ROCHE ELECSYS FOLATE III, ROCHE ELECSYS RBC FOLATE HEMOLYSING REAGENT, ROCHE ELECSYS FOLATE III CALSET, ROCHE ELECSYS
Device Facts
| Record ID | K082340 |
|---|---|
| Device Name | ROCHE ELECSYS FOLATE III, ROCHE ELECSYS RBC FOLATE HEMOLYSING REAGENT, ROCHE ELECSYS FOLATE III CALSET, ROCHE ELECSYS |
| Applicant | Roche Diagnostics Corp. |
| Product Code | CGN · Clinical Chemistry |
| Decision Date | Jun 19, 2009 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1295 |
| Device Class | Class 2 |
Indications for Use
Elecsys Folate III: Binding assay for the in vitro quantitative determination of folate in human serum and plasma. The binding assay is intended for use on Elecsys and cobas e immunoassay analyzers. Measurements obtained by these devices are used in the diagnosis and treatment of anemias. For in vitro diagnostic use. Elecsys RBC Folate Hemolyzing Reagent: Elecsys RBC Folate Hemolyzing Reagent is used together with the Elecsys Folate III assay for the quantitative determination of folate in erthrocytes (RBC (red blood cell) folate). Binding assay for the in vitro quantitative determination of folate in human serum and plasma. The binding assay is intended for use on Elecsys and cobas e immunoassay analyzers. Measurements obtained by these devices are used in the diagnosis and treatment of anemias. Elecsys Folate III CalSet: Elecsys Folate III CalSet is used for calibrating the quantitative Elecsys Folate III assay on the Elecsys and cobas e immunoassay analyzers. Elecsys Folate III CalCheck: Elecsys Folate III CalCheck is used for the verification of the calibration established by the Elecsys Folate III reagent on the indicated Elecsys and cobas e immunoassay analyzers. Elecsys PreciControl Anemia: Elecsys PreciControl Anemia is used for the quality control of specified Elecsys immunoassays on Elecsys and cobas e immunoassay analyzers.
Device Story
The Elecsys Folate III system is an in vitro diagnostic immunoassay for measuring folate levels in human serum, plasma, and erythrocytes. The system utilizes a competitive electrochemiluminescent immunoassay principle where sample folate competes with biotin-labeled folate for binding sites on ruthenium-labeled folate binding protein (FBP). The RBC Folate Hemolyzing Reagent is used to lyse erythrocytes in anticoagulated whole blood to liberate intracellular folate for measurement. The assay is performed on Roche Elecsys and cobas e immunoassay analyzers. Results are calculated via a 2-point calibration curve and a master curve provided by the reagent barcode. The system includes dedicated calibrators (CalSet), calibration verifiers (CalCheck), and quality control serum (PreciControl Anemia). Healthcare providers use the quantitative folate results to assist in the diagnosis and clinical management of anemia. The device is intended for professional use in clinical laboratory settings.
Clinical Evidence
Bench testing only. Precision evaluated per CLSI EP5-A2 (n=84 per sample). Linearity confirmed across 1.5-20 ng/mL (serum) and 46.5-620 ng/mL (RBC). Method comparison with predicate (n=101 serum, n=98 whole blood) showed strong correlation (r=0.963 and r=0.921 respectively). Interference testing performed for endogenous substances and common pharmaceuticals.
Technological Characteristics
Electrochemiluminescent immunoassay; competitive binding principle using ruthenium-labeled folate binding protein. Components include lyophilized human serum-based calibrators and controls (buffered with 50mM HEPES, preserved with 0.5% Bronidox L). Compatible with Elecsys 2010, cobas e 411, MODULAR ANALYTICS E170, and cobas e 601 analyzers. Measuring range 1.5-20.0 ng/mL. Connectivity via instrument-specific barcode master curves.
Indications for Use
Indicated for the quantitative determination of folate in human serum, plasma, and erythrocytes to aid in the diagnosis and treatment of anemias. For prescription use only.
Regulatory Classification
Identification
A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow.
