EUROIMMUN Anti-BP230-CF ELISA (IgG)
Device Facts
| Record ID | K193115 |
|---|---|
| Device Name | EUROIMMUN Anti-BP230-CF ELISA (IgG) |
| Applicant | Euroimmun Us, Inc. |
| Product Code | OEG · Immunology |
| Decision Date | Sep 17, 2020 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.5660 |
| Device Class | Class 2 |
Indications for Use
The EUROIMMUN Anti-BP230-CF ELISA (IgG) test kit is intended for the qualitative or semi-quantitative determination of immunoglobulin class IgG antibodies against BP230 in human serum and plasma (K3-EDTA, Li+heparin, Na+-citrate). It is used as an aid in the diagnosis of bullous pemphigoid, in conjunction with other laboratory and clinical findings.
Device Story
EUROIMMUN Anti-BP230-CF ELISA (IgG) is an in vitro diagnostic test kit; utilizes enzyme-linked immunosorbent assay (ELISA) technology. Input: human serum or plasma samples. Process: patient antibodies bind to BP230 antigen-coated microplate wells; secondary enzyme-labeled anti-human IgG conjugate added; substrate reaction produces color intensity proportional to antibody concentration. Output: qualitative or semi-quantitative IgG antibody levels. Used in clinical laboratory settings by trained laboratory personnel. Results interpreted by physicians alongside clinical findings to aid bullous pemphigoid diagnosis.
Clinical Evidence
Clinical study evaluated 421 samples (168 bullous pemphigoid, 253 control diseases). Clinical sensitivity was 50.6% (95% CI: 42.8–58.4%). Clinical specificity was 97.6% (95% CI: 94.9–99.1%) across various dermatological and autoimmune conditions. Method comparison with predicate (N=202) showed 85.6% overall agreement. Normal population study (N=438) showed 2.1% prevalence of positive results.
Technological Characteristics
ELISA-based immunological test system. Components include microplate coated with BP230 antigen, enzyme conjugate, substrate, and wash buffer. Qualitative/semi-quantitative detection of IgG antibodies. Standard laboratory equipment required for incubation and photometric measurement.
Indications for Use
Indicated for qualitative or semi-quantitative detection of IgG antibodies against BP230 in human serum and plasma to aid in the diagnosis of bullous pemphigoid. For prescription use only.
Regulatory Classification
Identification
A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).
Predicate Devices
- MESACUP BP180 ELISA Kit and MESACUP BP230 ELISA Kit (K071961)
Related Devices
- K083615 — EUROIMMUN ANTI BP 180-4X ELISA (IGG) · Euroimmun Us, Inc. · Mar 16, 2009
- K071961 — MESACUP MODELS BP180 AND BP230 ELISA KITS · Mbl International Corporation · Aug 25, 2008
Submission Summary (Full Text)
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FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY ONLY
## I Background Information:
A 510(k) Number
K193115
B Applicant
EUROIMMUN US, Inc.
C Proprietary and Established Names
EUROIMMUN Anti-BP230-CF ELISA (IgG)
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| OEG | Class II | 21 CFR 866.5660 - Multiple Autoantibodies Immunological Test System | IM - Immunology |
## II Submission/Device Overview:
A Purpose for Submission:
New Device
B Measurand:
Anti-Bullous Pemphigoid (BP) 230 IgG Autoantibodies
C Type of Test:
Qualitative or Semi-Quantitative, ELISA
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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K193115 - Page 2 of 12
# III Intended Use/Indications for Use:
## A Intended Use(s):
See Indications for Use below.
## B Indication(s) for Use:
The EUROIMMUN Anti-BP230-CF ELISA (IgG) test kit is intended for the qualitative or semi-quantitative determination of immunoglobulin class IgG antibodies against BP 230 in human serum and plasma (K3-EDTA, Li+-heparin, Na+-citrate). It is used as an aid in the diagnosis of bullous pemphigoid, in conjunction with other laboratory and clinical findings.
