High Sensitivity Cardiac C-Reactive Protein (CCRP) reagent, when used in conjunction with IMMAGE® 800 Immunochemistry Systems and Calibrator 5 Plus, is intended for the quantitative determination of C-Reactive protein in human serum or plasma by rate turbidimetry.

Measurement of C-Reactive protein (CRP) aids in evaluation of stress, trauma, infection, inflammation, surgery, and associated diseases. Cardiac CRP assays are indicated for use as an aid in the identification and stratification of individuals at risk for future cardiovascular disease. When used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, CRP may be useful as an independent marker of prognosis for recurrent events in patients with stable coronary disease or acute coronary syndrome.

CAL 5 Plus (Calibrator 5 Plus), when used in conjunction with Beckman Coulter reagents, is intended for use on IMMAGE® Immunochemistry Systems for the calibration of Anti-Streptolysin O (ASO), C-Reactive Protein (CRP) and Rheumatoid Factor (RF).

Device Description

High Sensitivity Cardiac C-Reactive Protein (CCRP) reagent is intended for the quantitative determination of C-Reactive protein in human serum or plasma by rate turbidimetry. The IMMAGE® 800 Immunochemistry Systems CCRP reagent is based on the highly sensitive Near Infrared Particle Immunoassay rate methodology. An anti-CRP antibody-coated particle binds to CRP in the patient sample resulting in the formation of insoluble aggregates causing turbidity. The rate of aggregate formation is directly proportional to the concentration of CRP in the sample.

CAL 5 Plus (Calibrator 5 Plus) is a frozen liquid serum matrix intended for use on IMMAGE® Immunochemistry Systems for the calibration of Anti-Streptolysin O (ASO), C-Reactive Protein (CRP) and Rheumatoid Factor (RF).

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Immage® 800 Immunochemistry Systems High Sensitivity Cardiac C-Reactive Protein (CCRP) Reagent, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a quantitative format for method comparison, linearity, or imprecision (e.g., "slope must be between X and Y"). However, it presents the results of these studies, and the FDA's decision to grant substantial equivalence implies that these results met their internal criteria for acceptance.

For the purpose of this analysis, I will infer the implicit acceptance criteria from the context of standard analytical performance requirements for diagnostic devices and the successful outcome of the 510(k) submission.

Performance Characteristic	Acceptance Criteria (Inferred)	Reported Device Performance (Immage® High Sensitivity Cardiac CCRP Reagent)
Method Comparison
Slope (vs. Predicate)	Close to 1.0	0.965 (0.2 to 60 mg/L)
		1.013 (0.2 to 10 mg/L)
Intercept (vs. Predicate)	Close to 0	0.334 (0.2 to 60 mg/L)
		-0.026 (0.2 to 10 mg/L)
R (Correlation Coefficient)	Close to 1.0	0.9962 (0.2 to 60 mg/L)
		0.9939 (0.2 to 10 mg/L)
Imprecision (Within-Run)	%CV typically < 5-10%	Level 1: 2.8% (Mean 0.807 mg/dL)
		Level 2: 3.0% (Mean 13.56 mg/dL)
		Level 3: 3.3% (Mean 51.538 mg/dL)
Imprecision (Total)	%CV typically < 5-10%	Level 1: 3.5% (Mean 0.807 mg/dL)
		Level 2: 3.1% (Mean 13.56 mg/dL)
		Level 3: 4.3% (Mean 51.538 mg/dL)
Stability (Calibrator)	At least 24 months	Predicted 32-33 months (based on accelerated studies)
Linearity	Device should demonstrate linearity across its stated analytical range (0.2 to 60.0 mg/L, extended to 1440.0 mg/L).	No specific data presented in the summary, but implied to be acceptable for 510(k) submission. Documentation notes "linearity experiments" were performed.

Note: The "acceptance criteria" are inferred based on typical industry standards for analytical performance. The document itself states that "The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence... Equivalence is demonstrated through method comparison, stability, linearity, and imprecision experiments." This indicates the reported performance met the internal criteria for FDA clearance.

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

Method Comparison Test Set:
- N: 157 samples (for range 0.2 to 60 mg/L) and 98 samples (for range 0.2 to 10 mg/L).
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). However, given it's a clinical diagnostic test, samples would typically be from human serum or plasma. It's common for such studies to use a combination of prospective patient samples and spiked samples to cover the analytical range. The document refers to "the patient sample," suggesting clinical samples were used.
Imprecision Test Set:
- N: 80 replicates per level (three levels tested).
- Data Provenance: Not explicitly stated. These would typically be internal quality control materials or pooled patient samples.

