(79 days)
Not Found (The document states "The Bayer Immuno 1 Ferritin Assay originally received 510(k) clearance when the system was first released in 1990." but does not provide the K number for this original clearance or any specific predicate device for the current submission, which is a change to an already cleared device.)
Not Found
No
The device description and performance studies focus on a standard immunoassay method and statistical analysis, with no mention of AI or ML.
No
This device is an in vitro diagnostic method intended to quantitatively measure ferritin in human serum to aid in the diagnosis of diseases; it does not provide any therapeutic function.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended to quantitatively measure ferritin (an iron-storage protein) in human serum" and that "Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism." This clearly defines it as an in vitro diagnostic method.
No
The device description clearly outlines a physical immunoassay method involving reagents, incubation, magnetic particles, washing, and photometric measurement on the Bayer Immuno 1 System, indicating it is a hardware-based in vitro diagnostic device, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "This in vitro diagnostic method is intended to quantitatively measure ferritin... in human serum... Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism..."
This clearly indicates that the device is intended for use outside of the body (in vitro) to analyze a human sample (serum) for the purpose of aiding in the diagnosis of diseases. This aligns directly with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
This in vitro diagnostic method is intended to quantitatively measure ferritin (an iron-storage protein) in human serum on the Bayer Immuno 1 System. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency anemia.
This diagnostic method is not intended for use on any other system.
Product codes (comma separated list FDA assigned to the subject device)
DBF
Device Description
The Bayer Immuno 1 Ferritin (FER) Method uses a homogenous sandwich immunoassay format. Samples are reacted with Ferritin Antibody Conjugate R1 (Antibody linked to FITC) and Ferritin Antibody Conjugate R2 (Antibody linked to calf intestine alkaline phosphatase) and incubated on the Immuno 1 system at 37°C. The anti-Ferritin antibody conjugates combine with sample ferritin to form a sandwich complex, followed by addition of monoclonal Immuno-Magnetic particle (mIMP) Reagent binds the antibody which After further incubacomplexes. tion, the mIMP/antibody complex is washed and a para-nitrophenyl phosphate substrate, which reacts with the enzyme conjugate, is added. The resulting paranitrophenoxide is monitored at 405 nm and 450 nm using a filter switch protocol. The dose/ response curve is proportional to the amount of ferritin in the sample.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
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Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
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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)
Imprecision:
- Estimates of imprecision were obtained from replicate analyses of human serum (Pools 1 & 2) and Bayer TEST point Ligand Controls (Controls 1 to 3) and then compared to Method Sheet recoveries using the current L6 Calibrator.
- Precision estimates using the 2500 ng/mL L6 calibrator were generated over 5 days using four replicates per day.
- Key results presented in Table 2 for both proposed and current calibrator sets, showing %CV values. For proposed: Pool-1 (mean 25.2, total %CV 2.6), Control 1 (mean 28.8, total %CV 2.2), Control 2 (mean 104.6, total %CV 1.3), Pool-2 (mean 206.7, total %CV 4.1), Control 3 (mean 237.4, total %CV 2.5).
Analytical Sensitivity:
- Estimated using Level 1 data from a performance study comparing multiple systems, reagents, and calibrator sets.
- Defined as two times the within-run standard deviation of the zero calibrator.
- Determined to be 0.3 ng/mL, unchanged from the current expected value.
Correlation/Methods Comparison Data:
- A total of 102 samples from outside sources were assayed in singlet using the current Bayer Immuno 1 Ferritin Assay (L6 = 1000 ng/mL) and compared to single results generated using the new extended range Ferritin (L6 = 2500 ng/mL).
- Three regression analysis plots were generated:
- n = 72: Assesses recoveries of all samples at concentrations less than 1000 ng/mL.
- Equation: y = 1.049x - 2.577, r = 0.999, Sy.x = 6.94, range = 30.2 - 966.7. All samples assayed 'neat'.
