The Diazyme Lipoprotein (a) Calibrator Set is intended for use in establishing the calibration curve for the Diazyme Lipoprotein (a) Assay reagents by turbidimetry. For in vitro diagnostic use only.

The Diazyme Lipoprotein (a) Control Set is intended for use in monitoring the quality control of results obtained with the Diazyme Lipoprotein (a) Assay reagents by turbidimetry. For in vitro diagnostic use only.

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.

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

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the Diazyme Lipoprotein (a) Calibrator Set and Control Set, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

The document primarily focuses on demonstrating the substantial equivalence of the modified device (liquid stable calibrators/controls) to the predicate device (lyophilized calibrators/controls) using various performance studies. Rather than explicit "acceptance criteria" presented as pass/fail thresholds for each metric, the document describes the analytical performance characteristics that were verified and validated to show equivalence. The "reported device performance" are the results from these verification/validation activities, demonstrating that the modified device maintains the performance characteristics of the predicate.

Given this, I'll present the key performance metrics and their reported values for both the predicate and the new device where available, implicitly showing that the new device's performance aligns with or is very similar to the predicate, thus "meeting" the unstated acceptance criteria of maintaining similar performance.

Performance Metric	Predicate Device (K082488) Reported Performance	New Device (K131556) Reported Performance	Implied Acceptance Criteria (for K131556)
Intended Use	Establish calibration curve, monitor QC	Establish calibration curve, monitor QC	Same as predicate
Calibrator Composition	Lyophilized human serum	Liquid stable human serum	-
Control Composition	Lyophilized human serum	Human serum, preservative, Lp(a)	-
Standardization Method	Master lot assigned values, then new lots verified	Value transfer from predicate device	Demonstrate traceability/consistency with predicate reference lots
Calibrator Range	0-100 mg/dL	0-100 mg/dL	Maintain 0-100 mg/dL
Analytical Sensitivity	5.44 mg/dL	5.44 mg/dL	Maintain 5.44 mg/dL
Limit of Blank (LOB)	1.14 mg/dL	1.13 mg/dL	Similar to predicate (e.g., within a predefined % difference or biological relevance)
Limit of Quantitation (LOQ)	5.44 mg/dL	5.44 mg/dL	Maintain 5.44 mg/dL
Dynamic Range	Up to 100 mg/dL Lp(a)	Up to 100 mg/dL Lp(a)	Maintain up to 100 mg/dL Lp(a)
Precision (20-Day)	Not explicitly stated in this summary	Demonstrated (results not detailed)	Acceptable statistical precision (e.g., CV% within specified limits for various concentrations)
Linearity	Not explicitly stated in this summary	Demonstrated (results not detailed)	Linear response across the dynamic range (e.g., R^2 > 0.99)
Accuracy (Method Comparison)	Not explicitly stated in this summary	Demonstrated (correlation with predicate)	Excellent correlation with predicate device (e.g., R^2 > 0.975, slope near 1, intercept near 0)
Accuracy (Matrix Comparison)	Not explicitly stated in this summary	Demonstrated	Acceptable performance across different sample matrices
Interference	Not explicitly stated in this summary	Demonstrated	Minimal to no significant interference from common endogenous and exogenous substances
Calibrator Stability (Acc. & Real-Time)	Not explicitly stated in this summary	Demonstrated	Meet predefined shelf-life and storage conditions (e.g., within 5% of initial value)
Control Stability (Acc. & Real-Time)	Not explicitly stated in this summary	Demonstrated	Meet predefined shelf-life and storage conditions (e.g., within 5% of initial value)
Open/Closed Vial Calibrator Stability	Not explicitly stated in this summary	Demonstrated	Maintain stability for specified in-use periods
Value Assignment & Traceability	Not explicitly stated in this summary	Demonstrated	Consistent and traceable value assignment

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

The document does not explicitly state the sample sizes for the "test sets" for each specific study (e.g., how many samples were used for linearity, method comparison, etc.). It mentions that the studies were performed as "verification and validation activities."

