(231 days)
No
The device description and performance studies detail a standard ELISA assay based on antibody binding and colorimetric detection, with no mention of AI or ML algorithms for data analysis or interpretation.
No
This device is an in vitro diagnostic (IVD) test intended for the quantitative determination of 25-OH Vitamin D and other hydroxylated vitamin D metabolites in human serum and plasma to assist in the assessment of vitamin D sufficiency. It is not designed to treat or prevent a disease, but rather to provide diagnostic information.
Yes
The device is intended for the “quantitative determination of 25-OH Vitamin D and other hydroxylated vitamin D metabolites in human serum and plasma,” and the results are to be used in conjunction with other clinical and laboratory data to “assist the clinician in the assessment of vitamin D sufficiency in adult populations.” This clearly indicates an intended diagnostic purpose.
No
The device is an ELISA test kit, which is a laboratory diagnostic device that relies on chemical reactions and physical components (microwell plate, reagents, etc.) to produce results, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "quantitative determination of 25-OH Vitamin D and other hydroxylated vitamin D metabolites in human serum and plasma... Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in adult populations." This clearly indicates the device is used to test samples taken from the human body (in vitro) to provide information for medical diagnosis or assessment.
- Device Description: The description details a "microwell ELISA plate," "calibrators," "controls," and various reagents used to perform a test on "human serum or plasma samples." This is a typical setup for an in vitro diagnostic assay.
- Test Procedure: The description of the ELISA test procedure involves adding patient samples to the microplate and performing a series of steps to measure the concentration of the analyte. This is a standard in vitro diagnostic testing method.
- Performance Studies: The document describes various performance studies (Precision, Limit of Blank, Limit of Detection, Linearity, Analytical Specificity, Interference, Comparison Studies, Matrix Comparison, Expected Values/Reference Range, Stability Studies) which are all standard evaluations for an IVD device to demonstrate its analytical performance.
- Predicate Device: The mention of a "Predicate Device" (K021163; IDS Immunodiagnostic Systems Ltd. OCTEIA 25-Hydroxy Vitamin D) is a strong indicator that this device is being compared to another legally marketed IVD.
- Reference Device(s): The listing of "Reference Device(s)" (multiple K numbers) further supports that this device is being evaluated against other established IVDs.
All of these points align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
EUROIMMUN's 25-OH Vitamin D ELISA is intended for the quantitative determination of 25-OH Vitamin D and other hydroxylated vitamin D metabolites in human serum and plasma (EDTA, Li-heparin). Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in adult populations.
Product codes
MRG
Device Description
EUROIMMUN 25-OH Vitamin D ELISA consists of a microwell ELISA plate coated with (sheep) monoclonal anti-25-OH vitamin D antibodies, 6 calibrators, 2 controls, Biotin, sample buffer, conjugate. wash buffer concentrate. enzyme TMB chromogen/substrate solution and stop solution.
This ELISA test kit is designed for the in vitro determination of 25-OH vitamin D in human serum or plasma samples. In the first analysis step, the calibrators and patient samples are diluted with biotin-labelled 25-OH vitamin D and added to microplate wells coated with (sheep) monoclonal anti-25-OH vitamin D antibodies. During the incubation an unknown amount of 25-OH vitamin D in the patient sample and a known amount of biotinlabelled 25-OH vitamin D compete for the antibody binding sites in the microplate wells plate. Unbound 25-OH vitamin D is removed by washing. For the detection of bound biotin-labelled 25-OH vitamin D, a second incubation is performed using peroxidase-labelled streptavidin. In a third incubation using the peroxidase substrate tetramethylbenzidine (TMB) the bound peroxidase promotes a colour reaction. The colour intensity is inversely proportional to the 25-OH vitamin D concentration in the sample. Results for the samples can be calculated directly using a standard curve.
