ELECSYS VITAMIN D ASSAY ELECSYS VITAMIN D CALSET ELECSYS PRECICONTROL VARIA 3 ELECSYS VITAMIN D CALCHECK 5
Device Facts
| Record ID | K113546 |
|---|---|
| Device Name | ELECSYS VITAMIN D ASSAY ELECSYS VITAMIN D CALSET ELECSYS PRECICONTROL VARIA 3 ELECSYS VITAMIN D CALCHECK 5 |
| Applicant | Roche Diagnostics |
| Product Code | MRG · Clinical Chemistry |
| Decision Date | Jul 24, 2012 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1825 |
| Device Class | Class 2 |
Indications for Use
The Elecsys Vitamin D assay is intended for the quantitative determination of total 25-hydroxy vitamin D in human serum and plasma. The Elecsys Vitamin D assay is to be used as an aid in the assessment of vitamin D sufficiency in adults. The electrochemiluminescence binding assay is intended for use on Elecsys and Cobas e immunoassay analyzers. Elecsys Vitamin D CalSet is used for calibrating the quantitative Elecsys Vitamin D assay on the Elecsys and cobas e immunoassay analyzers. The Elecsys Vitamin D CalCheck 5 is an assayed control for use in calibration verification and for use in the verification of the assay range established by the Elecsys Vitamin D reagent on the indicated Elecsys and cobas e immunoassay analyzers. Elecsys PreciControl Varia 3 is used for quality control of specified Elecsys immunoassays on Elecsys and cobas e immunoassay analyzers.
Device Story
The Elecsys Vitamin D assay is a competitive electrochemiluminescence immunoassay for use on Elecsys and cobas e analyzers. The device processes human serum or plasma samples; pretreatment reagents release endogenous vitamin D from binding proteins. Ruthenium-labeled vitamin D binding protein binds to the sample's vitamin D; biotinylated vitamin D is added to occupy remaining binding sites. Streptavidin-coated microparticles capture the biotinylated complex. The analyzer measures electrochemiluminescence emission to quantify total 25-hydroxy vitamin D. Results are calculated via a 2-point calibration curve. The assay aids clinicians in assessing vitamin D sufficiency in adult patients. The system includes dedicated calibrators (CalSet), controls (PreciControl Varia 3), and calibration verification materials (CalCheck 5).
Clinical Evidence
Bench testing only. Performance evaluated via precision (within-run CV 1.6-7.2%, total CV 2.9-10.3%), analytical sensitivity (LoB 2.00 ng/mL, LoD 3.00 ng/mL, LoQ 5.00 ng/mL), and specificity. Method comparison against LC-MS/MS (n=290, r=0.85) and Abbott Architect (n=165, r=0.91) provided. No clinical prospective/retrospective studies on patient outcomes reported.
Technological Characteristics
Competitive protein binding immunoassay. Reagents: dithiothreitol, NaOH, streptavidin-coated microparticles, ruthenium-labeled vitamin D binding protein, biotinylated vitamin D. Energy source: electrochemiluminescence. Form factor: automated analyzer-based (cobas e411). Connectivity: analyzer-integrated. Standardization: traceable to LC-MS/MS and NIST standards.
Indications for Use
Indicated for quantitative determination of total 25-hydroxyvitamin D in human serum and plasma as an aid in assessing vitamin D sufficiency in adults. For prescription use on Elecsys and cobas e immunoassay analyzers.
Regulatory Classification
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.
Special Controls
*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.
Predicate Devices
- Abbott Architect 25-OH Vitamin D (K110619)
- Elecsys hGH CalSet (K103221)
- PreciControl Multimarker (K102157)
- Elecsys T4 CalCheck 5 (K112528)
Related Devices
- K210901 — Elecsys Vitamin D total III · Roche Diagnostics · Sep 1, 2021
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE
A. 510(k) Number:
k113546
B. Purpose for Submission:
New assay
C. Measurand:
25-OH Vitamin D
D. Type of Test:
Quantitative, automated electrochemiluminescence immunoassay
E. Applicant:
Roche Diagnostics
F. Proprietary and Established Names:
Elecsys Vitamin D assay, Elecsys Vitamin D CalSet, Elecsys PreciControl Varia 3, and Elecsys Vitamin D Calcheck 5.
