The Stratus® CS Acute Care™ D-dimer assay (DDMR) is an in vitro diagnostic test for the quantitative measurement of cross-linked fibrin degradation products (D-dimer) in human citrated or heparinized plasma on the Stratus® CS analyzer. The Stratus® CS Acute Care™ DDMR assay is intended for use in conjunction with a non-high clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) disease and as an aid in the diagnosis of venous thromboembolism (VTE) [deep vein thrombosis (DVT) or pulmonary embolism (PE)]. This assay is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings.

Device Description

The Stratus® CS Acute Care™ D-Dimer method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology. In this procedure, dendrimer linked monoclonal antibody is added to the center portion of a square piece of glass fiber paper in the DDMR TestPak. This antibody recognizes a distinct antigenic site on the D-dimer molecule. Sample is then added onto the paper where it reacts with the immobilized antibody. After a short incubation, a conjugate consisting of enzyme-labeled monoclonal antibody directed against a second distinct antigenic site on the D-dimer molecule is pipetted onto the reaction zone of the paper. During this second incubation period, enzyme-labeled antibody reacts with the bound D-dimer, forming an antibodyantigen-labeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the Stratus® CS STAT Fluorometric Analyzer (Stratus® CS analyzer) by applying a substrate wash solution to the center of the reaction zone. By including substrate for the enzyme within the wash solution, initiation of enzyme activity occurs simultaneously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of D-dimer in the sample. The reaction rate can then be measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessor within the analyzer.

AI/ML Overview

Acceptance Criteria and Device Performance for Stratus® CS Acute Care™ D-Dimer Assay

This document summarizes the acceptance criteria and performance of the Stratus® CS Acute Care™ D-Dimer assay as described in the provided 510(k) summary (K110303).

1. Table of Acceptance Criteria and Reported Device Performance

The study evaluated the performance of the Stratus® CS Acute Care™ D-Dimer assay against a clinical cutoff of 450 ng/mL [µg/L] (FEU) for the exclusion of Pulmonary Embolism (PE).

Acceptance Criteria (Implied by Predicate Device Equivalence and Clinical Relevance for PE Exclusion):
While explicit numerical acceptance criteria for sensitivity, specificity, and NPV are not directly stated as pass/fail thresholds, the study aims to demonstrate substantial equivalence to the Innovance D-Dimer assay and clinical utility for PE exclusion, implying that the performance metrics should be comparable to or ideally exceed those required for safe and effective PE exclusion. For D-dimer assays used to exclude PE, high sensitivity and negative predictive value (NPV) are critical. The reported values are generally considered acceptable for this application.

Reported Device Performance:

Citrated Plasma: In all patients

Instrument	PE Patients (n)	Cutoff ng/mL [µg/L] FEU	Sensitivity (CL) %	Specificity (CL) %	NPV (CL) %
Stratus® CS analyzer	655	450	98.9 (94.1 – 100.0)	42.5 (38.3 – 46.7)	99.6 (97.7 – 100.0)

Citrated Plasma: In Patients with low and moderate pre-test probability

Instrument	PE Patients (n)	Cutoff ng/mL [µg/L] FEU	Sensitivity (CL) %	Specificity (CL) %	NPV (CL) %
Stratus® CS analyzer	625	450	98.7 (92.9 – 100.0)	43.0 (38.8 – 47.3)	99.6 (97.7 – 100.0)

Heparinized Plasma: In all patients

Instrument	PE Patients (n)	Cutoff ng/mL [µg/L] FEU	Sensitivity (CL) %	Specificity (CL) %	NPV (CL) %
Stratus® CS analyzer	427	450	98.3 (91.1 – 100.0)	29.7 (25.1 – 34.7)	99.1 (95.0* – 100.0)
*95.04

