VITROS IMMUNODIAGNOSTIC PRODUCTS: NTX CALIBRATORS, NTX REAGENT PACK, NTX CONTROLS

K983674 · Ortho-Clinical Diagnostics, Inc. · JMM · Jan 29, 1999 · Clinical Chemistry

Device Facts

• Record ID: K983674
• Device Name: VITROS IMMUNODIAGNOSTIC PRODUCTS: NTX CALIBRATORS, NTX REAGENT PACK, NTX CONTROLS
• Applicant: Ortho-Clinical Diagnostics, Inc.
• Product Code: JMM · Clinical Chemistry
• Decision Date: Jan 29, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1400
• Device Class: Class 1

Intended Use

Vitros NTx Reagent Pack - For in-vitro quantitative measurement of cross linked N-telopeptides of type I collagen (NTx) in human urine as an indicator of human bone resorption. A single NTx value cannot provide the rate of bone resorption as reported results do not contain a measure of time. Use of this test has not been established in primary hyperparathyroidism or hyperthyroidism. Vitros NTx Calibrators - For in-vitro use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of NTx in human urine. Vitros NTx Controls - For in-vitro use in the monitoring of the performance of the VITROS Immunodiagnostic System when used for the quantitative measurement of NTx in human urine.

Device Story

VITROS Immunodiagnostic Products NTx assay measures cross-linked N-telopeptides of type I collagen (NTx) in human urine; serves as indicator of bone resorption. System utilizes VITROS Immunodiagnostic System instrumentation; employs solid-phase immunoassay with enzyme-labeled tracer and mouse monoclonal anti-NTx antibody. Sample (25 µL urine) processed via automated system; luminescence used as signal for quantitative determination. Used in clinical laboratory settings by trained personnel. Output provides quantitative NTx concentration (nM BCE); assists clinicians in evaluating bone resorption status. Benefits include standardized, automated measurement compared to manual microwell plate reader methods.

Clinical Evidence

Clinical performance established via comparison with predicate device using patient specimens across various clinical categories. Deming's regression analysis yielded: VITROS NTx assay = 0.957 x Osteomark NTx test + 6.5 (nM BCE/mM creatinine). Additional analytical testing performed for sensitivity, specificity, precision, dilution, and expected values.

Technological Characteristics

Solid-phase immunoassay; enzyme-labeled tracer; mouse monoclonal anti-NTx antibody. Instrumentation: VITROS Immunodiagnostic System. Sample volume: 25 µL. Incubation: 30 minutes at 37°C. Calibration range: 0-3000 nM BCE. Automated system utilizes luminescence signal detection.

Indications for Use

Indicated for in-vitro quantitative measurement of cross-linked N-telopeptides of type I collagen (NTx) in human urine to assess bone resorption. Not established for use in primary hyperparathyroidism or hyperthyroidism.

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

• Osteomark NTx Test (K980518)

Submission Summary (Full Text)

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JAN 29 1999

Undate: December 23, 1998

### 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: 49836

#### 1. Submitter name, address, contact

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 [phone]

Contact Person: Anne Zavertnik

Date 510(k) prepared: October 19, 1998

#### 2. Device Name

Trade or Proprietary Name: VITROS Immunodiagnostic Products NTx assay Common Name: NTx assay

Classification Name: NTx assay for the in vitro quantitative measurement of cross linked Ntelopeptides of type I collagen (NTx) in human urine.

#### 3. Predicate Device

The VITROS Immunodiagnostic Products NTx assay is substantially equivalent to the Osteomark NTx Test (K980518)

#### 4. Device Description

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum, plasma and urine. Coated microwells are used as the solid phase separation system.

The system is comprised of three main elements:

- 1. The VITROS Immunodiagnostic Products (in this case VITROS Immunodiagnostic Products NTx Reagent Pack, VITROS Immunodiagnostic Products NTx Calibrators, which are combined by the VITROS Immunodiagnostic System to perform the VITROS NTx assay).

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### 510(k) Summary, continued

2. The VITROS Immunodiagnostic System - instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).

3. Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 510(k) pre-market notification (K984310).

The VITROS System and common reagents are dedicated specifically only for use with the VITROS Immunodiagnostic Products range of immunoassay products.

#### 5. Device Intended Use

The VITROS NTx assay is intended for the in vitro quantitative measurement of cross linked N-telopeptides of type I collagen (NTx) in human urine as an indicator of human bone resorption.

