(155 days)
The Viral Capsid Antigen (VCA) IgM kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgM antibodies in human serum to VCA antigen. The Clark anti-VCA IgM assay may be used in conjunction with other Epstein-Barr serologies (EA-D IgG, VCA IgG, EBNA-1 IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis in the adult population.
The Wampole Epstein-Barr Viral Capsid Antigen (VCA) IgM kit is an Enzyme-Linked Immunosorbent Assays (ELISA) for the qualitative determination of IgM antibodies in human serum to VCA antigen. The Wampole anti-VCA IgM assay may be used in conjunction with other Epstein-Barr serologies (VCA IgG, EBNA-1 IgG, EA-D IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis. For In Vitro Diagnostic Use Only. The VCA IgM ELISA test is an enzyme linked immunosorbent assay to detect IgM antibodies to Epstein-Barr Viral Capsid antigen. Afinity purified gp125 VCA antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgM is added to each well. If antibody is present it will bind to the antibody attached to the antigen on the well. After incubation the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present the substrate will undergo a color change. After an incubation period the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.
Here's a breakdown of the acceptance criteria and the study details for the Wampole VCA IgM ELISA Test Kit, based on the provided text:
Acceptance Criteria and Device Performance
The acceptance criteria for the Wampole VCA IgM ELISA Test Kit are based on its performance in terms of sensitivity and specificity, as demonstrated by the serum characterization study.
| Acceptance Criteria Category | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Sensitivity | High relative sensitivity for acute EBV cases | 97.4% (95% CI: 92.2%-100%) for Acute cases |
| Specificity (Seronegative) | High relative specificity for seronegative individuals | 96.4% (95% CI: 89.4%-100%) for Seronegative cases |
| Specificity (Seropositive) | High relative specificity for seropositive individuals | 99.0% (95% CI: 97.0%-100%) for Seropositive cases |
| Overall Agreement | High overall agreement with serological characterization | 98.2% (95% CI: 96.1%-100%) |
| Cross-Reactivity | No cross-reactivity with common interfering antibodies (HSV, CMV, VZV, RF) | Demonstrated no cross-reactivity (all VCA IgM results were negative, while alternate assays were positive) |
Note: The document does not explicitly state numerical acceptance thresholds (e.g., "sensitivity must be >95%"). Instead, the reported performance metrics serve as the basis for demonstrating substantial equivalence to the predicate device.
Study Details
1. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 166 selected serum samples.
- Data Provenance: The text states, "One hundred and sixty six selected serum were tested at a clinical lab." This suggests the data is retrospective, as the serum samples were "selected" and "characterized," implying they were already collected and categorized before the study. The country of origin is not specified, but the submission is to the U.S. FDA, so it's likely U.S.-based or from a region with similar clinical practices.
2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts used to establish the ground truth. The ground truth ("seronegative," "acute," or "seropositive" EBV infection) was established based on a panel of other Epstein-Barr serologies (VCA IgM, heterophile antibody, EBNA IgG, VCA IgG). It is implied that these serological profiles, rather than individual expert opinions, served as the basis for characterization.
3. Adjudication Method for the Test Set
The document does not detail an adjudication method. The characterization of serum samples (acute, seropositive, seronegative) was based on the presence or absence of specific markers from a panel of EBV serologies. It's an objective classification based on laboratory results, not subjective interpretation requiring adjudication.
4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not reported. This study evaluates an in vitro diagnostic device (ELISA kit), not an AI system or imaging device where human reader performance would be a primary metric.
5. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this study represents a standalone performance evaluation of the Wampole VCA IgM ELISA Test Kit. The test kit itself is the "algorithm" or device being evaluated, and its performance (sensitivity, specificity, precision, cross-reactivity) is assessed directly against the established ground truth of the serum samples. There is no human-in-the-loop interaction being measured for diagnostic performance, other than the standard laboratory procedures for running the assay.
6. The Type of Ground Truth Used
The ground truth used was expert serological characterization. This was based on a panel of established serological markers for Epstein-Barr Virus infection:
- Acute: VCA IgM present, EBNA IgG absent, Heterophile antibody present.