G. Regulatory Information:
1. Regulation section:
21 CFR 862.1825, Vitamin D Test System; 21 CFR 862.1150, Calibrator; 21 CFR 862.1660, Quality Control Material
2. Classification:
Class II, (controls – Class I, reserved)
3. Product code:
MRG, JIT, JJY, JJX
4. Panel:
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Chemistry (75)
## H. Intended Use:
1. Intended use(s):
See indications for use.
2. Indication(s) for use:
The Elecsys Vitamin D assay is intended for the quantitative determination of total 25-hydroxy vitamin D in human serum and plasma. The Elecsys Vitamin D assay is to be used as an aid in the assessment of vitamin D sufficiency in adults. The electrochemiluminescence binding assay is intended for use on Elecsys and Cobas e immunoassay analyzers.
Elecsys Vitamin D CalSet is used for calibrating the quantitative Elecsys Vitamin D assay on the Elecsys and cobas e immunoassay analyzers.
The Elecsys Vitamin D CalCheck 5 is an assayed control for use in calibration verification and for use in the verification of the assay range established by the Elecsys Vitamin D reagent on the indicated Elecsys and cobas e immunoassay analyzers.
Elecsys PreciControl Varia 3 is used for quality control of specified Elecsys immunoassays on Elecsys and cobas e immunoassay analyzers.
3. Special conditions for use statement(s):
For prescription use only.
4. Special instrument requirements:
Performance studies were conducted on the cobas e411 Analyzer
## I. Device Description:
The devices cleared under this 510(k) are:
(1) Elecsys Vitamin D Assay
(2) Elecsys Vitamin D CalSet
(3) Elecsys PreciControl Varia 3
(4) Elecsys Vitamin D CalCheck 5
The assay consists of
Pre-treatment reagent 1 – dithiothreitol;
Pretreatment reagent 2 – NaOH;
Solution M containing streptavidin-coated microparticles with preservative;
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R1 - Ruthenium labeled vitamin D binding protein in buffer with human albumin and preservative;
R2- Biotinylated vitamin D (25-OH) in buffer with preservative
The Vitamin D Calset contains two bottles of Vitamin D 25-OH in two concentration ranges (approximately 2 and 37 ng/mL) in a human serum matrix with preservative.
The Vitamin D Calcheck 5 contains 5 levels of lyophilized synthetic Vitamin D (25-OH) from human serum with preservative.
The Preciconcontrol Varia 3 contains three levels of lyophilized serum-based control. Analytes include Vitamin D, as well as analytes previously cleared under k111506 (Vitamin B12, Ferritin, Folate III, β-Crosslaps/Serum (β-CTx), Osteocalcin, Parathyroid Hormone (PTH)).
Package inserts for the above materials that contain human blood or serum matrices include the following statement:
All human material should be considered potentially infectious. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods applied were FDA-approved or cleared in compliance with the European Directive 98/79/EC, Annex II, List A. However, as no testing method can rule out the potential risk of infection with absolute certainty, the material should be handled with the same level of care as a patient specimen.
