(347 days)
Not Found
No
The device description and performance studies focus on a standard ELISA assay and its components, with no mention of AI or ML algorithms for data analysis or interpretation.
No
This device is an in vitro diagnostic test used to aid in diagnosis, not to provide therapy or treatment.
Yes
The Intended Use / Indications for Use section explicitly states that the test kit "is used as an aid in the diagnosis of primary membranous glomerulonephritis (pMGN)".
No
The device description clearly outlines a physical test kit containing a microwell plate, calibrators, controls, reagents, and solutions, which are all hardware components.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "qualitative or semiquantitative determination of IgG class autoantibodies against phospholipase A2 receptor (PLA2R) in human serum." This involves testing a sample taken from the human body (serum) in vitro (outside the body).
- Aid in Diagnosis: It is used as an "aid in the diagnosis of primary membranous glomerulonephritis (pMGN), in conjunction with other laboratory and clinical findings." This clearly indicates its role in the diagnostic process.
- Device Description: The description details a "microwell ELISA plate," "calibrators," "controls," and various reagents used for a laboratory test performed on a biological sample.
- Performance Studies: The inclusion of performance studies (sensitivity and specificity) based on testing human samples further supports its classification as an IVD.
- Predicate Device: The mention of a predicate device (K132379; EUROIMMUN Anti-PLA2R IFA (IgG)) which is also an IVD, reinforces this classification.
All these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The EUROIMMUN Anti-PLA2R ELISA (IgG) test kit is intended for the qualitative or semiquantitative determination of IgG class autoantibodies against phospholipase A2 receptor (PLA2R) in human serum. It is used as an aid in the diagnosis of primary membranous glomerulonephritis (pMGN), in conjunction with other laboratory and clinical findings.
Product codes (comma separated list FDA assigned to the subject device)
PGV
Device Description
The EUROIMMUN Anti-PLA2R ELISA (IgG) consists of a microwell ELISA plate coated with PLA2R antigen, 5 calibrators, positive and negative control, peroxidase-labelled anti-human IgG conjugate, sample buffer, wash buffer concentrate, TMB chromogen/substrate solution and stop solution.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
For Prescription Use Only.
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)
Analytical Performance Characteristics:
- Reproducibility:
- Intra- and Inter-Assay Reproducibility: Determined using samples at different points on the calibration curve. Intra-Assay CVs based on 20 determinations; Inter-Assay CVs on 30 determinations over 10 runs on 5 days. Acceptance criteria: CVs
N/A
0
JUN 2 7 2014
PREMARKET NOTIFICATION 510(K) SAFETY AND EFFECTIVENESS SUMMARY
(As required by 21 CFR § 807.92)
- A. 510(k)Number: K132195
- B. Purpose for Submission: New Device
- C. Measurand: Anti-PLA2R Autoantibodies
- D. Type of Test: Qualitative or Semi-Quantitative Enzyme Immunoassay
- E. Applicant: EUROIMMUN US INC.
- F. Proprietary and Established Names: EUROIMMUN Anti-PLA2R ELISA (IgG)
G. Regulatory Information:
-
- Regulation: 21 CFR 866.5780 - Anti-phospholipase A2 receptor immunological test system
-
- Classification: Class II
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- Product code: PGV - Anti-phospholipase A2 receptor
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- Panel: Immunology
H. Intended Use:
-
- Intended Use(s):
The EUROIMMUN Anti-PLA2R ELISA (IgG) test kit is intended for the qualitative or semiquantitative determination of IgG class autoantibodies against phospholipase A2 receptor (PLA2R) in human serum. It is used as an aid in the diagnosis of primary membranous glomerulonephritis (pMGN), in conjunction with other laboratory and clinical findings.
- Intended Use(s):
-
Indication(s) for Use: 2. Same as Intended Use.
-
- Special Conditions for the Use Statement(s): For Prescription Use Only.
-
- Special Instrument Requirements: Microwell plate reader capable of measuring OD at 450nm for dual wavelength readings.
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EUROIMM
I. Device Description:
The EUROIMMUN Anti-PLA2R ELISA (IgG) consists of a microwell ELISA plate coated with PLA2R antigen, 5 calibrators, positive and negative control, peroxidase-labelled anti-human IgG conjugate, sample buffer, wash buffer concentrate, TMB chromogen/substrate solution and stop solution.
