The PLAC® Test Reagent Kit is a turbidimetric immunoassay for the quantitative determination of Lp-PLA2 (lipoprotein-associated phospholipase A2) in human plasma or serum on automated clinical chemistry analyzers, to be used in conjunction with clinical evaluation and patient risk assessment as an aid in predicting risk for coronary heart disease, and ischemic stroke associated with atherosclerosis.

Device Description

The PLAC® Test Reagent Kit consists of separately packaged reagents, calibrators and controls for the measurement of Lp-PLA2 in serum or plasma on automated clinical chemistry analyzers.

PLAC® Test Reagent Kit

R1 Buffer solution with protein stabilizers
R2 Suspension of polymeric microparticles coated with mouse monoclonal antibodies specific to Lp-PLA2 (2C10 and 4B4).

The PLAC® Test Reagent Kit is based on turbidimetric immunoassay technology utilizing two Lp-PLA3-specific monoclonal antibodies (2C10 and 4B4) coated to polymeric microparticles. A set of Lp-PLA2 calibrators is used to plot a standard curve of absorbance (y-axis) versus Lp-PLA2 concentration in ng/mL (x-axis) from which the Lp-PLA2 concentration in the test sample can be determined. The concentration of Lp-PLA, in each sample and control is then interpolated from the standard curve using a spline curve fit with appropriate calibration curve fitting software. The kit expiration date and storage conditions are indicated on the package.

AI/ML Overview

The provided text describes the acceptance criteria and the study that proves the device meets those criteria for the PLAC® Test Reagent Kit.

Here's the breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Methods Comparison Data

Acceptance Criteria	Reported Device Performance (PLAC® Test Reagent Kit vs. PLAC® Test ELISA Kit)
Slope: 0.9 to 1.1	1.09
Intercept: ≤ 50 ng/mL	-1.7 ng/mL
Correlation Coefficient (R): ≥ 0.90	0.92

Imprecision Testing (Acceptance criteria are implied by the reported low %CVs, indicating good precision. Specific numerical acceptance criteria for %CV are not explicitly stated but are generally understood to be low for assays.)

Sample/Control	Mean Concentration Lp-PLA2 (ng/mL)	Intra-assay %CV (n=40)	Inter-assay %CV (n=40)	Total Assay %CV (n=80)
Serum 1	56.2	2.5%	4.6%	5.3%
Serum 2	250.1	1.0%	2.7%	2.9%
Buffer Control 1	191.2	0.7%	0.9%	1.4%
Buffer Control 2	370.8	1.0%	0.7%	1.6%

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

Sample Size for Test Set:
- Methods Comparison: n = 742 (number of samples used for the comparison between the predicate and modified device).
- Imprecision Testing: n = 40 for intra-assay and inter-assay, leading to a total of n = 80 for total assay %CV (per sample/control type).
Data Provenance: The document does not specify the country of origin of the data. It also does not explicitly state whether the data was retrospective or prospective, though method comparison and imprecision studies are typically prospective tests performed during device development and validation.

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

This device is an in vitro diagnostic reagent kit for measuring a biomarker. The "ground truth" for such devices is typically established by reference methods or clinical outcomes. Experts are not usually involved in establishing ground truth in the same way as they would be for image-based diagnostics.

In this case, the predicate device (PLAC® Test ELISA Kit) serves as the reference method for the methods comparison study, effectively establishing the "ground truth" against which the new device's measurements are compared.

4. Adjudication Method for the Test Set

Not applicable for this type of in vitro diagnostic device study. Adjudication methods are typically used in studies where human interpretation of data (e.g., medical images) is being assessed, often to resolve discrepancies between multiple readers. Here, the comparison is quantitative between two analytical methods.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for evaluating the impact of AI on human reader performance, usually in diagnostic imaging. The PLAC® Test Reagent Kit is an automated quantitative immunoassay, not an AI-powered diagnostic imaging tool that assists human readers.

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

Yes, the performance data presented (Methods Comparison and Imprecision Testing) represents the standalone performance of the PLAC® Test Reagent Kit as an automated turbidimetric immunoassay. This is an "algorithm only" in the sense that the device itself performs the quantitative measurement without direct human-in-the-loop interpretative steps during the assay run.

7. The Type of Ground Truth Used

The "ground truth" in this context is the measurements obtained from the legally marketed predicate device, the PLAC® Test ELISA Kit. For the imprecision studies, the ground truth is the inherent concentration of the analyte in the tested samples/controls.

8. The Sample Size for the Training Set

The document does not specify a separate training set. For in vitro diagnostic assays, particularly those based on established immunoassay principles, a dedicated "training set" in the machine learning sense is not typically used. The development and optimization of the assay (e.g., antibody selection, reagent formulation, calibration curve fitting algorithm) would precede the validation studies, but these development activities don't usually involve a distinct "training set" with established ground truth in the same way an AI algorithm does.

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

As no explicit training set is mentioned for an AI/algorithm-based device, this question is not directly applicable. The "training" or optimization of such an assay involves laboratory development and analytical characterization, with the "ground truth" reflecting accurate and precise measurements of Lp-PLA2 concentration, often established using highly characterized reference materials or established laboratory methods during the assay development phase. The information provided focuses on the validation against a predicate device and within-device performance.

Summary

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510(k) Summary

KIDBS 3

1.0 Submitted By:

Lynne McBride Director of Regulatory Affairs diaDexus 343 Oyster Point Blvd South San Francisco, California 94080 Telephone: 650-246-6423 Fax: 650-246-6439

JAN - 3 2011

2.0 Date Submitted

June 30, 2010

3.0 Device Name(s):

PLAC® Test Reagent Kit

4.0 Classification

Reagent:

866.5600 Low-density lipoprotein immunological test system NOE; test, system, immunoassay, lipoprotein-associated phospholipase a2

5.0 Legally Marketed Device

Predicate	PredicateManufacturer	DocketNumber
PLAC® Test ELISA Kit	diaDexus	K062234

6.0 Device Description

The PLAC® Test Reagent Kit consists of separately packaged reagents, calibrators and controls for the measurement of Lp-PLA2 in serum or plasma on automated clinical chemistry analyzers.