J. Substantial Equivalence Information:
1. Predicate device name(s):
ARCHITECT 25-OH Vitamin D assay (k110619)
Elecsys hGH CalSet (k103221)
Predicate Device: Elecsys PreciControl Multimarker (k102157)
Predicate Device: Elecsys T4 CalCheck 5 (k112528)
2. Predicate 510(k) number(s):
k110619
k103221
k102157
k112528
3. Comparison with predicate:
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| | | |
| --- | --- | --- |
| Feature | Elecsys Vitamin D Assay | Predicate Device: Abbott Architect 25-OH Vitamin D (K110619) |
| General Assay Features | | |
| Intended Use/Indications for Use | The Vitamin D assay is intended for the quantitative determination of total 25-hydroxyvitamin D in human serum and plasma. This assay is to be used as an aid in the assessment of vitamin D sufficiency in adults. | Same |
| Assay Technology | Quantitative protein binding assay | Quantitative immunoassay |
| Detection Protocol | Electrochemiluminescence | Chemiluminescence |
| Sample Type | Human serum and plasma treated with K2-EDTA, K3-EDTA or lithium heparin. | Human serum, plasma treated with lithium heparin, sodium heparin, potassium EDTA, or sodium citrate. |
| Reagents | The Elecsys Vitamin D assay is a competitive binding assay which includes vitamin D (25-OH) labeled with biotin, and a ruthenium labeled vitamin D binding protein, and streptavidin coated microparticles. | The Abbott Architect 25-OH Vitamin D assay is a competitive one-step delayed immunometric assay which includes anti-vitamin D coated microparticles, an assay diluent, and biotinylated vitamin D anti-biotin acridinium labeled conjugate. |
| Calibration | Elecsys Vitamin D CalSet, 2 levels | Architect 25-OH Vitamin D Calibrators, 6 levels |
| Traceability / Standardization | The Elecsys Vitamin D Assay has been standardized against LC-MS/MS which in turn has been standardized to the NIST standard. | Architect 25-OH Vitamin D is traceable to a manufacturer's internal standard (Primary Calibrator), which is anchored against Absorbance at 264 nm. |
| Measuring Range | 5-60 ng/mL | 13-96 ng/mL |
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| Characteristic | CalSet for Elecsys Vitamin D Assay | Predicate Device: Elecsys hGH CalSet (K103221) |
| --- | --- | --- |
| Intended Use | Elecsys Vitamin D CalSet is used for calibrating the quantitative Elecsys Vitamin D assay on the Elecsys and cobas e immunoassay analyzers. | Elecsys hGH CalSet is used for calibrating the quantitative Elecsys hGH assay on the Elecsys and cobas e immunoassay analyzers. |
| Levels | Two | Same |
| Matrix | Human serum | Same |
| Format | Lyophilized | Same |
| Characteristic | Elecsys PreciControl Varia 3 | Predicate Device: Elecsys PreciControl Multimarker (K102157) |
| --- | --- | --- |
| Intended Use | Elecsys PreciControl Varia 3 is used for quality control of Elecsys immunoassays on the Elecsys and cobas e immunoassay analyzers. | Elecsys PreciControl Multimarker is used for quality control of specified Elecsys immunoassays on the Elecsys and cobas e immunoassay analyzers. |
| Levels | Three | Two |
| Format | Lyophilized | Same |
| Matrix | Human serum | Equine serum |
| Characteristic | Elecsys Vitamin D CalCheck 5 | Predicate Device: Elecsys T4 CalCheck 5 (K112528) |
| --- | --- | --- |
| Intended Use | The Elecsys Vitamin D CalCheck 5 is an assayed control for use in calibration verification and for use in the verification of the assay range established by the Elecsys Vitamin D reagent on the indicated Elecsys and cobas e immunoassay analyzers. | The Elecsys T4 CalCheck 5 is an assayed control for use in calibration verification and for use in the verification of the assay range established by the Elecsys T4 reagent on the indicated Elecsys and cobas e immunoassay analyzers. |
| Analyte | (25-OH) Vitamin D | Thyroxine (T4) |
| Levels | Five | Same |
| Matrix | Human serum | Check 1: BSA/Buffer matrix Check 2-5: human serum |
| Format | Lyophilized | Same |
# K. Standard/Guidance Document Referenced (if applicable):
CLSI EP6, Evaluation of Linearity of Quantitative Measurement Procedures: A statistical Approach.
CLSI EP5, Evaluation of Precision Performance of Clinical Chemistry Devices.
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CLSI EP7, Interference Testing in Clinical Chemistry.
# L. Test Principle:
The Elecsys Vitamin D Assay is a competitive protein binding assay which uses Vitamin D Binding Protein for detection of 25-Hydroxyvitamin D. The sample is treated with pretreatment reagent in the first incubation period. This releases vitamin D from the endogenous vitamin D binding protein present in the patient's sample. In the next incubation, vitamin D binding protein labeled with ruthenium is added and a complex is formed between the vitamin D (25-OH) and the ruthenylated vitamin D binding protein. In the $3^{\text{rd}}$ and final incubation, streptavidin-coated microparticles are added along with vitamin D (25-OH) labeled with biotin. Any unbound ruthenium labeled vitamin D binding proteins become occupied with biotin-labeled vitamin D (25-OH). The complex consisting of the ruthenylated vitamin D binding protein and the biotinylated vitamin D (25-OH) becomes bound to the solid phase via interaction of the biotin and streptavidin. The reaction mixture is aspirated into the measuring cell where the electrochemiluminescence emission is detected. Results are determined using a calibration curve that is generated on each instrument by a 2 point calibration provided with the reagent bar code.
