(104 days)
The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.
For determination of:
- Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® .
- . Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
- . Fibrinogen (Fbg) with Dade® Thrombin Reagent
- . Coagulation Factor V with Dade® Innovin®
- . Coagulation Factor VII with Dade® Innovin®
- . Protein C with Protein C Reagent
- . Antithrombin (AT) with INNOVANCE® Antithrombin
- Protein C with Berichrom® Protein C
- D-dimer with INNOVANCE® D-Dimer
The performance of this device has not been established in neonate and pediatric patient populations.
Coagulation Factor V Deficient Plasma:
In vitro diagnostic reagent for the determination of the activity of coagulation factor V in human plasma.
Coagulation Factor II, VII and X Deficient Plasmas:
In vitro diagnostic reagents for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods.
Protein C Reagent:
Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma.
Berichrom® Protein C:
For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies.
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 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.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Sysmex® CS-5100 device:
The document describes the performance data for the Sysmex® CS-5100 automated blood coagulation analyzer, specifically for the applications: 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 studies aim to demonstrate substantial equivalence to a predicate device, the Sysmex® CA-1500.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for substantial equivalence are implicitly based on demonstrating comparable performance to the predicate device. The studies aim to show that results from the new device are sufficiently similar to those from the predicate and that the new device's precision, detection capability, and linearity fall within acceptable ranges for clinical laboratory use.
| Study Type | Acceptance Criteria (Implicit from predicate comparison / CLSI guidelines) | Reported Device Performance (Sysmex® CS-5100) |
|---|---|---|
| Method Comparison | Passing-Bablok regression: Slope close to 1, Intercept close to 0, high correlation coefficient (r) with the predicate device. Bland-Altman plots to show agreement. | Coagulation Factor V: y = 1.017x + 0.185 (r=0.984)Coagulation Factor VII: y = 1.051x - 0.241 (r=0.989)Protein C (C Reagent): y = 0.988x - 0.413 (r=0.987)Protein C (Berichrom): y = 0.950x + 0.375 (r=0.992)Conclusion: All applications met predetermined acceptance criteria, showing equivalent results. |
| Reproducibility (Within Run) | Coefficients of Variation (CV%) within clinically acceptable limits for precision. | Coagulation Factor V: 2.40 - 3.16%Coagulation Factor VII: 1.33 - 2.00%Protein C (C Reagent): 2.53 - 3.22%Protein C (Berichrom): 1.48 - 6.85% |
| Reproducibility (Between Run) | Coefficients of Variation (CV%) within clinically acceptable limits for precision. | Coagulation Factor V: 3.29 - 4.24%Coagulation Factor VII: 0.65 - 1.29%Protein C (C Reagent): 1.73 - 3.86%Protein C (Berichrom): 0.00 - 1.04% |
| Reproducibility (Between Day) | Coefficients of Variation (CV%) within clinically acceptable limits for precision. | Coagulation Factor V: 0.00 - 0.59%Coagulation Factor VII: 0.94 - 1.97%Protein C (C Reagent): 0.00 - 1.01%Protein C (Berichrom): 0.39 - 1.16% |
| Reproducibility (Total CV) | Coefficients of Variation (CV%) within clinically acceptable limits for precision. | Coagulation Factor V: 4.83 - 6.85%Coagulation Factor VII: 3.39 - 5.03%Protein C (C Reagent): 4.54 - 7.15%Protein C (Berichrom): 3.22 - 7.92% |
| Detection Capability (LoQ) | Measured Limit of Quantitation (LoQ) ≤ Lower Limit of Clinically Reportable Range (CLRR), with Maximum Total Error within acceptance. | Coagulation Factor V: LoQ = 4.80% (CLRR = 6.0%), Max Total Error = 0.74%Coagulation Factor VII: LoQ = 3.39% (CLRR = 6.0%), Max Total Error = 0.27%Protein C (C Reagent): LoQ = 9.35% (CLRR = 10.1%), Max Total Error = 2.91%Protein C (Berichrom): LoQ = 8.32% (CLRR = 10.0%), Max Total Error = 2.07%Conclusion: All data met predetermined acceptance criteria and support the lower limit of the clinically reportable range claim. |
| Linearity & Measuring Range | Measured Linear Range ≥ Clinically Reportable Range. | Coagulation Factor V: Linear Range = 3.4 – 180.7% (CLRR = 6.0 – 149.0%)Coagulation Factor VII: Linear Range = 4.3 – 179.5% (CLRR = 6.0 – 149.0%)Protein C (C Reagent): Linear Range = 7.0 – 187.7% (CLRR = 10.1 – 131.0%)Protein C (Berichrom): Linear Range = 7.1 – 181.3% (CLRR = 10.0 – 138.0%)Conclusion: All reagents met the predetermined acceptance criteria and support the clinically reportable range claim. |
| Reference Interval | Established reference intervals for healthy populations. | Coagulation Factor V: 80.8% of norm (5th Percentile)Coagulation Factor VII: 67.6% of norm (5th Percentile)Protein C (C Reagent): 76.4% of norm (5th Percentile)Protein C (Berichrom): 83.0% of norm (5th Percentile) |
2. Sample Sizes Used for the Test Set and Data Provenance
-
Method Comparison:
- Coagulation Factor V: N = 609 total samples (133, 151, 148, 177 across 4 sites)
- Coagulation Factor VII: N = 505 total samples (121, 145, 102, 137 across 4 sites)
- Protein C (C Reagent): N = 624 total samples (138, 176, 110, 200 across 4 sites)
- Protein C (Berichrom): N = 531 total samples (127, 149, 130, 125 across 4 sites)
- Data Provenance: Four external sites in the United States. The samples were "patient samples" and seem to be prospective as they were measured on both devices in random order for comparison.
