The Diazyme high sensitivity C-reactive protein (hsCRP) assay is for the in vitro quantitative determination of C-reactive protein (CRP) in human serum and plasma on automated clinical chemistry analyzers. Measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. For in vitro diagnostic use only.

The Diazyme hsCRP assay calibrator set is intended for use in the calibration of the C-reactive protein (CRP) assay. For in vitro diagnostic use only.

The Diazyme hsCRP assay control set is intended for use as quality controls for the Diazyme hsCRP assay. For in vitro diagnostic use only.

Device Description

Diazyme hsCRP assay is based on a latex enhanced immunoturbidimetric assay. When an antigen-antibody reaction occurs between CRP in a sample and anti-CRP which has been sensitized to latex particles, agglutination results. This agglutination is detected as an absorbance change (570 nm), with the magnitude of the change being proportional to the quantity of CRP in the sample. The actual concentration is then determined by the interpolation from a calibration curve prepared from calibrators of known concentration.

Diazyme hsCRP Assay calibrator set is intended for use with the Diazyme hsCRP Assay kit. Five calibration levels are needed for each run. Calibrators are treated exactly the same as patient samples.

Diazyme hsCRP Assay 3-point control set is intended for use with the Diazyme hsCRP Assay kit. Controls are treated exactly the same as patient samples. The quality controls assist laboratory users in verification steps ensuring that the assay reagents are functioning correctly.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Diazyme hsCRP Assay Kit, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

The acceptance criteria for this device are not explicitly stated in a quantitative manner (e.g., "correlation coefficient must be ≥ 0.95"). Instead, the submission demonstrates substantial equivalence to the predicate device by showing comparable performance metrics. The reported device performance serves as the evidence that these implicit "acceptance criteria" (i.e., being substantially equivalent to the predicate) have been met.

Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Implied Acceptance Criteria (Substantial Equivalence)	Reported Device Performance (Diazyme hsCRP Assay)
Working/Linear Range	Comparable to predicate (0.1-20 mg/L CRP)	Linear Range: 0.2-20 mg/L CRP
Precision (CV%)	Comparable to predicate (0.43-5.7%)	Precision: CV% of 0.7% - 7.3%
Accuracy (Correlation Coefficient)	Comparable to predicate (~0.996)	Correlation Coefficient: 0.99
Accuracy (Slope/Intercept)	Comparable to predicate (y = 1.06/-0.19 against Dade-Behring N hsCRP)	Slope: 1.0133, Y-intercept: 0.0196 (against Roche Tina-Quant hsCRP)
Interference	Less than 10% deviation from specified interferents.	Achieved for listed substances at specified concentrations.

Study Details

This device is a diagnostic assay, and as such, the studies described are clinical analytical performance studies, not typically involving human reader assessment (like an MRMC study) or needing a ground truth established by experts for imaging.

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

Accuracy/Method Comparison Study:
- Sample Size: 57 human serum samples
- Data Provenance: Not explicitly stated, but originating from human serum samples. The study compared the new device against a predicate method, suggesting samples were collected for this purpose (likely prospective or from a banked collection). No country of origin is mentioned.
Precision Study:
- Sample Size:
  - 3 levels of serum-based controls: 80 measurements each (2 runs/day x duplicates x 20 days)
  - 1 serum sample (approx. 3.6 mg/L CRP): 80 measurements (2 runs/day x duplicates x 20 days)
  - 1 serum sample (approx. 15.6 mg/L CRP): 20 measurements (2 runs/day x duplicates x 5 days)
- Data Provenance: Not explicitly stated, but likely laboratory-prepared controls and collected serum samples. No country of origin is mentioned.
Interference Study:
- Sample Size: Not specified for the number of interfered samples, but for each interfering substance, the effect was evaluated at specific concentrations.
- Data Provenance: Not specified, but likely laboratory-prepared samples with added interferents.

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

N/A. This is an in vitro diagnostic assay; the "ground truth" for the test set in the accuracy study was established by the predicate device's measurement of CRP concentrations in the same samples. The precision study used controls with known, established CRP concentrations, and serum samples which had their CRP levels determined by the device itself via repeated measurements.

4. Adjudication Method for the Test Set

N/A. Not applicable for this type of in vitro diagnostic assay.

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

No. An MRMC study is not relevant for this in vitro diagnostic assay, which directly measures an analyte concentration rather than requiring human interpretation of clinical cases.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, in essence, the "standalone" performance is what these analytical studies evaluate. The Diazyme hsCRP Assay is an automated system for quantitative determination of CRP without direct human interpretation of results in the way an imaging AI algorithm would be. The precision, accuracy, and interference studies demonstrate the standalone performance of the assay kit.