# M. Performance Characteristics (if/when applicable):
Evaluations described below were performed on the cobas e 411
# 1. Analytical performance:
# a. Precision/Reproducibility:
Precision of the Elecsys® Vitamin D assay was evaluated according to CLSI EP5-A2 guideline. Two reagent lots were evaluated. The protocol consisted of testing 2 replicates of each control (PC Varia = PreciControl Varia 3) and human sera (HS) per run, 2 runs per day for 21 days. The human sera were all native, single donors. Repeatability and Intermediate precision were calculated. Results are tabulated below:
| Lot 1 | | Repeatability | | Intermediate (within lab) precision | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (ng/mL) | SD (ng/mL) | CV (%) (UCL* 95%) | SD (ng/mL) | CV (%) (UCL* 95%) | n |
| Human serum 1 | 52.6 | 0.858 | 1.6 (2.0) | 1.5 | 2.9 (3.6) | 84 |
| Human serum 2 | 6.2 | 0.445 | 7.2 (8.8) | 0.64 | 10.3 (12.3) | 84 |
| Human serum 3 | 13 | 0.618 | 4.7 (5.8) | 1.09 | 8.4 (10.4) | 84 |
| Human serum 4 | 23.2 | 0.666 | 2.9 (3.5) | 1.24 | 5.3 (6.6) | 84 |
| Human serum 5 | 43.5 | 1.04 | 2.4 (2.9) | 1.46 | 3.4 (4.0) | 84 |
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| Human serum 6 | 11.2 | 0.566 | 5.1 (6.2) | 0.849 | 7.6 (9.0) | 84 |
| --- | --- | --- | --- | --- | --- | --- |
| Lot 2 | | Repeatability | | Intermediate (within lab) precision | | |
| Sample | Mean (ng/mL) | SD (ng/mL) | CV (%) (UCL* 95%) | SD (ng/mL) | CV (%) (UCL* 95%) | n |
| Human serum 1 | 55.5 | 1.07 | 1.9 (2.4) | 1.38 | 2.5 (2.9) | 84 |
| Human serum 2 | 6.08 | 0.467 | 7.7 (9.4) | 0.583 | 9.6 (11.3) | 84 |
| Human serum 3 | 13.8 | 0.557 | 4.0 (4.9) | 0.803 | 5.8 (6.8) | 84 |
| Human serum 4 | 24.6 | 1.12 | 4.6 (5.6) | 1.25 | 5.1 (5.9) | 84 |
| Human serum 5 | 44.7 | 0.871 | 1.9 (2.4) | 1.28 | 2.9 (3.4) | 84 |
| Human serum 6 | 8.44 | 0.695 | 8.2 (10.1) | 0.918 | 10.9 (13.0) | 84 |
| Human serum 7 | 11.4 | 0.649 | 5.7 (7.0) | 0.843 | 7.4 (8.7) | 84 |
| | | Repeatability | | Intermediate (within lab) precision | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (ng/mL) | SD (ng/mL) | CV (%) (UCL* 95%) | SD (ng/mL) | CV (%) (UCL* 95%) | n |
| PC Varia 0 | 11.6 | 0.529 | 4.6 (5.6) | 0.705 | 6.1 (7.1) | 84 |
| PC Varia 1 | 17.0 | 0.745 | 4.4 (5.4) | 0.964 | 5.7 (6.8) | 84 |
| PC Varia 2 | 31.1 | 0.802 | 2.6 (3.1) | 1.08 | 3.5 (4.1) | 84 |
# b. Linearity/assay reportable range:
Linearity of the Elecsys Vitamin D assay was evaluated according to CLSI EP6-A.
A high analyte serum sample was diluted with a low analyte serum sample (depleted) to prepare concentrations throughout the measuring range and samples were assayed in 3-fold determination within a single run.
The linear regression equation yielded slope of 1.07 and intercept of $-1.13$ ( $r^2 = 0.996$ ) for the measured sample ranged from 0 to 62 (0, 3,7,12,18,22,28,32,38,44,48,52,56,60,62) ng/mL.
The results of the study support the sponsor's claim that the assay is linear across the measuring range of $5 - 60\mathrm{ng / mL}$ .