- n = 30: Assesses samples greater than 1000 ng/mL but less than 2500 ng/mL. Current method samples diluted 1:5 in Level 1 calibrator, proposed method samples were neat (undiluted).
- Equation: y = 0.975x + 291.1, r = 0.931, Sy.x = 162.2, range = 812-2412.
- n = 102 (all data points): Combines the above.
- Equation: y = 1.162x - 9.21, r = 0.990, Sy.x = 101.7, range = 30.2-2412. Open circles represent samples assayed neat, while closed circles represent samples diluted 1:5.
- n = 72: Assesses recoveries of all samples at concentrations less than 1000 ng/mL.
Dilution of Over-Range Samples:
- Six samples with concentrations greater than 2500 ng/mL were diluted 1:10 (1 part sample to 9 parts Bayer Immuno 1 Ferritin Level 1 Calibrator) and tested using both Current (L6 = 1000 ng/mL) and Proposed (L6 = 2500 ng/mL) calibration curves.
- t-test (paired two sample for means): Determined no statistical difference between recoveries by the two calibration curves (t Stat = -1.725, t Critical two-tail = 2.571).
- Regression analysis: Confirmed that the diluted recoveries were equivalent (r ≥ 0.975, slope ≥ 0.975). For diluted samples, the regression analysis showed y = 0.991x + 185.7, r = 0.998, Sy.x = 201.9, n = 6, range = 2589 to 10108.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Analytical Sensitivity: 0.3 ng/mL.
Precision metrics: Within %CV and Total %CV values provided in Table 2.
Correlation coefficients (r) for method comparisons: 0.999, 0.931, 0.990, 0.998.
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.
Not Found (The document states "The Bayer Immuno 1 Ferritin Assay originally received 510(k) clearance when the system was first released in 1990." but does not provide the K number for this original clearance or any specific predicate device for the current submission, which is a change to an already cleared device.)
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.
Not Found
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
§ 866.5340 Ferritin immunological test system.
(a)
Identification. A ferritin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia.(b)
Classification. Class II (performance standards).
0
Attachment 4
OCT 22 1998
KG82714
Bayer Immuno 1 ™ System
Ferritin Assay
510(k) Method Sheet Summary
Submitted by:
D. Becker
P. Dillon M. Dombalagian J. Monticello T. Nguyen
J. Roman G. Struve R. Weiss J. Wilson
23 July, 1998
Image /page/0/Picture/11 description: The image shows the Bayer company logo. The word "Bayer" is written in a bold, sans-serif font. To the right of the word is a circle with the word "Bayer" written vertically three times. A thick black line is located underneath the company name.
1
TABLE OF CONTENTS
| Page | ||
|---|---|---|
| 1.0 | Overview | 3 |
| 2.0 | Introduction | 4 |
| 3.0 | Assay Description | 5 |
| 4.0 | Calibrators Overview | 5 |
| 5.0 | Stability of New 2500 ng/mL Calibrator | 6 |
| 6.0 | Imprecision | 6 |
| 7.0 | Analytical Sensitivity | 7 |
| 8.0 | Correlation Data | 7 |
| 9.0 | Specificity | |
| Cross-Reactivity | 8 | |
| 10.0 | Dilution of Over-Range Samples | 9 |
| 11.0 | Determination of Reference Intervals | 9 |
.
.
2
1.0 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
The Bayer Immuno 1 Ferritin Assay originally received 510(k) clearance when the system was first released in 1990. In response to customer inquiries, we are proposing an increase in the concentration of the Level 6 calibrator from 1000 ng/mL to 2500 ng/mL.
This change will prevent unnecessary dilution of high concentration samples required by many customers using this assay while monitoring renal dialysis patients, where the Ferritin levels often exceed 1000 ng/mL.
We propose only two changes to the Method Sheet: Communication of the new calibrator levels and a correlation showing sample recoveries are unchanged between the L6 at 1000 ng/mL and the L6 at 2500 ng/mL. This report summarizes R&D data generated to show that new assay performance is equivalent to previously demonstrated performance.