7. The Type of Ground Truth Used

Accuracy/Method Comparison Study: The ground truth was established by the predicate device (Roche Tina-Quant hsCRP assay) measuring CRP concentrations in the same human serum samples.
Precision Study: The ground truth for the control samples was their known, established CRP concentrations. For the serum samples, their "true" value was effectively taken as the mean of the numerous repeated measurements.
Interference Study: The ground truth was the expected CRP concentration in samples without interferents, to determine the deviation caused by the interfering substances.

8. The Sample Size for the Training Set

N/A. This device is an immunoturbidimetric assay, not an AI/machine learning algorithm that requires a "training set" in the conventional sense. Its performance is based on chemical reactions and optical detection.

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

N/A. As stated above, this device does not use a training set in the AI/ML context.

Summary

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K103557

510(k) Summary

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

Submitter's name:	Diazyme Laboratories
Submitter's address:	12889 Gregg CourtPoway, CA 92064USA
Name of Contact Person:	Dr. Abhijit DattaDiazyme Laboratories12889 Gregg CourtPoway, CA 92064Phone: 858-455-4762Fax: 858-455-2120
Date the Summary was Prepared:	April 19, 2011
Name of the Device	hsCRP Assay KithsCRP Assay Calibrator SethsCRP Assay Control Set
Trade Name:	Diazyme hsCRP Assay KitDiazyme hsCRP Assay Calibrator SetDiazyme hsCRP Assay Control Set
Common/Usual Name	CRP Assay
Device Classification Name	hsCRP Test System
Product code:	DCK (Cardiac C-Reactive Protein, Antigen, Antiserum,and Control)JIT - Calibrator, SecondaryJJX - Single (specified) Analyte Controls (Assayed and Unassayed)
Panel:	Immunology (82)
Submission Type	510k

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Regulation Number

21CFR 866.5270

Device Class

Class II

Predicate Device:

Roche TINA-QUANT CRP (LATEX) HS TEST SYSTEM (C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE)

Manufacturing Address	Diazyme Laboratories12889 Gregg CourtPoway, CA 92121USA
Establishment Registration	2032900

Description of the Device:

Clinical Significance

CRP (C-reactive protein) is an acute phase protein whose concentration is seen to increase as a result of the inflammatory process, most notably in response to pneumococcal (bacterial) infectious, histolytic disease and a variety of disease states. Originally discovered by Tillet et al. in 1930 in patient sera with acute infection. CRP has now come to be used as a marker or general diagnostic indicator of infections and inflammation, in addition to serving as a monitor of patient response to therapy and surgery. Furthermore, regular measurements of CRP in infants can be a useful aid in the early diagnosis of infectious disease.

Assav Principle

Diazyme hsCRP Assay calibrator set is intended for use with the Diazyme hsCRP Assay kit. Five calibration levels are needed for each run. Calibrators are treated exactly the same as patient samples.

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Users are instructed to verify the calibration curve with the controls and run controls each time a new lot of reagents are received.

Indications for Use:

The Diazyme hsCRP assay Calibrator set is intended for use in the calibration of the C-reactive protein (CRP) assay. For in vitro diagnostic use only.

The Diazyme hsCRP assay Control set is intended for use as quality controls for the Diazyme hsCRP assay. For in vitro diagnostic use only.

Roche Tina-Quant CRP K042485	Diazyme hsCRP Assay
Reagent 1buffer solution, ready to use	Reagent 1100 mM Tris-buffer solution with 0.09% so-dium azide, ready to use
Reagent 2Suspension of anti-human CRP coated latexparticles, ready to use	Reagent 2Suspension of latex particles (<0.5%) coatedwith goat anti-human CRP with 0.09% so-dium azide, ready to use.
CalibratorsReady to use liquid calibrators containing C-reactive protein	CalibratorsReady to use liquid calibrators prepared fromhuman serum, purified human C-reactiveprotein, and 0.09% sodium azide
Calibrator set1 x 1.0 mL Calibrator 01 x 1.0 mL Calibrator 11 x 1.0 mL Calibrator 21 x 1.0 mL Calibrator 31 x 1.0 mL Calibrator 41 x 1.0 mL Calibrator 5	Calibrator set1 x 1.0 mL Calibrator 11 x 1.0 mL Calibrator 21 x 1.0 mL Calibrator 31 x 1.0 mL Calibrator 4
Control Set serum based3 x 1.0mL Control 13 x 1.0mL Control 2	Control Set serum based1 x 3.0mL Control 11 x 3.0mL Control 2

Table 1 Summary of Assay Kit Components

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Comparison of new device to predicate: The charts below identify similarities and differences between the predicate device and the Diazyme hsCRP Assay.