- Seropositive (Past infection): VCA IgG present, EBNA IgG present, VCA IgM absent, Heterophile antibody absent.
- Seronegative: VCA IgG absent, EBNA IgG absent, VCA IgM absent, Heterophile antibody absent.
This method relies on established clinical and laboratory diagnostic criteria to define the true state of EBV infection for each sample.
7. The Sample Size for the Training Set
The document does not report a separate training set or its sample size. This type of diagnostic device (ELISA kit) typically undergoes development and optimization before an official performance study. The data presented here is for the validation/test phase of the device.
8. How the Ground Truth for the Training Set Was Established
As no specific training set is reported, the method for establishing its ground truth is also not mentioned. For the development and optimization of such assays, manufacturers generally use well-characterized clinical samples or panels from reference laboratories.
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11980596
.
ﻣﻨﻬﺎ ﺑ
JUL 22 1998
Summary of Safety and Effectiveness Information VCA IgM ELISA Test Kit
- I. Trinity Biotech US PO Box 1059 Jamestown, NY 14702-1059 Contact person: Ron Cruver Telephone: 716-483-3851 Date of preparation: Feb 11,1998
II. Description of Device
The Wampole Epstein-Barr Viral Capsid Antigen (VCA) IgM kit is an Enzyme-Linked Immunosorbent Assays (ELISA) for the qualitative determination of IgM antibodies in human serum to VCA antigen. The Wampole anti-VCA IgM assay may be used in conjunction with other Epstein-Barr serologies (VCA IgG, EBNA-1 IgG, EA-D IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis.
For In Vitro Diagnostic Use Only.
The VCA IgM ELISA test is an enzyme linked immunosorbent assay to detect IgM antibodies to Epstein-Barr Viral Capsid antigen. Afinity purified gp125 VCA antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgM is added to each well. If antibody is present it will bind to the antibody attached to the antigen on the well. After incubation the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present the substrate will undergo a color change. After an incubation period the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.
III. Predicate Device
The VCA IgM ELISA test is substantially equivalent to EBV serology. Equivalence is demonstrated by the following comparative results:
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Performance Characteristics
1. Sensitivity and Specificity Based on Serum Characterization
One hundred and sixty six selected serum were tested at a clinical lab. The serum from the study were characterized as seronegative ( no serological evidence of past or present EBV infection), acute (VCA IgM and heterophile antibody present, EBNA IgG absent), or seropositive (presence of VCA IgG antibodies and EBNA IgG, no evidence of VCA IgM or heterophile antibody, indicative of past infection). The sensitivity, specificity and agreement of the assay was determined based on this characterization. It was assumed that the VCA IgM response should be negative for seronegative, and convalescent serum, and positive for acute serum. The results are summarized in Table 1.
Table 1
| AcuteVCA IgM+EBNA IgG -Heterophile + | SeropositiveVCA IgG+EBNA IgG+VCA IgM-Heterophile - | SeronegativeVCA IgG-EBNA IgG -VCA IgM -Heterophile - | ||
|---|---|---|---|---|
| WampoleVCA IgM | Positive | 37 | 1 | 1 |
| Equivocal | 1 | 0 | 0 | |
| Negative | 1 | 98 | 27 | |
| Total | 39 | 99 | 28 |
| Relative Sensitivity (Acute) | = 37/38 = 97.4% | 95% Confidence Interval = 92.2%-100% |
|---|---|---|
| Relative Specificity (Seronegative) | = 27/28 = 96.4% | 95% Confidence Interval = 89.4%-100% |
| Relative Specificity (Seropositive) | = 98/99 = 99.0% | 95% Confidence Interval = 97.0%-100% |
| Relative Agreement | = 162/165 = 98.2% | 95% Confidence Interval = 96.1%-100% |
Equivocal results were not included in the calculations.
Equivocal results were not retested. They were reported as equivocal.
The 95% confidence intervals were calculated using the normal method.
