Stratus® CS Acute Care™ CardioPhase® hsCRP TestPak: The Stratus® CS Acute Care™ CardioPhase® hsCRP assay is an in vitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in lithium and sodium heparin plasma. In acute phase response, increased levels of a number of plasma proteins, including C-reactive protein, is observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurements of hsCRP, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events, in patients with stable coronary disease or acute coronary syndromes.

Stratus® CS Acute Care™ CardioPhase® hsCRP CalPak: The Stratus® CS Acute Care™ CardioPhase® high sensitivity CRP Calibrator, is an in vitro diagnostic product intended to be used for calibration of the Acute Care™ CardioPhase® method on the Stratus® CS analyzer.

Stratus® CS Acute Care™ CardioPhase® hsCRP DilPak: The Stratus® CS Acute Care™ CardioPhase® high sensitivity CRP Dilution Pak, is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ CardioPhase® TestPak, for the measurement of samples with elevated levels of C-reactive protein.

Device Description

The Stratus® CS Acute Care™ CardioPhase® hsCRP method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the Stratus® CS Acute™ Care CardioPhase® hsCRP device:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Specific Metric	Predicate Device (Dade Behring CardioPhase® hsCRP on BN™ System)	Test Device (Stratus® CS Acute™ Care CardioPhase® hsCRP) Performance
Method Comparison (Regression Analysis)	Slope (0-50 mg/L)	N/A (Standard for comparison)	0.952
	Intercept (0-50 mg/L)	N/A (Standard for comparison)	0.098
	Correlation Coefficient (0-50 mg/L)	N/A (Standard for comparison)	0.999
	Slope (0-10 mg/L)	N/A (Standard for comparison)	0.997
	Intercept (0-10 mg/L)	N/A (Standard for comparison)	0.047
	Correlation Coefficient (0-10 mg/L)	N/A (Standard for comparison)	0.995
	Slope (0-5 mg/L)	N/A (Standard for comparison)	1.002
	Intercept (0-5 mg/L)	N/A (Standard for comparison)	0.042
	Correlation Coefficient (0-5 mg/L)	N/A (Standard for comparison)	0.994

Study Details:

Sample size used for the test set and the data provenance:
- Sample Size: 154 plasma samples.
- Data Provenance: Not explicitly stated regarding country of origin or retrospective/prospective nature. However, it is a method comparison study using patient samples, which are typically retrospective or collected prospectively for validation purposes. Given the nature of a 510(k) submission for substantial equivalence to a legally marketed device, these are likely clinical samples run on both systems.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not provided in the summary. For this type of in vitro diagnostic device (quantitative assay), the "ground truth" is typically the measurement obtained from the predicate device itself, or a validated reference method against which both the predicate and new device are compared. Expert consensus in the traditional sense (e.g., radiologist review) is not applicable here.
Adjudication method for the test set:
- This information is not applicable for this type of quantitative assay comparison. Adjudication methods like 2+1 or 3+1 are used for subjective interpretations (e.g., image readings) where disagreement between multiple readers needs to be resolved. In this case, the comparison is quantitative, comparing numerical results from two different assay systems.
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 was not done. This is an in vitro diagnostic device (an assay for C-reactive protein) and does not involve human readers interpreting AI outputs. The "device" itself is an analytical instrument and reagents.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, in spirit. The study evaluates the performance of the "algorithm" (the Stratus® CS Acute™ Care CardioPhase® hsCRP assay) by comparing its quantitative results to a predicate device. This is a standalone evaluation of the analytical performance of the automated assay system, without human interpretation as part of the core measurement.
The type of ground truth used:
- The "ground truth" for this study is the measurement obtained from the legally marketed predicate device, the Dade Behring CardioPhase® hsCRP assay, performed on the BN™ System. The study aims to demonstrate that the new device produces results substantially equivalent to an already accepted method.
The sample size for the training set:
- This information is not provided in the summary. For a non-AI based assay like this, there isn't typically a "training set" in the machine learning sense. Assay development involves optimizing reagents and protocols, and validation studies (like the one reported) are performed once development is complete.
How the ground truth for the training set was established:
- This information is not applicable as there is no mention of a "training set" in the context of an AI/machine learning algorithm. For traditional IVDs, assay development and internal validation would precede the formal comparison study.

