The Diazyme Lp(a) is intended as a latex particle enhanced immunoturbidimetric assay for the in vitro quantitative determination of lipoprotein(a) [Lp(a)] concentration in human serum er plasma (EDTA) on Clinical Chemistry Systems. The measurement of Lp(a) is useful in evaluating lipid metabolism disorders and assessing atherosclerotic cardiovascular diseases in specific populations, when used in conjunction with clinical evaluation.

Diazyme Lp(a) Control is intended for use in monitoring the quality control of results obtained with the Diazyme Lp(a) reagents by turbidimetry.

Diazyme Lp(a) standard is intended for use in establishing the calibration curve for the Diazyme Lp(a) reagents by turbidimetry.

Device Description

The Diazyme Lipoprotein (a) Assay is based on a latex enhanced immunoturbidimetric assay. Lp(a) in the sample binds to specific anti-Lp(a) antibody, which is coated on latex particles, and causes agglutination. The degree of the turbidity caused by agglutination can be measured optically and is proportional to the amount of Lp(a) in the sample.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Diazyme Lp(a) Assay, based on the provided text:

Acceptance Criteria and Device Performance

The provided document describes the Diazyme Lp(a) Assay by comparing its performance to a predicate device (Denka Lp(a) Assay) and reporting specific performance characteristics such as precision and accuracy. The "acceptance criteria" are implied by the performance of the legally marketed predicate device and the new device demonstrating "good agreement" and "substantially similar" results.

Acceptance Criterion (Implied by Predicate/Good Agreement)	Reported Diazyme Lp(a) Assay Performance
Reportable Range (Serum)	5.44 mg/dL to 100.0 mg/dL (Predicate: 0.5mg/dL to 80.0 mg/dL)
Reportable Range (Plasma)	5.44 mg/dL to 100.0 mg/dL (Predicate: 0.5mg/dL to 80.0 mg/dL)
Precision/Serum (Within Run)	1.1% - 2.6% (Predicate: 1.26% - 2.00%)
Precision/Serum (Total)	2.4% - 3.6% (Predicate: 0.99% - 2.22%)
Accuracy/Serum (Correlation Coefficient)	0.998 (Predicate: 0.989)
Accuracy/Serum (Slope/Intercept)	y = 0.9895x + 0.0279 (Predicate: y = 1.108x - 1.44)
Accuracy/Plasma (Correlation Coefficient)	0.9803 (Predicate: 0.990)
Accuracy/Plasma (Slope/Intercept)	y = 1.044x + 0.0407 (Predicate: y = 1.079x - 0.16)
Interference (Triglycerides)	Less than 10% interference at 1000 mg/dL
Interference (Ascorbic acid)	Less than 10% interference at 10 mmol/L
Interference (Bilirubin)	Less than 10% interference at 40 mg/dL
Interference (Bilirubin Conjugated)	Less than 10% interference at 40 mg/dL
Interference (Hemoglobin)	Less than 10% interference at 1000 mg/dL

Note: The acceptance criteria are based on demonstrating "substantial equivalence" to the predicate device. This implies that the new device's performance should be comparable and within acceptable analytical limits, which are not explicitly defined as numerical thresholds beyond the reported performance metrics. The statement "good agreement with legally marketed assay" and "no significant deviation" act as the overarching acceptance criteria for accuracy.

Study Details

Sample Size used for the test set and the data provenance:
- Test Set Sample Size:
  - Accuracy (Correlation studies): 76 serum samples.
  - Precision: Three levels of serum specimens. While not explicitly stating the number of unique patient samples, the study design involved testing these three levels with 2 runs per day, with duplicates, over 20 working days.
  - Interference: Human serum samples were used, but the exact number is not specified.
- Data Provenance: Not explicitly stated, but the samples are "human serum" and "human plasma." There is no mention of country of origin or whether the data was retrospective or prospective.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This device is an in vitro diagnostic assay that quantifies a biomarker (Lp(a)). The "ground truth" for such assays is typically established by comparative methods, such as a legally marketed predicate device or a reference method. It does not involve human expert interpretation of images or clinical findings in the same way as, for example, a radiology AI device. Therefore, no information on human experts establishing ground truth for the test set or their qualifications is provided or relevant in this context.
Adjudication method for the test set:
- Not applicable. As explained above, this is a quantitative diagnostic assay where the "ground truth" is typically the result from a reference method or predicate device, not subject to human expert adjudication. The comparison method is direct measurement against the predicate device.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not applicable. This is an in vitro diagnostic assay, not an AI-powered diagnostic imaging device that assists human readers. Therefore, an MRMC study and AI-assisted performance improvement are not relevant.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is primarily a standalone device performance study. The Diazyme Lp(a) Assay is an automated quantitative assay. The reported performance metrics (precision, accuracy, interference) are for the device itself operating without human interpretation of its primary output beyond standard laboratory procedures for running an assay. The comparison against the predicate device reflects the standalone performance.
The type of ground truth used:
- The "ground truth" for the accuracy study was established by comparison with an existing commercial Lp(a) assay method (the predicate device, Denka Lp(a) Assay, K013359). This is a common method for establishing accuracy and substantial equivalence for in vitro diagnostic devices.
The sample size for the training set:
- No information about a "training set" is provided. This is typical for in vitro diagnostic assays based on chemical/immunological reactions, as they are not machine-learning algorithms that require a training phase with labeled data in the same way an AI device does. The device's performance characteristics are determined through analytical validation studies (precision, accuracy, interference, linearity, etc.).
How the ground truth for the training set was established:
- Not applicable, as no training set for an AI/machine learning algorithm is mentioned or relevant for this type of in vitro diagnostic device.

