Cholestech LDX high sensitivity C-Reactive Protein (hs-CRP) is an in vitro diagnostic test for the quantitative determination of CRP in whole blood or serum. Measurement of CRP is useful as an aid in the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases.

Device Description

The Cholestech LDX System combines immunoassay and solid-phase technology to measure CRP. Samples used for testing can be whole blood from a fingerstick (collected in a lithium heparin coated capillary tube), venous whole blood or serum. The sample is applied to a Cholestech LDX hs-CRP cassette. The cassette is then placed into the Cholestech LDX Analyzer where a unique system on the cassette separates the plasma from the blood cells. The resultant color in the reaction is measured by reflectance photometry. A brown magnetic stripe on each cassette contains the calibration information required for the Cholestech LDX Analyzer to convert the reflectance reading to the CRP concentration in mg/L.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Metric	Acceptance Criteria	Reported Device Performance (Cholestech LDX hs-CRP)
Accuracy (vs. Predicate)	Slope (Serum)	Not explicitly stated, implied to be close to 1	1.01
	Y-intercept (Serum)	Not explicitly stated, implied to be close to 0	0.22
	"r" (Serum)	Not explicitly stated, implied to be close to 1	0.975
	Slope (Whole Blood)	Not explicitly stated, implied to be close to 1	1.06
	Y-intercept (Whole Blood)	Not explicitly stated, implied to be close to 0	0.07
	"r" (Whole Blood)	Not explicitly stated, implied to be close to 1	0.976
	Slope (Fingersticks)	Not explicitly stated, implied to be close to 1	1.08
	Y-intercept (Fingersticks)	Not explicitly stated, implied to be close to 0	-0.02
	"r" (Fingersticks)	Not explicitly stated, implied to be close to 1	0.981
Assay Range	Range	0.2 to 10 mg/L	0.2 to 10 mg/L
Hematocrit Tolerance	Tolerance	N/A (implied to be within acceptable limits)	30-55%
Interference	Interference %	Less than 10%	Less than 10% interference
Precision	%CV (Low Control)	N/A (implied clinical acceptability)	14.3%
	%CV (High Control)	N/A (implied clinical acceptability)	11.5%
	%CV (Serum Sample @ 6.5 mg/L)	N/A (implied clinical acceptability)	11.4%

Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria for slope, y-intercept, and "r" values. However, for a device claiming substantial equivalence to a predicate, the expectation is that these metrics demonstrate a strong correlation and agreement with the predicate. The reported values of r (correlation coefficient) being close to 1 (0.975, 0.976, 0.981) and slopes being close to 1 (1.01, 1.06, 1.08) with small y-intercepts (-0.02, 0.07, 0.22) indicate good agreement and likely meet the implicit acceptance criteria for substantial equivalence. The assay range and interference criteria are explicitly stated and met. Precision values are reported but no explicit acceptance thresholds are provided.

2. Sample Size and Data Provenance

Test Set Sample Sizes:
- Accuracy (Serum vs. Predicate): 70 matched serum samples
- Accuracy (Whole Blood vs. Predicate): 76 whole blood samples (both venous and fingerstick)
- Precision: 2 levels of controls (Low and High) and one serum sample (6.5 mg/L). Each control was tested in duplicate, twice a day, over 20 days (total 80 replicates per level).
- Hematocrit Tolerance & Interference: No specific sample sizes provided, but tested with "evaluated levels" of endogenous substances.
Data Provenance: Not explicitly stated, but clinical studies for such devices typically involve samples from a geographically diverse patient population. The document does not specify country of origin or whether the data was retrospective or prospective. Given the nature of a 510(k) submission for an in vitro diagnostic, it is generally assumed to be prospective clinical study data collected for the purpose of demonstrating device performance.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

Number of Experts: Not applicable. This study does not involve expert readers assessing images or clinical cases to establish ground truth.
Qualifications of Experts: Not applicable.

4. Adjudication Method (Test Set)

Adjudication Method: Not applicable. This study does not involve expert adjudication as it is a quantitative diagnostic test compared to a predicate device. The "ground truth" is established by the predicate device's measurement.

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

Was it done? No. This is not an imaging AI device that relies on human interpretation. It's an in vitro diagnostic test that provides a quantitative measurement.

6. Standalone (Algorithm Only) Performance Study

Was it done? Yes. The entire accuracy study comparing the Cholestech LDX hs-CRP device to the Dade Behring N high sensitivity CRP test is a standalone performance study. The device's output (CRP concentration) is directly compared to the predicate's output. There is no human-in-the-loop component in the measurement itself.