## C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
## D Special Instrument Requirements:
Microtiter plate reader capable of measuring optical densities at 450 nm and a reference wavelength of between 620 nm and 650 nm
# IV Device/System Characteristics:
## A Device Description:
The Anti-BP230-CF ELISA (IgG) test kit is composed of six ready-to-use microplate strips containing eight individual break-off wells in a frame, three levels of calibrators (2 mL each, at 2, 20, and 200 RU/mL human IgG), positive and negative controls (2.0 mL each), 1x12 mL bottle peroxidase-labelled rabbit anti-human IgG, 1x100 mL bottle sample buffer, 1x12 mL bottle TMB/H₂O₂ chromogen/substrate, 1x12 mL bottle stop solution, and a 1x100 mL bottle of 10X concentrated wash solution.
## B Principle of Operation:
The test kit contains six microplate strips each with eight break-off reagent wells coated with BP230-CF. Diluted patient samples (1:101 in the sample buffer), calibrators and controls are added to the wells and incubated for 30 minutes at 18–25°C. The wells are washed to remove any unbound proteins and non-specific antibodies and rabbit anti-human IgG HRP enzyme conjugate is added to each well. After incubation for 30 minutes at 18–25°C, the wells are washed to remove any unbound HRP enzyme conjugate and 3,3,5,5 tetramethylbenzidine (TMB) enzyme substrate is added. After an additional incubation for 15 minutes at 18–25°C, a stop solution is added. The test strips are placed in a microplate reader and the optical density of the color is measured at a wavelength of 450 nm and a reference wavelength between 620 nm and 650 nm within 30 minutes. The amount of antigen-specific bound antibody is proportional to the color intensity.
# V Substantial Equivalence Information:
## A Predicate Device Name(s):
MESACUP BP180 ELISA Kit and MESACUP BP230 ELISA Kit
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B Predicate 510(k) Number(s):
K071961
C Comparison with Predicate(s):
| Device & Predicate Device(s): | K193115 | K071961 |
| --- | --- | --- |
| Device Trade Name | EUROIMMUN Anti-BP230-CF ELISA (IgG) | MESACUP BP180 ELISA Kit and MESACUP BP230 ELISA Kit |
| General Device Characteristic Similarities | | |
| Intended Use / Indications For Use | The EUROIMMUN Anti-BP230-CF ELISA (IgG) test kit is intended for the qualitative or semi-quantitative determination of immunoglobulin class IgG antibodies against BP230 in human serum and plasma (K3-EDTA, Li+-heparin, Na+-citrate). It is used as an aid in the diagnosis of bullous pemphigoid, in conjunction with other laboratory and clinical findings. | The MESACUP BP180 Test is a semi-quantitative, enzyme-linked immunosorbent assay (ELISA) for the detection of anti BP180 antibodies in human serum. The MESACUP BP180 Test is intended for in-vitro diagnostic use as an aid in the diagnosis of bullous pemphigoid in conjunction with other laboratory and clinical findings. Patients with bullous pemphigoid are known to have either BP180 or BP230 or both types of antibodies in serums. It is recommended that each patient be tested for both BP180 and BP230 antibodies.
The MESACUP BP230 Test is a semi-quantitative, enzyme-linked immunosorbent assay (ELISA) for the detection of anti BP230 antibodies in human serum. The MESACUP BP230 Test is intended for in-vitro diagnostic use as an aid in the diagnosis of bullous pemphigoid in conjunction with other laboratory and clinical findings. Patients with bullous pemphigoid are known to have either BP180 or BP230 or both types of antibodies in serums. It is recommended that each patient be tested for both BP180 |
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| | | and BP230 antibodies. |
| --- | --- | --- |
| Technology | ELISA, photometric | Same |
| Assay Platform | 48-well microtiter plates | Same |
| Substrate | TMB / H2O2 | Same |
| Wash Buffer | 10x concentration | Same |
| Sample Dilution | 1:101 | Same |
| General Device Characteristic Differences | | |
| Assay Type | Qualitative or semi-quantitative | Semi-quantitative |
| Sample Matrix | Serum and plasma | Serum |
| Antigen | Recombinant purified C-terminal section of the human 230 kDa BP antigen | Recombinant purified BP230-N and BP230-C antigen |
| Conjugate | Peroxidase-labelled anti-human IgG (rabbit) | Peroxidase-labelled anti-human IgG (goat) |
| Controls | 1 Positive Control
1 Negative Control | No controls supplied (recommendation that user create own controls) |
| Calibrators | 3 Calibrators: 2, 20 and 200 RU/mL | 2 Calibrators: 0 and 100 U/mL |
| Measuring Range | 2.75–200 RU/mL | 5–150 U/mL |
| Reported Results | Ratio (Qualitative)
RU/mL (Semi-quantitative) | U/mL (Semi-quantitative) |
| Interpretation | Ratio result*:
<1.0: negative
≥1.0: positive
RU/mL result:
<20: negative
≥20: positive | U/mL result:
<9: negative
≥9: positive |
* Ratio = OD of sample / OD of calibrator 2 (20 RU/mL)
VI Standards/Guidance Documents Referenced:
- CLSI EP6-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
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VII Performance Characteristics (if/when applicable):
A Analytical Performance:
1. Precision/Reproducibility:
All studies were evaluated based on semi-quantitative measurement (RU/mL) and qualitative interpretation (positive: ratio ≥1.0; negative: ratio <1.0) calculated by the ratio of OD of the sample to the OD of the cut-off, Calibrator 2 (20 RU/mL).
