(120 days)
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No
The summary describes a standard immunoassay and analyzer, with no mention of AI or ML in the device description, intended use, or performance studies. The analysis focuses on traditional analytical performance characteristics and comparisons to predicate and reference methods.
No.
This device is an in vitro diagnostic assay intended for the quantitative determination of total 25-hydroxyvitamin D to assess vitamin D sufficiency. It does not provide any therapeutic intervention.
Yes
Explanation: The "Intended Use / Indications for Use" section states that the assay is "intended for the quantitative determination of total 25-hydroxyvitamin D in human serum and plasma" and "to be used as an aid in the assessment of vitamin D sufficiency in adults." This is a clear indication that the device measures a biological marker to assist in a medical assessment, which is the definition of a diagnostic device.
No
The device is an in vitro diagnostic assay (reagent kit) intended for use on a specific immunoassay analyzer (cobas e 411). It involves chemical reactions and the use of physical components (reagents, calibrators, controls) to measure a substance in a biological sample. While the analyzer itself likely contains software, the device being described in this summary is the assay kit, which is a hardware/chemical component.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the Elecsys Vitamin D total II assay is intended for the quantitative determination of total 25-hydroxyvitamin D in human serum and plasma. This is a test performed on biological samples in vitro (outside the body) to provide information about a patient's health status.
- Device Description: The "Device Description" further clarifies that it is an "in vitro quantitative determination" assay.
- Components: The description includes components like CalSet (calibrator), PreciControl (quality control), and CalCheck (calibration verification), which are typical components of IVD systems used to ensure the accuracy and reliability of the test results.
- Performance Studies: The extensive list of performance studies (Precision, Analytical Sensitivity, Linearity, Interferences, Method Comparison, Stability) are all standard evaluations required for IVD devices to demonstrate their analytical and clinical performance.
- Predicate Device: The mention of a "Predicate Device" (K113546; Elecsys Vitamin D Assay) is common in regulatory submissions for IVDs, where a new device is compared to a previously cleared device.
All of these points strongly indicate that the Elecsys Vitamin D total II assay and its associated components are intended for use as an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Elecsys Vitamin D total II
The Elecsys Vitamin D total II 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. The electrochemiluminescence binding assay is intended for use on the cobas e 411 immunoassay analyzer.
CalSet Vitamin D total II
CalSet Vitamin D total II is used for calibrating the quantitative Elecsys Vitamin D total II assay on the cobas e 411 immunoassay analyzer.
PreciControl Vitamin D total II
PreciControl Vitamin D total II is used for quality control of the Elecsys Vitamin D total II assay on the cobas e 411 immunoassay analyzer.
CalCheck Vitamin D total II
This CalCheck set is an assayed control for use in calibration verification of the assay range established by the Elecsys Vitamin D total II reagent on the cobas e 411 immunoassay analyzer.
Product codes (comma separated list FDA assigned to the subject device)
MRG, JIT, JJX
Device Description
Elecsys Vitamin D total II is a second generation assay by Roche Diagnostics for the in vitro quantitative determination of 25-hydroxyvitamin D in human serum and plasma. It is intended for use on the cobas e 411 immunoassay analyzer. The cobas e family of analyzers employs the electrochemiluminescence "ECLIA" technology. The assay is a 27 minute assay utilizing a competition principle and a pretreatment step to release the bound 25-hydroxyvitamin D from the vitamin D binding protein.
Results are determined via a calibration curve which is instrument specifically generated by 2-point calibration against the master curve for that reagent lot.
Reagents
The Elecsys Vitamin D total II reagent working solutions include:
- Pretreatment rackpack (kit placed on instrument) .
- Pretreatment Reagent 1 (Dithiothreitol) -
- Pretreatment Reagent 2 (Sodium hydroxide) -
- Rackpack (kit placed on instrument) .
- -Streptavidin-coated microparticles
- -Reagent 1 (ruthenium labeled vitamin D binding protein)
- Reagent 2 (biotinylated 25-hydroxyvitamin D) -
Calibrator
The assay will be calibrated using the CalSet Vitamin D total II, which is a two concentration level set of lyophilized human serum matrix that are traceable to the ID-LC-MS/MS 25-hydroxyvitamin D Reference Measurement Procedure. The ID-LC-MS/MS is traceable to the National Institute of Standards and Technology Standard Reference Material 2972. The CalSet includes:
- Cal 1 (approximately 2 ng/mL 25-hydroxyvitamin D in human serum matrix) .
- Cal 2 (approximately 45 ng/mL 25-hydroxyvitamin D in human serum matrix) .
Control
PreciControl Vitamin D total II is used for the quality control verification of the performance of the assay on the cobas e 411 analyzer. The control materials are lyophilized serum based on human serum in two concentration ranges.
Calibration Verification Materials
CalCheck Vitamin D total II is used for the calibration verification and the assessment of the measuring range as needed by the laboratory certification agencies such as College of American Pathologists or CLIA certification. The CalChecks are a customer convenience product and not required to assess the performance.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
Not Found
Anatomical Site
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Indicated Patient Age Range
Adults
Intended User / Care Setting
Not Found
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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Non-clinical performance evaluation for Elecsys Vitamin D total II executed with the study briefly summarized.
Precision
Precision was evaluated on a single cobas e 411 analyzer according to CLSI guideline EP5-A3 using one reagent lot for evaluation. The protocol consisted of testing 2 replicates of each of two levels of control, PreciControl Vitamin D total II and five human sera per run, 2 runs per day for 21 days. The samples were run in randomized order on the cobas e 411 analyzer. Serum samples used were all single donors (native as well as spiked).
