(101 days)
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.
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.
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.
§ 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.