-
Reproducibility Studies:
- The sample types used for reproducibility studies are not specified as patient samples, but rather analytical samples (possibly controls or pooled plasma). The N for actual samples per run is not explicitly given, but the study design involved "two runs per day, with two replicates per run, at each of the three sites."
- Data Provenance: Two external sites in Germany and one external site in the United States. These are prospective studies performed over 20 days.
-
Detection Capability (LoQ) and Linearity Studies:
- Sample sizes are not explicitly stated for these studies, but they involve different concentrations or dilutions to determine the limits.
- Data Provenance: Not specified, but likely from laboratory settings where the devices were tested.
-
Reference Interval Studies:
- Coagulation Factor V, VII, Protein C (C Reagent), Protein C (Berichrom): N = 194 for each.
- Data Provenance: Three clinical study sites in the United States. This is a prospective study of a "study population."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- No human "experts" established ground truth for the test set. This device is an automated in vitro diagnostic analyzer. The ground truth, in this context, is the accurately measured value of the coagulation factors and protein C using the predicate device (Sysmex® CA-1500) or established clinical analytical methods, which the new device (Sysmex® CS-5100) is compared against. Clinical laboratory standards (CLSI guidelines) are followed to ensure the validity of these reference measurements.
4. Adjudication Method
- Not applicable as this is an automated analytical device rather than a diagnostic imaging or classification system involving human interpretation. The "ground truth" or reference values are obtained through the predicate device or validated laboratory methods, not through human adjudication of ambiguous cases.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done. This type of study is relevant for diagnostic systems where human readers interpret output (e.g., medical images). The Sysmex® CS-5100 is an automated analyzer, and its performance is evaluated by comparing its quantitative results against a predicate device's results, not by comparing human reader performance with and without AI assistance.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- Yes, this is a standalone study. The Sysmex® CS-5100 is an automated instrument with an algorithm (its internal measurement and calculation processes) that generates results without real-time human intervention in the measurement process itself. The performance data presented (method comparison, reproducibility, detection capability, linearity) describe the intrinsic performance of the device's analytical capabilities. While human technicians operate and maintain the device, the core measurement is "algorithm only."
7. Type of Ground Truth Used
- Predicate Device/Method comparison: For the method comparison studies, the "ground truth" for demonstrating substantial equivalence was the measurements obtained from the predicate device (Sysmex® CA-1500).
- Established analytical methods/standards: For reproducibility, detection capability, and linearity studies, the "ground truth" refers to the expected statistical performance (e.g., target CVs, expected linear range) according to CLSI guidelines and accepted laboratory practice for quantitative measurement methods.
- Reference Intervals: For reference interval studies, the "ground truth" is derived from the measurements in a healthy population to establish the normal range, as per CLSI guidelines EP28-A3c.
8. Sample Size for the Training Set
- The document does not explicitly mention a "training set" in the context of machine learning or AI algorithm development. This device is an automated analyzer, and its operational parameters and internal algorithms would typically be developed and validated by the manufacturer using extensive internal testing and calibration with known standards and samples, rather than a distinct "training set" in the AI sense. The studies described are for validation and verification of the final product.
9. How the Ground Truth for the Training Set Was Established
- Given that a "training set" in the AI sense is not explicitly described or applicable in the provided context for this type of IVD device, this question is not directly answerable from the document. The development of such an analyzer involves engineering design, physical and chemical principles, and calibration with reference materials, rather than training an algorithm on a 'ground truth' dataset in the same way an AI for image classification would be trained.
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird-like symbol composed of three overlapping profiles facing to the right. The profiles are arranged in a way that creates a sense of depth and movement. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the symbol.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
December 12, 2016
Siemens Healthcare Diagnostics Products GmbH Petra M. Dissmann, Ph.D. Regulatory Affairs Manager Emil-von-Behring Strasse 76 35041 Marburg, Germany
Re: K162420 Trade/Device Name: Sysmex® CS-5100 Coagulation Factor V Deficient Plasma Coagulation Factor II. VII and X Deficient Plasmas Protein C Reagent Berichrom® Protein C Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: JPA, GGP, GJT Dated: September 12, 2016 Received: September 13, 2016
Dear Dr. Dissmann:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. Isting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
{1}------------------------------------------------
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely.