Results:
Repeatability:
HS1: mean 11.1 ng/mL, SD 0.725 ng/mL, CV 6.6%
HS2: mean 20.8 ng/mL, SD 0.849 ng/mL, CV 4.1%
HS3: mean 25.6 ng/mL, SD 0.774 ng/mL, CV 3.0%
HS4: mean 47.5 ng/mL, SD 0.749 ng/mL, CV 1.6%
HS5: mean 92.6 ng/mL, SD 1.76 ng/mL, CV 1.9%
Intermediate:
HS1: mean 11.1 ng/mL, SD 0.965 ng/mL, CV 8.7%
HS2: mean 20.8 ng/mL, SD 1.09 ng/mL, CV 5.2%
HS3: mean 25.6 ng/mL, SD 1.43 ng/mL, CV 5.6%
HS4: mean 47.5 ng/mL, SD 1.77 ng/mL, CV 3.7%
HS5: mean 92.6 ng/mL, SD 2.40 ng/mL, CV 2.6%
Analytical Sensitivity
Limit of Blank (LoB): Experimental Design included three reagent lots evaluated on one cobas e 411 analyzer, six runs over three or more days with one blank sample with ten replicates per run. The zero-level (blank) sample used was a Vitamin D depleted human serum sample pool. In total, 60 determinations for analyte free samples have been obtained. The LoB was calculated according to CLSI EP17-A2. Result: 2 ng/mL
Limit of Detection (LoD): Experimental Design included three reagent lots evaluated on one cobas e 411 analyzer, six runs over three or more days with five samples with two replicates/sample/run. The five samples were low-level human serum sample pools (diluted). A pooled estimate of the precision (SD total) for the 5 low-level samples was calculated. The LoD was calculated according to CLSI EP17-A2. Result: 3 ng/mL
Limit of Quantitation (LoQ): Experimental Design included three reagent lots evaluated on one cobas e 411 analyzer, one run per day over five days. Five replicates per each sample per run with at least four low level samples of serum, Li -heparin, K2-EDTA and K3-EDTA plasma and 25 replicates/sample/reagent lot. The mean value and the intermediate precision (CV) and standard deviation (SD) for each LoQ sample were calculated. LoQ samples were sorted according to the concentration of their measured mean value. LoQ is defined as the mean value of that sample which is the first that fulfills the specification for the intermediate precision and for which no sample with higher concentration exists that exceeds this specification. Result: 5 ng/mL
Linearity/Assay Reportable Range
The linearity study was conducted on the Elecsys Vitamin D total II assay to demonstrate that measurements across the claimed measuring range for each parameter are linear. The study was performed according to CLSI guideline EP6-A using serum and plasma samples on the cobas e 411 immunoassay analyzer. A high analyte serum and K3-EDTA plasma sample (single donors, spiked) was diluted with a depleted low analyte human serum. At least 9 concentrations (dilutions) throughout the measuring range were prepared. Samples were assayed in 3-fold determination within a single run. The linearity data were analyzed with regards to linear, quadratic and cubic polynomials according to CLSI EP6-A. Measuring Range: 5 - 100 ng/mL.
High Dose Hook Effect
The high-dose hook effect of the Elecsys Vitamin D total II assay was assessed on the cobas e 411 analyzer in two-fold determination. One human serum sample was spiked with analyte to achieve a high 25-OH Vitamin D concentration of approx. 10,000 ng/mL. A dilution series was performed using a low level analyte (Vitamin D depleted) serum. The hook concentration reported corresponds to the highest analyte concentration that generates a signal within the primary measuring range of the assay.
Human Anti-Mouse Antibodies (HAMA)
The effect of the presence of human anti-mouse antibodies on the Elecsys Vitamin D total II assay was assessed on the cobas e 411 immunoassay analyzer. The specified HAMA-serum (HAMA L2) and the related basis serum (without interferent) was measured in two-fold determination each. Recovery of the HAMA-serum compared to the basis serum was calculated.
Endogenous Interferences
Hemolysis/Bilirubin/Lipemia/Biotin: The purpose of this study was to evaluate endogenous substances for potential interference with the parameters measured with the Elecsys Vitamin D total II on the cobas e 411 immunoassay analyzer using human serum samples (single donors, native as well as spiked). For each interfering substance three human serum samples containing low, mid and high concentrations of 25-OH Vitamin D were tested in accordance with CLSI EP07-A2. Results:
Hemolysis ≤ 600 mg/dL
Bilirubin ≤ 66 mg/dL
Intralipid ≤ 300 mg/dL
Biotin ≤ 30 ng/mL
Serum albumin ≤ 7 g/dL
Cholesterol ≤ 300mg/dL
Triglyceride ≤ 300 mg/dL
Rheumatoid Factor 10 times higher concentration as typically found in native serum. Results from these spiked serum samples were matched against the unspiked references and the % cross-reactivity (normalized and nonnormalized) was calculated. The analysis was done in nmol/L to take into account i) the different molecular weights of the vitamin D metabolites and ii) the 1:1 equimolar binding of metabolite and vitamin D binding protein. Results:
25-hydroxyvitamin D3: 100%
25-hydroxyvitamin D2: 93.7%
24, 25-dihydroxyvitamin D3: 13.7%
3-epi-25-hydroxyvitamin D3: 112.8%
3-epi-25-hydroxyvitamin D2: 91.4%
Exogenous Interferences – Drugs
The effect on quantitation of analyte in the presence of drugs was determined by comparing values obtained from samples spiked with 16 commonly and 3 specially used pharmaceutical compounds with the reference sample (unspiked). Two human serum samples (single donors, native as well as spiked) were used and tested on the cobas e 411 immunoassay analyzer. The analyte concentration of the samples were approximately 30 and 70 ng/mL. The drug concentrations tested are according to the recommendation (if available) given in the CLSI guideline EP7-A2. When concentrations are not given in the guideline, concentrations of at least 3-times of the maximum recommended daily dose were tested. The two serum samples were divided into aliquots and spiked with the potential interferents. The reference sample without interferent was spiked with the respective amount of solvent only. The Elecsys Vitamin D total II concentration of the spiked aliquots was determined in 10-fold determination and compared to the Vitamin D total II result determined for the reference aliquot (also in 10-fold determination) on one cobas e 411 immunoassay analyzer.
Sample Matrix Comparison
The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys Vitamin D total II Immunoassay was determined by comparing values obtained from samples (single donors - native, diluted as well as spiked) drawn into serum, Li-Heparin, K2-EDTA- , K3-EDTA-plasma primary tubes and Plasma Gel Separation Tubes (Li-Heparin). A minimum of 40 serum/plasma pairs per sample material were tested in singleton with one reagent lot on one cobas e 411 immunoassay analyzer. Potential effects are assessed by Passing/Bablok regression analysis. Sample Anticoagulants: Li-heparin, K2-EDTA, K3-EDTA, PST tubes for corresponding plasma types. Sample Type/Matrix: Human serum, plasma.
Method Comparison to Predicate
A method comparison was performed using the Elecsys Vitamin D total II assay (candidate device, Y) and the Elecsys Vitamin D Assay (predicate device, X) to assess the bias between the two assays (for information only). A total of 105 serum samples (single donors, native) were measured in singleton on the cobas e 411 analyzer in one run covering the entire measuring range. Vitamin D values ranged between 6.1 and 55.9 ng/mL for the Reference Method (X) according to the recommendations of CLSI EP9-A2.
Results: Passing Bablok y = 0.867x + 0.724, T = 0.840.
