IMMULITE PYRILINKS-D

K971312 · Diagnostic Products Corp. · JMM · May 27, 1997 · Clinical Chemistry

Device Facts

• Record ID: K971312
• Device Name: IMMULITE PYRILINKS-D
• Applicant: Diagnostic Products Corp.
• Product Code: JMM · Clinical Chemistry
• Decision Date: May 27, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1400
• Device Class: Class 1

Intended Use

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.

Device Story

IMMULITE® Pyrilinks®-D is a solid-phase, chemiluminescent enzyme immunoassay used with the IMMULITE® Automated Immunoassay Analyzer. The device measures deoxypyridinoline (DPD) in urine samples to assess bone resorption rates. Operation involves introducing the patient sample and alkaline phosphatase-conjugated DPD into a test unit containing a polystyrene bead coated with monoclonal anti-DPD antibodies. DPD in the sample competes with enzyme-labeled DPD for binding sites. After incubation and centrifugal washing, a phosphate ester of adamantyl dioxetane substrate is added. Alkaline phosphatase hydrolyzes the substrate, producing an unstable intermediate that emits light. A luminometer measures photon output, which is inversely proportional to the DPD concentration in the sample. The device is used in clinical laboratory settings by trained personnel. Results assist healthcare providers in evaluating bone metabolism and monitoring conditions where bone resorption exceeds formation, aiding in the management of bone health.

Clinical Evidence

Method comparison study performed on 75 patient urine samples. Comparison between IMMULITE® Pyrilinks®-D and Metra Biosystems® Pyrilinks®-D. Results showed mean values of 70 nM for both systems. Linear regression analysis yielded a slope of 1.00, intercept of 0.57 nM, and correlation coefficient (r) of 0.966. No other clinical data provided.

Technological Characteristics

Solid-phase chemiluminescent immunoassay. Components: polystyrene bead coated with monoclonal anti-DPD antibody, alkaline phosphatase-conjugated DPD, phosphate ester of adamantyl dioxetane substrate. Energy source: automated luminometer. Connectivity: integrated with IMMULITE® Automated Immunoassay Analyzer. Format: automated test unit. Detection principle: competitive binding with chemiluminescent signal generation.

Indications for Use

Indicated for the quantitative measurement of deoxypyridinoline (DPD) in urine as an indicator of bone resorption in patients undergoing metabolic bone assessment.

Regulatory Classification

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.

Predicate Devices

• Metra Biosystems® Pyrilinks®-D (K952320)

Submission Summary (Full Text)

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05/20/97 TUE 15:21 FAX [phone] DIAGNOSTIC PRODUCTS CORP. 0002
Diagnostic Products Corporation
IMMULITE Pyrilinks-D
May 14, 1997 MAY 27 1997

# 510 (k) Summary
## Safety and Effectiveness

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: | Diagnostic Products Corporation
5700 West 96th Street
Los Angeles, California 90045-5597 |
| --- | --- |
| Telephone Number: | [phone] |
| Facsimile Number: | [phone] |
| Contact Person: | Edward M. Levine, Ph.D.
Director of Clinical Affairs |
| Date of Preparation: | May 14 1997 |
| Device Name: | IMMULITE® Pyrilinks®-D |
| Trade: | Reagent system for the determination of deoxypyridinoline in urine. |
| Catalog Number: | LKPD1 (100 tests), LKPD5 (500 tests) |
| Classification: | Class I device, 75-JMM |
| CLIA Complexity Category | Moderate, based on previous classification of analogous tests |
| Manufacturer: | Diagnostic Products Corporation
5700 West 96th Street
Los Angeles, California 90045-5597 |
| Establishment Registration Number: | DPC's Registration Number is 2017183 |
| Substantially Equivalent Predicate Device: | Metra Biosystems® Pyrilinks®-D
(K952320) |
| Description of Device: | IMMULITE® Pyrilinks®-D is a clinical device for use with the IMMULITE® Automated Immunoassay Analyzer |
| Intended Use of the Device: | 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, pyridinoline (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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05/20/97 TUE 15:22 FAX [phone] DIAGNOSTIC PRODUCTS CORP 003

Diagnostic Products Corporation
IMMULITE Pyrilinks-D
May 14, 1997

into the circulation during the bone resorption process. DPD is excreted unmetabolized 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 Immunoassay 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 yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission 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 luminometer is 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 coated on the strip to capture DPD. 50 μL of diluted standards, controls, and samples are added to each microtiter well of the anti-DPD coated strips. 100 μL of cold enzyme conjugate is then added to each well, the 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 each well. After the wells are incubated for 60 minutes at room temperature, 100 μL of stop solution is added and the optical density is read at 405 nm. The concentration of DPD in the sample is determined from the standard curve using quantitation software with a 4-parameter calibration curve fitting equation.

**Performance Equivalence:**

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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05/20/97 TUE 15:22 FAX [phone] DIAGNOSTIC PRODUCTS CORP 004
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:

$$
(\text{IMMULITE}^{\bullet} \text{Pyrilinks}^{\bullet}\text{-D}) = 1.00 \times (\text{Metra Biosystems}^{\bullet} \text{Pyrilinks}^{\bullet}\text{-D}) + 0.57 \text{nM} \quad r = 0.966
$$

## Conclusion:

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

Edward M. Levine, Ph.D.
Director of Clinical Affairs
Date: 5/14/97

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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration
2098 Gaither Road
Rockville MD 20850

MAY 27 1997

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

Re: K971312
IMMULITE Pyrilinks-D Assay
Regulatory Class: I
Product Code: JMM
Dated: April 7, 1997
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 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 (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 Good Manufacturing Practice for Medical Devices: General (GMP) regulation (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 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.

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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 [phone].

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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,

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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1/07 TUE 15:22 FAX [phone] DIAGNOSTIC PRODUCTS CORP

510(k) Number (if known): K971312

Device Name: IMMULITE® Pyrilinks®-D

Indications For Use:

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

(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)

OR

Over-The-Counter Use

(Optional Format 1-2-96)