Precision: Single-site precision was investigated using six native patient serum samples with values at different points on the calibration curve. A total of 80 determinations per sample were obtained in 40 different runs on 20 different days (with two runs per day and two replicates per run). For semi-quantitative determination, the standard deviations (SD) and coefficients of variation (CV) of repeatability (within-run), between-run, between-day, and within-lab (total) imprecision were calculated and the results are summarized in the following table:
| | | Within-Run | | Between-Run | | Between-Day | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (RU/mL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 4.7 | 0.4 | 9.5 | 0.3 | 6.4 | 0.3 | 5.9 | 0.6 | 12.9 |
| 2 | 14.9 | 0.8 | 5.3 | 1.1 | 7.7 | 0.9 | 5.9 | 1.6 | 11.0 |
| 3 | 19.0 | 1.6 | 8.2 | 0.7 | 3.5 | 1.2 | 6.3 | 2.1 | 11.0 |
| 4 | 24.8 | 1.7 | 6.9 | 1.4 | 5.5 | 1.4 | 5.7 | 2.6 | 10.5 |
| 5 | 109.0 | 3.4 | 3.1 | 5.0 | 4.6 | 2.9 | 2.7 | 6.7 | 6.2 |
| 6 | 130.3 | 4.9 | 3.8 | 5.4 | 4.2 | 3.7 | 2.9 | 8.2 | 6.3 |
The single-site imprecision was analyzed using qualitative determination, and the following results were obtained:
| Sample | Mean Ratio | Range of Ratio | Expected Result | Pos/Neg | Agreement (%) |
| --- | --- | --- | --- | --- | --- |
| 1 | 0.3 | 0.3–0.4 | Negative | 0 / 80 | 100.0 |
| 2 | 0.8 | 0.6–0.9 | Negative | 0 / 80 | 100.0 |
| 3 | 1.0* | 0.7–1.1 | Negative | 18 / 62 | 77.5 |
| 4 | 1.1 | 1.0–1.2 | Positive | 76 / 4 | 95.0 |
| 5 | 3.3 | 2.6–3.7 | Positive | 80 / 0 | 100.0 |
| 6 | 3.8 | 3.4–4.3 | Positive | 80 / 0 | 100.0 |
* mean ratio rounded from 0.95
Lot-to-Lot Reproducibility: Between-lot reproducibility was investigated using nine native patient serum samples with values at different points on the calibration curve. A total of 90 determinations were obtained per sample by testing with three lots on five different days (with two runs per day and three replicates per run). For semi-quantitative determination, the SD and %CV of within-run, between-run, between-lot and total imprecision were calculated, and the results are summarized in the following table:
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Between-lot reproducibility was analyzed using qualitative determination, and the following results were obtained:
| | | Within-Run | | Between-Run | | Between-Lot | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (RU/mL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 4.5 | 0.5 | 11.6 | 0.6 | 14.2 | 0.1 | 3.0 | 0.8 | 18.6 |
| 2 | 14.1 | 1.8 | 12.5 | 0.8 | 5.7 | 0.4 | 2.5 | 2.8 | 14.9 |
| 3 | 14.1 | 1.1 | 7.6 | 1.0 | 7.3 | 0.0 | 0.0 | 1.5 | 10.5 |
| 4 | 16.9 | 0.7 | 3.9 | 1.0 | 5.9 | 0.6 | 3.3 | 1.5 | 8.7 |
| 5 | 17.8 | 0.8 | 4.6 | 1.1 | 6.0 | 0.5 | 3.0 | 1.5 | 8.7 |
| 6 | 18.1 | 1.3 | 7.3 | 1.7 | 9.5 | 0.6 | 3.5 | 2.6 | 14.4 |
| 7 | 22.0 | 1.7 | 7.8 | 0.7 | 3.1 | 1.7 | 7.7 | 2.6 | 11.9 |
| 8 | 102.7 | 5.1 | 4.9 | 5.4 | 5.3 | 0.0 | 0.0 | 8.7 | 8.5 |
| 9 | 124.4 | 7.3 | 5.9 | 8.2 | 6.6 | 0.0 | 0.0 | 11.6 | 9.4 |