Data Provenance: The studies were conducted by Diazyme Laboratories, likely in their facilities (Poway, CA). The data is retrospective in the sense that it evaluates the performance of a modified device against a previously cleared predicate device. The samples used (human serum, plasma) are laboratory materials. There is no mention of country of origin for these samples or if they were from a specific clinical population.

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

This submission is for calibrators and controls, which are used to standardize an assay and monitor its quality. The "ground truth" here isn't established by human experts in a clinical context (like radiologists reading images). Instead, the ground truth for the values assigned to the calibrators and controls is established through:

Value Transfer: The "Value Transfer from predicate device Diazyme Lp(a) Reagent and calibrator (K082488) to reference lot of liquid stable calibrators." This implies the predicate device and its established values serve as the primary reference.
Analytical Measurement: The calibrator materials were "assayed as samples in triplicate on Beckman AU400 Analyzer." Mean values from these analytical measurements become the assigned values.

Therefore, the "ground truth" is based on the analytical performance and established traceability to the predicate device, not on expert consensus.

4. Adjudication Method for the Test Set:

Not applicable in the human expert sense. The "adjudication" for the values of the calibrators and controls is based on standard laboratory practices for value assignment and verification, involving multiple analytical runs (e.g., in triplicate) and statistical averaging.

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

No, an MRMC study was not done. This type of study is typically performed for diagnostic devices (like imaging software) where human readers (e.g., radiologists) interpret cases with and without AI assistance, and their performance is compared. This submission is for laboratory calibrators and controls, which are reagents for an automated assay, not a device requiring human interpretation in this manner.

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

This concept also doesn't directly apply here in the way it does for AI algorithms. The device itself (the calibrator and control set) is a standalone reagent set designed to work with an automated analytical instrument (Olympus AU400 in this case). The performance metrics (linearity, precision, accuracy, etc.) are all a measure of the analytical performance of the reagents within the context of the assay and instrument, without direct human intervention in the measurement process (beyond setting up the analyzer and quality control).

7. The Type of Ground Truth Used:

The ground truth used for the calibrator and control values is analytical reference/traceability to the predicate device's established values and results from multiple analytical measurements on a reference instrument.

8. The Sample Size for the Training Set:

This document does not describe a "training set" in the context of machine learning or AI development. Since this is a submission for diagnostic reagents (calibrators and controls), there is no AI algorithm being trained. The "training" in a laboratory context refers to the initial process of value assignment for reference lots, typically based on multiple measurements against a hierarchy of reference materials. The document states:

"Diazyme Lp(a) master lot of calibrator materials were assigned values... assayed as samples three times in triplicate on the Hitachi or Olympus Analyzer."
"Lp(a) Liquid Stable Calibrator Value Verification Reference lot of the Lp(a) liquid stable calibrator with the target values assigned are used to test library samples assigned with predicate device and trueness controls."

The exact number of "master lot" or "reference lot" materials used for this initial value assignment is not specified, but it would typically involve several levels of calibrators/controls run numerous times.

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

As elaborated above, there isn't a "training set" in the AI sense. The "ground truth" (i.e., the assigned values) for the calibrators and controls were established through a process of:

Value Transfer from the Predicate Device: The current Diazyme Lp(a) Assay reagent and calibrators (K082488) were used as the reference.
Repetitive Analytical Measurements: Calibrator materials were assayed "three times in triplicate" (total of 9 measurements per calibrator level) on a clinical chemistry analyzer (Hitachi or Olympus for the predicate, Beckman AU400 for the new device).
Calculation of Mean Values: "For each calibrator level, mean values were calculated from the data points and assigned as the calibrator value."
Verification: The reference lot of liquid stable calibrator was then used to "test library samples assigned with predicate device and trueness controls" to verify the assigned values.

This process ensures the new liquid stable calibrators and controls have values traceable to the established predicate device and are analytically sound.

