The IMMULITE® IMMULITE® 1000 High Sensitivity CRP assay is intended for use as follows: For in vitro diagnostic use with the IMMULITE/IMMULITE 1000 Analyzer for the quantitative measurement of C-Reactive protein (CRP) in serum or plasma as an aid in the detection and evaluation of infection, tissue injury and inflammatory disorders, and associated diseases. Measurements may also be used as an aid in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndrome may be useful as an independent marker for recurrent events in patients with stable coronary disease or acute coronary syndrome.

IMMULITE® 2000 High Sensitivity CRP assay is intended for use as follows: For in vitro diagnostic use with the IMMULITE 2000 Analyzer - for the quantitative measurement of C-Reactive protein (CRP) in serum or plasma as an aid in the detection and evaluation of infection, tissue injury and inflammatory disorders, and associated diseases. Measurements may also be used as an aid in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndrome may be useful as an independent marker for recurrent events in patients with stable coronary disease or acute coronary syndrome.

Device Description

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP is a solid-phase, chemiluminescent immunometric assay. The assay utilizes a 14-inch polystyrene bead coated with anti-ligand. The bead is co-incubated with sample, murine monoclonal anti-CRP, and alkaline phosphatase (bovine calf intestine)-conjugated to rabbit polyclonal anti-CRP in buffer for 30 minutes on each IMMULITE/IMMULITE 1000 and IMMULITE 2000 platform. Unbound enzyme conjugate is removed by a centrifugal wash procedure. Substrate is added and the resulting chemiluminescence is read in the luminometer.

AI/ML Overview

The IMMULITE®/IMMULITE® 1000 and IMMULITE® 2000 High Sensitivity CRP assays are immunological test systems designed for the quantitative measurement of C-Reactive protein (CRP) in serum or plasma. These devices are intended to aid in the detection and evaluation of infection, tissue injury, inflammatory disorders, associated diseases, and in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP measurements, when used with traditional clinical evaluations of acute coronary syndrome, may also serve as an independent marker for recurrent events in patients with stable coronary disease or acute coronary syndrome.

1. Table of Acceptance Criteria and Reported Device Performance:

Performance Characteristic	Acceptance Criteria (from predicate/literature)	IMMULITE/IMMULITE 1000 Performance (Reported)	IMMULITE 2000 Performance (Reported)
Working Range	Predicate: 0.175 to 1100 mg/L	0.3 to 100 mg/L	0.2 to 100 mg/L
Analytical Sensitivity	Predicate: 0.175 mg/L	0.1 mg/L	0.1 mg/L
Functional Sensitivity	Not reported in predicate	0.3 mg/L (at 10% CV)	0.2 mg/L (at 10% CV)
Precision (Intra-assay CV%)	Predicate not explicitly stated for specific levels. Literature-based expectations for CRP assays.	Did not exceed 6.0% (0.3-78 mg/L)	Did not exceed 8.7% (0.23-93.7 mg/L)
Precision (Inter-assay CV%)	Predicate not explicitly stated for specific levels. Literature-based expectations for CRP assays.	Not greater than 7.5% (0.8 mg/L), 6% (1.5 mg/L), 4.8% (3.1 mg/L), 4.9% (15.0 mg/L). Did not exceed 10% (0.3-78 mg/L).	Not greater than 7.1% (0.85 mg/L), 3.1% (3.2 mg/L), 3.3% (12.3 mg/L). Did not exceed 8.7% (0.23-93.7 mg/L).
Linearity	Demonstrated	Demonstrated within precision of the assay	Demonstrated within precision of the assay
Spiked Recovery	Demonstrated	Demonstrated within precision of the assay	Demonstrated within precision of the assay
Interference (Bilirubin)	Predicate: No significant interference up to 230 mg/L	No effect up to 200 mg/L	No effect up to 200 mg/L
Interference (Hemoglobin)	Predicate: No significant interference up to 36 g/L (36000 mg/L)	No effect up to 570 mg/L	No effect up to 512 mg/L
Interference (Triglycerides)	Predicate: No significant interference up to 7.4 g/L (7400 mg/L)	No effect up to 3000 mg/L	No effect up to 3000 mg/L
Cross-Reactivity	Not specified for predicate	No cross-reactivity (HSA, IgG, Transferrin)	No cross-reactivity (HSA, IgG, Transferrin)
High Dose Hook Effect	Not reported in predicate	No hook effect up to 3780 mg/L	No hook effect up to 3780 mg/L
Method Comparison (Regression)	Substantial equivalence to predicate (slope ~1, intercept ~0, r > 0.95 generally for IVDs)	IMMULITE/IMMULITE 1000 vs. Dade Behring HSCRP: Full range (N=175): slope = 0.952, intercept = 0.022, r = 0.996 <10 mg/L range (N=165): slope = 0.943, intercept = 0.030, r = 0.987	IMMULITE 2000 vs. Dade Behring HSCRP: Full range (N=185): slope = 1.010, intercept = -0.0888, r = 0.995 <10 mg/L range (N=175): slope = 1.0006, intercept = -0.0818, r = 0.993