Site-to-Site Reproducibility: Between-site reproducibility was investigated using six native patient serum samples with values at different points on the calibration curve. A total of 90 determinations were obtained per sample by testing at three sites for five different days (with two runs per day and three replicates per run). For semi-quantitative determination, the SD and $\% \mathrm{CV}$ for within-run, between-run, between-site and total reproducibility were calculated, and the results are summarized in the following table:
| | | Within-Run | | Between-Run | | Between-Site | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean (RU/mL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 4.8 | 0.3 | 7.2 | 0.4 | 7.7 | 0.3 | 5.7 | 0.6 | 12.3 |
| 2 | 16.8 | 0.9 | 5.6 | 0.8 | 4.5 | 1.2 | 7.4 | 1.9 | 11.1 |
| 3 | 18.0 | 0.9 | 5.0 | 0.6 | 3.5 | 1.5 | 8.3 | 2.0 | 11.0 |
| 4 | 20.9 | 1.9 | 8.9 | 2.0 | 9.5 | 2.4 | 11.3 | 3.6 | 17.4 |
| 5 | 91.6 | 5.2 | 5.7 | 4.2 | 4.5 | 8.5 | 9.3 | 11.0 | 12.0 |
| 6 | 128.3 | 5.7 | 4.5 | 6.5 | 5.1 | 9.5 | 7.4 | 13.6 | 10.6 |
Between-site reproducibility was analyzed using qualitative determination, and the following results were obtained:
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| Sample | Mean Ratio | Range of Ratio | Expected Result | Pos / Neg | Agreement (%) |
| --- | --- | --- | --- | --- | --- |
| 1 | 0.3 | 0.2–0.4 | Negative | 0 / 90 | 100.0 |
| 2 | 0.9 | 0.6–1.0 | Negative | 1 / 89 | 98.9 |
| 3 | 0.9 | 0.7–1.1 | Negative | 10 / 80 | 88.9 |
| 4 | 1.0 | 0.7–1.2 | Positive | 49 / 41 | 54.4 |
| 5 | 2.7 | 2.2–3.5 | Positive | 90 / 0 | 100.0 |
| 6 | 3.5 | 2.7–4.3 | Positive | 90 / 0 | 100.0 |
2. Linearity:
The linearity of EUROIMMUN Anti-BP230-CF ELISA was evaluated based on the CLSI guideline EP06-A. The sample preparations covered the range of 2.0 to 202.33 RU/mL using two sets of samples. Each set included 11 sample dilutions and was measured in a run with four replicates per sample dilution; the mean of the four replicates for each sample was calculated. The linear regression analysis of observed value (RU/mL) vs. expected value (RU/mL) of samples was performed. The results support that the EUROIMMUN Anti-BP230-CF ELISA assay was linear for the claimed measuring range, 2.75–200 RU/mL.
3. Analytical Specificity/Interference:
To investigate the influence from the potential endogenous interferents, three samples at different anti-BP230-CF antibody concentrations (negative, low positive, high positive) were prepared for testing rheumatoid factor and five samples with different anti-BP230-CF antibody concentrations (two negatives, one low positive, and two high positives) were prepared for testing hemoglobin, triglycerides, and bilirubin. The recovery in relation of the spiked sample with interferent to the unspiked sample without interferent was calculated. No interference (the recovery within 85–115%) was observed for concentrations of up to 1,000 mg/dL for hemoglobin, 2,000 mg/dL for triglycerides, 40 mg/dL for bilirubin, and 1,000 IU/mL for rheumatoid factor.
