DRX NTX OR, OSTEOMARK NTX DIRECT RESPONSE

K984530 · Metrika, Inc. · JFY · Aug 10, 1999 · Clinical Chemistry

Device Facts

• Record ID: K984530
• Device Name: DRX NTX OR, OSTEOMARK NTX DIRECT RESPONSE
• Applicant: Metrika, Inc.
• Product Code: JFY · Clinical Chemistry
• Decision Date: Aug 10, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1225
• Device Class: Class 2

Intended Use

Osteomark NTx Point of Care (POC) is a urinary assay for the quantitative measure of the excretion of cross-linked N-telopeptides of type I collagen (NTx) normalized to urinary creatinine (nM Bone Collagen Equivalents/mM creatinine). The test is used to monitor bone resorption changes following initiation of antiresorptive therapy (e.g., hormone replacement therapy).

Device Story

Osteomark NTx POC is a single-use, disposable, four-channel reflectance photometer for professional use in physician office laboratories. Device utilizes dry reagent chemistry strips within a sealed plastic case. Input: second morning void urine sample. Operation: sample added to strips; NTx measured via competitive inhibition immunoassay using blue microparticle-conjugated anti-NTx antibodies; creatinine measured via enzymatic assay producing blue color intensity proportional to concentration. Internal LEDs and silicon photodetectors measure reflectance before and after sample addition. Device calculates NTx/creatinine ratio using stored calibration parameters. Output: numerical concentration (nM BCE/mM creatinine) displayed on LCD. Results assist clinicians in monitoring bone resorption changes following antiresorptive therapy initiation. Device is not a sole diagnostic tool; results interpreted alongside medical history and other biochemical markers.

Clinical Evidence

Clinical accuracy evaluated by comparing Osteomark NTx POC to predicate laboratory methods using 235 urine samples across three physician office laboratory sites (correlation coefficient r=0.79). Precision testing (n=5/day over 4 days) showed total pooled imprecision %CV of 13.3% at 25 nM BCE/mM creatinine and 12.8% at 100 nM BCE/mM creatinine. Retrospective study of 50 HRT-treated women (200 samples) demonstrated device ability to measure expected 48% decrease in NTx concentration after 6 months of therapy, with significant correlation to BMD changes (r=-0.33).

Technological Characteristics

Four-channel reflectance photometer; dry reagent chemistry strips; LED light source; silicon photodetectors; LCD display. Measures NTx via competitive inhibition immunoassay and creatinine via enzymatic assay. Standalone device; professional use. No specific material standards cited.

Indications for Use

Indicated for patients undergoing antiresorptive therapy (e.g., hormone replacement therapy) to monitor changes in bone resorption via quantitative measurement of urinary NTx normalized to creatinine.

Regulatory Classification

Identification

A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

Predicate Devices

• Osteomark NTx EIA (K961562)
• Creatinine Plus (K854766)

Submission Summary (Full Text)

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

K984530

M = T R I K A

Metrika, Inc. 510 Oakmead Parkw Sunnyvale, CA 94086

main 408 524 2255 fax [phone]

# 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.

The assigned 510(k) number is K984530.

| 807.92 (a)(1): Name: | Metrika, Inc. |
|----------------------|--------------------------------------------|
| Address: | 510 Oakmead Parkway<br>Sunnyvale, CA 94086 |
| Phone: | [phone] |
| FAX: | [phone] |
| Contact: | Stephen J. Hardt |

#### 807.92 (a)(2): Device name- trade name and common name, and classification

| Trade name: | DRx® NTx or Osteomark® NTx Point of Care (POC) |
|-----------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common Name: | urinary assay for quantitative ratio of cross-linked N-<br>telopeptides of type I collagen (NTx) divided by creatinine<br>(nM Bone Collagen Equivalents [BCE]/mM creatinine) |
| Classification: | ratio numerator: 21 CFR 862.1400, Hydroxyproline Test<br>System<br>ratio denominator: 21 CFR 862.1225 Creatinine Test System |

#### 807.92 (s)(3): Identification of the legally marketed predicate device

Osteomark® NTx POC is substantially equivalent to two commercially available predicate devices; Osteomark® NTx EIA (Ostex International Inc., Seattle, WA), is a stand-alone NTx kit, and is the predicate device for the numerator of the ratio. Creatinine Plus (Boehringer-Mannheim Corporation [Roche], Indianapolis, IN) is a creatinine assay, and is the predicate device for the denominator value. Osteomark® NTx POC reports a single corrected result (NTx/creatinine), while Osteomark NTx EIA requires a separate creatinine determination (no method specified) in order to report the final corrected result.