Leonthena R. Carrington -S
Leonthena R. Carrington, MS. MBA. MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K162420
Device Name
Sysmex® CS-5100, Coagulation Factor V Deficient Plasma, Coagulation Factor II, VII and X Deficient Plasmas, Protein C Reagent, Berichrom® Protein C
Indications for Use (Describe)
Sysmex® CS-5100:
The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.
For determination of:
- Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® .
- . Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
- . Fibrinogen (Fbg) with Dade® Thrombin Reagent
- . Coagulation Factor V with Dade® Innovin®
- . Coagulation Factor VII with Dade® Innovin®
- . Protein C with Protein C Reagent
- . Antithrombin (AT) with INNOVANCE® Antithrombin
- Protein C with Berichrom® Protein C
- D-dimer with INNOVANCE® D-Dimer
The performance of this device has not been established in neonate and pediatric patient populations.
Coagulation Factor V Deficient Plasma:
In vitro diagnostic reagent for the determination of the activity of coagulation factor V in human plasma.
Coagulation Factor II, VII and X Deficient Plasmas:
In vitro diagnostic reagents for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods.
Protein C Reagent:
Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma.
Berichrom® Protein C:
For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies.
Type of Use (Select one or both, as applicable)X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
{3}------------------------------------------------
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{4}------------------------------------------------
510(k) Summary
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of 21 CFR 8807.92 and follows the FDA guidance 'The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]', issued July 28, 2014.
Submitter 1
Siemens Healthcare Diagnostics Products GmbH Emil-von-Behring-Str. 76 35041 Marburg, Germany Contact Person: Dr. Petra M. Dissmann Email: petra.dissmann@siemens.com Phone: + 49 6421 39 2009 Facsimile: + 49 6421 39 4977 Date Prepared: August 29, 2016 2 Device Name of Device: Sysmex® CS-5100 Common or Usual Name: Automated Coagulation Instrument Classification Name: Multipurpose system for in vitro coagulation studies (21 CFR 864.5425) Regulatory Class: Class II Product Code: JPA 510(k) Review Panel Hematology 3 Predicate Device Name of Device: Sysmex® CA-1500 (K011235) Common or Usual Name: Automated Coagulation Instrument Classification Name: Multipurpose system for in vitro coagulation studies (21 CFR 864.5425) Regulatory Class: Class II Product Code: JPA 510(k) Review Panel Hematology
The predicate has not been subject to a design-related recall for any of the applications associated with this premarket notification. No reference devices were used in this submission.
{5}------------------------------------------------
| Reagent Applications that are the subject of this 510(k) notification | |||||
|---|---|---|---|---|---|
| ApplicationIntended Use | 510(k)Numberrelated toapplication onpredicate device | RegulationNumber | RegulatoryClass | ProductCode | Panel |
| Coagulation Factor Vwith Dade® Innovin®In vitro diagnosticreagent for thedetermination of theactivity of coagulationfactor V in humanplasma. | K993299 | 864.7290 | Class II | GJT | Hematology |
| Coagulation Factor VIIwith Dade® Innovin®In vitro diagnosticreagents for thedetermination of theactivity of coagulationfactor II (prothrombin),coagulation factor VIIand coagulation factor Xin human plasma bycoagulometric methods. | K993299 | 864.7290 | Class II | GJT | Hematology |
| Protein C withProtein C ReagentProtein C Reagent is acoagulation test for thequantitativedetermination of proteinC activity in humanplasma. | K000649 | 864.7290 | Class II | GGP | Hematology |
| Protein C withBerichrom® Protein CFor the quantitativedetermination offunctionally activeprotein C using achromogenic substrate asan aid in the diagnosis ofinherited and acquireddeficiencies. | K001645 | 864.7290 | Class II | GGP | Hematology |
{6}------------------------------------------------
Device Description / Test Principle 4
The Sysmex® CS-5100 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated
- Reagents ●
- Controls
- Calibrators ●
- Consumable materials ●
The subject of this 510(k) notification are reagent applications which perform the coagulation tests Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent and Protein C with Berichrom® Protein C.
The analysis principles used on the instrument are reflected by the reagent application testing provided in this 510(k) notification and is described in the below table.
| Table of Sysmex® CS-5100 Analysis Principles | |||
|---|---|---|---|
| Reagent | Application | Methodology | |
| Dade® Innovin® withCoagulation Factor VDeficient Plasma | Coagulation Factor V withDade® Innovin® | Clotting(extrinsic pathway) | |
| Dade® Innovin® withCoagulation FactorVII Deficient Plasma | Coagulation Factor VII withDade® Innovin® | Clotting(extrinsic pathway) | |
| Protein C Reagent | Protein C withProtein C Reagent | Clotting | |
| Berichrom® Protein C | Protein C withBerichrom® Protein C | Chromogenic |
The intended Environment of Use is a clinical central/hospital laboratory.