2. Sample Sizes Used for the Test Set and Data Provenance:

The available document describes performance studies, clinical comparisons, and assay characteristics for both the IMMULITE/IMMULITE 1000 and the IMMULITE 2000 assays.

Method Comparison (Test Set):
- IMMULITE/IMMULITE 1000 vs. Dade Behring N HSCRP:
  - Full range (0.3 to 22.9 mg/L): N=175 samples
  - Range < 10 mg/L (0.3 to 9.4 mg/L): N=165 samples (a subset of the full range)
- IMMULITE 2000 vs. Dade Behring N HSCRP:
  - Full range (0.2 to 22.9 mg/L): N=185 samples
  - Range < 10 mg/L (0.2 to 9.4 mg/L): N=175 samples (a subset of the full range)
Data Provenance: The document does not explicitly state the country of origin for the samples used in the method comparison or whether the data was retrospective or prospective. Given the nature of a 510(k) submission and the context of comparing a new device to an existing predicate, it's highly probable that these were prospective studies conducted using patient samples in a clinical laboratory setting. However, this is not definitively stated.

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

This information is not applicable to the provided document. The "ground truth" for the method comparison studies was established by the measurement results from the legally marketed predicate device, the Dade Behring N High Sensitivity CRP assay. There were no human experts or diagnosticians establishing ground truth for these quantitative measurements.

4. Adjudication Method for the Test Set:

This information is not applicable to the provided document. Adjudication methods are typically used in clinical studies where subjective interpretations (e.g., image readings, clinical assessments) are made by multiple experts, and disagreements need to be resolved. In this context of quantitative laboratory assays, the comparison is directly between the numerical results of two different analytical methods, not subjective expert interpretations.

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:

This information is not applicable to the provided document. The device is an in vitro diagnostic assay (a laboratory test) that provides a quantitative measurement. It is not an AI-assisted diagnostic tool that human readers would interpret or use to improve their performance. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not relevant to this device.

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

This information is partially applicable to the provided document. The performance characteristics described (Working Range, Analytical Sensitivity, Functional Sensitivity, Precision, Linearity, Spiked Recovery, Interfering Substances, Cross-Reactivity, High Dose Hook Effect) represent the "standalone" performance of the IMMULITE/IMMULITE 1000 and IMMULITE 2000 assays. These are objective measurements of the device's analytical capabilities without human interpretation influencing the numerical result. The method comparison study also assesses the standalone numerical output against a predicate. While a human initiates the test and reviews the result, the core performance reported is the algorithm/assay's ability to accurately quantify CRP.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):

The ground truth for the performance studies and method comparison was primarily:

Reference Standards: The assays are standardized to WHO IS 85/506 and CRM 470 reference standards.
Predicate Device Measurements: For the method comparison, the measurements obtained from the legally marketed Dade Behring N High Sensitivity CRP assay served as the comparator or "ground truth" to demonstrate substantial equivalence.
Established Analytical Methods: For other performance characteristics (e.g., precision, linearity), standard analytical methodologies and established quality control practices define the expected performance against internal standards or known concentrations.

8. The Sample Size for the Training Set:

The document describes a 510(k) submission for an in vitro diagnostic assay, which typically does not involve machine learning algorithms that require "training sets" in the conventional sense. The performance characteristics and comparison studies are analogous to "test sets" for verifying the analytical performance of the assay.