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
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# Calibrator
## Calset Components:
The Elecsys Vitamin D Calset contains 25-hydroxyvitamin D in a lyophilized human serum matrix. Target values are 2.0 [target range: 1.0 to 3.0] and 37.0 ng/mL (target range: 33.0-41.0).
## Traceability/value assignment:
The values are standardized against an LCMS/MS assay which is in turn standardized against the NIST standard. The Elecsys Vitamin D CalSet assigned values are determined with the Elecsys Vitamin D assay. A master calibrator set is available and traceable to a reference method (LC-MS/MS). The assigned values for Elecsys Vitamin D CalSet are read from the master calibration curve.
## Stability:
Calset stability is evaluated under the manufacturer’s recommended storage conditions including: after reconstitution, after freeze-thaw conditions, and unopened.
The sponsor claims that the CalSet is stable at up to hundred twenty (120) hours at 2 to 8°C; up to ninety (90) days at -15 to -25°C and for one freeze/thaw cycle (Table 14). Stability protocols and acceptance criteria were reviewed and found to be adequate.
# Control materials:
## Components:
Lyophilized Synthetic 25-OH Vitamin D in a human serum matrix, at target levels of 13, 17, 32 ng/mL. This control material also contains additional analytes previously cleared under k060755, k971833, k082340, k993706, k051297 and k070709.
## Value assignment:
Values are assigned for each lot of Elecsys® PreciControl Varia 3 in combination with each assay reagent lot available. The controls are run in duplicate on a minimum of 3 analyzers (minimum n=6). The assigned value of each control level is defined as the median value obtained.
## Stability:
Studies to support the claimed storage for unopened at 2-8°C up to the stated expiration date, for reconstituted at 2 - 8°C: 72 hours, and at -20°C: 31 days (freeze only once), on - analyzers at 20-25°C: up to 5 hours were reviewed. Stability protocols and acceptance criteria were reviewed and found to be adequate.
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# Calcheck
## Components:
Five levels of lyophilized synthetic 25-OH Vitamin D in a human serum matrix.
| Level | Target Value [ng/mL] | Target Range [ng/mL] |
| --- | --- | --- |
| Check 1 | ≤1 | – |
| Check 2 | 15 | 13 - 17 |
| Check 3 | 30 | 27 - 33 |
| Check 4 | 48 | 44 - 52 |
| Check 5 | 60 | 56 - 64 |
## Value assignment:
For each Elecsys Vitamin D CalCheck 5 lot manufactured, the CalChecks are run in duplicate on at least three E170/cobas e 601/cobas e 602 analyzer measuring cells. The assigned value of each CalCheck is defined as the median value obtained over at least 6 determinations (duplicate runs on at least 3 analyzers) of the respective CalCheck.
## Stability:
The package insert claim for stability of reconstituted Elecsys Vitamin D CalCheck 5 is up to 5 hours at 20-25°C. The CalCheck products are not stored on-board the analyzer, therefore no on-board stability claims are made. Stability protocols and acceptance criteria were reviewed and found to be adequate.
## d. Detection limit:
The LoB and LoD were determined according to protocols in CLSI EP-17 to support the LoB claim of 2 ng/mL and LoD claim of 3 ng/mL.
LoQ: The precision at low concentrations was determined to support the lower assay limit. Eight native human serum sample pools with concentrations ranging from 2.25 to 20.5 ng/mL were tested once per run, 2 runs per day over 5 days. The mean, standard deviation and coefficient of variation for each sample were calculated. LoQ is calculated to be 5.00 ng/mL. The CV at this concentration is less than ≤ 20%.
## e. Analytical specificity:
### Cross reactivity:
Cross-reactivity from compounds listed below were evaluated. Results are tabulated:
| Cross-reactant | cross reactivity (%) |
| --- | --- |
| Vitamin D3 (25-OH) | 100 |
| Vitamin D2 (25-OH) | 92 |
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| 24,25-OH Vitamin D3 | 149 |
| --- | --- |
| 1,25-OH Vitamin D3 | not detectable |
| 1,25-OH Vitamin D2 | not detectable |
| Vitamin D3 | not detectable |
| Vitamin D2 | not detectable |
| C3-epimers 25-OH D3 | 91 |
## Exogenous interferents:
Two samples with approx. 10 and 26 ng/mL (25-OH) Vitamin D were divided into aliquots and spiked with potential interferents. Concentrations tested were equal to or greater than concentrations listed in the CLSI EP7 guideline. Recovery was evaluated relative to a control samples without interferent. Compounds tested are shown in the table below. Test samples containing these compounds all recovered within +/- 10% of the control sample.
