(125 days)
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No
The device description and performance studies detail a standard ELISA/EIA assay for measuring a specific biomarker. There is no mention of AI, ML, or any computational methods beyond standard spectrophotometric measurement and calculation using a calibration curve.
No
The device is an in vitro diagnostic (IVD) test that quantitatively measures NTx levels in serum to aid in predicting skeletal response to antiresorptive therapy and monitoring bone resorption changes. It does not provide any therapy or treatment.
Yes
The device aids in predicting skeletal response to antiresorptive therapy and monitoring bone resorption by providing a quantitative measure of NTx in serum, which are diagnostic purposes.
No
The device is a laboratory assay (ELISA/EIA) that involves physical reagents and a microplate, which are hardware components. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device provides a quantitative measure of NTx in serum "as an indicator of human bone resorption." It is used to aid in predicting and monitoring skeletal response to antiresorptive therapy. This clearly indicates that the device is used to examine specimens derived from the human body (serum) to provide information for medical purposes (assessing bone resorption and guiding treatment).
- Device Description: The description details a laboratory test (ELISA/EIA) performed on human serum samples. This is a typical characteristic of an in vitro diagnostic device.
- Specimen Type: The device analyzes human serum, which is a biological specimen taken from the human body.
- Care Setting: The intended user is clinical laboratories, which are the typical settings where IVD tests are performed.
All of these factors align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological state, state of health, or disease.
N/A
Intended Use / Indications for Use
Osteomark® NTx Serum EIA provides a quantitative measure of cross-linked Ntelopeptides of type I collagen (NTx) in serum as an indicator of human bone resorption. Serum NTx level is used to aid in predicting skeletal response (bone mineral density) to antiresorptive therapy and in monitoring bone resorption changes following initiation of antiresorptive therapy. Prior to initiating antiresorptive therapy, serum NTx level is used to determine the probability for a decrease in bone mineral density after one year in postmenopausal women treated with hormonal antiresorptive therapy relative to those treated with calcium supplement.
Product codes
JMM
Device Description
The Osteomark NTx Serum EIA is a competitive-inhibition enzyme-linked immunosorbent assay (ELISA/EIA) for quantitative determination of NTx present in human serum.
NTx is adsorbed to a 96-well microplate: Diluted samples are added to the microplate wells, followed by a horseradish peroxidase labeled monoclonal antibody. NTx in the specimen competes with the NTx epitope on the microtiter plate for antibody binding sites. Following a wash step, the amount of labeled antibody bound is measured by colorimetric generation of a peroxide substrate. NTx concentration is determined spectrophotometrically and calculated using a standard calibration curve. Assay values are reported in nanomoles Bone Collagen Equivalents per liter (nM BCE).
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
Bone
Indicated Patient Age Range
Adult (premenopausal women, postmenopausal women, men)
Intended User / Care Setting
Clinical Laboratories
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Expected Values Study:
- Multi-center, cross-sectional study for normal premenopausal women:
- Sample size: 257 premenopausal women
- Mean age: 36 years (range 25-49)
- Results: Mean 12.6 nM BCE, Std Dev 3.2, Range 6.2 - 19.0 nM BCE
- Multi-center, cross-sectional study for men:
- Sample size: 176 men
- Mean age: 51 years (range 31-80)
- Results: Mean 14.8 nM BCE, Std Dev 4.7, Range 5.4 - 24.2 nM BCE
Intra-subject Variability Study (Postmenopausal Women):
- Short-term (3 days): n=271, 7.3% variability
- Long-term (2 months): n=261, 8.7% variability
Intra-subject Variability Study (Men):
- Short-term (4 days): n=32, 9.1% variability
- Long-term (3 months): n=27, 9.5% variability
Assay Reproducibility and Precision:
- Intra-assay variability: 2.6% (determined by testing four human serum specimens, NCCLS Precision Performance Guideline EP5-T2)
- Inter-assay variability: 6.9% (determined by testing eight human serum specimens)
- Total assay precision:
- Level I Serum Control: 13.99% Coefficient of Variation
- Level II Serum Control: 11.92% Coefficient of Variation
Antigen Recovery:
- Method: Adding known amounts of NTx to nine serum specimens of known NTx concentration.