J. Substantial Equivalence Information:
- Predicate device name (s): 1. EUROIMMUN Anti-PLA2R IFA (IgG)
-
- Predicate 510(k) number(s): K132379
-
- Comparison with predicate:
Similarities
| Item | New device | Predicate device |
|---|---|---|
| Manufacturer | EUROIMMUN AG | Same |
| Intended use | Detection of IgG antibodies against PLA2R | Same |
| Sample types | Serum | Same |
| Controls | 2 controls: 1 positive, 1 negative | Same |
| Reagent preparation | All reagents are ready to use, except for the wash | |
| buffer. | Same |
Differences
| Item | New device | Predicate device |
|---|---|---|
| Assay format | Qualitative or semi-quantitative (using either all | |
| calibrators or the cut-off calibrator only) | Qualitative | |
| Antigen | Recombinant PLA2R (type M) | PLA2R transfected cells and |
| control-transfected cells | ||
| Reagents | 96 well microplate, 5 Calibrators (2, 20, 100, 500 | |
| and 1500 RU/ml), Conjugate (anti-human IgG | ||
| labeled with horseradish peroxidase), Sample | ||
| buffer, Wash buffer (10x concentrate), Substrate | ||
| solution (TMB), Stop solution (0.5 M sulphuric | ||
| acid), 2 Controls, | BIOCHIP slides, Conjugate | |
| (fluorescein-labeled anti-human | ||
| IgG), Salt for PBS pH 7.2, Tween | ||
| 20, Embedding medium, Cover | ||
| glasses, 2 Controls | ||
| Sample dilution | 1:101 | 1:10 |
| Procedure | ELISA: Sample incubation with micro-well | |
| antigen coated plate, followed by a wash step, | ||
| incubation with conjugate, wash step, incubation | ||
| with substrate, addition of stop solution, | ||
| photometric reading | IFA: Sample incubation with | |
| tissues/cells, followed by a wash | ||
| step, incubation with conjugate, | ||
| wash step, embedding, | ||
| fluorescence microscopy reading | ||
| Reported results | Qualitative, RU/ml or Ratio | Qualitative |
| Cut-off level | Qualitative: Ratio 1.0 | |
| Semi-quantitative: 20 RU/ml | 1:10 dilution |
K. Standard/Guidance Document Referenced (if applicable):
None Referenced.
L. Test Principle:
Patient samples are diluted 1:101 in sample buffer, 100 µl of each diluted patient sample and pre-diluted controls and calibrators are added to the antigen coated microtiter wells and incubated for 30 minutes at room temperature. After incubation the microtiter well strips are washed with wash buffer to remove unbound antibodies and 100 ul of the anti-human IgG enzyme conjugate reagent is added to each microtiter well. After an additional 30-minutes incubation at room temperature, the microtiter wells are again washed 3 times with 300 µl of wash buffer to remove any unbound enzyme conjugate and 100 µl of
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the chromogen substrate is added. The strips are incubated for 15 minutes at room temperature and 100 ul stop solution is added. The microtiter plates are placed in an ELISA reader and read at a wavelength of 450 nm and a reference wavelength of between 620 nm and 650 nm within 30 minutes.
M. Analytical Performance Characteristics (where applicable):
-
- Reproducibility
- Intra- and Inter-Assay Reproducibility: a.
Intra- and Inter-Assay coefficients of variation (CV) were determined using samples with values at different points on the calibration curve. The Intra-Assay CVs are based on 20 determinations and the Inter-Assay CVs on 30 determinations performed in 10 different runs on 5 different days (with 3 replicates per run). Tests were performed according to the package insert with the same lot and by the same technician. Acceptance criterium was that the CV's show results below 12% for positive and borderline samples. Acceptance criterium for negative samples was that all qualitative results be negative. Acceptance criterium for the ratio-based results was that all qualitative results (positive, borderline, negative) of the samples be in line with the expected result.