Method Comparison to Reference Method
A total of 111 native single donor patient serum samples (reference sample set provided by the Vitamin D Standardization and Certification Program with assigned values by the RMP at CDC, independent from the samples used for standardization) were measured in singleton on the cobas e 411 analyzer in one run covering the entire measuring range. 25-hydroxyvitamin D values ranged between 5.64 and 92.8 ng/mL for the Reference Method.
Results: Passing Bablok y = 0.937x - 0.360, T = 0.902.
Reagent Stability
Three studies were executed with two studies completed including:
- Study 1: Reagent stability after first opening at 2-8°C (56 days) .
- Study 2: On board reagent stability (28 days) .
- Study 3: A real-time stability study is ongoing to support shelf-life stability claim. .
Reagent Stability After First Opening: Reagent stability after first opening for the Elecsys Vitamin D total II assay was tested on one cobas e 411 immunoassay analyzer. A fresh reagent rackpack was placed on the analyzer and calibrated. Reference values for the samples tested were determined. After initial measurement the kit was removed from the analyzer and kept at 2-8 °C up to 64 days. After 64 days the kit was placed on the analyzer again, calibrated and the test samples were determined. Samples tested in duplicate include five human serum (HS) samples and two controls (PreciControl Vitamin D total II) for run qualification. The human serum samples used were all single donors (native as well as spiked).
On-board Reagent Stability: Reagent On-board Stability for the Elecsys Vitamin D total II assay was tested on one cobas e 411 immunoassay analyzer. A fresh Reagent Rack-Pack was placed on the analyzer and calibrated. All samples were measured on day 0. On day 8, 15, 22, 29 and day 36, the same samples were measured with the same reagent kit kept at 20℃ ± 3℃ (on-board condition) using the calibration curves established on day 0, 8, 15, 22 and 29, respectively. Samples tested include five human serum (HS) samples and two controls (PreciControl Vitamin D total II) for run qualification. Each sample was tested in two-fold determination. The human serum samples used were all single donors (native as well as spiked).
Real-time Stability: In the ongoing real-time stability study, the Elecsys Vitamin D total II reagent is stored at 2-8°C. The stored assay reagents are tested at time point T=0 (after manufacturing) and at specified intervals over the shelf life of the device up to the planned shelf life plus one month. Testing will be performed using three human serum samples (stored at -80°C). The average on-test recovery value will be calculated as percent recovery compared to the reference value measured at T=0 for the human serum samples.
Calibrator Stability
Five studies were performed in order to verify the stability claims for the CalSet Vitamin D total II.
- Study 1: Stability at -20℃ after reconstitution .
- Study 2: Stability at 2-8°C after reconstitution .
- Study 3: On-board stability at 20-25℃ after reconstitution .
- . Study 4: Accelerated stability at 35°C
- Study 4: Real-time stability .
Stability at -20°C after reconstitution: The on-test and reference materials were tested in duplicate on the cobas e 411 immunoassay analyzer. The on-test material was reconstituted and stored in closed vials for 14 weeks at -20°C. The on-test signal recovery was calculated as percent of the reference value.
Stability at 2-8°C after reconstitution: The on-test and reference materials were tested in duplicate on the cobas e 411 immunoassay analyzer. The on-test material was reconstituted and stored in closed vials for 73 hours at 2-8°C. The on-test signal recovery was calculated as percent of the reference value.
On-board stability at 20-25°C after reconstitution: The on-test and reference materials were tested in duplicate on the cobas e 411 immunoassay analyzer. The on-test material was reconstituted and stored in open vials for 7 hours at 20-25°C. The on-test signal recovery was calculated as percent of the reference value.
Accelerated stability at 35°C: The on-test and reference materials were tested in duplicate on the cobas e 411 immunoassay analyzer. The on-test material was stored lyophilized (as supplied to the user) at 35°C for 3 weeks. The reference material was a set of CalSet Vitamin D total II (stored at 2 - 8°C). After 3 weeks, the on-test and reference materials were tested in duplicate. The on-test signal recovery was calculated as a percent of the reference value.
Real-time stability: In the on-going real-time stability study, the CalSet Vitamin D total II test material is stored at 2-8°C. The CalSets are tested in duplicate at specified intervals over the shelf life of the device up to the planned shelf life plus one month (16 months). Real-time stability is calculated based on the recovery of signal of stressed calibrator (stored at 2-8°C) vs. unstressed calibrator (stored at -80°C). At the specified intervals over the shelf life, the mean value of the stressed calibrator was calculated as percent recovery of the unstressed value (each tested in duplicates at the same time point).
PreciControl Vitamin D total II Stability
Three studies were performed in order to verify the stability claims for the PreciControl Vitamin D total II.
- Study 1: Stability after Reconstitution .
- Study 2: Accelerated Stability .
- Study 3: Real-time Stability .
Stability after reconstitution: The on-test and reference materials were tested in duplicate. The on-test material was reconstituted and stored for 32 days at -20℃, 73 hours at 2 - 8℃ and for 6 hours at 20 - 25℃. The reference material was freshly reconstituted PreciControl Vitamin D total II stored at 2 – 8°C. The deviation of the on-test material compared to the reference value was calculated. The PreciControl Vitamin D total II was evaluated in duplicate on the cobas e 411 immunoassay analyzer.
Accelerated Stability: The on-test material was stored lyophilized (as supplied to the user) at 35°C for 3 weeks. The reference material was PreciControl Vitamin D total II stored at 2 - 8℃. After 3 weeks, the ontest and reference material was tested in duplicate. The deviation of the on-test material compared to the reference value was calculated. The PreciControl Vitamin D total II was evaluated in duplicate on the cobas e 411 immunoassay analyzer.
Real-time Stability: In the on-going real-time stability study, the PreciControl Vitamin D total II on-test material is stored at 2 - 8°C. The controls are tested at specified intervals over the shelf life of the device up to the planned shelf life plus one month. Data for the time-points after manufacturing, 7, 10, 13 and 16 months tested in duplicate will be available. The deviation of the on-test material compared to the reference value (stored at -80°C) will be calculated.
Calibration Stability
Two studies were completed, including:
- . Study 1: Lot calibration stability
- Study 2: On-board calibration stability .
Lot Calibration Stability: Calibration of an Elecsys Vitamin D total II reagent lot is recommended every 12 weeks (3 months). During that time period fresh reagent kits of the same lot can be used without calibration using the calibration curve of the day 0 reagent kit. Elecsys Vitamin D total II was calibrated with a fresh reagent kit on day 0 using a cobas e 411 immunoassay analyzer. After 13 weeks a new reagent kit of the same lot was used and recovery of samples was determined using the calibration curve of day 0. Five human serum (HS) samples and two controls (PreciControl Vitamin D total II) for run qualification were tested; each sample was tested with two-fold determination. Pools of human serum samples were used (native as well as spiked).
