SPQ TEST SYSTEM by DIASORIN, INC.

The SPQTM Antibody Reagent Set for Lp(a) is designed for the quantitative determination of human lipoprotein(a) in human serum by immunoprecipitin analysis using a turbidimetric clinical analyzer. The measurement of Lp(a) is indicated for use in conjunction with clinical evaluation, patient risk assessment and other lipoprotein tests to evaluate disorders of lipid metabolism and to assess coronary heart heart disease (CHD) in male Caucasian populations.

Device Description

The SPQ™ Test System for Lp(a) provides the quantitative determination of human lipoprotein(a) by automated immunoprecipitin analysis. Standards, controls, and samples are pipetted undiluted into sample cups. Microvolumes of these samples and a polymeric enhancer are pipetted into individual cuvettes. Following an initial incubation and measurement of sample blank, undiluted antiserum is added to the cuvettes. The sample and antiserum are mixed in the reaction cuvettes. Reaction temperature is controlled at 37°C. Insoluble antibody complexes form immediately, producing turbidity in the mixture and increasing the amount of light scattered by the solution. The amount of antigen-antibody complex formed, and thus the amount of light scatter, is proportional to the amount of lipoprotein(a) in the initial sample. The solution absorbance is measured after a 10 minute incubation period.

A calibration curve is generated by analyzing a series of calibrators with known concentrations of lipoprotein(a) and using the instrument's data reduction capability or manually plotting the change in absorbance versus lipoprotein(a) concentration. Concentrations of lipoprotein(a) within the controls and samples are interpolated from the calibration curve.

The test is designed for use on instruments capable of immunoprecipitin analysis, as the Cobas FARA II. The instruments measure the amount of light scattering in the reaction cuvettes due to the formation of insoluble antigen-antibody complexes. The systems are capable of storing a calibration curve. This assay is not designed for manual use.

AI/ML Overview

Here's an analysis of the provided text, focusing on acceptance criteria and study details:

Device & Intended Use:
The device under consideration is the SPQ™ Test System Antibody Reagent Set for Lp(a). It's an immunoprecipitin assay for the quantitative determination of human lipoprotein(a) in human serum using a turbidimetric clinical analyzer. Its intended use is to evaluate lipid metabolism disorders and assess coronary heart disease (CHD) in male Caucasian populations, in conjunction with clinical evaluation, patient risk assessment, and other lipoprotein tests.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in a quantitative format (e.g., "correlation coefficient must be > X"). However, based on the reported performance, we can infer what was considered acceptable for market clearance. The "performance data" section effectively serves as a demonstration of meeting implied acceptance criteria by showing good correlation, discrimination between populations, and reproducibility within reasonable limits for an immunoassay.

Performance Metric	Implied Acceptance Criterion (Inferred)	Reported Device Performance
Clinical Correlation	Statistically significant difference between normal and diseased populations.	Median Lp(a) levels statistically significantly different (Normal: 11.6 mg/dL, Diseased: 26.3 mg/dL).
Correlation to Reference Method (Northwest Lipid Research Laboratory)	High correlation (e.g., >0.95 or similar to predicate).	0.962 (equivalent to predicate).
Correlation to Predicate Device (Strategic Diagnostics Macra assay)	High correlation (e.g., >0.95).	0.961.
Recovery of Lp(a) Polymorphs	No significant departure from parallelism across the molecular weight range.	No departure from parallelism observed.
Reproducibility (Within-Run %CV)	Acceptable within-run variability for a clinical immunoassay (typically <10-15%, lower for higher concentrations).	Ranged from 2.0% to 9.4%.
Reproducibility (Total %CV)	Acceptable total variability for a clinical immunoassay (typically <15-20%, lower for higher concentrations).	Ranged from 3.6% to 13.9%.