Predicate Devices
- Elecsys Folate II Assay (k043318)
- Elecsys RBC Folate Hemolyzing Reagent (k051292)
- Elecsys Folate II CalSet II (k042490)
- Elecsys Folate II CalCheck II (k043320)
- Elecsys PreciControl Anemia (k051517)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k082340
B. Purpose for Submission:
New Device
C. Measurand:
Folate
D. Type of Test:
Quantitative immunoassay
E. Applicant:
Roche Diagnostics, Inc.
F. Proprietary and Established Names:
Roche Elecsys Folate III, Roche Elecsys RBC Folate Hemolysing Reagent, Roche Elecsys Folate III CalSet, Roche Elecsys Folate III CalCheck
G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CGN | II | 862.1295 | 75 |
| JIT | II | 862.1150 | 75 |
| JJY | I (reserved) | 862.1660 | 75 |
| JJX | I (reserved) | 862.1660 | 75 |
H. Intended Use:
1. Intended use(s):
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(1) Elecsys Folate III: Binding assay for the in vitro quantitative determination of folate in human serum and plasma. The binding assay is intended for use on Elecsys and cobas e immunoassay analyzers. Measurements obtained by these devices are used in the diagnosis and treatment of anemias. For in vitro diagnostic use.
(2) Elecsys RBC Folate Hemolyzing Reagent: Elecsys RBC Folate Hemolyzing Reagent is used together with the Elecsys Folate III assay for the quantitative determination of folate in erthrocytes (RBC (red blood cell) folate). Binding assay for the in vitro quantitative determination of folate in human serum and plasma. The binding assay is intended for use on Elecsys and cobas e immunoassay analyzers. Measurements obtained by these devices are used in the diagnosis and treatment of anemias.
(3) Elecsys Folate III CalSet: Elecsys Folate III CalSet is used for calibrating the quantitative Elecsys Folate III assay on the Elecsys and cobas e immunoassay analyzers.
(4) Elecsys Folate III CalCheck: Elecsys Folate III CalCheck is used for the verification of the calibration established by the Elecsys Folate III reagent on the indicated Elecsys and cobas e immunoassay analyzers.
(5) Elecsys PreciControl Anemia: Elecsys PreciControl Anemia is used for the quality control of specified Elecsys immunoassays on Elecsys and cobas e immunoassay analyzers.
2. Indication(s) for use:
See indications for use above
3. Special conditions for use statement(s):
For prescription use only
4. Special instrument requirements:
Roche Elecsys 2010/cobas e411
I. Device Description:
The Elecsys Folate III assay consists of the following:
Pretreatment reagent 1: Sodium 2-mercaptoethanesulfonate
Pretreatment reagent 2: Sodium hydroxide 25
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Streptavidin-coated microparticles with preservative.
R1: Ruthenium labeled folate binding protein, stabilizers and preservatives
R2: Biotinylated folate, stabilizers and preservatives
The Elecsys RBC Folate Hemolyzing reagent consists of ascorbic acid.
The Folate III Calset consists of lyophilized human serum with folic acid in two concentration ranges.
The Elecsys Folate III CalCheck consists of human serum with added folic acid at three concentration levels.
The Elecsys PreciControl Anemia consists of lyophilized human serum matrix in three concentration ranges. 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
J. Substantial Equivalence Information:
1. Predicate device name(s):
Elecsys Folate II Assay
Elecsys RBC Folate Hemolyzing Reagent
Elecsys Folate II CalSet II
Elecsys Folate II CalCheck II
Elecsys PreciControl Anemia
2. Predicate K number(s):
k043318
k051292
k042490
k043320
k051517
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3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate (k043318) |
| Assay Protocol | Electrochemiluminescent Immunoassay | Electrochemiluminescent Immunoassay |
| Instrument Platform | Roche Elecsys 2010/cobas e 411 | Roche Elecsys 2010/cobas e 411 |
| Calibration frequency | Once per reagent lot and •After 1 month when using same reagent lot •After 7 days when using same reagent kit •As required per QC findings or pertinent regulations | Once per reagent lot and •After 1 month when using same reagent lot •After 7 days when using same reagent kit •As required per QC findings or pertinent regulations |
