(222 days)
Not Found
No
The description details a standard enzyme immunoassay (ELISA) for detecting antibodies. There is no mention of AI, ML, or any computational analysis beyond standard quantitative measurement of color intensity.
No
This device is for in vitro diagnostic (IVD) use to detect antibodies for diagnostic purposes, not for treating or preventing a disease.
Yes
The 'Intended Use / Indications for Use' section explicitly states that the results obtained with this test "assist in serological diagnosis of EBV infection."
No
The device is an in vitro diagnostic test that uses physical reagents and a microtest plate to perform an ELISA assay, which is a hardware-based process.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device is for the "qualitative detection of IgM antibodies to the Epstein-Barr Virus early antigens (EA) p54 and p138 in human serum or plasma." This is a test performed in vitro (outside the body) on a biological sample (serum or plasma) to provide information about a patient's health status (presence of EBV infection).
- Device Description: The description details an "enzyme immunoassay" (ELISA), which is a common laboratory technique used for in vitro diagnostic testing. It describes the use of recombinant antigens immobilized on a solid phase to detect antibodies in a patient sample.
- Performance Studies: The document describes a clinical study evaluating the performance of the device using patient samples, which is typical for the validation of an IVD.
- Predicate Device: The mention of a "Predicate Device" (K822734; EBV IgM Test by Gull Laboratories, Inc.) is a strong indicator that this device is being submitted for regulatory review as an IVD, as predicate devices are used for comparison in the regulatory process for new IVDs.
All of these points align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Biotest EA IgM ELISA is an enzyme immunoassay using recombinant antigens for the qualitative detection of IgM antibodies to the Epstein-Barr Virus early antigens (EA) p54 and p138 in human serum or plasma. Results obtained with this test, in conjunction with other clinical and patient data obtained in assays for other Epstein-Barr virus-specific antibodies such as anti-Early Antigen IgG and anti-EBNA-1 IgG, assist in serological diagnosis of EBV infection in pediatric and adult populations.
Product codes
LSE
Device Description
Using recombinant DNA technology, Biotest has developed three highly purified EBV antigens for use in their ELISA test system.
- EBNA-1 p72: Major antigen of the EBNA complex. The recombinant protein does not contain the glycine-alanine copolymer, a structural feature of EBNA-1, which shows cross-reactivities with certain autoantibodies and CMV (IgM response).
- EA-D p64: Early antigen. Dominant immunogen of the EA-D complex.
- EA p138: Early antigen and major DNA binding protein. This highly reactive antigen is not detectable in EA immunofluorescence assays based on chemically induced Raji cells (deletion within the Raji genome).
The EBV immune status will be determined by the detection of specific antibodies directed against EBV proteins according to the principle of the indirect ELISA. The antigens are purified to apparent homogeneity and immobilized on the solid phase (microtest plate, 96 wells). If the patient's serum contains specific antibodies they will bind during the first incubation. Non-specific antibodies are removed by washing steps. During a second incubation the captured IgM antibodies are labeled. This is performed by addition of murine monoclonal anti-human IgM antibody-enzyme-conjugates. The final reaction converts a colorless substrate to a colored product. The concentration of color after a definite time is related to the concentration of antibody in the serum sample.
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
pediatric and adult populations.
Intended User / Care Setting
Not Found
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
The performance of the Biotest EA IgM ELISA was evaluated in a clinical study of 408 patient samples conducted at two geographically distinct locations. Samples were obtained from both pediatric and adult patients (ages 1 to 74) representing acute (139), late acute (34), recent past (12), past (120), reactivation (22), past/probable reactivation (11), and negative (70) disease stages of EBV infection.
Annotation protocol: Two methods were used to evaluate the performance of the Biotest EA IgM ELISA: direct comparison with commercially available or published EA IgM IFA tests, and comparison with clinical interpretation (stage of infection based on antibody patterns and clinical diagnosis at the time the specimen was drawn).