However, the "Expected Values" section mentions: "A study performed on 100 apparently healthy volunteers yielded a median of 1.4 mg/L and an upper 97.5th percentile of 11 mg/L." This could be considered a reference range study, but it's not a "training set" for an algorithm.

The document states that assay reagents, components, and performance characteristics "remain as previously established in 510(k) K003372." This implies that the current submission builds upon previous extensive validation data, which would have involved numerous samples (calibrators, controls, patient samples) used in the development and initial validation of the original IMMULITE hsCRP assays. The sample sizes for those earlier studies are not detailed in this specific document.

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

As there is no "training set" for a machine learning algorithm described, this question is not directly applicable. If considering the development and validation of the original assays (from K003372), the "ground truth" for calibrators and controls would be established through highly characterized reference materials (like WHO IS 85/506 and CRM 470) and rigorous analytical chemistry methods. For patient samples used in method development, the "ground truth" would be the measurements obtained from an established, clinically accepted reference method or comparison to other well-validated commercial assays.

Summary

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SUMMARY OF SAFETY AND EFFECTIVENESS

Assigned 510(k) Number

The assigned 510(k) number is

DEC 2 2 2006

Sponsor Name and Address

Diagnostic Products Corporation Corporate Offices 5210 Pacific Concourse Drive Los Angeles, CA 90045-6900 (310) 645-8200

Contact

Deborah L. Morris Director, Clinical Affairs and Regulatory Submissions (310) 645-8200 extension 7426 dmorris@dpconline.com

Device Name

Trade Name:	IMMULITE®/IMMULITE® 1000,IMMULITE® 2000
Common Name:	High Sensitivity C-Reactive Protein
Classification	21 CFR 866.5270
Product Code	NQD
DPC Catalog Numbers:	LKCRP (100 tests), L2KCRP2 (200 tests),L2KCRP6 (600 tests)

Description of Device

Indications for Use

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The IMMULITE® IMMULITE® 1000 High Sensitivity CRP assay is intended for use as follows:

For in vitro diagnostic use with the IMMULITE/IMMULITE 1000 Analyzer for the quantitative measurement of C-Reactive protein (CRP) in serum or plasma as an aid in the detection and evaluation of infection, tissue injury and inflammatory disorders, and associated diseases. Measurements may also be used as an aid in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndrome may be useful as an independent marker for recurrent events in patients with stable coronary disease or acute coronary syndrome.

IMMULITE® 2000 High Sensitivity CRP assay is intended for use as follows: For in vitro diagnostic use with the IMMULITE 2000 Analyzer - for the quantitative measurement of C-Reactive protein (CRP) in serum or plasma as an aid in the detection and evaluation of infection, tissue injury and inflammatory disorders, and associated diseases. Measurements may also be used as an aid in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndrome may be useful as an independent marker for recurrent events in patients with stable coronary disease or acute coronary syndrome.

Manufacturing Site

IMMULITE® IMMULITE® 1000 and IMMULITE 2000 High Sensitivity CRP assays are manufactured by Diagnostic Products Corporation at the following locations:

Diagnostic Products Corporation Reagent Manufacturing Division 5700 West 96th Street Los Angeles, CA 90045-5597 FDA Establishment #: 2017183

Diagnostic Products Corporation Corporate Offices 5210 Pacific Concourse Drive Los Angeles, CA 90045-6900 FDA Establishment #: 3005250747

Comparison to the Predicate

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assay reagents, components and all assay performance characteristics remain as previously established in 510(k) K003372.

A summary of the features of the IMMULITE/IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assay and the predicate device, Dade Behring N High Sensitivity CRP, (K991385/K033908) is presented below.