Antibodies: sheep monoclonal antibodies which identify specifically 25-OH vitamin D3 and 25-OH vitamin D2.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
adult populations
Intended User / Care Setting
For prescription use only.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies
Precision/Reproducibility:
The reproducibility of the test was investigated following CLSI standard EP05-A2. Intra- and Inter-Assay coefficients of variation (CV) were determined using samples with values at different points on the calibration curve. All samples were natural serum samples collected freshly in-house from obvious healthy blood donors. After initial screening, 2 of 8 samples (No. 7 and 8) were spiked. All samples were then aliquoted and stored at -20°C. The intra-Assay CVs are based on 40 determinations and the Inter-Assay CVs on 40 determinations performed in 10 different runs on 5 different days (with 4 replicates per run) according to the package insert. Acceptance criterion was that the CV's show results below 12% for samples over 10 ng/ml and results below 20% for concentrations below 10 ng/ml.
The lot-to-lot reproducibility of the test was investigated following CLSI standard EP05-A2. Inter-lot coefficients of variation (CV) were determined using samples with values at different points on the calibration curve. All samples were natural serum samples collected freshly in-house from obvious healthy blood donors. After initial screening, 2 of 8 samples (No. 7 and 8) were spiked. The inter-lot CVs are based on 32 determinations performed in 8 different runs on 4 different lots (with 2 runs per lot and 4 replicates per run) according to the package insert. Acceptance criterion was that the CV's show results below 12% for samples over 10 ng/ml and results below 20% for concentrations below 10 ng/ml.
Limit of Blank, Limit of Detection and Functional Sensitivity:
Limit of blank (LoB), limit of detection (LoD) and functional sensitivity (FS) were investigated following CLSI standard EP17-A.
LoB was determined as the concentration corresponding to the mean OD of the zero calibrator minus 1.645 times the standard deviation using the mean of 60 replicates for calibrator 1 (0 ng/ml) and the mean of 20 replicates for calibrator 2 (4 ng/ml). LoB was found to be 0.4 ng/ml.
LoD was determined as the LoB plus 1.645 times the standard deviation of 200 determinations from 5 samples in the low range of 2 to 10 ng/ml, measured in 5 independent runs with 8 replicates per run. The mean LoD was found to be 1.8 ng/ml.
Functional sensitivity is defined as the lowest concentration at which the potential regression line crosses the 20% CV line and was determined from a plot of the mean concentrations (X-axis) vs. % CVs (Y-axis). Functional sensitivity was found to be 4.0 ng/ml. Results below 4 ng/mL are reported as "
§ 862.1825 Vitamin D test system.
(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.
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. اُ
510(K) SAFETY & EFFECTIVENESS SUMMARY
| Submitter | EUROIMMUN US INC. | |
|---|---|---|
| 1100 The American Road | ||
| Morris Plains, NJ 07950 | ||
| Tel: 973.656.1000/1.800.913.2022 | JUL 17 2013 | |
| Fax: 973.656.1098 | ||
| Michael Locke | ||
| Director of Regulatory Affairs | ||
| E-mail: M.Locke@euroimmun.us | ||
| Date Prepared | July 3, 2013 | |
| Submission Type | 510(k) | |
| Device Trade/Proprietary Names | 25-OH Vitamin D ELISA | |
| Device Common/Usual Name or Classification Name | Vitamin D Test System | |
| Classification Number/Class | 21 CFR § 862.1825 - Vitamin D Test System - Class II | |
| Product Code | MRG - Vitamin D Test system | |
| Panel | Clinical Chemistry and Toxicology |
As required by 21 CFR § 807.92, the following is in sufficient detail to provide an understanding of the basis for a determination of substantial equivalence.
510(k) Number
Standard/Guidance Document Referenced (if applicable): None referenced.
. .
1
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510(K) SAFETY & EFFECTIVENESS SUMMARY
Traceability /Value Assignment of Calibrators and Controls
As there is no international standard, the Traceability: calibrators and controls are calibrated gravimetrically using UV-Vis (264nm) verified stock standards and compared with NIST standards (National Institute of Standards and Technology, USA), DEQAS (Vitamin D External Quality Assessment Scheme, UK) quality assessment data and in-house quality control sera.