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Clinical study, Sensitivity/Specificity, Cross Reactivity, Reproducibility
Sample Size: 408 patient samples (for sensitivity/specificity)
Standalone Performance: Not Found
Key Results:
Sensitivity/Specificity:
Results of the direct comparison with VCA IgM/IgG IFA for both sites combined demonstrated a relative sensitivity of 84.1% and a relative specificity of 89.4%.
Clinical Interpretation based results: Total Clinical Sensitivity = 98.2% (C.I. = 96.2 to 99.3%), Total Clinical Specificity = 97.1% (C.I. = 90.1 to 99.7%), Total Clinical Agreement = 98.0%.
Cross Reactivity: No cross reactivity was observed when the Biotest EA IgM ELISA was used to test samples from patients acutely infected with: Herpes Simplex Virus I/II (4 of 5 samples non-reactive), Varicella Zoster Virus (5 of 11 samples non-reactive), Cytomegalovirus (3 of 9 samples non-reactive), and Toxoplasma (4 of 5 samples non-reactive). No cross reactivity was observed in tests of rheumatoid factor positive (n = 10), antinuclear antibody positive (n = 5) and ASL positive (n = 15) samples.
Reproducibility:
Inter-Run (Site 1, n=11) %C.V. range: 9.7 - 16.9
Intra-Run (Site 1, n=8) %C.V. range: 2.8 - 6.3
Inter-Run (Site 2, n=5) %C.V. range: 3.1 - 7.7
Intra-Run (Site 2, n=24) %C.V. range: 6.2 - 14.7
Inter-Lab (n=14) %C.V. range: 7.9 - 15.7
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Relative Sensitivity (Direct Comparison): 84.1%
Relative Specificity (Direct Comparison): 89.4%
Relative Agreement (Direct Comparison): 87.0%
Clinical Interpretation based results:
Sensitivity by infection stage: Acute 99.2%, Convalescent 97.8%, Past 97.5%, Reactivation 96.9%.
Specificity by infection stage: Negative 97.1%.
Total Clinical Sensitivity = 98.2%
Total Clinical Specificity = 97.1%
Total Clinical Agreement = 98.0%
Predicate Device(s):
Reference Device(s):
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.3235 Epstein-Barr virus serological reagents.
(a)
Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).(b)
Classification. Class I (general controls).
0
JUN g 1999
:
ATTACHMENT I
REVISED 510(k) SUMMARY
57
1
510(k) Summary of Information Respecting Safety and Effectiveness
- A. Name and Address of Submitter Biotest Diagnostics Corporation Company Name and Address: 66 Ford Road, Suite 131 Denville, NJ 07834 (609) 397-8511 Telephone: (609) 397-8224 FAX: Patricia E. Bonness, Official Correspondent Contact Person: Date 510fk) Summary was Prepared: October 26, 1998 B. Device Names Biotest Anti-EBV Recombinant Proprietary Name: EA IgM EBV EA IgM Common Name: Epstein-Barr virus serological reagents Classification Name:
- C. Legally Marketed Device
Biotest Diagnostics claims substantial equivalence to the EBV IgM Test (K822734) currently in commercial distribution by Gull Laboratories, Inc., Salt Lake City, UT.
D. Device Description
Using recombinant DNA technology, Biotest has developed three highly purified EBV antigens for use in their ELISA test system.
- EBNA-1 p72: Major antigen of the EBNA complex. The recombinant protein does not contain the glycine-alanine copolymer, a structural feature of EBNA-1, which shows cross-reactivities with certain autoantibodies and CMV (IgM response).
- EA-D p64: Early antigen. Dominant immunogen of the EA-D complex.
- EA p138: Early antigen and major DNA binding protein. This highly reactive antigen is not detectable in EA immunofluorescence assays based on chemically induced Raji cells (deletion within the Raji genome).