Summary

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MAY - 4 2005

510(k) Summary for Stratus® CS Acute™ Care CardioPhase® hsCRP

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: K0600369

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

Dade Behring Inc. Glasgow Site P.O. Box 6101 Newark, Delaware 19714

Dade Behring Inc. Contact Information: Glasgow Site P.O. Box 6101 Newark, Delaware 19714 Attn: Kathleen Dray-Lyons Tel: 781-826-4551 Fax: 781-826-2497
Preparation date: February 10, 2006
Stratus® CS Acute Care™ CardioPhase® hsCRP TestPak
Stratus® CS Acute Care™ CardioPhase® hsCRP CarPak
Stratus® CS Acute Care™ CardioPhase® hsCRP DilPak 2. Device Name: Classification: Class II
21 CFR 866.5270; 862.1150 Panel: Immunology (81) Product Code: NQD; JIT

3. Identification of the Legally Marketed Device:

Dade Behring CardioPhase hsCRP- K033908

000112

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Dade Behring Inc. Stratus® CS Acute Care™ CardioPhase® hsCRP 510(k) Notification

4. Device Description:

The Stratus® CS Acute Care™ CardioPhase® hsCRP method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology.

ર. Device Intended Use:

Stratus® CS Acute Care™ CardioPhase® hsCRP TestPak:

The Stratus® CS Acute Care™ CardioPhase® hsCRP assay is an in vitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in lithium and sodium heparin plasma. In acute phase response, increased levels of a number of plasma proteins, including C-reactive protein, is observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurements of hsCRP, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events, in patients with stable coronary disease or acute coronary syndromes.

Stratus® CS Acute Care™ CardioPhase® hsCRP CalPak:

The Stratus® CS Acute Care™ CardioPhase® high sensitivity CRP Calibrator, is an in vitro diagnostic product intended to be used for calibration of the Acute Care™ CardioPhase® method on the Stratus® CS analyzer.

Stratus® CS Acute Care™ CardioPhase® hsCRP DilPak:

The Stratus® CS Acute Care™ CardioPhase® high sensitivity CRP Dilution Pak, is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ CardioPhase® TestPak, for the measurement of samples with elevated levels of Creactive protein.

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

The Stratus® CS Acute Care™ CardioPhase® hsCRP assay is substantially equivalent to the Dade Behring CardioPhase hsCRP assay (K033908). The Stratus® CS Acute Care™ CardioPhase® hsCRP assay, like the Dade Behring CardioPhase® hsCRP assay is an in vitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP).

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7. Device Performance Characteristics:

The Stratus® CS Acute Care™ CardioPhase "hsCRP assay was compared to the Dade
Behring CardioPhase® hsCRP assay by evaluating 154 plasma samples with concentrations ranging from 0.20 to 48.05 mg/L. Regression analysis of the results yielded the following equations:

Comparative Method	Range ofSample values	Slope	Intercept	CorrelationCoefficient	N
Dade BehringCardioPhase ® hsCRP,performed on the BN™System	0 – 50 mg/L	0.952	0.098	0.999	154
	0 – 10 mg/L	0.997	0.047	0.995	123
	0 – 5 mg/L	1.002	0.042	0.994	107

Method Comparison Study

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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its wings spread, and three ribbon-like shapes extending from its body. 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 2098 Gaither Road Rockville MD 20850

Ms. Kathleen Dray-Lyons Manager, Regulatory Affairs and Compliance Dade Behring Inc. Glasgow Building 500 PO Box 6101, M/S 514 Newark DE 19714

IV - 4 222

Re: K060369

Trade/Device Name: Stratus® CS Acute Cute™ CardioPhase® hsCRP TestPak Stratus® CS Acute Cute™ CardioPhase® hsCRP CalPak Stratus® CS Acute Cute™ CardioPhase® hsCRP DilPak Regulation Number: 21 CFR& 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: NQD, JIT Dated: February 10, 2006 Received: February 13, 2006

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

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Alberto Gutt

Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications Statement

Stratus® CS Acute Care™ CardioPhase® hsCRP Device Name:

Indications for Use:

Stratus® CS Acute Care™ CardioPhase® hsCRP TestPak:

Stratus CS Acute Care™ CardioPhase® hsCRP CalPak:

Stratus® CS Acute Care™ CardioPhase® hsCRP DilPak:

The Stratus® CS Acute Care™ CardioPhase® high sensitivity CRP Dilution Pak, is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ CardioPhase® hsCRP TestPak, for the measurement of samples with elevated levels of C- reactive protein.

Prescription Use (Per 21 CFR 801 Subpart D)

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

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benner

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

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Regulation Number and Section

§ 866.5270 C-reactive protein immunological test system.

(a)
Identification. A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.(b)
Classification. Class II (performance standards).