| CalSet and CalCheck Format | Lyophilized | Lyophilized |
| Precicontrol Matrix | Human serum | Human serum |
| Precicontrol Format | Lyophilized | Lyophilized |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate (k043318) |
| Sample type | Serum/whole blood | Serum/whole blood |
| CalSet and CalCheck Matrix | Human serum preserved with 0.5% Bronidox L and buffered with 50mM HEPES | Human serum |
| Preci-control Anemia | Target values updated for Folate III assay | Target values updated for Folate II assay |
| Calibrator | Elecsys Folate III CalSet | Elecsys Folate II CalSet II |
| Control Traceability | Standardized against the Elecsys Folate II assay | Standardized against the Elecsys Folate assay |
| Measuring Range | 1.5 - 20.0 ng/mL | 0.600 - 20.00 ng/mL |
| Analytical Sensitivity | Limit of Blank = 0.640 ng/mL Limit of Detection = 1.5 ng/mL Limit of Quantitation = 2.0 ng/mL | Lower Detection Limit = 0.6 ng/mL |
K. Standard/Guidance Document Referenced (if applicable):
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CLSI EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantitation
CLSI EP05-A2, Evaluation of Precision Performance of Quantitative Measurement Methods
## L. Test Principle:
Serum samples:
First, the serum sample is incubated with the folate pretreatment reagents to release bound folate from endogenous folate binding proteins. Then, the pretreated sample is incubated with the ruthenium labeled folate binding protein and a folate complex is formed, the amount of which is dependent upon the analyte concentration in the sample. Next, streptavidin-coated microparticles and folate labeled with biotin are added and the unbound sites of the ruthenium labeled folate binding protein become occupied, with formation of a ruthenium labeled folate binding protein-folate biotin complex. The entire complex is bound to the solid phase via interaction of biotin and streptavidin. The reaction mixture is then aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are washed away and application of a voltage to the electrode induces chemiluminescent emission which is measured by a photomultiplier. Results are determined via a calibration curve.
Whole blood samples:
Whole blood treated with anticoagulants (heparin or EDTA) is diluted with ascorbic acid solution and incubated. Lysis of the erythrocytes takes place releasing the intracellular folate. The hemolysate is then used as a "pre-diluted" sample (analogously to serum) for subsequent measurement in the Elecsys Folate III assay. The hematocrit value determined in whole blood and the dilution effect brought about by pretreatment of the sample is to be taken into account when calculating the erythrocyte folate concentration.
## M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Elecsys Folate III Reagent Precision
Precision of the Elecsys Folate III reagent was evaluated on the Elecsys 2010/cobas e411 Immunoassay analyzer according to CLSI EP5-A2 guideline. The protocol consisted of testing 2 replicates of each control (PC=PreciControl) or human serum sample pools (HS=human serum) per run, 2 runs per day for 21 days. Total and within run precision was calculated according to EP5-A2. The results are summarized below.
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Within Run Precision Elecsys 2010/cobas e411
| Sample | Mean (ng/mL) | SD (ng/mL) | CV (%) | n |
| --- | --- | --- | --- | --- |
| HS Pool 1 | 3.41 | 0.239 | 7.0 | 84 |
| HS Pool 2 | 7.88 | 0.339 | 4.3 | 84 |
| HS Pool 3 | 16.6 | 0.498 | 3.0 | 84 |
| PC Anemia 2 | 7.33 | 0.415 | 5.7 | 84 |
| PC Anemia 3 | 15.8 | 0.734 | 4.7 | 84 |
Elecsys RBC Folate Hemolyzing Reagent Precision
In addition to testing precision of the Elecsys Folate III reagent, precision studies were also performed on the hemolysate application, Elecsys RBC Folate. The same protocol as described above for the serum folate application was used to test human whole blood samples with the RBC folate reagent. The results are summarized below.