2
| Biotest
Anti-EBV
| recombinant | recombinant antigens | monoclonal secondary antibody (HRP-conjugated) | |||
|---|---|---|---|---|---|
| p72 | p54 | p134 | anti-human IgG | anti-human IgM | |
| EA IgM | X | X | X | ||
| EA IgG | X | X | X | ||
| EBNA IgG | X | X |
Biotest Anti-EBV ELISA TESTS
The EBV immune status will be determined by the detection of specific antibodies directed against EBV proteins according to the principle of the indirect ELISA. The antigens are purified to apparent homogeneity and immobilized on the solid phase (microtest plate, 96 wells). If the patient's serum contains specific antibodies they will bind during the first incubation. Non-specific antibodies are removed by washing steps. During a second incubation the captured IgM antibodies are labeled. This is performed by addition of murine monoclonal anti-human IgM antibody-enzyme-conjugates. The final reaction converts a colorless substrate to a colored product. The concentration of color after a definite time is related to the concentration of antibody in the serum sample.
E. Intended Use
The Biotest EA IgM ELISA is an enzyme immunoassay using recombinant antigens for the qualitative detection of IgM antibodies to the Epstein-Barr Virus early antigens (EA) p54 and p138 in human serum or plasma. Results obtained with this test, in conjunction with other clinical and patient data obtained in assays for other Epstein-Barr virus-specific antibodies such as anti-Early Antigen IgG and anti-EBNA-1 IgG, assist in serological diagnosis of EBV infection in pediatric and adult populations.
3
- Comparison with Predicate Device F.
:
।
(
ﻧﮯ
A summary comparison of the features of the Biotest EA IgM and the Gull VCA IGM test kits is provided in Table 1 below:
Table 1 Feature Comparison of Biotest and Gull EBV IgM Test Kits
| Biotest | Gull | |
|---|---|---|
| Intended Use | Detection of IgM antibodies | |
| to EBV EA | ||
| Qualitative only | Detection of IgM antibodies | |
| to EBV VCA | ||
| Qualitative only | ||
| Assay Method | ELISA | Indirect fluorescent antibody (IFA) |
| Reactive Ingredients | Recombinant EBV (EA p54/p138) | |
| Peroxidase-conjugated monoclonal | ||
| anti-human IgM (mouse) | HR1, Burkitt's lymphocytic cells | |
| Fluorescein-labeled | ||
| anti-human IgM | ||
| Specimen: Type | ||
| Min. Volume | ||
| Storage | Serum or plasma | |
| 25 µl | ||
| 2 - 8°C or -20°C | Serum | |
| 15 µl of 1:10 and 1:40 dilutions | ||
| 2 - 8°C/7days or -20°C | ||
| Controls | Negative | |
| Positive | Negative | |
| Positive | ||
| Chromogen | TMB | Fluorescein |
| Results: | ||
| Evaluation | spectrophotometer @ 450 nm | Fluorescence microscope |
| Kit Size | 96 tests | 50 or 100 tests |
୧୦
4
G. Performance Data
Sensitivity/Specificity
The performance of the Biotest EA IgM ELISA was evaluated in a clinical study of 408 patient samples conducted at two geographically distinct locations. Samples were obtained from both pediatric and adult patients (ages 1 to 74) representing acute (139), late acute (34), recent past (12), past (120), reactivation (22), past/probable reactivation (11), and negative (70) disease stages of EBV infection.
Two methods were used to evaluate the performance of the Biotest EA IgM ELISA: direct comparison with commercially available or published EA IgM IFA tests, and comparison with clinical interpretation (stage of infection based on antibody patterns and clinical diagnosis at the time the specimen was drawn).
Results of the direct comparison with VCA IgM/IgG IFA for both sites combined demonstrated a relative sensitivity of 84.1% and a relative specificity of 89.4%.
Table 1
Clinical Site 1 Direct Comparison to VCA IgM/IgG IFA
| VCA IgM/IgG IFA | |||
|---|---|---|---|
| + | - | Total | |
| Biotest + | 73 | 13 | 86 |
| Biotest - | 14 | 108 | 122 |
| Total | 87 | 121 | 208 |
Relative Sensitivity = 83.9% Relative Specificity = 89.3% Relative Agreement = 87.0% (C.I. = 74.5 to 90.9%) (C.I. = 83.7 to 94.8%)
5
Table 2
| VCA IgM/IgG IFA | |||
|---|---|---|---|
| + | - | Total | |
| Biotest + | 80 | 11 | 91 |
| Biotest - | 15 | 94 | 109 |
| Total | 95 | 105 | 200 |
Clinical Site 2 Direct Comparison to VCA IgM/IgG IFA
《《 Relative Sensitivity = 84.2% Relative Specificity = 89.5% Relative Agreement = 87.0%
..............................................................................................................................................................................