For the potential exogenous interferents, four test samples with different anti-BP230-CF antibody concentrations (two negatives, one low positive, one high positive) were spiked with potential exogenous interferent substances (mycophenolic acid, cyclophosphamide monohydrate, prednisone, and azathioprine). The recovery in relation of the spiked sample with interferent to the unspiked sample without interferent was calculated. No interference (the recovery within 85–115%) was observed for concentrations of up to 4.2 mg/dL for mycophenolic acid, 54.9 mg/dL for cyclo-phosphamide monohydrate, 0.0099 mg/dL for prednisone, and 0.258 mg/dL for azathioprine.
4. Assay Reportable Range:
The assay reportable range of the Anti-BP230-CF ELISA is 2.75 to 200 RU/mL.
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
a. Traceability: A recognized standard or reference material for anti-BP230 antibodies is not available. The assay is calibrated in relative arbitrary units (RU/mL) in semi-quantitative mode. Alternatively, results may be given in ratios of the cut-off calibrator (Calibrator 2, 20 RU/mL) and then defined as positive or negative in qualitative mode.
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b. Shelf-life Stability: In the real-time stability study for sealed products, aliquots of the reagents were stored at 2–8°C. Three different reagent lots were used for testing samples (three positive samples, calibrators and controls) at 0, 3, 6, 12, 18, and 24 months. The results of the study support a claim that the EUROIMMUN Anti-BP230-CF ELISA kit is stable for up to 12 months at 2–8°C.
c. Open-vial Reagent Stability: In the real-time stability study for open-vial products, aliquots of the reagents were opened and stored at 2–8°C. Three different reagent lots were used for testing samples (three positive samples, calibrators and controls) at 0, 3, 6, and 12 months. The results of the study support a claim that the EUROIMMUN Anti-BP230-CF ELISA reagents in open vials are stable for up to 6 months at 2–8°C.
6. Detection Limit:
Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ) were determined per CLSI EP17-A2.
For LoB, a set of four native negative (blank) human samples in the range below the measuring interval was obtained from four healthy individuals. Each sample was run in 15 replicates (five replicates per run x one run per day x three days) using two lots of reagents to reach a total of 60 measurements per lot. The LoB of the Anti-BP230-CF ELISA was found to be 1.53 RU/mL.
For LoD, a set of four samples with low measurand concentrations near the lower end of the measuring interval was investigated. Each sample was run in 15 replicates (five replicates per run x one run per day x three days) using two lots to reach a total of 60 measurements per lot. The LoD of the Anti-BP230-CF ELISA was found to be 2.35 RU/mL.
For LoQ, another set of four low measurand content samples from the lower end of the measuring interval was investigated. Each sample was run in 15 replicates (five replicates per run x one run per day x three days) using two lots to reach a total of 60 measurements per lot. Based on the functional sensitivity analysis, the LoQ of the Anti-BP230-CF ELISA was defined as the lowest concentration that met %CV ≤ 20% and was found to be 2.75 RU/mL.
7. Assay Cut-Off:
The Anti-BP230-CF ELISA is determined to be negative for <20 RU/mL and positive for ≥20 RU/mL in the semi-quantitative analysis, and negative for a ratio of <1.0 and positive for a ratio of ≥1.0 in the qualitative analysis.