- Results: Average antigen recovery of 100% across the assay range.
Dilutional Linearity:
- Method: Serial dilutions of five serum specimens with high nM BCE values into a serum specimen with a known low nM BCE value.
- Results: Average linearity of 98%.
Clinical Study: Use of Osteomark NTx Serum EIA in Postmenopausal Women Treated With HRT
- Study type: Clinical trial
- Objective: To determine the ability of Osteomark NTx Serum EIA to monitor the effect of HRT on bone resorption and to determine the probability for a decrease in BMD after one year if treated with only calcium supplements relative to those treated with supplements and HRT.
- Key results:
- Prior to HRT, mean baseline was 15.9 nM BCE in HRT group (significantly higher than premenopausal mean).
- In HRT group, mean values fell significantly to 12.2 nM BCE after 3 months (-22.9% decrease).
- Mean values in calcium group remained constant (15.4 nM BCE at baseline, 15.8 nM BCE after 12 months).
- In the lowest NTx quartile (≤12.5 nM BCE), no statistically significant difference between HRT and calcium groups in likelihood of bone loss over 1 year.
- A high baseline NTx (≥18.1 nM BCE) indicated a 6 times higher risk of BMD loss if not treated with HRT.
Clinical Study: Use of Osteomark NTx Serum EIA in Postmenopausal Women Treated With Bisphosphonate
- Study type: Randomized, double-blind clinical study
- Setting: Regional specialty hospital in the northeast United States.
- Objective: To determine if early changes in Osteomark NTx Serum EIA following treatment with bisphosphonate alendronate sodium predicts an increase in BMD.
- Key results:
- In alendronate treated group, mean Osteomark NTx Serum EIA values after 6 months (11.0 nM BCE) were significantly lower than baseline (16.1 nM BCE).
- Subjects with the highest baseline values (≥ 16.6 nM BCE) had the greatest gain in PA spine BMD (5.76%).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
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Predicate Device(s)
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Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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.
0
1983457
Summary of Sales of the Summary of Safety and Effectiveness Summary of Safety and Effectiveness
Assay Principles
The Osteomark NTx Serum EIA is a competitive-inhibition enzyme-linked immunosorbent assay (ELISA/EIA) for quantitative determination of NTx present in human serum.
NTx is adsorbed to a 96-well microplate: Diluted samples are added to the microplate wells, followed by a horseradish peroxidase labeled monoclonal antibody. NTx in the specimen competes with the NTx epitope on the microtiter plate for antibody binding sites. Following a wash step, the amount of labeled antibody bound is measured by colorimetric generation of a peroxide substrate. NTx concentration is determined spectrophotometrically and calculated using a standard calibration curve. Assay values are reported in nanomoles Bone Collagen Equivalents per liter (nM BCE).
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Kit Components
Supplied Materials sufficient for 96 wells
| Instructions for Use | 1 booklet |
|---|---|
| Antigen Coated 96-Well Plate, 12 1x8 well strips | 1 plate |
| Specimen Diluent | 40 mL bottle |
| Calibrators: | |
| 0 nM BCE Calibrator | 20.0 mL vial |
| 1 nM BCE Calibrator | 0.4 mL vial |
| 5 nM BCE Calibrator | 0.4 mL vial |
| 10 nM BCE Calibrator | 0.4 mL vial |
| 20 nM BCE Calibrator | 0.4 mL vial |
| 40 nM BCE Calibrator | 0.4 mL vial |
| Level I Serum Control | 0.4 mL vial |
| Level II Serum Control | 0.4 mL vial |
| Antibody Conjugate Concentrate | 0.4 mL vial |
| Antibody Conjugate Diluent | 25 mL bottle |
| 30X Wash Concentrate | 125 mL bottle |
| Chromogen Reagent | 0.9 mL vial |
| Buffered Substrate | 30 mL bottle |
| Stopping Reagent | 30 mL bottle |
| Plate Sealers | 1 pad |
2
Expected Values
A multi-center, cross-sectional study was conducted at five regional sites to determine the reference range for normal premenopausal women (mean age 36 years, range 25-49). Male reference range was determined from a multi-center, cross-sectional study conducted at three regional sites (mean age 51 years, range 31-80).6
| | Mean* | Std Dev | Range
(mean ± 2 Std Dev) | N |
|-------|-------|---------|-----------------------------|-----|
| Women | 12.6 | 3.2 | 6.2 - 19.0 | 257 |
| Men | 14.8 | 4.7 | 5.4 - 24.2 | 176 |
*expressed as nM BCE
When the premenopausal women expected value range is log-transformed, the range is 7.7 - 19.3 nM BCE. The log-transformed male reference range is 8.1 - 24.8 nM BCE. These reference ranges are provided as guidelines only. Each laboratory should establish their own reference range.
