)	SitesCombined(%CV)
Prothrombin Time using Dade®Innovin®(8.7 - 90.0 sec)	9.27 - 79.67 seconds	0.00 – 0.95
Prothrombin Time (INR) using Dade®Innovin® (0.93 - 8.00 INR)	1.02 - 7.76INR	0.09 - 1.21
Activated Partial ThromboplastinTime using Dade® Actin® FSL(20.0 - 139.0 sec)	22.02 - 123.25 seconds	0.04 - 5.16
Fibrinogen quantitation using Dade®Thrombin Reagent(50 – 860 mg/dL)	56.2 - 752.6 mg/dL	0.97 - 3.96
Antithrombin quantitation usingINNOVANCE® Antithrombin(9.0 – 128.0% of norm)	10.17 - 119.41% of norm	0.85 — 2.88
D-dimer quantitation usingINNOVANCE® D-Dimer (0.19 - 35.20mg/L FEU)	0.25 - 33.81 mg/L FEU	0.61 - 2.93

CS-5100: Reproducibility Summary Table, Total CV (Within Site)
Application(CRR/Clotting timerange)	SampleRange (meanof all sites)	Site 01Total WithinSite (%CV)	Site 02Total WithinSite (%CV)	Site 03Total WithinSite (%CV)	SitesCombined(%CV)
Prothrombin Timeusing Dade®Innovin®(8.7 - 90.0 sec)	9.27 - 79.67seconds	0.82 - 2.42	0.52 - 1.39	1.00 - 4.17	0.86 - 2.95
Prothrombin Time(INR) using Dade®Innovin® (0.93 –8.00 INR)	1.02 - 7.76INR	0.73 - 4.12	0.49 - 1.36	0.86 - 3.00	0.72 - 2.96
Activated PartialThromboplastinTime using Dade®Actin® FSL(20.0 - 139.0 sec)	22.02 –123.25seconds	0.85 - 6.78	0.58 – 3.95	0.72 - 5.37	1.00 - 7.45

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CS-5100: Reproducibility Summary Table, Total CV (Within Site)
Fibrinogenquantitation usingDade® ThrombinReagent(50 - 860 mg/dL)	56.2 - 752.6mg/dL	1.31 - 6.18	1.29 – 3.52	1.60 - 2.94	2.08 - 4.33
Antithrombinquantitation usingINNOVANCE®Antithrombin(9.0 - 128.0% ofnorm)	10.17 -119.41% ofnorm	1.07 - 3.53	1.17 - 5.53	1.55 - 5.44	1.81 - 5.64
D-dimerquantitation usingINNOVANCE® D-Dimer (0.19 - 35.20mg/L FEU)	0.25 - 33.81mg/L FEU	2.0 - 6.40	1.31 - 2.21	2.16 - 4.58	2.05 - 5.51

7.3 Detection Capability Results

Detection capability studies were measured for the calibrated assays on the Sysmex CS-5100: Fibrinogen with Dade® Thrombin Reagent, Antithrombin with INNOVANCE® Antithrombin, and D-dimer with INNOVANCE® D-Dimer. 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 pre-determined acceptance criteria and support the lower limit of the clinical reportable range claim.

Sysmex CS-5100: Summary of Limit of Quantitation Studies
Reagent	Lower Limit ofClinical ReportableRange	Measured Limit ofQuantitation	Maximum TotalError (%) Result
Fibrinogen quantitation usingDade® Thrombin Reagent	50 mg/dL	46.1 mg/dL	16.66%
Antithrombin quantitation usingINNOVANCE® Antithrombin	9.0% of norm	8.783% of norm	27.34%
D-dimer quantitation usingINNOVANCE® D-Dimer	0.19 mg/L FEU	0.146 mg/L FEU	31.76%

The Sysmex CS-5100 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.

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Linearity & Measuring Range 7.4

Linearity studies were performed for the following calibrated assays on the Sysmex CS-5100: 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-5100 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 noncalibrated assays. 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
Reagent	Measured Linear Range	Clinical ReportableRange
Prothrombin Time (seconds)using Dade® Innovin®	Not applicable	8.7 - 90.0 seconds
Prothrombin Time (INR)using Dade® Innovin®	Not applicable	0.93 - 8.00 INR
Activated PartialThromboplastin Time(seconds) using Dade®Actin® FSL	Not applicable	20.0 - 139.0 seconds
Fibrinogen quantitation(mg/dL) using Dade®Thrombin Reagent	40.300 to 1124.000 mg/dL	50 to 860 mg/dL
Antithrombin quantitation(% of norm) usingINNOVANCE® Antithrombin	6.280 to 152.300% of norm	9.0 to 128.0% of norm
D-dimer quantitation (mg/LFEU) using INNOVANCE®D-Dimer	0.149 to 50.862 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. The study population did not include neonate and pediatric sample populations.