Heparinized Plasma: In Patients with low and moderate pre-test probability

Instrument	PE Patients (n)	Cutoff ng/mL [µg/L] FEU	Sensitivity (CL) %	Specificity (CL) %	NPV (CL) %
Stratus® CS analyzer	401	450	97.9 (88.7 – 100.0)	29.9 (25.2 – 35.0)	99.1 (94.9 – 100.0)

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

Citrated Plasma: 730 consecutive patients initially, 655 patients remaining after exclusions for final analysis.
Heparinized Plasma: 468 consecutive patients initially, 427 patients remaining after exclusions for final analysis.
Data Provenance: The study was a multi-center study. The document does not specify the countries of origin but states it's a "multi-center study." The data is prospective, collected from consecutive patients presenting to the emergency department with suspected PE.

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

The document does not explicitly state the number of experts used to establish the ground truth or their qualifications in detail. However, the ground truth for PE diagnosis appears to be established through a combination of imaging methods (e.g., spiral CT and/or VQ scan) for patients with positive D-dimer and/or high PTP, and a three-month follow-up for patients with negative D-dimer/low/moderate PTP or negative imaging results. This implies that the diagnosis of PE was made by medical professionals (e.g., radiologists, clinicians) utilizing established diagnostic protocols but does not specify individual expert roles for establishing a "ground truth" for the test set.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1) for establishing the ground truth diagnoses. The diagnostic process involved imaging (spiral CT, VQ scan) and clinical follow-up for three months. It is implied that standard clinical practices and interpretations were followed for these diagnostic procedures, rather than a specific consensus or adjudication process among multiple independent experts to establish the ground truth for each case.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not performed. This study focuses on the performance of the device (assay) itself in a standalone manner, rather than as an aid to human interpretation.

6. If a Standalone Study Was Done

Yes, a standalone study of the algorithm's performance (the D-dimer assay) was done. The reported sensitivity, specificity, and negative predictive value are directly from the assay's performance against the established clinical ground truth for PE. There is no human-in-the-loop component for these reported performance metrics.

7. The Type of Ground Truth Used

The ground truth used was a combination of:

Imaging Data: Spiral CT and/or VQ scans were used for patients with positive D-dimer results and/or high pre-test probability (PTP).
Outcomes Data (Clinical Follow-up): Patients with negative D-dimer results and low or moderate PTP (or negative imaging results) were followed for three months to evaluate potential development of PE. This follow-up serves as an outcome-based ground truth to confirm the absence of PE.

8. The Sample Size for the Training Set

The document does not specify a separate training set. This 510(k) submission describes a clinical validation study, implying that the D-dimer assay and its cutoff of 450 ng/mL [µg/L] (FEU) were already established, likely based on previous research or predicate device characteristics. The study described here acts as a test set for validating the performance of the assay rather than for training a new algorithm.

9. How the Ground Truth for the Training Set Was Established

As no explicit training set is described, the method for establishing ground truth for a training set is not applicable to the information provided. The study focuses on evaluating the assay's performance on a validation dataset.

Summary

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MAY 16 2011

510(k) Summary for Stratus CS Acute Care DDMR Assay

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: _ K 110303

1. Manufacturer's Name, Address, Telephone, and Contact Person, Date of Preparation:
  Manufacturer:

Siemens Healthcare Diagnostics Products GmbH Emil-von-Behring Str. 76 D-35001, Marburg Germany

Contact Information:

Siemens Healthcare Diagnostics Inc. Glasgow Site P.O. Box 6101 Newark, Delaware 19714 Attn: Kathleen Dray-Lyons Tel: 781-826-4551 Fax: 781-826-2497

Preparation date:

April 19, 2011

Device Name/ Classification: Stratus® CS Acute Care™ D-Dimer assay 2.
Class:

Panel:

Fibrinogen and Fibrin Split Product, Antigen, Antiserum and controls, Class II 21 CFR 864.7320 Hematology (HE) DAP

3. Identification of the Legally Marketed Device:

Innovance D-Dimer - K093626

4. Device Description:

Product Code:

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period, enzyme-labeled antibody reacts with the bound D-dimer, forming an antibodyantigen-labeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the Stratus® CS STAT Fluorometric Analyzer (Stratus® CS analyzer) by applying a substrate wash solution to the center of the reaction zone. By including substrate for the enzyme within the wash solution, initiation of enzyme activity occurs simultaneously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of D-dimer in the sample. The reaction rate can then be measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessor within the analyzer.