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

Not Applicable. This device is a diagnostic reagent for quantitative measurement of a biomarker (CRP). The "ground truth" for quantitative assays is established by reference methods or established predicate devices, not by expert consensus in the way image-based or clinical diagnostic (e.g., physician-interpreted) devices use experts.
- The "ground truth" for the method comparison study was the results obtained from the Dade Behring CardioPhase hsCRP predicate device.

4. Adjudication Method for the Test Set

Not Applicable. As described above, this is a quantitative measurement device, not one requiring human interpretation and subsequent adjudication of discrepancies. The comparison is statistical against a predicate device.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. An MRMC study is not relevant for this type of in vitro diagnostic device (reagent for quantitative measurement). MRMC studies are used for devices that involve human interpretation of images or other data, often to assess the impact of AI assistance on diagnostic accuracy.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes. This is a standalone performance study. The Immage® High Sensitivity Cardiac CCRP Reagent, when used with the IMMAGE® 800 Immunochemistry Systems, directly provides a quantitative result. There is no human interpretation of raw data or "human-in-the-loop" decision-making that modifies the final reported CRP concentration from the device. The reported values are the output of the algorithm/reagent system itself.

7. Type of Ground Truth Used

Predicate Device Results (Comparative Ground Truth): For the method comparison, the "ground truth" was effectively the results obtained from the legally marketed Dade Behring CardioPhase hsCRP predicate device. The goal was to show substantial equivalence, meaning the new device's results correlate highly and agree well with the predicate.
Quantitative Analytical Targets: For imprecision and linearity studies, the "ground truth" would be established concentrations in quality control materials or spiked samples.

8. Sample Size for the Training Set

Not explicitly stated in the summary. This document is a 510(k) summary, which focuses on validation data rather than detailed development or training data. For a reagent (chemical/immunological assay), the "training set" doesn't typically refer to a data set for machine learning in the same way it would for an AI algorithm. Instead, it would refer to the samples and experiments used during the assay development and optimization phase to establish reagents, reaction conditions, and calibration curve parameters. This detailed development data is not usually included in a 510(k) summary.

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

Not explicitly stated in the summary. Similar to point 8, the "ground truth" for developing and optimizing an analytical reagent would involve:
- Known concentrations: Using reference materials or gravimetrically prepared standards with known CRP concentrations.
- Comparison to existing methods: Benchmarking against established reference methods or predicate devices during development to refine the assay's performance and ensure it meets desired analytical characteristics (sensitivity, specificity, dynamic range).

This process is part of the extensive R&D phase that precedes the formal validation studies presented in the 510(k) submission.

Summary

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K07/002

Summary of Safety & Effectiveness Immage® 800 Immunochemistry Systems High Sensitivity Cardiac C-Reactive Protein (CCRP) Reagent

1.0 Submitted By:

Tara Viviani Senior Regulatory Affairs Specialist Beckman Coulter, Inc. 200 S. Kraemer Blvd., W-110 Brea, California 92822-8000 Telephone: (714) 961-3626 FAX: (714) 961-4234

JUN 2 1 2007

Date Submitted: 2.0

April 6, 2007

3.0 Device Name(s):

3.1 Proprietary Names

Immage® Immunochemistry Systems High Sensitivity Cardiac C-Reactive Protein (CCRP) Reagent Beckman CAL 5 Plus

Classification Name 3.2

C-Reactive Protein immunological test system (21 CFR § 866.5270) Calibrator, multi-analyte mixture (21 CFR § 862.1150)

4.0 Predicate Device:

Candidate(s)	Predicate	Manufacturer	DocketNumber
IMMAGE ImmunochemistrySystems High SensitivityCardiac CCRP Reagent	Dade BehringCardioPhase hsCRP	Dade BehringInc.*	K033908
IMMAGE ImmunochemistrySystems High SensitivityCardiac CCRP Reagent	IMMAGE ImmunochemistrySystems High SensitivityCRPH Reagent	BeckmanCoulter, Inc	K010236
Beckman CAL 5 Plus	Beckman Cal 5 Plus	BeckmanCoulter, Inc.	K926236/A

*Dade Behring Inc. (Newark, DE)

5.0 Description:

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6.0 Intended Use:

CAL 5 Plus (Calibrator 5 Plus). when used in coniunction with Beckman Coulter reagents. is intended for use on IMMAGE® Immunochemistry Systems for the calibration of Anti-Streptolysin O (ASO), C-Reactive Protein (CRP) and Rheumatoid Factor (RF).