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Item	IMMULITE/IMMULITE 1000 andIMMULITE 2000 High Sensitivity CRP	Dade Behring N High SensitivityCRP using BN™ Systems
Assay Type	Chemiluminescent immunometric	Particle enhanced immunoephelometry
Antibody	Anti-CRP Murine monoclonal and rabbitpolyclonal anti-CRP	Mouse monoclonal Anti-CRP
Expected Values	Expected high sensitivity CRP values forhealthy individuals has been established in theliterature as <3 mg/L.A study performed on 100 apparently healthyvolunteers yielded a median of 1.4 mg/L andan upper 97.5th percentile of 11 mg/L.The AHA/CDC Scientific Statementconcerning inflammation and cardiovascularmarkers reports that hsCRP values < 1 mg/Lare low risk for cardiovascular diseaseprediction; values between 1-3 mg/L areaverage risk for cardiovascular diseaseprediction; and values > 3 mg/L are high riskfor cardiovascular disease prediction.Increases in CRP are non-specific and shouldnot be interpreted without a complete clinicalhistory.Consider these limits as guidelines only. Eachlaboratory should establish its own referenceranges.	Expected values for healthy individualsas noted in the literature is <3 mg/L.The normal range of CRP in the serumof 2147 apparently healthy individualsusing the CardioPhase hsCRP Assay wasfound to be90% 1.69 mg/L95% 2.87 mg/LA subset of the Stanisless Cohort wasexamined in this study. The cohortsubset used consisted of 1151 males and996 females ranging in age from 5 to 71years. All participants were of Europeanancestry and free of previouslydiagnosed serious or chronic disease(such as cancer or cardiovasculardisease) and excluded individuals takinganti-inflammatory drugs or antibiotics.As CRP is a nonspecific indicator for awide range of disease processes, and asthe reference individuals are affected bymany factors that may differ for eachpopulation studied, each laboratoryshould determine its own referenceinterval.
Referencestandards	WHO IS 85/506 and CRM 470	CRM 470
Indications forUse	For in vitro diagnostic use with theIMMULITE/IMMULITE 1000 andIMMULITE 2000 Analyzers — for thequantitative measurement of C-Reactiveprotein (CRP) in serum or plasma as an aid inthe detection and evaluation of infection,tissue injury and inflammatory disorders andassociated diseases. Measurements may alsobe used as an aid in the identification ofindividuals at risk for future cardiovasculardisease. High sensitivity CRP (hsCRP)measurements when used in conjunction withtraditional clinical laboratory evaluation ofacute coronary syndrome may be useful as anindependent marker for recurrent events inpatients with stable coronary disease or acutecoronary syndrome.	N High Sensitivity CRP is an in vitrodiagnostic reagent for the quantitativedetermination of C-reactive protein(CRP) in human serum, and heparin andEDTA plasma by means of particleenhanced immunoephelometry using theBN Systems. In acute phase response,increased levels of a number of plasmaproteins, including C-reactive protein isobserved. Measurement of CRP isuseful for the detection and evaluation ofinfection, tissue injury, inflammatorydisorders and associated diseases.Measurements may also be used as anaid in the identification of individuals atrisk for future cardiovascular disease.High sensitivity CRP (hsCRP)measurements when used in conjunction
Item	IMMULITE/IMMULITE 1000 andIMMULITE 2000 High Sensitivity CRP	Dade Behring N High SensitivityCRP using BNTTM Systems
		with traditional clinical laboratoryevaluation of acute coronary syndromesmay be useful as an independent markerfor recurrent events in patients withstable coronary disease or acute coronarysyndromes.
Working Range	IMMULITE/IMMULITE 1000: 0.3 to 100mg/LIMMULITE 2000: 0.2 to 100 mg/L	0.175 to 1100 mg/L
AnalyticSensitivity	IMMULITE/IMMULITE 1000: 0.1 mg/LIMMULITE 2000: 0.1 mg/L	0.175 mg/L
FunctionalSensitivity	IMMULITE/IMMULITE 1000: 0.3 mg/LIMMULITE 2000: 0.2mg/L	Not reported in the package insert
Sample Type	Serum and Heparinized plasma	Serum, heparinized, and EDTA plasma
Interferences	No significant interference from conjugatedbilirubin (up to 200 mg/L), hemoglobin (up to570 mg/dL for IMMULITE/IMMULITE1000, and 512 mg/dL for IMMULITE 2000),or triglycerides (up to 3000 mg/dL).No cross-reactivity with human serumalbumin, human IgG, or transferrin	No significant interference frombilirubin (up to 230 mg/L), hemoglobin(up to 36 g/L) or triglycerides (up to 7.4g/L).
Hook Effect	IMMULITE/IMMULITE 1000: No high dosehook effect up to 3780 mg/LIMMULITE 2000: No high dose hook effectup to 3780 mg/L	Not reported in the package insert.
CalibrationInterval	Recommended 2 week adjustment interval	Reference curve valid for 4 weeks andbeyond as indicated by control results

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Standards/Guidance Documents Referenced

Guidance for Industry and FDA Staff: "Review Criteria for Assessment of C-Reactive Protein (CRP), High Sensitivity C-Reactive Protein (hsCRP) and Cardiac C-Reactive Protein CCRP Assays", issued September 22, 2005.