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

### 807.92 (a)(4): Device Description

The Osteomark® NTx POC device is a single-use, disposable four-channel reflectance photometer integrated with dry reagent chemistry strips and contained within a sealed plastic case. Each unit consists of:

- an optics subassembly that also supports the reagent strips .
- electronics, batteries, photodetectors, and light emitting diodes (LEDs). ●
- . plastic parts
- two reagent strips ●
- a desiccant ●
- a liquid crystal display (LCD) ●

The reagent strips capillary transport with various chemical reactions. The first strip is an immunoassay for measuring the NTx, and the second strip is a general chemistry assay for measuring the creatinine. In both strips, a blue color is measured in discrete test zones. The test zones are the areas where the specific reaction occurs and concentrations are measured.

The NTx reaction proceeds as follows: anti-NTx antibody, conjugated to blue microparticles, migrate across the strip upon the addition of urine sample. The amount of blue microparticles captured on the test zones is proportional to the amount of NTx in the sample.

The creatinine reaction proceeds as follows: the addition of the urine sample solubilizes enzymes immobilized in the strip test zones. A cascade of enzymatic reactions mediates the production of hydrogen peroxide from the oxidation of creatinine. In the presence of horseradish peroxidase and a color indicator, a blue color is generated from the hydrogen peroxide with an intensity proportional to the concentration of creatinine in the sample.

The LEDs and silicon photodetectors compare the reflectances of the color intensities before and after the sample addition. Based on the calibration parameters stored in memory, the numerical concentrations of NTx and creatinine are calculated. Assay results are expressed in nM Bone Collagen Equivalents (BCE) divided by mM creatinine (nM BCE/mM creatinine).

### 807.92 (a)(5): Intended use

Osteomark® NTx POC is a urinary assay for the quantitative measure of the excretion of cross-linked N-telopeptides of type I collagen (NTx) normalized to urinary creatinine (nM Bone Collagen Equivalents/mM creatinine). The test is used to monitor bone resorption changes following initiation of antiresorptive therapy (e.g., hormone replacement therapy).

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

# 807.92 (a)(6): Technological Similarities and Differences to the Predicate

| CHARACTERISTIC | Osteomark® POC<br>K984530 | Osteomark® EIA<br>K961562 | CREATININE Plus<br>K854766 |
|-----------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | DRx® NTx is a urinary<br>assay for the<br>quantitative measure of<br>the excretion of cross-<br>linked N-telopeptides of<br>type I collagen (NTx)<br>normalized to urinary<br>creatinine (nM Bone<br>Collagen<br>Equivalents/mM<br>creatinine). The test is<br>used to monitor bone<br>resorption changes<br>following initiation of<br>antiresorptive therapy<br>(e.g., HRT). | Osteomark is a urinary<br>assay that provides a<br>quantitative measure of<br>the excretion of cross-<br>linked N-telopeptides of<br>type I collagen (NTx) as<br>an indicator of human<br>bone resorption.<br>Measurement of NTx is<br>intended for use in the<br>therapeutic monitoring<br>of antiresorptive<br>therapies, and in<br>predicting skeletal<br>response to hormonal<br>antiresorptive therapy. | Creatinine Plus is for the<br>quantitative determination<br>of creatinine in serum.<br>plasma, or urine.<br>Creatinine measurements<br>are used in the diagnosis<br>and treatment of renal<br>diseases, in monitoring<br>renal dialysis, and as a<br>calculation basis for<br>measuring other urine<br>analytes. |
| Analyte(s) | NTx (nM BCE)/<br>creatinine (mM) | NTx (nM BCE) | Creatinine conversion of<br>mg/dL to mM:<br>$mg/dL + 11.3 = mM$ |
| Testing Matrix<br>(Specimen Type) | urine: second morning<br>void | urine: 24-hour or second<br>morning void | serum. plasma, or urine |
| Testing Environment | professional use | professional use | professional use |
| Risk to Patient | not a sole discriminate;<br>NTx results are<br>interpreted along with<br>medical histories and<br>other biochemical<br>markers | not a sole discriminate;<br>NTx results are<br>interpreted along with<br>medical histories and<br>other biochemical<br>markers | N/A |

# Similarities Between Osteomark® NTx POC and Osteomark NTx EIA / Creatinine Plus

# Differences Between DRx® NTx and Osteomark / Creatinine Plus

| CHARACTERISTIC | Osteomark® POC | Osteomark® EIA | CREATININE Plus |
|----------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Methodology/Testing<br>Platforms | Osteomark® NTx POC<br>is a four channel,<br>"ratioing" reflectance<br>photometer, (plus an<br>internal reference<br>channel), with integral<br>dry chemistry strips<br>(competitive inhibition<br>immunoassay for NTx;<br>enzymatic assay for<br>creatinine). | Osteomark EIA is a<br>standard competitive<br>inhibition enzyme-linked<br>immunosorbent assay<br>(ELISA). | The Creatinine Plus assay<br>consists of enzymatic<br>reactions where creatinine<br>is converted to red<br>benzoquinone imine dye<br>(red) in the presence of<br>creatininase, creatinase,<br>sarcosine oxidase, and<br>peroxidase. |
| Reportable Ranges | ratio: 2-350 nM<br>BCE/mM creatinine | NTx: 20-3000 nM BCE | Creatinine (urine, pre-dil.<br>1/10): 0.03 - 35.4 mM |

The differences in the two testing platforms do not raise new issues of safety and effectiveness.