In a study of postmenopausal women', short-term (3 days) and long-term (2 months) intra-subject variability was determined to be 7.3% (n=271) and 8.7% (n=261), respectively. In a subset of the above male reference range study population, the shortterm (4 days) intra-subject variability was 9.1% (n=32), and the long-term (3 months) intra-subject variability was 9.5% (n=27).
Performance Characteristics
Assay Reproducibility and Precision
Intra-assay variability was determined by testing four human serum specimens following NCCLS Precision Performance Guideline EP5-T2 with BCE values distributed throughout the calibration range of the assay. From these test results the Osteomark NTx Serum EIA intra-assay variability is established as 2.6%.
3
Inter-assay variability was determined by testing eight human serum specimens with BCE values distributed throughout the calibration range of the assay. From these test results the Osteomark NTx Serum EIA inter-assay variability is established as 6.9%.
Total assay precision was evaluated by testing the Level I Serum Control and the Level II Serum Control at four clinical laboratories. Estimate of the total precision percent coefficient of variation for the Level I Serum Control was 13.99% and for the Level II Serum Control was 11.92%.
Antigen Recovery was evaluated by adding known amounts of NTx to each of nine serum specimens of known NTx concentration. Recovery represented the observed assay value of the "spiked" specimens, calculated as a percent of the expected serum value (baseline serum value plus added antigen (NTx) value). Results demonstrated an average antigen recovery of 100% across the assay range.
Dilutional linearity was evaluated by performing serial dilutions of five serum specimens with high nM BCE values into a serum specimen with a known low nM BCE value. Percent linearity was determined as the measured value divided by the expected value multiplied by 100. Results demonstrated an average linearity of 98%.
Clinical Studies
Use of Osteomark NTx Serum EIA in Postmenopausal Women Treated With HRT A clinical trial was conducted to determine the ability of the Osteomark NTx Serum EIA to monitor the effect of hormone replacement therapy (HRT) on bone resorption and to determine the probability for a decrease in bone mineral density (BMD) after one year if treated with only calcium supplements relative to those treated with supplements and HRT.4 Results of the study supported these clinical uses. Prior to HRT initiation,
4
Osteomark NTx Serum EIA mean baseline values in this group were 15.9 nM BCE, significantly higher than the premenopausal mean of 12.6 nM BCE. In the HRT group, mean values fell significantly after 3 months of therapy to 12.2 nM BCE, a -22.9% decrease. Mean values in the calcium group remained constant throughout the 12 month study; 15.4 nM BCE at baseline and 15.8 nM BCE after 12 months. Examination of the contrast between the HRT and calcium only groups provides information regarding risk of BMD loss. In the lowest NTx quartile (≤12.5 nM BCE), there was no statistically significant difference between the HRT and calcium groups in the likelihood of bone loss over 1 year. A high baseline NTx (≥18.1 nM BCE) indicated a 6 times higher risk of BMD loss if not treated with HRT.
Use of Osteomark NTx Serum EIA in Postmenopausal Women Treated With Bisphosphonate
A study was conducted at a regional specialty hospital in the northeast United States to determine if early changes in Osteomark NTx Serum EIA following treatment with the bisphosphonate alendronate sodium predicts an increase in BMD.5 In this randomized, double-blind clinical study, women were randomized to either placebo or 5-10 mg alendronate sodium. In the alendronate treated group, mean Osteomark NTx Serum EIA values after 6 months of treatment, 11.0 nM BCE, were significantly lower than baseline, 16.1 nM BCE. Stratification of baseline Osteomark NTx Serum EIA demonstrate that subjects with the highest values (≥ 16.6 nM BCE) had the greatest gain in PA spine BMD (5.76%).