| | |
| --- | --- |
| Drug | Conc. of spiked drug
[ng/mL – unless noted otherwise] |
| Acetylcysteine | 1663 |
| Ampicillin-Na | 1000 |
| Ascorbic acid | 300 |
| Cyclosporine | 105 |
| Cefoxitin | 660 |
| Heparin | 5000 U |
| Intralipid | < 400 mg/dL |
| Levodopa | 140 |
| Methyldopa +1.5 | 15 |
| Metronidazole | 200 |
| Phenylbutazone | 400 |
| Doxycycline | 30 |
| Acetylsalicylic Acid | 1000 |
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| Rifampicin | 64 |
| --- | --- |
| Acetaminophen | 200 |
| Ibuprofen | 500 |
| Theophylline | 100 |
In addition, the presence of any of the following: bondronate (50 mg/L), alpha-calcidol (0.003 mg/L), alendronate (350 mg/L), pamidronate (90 mg/L), zolendronate (4 mg/L) and PTH 1-34 (0.02 mg/L) showed no significant interference (defined by the sponsor as recovery within 10%).
## Endogenous interferents:
Potential interference from endogenous substances was evaluated. For each interfering substance 3 serum samples containing low (10 ng/mL), mid (30 ng/mL) and high (50 ng/mL) concentrations of Vitamin D were tested. No significant interference is defined by the sponsor as <10% difference between the spiked and control samples. The highest concentrations at which no significant interference was observed are shown below:
**Hemoglobin:** < 200 mg/dL (The sponsor notes in the package insert that samples showing visible signs of hemolysis may cause interference and hemoglobin >2g/dL may lead to elevated results
**Biotin:** < 70 ng/mL.
**Lipemia:** < 400 mg/dL.
**Bilirubin:** No interference up to <66
**Cholesterol:** Cholesterol at varying levels was spiked into human serum samples containing Vitamin D concentration near 10 ng/mL. Recoveries for samples containing < 380 mg/dL cholesterol were within the manufacturers acceptance criteria of +/- 90%.
**Serum proteins:** Albumin and IgG were spiked into human serum samples at concentrations ranging from near 4 g/dL to >7 g/dL. Vitamin D in the samples ranged from near 20 ng/mL to near 45 ng/mL. Percent recovery observed up to 7 g/dL albumin was within +/- 90%.
Percent recovery for samples containing up to 3.5 g/dL IgG was within +/-10%. Higher concentrations of IgG interfered with the assay.
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# f. Assay cut-off:
Not applicable – this is a quantitative assay.
# 2. Comparison studies:
# a. Method comparison with predicate device:
A method comparison was performed with a predicate device (k110619). A total of 165 human serum samples from US blood donors were measured (in singlicate). Results of the Deming Regression analysis are presented in the following table.
| N | 165 |
| --- | --- |
| Range (ng/mL) | 7 – 58 ng/mL (13-63 ng/mL on the predicate device) |
| Slope (95% CI) | 1.01 (0.94 – 1.08) |
| Intercept (ng/mL) (95% CI) | 0.53(-1.11 – 2.18) |
| Correlation Coefficient (Pearson's r) (95% CI) | 0.92 [0.90 to 0.94] |
| Sy/x (ng/mL) | 4.6 |
# b Matrix comparison:
Anticoagulants:
The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys® Vitamin D assay was determined by comparing values obtained from samples (single donors, native as well as spiked) drawn into Serum, Li-Heparin, $\mathrm{K}_2$ -EDTA-, $\mathrm{K}_3$ -EDTA-plasma primary tubes and Li-Heparin Plasma Gel Separation Tubes. Forty serum/plasma pairs per sample material were tested with one reagent lot on one Cobas e 411 Immunoassay Analyzer. Samples range tested ranged from 5.6 to $58~\mathrm{ng / mL}$ .
