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 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).

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Metrika DRx® NTx (Osteomark® NTx Point of Care) device, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Specific Metric	Acceptance Criteria (Implied)	Reported Device Performance
Accuracy	Linear Regression (Osteomark NTx POC vs. Predicate)	Close to y = x	$y = 1.12x + 6$
	Correlation Coefficient (r)	High correlation (e.g., > 0.80)	0.79
Precision	Total Pooled Imprecision (%CV) - Low Level	(Not explicitly stated)	13.3% (within-day range 7.5% to 22.1%)
	Total Pooled Imprecision (%CV) - High Level	(Not explicitly stated)	12.8% (within-day range 4.0% to 20.4%)
Analytical Sensitivity	NTx sensitivity	(Not explicitly stated)	30 nM BCE
	Creatinine sensitivity	(Not explicitly stated)	2 mM
Linearity	NTx Dynamic Range	(Not explicitly stated)	30 nM to 1300 nM
	Creatinine Dynamic Range	(Not explicitly stated)	2 mM to 25 mM
Analytical Specificity	Interference	Differences < 15%	Not affected (differences < 15%) by most potential interferents. Interference noted with very high levels of calcium (> 4mg/mL), chloride (> 300 mM), and C. albicans and E. coli (both 1.5 x 10^3).
Clinical Performance	Monitoring HRT (NTx decrease post-therapy)	Significant decrease expected	Mean NTx values fell significantly after 6 months of therapy to 33 nM BCE/mM creatinine, a 48% decrease from baseline (pre-HRT: 67 nM BCE/mM creatinine).
	Correlation with lab method (HRT study)	High correlation	r = 0.66 (baseline), r = 0.46 (12 months)
	Correlation with Spine BMD (HRT study)	Significant correlation	Significant correlations (r = -0.33) observed between percent change in spine BMD at 1 year and percent change in Osteomark® NTx POC from baseline to 6 months.

Note regarding Acceptance Criteria: The document does not explicitly state numerical acceptance criteria for many metrics. The "Implied Acceptance Criteria" column infers what might be considered acceptable based on typical clinical assay performance or the statement that studies "demonstrated substantial equivalence." The FDA's successful clearance implies that the reported performance was deemed acceptable.

Study Details

Sample size used for the test set and the data provenance:
- Accuracy Study: 235 urine samples.
  - Provenance: This dataset was used for comparative testing between Osteomark® NTx POC and the two predicate methods. The samples were assayed by Osteomark® NTx POC across three "POLtype" clinical sites (Physician Office Laboratories) and by the predicate methods at a reference laboratory. It is implied these were prospective samples collected for the purpose of the study, given they were tested at clinical sites. The country of origin is not specified but is implicitly the USA given the FDA submission.
- Clinical Performance (HRT Monitoring): 200 samples from 50 HRT-treated women.
  - Provenance: Retained samples from a published study. This indicates a retrospective analysis of previously collected samples. Country of origin not specified.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Accuracy Study: The ground truth for the accuracy study was established by predicate methods (Osteomark® NTx EIA and Creatinine Plus) performed at a reference laboratory. These are established analytical methods, not subjective expert assessment. Therefore, no human "experts" in the traditional sense (e.g., radiologists) were used to establish ground truth for this aspect. The expertise lies in the validated predicate assays themselves.
- Clinical Performance (HRT Monitoring): The ground truth for comparing NTx changes and correlation with BMD comes from the reference method (Osteomark NTx EIA) and Bone Mineral Density (BMD) measurements. Again, these are objective measurements, not subjective expert interpretation.
Adjudication method for the test set:
- Not applicable. The ground truth was established by laboratory measurements using predicate devices and BMD measurements, not through expert consensus requiring adjudication.
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:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) assay that provides quantitative measurements, not an AI-assisted diagnostic imaging device requiring human reader interpretation. Therefore, the concept of human readers improving with/without AI assistance does not apply.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the device itself provides a standalone result (NTx/creatinine ratio). The accuracy and precision studies evaluate the performance of this device in isolation, comparing its output to predicate methods. While a professional user operates the device, the device's measurement and calculation of the final result (NTx/creatinine) are entirely automated ("algorithm only"). The intended use states "professional use," indicating human operation, but the core analytical performance is standalone.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Analytical Ground Truth: For accuracy and linearity, the ground truth was established by measurements obtained from legally marketed predicate devices (Osteomark® NTx EIA and Creatinine Plus) in a reference laboratory setting.
- Clinical Ground Truth: For the HRT monitoring study, the ground truth included measurements from the predicate Osteomark NTx EIA and Bone Mineral Density (BMD) measurements, which are established clinical outcome measures for bone health.
The sample size for the training set:
- The document does not explicitly mention a "training set" in the context of machine learning or AI. This device is a quantitative assay based on dry reagent chemistry and reflectance photometry, not a machine learning algorithm that requires a distinct training phase. Therefore, the concept of a training set for an AI model is not applicable here. The assay's internal calibration parameters are "stored in memory," suggesting a pre-determined calibration process rather than an adaptive training set.
How the ground truth for the training set was established:
- As there is no "training set" in the context of an AI/ML algorithm, this question is not applicable. The device relies on established scientific principles of immunoassay and enzymatic reactions with internal calibration.