| n = 20 | Anti-PLA2R ELISA (IgG); RU/ml | |||||||
|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | |
| Mean Value | 2 | 12 | 18 | 26 | 48 | 109 | 782 | |
| StDev | 0.1 | 0.5 | 0.5 | 0.9 | 1.5 | 3.0 | 33.5 | 48.7 |
| %CV | 10.9 | 4.2 | 2.6 | 3.4 | 3.1 | 2.8 | 4.3 | 5.7 |
| Intra-Assay Reproducibility |
|---|
| Anti-PLA2R ELISA (IgG); Ratio | ||||||||
|---|---|---|---|---|---|---|---|---|
| n = 20 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
| Mean Value | 0.1 | 0.6 | 0.9 | 1.3 | 2.0 | 4.2 | 7.5 | 7.6 |
| Range | 0.1 - 0.1 | 0.5 - 0.6 | 0.9 - 0.9 | 1.2 - 1.4 | 1.9 - 2.1 | 4.0 - 4.3 | 7.4 - 7.6 | 7.5 - 7.7 |
| Expected | neg | neg | bl | pos | pos | pos | pos | pos |
| % Positive | 0% | 0% | 0% | 100% | 100% | 100% | 100% | 100% |
| % Borderline | 0% | 0% | 100% | 0% | 0% | 0% | 0% | 0% |
| % Negative | 100% | 100% | 0% | 0% | 0% | 0% | 0% | 0% |
Inter-Assay Reproducibility
| n = 30 | Anti-PLA2R ELISA (IgG); RU/ml | |||||||
|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | |
| Mean Value | 2 | 12 | 20 | 28 | 51 | 110 | 793 | 884 |
| StDev | 1.2 | 1.0 | 1.7 | 1.1 | 3.2 | 11.2 | 81.4 | 87.5 |
| %CV | --- | 7.9 | 8.6 | 4.2 | 6.2 | 10.2 | 10.3 | 9.9 |
| n = 30 | Anti-PLA2R ELISA (IgG); Ratio | |||||||
|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | |
| Mean Value | 0.1 | 0.6 | 1.0 | 1.3 | 2.2 | 3.7 | 7.8 | 7.9 |
| Range | 0.1 - 0.3 | 0.5 - 0.6 | 0.8 - 1.1 | 1.2 - 1.4 | 1.8 - 2.5 | 3.0 - 4.3 | 6.6 - 8.9 | 7.0 - 8.9 |
| Expected | neg | neg | pos | pos | pos | pos | pos | pos |
| % Positive | 0% | 0% | 27% | 100% | 100% | 100% | 100% | 100% |
| % Borderline | 0% | 0% | 73% | 0% | 0% | 0% | 0% | 0% |
| % Negative | 100% | 100% | 0% | 0% | 0% | 0% | 0% | 0% |
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Repeatability & Reproducibility (Total Imprecision) b.
- Repeatability
Investigated using samples with values at different points on the calibration curve. Within-run, between-run, between-day and total standard deviations (SD) and coefficients of variation (CV) were calculated based on 150 determinations per sample performed in 6 different runs on 3 different days (with 2 runs per day and 25 replicates per run) according to the package insert with the same lot and by the same technician. Acceptance criterium was that the CV's show results below 12% for positive and borderline samples. Acceptance criterium for negative samples was that all qualitative results be negative. Acceptance criterium for the ratio-based results was that all qualitative results (positive, borderline, negative) of the samples be in line with the expected result.