Indications for Use

Indications for Use
Roche Tina-Quant CRP K042485	Diazyme hsCRP Assay	Equivalency
The Tina-quant® CRP (Latex) High Sensi-tive Immmunoturbidimetric assay is for thein vitro quantitative determination of C-reactive protein (CRP) in human serum andplasma on Roche automated clinical chem-istry analyzers.	The Diazyme high sensitivity C-reactiveprotein (hsCRP) assay is for the in vitroquantitative determination of C-reactiveprotein (CRP) in human serum and plasmaon automated clinical chemistry analyzers.	Same exceptfor cardiacclaim withRoche
Highly sensitive measurement of CRP is ofuse for the detection and evaluation of in-flammatory disorders and associated dis-eases, infection and tissue injury. Measure-ment of CRP may also be used as an aid inthe assessment of the risk of future coronaryheart disease. When used as an adjunct toother laboratory evaluation methods ofacute coronary syndromes, it may also be anadditional independent indicator of recur-rent event prognosis in patients with stablecoronary disease or acute coronary syn-drome	Measurement of CRP is of use for the de-tection and evaluation of inflammatory dis-orders and associated diseases, infectionand tissue injury. For in vitro diagnostic useonly.

Principle

Roche Tina-Quant CRP K042485	Diazyme hsCRP Assay	Equivalency
Particle-enhanced immunoturbidimetric as-say· Sample and addition of R1 (buffer)· Addition of R2 (anti-CRP antibody-latex)and start of reaction:Anti-CRP antibodies coupled to latex mi-croparticles react with antigen in the sampleto form an antigen/antibody complex. Fol-lowing agglutination, this is measured tur-bidimetrically.	Diazyme's CRP assay is based on a latexenhanced immunoturbidimetric assay.When an antigen-antibody reaction occursbetween CRP in a sample and anti-CRPwhich has been sensitized to latex particles,agglutination results. This agglutination isdetected as an absorbance change (570 nm),with the magnitude of the change beingproportional to the quantity of CRP in thesample. The actual concentration is then de-termined by the interpolation from a cali-bration curve prepared from calibrators ofknown concentration.	Same

Test Objective

Roche Tina-Quant CRP K042485	Diazyme hsCRP Assay	Equivalency
------------------------------	---------------------	-------------

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For the in vitro quantitative determination of CRP in human serum or plasma.	For the in vitro quantitative determination of CRP in human serum or plasma.	Same
-------------------------------------------------------------------------------------	-------------------------------------------------------------------------------------	------

Type of Test

Roche Tina-Quant CRP K042485	Diazyme hsCRP Assay	Equivalency
Quantitative	Quantitative	Same

Specimen Type

Roche Tina-Quant CRP K042485	Diazyme hsCRP Assay	Equivalency
Human serum or plasma.	Human serum or plasma.	Same

Product Type

Roche Tina-Quant CRP K042485	Diazyme hsCRP Assay	Equivalency
Assay reagent kit, calibrator kit, quality con-trol kit.	Assay reagent kit, calibrator kit, quality con-trol kit.	Same

Performance

Roche Tina-Quant CRP K042485	Diazyme hsCRP Assay
Working Range: 0.1-20 mg/L CRP	Linear Range: 0.2-20 mg/L CRP
Precision: CV% of 0.43 - 5.7%	Precision: CV% of 0.7% - 7.3%
Accuracy (vs Dade-Behring N hsCRP):	Accuracy (vs. Roche Tina-Quant hsCRP):
Correlation Coefficient: 0.996Slope/Intercept: y = 1.06/-0.19	Correlation Coefficient: 0.99Slope/ y Intercept: y = 1.01/0.0196

Calibrator Comparison

C.f.a.s. Proteins K011226	Diazyme hsCRP Assay	Equivalency
Separately packaged lot specific calibratorkit. Liquid stable.	Separately packaged lot specific calibratorkit. Liquid stable.	Same

Control Comparison

Control Comparison
Roche CRP T Control N K982087, Preci-norm Protein Control K871027	Diazyme hsCRP Assay	Equivalency
Separately packaged quality control kitdesigned for specific assay.	Separately packaged quality control setdesigned for specific assay.	Same

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Performance Testing Summaries:

Method Comparison Study Summary

Human serum samples were tested with the Diazyme hsCRP Assay and the obtained results were compared to the predicate method. A total of 57 samples (ranging from 0.19 to 18.97 mg/L of CRP) were tested in both assays. The above described accuracy study showed that the Diazyme hsCRP Assay results correlated well with predicate method with a correlation coefficient of 0.99 with a slope of 1.0133 and 0.0196 y intercept.