Precision Elecsys 2010/cobas e411
| Sample | Mean (ng/mL) | SD (ng/mL) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Whole blood 1 | 229 | 16.1 | 7.0 | 84 |
| Whole blood 2 | 350 | 25.2 | 7.2 | 84 |
| Whole blood 3 | 481 | 34.6 | 7.2 | 84 |
Total Precision Elecsys 2010/cobas e411
| Sample | Mean (ng/mL) | SD (ng/mL) | CV (%) | n |
| --- | --- | --- | --- | --- |
| HS Pool 1 | 3.41 | 0.452 | 13.3 | 84 |
| HS Pool 2 | 7.88 | 0.550 | 7.0 | 84 |
| HS Pool 3 | 16.6 | 0.827 | 5.0 | 84 |
| PC Anemia 2 | 7.33 | 0.467 | 6.4 | 84 |
| PC Anemia 3 | 15.8 | 0.986 | 6.3 | 84 |
Within Run Precision Elecsys 2010/cobas e411
| Sample | Mean (ng/mL) | SD (ng/mL) | CV (%) | n |
| --- | --- | --- | --- | --- |
| Whole blood 1 | 229 | 12.2 | 5.3 | 84 |
| Whole blood 2 | 350 | 17.0 | 4.9 | 84 |
| Whole blood 3 | 481 | 25.7 | 5.3 | 84 |
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b. Linearity/assay reportable range:
The linearity of the Elecsys Folate III was evaluated on the Elecsys 2010/cobas e411 Immunoassay analyzer. Serum linearity was determined by diluting three high analyte level serum patient samples. Samples 1 & 2 were diluted with Elecsys Universal Diluent and Sample 3 was diluted with low analyte level serum. Mixtures of 10 different concentrations of folate were tested. The expected values were generated using the concentrations measured in the diluted and the undiluted patient sample and then applying the dilution factors. The percent recovery was determined by dividing the measured concentration with the expected concentration. The sample concentrations tested ranged from 20 ng/mL to 1.19 ng/mL. All of the results were within ≤ 0.75 ng/mL for results ≤ 5 ng/mL and ≤15% for results greater than 5 ng/mL. The results demonstrated that the assay was linear across the claimed measuring range of 1.5 to 20 ng/mL.
RBC linearity was determined by diluting one high level RBC hemolysate sample to concentrations evenly spaced across the measuring range. Eleven concentrations across the measuring range were tested. The linearity data were analyzed with regards to linear, quadratic and cubic polynomials. In a first step, a linearity check was performed with a first order (linear) regression and then with higher order models (quadratic and cubic). The result has shown that higher orders are not significant. The sample concentrations tested ranged from 0 ng/mL to 653 ng/mL. All of the results were within the sponsors acceptance criteria and demonstrated that the assay was linear across the claimed measuring range of 46.5 to 620 ng/mL. The analyzer calculates this value by automatically correcting for the 1:31 pre-dilution that occurs during the hemolysis step.
This assay has a measuring range of 1.5- 20 ng/dL for serum folate and 46.5- 620 ng/dL for RBC folate.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The CalSet, CalCheck and the PreciControl Anemia products are assayed and compared to Roche master calibrators, which are traceable to an in-house standard, and target values and ranges are assigned. Values are assigned using multiple Elecsys® 2010/ cobas e® 411 analyzers. Several runs are performed on each analyzer platform with duplicate determinations for each sample. The target value is then calculated as the median of the determined values.
Stability testing protocols and acceptance criteria were described and found to be
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acceptable. The CalSet, CalCheck, and PreciControl Anemia are stable until the expiration date printed on the vial when stored unopened at $2 - 8^{\circ}\mathrm{C}$. Reconstituted CalSet vials are stable for 5 hours at $20 - 25^{\circ}\mathrm{C}$, 3 days at $2 - 8^{\circ}\mathrm{C}$, and 3 months at $-20^{\circ}\mathrm{C}$. Reconstituted CalCheck vials are stable for 4 hours at $20 - 25^{\circ}\mathrm{C}$. PreciControl Anemia vials are stable for 8 hours at $20 - 25^{\circ}\mathrm{C}$, 5 hours on the analyzers at $20 - 25^{\circ}\mathrm{C}$, 3 days at $2 - 8^{\circ}\mathrm{C}$, and 3 months at $-20^{\circ}\mathrm{C}$.
d. Detection limit:
The Limit of Blank (LOB) and Limit of Detection (LOD) were determined in accordance with CLSI EP17-A requirements. One human serum sample pool, free of analyte, was used in the LOB experiment. Five low-level human serum samples were used in the LOD experiment. Analyte levels were determined by testing on the Elecsys 2010/cobas e411 Immunoassay analyzer. Each of these samples was evaluated $n = 60$ on multiple runs over 3 days on multiple analyzers and reagent lots. The Limit of Blank was determined as the 95th percentile of measurements of blank samples. In this case, after a top-down ranking of the 60 measured concentrations, the mean of the concentrations at position #57 and #58 = LoB = (0.632 + 0.634)/2 = 0.633 ng/mL. The LoB claim in the package insert is $0.640\mathrm{ng / mL}$. The LOD was calculated as LOD = LOB + 1.6529 x SD total = $0.633 + 1.6529 \times 0.2827 = 1.10\mathrm{ng / mL}$. In the labeling, Roche claims an LoD of $\leq 1.5\mathrm{ng / mL}$.