Clinical Laboratory Standard Institute (CLSI). Protocols for the Determination of Limits of Detection and Limits of Quantitation; Approved Guideline. CLSI document EP17-A Vol 24 No 34. CLSI 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2004.

Clinical Laboratory Standard Institute (CLSI). Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition. CLSI document EP5-A2. CLSI, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2004.

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Working Range

The IMMULITE/IMMULITE 1000 High Sensitivity CRP reportable range is 0.3 to 100 mg/L and the IMMULITE 2000 High Sensitivity CRP reportable range is 0.2 to 100 mg/L.

Standardization

The IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assays are standardized to both the WHO IS 85/506 and CRM 470 reference standards.

Analytical Sensitivity

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assays' analytical sensitivity is 0.1 mg/L as previously reported and cleared in Pre-market Notification 510(k) K003372 for IMMULITE/IMMULITE 1000 and IMMULITE 2000 hsCRP.

Functional Sensitivity

The IMMULITE / MMULITE 1000 High Sensitivity CRP assay's functional sensitivity (lowest concentration that can be measured with a total CV% of 10%) is 0.3 mg/L.

The IMMULITE 2000 High Sensitivity CRP assay's functional sensitivity (lowest concentration that can be measured with a total CV% of 10%) is 0.2 mg/L.

Precision

As previously reported and cleared in Pre-market Notification 510(k) K003372 IMMULITE/IMMULITE 1000 High Sensitivity CRP intra- and inter-assay CV% were not greater than 7.5% at 0.8 mg/L, 6% at 1.5 mg/L, 4.8% at 3.1 mg/L, and 4.9% at 15.0 mg/L. Intra-assay CV% did not exceed 6.0% for all samples tested over the range 0.3 mg/L to 78 mg/L. Inter-assay CV% did not exceed 10% for all samples tested over the range 0.3 mg/L to 78 mg/L.

As previously reported and cleared in Pre-market Notification 510(k) K003372 IMMULITE 2000 High Sensitivity CRP intra- and inter-assay CV% were not greater than 7.1% at 0.85 mg/L, 3.1% at 3.2 mg/L, and 3.3% at 12.3 mg/L. Intra-assay CV% did not exceed 8.7% for all samples tested over the range 0.23 mg/L to 93.7 mg/L. Interassay CV% did not exceed 8.7% for all samples tested over the range 0.23 mg/L to 93.7 mg/L.

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Linearity

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assays demonstrate linearity of dilution within the precision of the assay as previously reported and cleared in Pre-market Notification 510(k) K003372 for IMMULITE/IMMULITE 1000 and IMMULITE 2000 hsCRP .

Spiked Recovery

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assays demonstrate accuracy of spiked recovery within the precision of the assay as previously reported and cleared in Pre-market Notification 510(k) K003372 for IMMULITE/IMMULITE 1000 and IMMULITE 2000 hsCRP.

Interfering substances

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assays demonstrate that presence of conjugated bilirubin in concentrations up to 200 mg/L has no effect on results within the precision of the assay as previously reported and cleared in Pre-market Notification 510(k) K003372 for IMMULITE/IMMULITE 1000 and IMMULITE 2000 hsCRP.

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assays demonstrate that presence of hemoglobin in concentrations up to 570 mg/L on IMMULITE/IMMULITE 1000 and 512 mg/L on IMMULITE 2000 has no effect on results within the precision of the assay as previously reported and cleared in Pre-market Notification 510(k) K003372 for the IMMULITE/IMMULITE 1000 and IMMULITE 2000 hsCRP.

The IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assays demonstrate that presence of triglycerides in concentrations up to 3,000 mg/L has no effect on results within the precision of the assay as previously reported and cleared in Pre-market Notification 510(k) K003372 for the IMMULITE/IMMULITE 1000 and IMMULITE 2000 hsCRP.