There is no proposed change to reagents - neither in their manufacture nor formulation.
| ng/mL | ||
|---|---|---|
| Calibrator | Current | Proposed |
| L1 | 0.0 | 0.0 |
| L2 | 10.0 | 10.0 |
| L3 | 40.0 | 40.0 |
| L4 | 100.0 | 100.0 |
| L5 | 500.0 | 1000.0 |
| L6 | 1000.0 | 2500.0 |
Table 1. Bayer Immuno 1 Ferritin Assay: Current and Proposed Calibrators
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2.0 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ferritin is an iron-containing protein predominantly found in the cytoplasm of hepatic and reticulo-endothelial cells. It is the primary storage compound from which iron is mobilized to the transferrin-bound serum pool and thus transferred to red blood cells for use in required body functions. In addition to intracellular ferritin, small but clinically significant amounts are found in circulating serum. The measurement of ferritin in serum is believed to reflect total iron stores of the body.
For this reason, it is important to be able to test ferritin levels from extremely low concentrations to very high concentrations.
Certain disease states are known to elevate serum ferritin concentrations independently of the patient's iron stores. These include hepatic diseases such as cirrhosis, drug or viralinduced necrosis, hepatitis, obstructive jaundice, primary hepatoma and metastatic cancer of the liver. Recently, customers have requested the ability to assay higher concentrations of ferritin without having to dilute patient samples. The Bayer Immuno 1 Ferritin Method in its current formulation allowed for a 2.5 fold increase in sample concentrations to be assaved by adding a new calibrator at 2500 ng/mL.
This change requires no change in formulation of assay reagents. A new Level 6 calibrator at 2500 ng/mL is produced and a previous L5 Calibrator at 500 ng/mL is deleted and replaced with the previous L6 of 1000 ng/mL.
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The Bayer Immuno 1 Ferritin (FER) Method uses a homogenous sandwich immunoassay format. Samples are reacted with Ferritin Antibody Conjugate R1 (Antibody linked to FITC) and Ferritin Antibody Conjugate R2 (Antibody linked to calf intestine alkaline
phosphatase) and incubated on the Immuno 1 system at 37°C. The anti-Ferritin antibody conjugates combine with sample ferritin to form a sandwich complex, followed by addition of monoclonal Immuno-Magnetic particle (mIMP) Reagent binds the antibody which After further incubacomplexes. tion, the mIMP/antibody complex is washed and a para-nitrophenyl phosphate substrate, which reacts with the enzyme conjugate, is added. The resulting paranitrophenoxide is monitored at 405 nm and 450 nm using a filter switch protocol. The dose/ response curve is proportional to the amount of ferritin in the sample.
Image /page/4/Figure/3 description: The image is a graph titled "Figure 1. Proposed New Calibration Curve for Bayer Immuno 1 Ferritin Assay." The graph shows concentration in ng/mL on the x-axis and rates in mA/min on the y-axis. The graph shows a curve that increases from approximately (0,0) to (2500, 5000). The text in the image notes that the calibrator at 500 ng/mL was not used to generate this curve and is shown only as a reference to the existing curve.
. . . . . . . . . . . . . . . . CALIBRATORS OVERVIEW 4.0 .....
Bayer SETpoint Ferritin Calibrators were first standardized to the World Health Organization (WHO) 1st International Standard (IS 80/602) and the linkage has been perpetuated by nested testing matches of subsequent master lots. Each production lot of calibrators is anchored against a Master Lot and value assigned by comparative analysis of twenty "new" calibrator replicates nested within twenty "master" calibrator replicates. A calibration curve is then generated with the new calibrators and acceptable control and serum pool recoveries are verified before release. Nominal new calibrator values are: 0.0, 10.0, 40.0, 100.0, 1000.0 and 2500.0 ng/mL.
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. . . . . . . . STABILITY OF NEW 2500 NG/ML CALIBRATOR 5.0 .......