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

Clinical Correlation Study:
- Sample Size: Not explicitly stated as "sample size." However, the study involved a "normal population with known cardiac risk factors" and a "population with known atherosclerotic heart disease." The number of individuals in these populations is not provided.
- Data Provenance: Not explicitly stated (e.g., country of origin). The study is retrospective in the sense that populations are identified by "known" conditions/risk factors.
Correlation Studies (vs. NWLRL and Macra):
- Sample Size: Not explicitly stated.
- Data Provenance: Not explicitly stated.
Recovery Study:
- Sample Size: Not explicitly stated how many "Lp(a) polymorphs" were tested or how many replicate measurements were made.
- Data Provenance: Not explicitly stated.
Reproducibility Study:
- Sample Size: 6 samples (spanning the assay range) + 2 control samples. Each sample/control was tested in duplicate, once a day for 7 days over a 2-week period. This results in 14 data points per sample/control per site (7 days * 2 replicates). The table shows N=42, which likely refers to the total number of individual measurements for each sample across all sites (3 sites * 7 days * 2 replicates = 42).
- Data Provenance: Not explicitly stated. It's a prospective study designed specifically for reproducibility assessment.

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

No information provided regarding the number or qualifications of experts used to establish ground truth for any of the studies (clinical correlation, correlation to reference/predicate, recovery, or reproducibility).
For the clinical correlation, the "known cardiac risk factors" and "known atherosclerotic heart disease" imply a clinical diagnosis was made by healthcare professionals, but no details are given about how these diagnoses were standardized or adjudicated for the purpose of the study.

4. Adjudication Method for the Test Set

No information provided on any explicit adjudication method (e.g., 2+1, 3+1).
For the clinical correlation, the basis for categorizing individuals into "normal" and "diseased" populations relies on "known" conditions, which presumes prior clinical assessment, but the study itself does not describe an active adjudication process for its test set.

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

No, an MRMC comparative effectiveness study was not done.
This device is an in vitro diagnostic (IVD) assay, not an imaging or diagnostic support AI device that would typically involve human readers. Its performance is measured directly through its quantitative output and correlation to reference methods and clinical outcomes, not by comparing human reader performance with and without AI assistance.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the provided performance data represents standalone performance.
The "SPQ Test System" is an automated immunoprecipitin analysis system. The data presented (clinical correlation, correlation to other assays, recovery, reproducibility) characterizes the performance of the device itself (the reagent set used on a turbidimetric analyzer like the Cobas FARA II) without requiring a human-in-the-loop to interpret its primary output (quantitative Lp(a) levels). A human then uses these quantitative results in conjunction with other clinical information, but the assay's performance is standalone.

7. The Type of Ground Truth Used

Clinical Correlation: Clinical diagnosis/categorization of individuals as "normal with cardiac risk factors" or "with known atherosclerotic heart disease." This relies on outcomes data and prior clinical evaluation.
Correlation to Reference Methods: The "Northwest Lipid Research Laboratory reference method" and the "Strategic Diagnostics Macra assay" served as the ground truth proxies for comparison.
Recovery Study: The "known concentrations of Lp(a) polymorphs" (implied, as the study evaluates quantitative recovery) serve as the intended ground truth.
Reproducibility Study: "Known" Lp(a) levels in the control samples and the average concentrations of test samples after multiple runs serve as the ground truth for assessing variability.

8. The Sample Size for the Training Set

Not applicable / No information provided.
This device is a reagent set for an immunoassay, not a machine learning algorithm that requires a separate "training set" in the conventional sense. The development of such assays typically involves optimization and validation steps, but these are not referred to as "training" in the context of AI/ML.

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

Not applicable. As stated above, this is not an AI/ML device that uses a "training set."

Summary

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MAR-31-99 WED 04:43 PM

AMERICANSTANDARDDIASORIN

31-99 WED 04:43

4/2/99

FAX NO. +301 497 1126 P. 04
K982708

510(K) SUMMARY

SUBMITTED BY:

Judith J. Smith DiaSorin, Inc. 9175 Guilford Rd. Suite 100 Columbia, MD 21046

NAME OF DEVICES: Trade Name:

SPQ Test System Antibody Reagent Set for Lp(a)

Immunoprecipitin assay for quantitative

Common Names/Descriptions:

Classification Names:

Strategic Diagnostics Macra Lp(a)

determination of Lp(a) levels

Lipoprotein a (Lp(a)) test

PREDICATE DEVICES:

DEVICE DESCRIPTION:

INTENDED USE: The SPQTM Antibody Reagent Set for Lp(a) is designed for the quantitative determination of human lipoprotein(a) in human serum by immunoprecipitin analysis using a turbidimetric clinical analyzer. The measurement of Lp(a) is indicated for use in conjunction with clinical evaluation, patient risk assessment and other lipoprotein tests to evaluate disorders of lipid metabolism and to assess coronary heart disease (CHD) in male Caucasian populations.