#### 6. Comparison to Predicate Device

The VITROS Immunodiagnostic Products NTx assay is substantially equivalent to Osteomark NTx test (predicate device), which was approved by FDA (K980518) for IVD use.

The relationship between the VITROS NTx assay and the predicate device, determined by Deming's Regression, is:

VITROS NTx assay = 0.957 x Osteomark NTx test + 6.5 (nM BCE/mM creatinine) Comparisons of the VITROS NTx assay and the predicate device were performed with samples from a variety of clinical categories.

In addition to the studies mentioned above, tests were performed to obtain analytical sensitivity, specificity, precision, dilution and expected values. Refer to the VITROS NTx assay package insert for VITROS NTx assay results.

Table 1 lists the similarities and differences of the device characteristics between the VITROS NTx assay with the predicate device, Osteomark NTx test .:

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## 510(k) Summary, continued

| | | | | | | Table 1 List of the assay characteristics |
|--|--|--|--|--|--|-------------------------------------------|
|--|--|--|--|--|--|-------------------------------------------|

| Device<br>Characteristic | VITROS NTx assay | Predicate<br>Device |
|-----------------------------------------|----------------------------------------------------------------|----------------------------------------------------------------|
| Calibration range<br>(Reportable Range) | 0 - 3000 nM BCE | 20 - 3000 nM BCE |
| Basic principle | Solid phase immunoassay | Solid phase immunoassay |
| Tracer | Enzyme labeled | Enzyme labeled |
| Instrumentation | VITROS<br>Immunodiagnostic System | Microwell plate reader |
| Sample type | Urine | Urine |
| Antibody | Mouse monoclonal anti-<br>NTx antibody in conjugate<br>reagent | Mouse monoclonal anti-<br>NTx antibody in<br>conjugate reagent |
| Sample volume | 25 µL | 25 µL |
| Incubation time and<br>temperature | 30 minutes at 37° C | 18-28° C for 90 minutes<br>(± 5 minutes). |

### 7. Conclusions

The data presented in the pre-market notification demonstrate that the VITROS NTx assay performs substantially equivalent to the predicate device, for which there is FDA clearance.

Equivalence was demonstrated using currently commercially available reagents along with patient specimens covering a variety of clinical categories.

The data presented in the premarket notification provide a reasonable assurance that the VITROS NTx assay is safe and effective for the stated intended use.

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JAN 2 9 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Anne Zavertnik Requlatory Affairs Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101

Re: K983674 Trade Name: VITROS Immunodiagnostic Products NTx assay Requlatory Class: I Product Code: JMM Dated: December 23, 1998 December 28, 1998 Received:

Dear Ms. Zavertnik:

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 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 Requlation (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. this response to your premarket notification Please note: 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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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

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# Statement of Intended Use (Appendix D)

| | Page 1 of 1 |
|--------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) Number (if known): | K983674 |
| Device Name: | VITROS Immunodiagnostic Products NTx Reagent Pack<br>VITROS Immunodiagnostic Products NTx Calibrators<br>VITROS Immunodiagnostic Products NTx Controls |
| Indications for Use: | Vitros NTx Reagent Pack - For <i>in-vitro</i> quantitative<br>measurement of cross linked N-telopeptides of type I collagen<br>(NTx) in human urine as an indicator of human bone resorption.<br>A single NTx value cannot provide the rate of bone resorption as<br>reported results do not contain a measure of time.<br>Use of this test has not been established in primary<br>hyperparathyroidism or hyperthyroidism. |
| | Vitros NTx Calibrators - For <i>in-vitro</i> use in the calibration of the<br>VITROS Immunodiagnostic System for the quantitative<br>measurement of NTx in human urine. |
| <div style="text-align:left">Jean Cooper<br/>(Division Sign-Off)<br/>Division of Clinical Laboratory Devices</div> | Vitros NTx Controls - For <i>in-vitro</i> use in the monitoring of the<br>performance of the VITROS Immunodiagnostic System when<br>used for the quantitative measurement of NTx in human urine. |
| 510(k) Number | K983674 |
| | (PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF<br>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)

Ortho-Clinical Diagnostics

VITROS Immunodiagnostic Products NTx Reagent Pack . VITROS Inmunodiagnostic Products NTx Calibrators VITROS Immunodiagnostic Products NTx Controls