High Sensitivity Cardiac C-Reactive Protein (CRPH) reagent, when used in conjunction with SYNCHRON LX® PRO System, UniCel® DxC 600/800 System(s) and SYNCHRON® Systems CAL 5 Plus, is intended for the quantitative determination of C-Reactive Protein in human serum or plasma bv rate turbidimetry.

Clinical Significance:
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.

Device Description

High Sensitivity Cardiac C-Reactive Protein (CRPH) reagent, is intended for the quantitative determination of C-Reactive Protein in human serum or plasma by rate turbidimetry. SYNCHRON® System(s) CRPH 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.

AI/ML Overview

Here's an analysis of the provided text regarding the SYNCHRON® Systems High Sensitivity Cardiac C-Reactive Protein (CRPH) Reagent, addressing your specific questions:

Acceptance Criteria and Device Performance Study

The submission focuses on establishing substantial equivalence to previously cleared devices through performance data rather than defining explicit acceptance criteria in the typical sense of a target performance metric (e.g., "sensitivity must be >90%"). Instead, the "acceptance criteria" are implied by the demonstration that the new device performs comparably to the predicate device and meets established analytical performance standards (linearity, imprecision).

The study that "proves the device meets the acceptance criteria" is the Summary of Performance Data presented in section 8.0.

1. Table of Acceptance Criteria and the Reported Device Performance

Parameter	Implied Acceptance Criteria (Demonstrated Equivalence/Analytical Performance)	Reported Device Performance (SYNCHRON Cardiac CRPH)
Method Comparison	Strong correlation with predicate device (Dade Behring CardioPhase hsCRP)	0.2 to 80 mg/L range:Slope: 1.048Intercept: 0.024Correlation Coefficient (r): 0.98990.2 to 10 mg/L range:Slope: 1.030Intercept: -0.008Correlation Coefficient (r): 0.9910
Imprecision	Low variability (e.g., %CV within acceptable clinical laboratory limits)	Within-Run Imprecision (N=80 for each level):- Level 1 (Mean 0.063 mg/dL): S.D. 0.0019 mg/dL, %C.V. 3.1- Level 2 (Mean 1.368 mg/dL): S.D. 0.0222 mg/dL, %C.V. 1.6- Level 3 (Mean 5.639 mg/dL): S.D. 0.0907 mg/dL, %C.V. 1.6Total Imprecision (N=80 for each level):- Level 1 (Mean 0.063 mg/dL): S.D. 0.0033 mg/dL, %C.V. 5.3- Level 2 (Mean 1.368 mg/dL): S.D. 0.0381 mg/dL, %C.V. 2.8- Level 3 (Mean 5.639 mg/dL): S.D. 0.1823 mg/dL, %C.V. 3.2
Linearity	Not explicitly detailed in the provided summary, but mentioned as performed
Stability	Not explicitly detailed in the provided summary, but mentioned as performed

2. Sample size used for the test set and the data provenance

Sample Size (Method Comparison):
- 269 samples for the 0.2 to 80 mg/L range comparison.
- 149 samples for the 0.2 to 10 mg/L range comparison.
Sample Size (Imprecision): 80 replicates for each of the 3 levels tested (total 240 measurements for within-run, and 240 for total imprecision).
Data Provenance: Not explicitly stated in the provided document (e.g., country of origin, retrospective or prospective). This information is typically found in the full study report, not necessarily in a 510(k) summary. Given the context of clinical laboratory testing, it's highly likely to be a prospective collection of human serum or plasma samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not Applicable. For an in vitro diagnostic (IVD) device like a C-Reactive Protein reagent, the "ground truth" is established by the results of a predicate quantitative assay, not by expert interpretation of images or patient data. The predicate method (Dade Behring CardioPhase hsCRP) serves as the reference standard whose results are compared to the new device.

4. Adjudication method for the test set

Not Applicable. As this is a quantitative chemical assay, there is no "adjudication" in the sense of reconciling differing expert opinions. The comparison is directly between the numerical results of two laboratory methods.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not Applicable. This is an IVD reagent (a laboratory test kit) for quantitative measurement, not an AI-assisted diagnostic imaging or interpretation device that involves human readers.

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

Yes, but framed differently. The "standalone performance" is essentially what's demonstrated in the Method Comparison and Imprecision studies. The SYNCHRON® Systems High Sensitivity Cardiac CRPH Reagent, in conjunction with the specified SYNCHRON LX 20 PRO System, UniCel® DxC 600/800 System(s), and SYNCHRON® Systems CAL 5 Plus, provides a quantitative result directly. There is no human intervention in the interpretation of the result to arrive at the CRP concentration, other than the standard laboratory procedures for running the test.

7. The type of ground truth used

The ground truth for the method comparison study was the results obtained from the predicate device, Dade Behring CardioPhase hsCRP.
For the imprecision study, the "ground truth" is the true concentration within the assayed samples, which the device aims to measure consistently. The reported mean values serve as the estimate of this truth for assessing variability.

8. The sample size for the training set

Not explicitly stated/Not applicable in the AI sense. For an IVD reagent, there isn't a "training set" in the context of machine learning or AI algorithms. The "training" for such reagents involves optimizing the chemical formulation and assay parameters based on extensive laboratory testing and validation during development. The provided document shows the performance verification data.

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

Not applicable in the AI sense. As there's no "training set" for an AI algorithm, there's no ground truth established in that manner. The development and optimization of the reagent formulation and assay procedure would have involved internal validation against known standards and reference materials, but these are part of the reagent's analytical design, rather than a "training set" for an algorithm.