Cross-Reactivity

The IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assays demonstrate no cross-reactivity to human serum albumin (HSA) at levels up to 1,000 mg/dL added HSA, human IgG at 1,000 mg/dL added IgG or transferrin at 1,000 mg/dL added tranferrin as previously reported and cleared in Pre-market Notification 510(k) K003372 for the IMMULITE/IMMULITE 1000 and IMMULITE 2000 hsCRP.

High Dose Hook Effect

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 High Sensitivity CRP assays demonstrate no high dose hook effect up to 3780 mg/L.

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Expected Values

Expected high sensitivity CRP values for healthy individuals has been established in the literature as <3 mg/L.

A study performed on 100 apparently healthy volunteers yielded a median of 1.4 mg/L and an upper 97.5th percentile of 11 mg/L.

The AHA/CDC Scientific Statement concerning inflammation and cardiovascular markers reports that hsCRP values < 1 mg/L are low risk for cardiovascular disease prediction; values between 1-3 mg/L are average risk for cardiovascular disease prediction; and values > 3 mg/L are high risk for cardiovascular disease prediction.

Increases in CRP are non-specific and should not be interpreted without a complete clinical history..

Consider these limits as guidelines only. Each laboratory should establish its own reference ranges.

Comparison of IMMULITE/IMMULITE 1000 and IMMULITE 2000 hsCRP Results to the Predicate Dade Behring N High Sensitivity CRP

IMMULITE/IMMULITE 1000 hsCRP versus Dade Behring N HSCRP

The IMMULITE/IMMULITE 1000 High Sensitivity CRP assay was compared to the Dade Behring N High Sensitivity CRP assay.

By linear regression {N=175, range 0.3 to 22.9 mg/L by Dade Behring, slope = 0.952 95%CI 0.939 to 0.965, intercept = 0.022 95%CI -0.0372 to 0.0817) Mean Dade Behring: 2.7 mg/L Mean IMMULITE: 2.6 mg/L

IMMULITE/IMMULITE 1000=0.952 Dade Behring + 0.022 mg/L; r = 0.996

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Image /page/7/Figure/0 description: This image is a scatter plot that compares IMMULITE mg/L to Dade Behring BNII mg/L. The x-axis represents Dade Behring BNII mg/L, ranging from 0 to 25, while the y-axis represents IMMULITE mg/L, ranging from -5 to 25. The data points are clustered around a regression line, which is described by the equation y = 0.9516x + 0.0222.

Using the same data set in the range no greater than 10 mg/L, by linear regression (N=165, range 0.3 to 9.4 mg/L by Dade Behring, slope = 0.943 95%CI 0.9195 to 0.9665, intercept = 0.0303 95%CI-0.0327 to 0.0933)

Mean Dade Behring: 1.9 mg/L Mean IMMULITE: 1.8 mg/L

IMMULITE/IMMULITE 1000= 0.943 Dade Behring + 0.030 mg/L; r = 0.987

Image /page/7/Figure/4 description: This image is a scatter plot that compares IMMULITE mg/L to Dade Behring BNII mg/L. The x-axis represents Dade Behring BNII mg/L, ranging from 0 to 10, while the y-axis represents IMMULITE mg/L, ranging from -1 to 9. The plot shows a strong positive correlation between the two variables, with data points clustered around a regression line represented by the equation y = 0.943x + 0.0303. There are also lines above and below the regression line.

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IMMULITE 2000 HSCRP VERSUS Dade Behring N HSCRP

The IMMULITE 2000 High Sensitivity CRP assay was compared to the Dade Behring N High Sensitivity CRP assay.

By linear regression (N=185, range 0.2 to 22.9 mg/L by Dade Behring, slope = 1.010 95%CI 0.9954 to 1.0246, intercept = - 0.0888 95% CI -- 0.1542 to -- 0.0235) Mean Dade Behring: 2.6 mg/L Mean IMMULITE 2000: 2.5 mg/L

IMMULITE 2000 = 1.01 Dade Behring - 0 .0888 mg/L; r = 0.995

Image /page/8/Figure/4 description: This image is a scatter plot comparing two different methods of measuring a substance, IMMULITE 2000 and Dade Behring BNII, both measured in mg/L. The x-axis represents Dade Behring BNII, and the y-axis represents IMMULITE 2000. The plot shows a strong positive correlation between the two methods, with data points clustered tightly around a regression line. The regression equation is given as y = 1.01x - 0.0888.