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Application	Sysmex CS-5100 Reference Interval
Prothrombin Time (seconds) usingDade® Innovin®	2.5th – 97.5th perc.9.6 – 12.3
Prothrombin Time (INR) usingDade® Innovin®	2.5th – 97.5th perc.0.93 – 1.15
Activated Partial ThromboplastinTime (seconds) using Dade®Actin® FSL	2.5th – 97.5th perc.23.9 – 29.9
Fibrinogen quantitation usingDade® Thrombin Reagent (mg/dL)	2.5th – 97.5th perc.194 – 448
Antithrombin quantitation usingINNOVANCE® Antithrombin(% of norm)	2.5th – 97.5th perc.80.7 – 121.9
D-dimer quantitation usingINNOVANCE® D-Dimer(mg/L FEU)	2.5th – 97.5th perc.<0.19 – 1.14

7.6 D-Dimer PE Exclusion Validation Study

The INNOVANCE® D-Dimer assay was evaluated on the Sysmex CS-5100 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. Of these 1930 patients, 96 were excluded for a total of 1834 patients.

All potentially eligible patients were evaluated using the Wells' rules to estimate their pre-test probability (PTP) with regard to PE, and then categorized into high, intermediate or low PTP. Patients with a high PTP score were excluded from enrollment.

Patients with no or a positive D-dimer result with the D-dimer assay used at the respective study center were evaluated by imaging methods, e.g. spiral CT and/or VO scan. Patients with a negative D-dimer result with the D-dimer assay used at the respective study center underwent imaging at the physician's discretion. All patients with a negative diagnosis of PE at presentation were followed up after three months to evaluate potential development of PE. Patients with unobtainable follow-up data were excluded from analysis resulting in n=1467 patients available for final analysis.

The overall prevalence of PE in the 1467 patients was 6.9 % (101 of 1467) with 6.0 % in the US population and 37.2 % in the European population. 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 <0.50 mg/L FEU was considered negative and a D-dimer result >0.50 mg/L FEU was considered positive. The instrument-specific sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) with lower bound (LCL) of two-sided 95%

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confidence interval were obtained with the INNOVANCE® D-Dimer clinical cut-off of 0.50
mg/L FEU. Results obtained for each study population are detailed below.

US	Reference (Imaging and 3-month follow-up)
		Positive	Negative	Total
INNOVANCE® D-Dimer onSysmex CS-5100	Positive	83	616	699
	Negative	2	723	725
	Total	85	1339	1424
Sensitivity %=	97.6	95% LCL=	91.8
Specificity %=	54.0	95% LCL=	51.3
NPV %=	99.7	95% LCL=	99.0
NPV* %=	99.2	95% LCL=	97.3
PPV %=	11.9	95% LCL=	9.7
PPV* %=	27.2	95% LC=	23.0

OUS	Reference (Imaging and 3-month follow-up)
		Positive	Negative	Total
INNOVANCE® D-Dimer onSysmex CS-5100	Positive	16	5	21
	Negative	0	22	22
	Total	16	27	43

Sensitivity %=	100.0	95% LCL=	79.4
Specificity %=	81.5	95% LCL=	61.9
NPV %=	100.0	95% LCL=	85.1
NPV* %=	100.0	95% LCL=	95.1
PPV %=	76.2	95% LCL=	54.9
PPV* %=	48.8	95% LCL=	26.6

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US and OUS		Reference (Imaging and 3-month follow-up)
		Positive	Negative	Total
INNOVANCE® D-Dimer onSysmex CS-5100	Positive	99	621	720
	Negative	2	745	747
	Total	101	1366	1467
Sensitivity %=	98.0	95% LCL=	93.0
Specificity %=	54.5	95% LCL=	51.9
NPV %=	99.7	95% LCL=	99.0
NPV* %=	99.4	95% LCL=	97.7
PPV %=	13.8	95% LCL=	11.4
PPV* %=	27.6	95% LCL=	23.5

*standardized to a prevalence of 15%

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 hardware and software verification and validation demonstrate that the Sysmex CS-5100 performs as intended in the specified use conditions.

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.

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.