PLAC® Test Reagent Kit

R1 Buffer solution with protein stabilizers
R2 Suspension of polymeric microparticles coated with mouse monoclonal antibodies specific to Lp-PLA2 (2C10 and 4B4). .

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7.0 Intended Use

REAGENT KIT

8.0 Similarities and Differences to the Predicate

	Similarities
Item	Predicate - K062234 PLAC Test ELISA Kit	Modified - PLAC Test Reagent Kit
Product IntendedUse/Indications	The diaDexus PLAC® Test ELISA Kit is anenzyme immunoassay for the quantitativedetermination of Lp-PLA2 (lipoprotein-associated phospholipase A2) in human plasmaand serum, to be used in conjunction withclinical evaluation and patient risk assessmentas an aid in predicting risk for coronary heartdisease, and ischemic stroke associated withatherosclerosis.	The PLAC® Test Reagent Kit is aturbidimetric immunoassay for thequantitative determination of Lp-PLA2(lipoprotein-associated phospholipase A2)in human plasma or serum on automatedclinical chemistry analyzers, to be used inconjunction with clinical evaluation andpatient risk assessment as an aid inpredicting risk for coronary heart disease,and ischemic stroke associated withatherosclerosis.
Key ReagentComponents	Anti-PLA2 (2C10) and anti-PLA2 (4B4)	same
Calibrators Matrix	Recombinant Lp-PLA2 antigen in a proteinstabilizing diluent	Same
Control Matrix	Recombinant Lp-PLA2 antigen in a proteinstabilizing diluent	same
Controls Levels	2	same

Similarities

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Differences
Item	Predicate - K062234 PLAC ELISA Kit	Modified - PLAC Test Reagent Kit
Measuring range	0-1000 ng/mL	25 to 500 ng/mL
Methodology	Dual monoclonal antibody sandwich ELISA readat 450 nm on a microwell plate reader	Immuno- Turbidimetric assay read at 570nm on clinical chemistry analyzers
ReagentConfiguration	Anti-Lp-PLA₂ mAb (2C10) coated stripwellsWash bufferEnzyme conjugate anti-Lp-PLA₂ mAb (4B4)-HRPTMB substrateStop solution	Two reagent systemR1- Buffer solution with protein stabilzersR2- antibody coated microparticles (mAbs 2C10 and 4B4)
Kit Configuration	Reagent, calibrators and controls all in one kit	Reagent, calibrators and controls inseparate kits.
Calibrator Levels	6 levels - 0,50,100, 250, 500, 1000 ng/ml	5 levels - 0, 50, 100, 250, 500 ng/ml
Reference Range	Median value is 235 ng/ml per populationstudied in 2006	Median value is 152 ng/mL per populationstudied in 2010
Samples Types	Serum, EDTA, Heparin	Serum, K₂EDTA

9.0 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. Assay equivalence is demonstrated through method comparison and imprecision studies.

Methods Comparison Data

PredicateMethod	Slope	Intercept	R	n	Acceptance Criteria	ModifiedProduct
PLAC® TestELISA Kit	1.09	-1.7	0.92	742	Slope 0.9 to 1.1Intercept ≤ 50 ng/mLr ≥0.90	PLAC® TestReagent Kit

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Imprecision Testing

Samples	Mean ConcentrationLp-PLA2 (ng/mL)	Intra-assay%CV n=40	Inter-assay%CV n=40	Total Assay%CV n=80
Serum 1	56.2	2.5%	4.6%	5.3%
Serum 2	250.1	1.0%	2.7%	2.9%
Buffer Control 1	191.2	0.7%	0.9%	1.4%
Buffer Control 2	370.8	1.0%	0.7%	1.6%

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

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Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three wings, representing service, science, and protection. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

diaDexus, Inc. c/o Nina Peled, PhD Regulatory Affairs Consultant 343 Oyster Point Blvd South San Francisco, CA 94080

JAN 0 3 2011

Re: ' K101853 PLAC® Test Reagent Kit Trade/Device Name: Regulation Number: 21 CFR 866.5600 Regulation Name: Low-density lipoprotein immunological test system Regulatory Class: Class II Product Code: NOE Dated: November 23, 2010 Received: November 24, 2010

Dear Dr. Peled,

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).

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.

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Page 2 -

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Viro 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 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) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

CJC.

Courmey 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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JAN - 3 2011

Indications for Use Form

510(k) Number (if known): ≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤≤

Device Name:

Indications for Use:

The PLAC® Test Reagent Kit is a turbidimetric immunoassay for the quantitative determination of Lp-PLA2 (lipoprotein-associated phospholipase A₂) in human serum or plasma on automated clinical chemistry analyzers, to be used in conjunction with clinical evaluation and patient risk assessment as an aid in predicting risk for coronary heart disease, and ischemic stroke associated with atherosclerosis.

Prescription Use X (Part 21 CFR 801 Subpart D)	AND/OR	Over-The-Counter Use (21 CFR 801 Subpart C)
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(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benson

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

510(k) K101853

Regulation Number and Section

§ 866.5600 Low-density lipoprotein immunological test system.

(a)
Identification. A low-density lipoprotein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein in serum may aid in the diagnosis of disorders of lipid (fat) metabolism and help to identify young persons at risk from cardiovascular diseases.(b)
Classification. Class II (performance standards).