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2. Precision.
The Wampole VCA IgM EIA was evaluated for precision by testing six sera ten times each on three different days at two different sites. The results are summarized in the table below.
Inter Site Precision Data
| Inter Site Precision (n=60) | |||
|---|---|---|---|
| Serum# | X | S.D. | C.V. |
| 1 | 1.55 | 0.230 | 14.87% |
| 2 | 1.55 | 0.172 | 11.11% |
| 3 | 4.61 | 0.491 | 10.67% |
| 4 | 3.09 | 0.389 | 12.59% |
| 5 | 0.35 | 0.215 | 62.22% |
| 6 | 0.04 | 0.039 | 94.67% |
| HPC* | 3.23 | 0.480 | 14.90% |
| CAL** | 2.00 | 0.110 | 5.49% |
| NC* | 0.01 | 0.016 | 192.25% |
X = Mean ISR Value
S.D. = Standard Deviation
C.V. = Coefficient of Variation
- HPC and NC n=6
** Cal n = 18
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- Cross-Reactivity. Sera containing IgM antibody detectable by ELISA to Herpes Simplex Virus I & II, Cytomegalovirus, and Varicella Zoster Virus were assayed. Sera containing rhuematoid factor (RF) were also assayed. The data summarized in Table 3 indicates that antibodies to Herpes Viruses and sera containing RF do not cross-react with the VCA IgM EIA kit.
| Specificity | VCA IgM | Alternate Assay | ||
|---|---|---|---|---|
| RF + | 0.04 | - | 1.87 | + |
| RF + | 0.03 | - | 1.82 | + |
| RF + | 0.01 | - | 1.73 | + |
| RF + | 0.01 | - | 1.80 | + |
| RF + | 0.02 | - | 1.85 | + |
| VZV M + | 0.33 | - | 3.28 | + |
| VZV M + | 0.10 | - | 5.46 | + |
| VZV M + | 0.04 | - | 4.98 | + |
| VZV M + | 0.08 | - | 2.34 | + |
| VZV M + | 0.03 | - | 2.18 | + |
| HSV 1 M + | 0.02 | - | 2.53 | + |
| HSV 1 M + | 0.02 | - | 1.65 | + |
| HSV 1 M + | 0.01 | - | 1.34 | + |
| HSV 1 M + | 0.01 | - | 1.32 | + |
| HSV 2 M + | 0.06 | - | 1.76 | + |
| HSV 2 M + | 0.05 | - | 1.60 | + |
| HSV 2 M + | 0.03 | - | 2.09 | + |
| HSV 2 M + | 0.04 | - | 1.96 | + |
| CMV M + | 0.07 | - | 1.23 | + |
| CMV M + | 0.04 | - | 1.92 | + |
| CMV M + | 0.04 | - | 3.83 | + |
| CMV M + | 0.06 | - | 1.32 | + |
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Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA". The caduceus symbol is composed of three curved lines that converge at the bottom.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
· · ·
JUL 22 1998
CLARK LABORATORIES, INC. c/o William L. Boteler, Jr. IMMUNO PROBE, INC. 1306 Bailes Lane, Suite F Frederick, MD 21701
Re: K980596 Trade Name: VCA IgM ELISA Requlatory Class: II Product Code: LSE Dated: April 22, 1998 Received: April 30, 1998
Dear Mr. Boteler:
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 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 requirement, 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 requlatory 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 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.
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Paqe 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 Butman
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
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Page 1 of 1
510(k) Number: K980596
Device Name: VCA IgM ELISA
Indications For Use: The Viral Capsid Antigen (VCA) IgM kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgM antibodies in human serum to VCA antigen. The Clark anti-VCA IgM assay may be used in conjunction with other Epstein-Barr serologies (EA-D IgG, VCA IgG, EBNA-1 IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis in the adult population.
PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) 双 【【日】【:】【
Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use V OR Over-The Counter Use (Per 21 CFR 801.109) (Optional Format 1-2-96)
Division of Clinical Laboratory Devices
510(k) Number K980596
§ 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).