{7}------------------------------------------------
Front View of the Instrument
Image /page/7/Figure/2 description: This image is a line drawing of a machine with several components labeled with numbers. The top section of the machine is labeled (1), and below it, a small component is labeled (2). The left cabinet door is labeled (3), while the top right corner features labels (4), (5), and (6). The middle section is labeled (7), and the right cabinet door is labeled (8).
- (1) Light shield lid: Open this cover to set reagents, perform maintenance, etc.
- (2) Power switch: Turns the power ON/OFF.
- (3) Left door: Holds the Pneumatic Unit inside. Open this door to adjust the positive pressure (0.22 MPa).
- (4) Alarm indicator LED: Indicates the instrument status.
- (5) Mechanical stop switch: Press this switch to immediately stop the instrument's mechanical movement.
- (6) Start button: Press this button to immediately start an analysis. This button is the same as the [Start] button on the IPU toolbar.
- (7) Sampler: Automatically transports samples that are set in the sample rack to the aspiration position.
- (8) Right door: Open the door for maintenance or to discard cuvettes.
{8}------------------------------------------------
Informational Processing Unit
Image /page/8/Figure/2 description: This image shows a computer setup with four labeled parts. The labels point to the monitor (1), the computer tower (2), the keyboard (3), and the mouse (4). The computer is a desktop model with a separate monitor, keyboard, and mouse.
- (1) Touch panel display: Displays the IPU screen. It can also be used as a touch panel.
- (2) IPU Main Unit: This is the Main Unit of IPU.
- Keyboard: Used to operate the IPU together with the touch panel. (3)
- (4) Mouse: Used to operate the IPU together with the touch panel.
Options and Accessories
Options and accessories that can be used for this instrument are as follows:
- (1) Waste tank (with float switch for waste tank): Waste fluids discharged from the Main Unit enter this tank.
- (2) Wand barcode reader: Reads barcodes to input sample numbers, rack numbers and reagent IDs.
- (3) 2D barcode reader: Reads barcodes to input calibrator's or reagent's assay sheet values, normal values and ISI values, and control's targets/limits.
- (4) IPU cart: The IPU (which includes the keyboard, PC and touch panel display), and the tanks for waste, rinse and CA Clean II can be placed on this cart.
- (5) External indicator light: The status of the instrument is indicated with a red, yellow or green light that can be seen when the operator is not directly in front of the instrument.
- (6) IPU holder: This is an optional holder for the IPU which includes the keyboard, PC and touch panel display which can be installed on the right side of the instrument to minimize the instrument footprint.
{9}------------------------------------------------
The instrument is capable of measuring in the following analysis modes:
- (1) Normal mode: Samples for all the analyses including re-analyses are taken into the instrument at the same time and analyzed. In a normal mode, a capped sample tube analysis can be performed. Automatic re-analysis can also be performed.
- (2) Micro-sample mode: Samples set in the sampler or STAT holder are taken into the instrument for each analysis through a secondary dispensing sample probe. When measurements are to be performed in Micro mode, sample tubes must be uncapped. The instrument detects capped tubes automatically and displays an error message. This analysis mode can be performed with less sample volume than normal mode (consult instruction manual for further information). However, automatic re-analysis cannot be performed.
5 Intended Use / Indications for Use
The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.
For determination of:
- Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® ●
- Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL ●
- Fibrinogen (Fbg) with Dade® Thrombin Reagent ●
- Coagulation Factor V with Dade® Innovin® ●
- Coagulation Factor VII with Dade® Innovin® ●
- Protein C with Protein C Reagent
- Antithrombin (AT) with INNOVANCE® Antithrombin ●
- Protein C with Berichrom® Protein C
- D-dimer with INNOVANCE® D-Dimer ●
The performance of this device has not been established in neonate and pediatric patient populations.
