Transferrin
Device Facts
| Record ID | K190495 |
|---|---|
| Device Name | Transferrin |
| Applicant | Biosystems S.A. |
| Product Code | DDG · Immunology |
| Decision Date | Mar 16, 2020 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.5880 |
| Device Class | Class 2 |
Indications for Use
Reagents for the measurement of transferrin concentration in human serum or plasma. The obtained values are useful as an aid in the diagnosis of iron deficiency anemia and hemochromatosis. This reagent is for use in the BioSystems BA analyzers.
Device Story
Transferrin assay uses turbidimetric principle to measure transferrin concentration in human serum or plasma samples. Input consists of patient sample mixed with goat anti-human transferrin antibodies; antigen-antibody complexes precipitate, causing light scattering proportional to transferrin concentration. Device is intended for use on BioSystems BA400 analyzers in clinical laboratory settings. Healthcare providers use quantitative output to assist in diagnosing iron deficiency anemia and hemochromatosis. System requires external protein calibrators for curve preparation.
Clinical Evidence
No clinical trials performed. Evidence consists of analytical bench testing: precision (CLSI EP05-A3), linearity (CLSI EP06-A), interference (CLSI EP07-A3), and detection limits (CLSI EP17-A2). Method comparison against predicate using 84 serum and 69 Li-heparin plasma samples showed high correlation (R² 0.993 and 0.997 respectively). Matrix equivalency confirmed with 40 paired samples.
Technological Characteristics
Turbidimetric immunoassay. Reagents: imidazole buffer, sodium azide, goat anti-human transferrin antibodies. Measuring range: 12–520 mg/dL. Traceable to ERM-DA470k/IFCC. Requires BioSystems BA400 analyzer. Shelf-life: 26 months at 2–8°C. On-board stability: 2 months.
Indications for Use
Indicated for the quantitative measurement of transferrin in human serum or plasma to aid in the diagnosis of iron deficiency anemia and hemochromatosis. For prescription use only.
Regulatory Classification
Identification
A transferrin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the transferrin (an iron-binding and transporting serum protein) in serum, plasma, and other body fluids. Measurement of transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders, such as iron deficiency anemia.
Predicate Devices
- Tina-quant Transferrin Ver.2 (K012393)
Submission Summary (Full Text)
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Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
I Background Information:
A 510(k) Number
K190495
B Applicant
BioSystems S.A.
C Proprietary and Established Names
Transferrin
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DDG | Class II | 21 CFR 866.5880 - Transferrin immunological test system | IM - Immunology |
II Submission/Device Overview:
A Purpose for Submission:
New Device
B Measurand:
Transferrin
C Type of Test:
Quantitative, Turbidimetry
III Intended Use/Indications for Use:
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A Intended Use(s):
See Indications for Use below.
B Indication(s) for Use:
Reagents for the measurement of transferrin concentration in human serum or plasma. The obtained values are useful as an aid in the diagnosis of iron deficiency anemia and hemochromatosis. This reagent is for use in the BioSystems BA analyzers.
C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
D Special Instrument Requirements:
BioSystems BA400 analyzer
IV Device/System Characteristics:
A Device Description:
The Transferrin assay consists of the following reagents:
A Reagent: 60 mL/vial, imidazole buffer 0.05 mol/L, sodium azide 0.95 g/L, pH 7.5.
B Reagent: 15 mL/vial, goat anti-human transferrin antibodies, sodium azide 0.95 g/L
Additional materials required but not provided are protein calibrators (BioSystems cod. 31075). The set contains 5 different levels and it should be used to prepare the calibration curve. The calibrators are supplied ready to use.
These reagents are intended to be used with the BioSystems BA analyzers.
B Principle of Operation:
The Transferrin reagent is a turbidimetric assay in which the transferrin in the sample precipitates in the presence of anti-human transferrin antibodies. The light scattering of the antigen-antibody complexes is proportional to the transferrin concentration and can be measured by turbidimetry.