Summary

{0}------------------------------------------------

K070626

Summary of Safety & Effectiveness SYNCHRON® Systems High Sensitivity Cardiac C-Reactive Protein (CRPH) 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) 961-4123

MAY - 4 2007

2.0 Date Submitted:

March 2, 2007

3.0 Device Name(s):

3.1 Proprietary Names

SYNCHRON® Systems High Sensitivity Cardiac C-Reactive Protein (CRPH) Reagent

3.2 Classification Name

C-Reactive Protein immunological test system (21 CFR § 866.5270)

4.0 Predicate Device:

Candidate(s)	Predicate	Manufacturer	Docket Number/(Product Code)
Synchron SystemsHigh Sensitivity CardiacCRPH Reagent	Dade BehringCardioPhase hsCRP	Dade BehringInc.*	K033908(NQD)
Synchron SystemsHigh Sensitivity CardiacCRPH Reagent	Synchron SystemsHigh SensitivityCRPH Reagent	BeckmanCoulter, Inc	K010597(DCK)

*Dade Behring Inc. (Newark, DE)

5.0 Description:

6.0 Intended Use:

High Sensitivity Cardiac C-Reactive Protein (CRPH) reagent, when used in conjunction with SYNCHRON LX 20 PRO System. UniCel® DxC 600/800 System(s) and SYNCHRON® Systems CAL 5 Plus, is intended for the quantitative determination of C-Reactive Protein in human serum or plasma by rate turbidimetry.

Clinical Significance:

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.

Beckman Coulter, Inc., Section 510(k) Notification

SYNCHRON® System High Sensitivity Cardiac C-Reactive Protein (CRPH) Reagent, SYN Cardiac CRPH Summary of Safety final.doc, March 2007

{1}------------------------------------------------

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
Synchron CardiacCRPHReagent	Intended Use	Same asDade BehringCardioPhase hsCRP
	Use of Latex particletechnology	Same asDade Behring CardioPhase hsCRP andSynchron CRPH
	Liquid stable reagent	The formulation is identical to LX System CRPHReagent.
	Single point adjustedCalibration model	Same as LX System CRPH Reagent
	Differences
Synchron CardiacCRPH Reagent	Antibody source	SYNCHRON Cardiac CRPH uses goat andmouse while the Dade Behring Kit uses mouseonly.
	Initial dilution range	SYNCHRON Cardiac CRPH initial dilution rangecovers from 0.02 to 8.0 mg/dL while the DadeBehring Kit covers from 0.31 to 20.0 mg/dL
	Extended dilution range	SYNCHRON Cardiac CRPH extended dilutionrange covers up to 38.0 mg/dL while the DadeBehring Kit covers uses multiple dilutions tocover the range from 0.016 to 1600.0 mg/dL
	Calibration model	SYNCHRON Cardiac CRPH uses a differentmodel equation for the predetermined calibrationcurve than SYNCHRON CRPH

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.

Analyte	Slope	Intercept	r	n	Predicate Method
Synchron Cardiac CRPH(0.2 to 80 mg/L)	1.048	0.024	0.9899	269	BehringCardioPhase hsCRP
Synchron Cardiac CRPH(0.2 to 10 mg/L)	1.030	-0.008	0.9910	149	BehringCardioPhase hsCRP

Method Comparison Study Results

SYNCHRON High Sensitivity Cardiac CRPH Reagent Imprecision Results

Sample	Mean (mg/dL)	S.D. (mg/dL)	%C.V.	N
Within-Run Imprecision
Level 1	0.063	0.0019	3.1	80
Level 2	1.368	0.0222	1.6	80
Level 3	5.639	0.0907	1.6	80
Total Imprecision
Level 1	0.063	0.0033	5.3	80
Level 2	1.368	0.0381	2.8	80
Level 3	5.639	0.1823	3.2	80

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.

Beckman Coulter, Inc., Section 510(k) Notification

SYNCHRON® System High Sensitivity Cardiac C-Reactive Protein (CRPH) Reagent, SYN Cardiac CRPH Summary of Safety final.doc, March 2007

{2}------------------------------------------------

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Beckman Coulter, Inc. c/o Ms. Tara Viviani Senior Regulatory Affairs Specialist 200 South Kraemer Blvd. M/S /W110 Brea, CA 92822-8000

MAY - 4 2007

Re: K070626

Trade/Device Name: Synchron® Systems High Sensitivity Cardiac C-Reactive Protein (CRPH) reagent Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system. Regulatory Class: Class II Product Code: NQD Dated: March 2, 2007 Received: March 6, 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).

Image /page/2/Picture/11 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The logo is black and white.

{3}------------------------------------------------

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 1egally 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 from me (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.

Jéan 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

{4}------------------------------------------------

Indications for Use

K070626 510(k) Number (if known):

Device Name:

SYNCHRON® Systems High Sensitivity Cardiac C-Reactive Protein (CRPH)

Reagent

Indications for Use:

Clinical Significance:

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.

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)

ion Sign-Off

Office of In Vitro Diagnostic Device

Evaluation and Safety

Page 1 of 1

Beckman Coulter, Inc., Section 510(k) Notification SYNCHRON® System High Sensitivity Cardiac C-Reactive Protein (CRPH) Reagent, SYN Cardiac CRPH510K_Section1.doc, March 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).