6 Comparison of Technological Characteristics with the Predicate Device
Both the subject and predicate instruments employ the same technological characteristics in that they automatically analyze various clotting tests using reagents, calibrators and controls previously cleared for automated coagulation analyzers. The reagents perform at least equally well on both the subject and predicate instruments. At a high level, the devices have the following same technological elements:
{10}------------------------------------------------
Similarities between CS-5100 and CA-1500
There are no technological differences between the subject and predicate devices. However the following minor changes exist between the subject and predicate devices:
| Similarities between CS-5100 and CA-1500 | ||
|---|---|---|
| Analyzer Component | Proposed DeviceSysmex® CS-5100 | Predicate DeviceSysmex® CA-1500 |
| Regulatory Classification | JPA, Class IISystem, Multipurpose for invitro coagulation studies | Same |
| Intended Use Statement | The Sysmex® CS-5100 is a fullyautomated blood coagulationanalyzer intended for in vitrodiagnostic use using plasmacollected from venous bloodsamples in 3.2% sodium citratetubes to analyze clotting,chromogenic and immunoassaymethods in the clinical laboratory.For determination of:• Prothrombin Time (PT) secondsand PT INR with Dade®Innovin®• Activated Partial ThromboplastinTime (APTT) with Dade®Actin® FSL• Fibrinogen (Fbg) with Dade®Thrombin Reagent• Coagulation Factor V withDade® Innovin®• Coagulation Factor VII withDade® Innovin®• Protein C with Protein C Reagent• Antithrombin (AT) withINNOVANCE® Antithrombin• Protein C with Berichrom®Protein C• D-dimer with INNOVANCE®D-DimerThe performance of this device hasnot been 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 Parameters:Prothrombin Time (PT); ActivatedPartial Thromboplastin Time(APTT); Fibrinogen (Clauss);Batroxobin Time; ExtrinsicFactors (II, V, VII, X); IntrinsicFactors (VIII, IX, XI, XII);Protein C.Chromogenic AnalysisParameters: Antithrombin III;Factor VIII; Plasminogen;Heparin; Protein C; a2-Antiplasmin.Immunologic Analysis Parameters:D-dimer.Calculated Parameters: PT Ratio;PT INR; PT %; DerivedFibrinogen; Factor Assays% Activity. |
| Sample Type | Human plasma3.2% sodium citrate | Same |
| Analyzer Component | Proposed DeviceSysmex® CS-5100 | Predicate DeviceSysmex® CA-1500 |
| Application type | Clotting Applications:Prothrombin Time (PT) withDade® Innovin®;Activated Partial ThromboplastinTime (APTT) withDade® Actin® FSL;Fibrinogen (Clauss) withDade® Thrombin Reagent;Coagulation Factor V withDade® Innovin®Coagulation Factor VII withDade® Innovin®Protein C with Protein C Reagent | Same |
| Chromogenic Application:Antithrombin withINNOVANCE® Antithrombin;Protein C withBerichrom® Protein C | Same | |
| Immuno-Chemical Application:D-dimer withINNOVANCE® D-Dimer | Same | |
| Calculated Application:PT INR with Dade® Innovin® | Same | |
| Specimen Processing | Automatic Pipetting and Dilution | Same |
| Random Access | Yes | Same |
| Liquid Level Sensing | Yes - reagent and sample | Same |
| Bar Code Reader | Sample + reagent | Same |
| STAT Testing | Yes | Same |
| Sampling Capabilities | Normal and Micro Mode | Same |
| Similarities between CS-5100 and CA-1500 | ||
| Analyzer Component | Proposed DeviceSysmex® CS-5100 | Predicate DeviceSysmex® CA-1500 |
| Sample Volumes (Plasma) | PT with Dade® Innovin® (50 µL)APTT with Dade® Actin® FSL(50 µL)Fibrinogen with Dade® ThrombinReagent (10 µL) | Same |
| Coagulation Factor V withDade® Innovin® (5 µL) | ||
| Coagulation Factor VII withDade® Innovin® (5 µL) | ||
| Protein C with Protein C Reagent(5 μL)Protein C with Berichrom®Protein C (15 µL) | ||
| Sample Volumes in Micro Mode(Plasma) | PT with Dade® Innovin® (50 µL)APTT with Dade® Actin® FSL(50 µL)Fibrinogen with Dade® ThrombinReagent (10 µL)Coagulation Factor V withDade® Innovin® (5 µL)Coagulation Factor VII withDade® Innovin® (5 µL)Protein C with Protein C Reagent(5 uL)Protein C with Berichrom®Protein C (15 µL) | Same |
| Rinse & Buffer Solutions | ||
| On-boardExternal | CA-CLEAN ICA-CLEAN IIDade® Owren's BufferWater | |
| Light Source | ||
| ChromogenicImmuno-chemical | Halogen LampHalogen Lamp | |
| Similarities between CS-5100 and CA-1500 | ||
| Analyzer Component | Proposed DeviceSysmex® CS-5100 | Predicate DeviceSysmex® CA-1500 |
| Wavelengths* used in Analysis*The default wavelength isnormally used to generate thereported value of the measurement.The sub-wavelength is run inparallel. If a light intensity erroroccurs by using the defaultwavelength the value from the sub-wavelength is used automatically. | Clotting Applications:Coagulation Factor V withDade® Innovin®(Default = 660 nm;sub-wavelength = none)Coagulation Factor VII withDade® Innovin®(Default = 660 nm;Sub-wavelength = none)Protein C with Protein C Reagent(Default = 660 nm;Sub-wavelength = none)Chromogenic Application:Antithrombin withINNOVANCE® Antithrombin(Default = 405 nm;Sub-wavelength = none)Protein C withBerichrom® Protein C(Default = 405 nm;Sub-wavelength = none) | Same |