	Serum Samples
n	57
Slope	1.0133
Intercept	0.0196
Correlation coeffi-	0.99
Range of values	0.19 to 18.97 mg/L of CRP

Precision Study Summary

The precision of the Diazyme hsCRP Assay was evaluated according to Clinical and Laboratory Standards Institute EP5-A guideline. In the study, three levels of serum based controls containing approximately 0.8, 1.6, and 8.7 mg/L of CRP, and a serum sample containing approximately 3.6 mg/L of CRP respectively was tested with 2 runs per day in duplicates over 20 working days. An additional serum sample containing approximately 15.6 mg/L of CRP was tested with 2 runs per day in duplicates over 5 days. Results were calculated using the EP Evaluator software precision statistic template and summarized in the following table:

Within-Run Precision
	Level 1:	Level 2:	Level 3:	Serum	Serum
N	80	80	80	80	20
Mean	0.85	1.75	8.62	3.62	15.56
SD	0.03	0.03	0.06	0.05	0.19
CV%	4.0%	1.7%	0.7%	1.4%	1.2%

Within-Run Precision

Total Precision

	Level 1:	Level 2:	Level 3:	Serum	Serum
N	80	80	80	80	20
Mean	0.85	1.75	8.62	3.62	15.56
SD	0.04	0.05	0.12	0.09	0.24
CV%	4.2%	2.6%	1.4%	2.4%	1.6%

Conclusion:

For three levels of CRP controls, 20-day reproducibility data showed that the Within-Run Precision was from 0.7 % to 4.0 % and the Total Precision was from 1.4 % to 4.2%. For one serum sample, 20-day reproducibility data showed that the Within-Run Precision was 1.4 % and the

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Total Precision was 2.4 %. For one serum sample, 5-day reproducibility data showed that the Within-Run Precision was 1.2 % and the Total Precision was 1.6 %.

Interference Study Summary

The following substances normally present in the blood produced less than 10% deviation when tested at levels equal to the concentrations listed below:

Interference	Concentration
Triglyceride	1000 mg/dL
Ascorbic Acid	176 mg/dL
Bilirubin	40 mg/dL
Bilirubin Conjugated	40 mg/dL
Hemoglobin	500 mg/dL
Rheumatoid Factor	400 IU/mL

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Public Health Service

Image /page/7/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's name in a circular arrangement around the perimeter. Inside the circle is an emblem of an abstract eagle or bird-like figure, which is a common symbol associated with the department.

Diazyme Laboratories c/o Dr. Abhijit Datta Director, Technical Operations 12889 Gregg Court Poway, CA 92064

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

APR 2 7 2011

K103557 Re:

Diazyme high sensitivity C-reactive protein (hsCRP) assay kit; Trade Name: Diazyme high sensitivity C-reactive protein (hsCRP) assay calibrator set; Diazyme high sensitivity C-reactive protein (hsCRP) assay control set Regulation Number: 21 CFR §866.5270 Regulation Name: C-reactive protein, Antigen, Antiserum and Control Regulatory Class: Class II Product Codes: DCK, JIT, JJX Dated: April 19, 2011 Received: April 20, 2011

Dear Dr. Datta:

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); 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).

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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 postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. 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 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Courtney C. Harper, 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 for Use

510(k) Number (If Known): K103557

Device Name: Diazyme high sensitivity C-reactive protein (hsCRP) assay kit, Diazyme high sensitivity C-reactive protein (hsCRP) assay calibrator set, Diazyme high sensitivity C-reactive protein (hsCRP) assay control set.

Indications for Use:

The Diazyme hsCRP assay calibrator set is intended for use in the calibration of the C-reactive protein (CRP) assay. For in vitro diagnostic use only.

The Diazyme hsCRP assay control set is intended for use as quality controls for the Diazyme hsCRP assay. For in vitro diagnostic use only.

Prescription Use X (Part 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 In Vitro Diagnostic Device Evaluation and Safety (OVD)

Carol C. Benson

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K103557

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).