)
1
(C.I. = 75.3 to 90.0%) (C.I. = 83.7 to 95.4%)
Table 3
Combined Site Results Direct Comparison to VCA IgM/IgG
| VCA IgM/IgG | |||
|---|---|---|---|
| + | - | Total | |
| Biotest + | 153 | 24 | 177 |
| Biotest - | 29 | 202 | 231 |
| Total | 182 | 226 | 408 |
Relative Sensitivity = 84.1% Relative Specificity = 89.4% Relative Agreement = 87.0%
(C.I. = 78.7 to 89.4%) (C.I. = 85.4 to 93.4%)
6
Results based on Clinical Interpretation of all patient samples where Biotest ELISA EA IgM antibody responses matched expected serological pattern analysis for each state of infection, including - Acute, Convalescent (Late Acute or Recent Past), Past, Reactivation and Probable Reactivation/past, and - Negative.
| Clinical Interpretation | |||||
|---|---|---|---|---|---|
| Acute | Convalescent | Past | Reactivation | Negative | |
| Result matches | |||||
| Biotest | 138 | 45 | 117 | 32 | 2 |
| Result does not | |||||
| match Biotest | 1 | 1 | 3 | 1 | 68 |
| Sensitivity | |||||
| Specificity | |||||
| 95% to C.I.% | 99.2% | ||||
| N/A | |||||
| 96.1 - 100 | 97.8% | ||||
| N/A | |||||
| 88.5 - 99.9 | 97.5% | ||||
| N/A | |||||
| 92.9 - 99.5 | 96.9% | ||||
| N/A | |||||
| 84.2 - 99.9 | N/A | ||||
| 97.1% | |||||
| 90.1 - 99.7 |
Total Clinical Sensitivity = 98.2% Total Clinical Specificity = 97.1% Total Clinical Agreement = 98.0% (C.I. = 96.2 to 99.3%) (C.I. = 90.1 to 99.7%)
Note: C.I. = 95% confidence intervals calculated by the exact method.
Cross Reactivity
No cross reactivity was observed when the Biotest EA IgM ELISA was used to test samples from patients acutely infected with:
| Herpes Simplex Virus I/II | 4 of 5 samples found non-reactive |
|---|---|
| Varicella Zoster Virus | 5 of 11 samples found non-reactive |
| Cytomegalovirus | 3 of 9 samples found non-reactive |
| Toxoplasma | 4 of 5 samples found non-reactive |
Further, no cross reactivity was observed in tests of rheumatoid factor positive (n = 10), antinuclear antibody positive (n = 5) and ASL positive (n = 15) samples.
7
Reproducibility
ﻜﺴﺎ
To evaluate the reproducibility of the Biotest EA IgM ELISA, a panel of 10 patient serum specimens (low to high positive) was tested at the clinical sites. The mean, standard deviation (S.D.) and coefficient of variation (C.V.) for inter-run, intra-run and inter-lab reproducibility are presented below.