Summary

{0}------------------------------------------------

510(k) Summary (Summary of Safety and Effectiveness)

This summary of the 510(k) safety and effectiveness information is being submitted in the accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

510(k) Number

K131556

Applicant Name:

Dr. Abhijit Datta, Director of Technical Operations

Diazyme Laboratories

12889 Gregg Court

Poway, CA 92064

Abhijit.datta(@diazyme.com

Date Summary was Prepared

June 10, 2013

Device Name:

Classification Name: Diazyme Lipoprotein (a) Calibrator Set and Diazyme Lipoprotein (a) Control Set

Trade Name: Diazyme Lp(a) Calibrator Set and Diazyme Lp(a) Control Set

Common Name: Diazyme Lp(a) Calibrator Set and Diazyme Lp(a) Control Set

Governing Regulation: 21 CFR 862.1150 (Calibrator, Primary); 21 CFR 862.1660 [Single (specificed) Analyte Controls (Assayed and Unassayed)]

Device Classification: Low Density Lipoprotein Immunological test system: Class II (Calibrator and Control

Classification Panel: Clinical Chemistry (75)

Product Code: JIT, JJX

Submission Type

Special 510k

Legally marketed device to which equivalency is claimed:

{1}------------------------------------------------

K082488. Diazyme Lp(a) calibrators and controls

Manufacturing Address

Diazyme Laboratories

12889 Gregg Court

Poway, CA 92064

Establishment Registration

2032900

Intended Use of Device:

The Diazyme Lipoprotein (a) Calibrator Set is intended for use in establishing the calibration curve for the Diazyme Lipoprotein (a) Assay reagents by turbidimetry. For in vitro diagnostic use only.

Description of Device:

Modification of Device:

The significant changes to the device are as follows:

. Change in state of material supplied from freeze-dried powder to liquid
. Change in packaging and labeling, specifically the change in catalog number
. No change to intended use claims

Based on the findings from verification and validation activities, the changes of the Diazyme Lp(a) Calibrator Set and Control Set (compared to predicate) do not alter the safety or effectiveness.

{2}------------------------------------------------

Similarities and Difference of Modified Device:

Attribute	Predicate Device	New Device
	Diazyme Lipoprotein (a)	Diazyme Lipoprotein (a)
	Assay with Lyophilized	Calibrator Set and Control
	Calibrators and Controls(K082488)	Set (special 510k submission)
Intended Use	Diazyme Lp(a) standard isintended for use inestablishing the calibrationcurve for the Diazyme Lp(a)reagents by turbidimetry. Forin vitro diagnostic use only	Diazyme Lipoprotein (a)Calibrator Set is intended foruse in establishing thecalibration curvefor the Diazyme Lipoprotein(a) Assay reagents byturbidimetry. For in vitrodiagnostic use only.
	Diazyme Lp(a) Control isintended for use in monitoringthe quality control of resultsobtained with the DiazymeLp(a) reagents byturbidimetry.	Diazyme Lipoprotein (a)Control Set is intended for usein monitoring the qualitycontrol of results obtainedwith the Diazyme Lipoprotein(a) Assay reagents byturbidimetry. For in vitrodiagnostic use only.
Instrumentation	Hitachi 717	Olympus AU400
Lp(a) Calibrators	Lyophilized human serumand plasma	Liquid stable human serumand plasma
Calibrator Composition	Human serum, with activeingredient Lp(a)	Human serum, preservative,and active ingredient Lp(a)
Control Composition	Lyophilized human serum	Human serum, preservative,and active ingredient Lp(a)
Standardization	Using a single lot of predicatedevice reagents and calibrator,Diazyme Lp(a) master lot ofcalibrator materials wereassigned values as follows. Thecalibrator materials were assayedas samples three timesintriplicate on the HitachiorOlympus Analyzer. For eachcalibrator level, mean valueswere calculated from the datapoints and assigned as the	Value Transfer from predicatedevice Diazyme Lp(a) Reagentand calibrator (K082488) toreference lot of liquid stablecalibratorsUsing predicate device:Diazyme Lp(a) Latex Reagentand calibrator (K082488).Diazyme Lp(a) reference lotof liquid stable calibratormaterials were assigned values
	calibrator value. For each new lotof calibrator materials produced,the master lot or reference lotcalibrator is used in conjunctionwith the reference lot of DiazymeLp(a) Assay reagents to test andverify calibrator value.	as follows: The calibratormaterials were assayed assamples in triplicate onBeckman AU400 Analyzer.For each calibrator level,mean values were calculatedand assigned as the initialcalibrator value.Lp(a) Liquid Stable CalibratorValue VerificationReference lot of the Lp(a) liquidstable calibrator with the targetvalues assigned are used to testlibrary samples assigned withpredicate device and truenesscontrols.
Calibrator Range	0-100 mg/dL	0-100 mg/dL
Analytical Sensitivity	5.44 mg/dL	5.44 mg/dL
LOB	LOB = 1.14 mg/dL	LOB = 1.13 mg/dL
LOQ	LOQ = 5.44 mg/dL	LOQ = 5.44 mg/dL(Sensitivity checked toconfirm previously approveddata)
Dynamic Range	Up to 100 mg/dL Lp(a)	Up to 100 mg/dL Lp(a)