5. Device Intended Use:

Medical device to which equivalence is claimed and comparison information: 6.

The Stratus® CS DDMR assay is substantially equivalent to the Innovance D-Dimer (K093626) assay. The Stratus® CS DDMR method, like the Innovance D-Dimer method, is intended for use in conjunction with a non-high clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) disease.

7. Device Performance Characteristics:

Clinical Performance of the Stratus® CS Acute Care™ D-Dimer assay to exclude PE in Citrated Plasma

The Stratus® CS Acute Care™ D-Dimer assay was evaluated on the Stratus® CS analyzer in a multi-center study to validate the exclusion of PE using fresh citrated plasma specimens collected from 730 consecutive patients presenting to the emergency department with suspected PE. Of these 730 patients, 75 were excluded for a total of 655 patients available for final analysis.

All patients were evaluated using the Wells' rules to estimate a high, moderate or low pretest probability (PTP) of PE. Patient specimens were tested with the Stratus® CS Acute Care™ D-Dimer assay and results were compared to a cutoff value of 450 ng/mL [[gg/L] (FEU), A D-dimer result <450 ng/mL [µg/L] (FEU) was considered negative and a D-dimer result ≥450 ng/mL [µg/L] (FEU) was considered positive.

Patients with a positive D-dimer result and/or a high PTP were evaluated by imaging methods, e.g. spiral CT and/or VQ scan. Patients with a negative D-dimer result and a low or moderate PTP (these patients underwent imaging at the physician's discretion), and patients with neqative imaging results, were followed for three months to evaluate potential development of PE.

The overall prevalence of PE in those patients available for final analysis was 14.0% (92/655). The following instrument-specific sensitivity, specificity and negative predictive value (NPV) with upper and lower 95% confidence limits (CL) were obtained with the Stratus® CS Acute Care™ D-Dimer clinical cutoff of 450 ng/mL [ug/L] (FEU).

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Citrated Plasma: In all patients

Instrument	PEPatients(n)	Cutoffng/mL [μg/L]FEU	Sensitivity(CL) %	Specificity(CL) %	NPV(CL) %
Stratus® CSanalyzer	655	450	98.9(94.1 –100.0)	42.5(38.3 –46.7)	99.6(97.7 –100.0)

Citrated Plasma: In Patients with low and moderate pre-test probability

Instrument	PEPatients(n)	Cutoffng/mL [μg/L]FEU	Sensitivity(CL) %	Specificity(CL) %	NPV(CL) %
Stratus® CSanalyzer	625	450	98.7(92.9 –100.0)	43.0(38.8 –47.3)	99.6(97.7 –100.0)

Clinical Performance of the Stratus® CS Acute Care™ D-Dimer assay to exclude PE in Heparinized Plasma

The Stratus® CS Acute Care™ D-Dimer assay was evaluated on the Stratus® CS analyzer in a multi-center study to validate the exclusion of PE using fresh heparinized plasma specimens collected from 468 consecutive patients presenting to the emergency department with suspected PE. Of these 468 patients, 41 were excluded for a total of 427 patients available for final analysis.

All patients were evaluated using the Wells' rules to estimate a high, moderate or low pre-test probability (PTP) of PE. Patient specimens were tested with the Stratus® CS Acute Care™ D-Dimer assay and results were compared to a cutoff value of 450 ng/mL [ug/L] (FEU). A D-dimer result <450 ng/mL [ug/L] (FEU) was considered negative and a D-dimer result ≥450 ng/mL [µg/L] (FEU) was considered positive.