Clinical Significance:

7.0 Comparison to Predicate(s):

The following table shows similarities and differences between the predicates identified in Section 4.0 of this summary.

	Similarities
ImmageCardiac CCRPReagent	Intended Use	Same as BehringCardioPhase hsCRP
	Use of Latexparticle technology	Same asDade Behring CardioPhase hsCRP and ImmageCRPH
	Liquid stablereagent	The formulation is identical to Immage CRPHReagent.
	Single pointadjustedCalibration model	Same as IMMAGE CRPH Reagent
Beckman CAL5 Plus	Formulation	Identical to Beckman CAL 5 Plus
	Differences
ImmageCardiac CCRPReagent	Antibody source	IMMAGE CCRP uses goat and mouse while theDade Behring Kit uses mouse only.
	Initial dilution range	The IMMAGE initial dilution range covers from 0.2to 60.0 mg/L while the Dade Behring Kit coversfrom 3.0 to 220 mg/L
	Extended dilutionrange	The IMMAGE extended dilution range covers up to1440.0 mg/L while the Dade Behring Kit covers therange from 0.16 to 16000.0 mg/L
	Calibration model	IMMAGE High Sensitivity Cardiac CCRP uses adifferent model equation for the predeterminedcalibration curve than IMMAGE CRPH.

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8.0 Summary of Performance Data:

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. Equivalence is demonstrated through method comparison, stability, linearity, and imprecision experiments.

Candidate	Slope	Intercept	R	N	Predicate Method
IMMAGE High SensitivityCardiac CCRP Reagent(0.2 to 60 mg/L)	0.965	0.334	0.9962	157	Dade BehringCardioPhase hsCRP
IMMAGE High SensitivityCardiac CCRP Reagent(0.2 to 10 mg/L)	1.013	-0.026	0.9939	98	Dade BehringCardioPhase hsCRP

Method Comparison Study Results

IMMAGE High Sensitivity Cardiac CCRP Reagent Imprecision Results

Sample	Mean (mg/dL)	S.D. (mg/dL)	%C.V.	N
		Within-Run Imprecision
Level 1	0.807	0.0229	2.8	80
Level 2	13.56	0.4109	3.0	80
Level 3	51.538	1.7181	3.3	80
		Total Imprecision
Level 1	0.807	0.0279	3.5	80
Level 2	13.56	0.4248	3.1	80
Level 3	51.538	2.1933	4.3	80

Beckman CAL 5 Plus Stability Testing Summary

StressTemperature	Duration ofIncubation	PredictedStability	Beckman StabilityClaim*
32°C	40 days	32 months	24 months
37°C	24 days	33 months	24 months
41°C	15.5 days	32 months	24 months

expiration dating placed on the packaging based in date of manufacture

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

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Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Beckman Coulter, Inc. Diagnostics Development Center c/o Ms. Tara Viviani Sr. Regulatory Affair Specialist 200 S. Kraemer Boulevard, W-110 P.O. Box 8000 Brea, CA 92822-8000

JUN 2 1 2007

Re: K071002

Trade/Device Name: Immage® Immunochemistry Systems High Sensitivity Cardiac C-Reactive Protein (CCRP), Cal 5 Plus (Calibrator 5 Plus) Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: NQD, JIX Dated: April 06, 2007 Received: April 09, 2007

Dear Ms. Viviani:

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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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) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Jean M. Cooper, M.S., D.V.M.

Yéan M. Cooper, M.S., D.V.M. 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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510(k) Number (if known): K071002

Device Name: Immage® Immunochemistry Systems High Sensitivity Cardiac C-Reactive Protein (CCRP) Beckman CAL 5 Plus

Reagent:

Indications for Use:

Clinical Significance:

Calibrator:

Indications for use:

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-the-Counter Use (21 CFR 807 Subpart C)

(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. Benam
ion Sign-Off

ion Sign-Off

Office of In Vitro Diagnostic Device
Evaluation and Safety

K07/002

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Beckman Coulter, Inc., Section 510(k) Notification IMMAGE® System High Sensitivity Cardiac C-Reactive Protein (CRPH) Reagent, Immage CCRP510k_Summary UPDATED.doc, April 2007

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).