DPC's IMMULITE® Pyrilinks"-D is a solid-phase, chemikaninescent enzyme immuneassay for use with the IMMULITE® Automated Analyzer and is designed for the quantitative measurement of deoxyppyridinoline (DPD) in urine. It is intended strictly for in vitro diagnostic use as an indicator of bone resorption.

Device Description

IMMULITE® Pyrilinks -D is a clinical device for use with the IMMULITE® Automated Immunoassay Analyzer. The IMMULITE® Pyrilinks -D assay is designed for the quantitative measurement of deoxypyridinoline in urine It is intended strictly for in vitro diagnostic use as an indicator of bone resorption. IMMULITE Pyrilinks -D is a solid-phase, chemiluminescent immunoassay for use with the IMMULITE Automated Inimunoassay Analyzer. The solid-phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with a monoclonal antibody specific for DPD. The patient sample and alkaline phosphatase-conjugated DPD are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37°C with intermittent agitation. During this time, DPD in the sample competes with enzyme-labeled DPD for a limited number of antibody-binding sites on the bead. Unbound material is then removed by a centrifugal wash, after which substrate is added and the Test Unit is incubated for a further 10 minutes. The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yead an unstable intermediate. The continuous production of this intermediate results in the sustained of light, thus improving precision by providing a window for multiple readings. The bound complex-and thus also the photon output, as measured by the luminometeris inversely proportional to the concentration of DPD in the sample.

AI/ML Overview

The provided document describes the safety and effectiveness summary for the IMMULITE® Pyrilinks -D device, focusing on its substantial equivalence to a predicate device, Metra Biosystems "Pyrilinks"-D.

Here's the breakdown of the acceptance criteria and the study that proves the device meets them:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state pre-defined acceptance criteria (e.g., a specific r-value or a range of acceptable mean differences). Instead, it presents a method comparison study to demonstrate "Performance Equivalence" and "substantially equivalent results" to the predicate device. The performance is assessed through linear regression analysis.

Acceptance Criteria (Implied for Substantial Equivalence)	Reported Device Performance (IMMULITE® Pyrilinks®-D vs. Metra Biosystems® Pyrilinks®-D)
Statistical Correlation (r-value)	r = 0.966
Linear Regression Equation	(IMMULITE® Pyrilinks®-D) = 1.00 (Metra Biosystems® Pyrilinks®-D) + 0.57 nM
Mean DPD Concentrations	IMMULITE® Pyrilinks®-D: 70 nM
	Metra Biosystems® Pyrilinks®-D: 70 nM

2. Sample sized used for the test set and the data provenance

Sample Size for Test Set: Seventy-five (75) patient urine samples.
Data Provenance: The document does not specify the country of origin of the data. It also does not explicitly state whether the study was retrospective or prospective, but the phrasing "was compared to" for patient samples suggests a retrospective or cross-sectional comparison of existing or freshly collected samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided. The "ground truth" for this type of immunoassay comparison is typically the result from the predicate device itself, which is assumed to be accurate. There's no mention of a separate expert panel establishing ground truth for the DPD concentrations.

4. Adjudication method for the test set

This information is not applicable and not provided. Imunoassay results are quantitative measurements, not subjective interpretations requiring adjudication.

5. 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

This is not an MRMC comparative effectiveness study involving human readers or AI. It is a direct comparison between two diagnostic devices. Therefore, this information is not applicable and not provided.

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

This statement refers to the performance of a diagnostic device (an immunoassay analyzer), which operates as a standalone system to quantify DPD in urine. There is no "human-in-the-loop" component in the sense of interpretative assistance; the device directly measures and reports DPD concentrations. The performance data presented (linear regression, r-value, mean concentrations) are reflective of this standalone device's output.

7. The type of ground truth used

The "ground truth" in this study is the measurement of deoxypyridinoline (DPD) in urine samples obtained from the predicate device, Metra Biosystems® Pyrilinks®-D. The study aims to demonstrate that the new IMMULITE® Pyrilinks®-D device provides results that are substantially equivalent to those of the established predicate device.