For calculating the limit of quantitation (LOQ), two human serum samples and three human serum sample pools (folate depleted) with concentrations ranging from 1.20 to $3.16\mathrm{ng / mL}$ were used to calculate the concentration which corresponds to an interassay coefficient of variation (CV) of $20\%$. The samples were tested once per day, for 10 days. The mean, standard deviation and coefficient of variation for each sample were calculated. As a result, by linear interpolation, a concentration of approximately $1.8\mathrm{ng / mL}$ generated a CV of $20\%$. The sponsor claims a functional sensitivity for the device of $2\mathrm{ng / mL}$.
The lower end to the RBC measuring range is defined as $46.5\mathrm{ng / mL}$ in the Package Insert. This concentration is derived from the serum/plasma Folate claimed LoD of $1.5\mathrm{ng / mL}$ (and dilution effect x31). Roche performed a functional sensitivity study. The study was performed using hemolysates on the Elecsys® 2010 / cobas e® 411 Immunoassay Analyzer. Eight hemolysates with concentrations ranging from 29.5 to $210\mathrm{ng / mL}$ were tested for 5 days, 2 runs per in singleton. The mean, standard deviation and coefficient of variation for each sample were calculated. As a result, a concentration of $54.8\mathrm{ng / mL}$ generated a CV of $15.8\%$. The claimed functional sensitivity of $2\mathrm{ng / mL}$ for serum/plasma Folate III would correspond to a calculated value of $62\mathrm{ng / mL}$ for RBC Folate (based on the dilution effect x31).
This assay has a measuring range of 1.5- 20 ng/dL for serum folate and 46.5-
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620 ng/dL for rbc folate.
# e. Analytical specificity:
The effects of interference by Biotin, Lipemia, Bilirubin, Rheumatoid Factor, Human IgG and Human IgA on the quantitation of Folate by the Elecsys Folate III assay were determined on the Elecsys 2010/cobas e411 Immunoassay Analyzer. Human serum samples, spiked with varying levels of interferent, were divided into two aliquots after collection. One aliquot was spiked with the interferent while the other aliquot was spiked with the same volume diluent. The interferent spiked sample was then diluted into the unspiked aliquot in $10\%$ increments. Percent recovery was calculated by comparing the measured folate concentration to the expected folate initial concentration. The sponsor defined significant interference as greater than $+/-0.5 \mathrm{ng/mL}$ , absolute deviation for samples $<= 5 \mathrm{ng/mL}$ and greater than $+/-10\%$ recovery for samples $>5 \mathrm{ng/mL}$ . The following results were obtained
| Endogenous Substances | Concentration Showing No Interference |
| --- | --- |
| Bilirubin | 33 mg/dL |
| Biotin | 21 ng/mL |
| Intralipid | 1500 mg/dL |
| IgG | 16 g/L |
| IgA | 4 g/L |
The labeling states the following regarding hemoglobin interference: Hemolysis may significantly increase folate values due to high concentrations of folate in red blood cells. Therefore, hemolyzed serum samples are not suitable for use in this assay.
18 commonly used pharmaceuticals were examined for potential effect on folate determination by the Folate III test system. Each drug was added to folate serum samples in two defined concentrations and the resulting samples were tested in triplicate using the Elecsys 2010/cobas e411 Immunoassay Analyzer. The median value was compared to the reference value (folate sample with no drug added) and the deviation from the reference value was calculated. The sponsor defined interference as $+/-$ 3SD of the reference value or $+/-$ 10% if the 3SD range $< +/-$ 10%. The results showed not significant interference at the concentrations below.