| Repeatability | |
|---|---|
| --------------- | -- |
| n = 150 | Anti-PLA2R ELISA (IgG); RU/ml | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Sample | Mean | Within-run | Between-run | Between-day | Total | ||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||
| 1 | 3 | 0.28 | 9.2 | 0.38 | 12.9 | 0.64 | 22.4 | 0.43 | 14.8 |
| 2 | 17 | 0.57 | 3.3 | 1.04 | 6.4 | 1.25 | 7.5 | 0.95 | 5.7 |
| 3 | 22 | 0.87 | 3.9 | 1.56 | 7.3 | 1.08 | 5.1 | 1.17 | 5.4 |
| 4 | 24 | 0.75 | 3.2 | 1.60 | 6.7 | 1.51 | 6.4 | 1.28 | 5.4 |
| 5 | 884 | 69.95 | 7.9 | 72.49 | 8.3 | 66.51 | 7.6 | 69.65 | 7.9 |
| 6 | 1356 | 65.65 | 4.8 | 33.59 | 2.5 | 45.60 | 3.4 | 48.28 | 3.6 |
| n = 150 | Anti-PLA2R ELISA (IgG); Ratio | |||||
|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | |
| Mean Value | 0.20 | 0.74 | 0.91 | 1.00 | 7.57 | 8.20 |
| Range | 0.16 - 0.25 | 0.68 – 0.81 | 0.76 - 1.27 | 0.83 – 1.17 | 6.34 - 8.22 | 7.45 – 8.72 |
| Expected | neg | bl | bl | pos | pos | pos |
| % Positive | 0% | 0% | 1% | 52% | 100% | 100% |
| % Borderline | 0% | 97% | 99% | 48% | 0% | 0% |
| % Negative | 100% | 3% | 0% | 0% | 0% | 0% |
Reproducibility (Lot-to-Lot)
Investigated using samples with values at different points on the calibration curve. Within-run, between-run, between-lot and total SD's and %CV's were calculated based on 18 determinations per sample performed in 3 different runs on 3 different days (with 3 runs per lot and 2 replicates per run) according to the package insert by the same technician. Acceptance criterium was that the CV's show results below 12% for positive and borderline samples. Acceptance criterium for negative samples was that all qualitative results be negative. Acceptance criterium for the ratiobased results was that all qualitative results (positive, borderline, negative) of the samples be in line with the expected result.
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EUROIMMU I II II II II
| Reproducibility | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| n = 18 | Anti-PLA2R ELISA (IgG); RU/ml | |||||||||
| Sample | Mean | Within-run SD | %CV | Between-run SD | %CV | Between-Batch SD | %CV | Total SD | %CV | |
| 1 | 3 | 0.45 | 16.4 | 0.15 | 5.4 | 0.33 | 11.9 | 0.31 | 11.2 | |
| 2 | 17 | 1.19 | 7.2 | 0.42 | 2.5 | 0.69 | 4.1 | 0.76 | 4.6 | |
| 3 | 23 | 1.46 | 6.5 | 0.30 | 1.3 | 0.99 | 4.4 | 0.91 | 4.0 | |
| 4 | 26 | 1.78 | 6.7 | 0.85 | 3.2 | 1.37 | 5.2 | 1.33 | 5.0 | |
| 5 | 304 | 15.71 | 5.2 | 6.48 | 2.1 | 10.61 | 3.5 | 10.93 | 3.6 | |
| 6 | 1260 | 127.19 | 10.1 | 35.80 | 2.8 | 33.53 | 2.7 | 65.51 | 5.2 | |
| n = 18 | Anti-PLA2R ELISA (IgG); Ratio | |||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | |||||
| Mean Value | 0.19 | 0.77 | 0.99 | 1.12 | 5.62 | 8.43 | ||||
| Range | 0.16-0.21 | 0.68-0.83 | 0.91-1.12 | 1.06 - 1.20 | 5.29-6.12 | 7.71-9.04 | ||||
| Expected | neg | neg | bl | pos | pos | pos | ||||
| % Positive | 0% | 0% | 28% | 100% | 100% | 100% | ||||
| % Borderline | 0% | 94% | 72% | 0% | 0% | 0% | ||||
| % Negative | 100% | 6% | 0% | 0% | 0% | 0% |
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Linearity/ Assay Reportable Range: C.
Five sets of 11-step-wise dilutions were prepared by mixing low and high analyte samples. The concentrations ranged from a low concentration of 2 RU/mL to high concentrations of 75 RU/mL, 133 RU/mL, 790 RU/mL, 1100 RU/mL, or 1642 RU/mL. The assay was shown to be sufficiently linear from 2 to1500 RU/mL. Results from the two lowest ranges and the range throughout the AMR are shown below.
Image /page/5/Figure/3 description: The image contains two graphs and two tables that show the expected versus measured concentration for two sets of data. The graphs show the mean, linear mean, 2nd order, and 3rd order concentrations. The tables provide statistical information such as R-squared values, coefficients, standard errors, t-values, p-values, and confidence intervals for each order. The equations and R-squared values for each order are also displayed on the graphs.