| Temperature Control | Sample incubation well:37 °C ± 1.0 °C | Same |
| Differences between CS-5100 and CA-1500 | ||
| Analyzer Component | Proposed DeviceSysmex® CS-5100 | Predicate DeviceSysmex® CA-1500 |
| Operating Principle | ||
| Clotting | Transmitted Light Detection(Absorbance) at 340, 405, 575, 660or 800 nm. Wavelengths 340 and 575are technically available but notvalidated in combination with theintended applications. | Scattered Light Detection at660 nm |
| Chromogenic | Transmitted Light Detection(Absorbance) at 340, 405, 575, 660,800 nm. Wavelengths 340, 575, 660,and 800 are technically available butnot validated in combination with theintended applications. | Transmitted Light Detection(Absorbance) at 405, 575, 800 nm |
| Immuno-Chemical | Transmitted Light Detection(Absorbance) at 340, 405, 575, 660or 800 nm. Wavelengths 340, 405,575, and 800 are technically availablebut not validated in combination withthe intended | Transmitted Light Detection(Absorbance) at 405, 575, or 800nm |
| Clotting Applications: | Clotting Applications: | |
| Wavelengths* used in Analysis*The default wavelength is normallyused to generate the reported valueof the measurement. Thesub-wavelength is run in parallel. Ifa light intensity error occurs byusing the default wavelength thevalue from the sub-wavelength isused automatically. | PT (seconds) withDade® Innovin®(Default = 660 nm;Sub-Wavelength = 800 nm)PT (INR) with Dade® Innovin®(Default = 660 nm;Sub-Wavelength= 800 nm) | PT (seconds) withDade® 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= 800 nm) | APTT with Dade® Actin® FSLActivated PTT Reagent(Default = 660 nm;Sub-Wavelength= none) | |
| Fibrinogen withDade® Thrombin Reagent(Default = 405 nm;Sub-Wavelength = none) | Fibrinogen withDade® Thrombin Reagent(Default = 660 nm;Sub-Wavelength = none) | |
| Differences between CS-5100 and CA-1500 | ||
| Analyzer Component | Proposed DeviceSysmex® CS-5100 | Predicate DeviceSysmex® CA-1500 |
| Wavelengths* used in Analysis*The default wavelength is normallyused to generate the reported valueof the measurement. Thesub-wavelength is run in parallel. Ifa light intensity error occurs byusing the default wavelength thevalue from the sub-wavelength isused automatically. | Immuno-chemical Application:D-dimer withINNOVANCE® D-Dimer(Default = 660 nm;Sub-Wavelength = none) | Immuno-chemical Application:D-dimer withINNOVANCE® D-Dimer(Default = 800 nm;Sub-Wavelength = none) |
| 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 ± 0.5 °CReagent probe: 37.5 ± 0.5 °C | Detector: 37 ± 1.0 °CReagent probe: 37 ± 1.0 °C |
| Reagent Cooling | 10 ± 2 °C, when ambienttemperature is 20 – 28 °C.During operation 4 – 15 °C, whenambient temperature is 15 – 30 °C | 15 ± 2 °C, when ambienttemperature is 15 - 30 °C |
| Pipetting Capabilities | Reagent probe:20 – 200 μLSample probe:4 – 270 μL | Reagent probe:3 – 200 μLSample probe:5 - 450 μL |
| Sample Volumes (Plasma) | Antithrombin withINNOVANCE® Antithrombin(14 μL)D-dimer with INNOVANCE®D-Dimer (15 μL) | Antithrombin withINNOVANCE® Antithrombin(10 μL)D-dimer with INNOVANCE®D-Dimer (13 μL) |
| Bidirectional Interfacecommunication protocols | CA-, ASTM-, CS- Protocol | CA-, ASTM-Protocol |
{11}------------------------------------------------
{12}------------------------------------------------
{13}------------------------------------------------
{14}------------------------------------------------
Differences between CS-5100 and CA-1500
{15}------------------------------------------------
The above described differences do not raise new questions as to safety and effectiveness of the new device.
7 Performance Data
The following performance data were provided in support of the substantial equivalence determination.
{16}------------------------------------------------
Method comparison 7.1
Method comparison studies designed according to EP09-A3 CLSI Guideline 'Measurement Procedure Comparison and Bias Estimation Using Patient Samples' were conducted at four external sites in the United States, all sites using the same protocol.
Samples were measured on both the predicate device (Sysmex® CA-1500) as well as the new device (Sysmex® CS-5100), in random order to eliminate any inherent bias. Results were compared by Passing-Bablok regression analysis as well as Bland-Altman plots. Results from each application met the predetermined acceptance criteria. The following summary of Passing-Bablok regression shows that the proposed and predicate devices provide equivalent results when used in a clinical setting.