B Comparison Studies:
1. Method Comparison with Predicate Device:
A panel of 202 clinical samples was tested with the EUROIMMUN Anti-BP230-CF ELISA and with the MBL MESACUP BP230 ELISA (predicate) according to their respective package inserts. The samples contained 101 bullous pemphigoid, 11 pemphigoid gestationis, 15 systemic sclerosis, 20 Sjögren’s syndrome, 15 rheumatoid arthritis, 20 systemic lupus erythematosus, and 20 diabetes mellitus type 1 (T1D) disease samples. Both RU/mL (semi-quantitative) and ratio (qualitative) assessments yielded the same results as shown in the following table:
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| Samples (N=202) | MBL MESACUP BP230 ELISA (predicate) | | | |
| --- | --- | --- | --- | --- |
| | | Positive | Negative | Total |
| EUROIMMUN Anti-BP230-CF ELISA (K193115) | Positive | 44 | 18 | 62 |
| | Negative | 11 | 129 | 140 |
| | Total | 55 | 147 | 202 |
| Sample (N=202) | No. Agreement | % Agreement | 95% C.I. |
| --- | --- | --- | --- |
| Positive Agreement | 44 / 55 | 80.0 | 67.0–89.6 |
| Negative Agreement | 129 / 147 | 87.8 | 81.3–92.6 |
| Overall Agreement | 173 / 202 | 85.6 | 80.0–90.2 |
The performance of the EUROIMMUN Anti-BP230-CF ELISA and MBL MESACUP BP230 ELISA assay was further analyzed by comparing the test result to clinical diagnosis using this sample cohort. The results are summarized in the following table.
| Disease Panel | Sample (N) | EUROIMMUN Anti-BP230-CF ELISA | MBL MESACUP BP230 ELISA (Predicate) |
| --- | --- | --- | --- |
| | | Positive% (n/N) | Positive % (n/N) |
| Bullous pemphigoid | 101 | 57.4 (58/101) | 49.5 (50/101) |
| Disease Panel | Sample (N) | EUROIMMUN Anti-BP230-CF ELISA | MBL MESACUP BP230 ELISA (Predicate) |
| --- | --- | --- | --- |
| | | Negative% (n/N) | Negative% (n/N) |
| Pemphigoid gestationis | 11 | 90.9 (10/11) | 90.9 (10/11) |
| Systemic sclerosis | 15 | 93.3 (14/15) | 100.0 (15/15) |
| Sjögren’s syndrome | 20 | 95.0 (19/20) | 90.0 (18/20) |
| Rheumatoid arthritis | 15 | 100.0 (15/15) | 100.0 (15/15) |
| Systemic lupus erythematosus | 20 | 100.0 (20/20) | 95.0 (19/20) |
| Diabetes mellitus type 1 | 20 | 95.0 (19/20) | 95.0 (19/20) |
| Total (non-BP) | 101 | 96.0 (97/101) | 95.0 (96/101) |
2. Matrix Comparison:
The usability of plasma in the Anti-BP230-CF ELISA was investigated using 31 sample sets each consisting with matched serum and corresponding plasma matrices (K3-EDTA, Li+-heparin, Na+-citrate). The samples covered relevant analyte levels across the measuring interval. Passing-Bablok regression was performed for the comparison of plasma to serum.
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The results in RU/mL are shown in the table below.
| | EDTA Plasma | Heparin Plasma | Citrate Plasma |
| --- | --- | --- | --- |
| N | 29 | 30 | 30 |
| Sample range (RU/mL) (serum) | 4.46–197.62 | 4.28–197.62 | 4.28–197.62 |
| Sample range (RU/mL) (plasma) | 3.84–188.65 | 3.12–91.19 | 3.03–183.73 |
| Slope (95% C.I.) | 0.99 (0.90–1.06) | 0.98 (0.94–1.01) | 0.98 (0.93–1.03) |
| Intercept (95% C.I.) | 0.71 (-2.00–8.47) | 1.18 (-1.66–3.91) | -0.36 (-1.73–3.64) |
| R² | 0.95 | 0.99 | 0.99 |
The results in Ratio are shown in the table below.