On-board Calibration Stability: Elecsys Vitamin D total II reagent kits can be stored on board of the analyzers for up to 7 days without a new calibration. Reagent On-board Calibration stability for the Elecsys Vitamin D total II assay was tested on one cobas e 411 immunoassay analyzer. A fresh Reagent Rack-Pack was placed on the analyzer and calibrated. All samples were measured on day 0. On day 8 the same samples were measured with the same reagent kit kept at 20°C ± 3°C (on-board condition) using the calibration curve established on day 0. Samples tested include five human serum (HS) samples and two controls (PreciControl Vitamin D total II) for run qualification. Each sample was tested in two-fold determination. Pools of human serum samples were used (native as well as spiked).
CalCheck Vitamin D total II Stability
Two studies were performed in order to verify the stability claims for the CalCheck Vitamin D total II.
- Study 1: Open Vial Stability .
- Study 2: Accelerated Stability .
- Study 3: Real-time Stability .
Open Vial Stability: The on-test and reference materials were tested in duplicate. The on-test material was reconstituted and stored for 6 hours at 25℃ (in an open vial). The reference material was a freshly reconstituted set of CalChecks. The on-test recovery was calculated as a percent of the reference value.
Accelerated Stability: The on-test material was stored lyophilized (as supplied to the user) at 35°C for 3 weeks. The reference material was a set of CalChecks (stored at 2-8°C). After 3 weeks, the test and reference materials were tested in duplicate. The on-test recovery was calculated as a percent of the reference value. One CalCheck Vitamin D total II lot was evaluated in duplicate on the cobas e 411 immunoassay analyzer.
Real-time Stability: In the on-going real-time stability study, the CalCheck Vitamin D total II test material is stored at 2-8°C. The CalChecks are tested at T=0 and at specified intervals over the shelf life of the device up to the planned shelf life plus one month. For the lot stability, data for the time-points at 0, 7, 13 and 19 months tested in duplicate will be available. The average on-test recovery value will be calculated as percent recovery compared to the unstressed reference value (stored at -20°C).
Sample Stability
No new data was collected using the Elecsys Vitamin D total II assay. Sample stability data generated with the Elecsys Vitamin D Assay (K113546) is applicable since the claims and sample materials did not change (sample stability is not dependent on assay reagent formulation).
External (Clinical) Testing
Clinical samples were collected at three US sites in order to establish the reference range values for the Elecsys Vitamin D total II assay. Serum samples were prospectively collected from approximately 200 apparently healthy adults at each of the three locations (northern site, midwest site and southern site) during summer and winter seasons (totaling approximately 600 Study Subjects). Study subjects were pre-screened to exclude subjects taking supplements or various drugs, those who were over or under weight, those with a medical history that might suggest variations in bone health, and pregnant and lactating women. Conditions such as parathyroid or thyroid disorders, and kidney disease, as well as electrolyte composition were determined by testing the samples. Those samples with properties outside of the published reference range for the particular test were excluded from the calculation of the Elecsys Vitamin D total II reference range study. They were assayed with Elecsys Vitamin D total II on the cobas e 411 immunoassay analyzer.
The Reference Interval for the total population of the Elecsys Vitamin D total II assay is 7.61 - 55.5 ng/mL.
N = 421, Mean = 25.8, Median = 23.6, 2.5th Percentile = 7.61 (90% CI 6.11, 8.44), 97.5th Percentile = 55.5 (90% CI 52.4, 64.5).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
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Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Elecsys Vitamin D Assay (K113546)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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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Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, stacked on top of each other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
February 8, 2017
ROCHE DIAGNOSTICS LINDA MCCAMMACK REGULATORY PROGRAM MANAGER 9115 HAGUE ROAD INDIANAPOLIS IN 46250
Re: K162840
Trade/Device Name: Elecsys Vitamin D total II. CalSet Vitamin D total II. CalCheck Vitamin D total II, PreciControl Vitamin D total II Regulation Number: 21 CFR 862.1825 Regulation Name: Vitamin D test system Regulatory Class: II Product Code: MRG, JIT, JJX Dated: December 22, 2016 Received: December 23, 2016
Dear Linda McCammack:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Katherine Serrano -S
For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K162840
Device Name Elecsys Vitamin D total II CalCheckVitamin D total II CalSet Vitamin D total II PreciControl Vitamin D total II
Indications for Use (Describe)
Elecsys Vitamin D total II
The Elecsys Vitamin D total II 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. The electrochemiluminescence binding assay is intended for use on the cobas e 411 immunoassay analyzer.
CalSet Vitamin D total II
CalSet Vitamin D total II is used for calibrating the quantitative Elecsys Vitamin D total II assay on the cobas e 411 immunoassay analyzer.
PreciControl Vitamin D total II
PreciControl Vitamin D total II is used for quality control of the Elecsys Vitamin D total II assay on the cobas e 411 immunoassay analyzer.
CalCheck Vitamin D total II
This CalCheck set is an assayed control for use in calibration verification of the assay range established by the Elecsys Vitamin D total II reagent on the cobas e 411 immunoassay analyzer.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
|---|---|
| --------------------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------- |
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Elecsys Vitamin D total II 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k).
The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the Elecsys Vitamin D total II Test System.
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| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague Road |
| P.O. Box 50416 | |
| Indianapolis, IN 46250-0457 | |
| Contact | Linda McCammack |
| Phone: (317) 521-7144 | |
| FAX: (317) 521-2324 | |
| Email: linda.mccammack@roche.com | |
| Date Prepared | September 19, 2016 |
| Proprietary Name | 1- Elecsys Vitamin D total II |
| 2-CalSet Vitamin D total II | |
| 3- PreciControl Vitamin D total II | |
| 4- CalCheck Vitamin D | |
| Common Name | 1-Vitamin D total |
| 2 -CalSet Vitamin D total II | |
| 3 - PreciControl Vitamin D total II | |
| 4 - CalCheck Vitamin D | |
| Classification Name | 1 - System, Test, Vitamin D, |
| 2 - Calibrator, Secondary, | |
| 3 - Single (Specified) Analyte Controls (Assayed and Unassayed), | |
| 4 - Single (Specified) Analyte Controls (Assayed and Unassayed) | |
| Product Codes, | |
| Regulation Numbers | 1 -MRG, 862.1825 |
| 2- JIT, 862.1150 | |
| 3- JJX, 862.1660 | |
| 4- JJX, 862.1660 | |
| Predicate Devices | Elecsys Vitamin D Assay (K113546) |
| Establishment Registration | For the Elecsys Vitamin D total II, the establishment registration numbers: |
| Roche Diagnostics GmbH in Mannheim, Germany is 9610126, | |
| Roche Diagnostics Penzberg, Germany is 9610529 | |
| Roche Diagnostics in the United States is 1823260 |
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DEVICE DESCRIPTION 1.