8. The sample size for the training set

The document does not mention a separate "training set" for the IMMULITE® Pyrilinks®-D in the context of this 510(k) summary. Immunoassays are developed and validated using a different process than machine learning algorithms, which typically involve distinct training and test sets. For this type of device, the "training" (development and optimization) would have been part of the product's R&D phase, not a specific "training set" as understood in AI studies.

9. How the ground truth for the training set was established

As there is no separate "training set" described in the provided summary, information on how its ground truth was established is not applicable and not provided. The focus of the 510(k) summary is on demonstrating equivalence to an existing device using a test set of patient samples.

Summary

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Diagnostic Products Corporation IMMULITE Pyrilinks-D May 14, 1997

2971312

510 (k) Summary Safety and Effectiveness

MAY 27 1997

This summary of safety and effectiveness information has been prepared in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92

Name: Address:

Telephone Number: Facsimile Number:

Contact Person:

Date of Preparation:

Device Name: Trade:

Catalog Number:

Classification: CLIA Complexity Category

Manufacturer:

Establishment Registration Number:

Substantially Equivalent Predicate Device:

Description of Device:

Intended Use of the Device:

Diagnostic Products Corporation 5700 West 96th Street Los Angeles, California 90045-5597

(213) 776-0180 (213) 776-0204

Edward M. Levine, Ph.D.

May 14 1997

IMMULITE® Pyrilinks -D Reagent system for the determination of deoxypyridinoline in urine.

LKPD1 (100 tests), LKPD5 (500 tests)

Class I device, 75-JMM Moderate, based on previous classification of analogous tests

Diagnostic Products Corporation 5700 West 96th Street Los Angeles, California 90045-5597

DPC's Registration Number is 2017183

Metra Biosystems " Pyrilinks"-D (K952320)

IMMULITE® Pyrilinks -D is a clinical device for use with the IMMULITE® Automated Immunoassay Analyzer

The IMMULITE® Pyrilinks -D assay is designed for the quantitative measurement of deoxypyridinoline in urine It is intended strictly for in vitro diagnostic use as an indicator of bone resorption

Summary and Explanation of the test:

Approximately 90% of the organic matrix of bone is type I collagen, a triple helical protein. Type I collagen of bone is crosslinked by specific molecules which provide rigidity and strength. Crosslinks of mature type I collagen in bone are the pyridinium crosslinks (PYD) and deoxypyridinoline (DPD). DPD is formed by the enzymatic action of lysyl oxidase on the amino acid lysine. DPD is released

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Diagnostic Products Corporation IMMULITE Pyrilinks-D May 14, 1997

into the circulation during the bone resorption process. DPD is excreted unmerabolized in urine and is unaffected by diet, making it suitable for assessing resorption.

Bone is constantly undergoing a metabolic process called remodeling. This includes a degradation process, bone resorption, mediated by the action of osteoblasts. Remodeling is required for the maintenance and overall health of bone and is tightly coupled; that is, resorption and formation are in balance. In abnormal states of bone metabolism, this process becomes uncoupled and, when resorption exceeds formation, this results in a net loss of bone. The measurement of specific degradation products of bone matrix provide analytical data of the rate of bone metabolism.

Technological Comparison to Predicate:

Diagnostic Products Corporation (DPC) asserts that DPC's IMMULITE® Pyrilinks -D is substantially equivalent to Metra Biosystems Pyrilinks -D. Both products are intended for in vitro diagnostic use,

IMMULITE Pyrilinks -D is a solid-phase, chemiluminescent immunoassay for use with the IMMULITE Automated Inimunoassay Analyzer. The solid-phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with a monoclonal antibody specific for DPD.

The patient sample and alkaline phosphatase-conjugated DPD are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37°C with intermittent agitation. During this time, DPD in the sample competes with enzyme-labeled DPD for a limited number of antibody-binding sites on the bead. Unbound material is then removed by a centrifugal wash, after which substrate is added and the Test Unit is incubated for a further 10 minutes.