V Substantial Equivalence Information:
A Predicate Device Name(s):
Tina-quant Transferrin Ver.2
B Predicate 510(k) Number(s):
K012393
C Comparison with Predicate(s):
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| Device & Predicate Device(s): | K190495 Device | K012393 Predicate |
| --- | --- | --- |
| Device Trade Name | Transferrin | TRSF2 Tina-quant Transferrin ver.2 |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Reagents for the measurement of transferrin concentration in human serum or plasma. The obtained values are useful as an aid in the diagnosis of iron deficiency anemia and hemochromatosis. This reagent is for use in the BioSystems BA analyzers. | In vitro test for the quantitative determination of transferrin in human serum and plasma on Roche/Hitachi cobas c systems. |
| Measurand | Transferrin | Same |
| Method | Immunological agglutination | Same |
| Assay type | Quantitative | Same |
| Traceability | ERM-DA470k/IFCC | Same |
| Sample Type | Serum and Li-heparin plasma | Same |
| General Device Characteristic Differences | | |
| Analyzer | BioSystems BA400 | Cobas c 311, 501/502 |
| Antibody soruce | Goat anti-human transferrin | Rabbit anti-human transferrin |
| Measuring range | 12 – 520 mg/dL | 10 – 520 mg/dL |
VI Standards/Guidance Documents Referenced:
CLSI EP05-A3, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Third Edition
CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition
CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline - Third Edition
CLSI EP07-A3 Interference Testing in Clinical Chemistry
VII Performance Characteristics (if/when applicable):
A Analytical Performance:
1. Precision/Reproducibility:
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Precision of the Ferritin assay was evaluated according to CLSI EP05-A3. Five different levels of human serum patient samples were used to carry out precision, with concentrations of 20.4 mg/dL, 123 mg/dL, 225 mg/dL, 402 mg/dL and 466 mg/dL. The study was conducted over 20 days, with two runs per day and two replicates per specimen, for a total of 80 measurements. The same five samples were used to assess lot-to-lot and instrument-to-instrument imprecision. For the lot-to-lot imprecision assessment, the study was conducted over five days, with two runs per day and with two replicates per one, using three reagent lots and one analyzer. For the instrument-to-instrument imprecisions assessment, the study was conducted over five days, with two runs per day and with two replicates per run, using three analyzers and one reagent lot. The results are summarized in the table below:
| Sample | Mean (mg/dL) | Within-Run | | Between-Run | | Between-Day | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| 1 | 20.4 | 0.52 | 2.6 | 1.3 | 6.2 | 1.4 | 6.7 | 0.73 | 3.6 |
| 2 | 123 | 1.1 | 0.9 | 2.3 | 1.9 | 2.6 | 2.1 | 1.3 | 1.1 |
| 3 | 225 | 1.5 | 0.7 | 4.5 | 2.0 | 4.7 | 2.1 | 2.9 | 1.3 |
| 4 | 402 | 7.2 | 1.8 | 8.9 | 2.2 | 11.4 | 2.8 | 7.4 | 1.8 |
| 5 | 466 | 8.1 | 1.7 | 9.3 | 2.0 | 12.3 | 2.7 | 7.0 | 1.5 |
| Sample | Mean (mg/dL) | Between-lot | | Between-Instrument | |
| --- | --- | --- | --- | --- | --- |
| | | SD | CV (%) | SD | CV (%) |
| 1 | 20.4 | 2.2 | 6.6 | 1.2 | 6.3 |
| 2 | 123 | 4.2 | 7.2 | 1.5 | 1.3 |
| 3 | 225 | 6.2 | 4.3 | 7.7 | 3.6 |
| 4 | 402 | 7.1 | 2.3 | 19.2 | 5.2 |
| 5 | 466 | 11.6 | 2.4 | 22.0 | 5.0 |
2. Linearity:
Linearity was evaluated according to CLSI guideline EP6-A. A dilution series with nine levels was prepared by diluting a high sample with a concentration of 641 mg/dL with the low concentration sample of 0 mg/dL to cover the measuring range. The results are summarized as follows:
| Analyte | Test Range | Slope (95% CI) | Intercept (95% CI) | R² |
| --- | --- | --- | --- | --- |
| Transferrin | 0–641 mg/dL | 1.01 (0.999–1.029) | -0.83 (-5.50–3.84) | 0.999 |
3. Analytical Specificity/Interference:
An interference study was performed in accordance with CLSI EP07-A3 guideline. Two human serum samples with two different analyte concentrations (178 mg/dL and 425 mg/dL) were spiked with increasing concentrations of potential endogenous and exogenous interferents and analyzed in duplicate.