Elecsys Vitamin D total II is a second generation assay by Roche Diagnostics for the in vitro quantitative determination of 25-hydroxyvitamin D in human serum and plasma. It is intended for use on the cobas e 411 immunoassay analyzer. The cobas e family of analyzers employs the electrochemiluminescence "ECLIA" technology. The assay is a 27 minute assay utilizing a competition principle and a pretreatment step to release the bound 25-hydroxyvitamin D from the vitamin D binding protein.
Results are determined via a calibration curve which is instrument specifically generated by 2-point calibration against the master curve for that reagent lot.
Reagents 1.1.
The Elecsys Vitamin D total II reagent working solutions include:
- Pretreatment rackpack (kit placed on instrument) .
- Pretreatment Reagent 1 (Dithiothreitol) -
- Pretreatment Reagent 2 (Sodium hydroxide) -
- Rackpack (kit placed on instrument) .
- -Streptavidin-coated microparticles
- -Reagent 1 (ruthenium labeled vitamin D binding protein)
- Reagent 2 (biotinylated 25-hydroxyvitamin D) -
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1.2. Calibrator
The assay will be calibrated using the CalSet Vitamin D total II, which is a two concentration level set of lyophilized human serum matrix that are traceable to the ID-LC-MS/MS 25-hydroxyvitamin D Reference Measurement Procedure. The ID-LC-MS/MS is traceable to the National Institute of Standards and Technology Standard Reference Material 2972. The CalSet includes:
- Cal 1 (approximately 2 ng/mL 25-hydroxyvitamin D in human serum matrix) .
- Cal 2 (approximately 45 ng/mL 25-hydroxyvitamin D in human serum matrix) .
1.3. Control
PreciControl Vitamin D total II is used for the quality control verification of the performance of the assay on the cobas e 411 analyzer. The control materials are lyophilized serum based on human serum in two concentration ranges.
1.4. Calibration Verification Materials
CalCheck Vitamin D total II is used for the calibration verification and the assessment of the measuring range as needed by the laboratory certification agencies such as College of American Pathologists or CLIA certification. The CalChecks are a customer convenience product and not required to assess the performance.
INTENDED USE 2.
Following are the Intended Uses for the Elecsys Vitamin D total II Test System.
Elecsys Vitamin D total II 2.1.
The Elecsys Vitamin D total II 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. The electrochemiluminescence binding assay is intended for use on the cobas e 411 immunoassay analyzer.
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CalSet Vitamin D total II 2.2.
CalSet Vitamin D total II is used for calibrating the quantitative Elecsys Vitamin D total II assay on the cobas e 411 immunoassay analyzer.
PreciControl Vitamin D total II 2.3.
PreciControl Vitamin D total II is used for quality control of the Elecsys Vitamin D total II assay on the cobas e 411 immunoassay analyzer.
2.4. CalCheck Vitamin D total II
The CalCheck set 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 total II reagent on the cobas e 411 immunoassay analyzer.
TECHNOLOGICAL CHARACTERISTICS 3.
Elecsys Vitamin D total II utilizes electrochemiluminescence "ECLIA" technology for the quantitative determination of 25-hydroxyvitamin D for the assessment of vitamin D sufficiency on the cobas e 411 immunoassay analyzer.
The following tables compare the Elecsys Vitamin D total II with its predicate device, Elecsys Vitamin D Assay (K113546).
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Assay Comparison Table 1:
| Feature | Predicate Device:
Elecsys Vitamin D Assay (K113546) | Candidate Device:
Elecsys Vitamin D total II |
|--------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use/
Indications for Use | This Vitamin D assay in 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. The electrochemiluminescence
binding assay is intended for use on Elecsys
and cobas e immunoassay analyzers. | This 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. The
electrochemiluminescence binding assay is
intended for use on the cobas e 411
immunoassay analyzer. |
| Assay Method | Competition principle binding protein | Same |
| Detection Method | Electrochemiluminescence | Same |
| Applications/Test
Time | 27 minutes | Same |
| Instrument Platform | Elecsys 2010, MODULAR ANALYTICS
E170, cobas e 411, cobas e 601, and
cobas e 602 | cobas e 411 |
| Sample/Reagent Ratio | 15 µL / 185 µL | 20 µL / 180 µL |
| Sample Type/Matrix | Human serum, plasma | Same |
| Sample Anticoagulants | Li-heparin, K2-EDTA, K3-EDTA,
Li-heparin PST. | Li-heparin, K2-EDTA,
K3-EDTA, PST tubes for corresponding
plasma types. |
| Calibrator | Vitamin D CalSet | CalSet Vitamin D total II |
| Calibration Method | 2-point calibration based on master curve for
specific reagent lot | Same |
| Calibration Interval | Calibration must be performed once per
reagent lot using fresh reagent ( 60.0 ng/mL
• 42.0 - > 60.0 ng/mL | Approximate target concentrations:
• ≤ 5 ng/mL
• 17.5 - 22.4 ng/mL
• 46.5 - 54.4 ng/mL
• 75.5 - 84.4 ng/mL
• 94.5 - > 100 ng/mL |
| Format | Lyophilized | Same |
| Handling | Reconstitute the contents of Check 1, Check 2,
Check 3, Check 4 and Check 5 with exactly 1.0
mL distilled or deionized water. Allow the
bottles to stand closed for 15 minutes. Mix
gently by inversion to ensure homogeneity. | Same |
| Storage and Stability | Reconstituted control serum:
• At 20-25°C – 5 hours | Same |
NON-CLINICAL PERFORMANCE EVALUATION 4.
Non-clinical performance evaluation for Elecsys Vitamin D total II executed with the study briefly summarized.
4.1. Precision
Repeatability and Intermediate Precision 4.1.1.
Precision was evaluated on a single cobas e 411 analyzer according to CLSI guideline EP5-A3 using one reagent lot for evaluation. The protocol consisted of testing 2 replicates of each of two levels of control, PreciControl Vitamin D total II and five human sera per run, 2 runs per day for 21 days. The samples were run in randomized order on the cobas e 411 analyzer. Serum samples used were all single donors (native as well as spiked).
Analytical Sensitivity 4.2.
Limit of Blank (LoB) 4.2.1.