7. Type of Ground Truth Used

Ground Truth Type: Predicate device measurement. The Dade Behring N High Sensitivity CRP test on the BN100 (K991385) is used as the reference standard to establish the "ground truth" for the accuracy study. This is a common approach for demonstrating substantial equivalence for new in vitro diagnostic devices.

8. Sample Size for the Training Set

Training Set Sample Size: Not applicable. This device is an in vitro diagnostic immunoassay, not a machine learning or AI algorithm that requires a "training set" in the conventional sense. The device's performance is determined by its inherent chemical and optical properties, and its "calibration information" is encoded on the magnetic stripe of each cassette, not learned from a dataset.

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

Ground Truth Establishment (Training Set): Not applicable, as there is no "training set" in the context of this device. The device's calibration is factory-set and encoded on each cassette.

Summary

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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.

The assigned 510(k) number is: KLYCS 79

Submitter Information (21 CFR 807.92(a)(1))

Cholestech Corporation Submitter: 3347 Investment Boulevard Hayward, CA 94545 phone: (510) 732-7200 (510) 732-7227 fax:

Thomas E. Worthy, PhD. Contact: Vice President, Research and Regulatory Affairs Cholestech Corporation.
March 1, 2004 Summary Date:

Name of Device and Classification (21 CFR 807.92(a)(2))

Name (trade):	Cholestech LDX high sensitivity C-Reactive Protein (hs-CRP)
Name (usual):	Immunoassay for the determination of C-Reactive Protein (CRP)
Classification:	21 CFR 866.5270, Class II, Product code DCK

Identification of Legally Marketed Predicate Device(s) (21 CFR 807.92 (a)(3))

LDX hs-CRP is substantially equivalent to the Dade Behring N High Sensitivity CRP assay on the BN100 (Dade Behring, Newark, DE). The LDX hs-CRP method is identical or similar to its predicate in terms of: intended use, measurement principle (immunoassay), undiluted sample measurement (assay) range, specimen type, and the requirement for an analyzer.

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Description of Device (21 CFR 807.92 (a)(4))

A brown magnetic stripe on each cassette contains the calibration information required for the Cholestech LDX Analyzer to convert the reflectance reading to the CRP concentration in mg/L.

Intended Use (21 CFR 807.92 (a)(5))

Cholestech LDX high sensitivity C-Reactive Protein (hs-CRP) is an in vitro diagnostic test for the quantitative determination of CRP in whole blood or serum.

Measurement of CRP is useful as an aid in the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases.

Similarities to the Predicate(s) (21 CFR 807.92 (a)(6))

A summary table of the similarities and differences between the LDX hs-CRP and the predicate device follows.

Device Name	LDX hs-CRP(new device)	Dade Behring N High Sensitivity CRPAssay(K991385)
Indicationsfor use	Cholestech LDX high sensitivity C-Reactive Protein (hs-CRP) test is anin vitro diagnostic test for thequantitative determination of C-reactive protein (CRP) in wholeblood or serum.Measurement of CRP is useful asan aid in the detection andevaluation of infection, tissue	N High Sensitivity CRP is an in vitrodiagnostic assay intended for the quantitativedetermination of C-reactive protein (CRP) inhuman serum and heparin- and EDTA- plasmaby means of particle enhancedimmunonephelometry using BN™ Systems. Inacute phase response, increased levels of anumber of plasma proteins, including C-reactive protein, are observed. Measurement

Comparison Table: Cholestech LDX bs-CRP vs Dade Behring BN100 high sensitivity CRP

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Device Name	LDX hs-CRP(new device)	Dade Behring N High Sensitivity CRPAssay(K991385)
	injury, inflammatory disorders andassociated diseases.	of CRP is useful for the detection andevaluation of infection, tissue injury,inflammatory disorders and associateddiseases
InstrumentRequired	Cholestech LDX Analyzer	Dade Behring BN-100 Nephelometer
Technology	Lateral flow immunoassay utilizingcolloidal gold particles coated withmonoclonal antibodies detected byreflectance spectrophotometry.	Agglutination of polystyrene particle coatedwith monoclonal antibodies detected bynephelometry
Assay Range	0.2 to 10 mg/L	0.175 to 11 mg/Lup to 1100 mg/dL with sample dilution
Sample Type	Whole blood (capillary and venous)and serum	Serum or plasma
CalibrationRequirements	No calibration performed by theuser; test information is encoded onthe magnetic stripe of the cassette,and the stripe is read by the LDXAnalyzer each time a cassette isrun.	Calibration required via the use of the N CRPStandard SY; under typical operatingconditions, the HS-CRP reagents must becalibrated every 4 weeks, and also with certainparts replacement or maintenance procedures.
TestingEnvironment	Professional-Use, point-of-care	Professional-Use, conventional laboratory