| Sysmex® CS-5100: Method Comparison Summary Table, Passing-Bablok regression | |||||
|---|---|---|---|---|---|
| Application(measuringinterval) | 1st Site | 2nd Site | 3rd Site | 4th Site | SitesCombined |
| CoagulationFactor Vwith Dade®Innovin®(6.0 - 149.0% of norm) | N = 133y = 1.013 x -0.205r = 0.991(r² = 0.983) | N = 151y = 1.048 x -1.431r = 0.992(r² = 0.983) | N = 148y = 0.974 x +0.853r = 0.988(r² = 0.975) | N = 177y = 1.036 x +1.319r = 0.974(r² = 0.950) | N = 609y = 1.017 x +0.185r = 0.984(r² = 0.969) |
| CoagulationFactor VIIwith Dade®Innovin(B)(6.0 - 149.0% of norm) | N = 121y = 1.040 x -1.567r = 0.993(r² = 0.986) | N = 145y = 1.017 x -0.914r = 0.993(r² = 0.986) | N = 102y = 1.081 x +0.724r = 0.995(r² = 0.991) | N = 137y = 1.117 x +0.261r = 0.987(r² = 0.974) | N = 505y = 1.051 x -0.241r = 0.989(r² = 0.978) |
| Protein Cwith ProteinC Reagent(10.1 - 131.0% of norm) | N = 138y = 1.005 x -1.892r = 0.996(r² = 0.993) | N = 176y = 1.006 x +1.483r = 0.994(r² = 0.988) | N = 110y = 0.891 x +0.714r = 0.993(r² = 0.986) | N = 200y = 0.973 x +0.644r = 0.984(r² = 0.968) | N = 624y = 0.988 x -0.413r = 0.987(r² = 0.974) |
| Protein CwithBerichrom®Protein C(10.0 - 138.0% of norm) | N = 127y = 0.963 x -0.922r = 0.995(r² = 0.991) | N = 149y = 0.935 x -1.805r = 0.992(r² = 0.984) | N = 130y = 0.923 x +2.610r = 0.995(r² = 0.990) | N = 125y = 0.985 x -0.302r = 0.994(r² = 0.987) | N = 531y = 0.950 x +0.375r = 0.992(r² = 0.984) |
{17}------------------------------------------------
Reproducibility Studies 7.2
Twenty-day precision studies were performed at two external sites in Germany and one external site in the United States. Testing followed the scheme of two runs per day, with two replicates per run, at each of the three sites according to CLSI EP05-A2 'Evaluation of Precision Performance of Quantitative Measurement Methods'. The order of the analysis of parameter, samples and quality control samples for each run and day varied to avoid an inherent bias to the study. One calibration curve of each calibrated application was used in the study. Within Run, Between Run, Between Day, and Total (within site) were calculated. The data is summarized in the following tables.
| Sysmex® CS-5100: Reproducibility Summary Table, Within Run | ||||
|---|---|---|---|---|
| Application(measuring interval) | 1st SiteWithin Run(%CV) | 2nd SiteWithin Run(%CV) | 3rd SiteWithin Run(%CV) | Sites Combined(%CV) |
| Coagulation Factor V withDade® Innovin®(6.0 - 149.0% of norm) | 2.43 - 3.52 | 1.94 - 2.96 | 2.38 - 3.42 | 2.40 - 3.16 |
| Coagulation Factor VII withDade® Innovin®(6.0 - 149.0% of norm) | 1.50 - 2.18 | 1.13 - 1.92 | 1.36 - 1.97 | 1.33 - 2.00 |
| Protein C withProtein C Reagent(10.1 - 131.0% of norm) | 3.00 - 3.83 | 2.11 - 2.94 | 1.80 - 2.47 | 2.53 - 3.22 |
| Protein C withBerichrom® Protein C(10.0 - 138.0% of norm) | 1.24 - 5.59 | 1.43 – 3.62 | 1.71 - 9.94 | 1.48 - 6.85 |
{18}------------------------------------------------
| Sysmex® CS-5100: Reproducibility Summary Table, Between Run | ||||
|---|---|---|---|---|
| Application(measuring interval) | 1st SiteBetweenRun(%CV) | 2nd SiteBetweenRun(%CV) | 3rd SiteBetweenRun(%CV) | Sites Combined(%CV) |
| Coagulation Factor V withDade® Innovin®(6.0 - 149.0% of norm) | 4.08 - 5.33 | 2.22 - 3.72 | 2.55 - 4.21 | 3.29 - 4.24 |
| Coagulation Factor VII withDade® Innovin®(6.0 - 149.0% of norm) | 0.39 - 1.80 | 0.00 - 0.93 | 0.64 - 1.09 | 0.65 - 1.29 |
| Protein C withProtein C Reagent(10.1 - 131.0% of norm) | 2.51 - 3.96 | 0.00 - 1.68 | 1.48 - 5.51 | 1.73 — 3.86 |
| Protein C withBerichrom® Protein C(10.0 - 138.0% of norm) | 0.00 - 2.56 | 0.00 - 1.44 | 0.00 - 1.14 | 0.00 - 1.04 |
| Sysmex® CS-5100: Reproducibility Summary Table, Between Day | ||||
|---|---|---|---|---|
| Application(measuring interval) | 1st SiteBetweenDay(%CV) | 2nd SiteBetweenDay(%CV) | 3rd SiteBetweenDay(%CV) | Sites Combined(%CV) |
| Coagulation Factor V withDade® Innovin®(6.0 - 149.0% of norm) | 0.00 - 0.00 | 0.88 - 2.61 | 0.00 - 2.72 | 0.00 - 0.59 |
| Coagulation Factor VII withDade® Innovin®(6.0 - 149.0% of norm) | 0.00 - 1.64 | 1.49 — 2.66 | 0.95 - 2.05 | 0.94 - 1.97 |
| Protein C withProtein C Reagent(10.1 - 131.0% of norm) | 0.00 - 1.57 | 0.00 - 2.31 | 0.00 - 0.52 | 0.00 - 1.01 |
| Protein C withBerichrom® Protein C(10.0 - 138.0% of norm) | 0.00 - 1.33 | 0.00 - 0.90 | 0.46 - 2.75 | 0.39 - 1.16 |