Shelf life dating for the new level of Bayer Immuno 1 Ferritin Calibrator will be determined by monitoring recoveries of other calibrators, controls and serum pools under real-time and elevated temperature stressed conditions and compared to -80°C stored components. Data for real-time stability will continue to be generated for at least two years. Additional performance testing will occur at specific time points to verify on-system stability claims for the life-time of the product.
6.0. . . . ··············································································································································································
The proposed new Level 6 calibrator does not impact imprecision estimates: no change will be made to the method sheet.
Estimates of imprecision were obtained from replicate analyses of human serum (Pools 1 & 2) and Bayer TEST point Ligand Controls (Controls 1 to 3) and then compared to Method Sheet recoveries using the current L6 Calibrator. Method Sheet Imprecision estimates were collected and computed following NCCLS document EP5-T2: Evaluation of Precision Performance of Clinical Chemistry Devices - Second Edition; Tentative Guideline.2 Precision estimates using the 2500 ng/mL L6 calibrator were generated over 5 days (instead of 20) using four replicates per day, instead of two.
| Proposed L6 Calibrator @ 2500 ng/mL | Current method Sheet | |||||||
|---|---|---|---|---|---|---|---|---|
| Pool-1 | Control 1 | Control 2 | Pool-2 | Control 3 | Control 1 | Control 2 | Control 3 | |
| mean = | 25.2 | 28.8 | 104.6 | 206.7 | 237.4 | 21.1 | 148.1 | 344.2 |
| Within SD = | 0.5 | 0.5 | 0.5 | 8.6 | 6.0 | 0.2 | 3.2 | 8.5 |
| Within %CV = | 1.9 | 1.8 | 0.5 | 4.1 | 2.5 | 1.0 | 2.1 | 2.5 |
| Total SD = | 0.6 | 0.6 | 1.4 | 8.6 | 6.0 | 1.5 | 7.4 | 17.1 |
| Total %CV = | 2.6 | 2.2 | 1.3 | 4.1 | 2.5 | 7.1 | 5.0 | 5.0 |
Table 2. Precision Observed for Bayer TEST point Controls and Human Serum Pools for Current and Proposed Calibrator Sets: Bayer Immuno 1 Ferritin Assay
Image /page/5/Figure/7 description: This image is a graph that shows the relationship between concentration Ferritin (ng/mL) and %CV. The x-axis represents the concentration of Ferritin in ng/mL, ranging from 0 to 250. The y-axis represents the %CV, ranging from 0.0 to 5.0. The graph includes two lines representing "Total %CV" and "Within %CV", as well as a dotted line indicating extrapolated %CV estimates to the left of the line.
Image /page/5/Figure/8 description: This image is titled "Figure 2 Graph of Within and Total-Run %CV for Bayer Immuno 1 Ferritin Assay." The image contains a title describing the contents of a graph. The graph is related to the Bayer Immuno 1 Ferritin Assay. The graph shows the Within and Total-Run %CV.
Bayer Immuno 1™ Ferritin 510(k) Application
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7.0. . . . . . . . . ··············································································································································································
An estimate of analytical sensitivity (minimal detectable concentration) of the method was determined using Level 1 data generated as part of a performance study comparing multiple systems. reagents and calibrator sets. Analytical Sensitivity is a multi-system estimate of two times the within-run standard deviation of the zero calibrator. This value was determined to be 0.3 ng/mL, unchanged from our current expected value.
·············································································································································································· 8.0. . . . . .
A total of 102 samples were obtained from outside sources including samples with values greater than the current method's highest calibrator at 1000 ng/mL. Each sample was assayed in singlet using the current Bayer Immuno 1 Ferritin Assay (L6 = 1000 ng/mL) and compared to single results generated using the new extended range Ferritin (L6 = 2500 ng/mL). Three regression analysis plots were generated. The first (n = 72) assesses recoveries of all samples at concentrations less than 1000 ng/mL and will be added to the two comparisons in the current Method Sheet. The second (n = 30) assesses samples greater than 1000 ng/mL, but less than 2500 ng/mL and tests the samples diluted 1:5 in Level 1 calibrator for the current method and neat (undiluted) using the proposed L6 Calibrator method. The third comparison (Figure 5) includes all 102 data points.