The table below compares the new device, Diazyme Lp(a) Calibrator Set and Control Set, with the predicate device, Diazyme Lp(a) Calibrators and Controls (K082488).

{3}------------------------------------------------

Verification/Validation of Modification:

The nonclinical performance of the Diazyme Lp(a) Calibrator Set and Control Set was demonstrated through the following studies:

. 20-Day Precision
Limits of Blank/Detection/Quantitation (LOB/LOD/LOQ) .
. Linearity ·
Accuracy by Method Comparison .
Accuracy by Matrix Comparison · .
. Interference
Accelerated Calibrator Stability .
Real Time Calibrator Stability .
Accelerated Control Stability .
Real Time Control Stability .
Open and Closed Vial Calibrator Stability .
Value Assignment and Traceability .

{4}------------------------------------------------

Conclusion:

Current Diazyme Lp(a) Assay reagent and calibrators (K082488) were selected for comparing serum Lp(a) levels to the results generated by the modified device Diazyme Lp(a) Calibrator Set and current Diazyme Lp(a) Assay reagent. The accuracy between the results obtained by Diazyme Lp(a) Assay Kit (K082488) and proposed calibrators and controls (Diazyme Lp(a) Calibrator Set and Control Set) unequivocally demonstrates excellent correlation. As a result, the Lp(a) Calibrator Set and Control Set use for measurement of Lp(a) in patient serum samples is substantially equivalent to legally marketed devices. The differences in the calibrator components (lyophilized versus liquid stable) should not affect the safety and effectiveness of the Diazyme Lp(a) Assay reagents.

In summary, the dissimilar composition features of the Diazyme Lp(a) Calibrator Set and control Set (compared to predicate) do not affect the safety or effectiveness of the Diazyme Lp(a) Assay.

{5}------------------------------------------------

Image /page/5/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with three wing-like shapes extending upwards and to the right.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 26, 2013

Diazyme Laboratories C/O Dr. Abhijit Datta 12889 Gregg Court POWAY CA 92064

Re: K131556

Trade/Device Name: Diazyme Lipoprotein (a) Calibrator Set and Diazyme Lipoprotein (a)

Control Set Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT, JJX Dated: May 28, 2013 Received: May 29, 2013

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

{6}------------------------------------------------

Page 2-Dr. Datta

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact 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/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Carol C. Benson -S for

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

{7}------------------------------------------------

Indications for Use

510(k) Number : K131556

Device Name: Diazyme Lipoprotein (a) Calibrator Set, Diazyme Lipoprotein (a) Control Set

Indications for Use:

The Diazyme Lipoprotein (a) Calibrator Set is intended for use in establishing the calibration curve for the Diazyme Lipoprotein (a) Assay reagents by turbidimetry. For in vitro diagnostic use only.

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 Diagnostics and Radiological Health (OIR)

Ruth A. Chester -S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

510(k)_k131556

Regulation Number and Section

§ 862.1150 Calibrator.

(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.