Experimental Design included three reagent lots evaluated on one cobas e 411 analyzer, six runs over three or more days with one blank sample with ten replicates per run. The zero-level (blank) sample used was a Vitamin D depleted human serum sample pool. In total, 60 determinations for analyte free samples have been obtained. The LoB was calculated according to CLSI EP17-A2.
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4.2.2. Limit of Detection (LoD)
Experimental Design included three reagent lots evaluated on one cobas e 411 analyzer, six runs over three or more days with five samples with two replicates/sample/run. The five samples were low-level human serum sample pools (diluted). A pooled estimate of the precision (SD total) for the 5 low-level samples was calculated. The LoD was calculated according to CLSI EP17-A2.
Limit of Quantitation (LoQ) 4.2.3.
Experimental Design included three reagent lots evaluated on one cobas e 411 analyzer, one run per day over five days. Five replicates per each sample per run with at least four low level samples of serum, Li -heparin, K2-EDTA and K3-EDTA plasma and 25 replicates/sample/reagent lot.
The mean value and the intermediate precision (CV) and standard deviation (SD) for each LoQ sample were calculated.
LoQ samples were sorted according to the concentration of their measured mean value. LoQ is defined as the mean value of that sample which is the first that fulfills the specification for the intermediate precision and for which no sample with higher concentration exists that exceeds this specification.
Linearity/Assay Reportable Range 4.3.
The linearity study was conducted on the Elecsys Vitamin D total II assay to demonstrate that measurements across the claimed measuring range for each parameter are linear. The study was performed according to CLSI guideline EP6-A using serum and plasma samples on the cobas e 411 immunoassay analyzer.
A high analyte serum and K3-EDTA plasma sample (single donors, spiked) was diluted with a depleted low analyte human serum. At least 9 concentrations (dilutions) throughout the measuring range were prepared. Samples were assayed in 3-fold determination within a single run.
The linearity data were analyzed with regards to linear, quadratic and cubic polynomials according to CLSI EP6-A.
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High Dose Hook Effect 4.4.
The high-dose hook effect of the Elecsys Vitamin D total II assay was assessed on the cobas e 411 analyzer in two-fold determination. One human serum sample was spiked with analyte to achieve a high 25-OH Vitamin D concentration of approx. 10,000 ng/mL. A dilution series was performed using a low level analyte (Vitamin D depleted) serum. The hook concentration reported corresponds to the highest analyte concentration that generates a signal within the primary measuring range of the assay.
Human Anti-Mouse Antibodies (HAMA) 4.5.
The effect of the presence of human anti-mouse antibodies on the Elecsys Vitamin D total II assay was assessed on the cobas e 411 immunoassay analyzer.
The specified HAMA-serum (HAMA L2) and the related basis serum (without interferent) was measured in two-fold determination each. Recovery of the HAMA-serum compared to the basis serum was calculated.
Endogenous Interferences 4.6.
Hemolysis/Bilirubin/Lipemia/Biotin 4.6.1.
The purpose of this study was to evaluate endogenous substances for potential interference with the parameters measured with the Elecsys Vitamin D total II on the cobas e 411 immunoassay analyzer using human serum samples (single donors, native as well as spiked).
For each interfering substance three human serum samples containing low, mid and high concentrations of 25-OH Vitamin D were tested in accordance with CLSI EP07-A2.
Triglycerides Interference 4.6.2.
One aliguot of each serum sample was spiked with the interfering substance (Triglyceride concentrate), another aliquot was spiked with the same volume of isotonic NaCl solution (dilution pool). The interfering pool was then diluted into the dilution pool in 10% increments. The recovery for each sample was calculated by comparison to the reference sample.
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Rheumatoid Factors Interference 4.6.3.
One aliquot of each serum sample was spiked with the interfering substance, and another aliquot with the same volume of the solvent (buffer matrix) of the interfering substance (dilution pool). The interfering pool was then diluted into the dilution pool in 10% increments. The recovery for each sample was calculated by comparison to the reference sample.
Total Protein/Albumin/Immunoglobulin (IgG)/Cholesterol Interference 4.6.4.
One aliquot of each serum sample was spiked with the interfering substances. Another aliquot without any additives (since the interfering substance is a lyophilisate) is used as dilution pool. The interfering pool was then diluted into the dilution pool in 10% increments.
Analytical Specificity/Cross-Reactivity 4.7.
A cross-reactivity study was conducted according to CLSI-EP7-A2 to evaluate the potential cross-reactivity of the assay with other vitamin D metabolites that occur in the human body during anabolism and catabolism. The potential cross-reactants were added at defined concentrations to native human sera with approximate 25-hydroxyvitamin D concentrations of 25, 40 and 60 ng/mL and analyzed with Elecsys Vitamin D total II on the cobas e 411analyzer. The concentrations of the cross-reactants where chosen i) to ensure results within the measuring range depending on their expected cross-reactivity and ii) to reflect at least a >10 times higher concentration as typically found in native serum. Results from these spiked serum samples were matched against the unspiked references and the % cross-reactivity (normalized and nonnormalized) was calculated.
The analysis was done in nmol/L to take into account i) the different molecular weights of the vitamin D metabolites and ii) the 1:1 equimolar binding of metabolite and vitamin D binding protein.
4.8. Exogenous Interferences – Drugs
The effect on quantitation of analyte in the presence of drugs was determined by comparing values obtained from samples spiked with 16 commonly and 3 specially used pharmaceutical compounds with the reference sample (unspiked). Two human serum samples (single donors,
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native as well as spiked) were used and tested on the cobas e 411 immunoassay analyzer. The analyte concentration of the samples were approximately 30 and 70 ng/mL.
The drug concentrations tested are according to the recommendation (if available) given in the CLSI guideline EP7-A2. When concentrations are not given in the guideline, concentrations of at least 3-times of the maximum recommended daily dose were tested.
The two serum samples were divided into aliquots and spiked with the potential interferents.
The reference sample without interferent was spiked with the respective amount of solvent only.
The Elecsys Vitamin D total II concentration of the spiked aliquots was determined in 10-fold determination and compared to the Vitamin D total II result determined for the reference aliquot (also in 10-fold determination) on one cobas e 411 immunoassay analyzer.
Sample Matrix Comparison 4.9.
The effect on quantitation of analyte in the presence of anticoagulants with the
Elecsys Vitamin D total II Immunoassay was determined by comparing values obtained from samples (single donors - native, diluted as well as spiked) drawn into serum, Li-Heparin, K2-EDTA- , K3-EDTA-plasma primary tubes and Plasma Gel Separation Tubes (Li-Heparin).