| Anticoagulant | Slope | Intercept | R |
| --- | --- | --- | --- |
| K2-EDTA plasma | 0.981 | -0.485 | 0.996 |
| K3-EDTA plasma | 0.983 | -1.00 | 0.996 |
| Li Heparin | 0.996 | -0.197 | 0.997 |
| Li Heparin separation tubes | 0.980 | 0.062 | 0.998 |
# 3. Clinical studies:
a. Clinical Sensitivity: Not applicable; Clinical sensitivity and specificity is
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not typically provided in 510(k)s for this type of assay.
b. Clinical specificity: See a, above.
c. Other clinical supportive data (when a. and b. are not applicable):
# 4. Clinical cut-off:
Not applicable; this is a quantitative assay.
# 5. Expected values/Reference range:
Serum samples were prospectively collected from apparently healthy adult subjects at three geographically distinct regions of the US and tested on the Elecsys® Vitamin D during late fall season. Serum samples were first tested for calcium, magnesium and phosphate levels. To confirm normal thyroid and parathyroid functions of the consented subjects, T4, TSH, and PTH levels were also tested. Apparently healthy was defined as patients with a normal medical history (based on physical knowledge) and normal nutritional status. The subject samples with missing results, results outside of the normal range of the above analytes or results that could be affected by the interference were excluded.
A total of 560 eligible subjects from all sites were used to compute the reference intervals. The intermediate $95\%$ nonparametric reference interval was computed. The analysis was performed separately for each site. N, min, max, 2.5, 50, 97.5, median, coverage for the $95\%$ reference interval, and $90\%$ nonparametric confidence for the 2.5 and the 97.5 quantile were computed for each site.
| Site | Population | N | Mean | Median | P2.5 | P97.5 |
| --- | --- | --- | --- | --- | --- | --- |
| All sites | All | 560 | 25.53 | 24.43 | 6.36 | 49.53 |
| | No VitD Supplement Usage | 380 | 24.54 | 23.28 | 7.26 | 47.04 |
| Site 1 | All | 139 | 27.53 | 25.33 | 10.19 | 50.99 |
| | No VitD Supplement Usage | 122 | 26.83 | 24.97 | 10.19 | 50.99 |
| Site 2 | All | 149 | 25.56 | 23.80 | 8.83 | 47.04 |
| | No VitD Supplement Usage | 106 | 24.48 | 23.05 | 8.09 | 46.49 |
| Site 3 | All | 142 | 23.81 | 23.31 | 4.48 | 48.63 |
| | No VitD Supplement Usage | 49 | 20.87 | 19.04 | 4.62 | 44.45 |
| Site 4 | All | 130 | 25.25 | 24.65 | 7.26 | 52.66 |
| | No VitD Supplement Usage | 36 | 20.87 | 19.04 | 4.62 | 44.45 |
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| Site | Population | N | Mean | Median | P2.5 | P97.5 |
| --- | --- | --- | --- | --- | --- | --- |
| | No VitD Supplement Usage | 103 | 23.65 | 22.74 | 6.97 | 42.71 |
| | | | | | | |
Percent of various ethnic backgrounds at the sites are shown below:
| | African American / Black | | American Indian/Alaska Native | | Asian | | Caucasian/ White | | Other | | Unknown | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | n | % | n | % | n | % | n | % | n | % | n | % | n | % |
| Site 1 | 47 | 33.8 | 0 | 0.0 | 0 | 0.0 | 91 | 65.5 | 0 | 0.0 | 1 | 0.7 | 139 | 100.0 |
| Site 2 | 3 | 2.0 | 1 | 0.7 | 3 | 2.0 | 140 | 94.0 | 2 | 1.3 | 0 | 0.0 | 149 | 100.0 |
| Site 3 | 16 | 11.3 | 3 | 2.1 | 2 | 1.4 | 113 | 79.6 | 6 | 4.2 | 2 | 1.4 | 142 | 100.0 |
| Site 4 | 16 | 12.3 | 0 | 0.0 | 8 | 6.2 | 104 | 80.0 | 2 | 1.5 | 0 | 0.0 | 130 | 100.0 |
| Grand Total | 82 | 14.6 | 4 | 0.7 | 13 | 2.3 | 448 | 80.0 | 10 | 1.8 | 3 | 0.5 | 560 | 100.0 |
# N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
# O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