5
References
-
- Garnero P., et. al. Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. J Clin Endo and Met. 79:1963-1700. 1994.
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- Garnero P., et. al. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res. 11:337-349. 1996.
-
- Prestwood K.M., et. al. The short-term effects of conjugated estrogen on bone turnover in older women. J. Clin Endo and Met. 79:366-371. 1994
-
- Chesnut C.H., et. al. Hormone replacement therapy in postmenopausal women: Urinary N-telopeptide of type I collagen monitors therapeutic effect and predicts response of bone mineral density. Am J Med. 102:29-37. 1997.
-
- Greenspan S.L., et. al. Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: A randomized clinical trial. J Bone Miner Res. 13:1431-1438. 1998.
-
- Orwoll E.S., et. al. Collagen N-telopeptide excretion in men: The effects of age and intra-subject variability. J. Clin Endo and Met. In Press.
-
- Weiss S., et. al. Determination of the intrasubject variability in NTx excretion in postmenopausal women. J Bone Miner Res. Vol. 12. Suppl. 1, pp. S506. 1997.
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OSTEOMARK NTx SERUM EIA QUICK REFERENCE GUIDE
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- Thoroughly read the Assay Procedure before you begin.
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- Allow all specimens and kit components to come to room temperature. Mix all reagents thoroughly.
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- Prepare working strength wash solution. Dilute 30X Wash Concentrate 1:30 with deionized water.
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- Plan the plate configuration, and create a plate map.
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- Prepare working strength antibody conjugate solution at a 1:101 dilution. You will need approximately 1 mL per strip.
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- Prepare 1:5 dilutions of all Calibrators, Controls and specimens in Specimen Diluent using microtubes or equivalent.
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- Pipette, in duplicate wells, 100 µL of each diluted Calibrator, Control or specimen into the microplate according to the plate map.
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- Pipette 100 uL of working strength antibody conjugate solution into each microwell. Gently swirl to mix, cover the plate with a plate sealer and incubate the plate at room temperature for 90 ± 5 minutes.
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- Prepare Chromogen Reagent/Buffered Substrate solution at a 1:101 dilution during the last 5 minutes of incubation. You will need approximately 2 mL per strip.
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- Wash microwells five (5) times with working strength wash solution. Blot on absorbent paper after the final wash.
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- Add 200 uL diluted Chromogen Reagent/Buffered Substrate to each microwell, gently swirl to mix, and incubate at room temperature for 30 ± 2 minutes.
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- Add 100 uL of Stopping Reagent to each microwell. Gently swirl the plate to mix.
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- Incubate at room temperature for five minutes and read the absorbance of each microwell at 450 nm. Calculate the results using a 4-parameter logistic curve fit.
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Public Health Service
2 1999 FEB
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Nancy Mallinak Vice President, Regulatory And Clinical Affairs Ostex International 2203 Airport Way South Suite 400 Seattle, Washington 98134
Re: K983457
Trade Name: Osteomark NTx Serum EIA Regulatory Class: I Product Code: JMM Dated: December 18, 1998 Received: December 22, 1998
Dear Ms. Mallinak:
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 Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic OS 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.
Image /page/7/Picture/10 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized design of three human profiles facing to the right, stacked on top of each other. The profiles are simple and abstract, with only the outlines of the faces visible. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the profiles.
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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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Page 1 of 1
K983457 S10 (k) NUMBER (IF KNOWN) : OSTEOMARK® NTx SERUM EIA DEVICE NAME: INDICATIONS FOR USE:
Osteomark® NTx Serum EIA provides a quantitative measure of cross-linked Ntelopeptides of type I collagen (NTx) in serum as an indicator of human bone resorption. Serum NTx level is used to aid in predicting skeletal response (bone mineral density) to antiresorptive therapy and in monitoring bone resorption changes following initiation of antiresorptive therapy. Prior to initiating antiresorptive therapy, serum NTx level is used to determine the probability for a decrease in bone mineral density after one year in postmenopausal women treated with hormonal antiresorptive therapy relative to those treated with calcium supplement.
Sean Cooper
(Division Sign-Off)
Division of Clinical Laboratory Devices 510(k) Number
(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)