Patients with a positive D-dimer result and/or a high PTP were evaluated by imaging methods, e.q. spiral CT and/or VQ scan. Patients with a neqative D-dimer result and a low or moderate PTP (these patients underwent imaging at the physician's discretion), and patients with negative imaging results, were followed for three months to evaluate potential development of PE.

The overall prevalence of PE in those patients available for final analysis was 14.1% (60/427). The following instrument-specific sensitivity, specificity and negative predictive value (NPV) with upper and lower 95% confidence limits (CL) were obtained with the Stratus® CS Acute Care™ D-Dimer clinical cutoff of 450 ng/mL [µg/L] (FEU).

Heparinized Plasma: In all patients

Instrument	PEPatients(n)	Cutoffng/mL [µg/L]FEU	Sensitivity(CL) %	Specificity(CL) %	NPV(CL) %
Stratus® CSanalyzer	427	450	98.3(91.1 -100.0)	29.7(25.1 -34.7)	99.1(95.0* -100.0)

*95.04

Heparinized Plasma: in Patients with low and moderate pre-test probability

Instrument	PEPatients(n)	Cutoffng/mL [µg/L]FEU	Sensitivity(CL) %	Specificity(CL) %	NPV(CL) %
Stratus® CSanalyzer	401	450	97.9(88.7 –100.0)	29.9(25.2 –35.0)	99.1(94.9 –100.0)

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Comparative Method	Slope	Intercept(ng/mL) [µg/L] FEU	CorrelationCoefficient	n
INNOVANCE® D-Dimer	0.950	-12.32	0.938	396

The range of samples: 54 to 4506 ng/mL [µg/L] FEU

8. Conclusion:

These studies demonstrate correlation and equivalent performance between the Innovance® D-Dimer assay and the Stratus® CS Acute Care™ D-Dimer assay.

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Image /page/4/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with three stripes forming its wing and tail. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Siemens Healthcare Diagnostics c/o Ms. Kathleen Ann Dray-Lyons Manager, Regulatory Affairs 500 GBC Drive P.O. Box 6101 Newark, DE 19714-6101

MAY 1 6 2011

Re: K110303

Trade/Device Name: Stratus CS® Acute Care™ DDMR Regulation Number: 21 CFR 864.7320 Regulation Name: Fibrinogen/Fibrin Degradation Products Assay Regulatory Class: Class II Product Code: DAP Dated: April 20, 2011 Received: April 21, 2011

Dear Ms. Dray-Lyons:

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. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter

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Page 2 - Ms. Kathleen Ann Dray-Lyons

will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

ia m chan

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

Stratus® CS Acute Care™ DDMR Device Name:

Indications For Use:

The Stratus® CS Acute Care™ D-dimer assay (DDMR) is an in vitro diagnostic test for the quantitative measurement of cross-linked fibrin degradation products (D-dimer) in human citrated or heparinized plasma on the Stratus® CS analyzer. The Stratus® CS Acute Care™ DDMR assay is intended for use in conjunction with a non-high clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) disease and as an aid in the diagnosis of venous thromboembolism (VTE) [deep vein thrombosis (DVT) or pulmonary embolism (PE)). This assay is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings.

Prescription Use _ x (Per 21 CFR 801 Subpart D) AND/OR

Over-The-Counter-Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation

Division Sign-Off

Office of in Vitro Diagnostic Device Evaluation and Safety

510(k) K 110303

Page 1 of

Regulation Number and Section

§ 864.7320 Fibrinogen/fibrin degradation products assay.

(a)
Identification. A fibrinogen/fibrin degradation products assay is a device used to detect and measure fibrinogen degradation products and fibrin degradation products (protein fragments produced by the enzymatic action of plasmin on fibrinogen and fibrin) as an aid in detecting the presence and degree of intravascular coagulation and fibrinolysis (the dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels).(b)
Classification. Class II (performance standards).