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

### 807.92 (b)(1): Brief Description of Nonclinical Data

ﮮ ﺩﮮ ﮯ ﮨﮯ ﺗ ﮯ ﺏ ﮞ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ ﮨﮯ ﺗﺎ

ند ۾ ھند تاريخ اپن ان ان ان

Studies were conducted that evaluated both NTx and creatinine for analytical sensitivity, analytical specificity, and linearity. The sensitivity of the NTx portion of the device was shown to be 30 nM BCE, while the sensitivity of the creatinine was shown to be 2 mM.

いー・バー・バー・バー

Osteomark® NTx POC results were not affected (differences less than 15%) by the addition of most potential interferents such as biological compounds, therapeutic agents, or microorganisms found routinely in urine. Interference was noted with very high levels of calcium (> 4mg/mL), chloride (> 300 mM), and C. albicans and E. coli (both 1.5 x 103).

Linearity studies confirmed dynamic ranges of 30 nM to 1300 nM for NTx, and 2 mM to 25 mM for creatinine.

# 807.92 (b)(2): Brief Description of Clinical Data

Accuracy was evaluated by comparative testing between Osteomark® NTx POC and the two predicate methods (NTx and creatinine). Two hundred thirty-five (235) urine samples were assayed by Osteomark® NTx POC among three "POLtype" clinical sites, and by the predicate methods at the reference laboratory. The data are summarized below (laboratory methods = X-axis).

| | n samples | Linear Regression Equation | Correlation Coefficient |
|-------------------|-----------|----------------------------|-------------------------|
| Osteomark NTx POC | 235 | $y = 1.12x +6$ | 0.79 |

CLINICAL LINEAR REGRESSION DATA

Precision testing was performed by three physician office laboratory (POL) sites. Each site tested two levels of NTx/creatinine ratios five times a day over four days. From this testing, the total pooled imprecision was calculated at each of the two levels. The percent coefficient of variation (%CV) at the lower level (approximately 25 nM BCE/mM creatinine) was 13.3% (within-day range 7.5% to 22.1%, n = 5), and the %CV at the higher level (approximately 100 nM BCE/mM creatinine) was 12.8% (within-day range 4.0% to 20.4%, n = 5).

ーー・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・

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

#### Use of DRx® NTx to Monitor the Effect of Antiresorptive Therapy (HRT)

Retained samples from a published study with HRT-treated women (n = 50, 200 samples) were tested with the Osteomark® NTx POC device to determine its ability to measure the expected decrease in NTx concentration following antiresorptive therapy. Prior to HRT initiation, NTx mean baseline values were 67 nM BCE/mM creatinine, significantly higher than the premenopausal mean of 44 nM BCE/mM creatinine. Mean NTx values fell significantly after 6 months of therapy to 33 nM BCE/mM creatinine, a 48% decrease from baseline. Osteomark® NTx POC values were correlated to the laboratory method, Osteomark NTx EIA, throughout the study (r = 0.66, at baseline; r = 0.46, at 12 months). Significant correlations were also observed between the percent change in spine BMD at 1 year and the percent change in Osteomark® NTx POC from baseline to 6 months (r = - 0.33).

#### 807.92 (b)(3): Conclusions from Nonclinical and Clinical Testing

Studies demonstrated substantial equivalence of Osteomark® NTx POC in terms of accuracy and precision to existing products already being marketed. Sensitivity and linearity studies confirmed the assay's reportable range, and cross reactivity studies confirmed the assay's specificity.

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

Image /page/5/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of an eagle or bird-like figure, composed of three curved lines that suggest wings or feathers. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

## AUG 10 1999

Ms. Erika B. Ammirati, R.A.C., MT(ASCP) Clinical/Regulatory Consultant Metrika. Inc. 510 Oakmead Parkway Sunnyvale, California 94086

Re: K984530

> Trade Name: Osteomark® NTx Point of Care Regulatory Class: II Product Code: JFY Regulatory Class: I Product Code: JMM Dated: June 9, 1999 Received: June 10, 1999

Dear Ms. Ammirati:

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.

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 vour 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.

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

#### 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/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

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

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

:

## 510(k) Number: K984530

Device Name: Osteomark® NTx Point of Care

### INDICATIONS FOR USE

Osteomark NTx Point of Care (POC) is a urinary assay for the quantitative measure of the excretion of cross-linked N-telopeptides of type I collagen (NTx) normalized to urinary creatinine (nM Bone Collagen Equivalents/mM creatinine). The test is used to monitor bone resorption changes following initiation of antiresorptive therapy (e.g., hormone replacement therapy).

Dean Cooge

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K984530

(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)