Image /page/6/Figure/4 description: The figure is a scatter plot comparing two different methods of measuring Immuno 1 Ferritin. The x-axis represents the current method, and the y-axis represents the proposed method, both measured in ng/mL. A line of best fit is plotted with the equation y = 1.049x - 2.577, and the correlation coefficient r = 0.999, Sy.x = 6.94, n = 72, and the range is 30.2 - 966.7. The text "All samples assayed 'neat'" is at the bottom of the figure.
Image /page/6/Figure/5 description: The image is a title for a figure. The title reads "Figure 3. Bayer Immuno 1 Ferritin Assays: Methods Comparison Data (undiluted samples)." The title indicates that the figure will be comparing different methods of ferritin assays. The figure is from Bayer Immuno 1.
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Image /page/7/Figure/0 description: This figure is a scatter plot comparing proposed Immuno 1 Ferritin to current Immuno 1 Ferritin. The x-axis represents current Immuno 1 Ferritin in ng/mL, while the y-axis represents proposed Immuno 1 Ferritin in ng/mL. The data points are scattered around a regression line, with the equation y = 0.975x + 291.1, a correlation coefficient of r = 0.931, Sy.x = 162.2, n = 30, and a range of 812-2412. The current samples were diluted 1:5.
Image /page/7/Figure/1 description: This figure is a scatter plot comparing two different methods of measuring Immuno 1 Ferritin levels. The x-axis represents the current method, while the y-axis represents the proposed method, both measured in ng/mL. The plot includes a regression line with the equation y = 1.162x - 9.21, a correlation coefficient of r = 0.990, Sy.x = 101.7, and n = 102, with a range of 30.2-2412. Open circles represent samples assayed neat, while closed circles represent samples diluted 1:5.
- Figure 4. Bayer Immuno 1 Ferritin Assays: Methods Comparison Data (samples >1000 ng/mL diluted for current method).
Figure 5. Bayer Immuno 1 Ferritin Assays: Methods Comparison Data (samples >1000 ng/mL diluted for current method).
. . . SPECIFICITY 9.0. . .
Interfering Substances
No reformulations were made to Reagents and the proposed new Level 6 calibrator will not impact specificity. No change will be made to the method sheet.
Cross Reactivity
No reformulations were made to Reagents and the proposed new Level 6 calibrator will not impact cross-reactivity. No change will be made to the method sheet.
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No reformulations were made to Reagents and the proposed new Level 6 Calibrator will not impact dilution of high samples. No changes will be made to the method sheet.
This was confirmed by dilution of six samples with concentrations greater than the upper limit of the new analytical range (> 2500 ng/mL). Each sample was diluted 1:10 (1 part sample to 9 parts Bayer Immuno 1 Ferritin Level 1 Calibrator) and tested using both the Current and the Proposed calibration curves.
Results were compared two ways. First a t-test (paired two sample for means) determined no statistical difference between recoveries by the two calibration curves.
Then, a regression analysis between the samples confirmed that the diluted recoveries were equivalent (r ≥ 0.975, slope ≥ 0.975).
- Table 3 T-Test comparing the Results Generated from Six Diluted Patient Samples. The t-Stat is less than the t Critical meaning we cannot say the two populations are different.
| t-Test: Paired Two Sample for Means | ||
|---|---|---|
| L6 = 1000 | L6 = 2500 | |
| Mean | 6074.9 | 6203.7 |
| Variance | 9600749 | 9454447 |
| Observations | 6 | 6 |
| Pooled Variance | 0.998274 | |
| Hypothesized Mean Difference | 0 | |
| df | 5 | |
| t Stat | -1.725 | |
| t Critical one-tail | 2.015 | |
| t Critical two-tail | 2.571 | |
| t Stat is |