| | EDTA Plasma | Heparin Plasma | Citrate Plasma |
| --- | --- | --- | --- |
| N | 31 | 31 | 31 |
| Sample range (Ratio) (serum) | 0.20–5.23 | 0.20–5.23 | 0.20–5.23 |
| Sample range (Ratio) (plasma) | 0.22–5.29 | 0.21–4.98 | 0.21–5.05 |
| Slope (95% C.I.) | 1.00 (0.93–1.06) | 0.98 (0.94–1.03) | 0.98 (0.94–1.02) |
| Intercept (95% C.I.) | -0.01 (-0.09–0.14) | 0.02 (-0.06–0.14) | -0.00 (-0.06–0.12) |
| R² | 0.96 | 0.99 | 0.99 |
# C Clinical Studies:
# 1. Clinical Sensitivity and Clinical Specificity:
A clinical study was performed using a total of 421 clinically characterized samples (168 from BP patients and 253 from patient with other control diseases). The samples were tested with the EUROIMMUN Anti-BP230-CF ELISA (IgG). The clinical sensitivity and specificity of the assay were evaluated based on the test results in semi-quantitative (RU/mL) and qualitative (ratio) determinations. Both RU/mL (semi-quantitative) and ratio (qualitative) assessments yielded the same results as shown in the following table:
| Clinical Sensitivity | | | | |
| --- | --- | --- | --- | --- |
| Panel | N (men, women) | Mean Age (range) | Positive (%) (n/N) | 95% C.I. |
| Bullous pemphigoid | 168 (73, 95) | 78 (46 – 98) | 50.6 (85/168) | 42.8 – 58.4 |
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| Clinical Specificity | | | | |
| --- | --- | --- | --- | --- |
| Panel | N (men, women) | Mean Age (range) | Negative (%) (n/N) | 95% C.I. |
| Pemphigus vulgaris | 15 (9, 6) | 50 (30 – 78) | 100.0 (15/15) | 78.2 – 100.0 |
| Pemphigus foliaceus | 15 (8, 7) | 63 (34 – 86) | 93.3 (14/15) | 68.1 – 99.8 |
| Linear IgA dermatosis | 17 (10, 7) | 54 (2 – 102) | 100.0 (17/17) | 80.5 – 100.0 |
| Epidermolysis bullous acquisita | 17 (4, 13) | 51 (16 – 92) | 88.2 (15/17) | 63.6 – 98.5 |
| Sjögren’s syndrome | 20 (1, 19) | 53 (16 - 77) | 95.0 (19/20) | 75.1 – 99.9 |
| Systemic lupus erythematosus | 20 (5, 15) | 42 (19 – 78) | 100.0 (20/20) | 83.2 – 100.0 |
| Systemic sclerosis | 15 (5, 10) | 62 (23 – 87) | 93.3 (14/15) | 68.1 – 99.8 |
| Rheumatoid arthritis | 15 (5, 10) | 63 (33 – 86) | 100.0 (15/15) | 78.2 – 100.0 |
| Diabetes mellitus type 1 | 20 (11, 9) | 39 (18 – 62) | 95.0 (19/20) | 75.1 – 99.9 |
| Hashimoto’s thyroiditis | 19 (1, 18) | 36 (10 – 64) | 100.0 (19/19) | 82.4 – 100.0 |
| Dermatitis herpetiformis | 20 (10, 10) | 55 (18 – 85) | 100.0 (20/20) | 83.2 – 100.0 |
| Dermatomyositis | 20* (2, 5) | 47 (24 – 62) | 100.0 (20/20) | 83.2 – 100.0 |
| Multiple sclerosis | 20 (7, 13) | Unknown | 100.0 (20/20) | 83.2 – 100.0 |
| Malignancy ** | 20 (8, 12) | 63 (19 – 88) | 100.0 (20/20) | 83.2 – 100.0 |
| TOTAL | 253 | | 97.6 (247/253) | 94.9 – 99.1 |
* gender information was unknown for 13 dermatomyositis samples
** 10 leukemia, 5 lymphoma, and 5 lung cancer samples were included
2. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable
D Clinical Cut-Off:
See assay cut-off
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# E Expected Value/Reference Range:
The expected value for the Anti-BP230-CF ELISA assay in the normal population is negative. Anti-BP230 antibodies were analyzed with the Anti-BP230-CF ELISA (IgG) using a panel of 438 sera from normal healthy adult blood donors (including 286 men and 152 women with an average age of 40 years old, ranging from 22 to 67 years). The samples were assayed according to the package insert and the results are summarized in the following table.
| Healthy Blood Donors (n = 438) | | |
| --- | --- | --- |
| | Semi-quantitative (RU/mL) | Qualitative (Ratio) |
| Positives (n) | 9 | 9 |
| Negatives (n) | 429 | 429 |
| Prevalence % (95% C.I.) | 2.1 (1.0 – 3.9) | 2.1 (1.0 – 3.9) |
| Range (min, max) | <2.75 to 94.4 | 0.004 to 3.3 |
| Mean | 8.6 | 0.4 |
| Median | 6.5 | 0.3 |
# 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.