KIT DESCRIPTION: The SPQ™ Test System for Lp(a) provides the quantitative determination of human lipoprotein(a) by automated immunoprecipitin analysis. Standards, controls, and samples are pipetted undiluted into sample cups. Microvolumes of these samples and a polymeric enhancer are pipetted into individual cuvettes. Following an initial incubation and measurement of sample blank, undiluted antiserum is added to the cuvettes. The sample and antiserum are mixed in the reaction cuvettes. Reaction temperature is controlled at 37°C. Insoluble antibody complexes form immediately, producing turbidity in the mixture and increasing the amount of light scattered by the solution. The amount of antigen-antibody complex formed, and thus the amount of light scatter, is proportional to the amount of lipoprotein(a) in the initial sample. The solution absorbance is measured after a 10 minute incubation period.

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PERFORMANCE DATA: All performance data were collected using the Cobas FARA II. Clinical Correlation: A clinical study was conducted with the SPQ Test System to assess whether the assay could detect a difference in Lo(a) levels between a normal population with known cardiac risk factors and a population with known atherosclerotic heart disease. The median Lp(a) level for the normal male population was 11.6 mg/dL, while the median level for the diseased male population was 26.3 mg/dL. The populations were statistically significantly different.

The assay was compared to the Northwest Lipid Research Laboratory reference method and to the Strategic Diagnostics Macra assay. The correlation coefficient to the NWLRL assay was 0.962 (equivalent to the correlation of the Macra assay to the NWLRL method) and the correlation to the Macra assay was 0.961.

Recovery: A study was performed to evaluate the quantitative recovery of different Lp(a) polymorphs which spanned the molecular weight range from 419 to 796 kD. A model of dilution parallelism was used to test whether the different polymorphs were recovered equivalently. Statistical analysis of the data obtained from this study showed that no departure from parallelism was observed.

Reproducibility: Reproducibility studies were performed at 3 sites using one lot of SPQ reagents. Assay reproducibility was determined by testing 6 samples that spanned the range of the assay as well as the 2 control samples. Samples were tested in duplicate once a day for 7 days over a 2 week period. The results are summarized below.

Sample	Meanmg/dL	WithinRun %CV	Total%CV
Level 1 Control	22.3	4.0	5.4
Level 2 Control	52.0	2.7	4.9
RP 1	9.9	9.4	13.9
RP 2	21.9	3.6	7.7
RP 3	45.2	3.1	6.1
RP 4	58.4	5.3	8.6
RP 5	71.9	2.6	4.9
RP 6	85.5	2.0	3.6
N	42

REPRODUCIBILITY RESULTS FOR SPQ LP(A) ASSAY - COMBINED SITES

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Public Health Service

APR 2 1999 Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Ms. Judith J. Smith DiaSorin, Inc. 9175 Guilford Road, Suite 100 Ouarry Park Place Columbia, Maryland 21046 Re: K982708 Trade Name: SPO Test System Antibody Reagent Set for Lp(a) Regulatory Class: II Product Code: DFC

II I Dated: March 4, 1999 Received: March 5, 1999

Dear Ms. Smith:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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.

IIS

JJX

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

Image /page/2/Picture/9 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three heads, representing the department's mission to protect the health of all Americans and provide essential human services. The eagle is encircled by the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA".

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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,

Steven Sutman

Steven I. Gutman, M.D. M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page 1 of 1

510(k) NUMBER: K982708

DEVICE NAME: Antibody Reagent Set for Lp(a) SPQ™ Test System

INDICATIONS FOR USE: The SPQTM Antibody Reagent Set for Lp(a) is designed for the quantitative determination of human lipoprotein(a) in human serum by immunoprecipitin analysis using a turbidimetric clinical analyzer. The measurment of Lp(a) is Indicated for use in conjunction with clinical evaluation, patient risk assessment and other lipoprotein tests to evaluate disorders of lipid metabolism and to assess coronary heart disease (CHD) in male Caucasian populations.

K982708 Jun Cooper

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K982708

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

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).