Summary

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K984530

M = T R I K A

Metrika, Inc. 510 Oakmead Parkw Sunnyvale, CA 94086

main 408 524 2255 fax 408 524 2252

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 ParkwaySunnyvale, CA 94086
Phone:	(408) 524-2255
FAX:	(408) 524-2252
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-telopeptides of type I collagen (NTx) divided by creatinine(nM Bone Collagen Equivalents [BCE]/mM creatinine)
Classification:	ratio numerator: 21 CFR 862.1400, Hydroxyproline TestSystemratio 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.

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807.92 (a)(4): Device Description

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).

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

CHARACTERISTIC	Osteomark® POCK984530	Osteomark® EIAK961562	CREATININE PlusK854766
Intended Use	DRx® NTx is a urinaryassay for thequantitative measure ofthe excretion of cross-linked N-telopeptides oftype I collagen (NTx)normalized to urinarycreatinine (nM BoneCollagenEquivalents/mMcreatinine). The test isused to monitor boneresorption changesfollowing initiation ofantiresorptive therapy(e.g., HRT).	Osteomark is a urinaryassay that provides aquantitative measure ofthe excretion of cross-linked N-telopeptides oftype I collagen (NTx) asan indicator of humanbone resorption.Measurement of NTx isintended for use in thetherapeutic monitoringof antiresorptivetherapies, and inpredicting skeletalresponse to hormonalantiresorptive therapy.	Creatinine Plus is for thequantitative determinationof creatinine in serum.plasma, or urine.Creatinine measurementsare used in the diagnosisand treatment of renaldiseases, in monitoringrenal dialysis, and as acalculation basis formeasuring other urineanalytes.
Analyte(s)	NTx (nM BCE)/creatinine (mM)	NTx (nM BCE)	Creatinine conversion ofmg/dL to mM:$mg/dL + 11.3 = mM$
Testing Matrix(Specimen Type)	urine: second morningvoid	urine: 24-hour or secondmorning void	serum. plasma, or urine
Testing Environment	professional use	professional use	professional use
Risk to Patient	not a sole discriminate;NTx results areinterpreted along withmedical histories andother biochemicalmarkers	not a sole discriminate;NTx results areinterpreted along withmedical histories andother biochemicalmarkers	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/TestingPlatforms	Osteomark® NTx POCis a four channel,"ratioing" reflectancephotometer, (plus aninternal referencechannel), with integraldry chemistry strips(competitive inhibitionimmunoassay for NTx;enzymatic assay forcreatinine).	Osteomark EIA is astandard competitiveinhibition enzyme-linkedimmunosorbent assay(ELISA).	The Creatinine Plus assayconsists of enzymaticreactions where creatinineis converted to redbenzoquinone imine dye(red) in the presence ofcreatininase, creatinase,sarcosine oxidase, andperoxidase.
Reportable Ranges	ratio: 2-350 nMBCE/mM creatinine	NTx: 20-3000 nM BCE	Creatinine (urine, pre-dil.1/10): 0.03 - 35.4 mM

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

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

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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).

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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.

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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.

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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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510(k) Number: K984530

Device Name: Osteomark® NTx Point of Care

INDICATIONS FOR USE

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)

Over-The-Counter Use (Optional Format 1-2-96)

Regulation Number and Section

§ 862.1225 Creatinine test system.

(a)
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.(b)
Classification. Class II.