Using the same data set in the range no greater than 10 mg/L by linear regression (N=175, range 0.2 to 9.4 mg/L by Dade Behring, slope = 1.0006 95%CI 0.9833 to 1.0179, intercept = - 0.0818 95%CI -0.1270 to -0.0367)

Mean Dade Behring: 1.8 mg/L Mean IMMULITE: 1.7 mg/L

IMMULITE 2000 = 1.0006 Dade Behring - 0.0818 mg/L; r = 0.993

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Image /page/9/Figure/0 description: This image is a scatter plot comparing IMMULITE 2000 mg/L and Dade Behring BNII mg/L. The x-axis represents Dade Behring BNII mg/L, ranging from 0 to 10, while the y-axis represents IMMULITE 2000 mg/L, ranging from -2 to 10. The plot shows a strong positive correlation between the two variables, with data points clustered around a regression line represented by the equation y = 1.0006x - 0.0818.

Conclusions

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 hsCRP assays demonstrate substantial equivalence to the Dade Behring N High Sensitivity CRP assay.

The IMMULITE/IMMULITE 1000 and IMMULITE 2000 hsCRP assays are thereby safe and effective for the following intended use:

The IMMULITE®/IMMULITE® 1000 High Sensitivity CRP assay is intended for in vitro diagnostic use with the IMMULITE/IMMULITE 1000 Analyzer -- for the quantitative measurement of C-Reactive protein (CRP) in serum or plasma as an aid in the detection and evaluation of infection, tissue injury and inflammatory disorders, and associated diseases. Measurements may also be used as an aid in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndrome may be useful as an independent marker for recurrent events in patients with stable coronary disease or acute coronary syndrome.

IMMULITE® 2000 High Sensitivity CRP assay is intended for in vitro diagnostic use with the IMMULITE 2000 Analyzer — for the quantitative measurement of C-Reactive protein (CRP) in serum or plasma as an aid in the detection and evaluation of infection, tissue injury and inflammatory disorders, and associated diseases. Measurements may also be used as an aid in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndrome may be useful as an

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independent marker for recurrent events in patients with stable coronary disease or acute coronary syndrome.

. .

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/11/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features a stylized eagle with three stripes forming its body and wing. The eagle faces right. Encircling the eagle is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Deborah L. Morris Director, Clinical Affairs and Regulatory Submissions Diagnostic Products Corporation Corporate Offices 5210 Pacific Concourse Drive Los Angeles CA 90045-6900

DEC 2 2 2006

K063057 Re:

Trade/Device Name: Immulite®/ Immulite® 1000 High Sensitivity CRP Immulite® 2000 High Sensitivity CRP Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: NQD Dated: September 15, 2006 Received: October 5, 2006

Dear Ms. Deborah L. Morris:

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.

Jean 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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Indications for Use

510(k) Number (if known): K063057

Device Name: IMMULITE® IMMULITE® 1000 High Sensitivity CRP IMMULITE® 2000 High Sensitivity CRP

Indications For Use:

The IMMULITE® 1000 High Sensitivity CRP assay is intended for use as follows: For in vitro diagnostic use with the IMMULITE/MMULTE 1000 Analyzer - for the quantitative measurement of C-Reactive protein (CRP) in serum or plasma as an aid in the detection and evaluation of infection, tissue injury and inflammatory disorders, and associated diseases. Measurements may also be used as an aid in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndrome may be useful as an independent marker for recurrent events in patients with stable coronary disease or acute coronary syndrome.
MMULITE® 2000 High Sensitivity CRP assay is intended for use as follows:

For in vitro diagnostic use with the IMMULITE 2000 Analyzer - for the quantitative measurement of C-Reactive protein (CRP) in serum or plasma as an aid in the detection and evaluation of infection, tissue injurv and inflammatory disorders, and associated diseases. Measurements may also be used as an aid in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndrome may be useful as an independent marker for recurrent events in patients with stable coronary disease or acute coronary syndrome.

AND/OR Prescription Use X (Part 21 CFR 801 Subpart D)

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 In Vitro Diagnostic Devices (OIVD)

Carol Benam
Sign-Off

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frice of In Vitro Diagnostic Device Valuation and Safety

063057

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).