The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yead an unstable intermediate. The continuous production of this intermediate results in the sustained of light, thus improving precision by providing a window for multiple readings. The bound complex-and thus also the photon output, as measured by the luminometeris inversely proportional to the concentration of DPD in the sample.

The Metra Biosystems Pyrilinks -D procedure is a competitive enzyme immunoassay in a microtiter stripwell format utilizing a monoclonal anti-DPD antibody costed on the strip to capture DPD, 50 xL of difuted standards, controls, and samples are added to each microtiter well of the arti-DPD coated strips. 100 he of cold enzyme conjugate is then added to each wells are covered and incubated in the dark for 2 hours at 2-8 °C. Each well is then washed three times with wash buffer and 150 µL of working substrate solution is added to cach wells are incubated for 60 minutes at room temperature, 100 uL of stop solution is added and the optical density is read at 405 mm, the concentration of DPD in the sample is determined from the standard curve using quantitation software with a 4-parameter callibration curve fitting equation.

Performance Equivalence:

ﻨﻢ ١٠٠٠ ﻳﺎ

Diagnostic Products Corporation asserts that the IMMULITE® Pyrilinks® D produces substantially equivalent results to other commercially marketed deoxypyridinoline assays, such as Metra Biosystems Pyrilinks"-D. Each product is intended strictly for in vitro diagnostic use as an indicator of bone resorption

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Diagnostic Products Corporation IMMULITE Pyrilinks-D May 14, 1997

Method Comparison:

The IMMULITE® Pyrilinks -D procedure was compared to the Metra Biosystems® Pyrilinks -D on seventy-five (75) patient urine samples, with DPD concentrations ranging from approximately 7.6 to 280 nM.

Mean Values: 70 nM (IMMULITE® Pyrilinks *- D) 70 nM (Metra Biosystems" Pyrilinks -D)

Linear regression analysis of IMMULITE® Pyrilinks -D values yielded the following statistics:

(IMMULITE® Pyrilinks"-D) = 1.00 (Metra Biosystems Pyrilinks -D) + 0.57 nM r = 0.966

Conclusion:

The data presenced in this summary of safety and effectiveness is the data that that that the Food and Drug Administration used in granting DPC substantial equivalence for IMMULITE® Pyrilinks -D.

Edward L. Leasure

Edward M. Levine, Ph.D. Director of Clinical Affairs

5/11/93

Date

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus, a symbol often associated with medicine and healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the caduceus. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 2 7 1997

Dennis Bush Clinical Research Associate Diagnostic Products Corporation 5700 West 96th Street Los Angeles, California 90045-5597

K971312 Re : IMMULITE Pyrilinks-D Assay Requlatory Class: I Product Code: JMM April 7, 1997 Dated: Received: April 9, 1997

Dear Mr. Bush:

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 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 reqistration, 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 (Premarket Approval), it may be subject to such additional controls. Existing major requlations 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 Good Manufacturing Practice for Medical Devices: General (GMP) requlation (21 CFR Part 820) and that, through periodic GMP inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in Please note: this response to your the Federal Register. 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.

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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 requlation (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/dsmamain.html".

Sincerely yours,
Steven Litman

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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510(k) Number (if known):_____________________________________________________________________________________________________________________________________________________ K971312

Device Name: IMMULITE® Pynlinks®-D

Indications For Use:

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

	rence of CDRH, Office of Device Evaluation (ODE)
	(Division Sign-Off)
	Division of Clinical Laboratory Devices
510(k) Number	K971312

Prescription Use (Per 21 CFR 801.109)

(Optional Format 1-2-96)

Over-The-Counter Use_

Regulation Number and Section

§ 862.1400 Hydroxyproline test system.

(a)
Identification. A hydroxyproline test system is a device intended to measure the amino acid hydroxyproline in urine. Hydroxyproline measurements are used in the diagnosis and treatment of various collagen (connective tissue) diseases, bone disease such as Paget's disease, and endocrine disorders such as hyperparathyroidism and hyperthyroidism.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.