| Drug Substances | Concentration Showing No Interference |
| --- | --- |
| Acetylcystein | 1662 mg/L |
| Biotin | 2100 mg/L |
| Intralipid | 1500 mg/dL |
| IgG | 16 g/L |
| IgA | 4 g/L |
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| Ampicillin-Na | 1000 mg/ L |
| --- | --- |
| Ascorbic acid | 60 mg/ L |
| Ca- Dobesilate | 200 mg/L |
| Cyclosporine | 20 mg/L |
| Cefoxitin | 660 mg/L |
| Heparin | 5000 U |
| Levodopa | 20 mg/L |
| Methyldopa | 20 mg/L |
| Metronidazole | 200 mg/L |
| Phenylbutazone | 400 mg/L |
| Doxycyclin | 50 mg/L |
| Acetylsalicylic Acid | 1000 mg/L |
| Rifampicin | 60 mg/L |
| Acetaminophen | 200 mg/L |
| Ibuprofen | 700 mg/L |
| Theophyllin | 100 mg/L |
| Human Erythropoietin | 2000 U |
f. Assay cut-off:
Not applicable
2. Comparison studies:
a. Method comparison with predicate device:
A method comparison study was performed by analyzing 101 serum samples ranging from $1.76\mathrm{ng / mL}$ to $20\mathrm{ng / mL}$ with the submitted Folate III assay and the previously cleared Folate II assay on the Elecsys 2010. Linear regression analysis was performed with the following results:
$$
\mathrm {y} = 1. 0 5 \mathrm {x} - 0. 4 0 \quad \mathrm {r} = 0. 9 6 3
$$
RBC Hemolysate:
A method comparison study was performed by analyzing 98 fresh whole blood samples ranging from $162 - 620\mathrm{ng / mL}$ (with values corrected for dilution factor (31)) with the submitted RBC Hemolysate Folate III assay and the previously cleared RBC Hemolysate Folate II assay on the Elecsys 2010/e411. Passing-Bablok and linear regression analysis was performed with the following results:
$$
\mathrm {y} = 1. 0 9 6 \mathrm {x} - 3. 8 7 4 \quad \mathrm {r} = 0. 9 2 1
$$
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b. Matrix comparison:
A matrix comparison study between matched K3-EDTA and Na-heparin hemolysate (whole blood samples diluted with ascorbic acid) was performed with the Elecsys Folate III Immunoassay on the Elecsys 2010 / cobas e 411 Immunoassay Analyzer. The results of the study show that the two anticoagulants have comparable performance across the measuring range. The samples tested had folate concentrations ranging from 101 - 588 ng/mL. Passing/Bablock regression analysis was performed with the following results:
$$
Y = 1.00 - 1.16
$$
$$
r = 0.992
$$
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable
b. Clinical specificity:
Not applicable
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable
4. Clinical cut-off:
Not applicable
5. Expected values/Reference range:
The reference interval for serum samples tested on the Elecsys 2010/cobas e411 (with N=261) was 7.3 - 26.1 ng/mL (2.5th - 97.5th percentile) with a median value of 14.0 ng/mL. The sample donors tested had homocysteine concentrations <15 umol/L, were between 18 and 65 years old, were apparently healthy and were fasting. Exclusion criteria were: pregnant and lactating women, body mass index >30 and subjects who take vitamins on the day of sample collection.
The data obtained in this reference interval study verifies data reported by The American Journal of Clinical Nutrition. The American Journal of Clinical Nutrition data is provided in the labeling as an additional reference.
Elecsys RBC Folate Hemolyzing Reagent
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The 262 Whole blood samples collected in this study were tested using the Elecsys RBC Folate Hemolyzing Reagent in combination with the Elecsys Folate III assay. As reported in the labeling, samples were tested on the Elecsys 2010/cobas e411 Immunoassay analyzer.
The reference interval for the Elecsys 2010/cobas e411 Immunoassay analyzer for whole blood was 499 - 1504 ng/mL (2.5th - 97.5th percentile) with a median value of 902 ng/mL. The sample donors tested had homocysteine concentrations <15 umol/L, were between 18 and 65 years old, were apparently healthy and were fasting. Exclusion criteria were: pregnant and lactating women, body mass index >30 and subjects who take vitamins on the day of sample collection.
For both studies, the Elecsys Folate III and the Elecsys RBC Folate, samples from the same 129 men and 133 women were tested.
## 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.
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