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 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). 2. The VITROS Immunodiagnostic System - instrumentation, which provides automated use of the immunoassay kits. 3. Common reagents used by the VITROS System in each assay.

AI/ML Overview

The provided text describes a 510(k) summary for the VITROS Immunodiagnostic Products NTx assay, asserting its substantial equivalence to a predicate device, the Osteomark NTx Test. The study primarily focuses on demonstrating this equivalence by comparing the performance of the new device against the predicate.

Here's an analysis of the acceptance criteria and study details based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The text does not explicitly state formal "acceptance criteria" with quantitative targets for accuracy, precision, sensitivity, or specificity in the way one might see for a completely novel device. Instead, the primary acceptance criterion is substantial equivalence to the predicate device, K980518.

The device performance is reported in the context of this equivalence:

Device Characteristic	Acceptance Criteria (Implicit: Substantially Equivalent to Predicate)	Reported Device Performance (VITROS NTx assay)	Comparison to Predicate Device (Osteomark NTx Test)
Calibration Range	Similar to predicate (20-3000 nM BCE)	0 - 3000 nM BCE	The VITROS assay has a wider lower range (0 vs 20).
Basic principle	Solid phase immunoassay	Solid phase immunoassay	Identical
Tracer	Enzyme labeled	Enzyme labeled	Identical
Instrumentation	Compatible with typical immunoassay readers	VITROS Immunodiagnostic System	Microwell plate reader (different specific instrument, but same type of system)
Sample type	Urine	Urine	Identical
Antibody	Mouse monoclonal anti-NTx antibody in conjugate reagent	Mouse monoclonal anti-NTx antibody in conjugate reagent	Identical
Sample volume	25 µL	25 µL	Identical
Incubation time & temperature	Similar incubation conditions	30 minutes at 37° C	18-28° C for 90 minutes (± 5 minutes) (Different, but likely within acceptable clinical range)
Correlation to Predicate	Strong linear relationship	VITROS NTx assay = 0.957 x Osteomark NTx test + 6.5 (nM BCE/mM creatinine)	Demonstrated through Deming's Regression
Clinical Performance	Equivalent performance across clinical categories	Comparisons performed with samples from a variety of clinical categories	Demonstrated equivalence
Analytical Studies	Satisfactory performance	Tests performed for analytical sensitivity, specificity, precision, dilution, and expected values	Results refer to the package insert

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

Test Set Sample Size: The text states, "Comparisons of the VITROS NTx assay and the predicate device were performed with samples from a variety of clinical categories." It also mentions "patient specimens covering a variety of clinical categories." However, no specific number or range for the sample size of the test set is provided.
Data Provenance: The text does not explicitly state the country of origin. It indicates that "currently commercially available reagents along with patient specimens" were used, implying the data
- Retrospective/Prospective: Not specified.

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

This type of information is not applicable to this study. The study focuses on the analytical performance and correlation of a diagnostic assay (measuring NTx levels in urine) against a legally marketed predicate device. The "ground truth" for each sample is assumed to be the measurement obtained by the predicate device and/or the actual NTx concentration in the urine sample, rather than an expert's interpretation of an image or clinical condition. Therefore, no experts were used to establish a ground truth in the context of interpretation or diagnosis.

4. Adjudication Method for the Test Set

Not applicable. As the study involves quantitative laboratory measurements and comparison to a predicate device, adjudication by a panel of human experts is not relevant. The comparison is based on numerical results and statistical correlation methods like Deming's Regression.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, a MRMC comparative effectiveness study was not done. This type of study is typically associated with imaging diagnostics or clinical assessments requiring human interpretation. This submission is for an in-vitro diagnostic (IVD) assay where performance is objectively measured by the instrument.

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

Yes, this is essentially a standalone performance study. The VITROS Immunodiagnostic System, which performs the NTx assay, operates as an automated system without direct human-in-the-loop performance affecting the measurement itself. The results are quantitative measurements generated by the instrument. The comparison to the predicate device is also a standalone comparison between two analytical methods.

7. The Type of Ground Truth Used

The ground truth used for this study is primarily the measurements obtained from the predicate device (Osteomark NTx Test) for the purpose of demonstrating substantial equivalence. Additionally, typical "ground truth" for analytical studies of IVDs would involve:

Reference materials/standards with known concentrations: Used for analytical sensitivity, specificity, and calibration.
Split samples analyzed by both devices: Demonstrating correlation between the new device and the predicate.

Pathology or outcomes data are not mentioned as direct ground truth for this specific 510(k) submission, whose primary goal is substantial equivalence for an analytical test.

8. The Sample Size for the Training Set

The text does not explicitly mention a "training set" or its size. For an IVD assay like this, the development process would involve extensive analytical characterization and optimization, which could be considered an internal "training." However, the document focuses on the validation against the predicate, not the internal development data.

9. How the Ground Truth for the Training Set was Established

Since no explicit "training set" is described, the method for establishing its ground truth is not provided. In the context of IVD development, ground truth during internal development (analogous to training) would typically involve:

Using international reference materials.
Comparing results to established laboratory methods.
Verifying against carefully characterized samples to ensure accuracy across the assay's dynamic range.

Summary

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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 (716) 453-3607

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 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

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).
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
--	--	--	--	--	--	-------------------------------------------

DeviceCharacteristic	VITROS NTx assay	PredicateDevice
Calibration range(Reportable Range)	0 - 3000 nM BCE	20 - 3000 nM BCE
Basic principle	Solid phase immunoassay	Solid phase immunoassay
Tracer	Enzyme labeled	Enzyme labeled
Instrumentation	VITROSImmunodiagnostic System	Microwell plate reader
Sample type	Urine	Urine
Antibody	Mouse monoclonal anti-NTx antibody in conjugatereagent	Mouse monoclonal anti-NTx antibody inconjugate reagent
Sample volume	25 µL	25 µL
Incubation time andtemperature	30 minutes at 37° C	18-28° C for 90 minutes(± 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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Image /page/3/Picture/2 description: The image shows a black and white logo. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN" around the left side of the circle. Inside the circle is a stylized image of an eagle.

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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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 regulation (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/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 PackVITROS Immunodiagnostic Products NTx CalibratorsVITROS Immunodiagnostic Products NTx Controls
Indications for Use:	Vitros NTx Reagent Pack - For in-vitro quantitativemeasurement 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 asreported results do not contain a measure of time.Use of this test has not been established in primaryhyperparathyroidism or hyperthyroidism.
	Vitros NTx Calibrators - For in-vitro use in the calibration of theVITROS Immunodiagnostic System for the quantitativemeasurement of NTx in human urine.
Jean Cooper(Division Sign-Off)Division of Clinical Laboratory Devices	Vitros NTx Controls - For in-vitro use in the monitoring of theperformance of the VITROS Immunodiagnostic System whenused for the quantitative measurement of NTx in human urine.
510(k) Number	K983674
	(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IFNEEDED)

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

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.