A minimum of 40 serum/plasma pairs per sample material were tested in singleton with one reagent lot on one cobas e 411 immunoassay analyzer. Potential effects are assessed by Passing/Bablok regression analysis.
4.10. Method Comparison to Predicate
A method comparison was performed using the Elecsys Vitamin D total II assay (candidate device, Y) and the Elecsys Vitamin D Assay (predicate device, X) to assess the bias between the two assays (for information only).
A total of 105 serum samples (single donors, native) were measured in singleton on the cobas e 411 analyzer in one run covering the entire measuring range. Vitamin D values ranged between 6.1 and 55.9 ng/mL for the Reference Method (X) according to the recommendations of CLSI EP9-A2.
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4.11. Method Comparison to Reference Method
A total of 111 native single donor patient serum samples (reference sample set provided by the Vitamin D Standardization and Certification Program with assigned values by the RMP at CDC, independent from the samples used for standardization) were measured in singleton on the cobas e 411 analyzer in one run covering the entire measuring range. 25-hydroxyvitamin D values ranged between 5.64 and 92.8 ng/mL for the Reference Method.
4.12. Reagent Stability
To test reagent stability, three studies were executed with two studies completed including:
- Study 1: Reagent stability after first opening at 2-8°C (56 days) .
- Study 2: On board reagent stability (28 days) .
- Study 3: A real-time stability study is ongoing to support shelf-life stability claim. .
4.12.1. Reagent Stability After First Opening
Reagent stability after first opening for the Elecsys Vitamin D total II assay was tested on one cobas e 411 immunoassay analyzer. A fresh reagent rackpack was placed on the analyzer and calibrated. Reference values for the samples tested were determined. After initial measurement the kit was removed from the analyzer and kept at 2-8 °C up to 64 days. After 64 days the kit was placed on the analyzer again, calibrated and the test samples were determined. Samples tested in duplicate include five human serum (HS) samples and two controls (PreciControl Vitamin D total II) for run qualification. The human serum samples used were all single donors (native as well as spiked).
4.12.2. On-board Reagent Stability
Reagent On-board Stability for the Elecsys Vitamin D total II assay was tested on one cobas e 411 immunoassay analyzer. A fresh Reagent Rack-Pack was placed on the analyzer and calibrated. All samples were measured on day 0. On day 8, 15, 22, 29 and day 36, the same samples were measured with the same reagent kit kept at 20℃ ± 3℃ (on-board condition) using the calibration curves established on day 0, 8, 15, 22 and 29, respectively. Samples tested include
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five human serum (HS) samples and two controls (PreciControl Vitamin D total II) for run qualification. Each sample was tested in two-fold determination. The human serum samples used were all single donors (native as well as spiked).
4.12.3. Real-time Stability
In the ongoing real-time stability study, the Elecsys Vitamin D total II reagent is stored at 2-8°C. The stored assay reagents are tested at time point T=0 (after manufacturing) and at specified intervals over the shelf life of the device up to the planned shelf life plus one month. Testing will be performed using three human serum samples (stored at -80°C). The average on-test recovery value will be calculated as percent recovery compared to the reference value measured at T=0 for the human serum samples.
4.13. Calibrator Stability
Five studies were performed in order to verify the stability claims for the CalSet Vitamin D total II.
- Study 1: Stability at -20℃ after reconstitution .
- Study 2: Stability at 2-8°C after reconstitution .
- Study 3: On-board stability at 20-25℃ after reconstitution .
- . Study 4: Accelerated stability at 35°C
- Study 4: Real-time stability .
4.13.1. Stability at -20°C after reconstitution
The on-test and reference materials were tested in duplicate on the cobas e 411 immunoassay analyzer. The on-test material was reconstituted and stored in closed vials for 14 weeks at -20°C. The on-test signal recovery was calculated as percent of the reference value.
4.13.2. Stability at 2-8°C after reconstitution
The on-test and reference materials were tested in duplicate on the cobas e 411 immunoassay analyzer. The on-test material was reconstituted and stored in closed vials for 73 hours at 2-8°C. The on-test signal recovery was calculated as percent of the reference value.
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4.13.3. On-board stability at 20-25°C after reconstitution
The on-test and reference materials were tested in duplicate on the cobas e 411 immunoassay analyzer. The on-test material was reconstituted and stored in open vials for 7 hours at 20-25°C. The on-test signal recovery was calculated as percent of the reference value.
4.13.4. Accelerated stability at 35°C
The on-test and reference materials were tested in duplicate on the cobas e 411 immunoassay analyzer. The on-test material was stored lyophilized (as supplied to the user) at 35°C for 3 weeks. The reference material was a set of CalSet Vitamin D total II (stored at 2 - 8°C). After 3 weeks, the on-test and reference materials were tested in duplicate. The on-test signal recovery was calculated as a percent of the reference value.
4.13.5. Real-time stability
In the on-going real-time stability study, the CalSet Vitamin D total II test material is stored at 2-8°C. The CalSets are tested in duplicate at specified intervals over the shelf life of the device up to the planned shelf life plus one month (16 months).
Real-time stability is calculated based on the recovery of signal of stressed calibrator (stored at 2-8°C) vs. unstressed calibrator (stored at -80°C). At the specified intervals over the shelf life, the mean value of the stressed calibrator was calculated as percent recovery of the unstressed value (each tested in duplicates at the same time point).
4.14. PreciControl Vitamin D total II
4.14.1. Value Assignment
The PreciControl Vitamin D total II assigned values are determined with the Elecsys Vitamin D total II assay. A native human serum sample panel (single donors) with RMP-assigned target values (RMP = Reference Measurement Procedure: ID-LC-MS/MS of the University of Ghent) is used for Reference Standardization to assign values to the Master Calibrators (sample curve consisting of human serum samples from single donors covering the entire measuring range). These Master Calibrators are for routine use in subsequent standardizations. The assigned values for PreciControl Vitamin D total II are read from the master calibration curve.
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Values are assigned for each lot of PreciControl Vitamin D total II in combination with each assay reagent lot available. The controls are run in duplicate on at least two (2) modules of the master analyzer platform. The assigned value of each control level is defined as the median value obtained over at least six (6) determinations of the respective control level.
4.14.2. Stability
Three studies were performed in order to verify the stability claims for the PreciControl Vitamin D total II.
- Study 1: Stability after Reconstitution .
- Study 2: Accelerated Stability .
- Study 3: Real-time Stability .
4.14.2.1. Stability after reconstitution
The on-test and reference materials were tested in duplicate. The on-test material was reconstituted and stored for 32 days at -20℃, 73 hours at 2 - 8℃ and for 6 hours at 20 - 25℃. The reference material was freshly reconstituted PreciControl Vitamin D total II stored at 2 – 8°C. The deviation of the on-test material compared to the reference value was calculated. The PreciControl Vitamin D total II was evaluated in duplicate on the cobas e 411 immunoassay analyzer.