Calibrators and controls are traceable to concentrations determined by UV spectrophotometric analysis. An in-house stock solution is prepared gravimetrically; and the antigen concentration is spectrophotometrically calculated using the OD coefficient of 18.2 at 264 nm to calculate the concentration from the absorbance value. This is used to build an intermediate stock volumetrically by dilution into horse serum. The intermediate stock is used in the manufacturing of lot specific calibrators and controls volumetrically.
- · The calibrator levels for each batch are confirmed by running a min. of 8 quality control sera covering the whole concentration range of the calibration curve measured in a minimum of 4 runs performed by 2 different technicians on 2 different days in duplicates. The quality control sera must fall within established target ranges. Initial values for the quality control sera are assigned using the predicate device in conjunction with liquid chromatography. Once confirmation of the calibrator values is established. the new calibrators are retested by a different person for final release.
- · 25-OH Vitamin D controls prepared in human serum were tested with 7 different released EUROIMMUN 25-OH Vitamin D lots, obtained from 20 independent runs, performed by 4 different persons on 9 different days. The obtained mean values were assigned as control target values. The control target ranges were assigned as mean ±3 SD (ng/mL). Target values were confirmed using two predicate devices (K021163; K112725) and a HPLC method.
Calibrators and controls are supplied in liquid form and are horse serum based with active ingredients of 0.09% ProClin 950 and 0.09% sodium azide. Avoid skin contact. Calibrators are 25-OH vitamin D3 spiked. No special treatment necessary for the use of the calibrators and controls except reagents must be mixed thoroughly before use either manually or by vortexing.
Caution: The serum contained in the calibrators and controls are of animal origin (horse). Handle kit reagents as if capable of transmitting an infectious agent. Appropriate precautions and good laboratory practices must be used in the storage, handling and disposal of the kit reagents. Disposal of kit reagents should be in accordance with local regulations.
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2
EUROIMMUN 25-OH Vitamin D ELISA 510(k) Sybmission K123660
Value Assignments: Target ranges for control materials are: C1 (low): 15 ng/mL (10-25 ng/mL) and C2 (high): 40 ng/mL (25-60 ng/mL). Testing and assignment of values involves a min. of 5 assays from a min. of 2 operators with 8 replicates, resulting in a min. of 40 determinations. The mean obtained values are assigned as control values. The controls are labeled with the assigned values as mean C1 ±50% and C2 ±30%.
Calibrator value assignments are based on an internal procedure; the initial value assignment for calibrators was performed using 2 predicate assays (K021163; K112725) and HPLC. The final values are verified & assigned by adjusting their initial values to meet the specified ranges when tested against the predicate assays. Once confirmation of the values is established, the new calibrators are tested again in bulk and final.
510(K): K123660
3
Device Description
EUROIMMUN 25-OH Vitamin D ELISA consists of a microwell ELISA plate coated with (sheep) monoclonal anti-25-OH vitamin D antibodies, 6 calibrators, 2 controls, Biotin, sample buffer, conjugate. wash buffer concentrate. enzyme TMB chromogen/substrate solution and stop solution.
This ELISA test kit is designed for the in vitro determination of 25-OH vitamin D in human serum or plasma samples. In the first analysis step, the calibrators and patient samples are diluted with biotin-labelled 25-OH vitamin D and added to microplate wells coated with (sheep) monoclonal anti-25-OH vitamin D antibodies. During the incubation an unknown amount of 25-OH vitamin D in the patient sample and a known amount of biotinlabelled 25-OH vitamin D compete for the antibody binding sites in the microplate wells plate. Unbound 25-OH vitamin D is removed by washing. For the detection of bound biotin-labelled 25-OH vitamin D, a second incubation is performed using peroxidase-labelled streptavidin. In a third incubation using the peroxidase substrate tetramethylbenzidine (TMB) the bound peroxidase promotes a colour reaction. The colour intensity is inversely proportional to the 25-OH vitamin D concentration in the sample. Results for the samples can be calculated directly using a standard curve.
Antibodies: sheep monoclonal antibodies which identify specifically 25-OH vitamin D3 and 25-OH vitamin D2.