Image /page/5/Figure/4 description: This image is a graph that shows the relationship between expected concentration and measured concentration. The x-axis represents the expected concentration, ranging from 0.000 to 140.000, while the y-axis represents the measured concentration, ranging from 0.000 to 60.000. The graph includes a trendline with the equation y=1E-05x^3-0.0033x^2+1.1549x-0.812, and the R-squared value for the trendline is 0.9988.
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Image /page/6/Figure/1 description: This image is a graph titled "Expected vs. Measured Concentrations (Set No. 3)". The graph plots the measured concentration on the y-axis against the expected concentration on the x-axis. There are three data sets plotted: Value 1, Value 2, and Mean, each with a corresponding linear trendline. The trendline equations and R-squared values are displayed on the graph, with the mean having a trendline equation of y=0.9595x-25.981 and an R-squared value of 0.9361.
- Traceability, Stability, Expected Values (Controls, Calibrators or Methods): d.
A recognized standard or reference material for anti-PLA2R antibodies is not available. The assay is calibrated in relative arbitrary units (RU/ml). Alternatively, results may be given in ratios.
Stability
Stability studies are conducted following the international standard EN 13640:2002: Stability testing of in vitro diagnostic reagents. Three production lots of all kit reagents are tested. Realtime testing at 2-8°C and accelerated testing at 37°C are conducted. The shelf-life stability is 12 months at 2-8°C. Open-vial stability of the kit is 6 months when stored at 2-8°C. The wash buffer was found to be stable for at least 28 days when diluted to working strength.
Controls & Calibrators
The calibrators and controls are derived from human materials. Human originated material is tested and found negative for HBsAg, anti-HCV, anti-HIV-1 and anti-HIV-2, diluted to the appropriate concentration, stabilized and colored.
Calibrators are adjusted to match the required performance criteria in use with the corresponding microtiter strip lot and the corresponding kit controls.
Negative and Positive Controls are included. The positive control is Ready for Use with a 3-4+ fluorescence. Negative control is Ready for Use and is autoantibody negative. EUROIMMUN US INC. recommends using the positive and negative controls undiluted for the screening protocol.
- Limit of Blank, Limit of Detection and Limit of Quantitation/Functional Sensitivity: e.
Limit of blank (LoB) and limit of detection (LoD) and limit of quantitation (LoQ)/functional sensitivity (FS) were investigated following CLSI standard EP17-A. The LoB was found to be 1.8 RU/ml & LoD of the Anti-PLA2R ELISA (IgG) was found to be 2.2 RU/ml.
The LoQ was estimated from the functional sensitivity which is defined as the lowest concentration at which the CV is 20%. From the same data LoB and LoD were calculated, the mean concentrations (X-axis) vs. % CVs (Y-axis) were plotted. The functional sensitivity was read from the potential regression line crossing the 20% CV line and was found to be approx. 1.4 RU/ml, which is in the range of the LoD and the lower limit of the measurement range of 2 RU/ml. Following CLSI standard EP17-A , "If this estimate is less than the defined goal for total error, then: LoQ = LoD"; 2.2 RU/ml.
f. Analytical Specificity:
Cross-reactivity: Cross reactivity was investigated using a panel of 65 clinically characterized sera positive for thyreoiditis, systemic lupus erythematosus (SLE), Sjögren's syndrome (SS),
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systemic sclerosis (SSc), rheumatoid arthritis (RA), cANCA, pANCA, GBM and Hepatitis B surface antigen (HBsAg). All 65 sera were negative in the Anti-PLA2R ELISA (IgG), so no cross reactivity was found.
Interference: To investigate the influence from hemoglobin, triglycerides and bilirubin, sera at anti-PLA2R concentrations were spiked with potential interfering substances and incubated with the test system according to the package insert. The recovery in relation to the unspiked sample without interferent was calculated. Acceptance criterium was that the individual recovery be within the range of 70 - 130 % and the mean of recoveries for each interferent be within the range of 85 - 115 %. No significant interference was observed for concentrations of up to 1000 mg/dl for hemoglobin, 2000 mg/dl for triglyceride and 40 mg/dl for bilirubin.
- g. Assay Cut-Off:
Qualitative evaluation: Ratio 1.0; Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
EF
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.