Summary

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Pre-market Notification Diazyme Lp(a) Assay

Koryyr

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	JAN 13 2009
Date the Summary was Prepared:	Aug 26, 2008; Dec 1, 2008
Name of the Device	Diazyme Lipoprotein (a) Assay
Trade Name:	Diazyme Lp(a) Assay
Common/Usual Name	Lp(a) Test System
Device Classification Name	Low Density Lipoprotein Immunological Test System
Product code:	DFC, JIS, JJX
Submission Type	510k
Regulation Number	866.5600, 862.1150, 862.1660
Device Class	II
Predicate Device:	For the Lipoprotein (a) Immunological Test System Lipo-protein test system, we are claiming equivalence to Lp(a)-LATEX SEIKEN ASSAY KIT manufactured by DenkaSeiken Co. Ltd

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Substantial Equivalence Information

l. Predicate device name(s):
Lp(a) Assay
1. Predicate 510(k) number(s):
  K013359

3. . Comparison with predicate:

Indications for Use

Diazyme Lp(a) Assay	Denka Lp(a) Assay	Equivalency
The Diazyme Lp(a) immunoassay isintended for the in vitro quantitativedetermination of Lipoprotein (a) in humanserum and plasma.	The Lp(a) Assay is a latex in vitro diag-nostic immunoassay for the quantitativedetermination of Lipoprotein (a) inhuman serum and plasma.	Same

Principle

Diazyme Lp(a) Assay	Denka Lp(a) Assay	Equivalency
The Diazyme Lipoprotein (a) Assay isbased on a latex enhanced immunoturbidi-metric assay. Lp(a) in the sample binds tospecific anti-Lp(a) antibody, which iscoated on latex particles, and causes agglu-tination. The degree of the turbidity causedby agglutination can be measured opticallyand is proportional to the amount of Lp(a)in the sample.	The Lp(a)-Latex Seiken Assay kit is a latex-enhanced immunoturbidimetric in vitro diag-nostic assay. Lp(a) in the sample binds to thespecific anti-Lp(a) antibody, which is ad-sorbed to latex particles and agglutinates. Theagglutination is detected as an absorbancechange when read on an automated chemistryanalyzer (at 700 nm). The magnitude of thechange is proportional to the quantity ofLp(a) in the sample. The actual concentrationis then determined by interpolation from acalibration curve prepared from calibrators ofknow concentrations.	Same

Test Objective

Diazyme Lp(a) Assay	Denka Lp(a) Assay	Equivalency
For the in vitro quantitative determinationof lipoprotein (a) in serum or plasma.	For the in vitro quantitative determinationof lipoprotein (a) in serum or plasma us-ing automated chemistry analyzers.	Same

Type of Test

Diazyme Lp(a) Assay	Denka Lp(a) Assay	Equivalency
Quantitative	Quantitative	Same

Specimen Type

Diazyme Lp(a) Assay	Denka Lp(a) Assay	Equivalency
Human serum and plasma	Human serum and plasma	Same

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Product Type

Diazyme Lp(a) Assay	Denka Lp(a) Assay	Equivalency
Calibrator, Reagent, Instrument	Calibrator, Reagent, Instrument	Same

Performance

Diazyme Lp(a) Assay	Denka Lp(a) Assay
Reportable Range:Serum: 5.44 mg/dL to 100.0 mg/dLPlasma: 5.44 mg/dL to 100.0 mg/dL	Reportable Range:Serum: 0.5mg/dL to 80.0 mg/dLPlasma: 0.5mg/dL to 80.0 mg/dL
Precision/Serum:Within Run: 1.1% - 2.6%Total: 2.4% - 3.6%	Precision/Serum:Within Run: 1.26% - 2.00%Total: 0.99% - 2.22%
Accuracy/Serum:Correlation Coefficient: 0.998Slope/Intercept:$y = 0.9895x + 0.0279$	Accuracy/Serum:Correlation Coefficient: 0.989Slope/Intercept:$y = 1.108x - 1.44$
Accuracy/Plasma:Correlation Coefficient: 0.9803Slope/Intercept:$y = 1.044x + 0.0407$	Accuracy/Plasma:Correlation Coefficient: 0.990Slope/Intercept:$y = 1.079x - 0.16$

Calibrator Comparison

Diazyme Lp(a) Assay	Denka Lp(a) Assay	Equivalency
Lyophilized form	Lyophilized form	Same

Control Comparison

Diazyme Lp(a) Assay	Denka Lp(a) Assay	Equivalency
Lyophilized form	Lyophilized form	Same

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Rationale for Considering the Device Substantially Equivalent to Devices Approved for Interstate Commerce

The Denka Lp(a) Assay (K013359) was selected for method comparison testing of human serum and plasma samples with the Diazyme Lp(a) Assay. Detailed performance characteristics and comparison analysis are given in this filing and demonstrate substantial equivalence to predicate device that is currently being legally marketed.