4.14.2.2. Accelerated Stability
The on-test material was stored lyophilized (as supplied to the user) at 35°C for 3 weeks. The reference material was PreciControl Vitamin D total II stored at 2 - 8℃. After 3 weeks, the ontest and reference material was tested in duplicate. The deviation of the on-test material compared to the reference value was calculated. The PreciControl Vitamin D total II was evaluated in duplicate on the cobas e 411 immunoassay analyzer.
4.14.2.3. Real-time Stability
In the on-going real-time stability study, the PreciControl Vitamin D total II on-test material is stored at 2 - 8°C. The controls are tested at specified intervals over the shelf life of the device up
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to the planned shelf life plus one month. Data for the time-points after manufacturing, 7, 10, 13 and 16 months tested in duplicate will be available. The deviation of the on-test material compared to the reference value (stored at -80°C) will be calculated.
4.15. Calibration Stability
To test calibration stability, two studies were completed, including:
- . Study 1: Lot calibration stability
- Study 2: On-board calibration stability .
- 4.15.1. Lot Calibration Stability
Calibration of an Elecsys Vitamin D total II reagent lot is recommended every 12 weeks (3 months). During that time period fresh reagent kits of the same lot can be used without calibration using the calibration curve of the day 0 reagent kit. Elecsys Vitamin D total II was calibrated with a fresh reagent kit on day 0 using a cobas e 411 immunoassay analyzer. After 13 weeks a new reagent kit of the same lot was used and recovery of samples was determined using the calibration curve of day 0. Five human serum (HS) samples and two controls (PreciControl Vitamin D total II) for run qualification were tested; each sample was tested with two-fold determination. Pools of human serum samples were used (native as well as spiked).
4.15.2. On-board Calibration Stability
Elecsys Vitamin D total II reagent kits can be stored on board of the analyzers for up to 7 days without a new calibration. Reagent On-board Calibration stability for the Elecsys Vitamin D total II assay was tested on one cobas e 411 immunoassay analyzer. A fresh Reagent Rack-Pack was placed on the analyzer and calibrated. All samples were measured on day 0. On day 8 the same samples were measured with the same reagent kit kept at 20°C ± 3°C (on-board condition) using the calibration curve established on day 0. Samples tested include five human serum (HS) samples and two controls (PreciControl Vitamin D total II) for run qualification. Each sample was tested in two-fold determination. Pools of human serum samples were used (native as well as spiked).
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4.16. CalCheck Vitamin D total II
The CalCheck Vitamin D total II matrix, human serum, is identical to the Master Calibrators (human serum sample panel) used for the Elecsys Vitamin D total II assay.
4.16.1. Value Assignment
For each CalCheck Vitamin D total II lot manufactured, the CalChecks are run in duplicate on at least two (2) modules with at least two runs. The assigned value of each CalCheck is defined as the median value obtained over at least six (6) determinations (runs) of the respective CalCheck.
4.16.2. Stability
Two studies were performed in order to verify the stability claims for the CalCheck Vitamin D total II.
- Study 1: Open Vial Stability .
- Study 2: Accelerated Stability .
- Study 3: Real-time Stability .
4.16.2.1. Open Vial Stability
The on-test and reference materials were tested in duplicate. The on-test material was reconstituted and stored for 6 hours at 25℃ (in an open vial). The reference material was a freshly reconstituted set of CalChecks. The on-test recovery was calculated as a percent of the reference value.
4.16.2.2. Accelerated Stability
The on-test material was stored lyophilized (as supplied to the user) at 35°C for 3 weeks. The reference material was a set of CalChecks (stored at 2-8°C). After 3 weeks, the test and reference materials were tested in duplicate. The on-test recovery was calculated as a percent of the reference value. One CalCheck Vitamin D total II lot was evaluated in duplicate on the cobas e 411 immunoassay analyzer.
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4.16.2.3. Real-time Stability
In the on-going real-time stability study, the CalCheck Vitamin D total II test material is stored at 2-8°C. The CalChecks are tested at T=0 and at specified intervals over the shelf life of the device up to the planned shelf life plus one month. For the lot stability, data for the time-points at 0, 7, 13 and 19 months tested in duplicate will be available. The average on-test recovery value will be calculated as percent recovery compared to the unstressed reference value (stored at -20°C).
4.17. Sample Stability
No new data was collected using the Elecsys Vitamin D total II assay. Sample stability data generated with the Elecsys Vitamin D Assay (K113546) is applicable since the claims and sample materials did not change (sample stability is not dependent on assay reagent formulation).
EXTERNAL (CLINICAL) TESTING 5.
Clinical samples were collected at three US sites in order to establish the reference range values for the Elecsys Vitamin D total II assay. Serum samples were prospectively collected from approximately 200 apparently healthy adults at each of the three locations (northern site, midwest site and southern site) during summer and winter seasons (totaling approximately 600 Study Subjects). Study subjects were pre-screened to exclude subjects taking supplements or various drugs, those who were over or under weight, those with a medical history that might suggest variations in bone health, and pregnant and lactating women. Conditions such as parathyroid or thyroid disorders, and kidney disease, as well as electrolyte composition were determined by testing the samples. Those samples with properties outside of the published reference range for the particular test were excluded from the calculation of the Elecsys Vitamin D total II reference range study. They were assayed with Elecsys Vitamin D total II on the cobas e 411 immunoassay analyzer.
The Reference Interval for the total population of the Elecsys Vitamin D total II assay is 7.61 - 55.5 ng/mL. The established reference ranges for Elecsys Vitamin D total II are provided below in Table 5.
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| N | Mean | Median | 2.5th Percentile
(90 % CIª) | 97.5th Percentile
(90 % CI) | Units |
|-----|------|--------|--------------------------------|--------------------------------|-------|
| 421 | 25.8 | 23.6 | 7.61
(6.11, 8.44) | 55.5
(52.4, 64.5) | ng/mL |
| Table 5: Results of 2.5th and 97.5th Percentiles for Elecsys Vitamin D total II | ||
|---|---|---|
| -- | --------------------------------------------------------------------------------- | -- |
a) Confidence interval
CONCLUSIONS 6.
The information provided in this 510(k) Premarket Notification will support a determination of substantial equivalence for Elecsys Vitamin D total II, CalSet Vitamin D total II, PreciControl Vitamin D total II and CalCheck Vitamin D total II. The data supports a safe, effective device which performs as well or better than the predicate devices.