{19}------------------------------------------------
| CS-5100: Reproducibility Summary Table, Total CV (Within Site and Sites Combined) | ||||
|---|---|---|---|---|
| Application(measuring interval) | 1st SiteTotal CVWithin Site(%CV) | 2nd SiteTotal CVWithin Site(%CV) | 3rd SiteTotal CVWithin Site(%CV) | Total CVSites Combined(%CV) |
| Coagulation Factor V withDade® Innovin®(6.0 - 149.0% of norm) | 4.85 - 6.06 | 3.75 - 5.06 | 3.54 - 5.30 | 4.83 - 6.85 |
| Coagulation Factor VII withDade® Innovin®(6.0 - 149.0% of norm) | 1.87 - 2.82 | 1.83 - 2.96 | 2.15 - 2.87 | 3.39 - 5.03 |
| Protein C withProtein C Reagent(10.1 - 131.0% of norm) | 4.25 - 5.51 | 2.45 - 4.10 | 2.49 - 6.04 | 4.54 - 7.15 |
| Protein C withBerichrom® Protein C(10.0 - 138.0% of norm) | 1.34 - 6.15 | 1.65 - 3.88 | 2.27 - 9.95 | 3.22 - 7.92 |
{20}------------------------------------------------
Detection Capability Results 7.3
Detection capability studies were measured for the calibrated assays on the Sysmex® CS-5100: Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent, and Protein C with Berichrom® Protein C. Studies were conducted following the CLSI document EP17-A2 'Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures'. Data for all tested reagents met the predetermined acceptance criteria and support the lower limit of the clinically reportable range claim.
| Sysmex® CS-5100: Summary of Limit of Quantitation Studies | |||
|---|---|---|---|
| Application | Lower Limit ofClinicallyReportableRange(% of norm) | Measured Limitof Quantitationbased onpredicate device(% of norm) | MaximumTotal Error(% of norm) |
| Coagulation Factor V withDade® Innovin® | 6.0 | 4.80 | 0.74 |
| Coagulation Factor VII withDade® Innovin® | 6.0 | 3.39 | 0.27 |
| Protein C withProtein C Reagent | 10.1 | 9.35 | 2.91 |
| Protein C withBerichrom® Protein C | 10.0 | 8.32 | 2.07 |
{21}------------------------------------------------
Linearity & Measuring Range 7.4
Linearity studies were performed for the calibrated assays on the Sysmex® CS-5100: Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent, and Protein C with Berichrom® Protein C. All reagents met the predetermined acceptance criteria and support the clinically reportable range claim. Studies were conducted as described in CLSI EP6-A 'Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach'.
| Sysmex® CS-5100: Linearity and Measuring Range Summary | ||
|---|---|---|
| Application | Measured Linear Range | Clinically Reportable Range |
| Coagulation Factor V withDade® Innovin® | 3.4 – 180.7% of norm | 6.0 – 149.0% of norm |
| Coagulation Factor VII withDade® Innovin® | 4.3 – 179.5% of norm | 6.0 – 149.0% of norm |
| Protein C withProtein C Reagent | 7.0 – 187.7% of norm | 10.1 – 131.0% of norm |
| Protein C withBerichrom® Protein C | 7.1 – 181.3% of norm | 10.0 – 138.0% of norm |
7.5 Reference Interval
Reference interval studies were conducted at three clinical study sites in the United States following the guidance of CLSI document EP28-A3c 'Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory'. The summary is provided below. The study population did not include neonate and pediatric sample populations.
| Sysmex® CS-5100: Reference Interval Summary Table | ||
|---|---|---|
| Application | N | Sysmex® CS-5100 Reference Interval |
| Coagulation Factor V withDade® Innovin® | 194 | 80.8% of norm (5th Percentile) |
| Coagulation Factor VII withDade® Innovin® | 194 | 67.6% of norm (5th Percentile) |
| Protein C withProtein C Reagent | 194 | 76.4% of norm (5th Percentile) |
| Protein C withBerichrom® Protein C | 194 | 83.0% of norm (5th Percentile) |
{22}------------------------------------------------
Conclusions 8
Because the predicate device was cleared based in part on the results of clinical studies, and because clinical settings are required for a well-validated device, clinical testing was required to support substantial equivalence.
The non-clinical data support the safety of the device.
The clinical data demonstrate that the Sysmex® CS-5100 performs comparably to the predicate device that is currently marketed for the same intended use.
The data submitted for this premarket notification demonstrates that the device raises no new concerns as to safety and effectiveness when compared to the predicate device, and is substantially equivalent to the predicate device.
§ 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.