| Inter-Run (n = 11) | Intra-Run (n = 8) | |||||
|---|---|---|---|---|---|---|
| Panel # | Mean | S.D. | % C.V. | Mean | S.D. | % C.V. |
| 1 | 1.799 | 0.175 | 9.7 | 1.801 | 0.065 | 3.6 |
| 2 | 1.013 | 0.171 | 16.9 | 1.140 | 0.032 | 2.8 |
| 3 - | 1.280 | 0.183 | 14.3 | 1.286 | 0.070 | 5.5 |
| 4 | 0.294 | 0.033 | 11.2 | 0.287 | 0.018 | 6.3 |
| 5 | 1.065 | 0.119 | 11.2 | 1.189 | 0.059 | 5.0 |
| 6 | 0.651 | 0.088 | 13.5 | 0.680 | 0.034 | 5.1 |
| 7 | 1.231 | 0.152 | 12.3 | 1.325 | 0.060 | 4.5 |
| 8 | 0.959 | 0.130 | 13.5 | 0.946 | 0.060 | 6.3 |
| 9 | 0.798 | 0.100 | 12.5 | 0.811 | 0.037 | 4.6 |
| 10 | 0.664 | 0.067 | 10.0 | 0.711 | 0.020 | 2.9 |
Site #1
Site #2
| Inter-Run (n = 5) | Intra-Run (n = 24) | |||||
|---|---|---|---|---|---|---|
| Panel # | Mean | S.D. | % C.V. | Mean | S.D. | % C.V. |
| 1 | 1.641 | 0.127 | 7.7 | 1.829 | 0.268 | 14.7 |
| 2 | 1.165 | 0.036 | 3.1 | 1.257 | 0.164 | 13.1 |
| 3 | 1.415 | 0.043 | 3.1 | 1.471 | 0.124 | 8.4 |
| 4 | 0.335 | 0.020 | 6.0 | 0.362 | 0.052 | 14.4 |
| 5 | 1.271 | 0.063 | 5.0 | 1.372 | 0.127 | 9.3 |
| 6 | 0.664 | 0.032 | 4.8 | 0.773 | 0.076 | 9.9 |
| 7 | 1.360 | 0.083 | 6.1 | 1.522 | 0.104 | 6.8 |
| 8 | 1.009 | 0.075 | 7.4 | 1.111 | 0.099 | 8.9 |
| 9 | 0.932 | 0.037 | 3.9 | 0.997 | 0.070 | 7.0 |
| 10 | 0.705 | 0.019 | 2.7 | 0.783 | 0.048 | 6.2 |
8
| Inter-Lab (n = 14) | |||
|---|---|---|---|
| Panel # | Mean | S.D. | % C.V. |
| 1 | 1.75 | 0.172 | 9.8 |
| 2 | 1.061 | 0.167 | 15.7 |
| 3 | 1.322 | 0.173 | 13.1 |
| 4 | 0.307 | 0.037 | 11.9 |
| 5 | 1.129 | 0.140 | 12.4 |
| 6 | 0.655 | 0.077 | 11.8 |
1.271
0.974
0.840
0.677
12.0
12.1
13.1
7.9
0.153
0.117
0.110
0.053
Inter-Lab (n = 14)
8
9
10
)
P
7 *
9
Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird-like figure with three stylized lines forming its body and wings.
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
JUN 9 1999
Ms. Patricia E. Bonness Official Correspondent Biotest Diagnostics Corporation 66 Ford Road Suite 131 Denville, New Jersey 07834
Re: K983842
Trade Name: Biotest Anti-EBV Recombinant EA IgM Regulatory Class: I Product Code: LSE Dated: March 15, 1999 Received: March 31, 1999
Dear Ms. Bonness:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition. FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
10
Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours.
Steven Autman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
11
Page _ of _
- J10(k) Number (if known): 4983892
Device Name: _________________________________________________________________________________________________________________________________________________________________
Indications For Use:
The Biotest EA IgM is an enzyme immunoassay for the detection of IgM antibodies to the Epstein-Barr Virus (EBV-EA (Early Antigens) p54/p138) in human serum or plasma.
It is indicated for use, in conjunction with other clinical and patient data obtained in assays for other Epstein-Barr antigens such as EBNA IgG and Early Antigen IgG, in the serological diagnosis of EBV infection.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
| Concurrence of CDRH, Office of Device Evaluation (ODE) | ||||
|---|---|---|---|---|
| Woody Dubois (Division Sign Off) | ||||
| Division of Clinical Laboratory Devices | ||||
| 510(k) NumberK983842 | 510(k) Number | K983842 | ||
| 510(k) Number | K983842 | |||
| Prescription Use X | ||||
| (Per 21 CFR 801.109) | OR | Over-The-Counter Use ______ | ||
| (Optional Format 1-2-96) |