EUROIMMUN 25-OH Vitamin D ELISA is intended for the quantitative determination of 25-OH Vitamin D and other hydroxylated vitamin D metabolites in human serum and plasma (EDTA, Li-heparin). Results are to be used in coniunction with other clinical and laboratory data to assist the clinician in the assessment of vitamin D sufficiency in adult populations.
Indication(s) for Use: Same as intended use.
Special Conditions for the Use Statement(s):
For prescription use only.
Special Instrument Requirements:
Microwell plate reader capable of measuring OD at 450nm and at 620nm for dual wavelength readings.
Predicate Device Name(s):
IDS Immunodiagnostic Systems Ltd. OCTEIA 25-Hydroxy Vitamin D
Predicate 510(k) Number(s): K021163
Continued on the next page
510(K): K123660
Intended Usel
Indications for Use
Substantial Equivalence:
4
EUROIMMUI
510(K) SAFETY & EFFECTIVENESS SUMMARY, Continued
Comparison of Assays, Similarities and Differences
The following table compares the EUROIMMUN 25-OH Vitamin D ELISA Test System with the Equivalence - predicate device.
Similarities
| Item | New Device | Predicate Device |
|---|---|---|
| Intended Use/ | ||
| Indication for Use | For the quantitative determination of 25-OH Vitamin D and | |
| other hydroxylated vitamin D metabolites in human serum | ||
| or plasma. Results are to be used in conjunction with other | ||
| clinical and laboratory data to assist the clinician in the | ||
| assessment of vitamin D sufficiency in adult populations. | Same | |
| Sample Type | Serum and Plasma | Same |
| Test Format | 96-well microplate assay | Same |
| Assay Components | Microtiterplate; Calibrators; Biotin labeled 25-OH Vitamin D; | |
| Avidin-Conjugate; Assay buffer; Washbuffer; Substrate; | ||
| Stop solution | Same | |
| Instrument | ELISA plate reader | Same |
| Measuring | ||
| Wavelength | 450/620nm | Same |
| Approximate Assay | ||
| Time | 3.5 hours | Same |
| Antigen Used in | ||
| Calibrators | 25-OH Vitamin D3 | Same |
| Assay Principle | Competitive immunoassay | Same |
| Reagent Storage | ||
| Temperature | 2-8 °C | Same |
| Test Methodology | Samples are diluted with buffer containing a reagent | |
| dissociating Vitamin D metabolites from its binding protein. | ||
| The diluted samples are incubated in microtiter wells which | ||
| are coated with sheep anti-25-OH vitamin D antibodies for 2 | ||
| hours at room temperature before aspiration and washing. | ||
| Peroxidase labeled avidin is added and binds to the | ||
| captured biotin, following a further wash step, color is | ||
| developed using a chromogenic substrate (TMB). Color | ||
| intensity is inversely proportional to the concentration of 25- | ||
| OH vitamin D. | Same | |
| Interpretation of | ||
| Results | Standard curve | Same |
| Traceability | Standardized using UV quantification of 25-OH vitamin | Same |
| Specificity | 25-OH Vitamin D and other hydroxylated vitamin D | |
| metabolites | Same | |
| Item | New Device | Predicate Device |
| Antibody | Monoclonal sheep anti-25-OH-Vitamin D IgG antibody | Polyclonal sheep anti-25-OH- |
| Vitamin D IgG antibody | ||
| Calibrators | 6 | 7 |
| Assay range | 4.0 - 120 ng/ml | 2.4 - 144 ng/ml |
| Sample Volume | 20 $\mu$ l | 25 $\mu$ l |
Differences
Continued on the next page
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5
Performance Characteristics
Precision/Reproducibility:
The reproducibility of the test was investigated following CLSI standard EP05-A2. Intra- and Inter-Assay coefficients of variation (CV) were determined using samples with values at different points on the calibration curve. All samples were natural serum samples collected freshly in-house from obvious healthy blood donors. After initial screening, 2 of 8 samples (No. 7 and 8) were spiked. All samples were then aliquoted and stored at -20°C. The intra-Assay CVs are based on 40 determinations and the Inter-Assay CVs on 40 determinations performed in 10 different runs on 5 different days (with 4 replicates per run) according to the package insert. Acceptance criterion was that the CV's show results below 12% for samples over 10 ng/ml and results below 20% for concentrations below 10 ng/ml. The following results were obtained:
Intra-Assay Reproducibility
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Inter-Assay Reproducibility
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The lot-to-lot reproducibility of the test was investigated following CLSI standard EP05-A2. Inter-lot coefficients of variation (CV) were determined using samples with values at different points on the calibration curve. All samples were natural serum samples collected freshly in-house from obvious healthy blood donors. After initial screening, 2 of 8 samples (No. 7 and 8) were spiked. The inter-lot CVs are based on 32 determinations performed in 8 different runs on 4 different lots (with 2 runs per lot and 4 replicates per run) according to the package insert. Acceptance criterion was that the CV's show results below 12% for samples over 10 ng/ml and results below 20% for concentrations below 10 ng/ml. The following results were obtained:
Lot 10 Lot Reproducibility
| Sample No. | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
|---|---|---|---|---|---|---|---|---|
| Mean (x): | 7.3 | 18.5 | 24.8 | 37.4 | 47.6 | 58.0 | 74.3 | 97.3 |
| SD. | 0.89 | 1.89 | 1.81 | 2.29 | 4.25 | 4.07 | 6.59 | 9.26 |
| CV,% | 12.2 | 10.2 | 7.3 | 6.1 | 8.9 | 7.0 | 8.9 | 9.5 |
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6
Limit of Blank, Limit of Detection and Functional Sensitivity: Limit of blank (LoB), limit of detection (LoD) and functional sensitivity (FS) were investigated following CLSI standard EP17-A.
LoB was determined as the concentration corresponding to the mean OD of the zero calibrator minus 1.645 times the standard deviation using the mean of 60 replicates for calibrator 1 (0 ng/ml) and the mean of 20 replicates for calibrator 2 (4 ng/ml). LoB was found to be 0.4 ng/ml.
| $[\mu_B]$ (OD) | 2.721 |
|---|---|
| $[\sigma_B]$ (OD) | 0.038 |
| $[\mu_{C1}]$ (OD) | 2.721 |
| $[\mu_{C2}]$ (OD) | 2.146 |
| LoB (OD) | 2.658 |
| LoB (ng/ml) | 0.43 |
LoD was determined as the LoB plus 1.645 times the standard deviation of 200 determinations from 5 samples in the low range of 2 to 10 ng/ml, measured in 5 independent runs with 8 replicates per run. The mean LoD was found to be 1.8 ng/ml.
| Sample | 1 | 2 | 3 | 4 | 5 |
|---|---|---|---|---|---|
| Concentration (ng/ml) | 2.0 | 4.0 | 6.0 | 8.0 | 10.0 |
| $\sigma$ s (ng/ml) | 0.731 | 0.810 | 0.783 | 0.919 | 0.834 |
| LoD (ng/ml) | 1.63 | 1.76 | 1.72 | 1.94 | 1.80 |
| Mean LoD (ng/ml) | 1.8 |
Functional sensitivity is defined as the lowest concentration at which the potential regression line crosses the 20% CV line and was determined from a plot of the mean concentrations (X-axis) vs. % CVs (Y-axis). Functional sensitivity was found to be 4.0 ng/ml. Results below 4 ng/mL are reported as " 50 | > 125 |
1Looker AC, Johnson CL, Lacher DA, Pfeiffer CM, Schleicher RL, Sempos CT. Vitamin D status: United States, 2001-2006. NCHS data brief, no 59. Hyattsville, MD: National Center for Health Statistics. 2011.
The Endocrine Society Clinical Practice Guideline (2011) recently suggested a higher target level of at least 30 na/mi:
| Status | (ng/ml) | (nmol/l) |
|---|---|---|
| Deficiency |