Brief Discussion of Nonclinical and Clinical Performance Data (21 CFR 807.92(b)(1,2,3)}

Assay range: 0.2- 10 mg/L .
Hematocrit tolerance: 30-55% .
Interference testing: less than 10% interference when challenged by evaluated levels of . endogenous substances
Precision: 2 levels of Controls (Low- ~1.2 mg/L CRP, and High- ~2.9 mg/L CRP) were . tested in duplicate, twice a day, over a 20 day period for a total of 80 replicates per level. The percent coefficient of variation (%CV) from the testing of the Low Control was 14.3%, and 11.5% from the testing of the High Control. When the same testing protocol was performed with a serum sample at 6.5 mg/L, the %CV was 11.4%.

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Accuracy: The LDX hs-CRP test was compared to the Dade Behring N high sensitivity CRP . test with 70 matched serum samples. Additionally, results obtained from testing 76 whole blood samples (both venous and fingerstick) on the LDX were compared to the serum results obtained on the Dade Behring N high sensitivity CRP. (Dade Behring N high sensitivity CRP on x-axis).

	n	slope	y-intercept	"r"	Range of Values
Serum	70	1.01	0.22	0.975	0.20 - 7.18 mg/L
Whole Blood	76	1.06	0.07	0.976	0.20 - 7.18 mg/L
Fingersticks	76	1.08	-0.02	0.981	0.20 - 8.65 mg/L

LDX hs-CRP vs Dade Behring N high sensitivity CRP

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its wing and body. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the eagle.

JUN 1 8 2004

Food and Drug Administratio 2098 Gaither Road Rockville MD 20850

Thomas E. Worthy, Ph.D. Vice President, Development and Regulatory Affairs Cholestech Corp. 3347 Investment Blvd. Hayward, CA 94545

K040579 Re:

K040377
Trade/Device Name: Cholestech LDX High-Sensitivity C-Reactive Protein (HS-CRP) Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCK Dated: May 19, 2004 Received: May 20, 2004

Dear Dr. Worthy:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave roviewed your betermined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the encreate) to the enactment date of the Medical Device Amendments, or to conninered pror to rial) 2011-11-11, accordance with the provisions of the Federal Food, Drug, de rices that have been require approval of a premarket approval application (PMA). and Cosmetic For (110) that the device, subject to the general controls provisions of the Act. The I ou may, merelore, mainer of the Act include requirements for annual registration, listing of general controls profisioning 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 your device is elassine additional controls. Existing major regulations affecting your device It may be subject to bach added 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 r lease be action and i bermination that your device complies with other requirements of the Act that I Dri has intatutes and regulations administered by other Federal agencies. You must or any it cacial statutes and regaranents, including, but not limited to: registration and listing (21 Comply with an the Tits Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2

This letter will allow you to begin marketing your device as described in your Section 510(k) I ms letter will anow you to ough manceing of substantial equivalence of your device to a legally premarket notification: "The PDF intentigation 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, If you desire specific mionitiation assessions of your device, please contact the Office of of questions on the promises and Safety at (301) 594-3084. Also, please note the In Vir o Diagliostic Do rios Branding by reference to premarket notification" (21CFR Part 807.97). Tegulation other general information on your responsibilities under the Act from the Tou may oounn outer gefarers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Jean M. Cooper, MS, Div.

Jean M. Cooper, MS, 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): K040579

Device Name: Cholestech LDX High-Sensitivity C-Reactive Protein (HS-CRP)

Indications For Use:

Cholestech LDX high sensitivity C-Reactive Protein (hs-CRP) is an in vitro diagnostic test for the Cholestech LDX high sensitive i tolen (no only in end in servin. Measurement of CRP is
quantitative determination C-reactive protein in whole blood or serving inflammatory quantitative determination citeactive protein in whole blood be of the counting to the matory
useful as an aid in the detection and evaluation of infection, tissue injury, in disorders, and associated diseases.

Prescription Use _ x x (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)

Carl C. Benson
Division Stop-Off

Office of In Vito Diognos Device Evaluation and Sc

K040579

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Regulation Number and Section

§ 866.5270 C-reactive protein immunological test system.

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