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No significant assay interference effects were observed in serum when tested with hemoglobin (500 mg/dL), unconjugated bilirubin (30 mg/dL), conjugated bilirubin (30 mg/dL), triglycerides (1625 mg/dL), rheumatoid factor (300 IU/mL), acetaminophen (20 mg/dL), ascorbic acid (30 mg/dL), N-acetyl-L-cysteine (10 mg/L), heparin (3000 U/L), deferoxamine (250 mg/L), dobesilate (200 mg/L), ampicillin (152 μmol/L), levodopa (20 mg/L), acetylsalicylic acid (3.62 mmol/L), ferrous sulfate (1.0 mmol/L), rifampicin (60 mg/L), EDTA (3.4 μmol/L), valproic acid (3467 μmol/L), phenylbutazone (400 mg/L), theophylline (222 μmol/L), cholesterol (13 mmol/L), metronidazole (701 μmol/L), prednisone (0.84 μmol/L), and methotrexate (2 mmol/L).
## Antigen Excess/Prozone Effect:
A study was performed to verify the prozone performance on the BioSystems BA400 analyzer. A total of 11 samples with different analyte concentrations were evaluated. No prozone effect was observed up to 3000 mg/dL.
## 4. Assay Reportable Range:
Transferrin: 12–520 mg/dL
## 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
### Traceability:
The calibration of the assay is traceable to ERM-DA470k/IFCC.
### Stability:
Real-time stability testing was conducted using human serum level samples with concentrations of 200 mg/dL and 400 mg/dL. Eight time points were tested, 0, 1, 3, 6, 10, 14, 20, 26 and 41 months. The results from this study support a shelf-life of 26 months when stored at the recommended storage temperature of 2–8°C.
Real-time stability study was carried out with open-vial reagents. Therefore, the results support the open-vial reagent shelf-life of 26 months when stored at the recommended storage temperature of 2–8°C.
On-board stability study supports reagent stability of up to 2 months when kept in the refrigerated compartment of the analyzer.
## 6. Detection Limit:
Detection capabilities studies for each analyte were evaluated based upon CLSI EP17-A2 guideline.
Limit of blank (LoB) study was performed by testing five blank samples comprised of albumin matrix. Samples were tested in replicates of four per run, one run per day for three days using two reagent lots, for a total of 60 observations per reagent lot, and for a total of 120 observations.
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Limit of detection (LoD) study was performed by testing five native serum samples with analyte concentrations close to expected detection limit for each analyte. Samples were tested in replicates of four per run, one run per day for three days using two reagent lots, for a total of 60 observations per reagent lot, and for a total of 120 observations.
Limit of Quantitation (LoQ) study was performed using five native serum samples. Samples were tested in replicates of four per run, one run per day for three days using two reagent lots, for a total of 60 observations per reagent lot, and for a total of 120 observations.
The results are as follows:
| Detection Limit Parameter | Transferrin (mg/dL) |
| --- | --- |
| LoB | 0.49 |
| LoD | 1.18 |
| LoQ | 12.0 |
7. Assay Cut-Off:
Not applicable
B Comparison Studies:
1. Method Comparison with Predicate Device:
A total of 84 human serum samples with transferrin concentrations across the assay measuring range were tested compared to the predicate device. Another study was conducted using a total of 69 human Li-heparin plasma samples with transferrin concentration covering the measuring range compared to the predicate device.
Passing Bablok regression analysis was performed to evaluate the analytical equivalence of the transferrin assay when compared to the predicate. The results are summarized as follows:
| Matrix | N | Range | Slope (95% CI) | Intercept (95% CI) | R² |
| --- | --- | --- | --- | --- | --- |
| Serum | 84 | 75.4–504 | 0.95 (0.92–0.98) | 7.91 (1.48–14.33) | 0.993 |
| Li-heparin plasma | 69 | 61.1–494.0 | 0.97 (0.95–0.99) | -0.01 (-4.81–4.31) | 0.997 |
2. Matrix Comparison:
Matrix comparison study was carried out using 40 paired specimens of serum and lithium-heparin plasma, across the assay measuring range. The results of the Passing-Bablok regression analysis support the equivalency of the two matrices, and are as follows:
| N | Slope (95% CI) | Intercept (95% CI) | R² |
| --- | --- | --- | --- |
| 40 | 0.94 (0.93–0.95) | 2.18 (0.42–5.63) | 0.999 |
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C Clinical Studies:
1. Clinical Sensitivity:
Not applicable
2. Clinical Specificity:
Not applicable
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable
D Clinical Cut-Off:
Not applicable
E Expected Values/Reference Range:
Transferrin (serum or plasma): 200–360 mg/dL
The reference range was verified by testing 20 apparently healthy subjects.
This range is given for orientation only, and each lab should establish their own reference range.
VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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