The Diazyme Lp(a) Assay is substantially similar to the approved predicate test. The minor differences in the performances of the tests should not affect the safety and effectiveness of the Diazyme Lp(a) Assay and offers users an in-vitro diagnostic device to measure Lp(a) in human serum and plasma.

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Description of the Device

Lipoprotein (a) is a cholesterol-rich lipoprotein particle found in human serum. There is substantial evidence linking lipoprotein (a) excess to a high risk for premature coronary heart disease (CHD), increased risk of myocardial infraction (MI) and stroke, and restenosis after angioplasty (PTCA) and coronary bypass procedures. Lipoprotein (a) has been called a powerful predictor of premature atherosclerotic vascular disease. Therefore measurement of lipoprotein(a) is now recommended in several patient subgroups for whom excess lipoprotein(a) may have important clinical consequences: (1) patients with premature athero-sclerosis, (2) patients with a strong family history of premature coronary heart disease (CHD), (3) patients with elevated LDL-C and greater than or equal to two risk factors, (4) patients who have had coronary angioplasty in whom lipoprotein(a) excess may increase the risk of restenosis, and (5) patients who have undergone coronary bypass graft surgery in whom Lp(a) excess may be associated with graft stenosis.

Intended Use of the Device:

The Diazyme Lipoprotein (a) [Lp(a)] Assay and Lipoprotein (a) Assay Calibrator Set are intended for the in vitro quantitative determination of lipoprotein (a) in serum or plasma.

Performance Testing Summaries

Precision

The precision of the Diazyme Lp(a) Enzymatic Assay was evaluated according to Clinical and Laboratory Standards Institute (formerly NCCLS) EP5-A guideline. In the study, three levels of serum specimens containing about 17.2, 43.2, and 70.0 mg/dL Lp(a) respectively are tested with 2 runs per day with duplicates over 20 working days.

Serum Testing	Level 1	Level 2	Level 3
Within-Run Precision	$C_v% = 2.6%$	$C_v% = 1.4%$	$C_v% = 1.1%$
Total Precision	$C_v% = 3.6%$	$C_v% = 3.3%$	$C_v% = 2.4%$

Accuracy

Correlation studies were performed by testing 76 serum samples in comparison with an existing commercial Lp(a) assay method. The result summary indicates good agreement with legally marketed assay.

Accuracy Summary:

Serum: Correlation Coefficient: 0.9983 Slope/Intercept:

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y = 0.9891x + 0.0947

Plasma: Correlation Coefficient: 0.9803 Slope/Intercept: y = 0.9895/0.0279

Interference

We have conducted interference studies by spiking human serum samples with substances normally present in serum and found less than 10% interference at the indicated concentrations.

Interference Study
Substance	Concentration
Triglycerides	1000 mg/dL
Ascorbic acid	10 mmol/L
Bilirubin	40 mg/dL
Bilirubin Conjugated	40 mg/dL
Hemoglobin	1000 mg/dL

Conclusion: Detailed comparison analysis presented in this 510k submission, together with linearity, precision and interference and other detailed studies, demonstrates that the Diazyme Lp(a) Assay has excellent accuracy and is safe and effective. There is no significant deviation between the results obtained by Diazyme Lp(a) Assay and the legally marketed predicate device (K013359) when testing clinical patient samples and is therefore substantially similar.

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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES. USA" arranged around the perimeter. Inside the circle is an abstract emblem resembling an eagle or bird-like figure with stylized feathers.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

General Atomics Diazyme Laboratories c/o Dr. Abhiiit Datta 12889 Gregg Court Poway, CA 92064

JAN 1 3 2009

Re: K082488

Trade/Device Name: Diazyme LP(a) assay Regulation Number: 21 CFR 866.5600 Regulation Name: Low-Density Lipoprotein Immunological Test System. Regulatory Class: Class II Product Code: DFC, JIT, JJX Dated: December 1, 2008 Received: December 4, 2008

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); 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 of your device to a results 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 (301) 594-3084. Also, please not the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 tolla die (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely vours.

Cott C. Hh

Courtney C. Harper, Ph.D. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

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Indication for Use

510(k) Number (if known): K082488

Device Name: Diazyme Lp(a) Assay

Indication For Use:

Diazyme Lp(a) Control is intended for use in monitoring the quality control of results obtained with the Diazyme Lp(a) reagents by turbidimetry.

Diazyme Lp(a) standard is intended for use in establishing the calibration curve for the Diazyme Lp(a) reagents by turbidimetry.

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 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 (OIVD)

Carol Benson

ﯽ

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

510(k) 1682488
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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).