(58 days)
The Trinity Biotech Captia™ Herpes Group IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative determination of IgG antibodies in human serum to Herpes simplex virus. The Herpes Group IgG ELISA kit may be used to determine serologic status in females of child bearing age, and to evaluate paired sera for the presence of a seroconversion of IgG as an aid in the diagnosis of Herpes simplex virus infection. It is not intended for determining the type of Herpes simplex virus.
The Herpes Group IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative determination of IgG antibodies in human serum to Herpes simplex virus. The Herpes Group IgG ELISA kit may be used to evaluate paired sera for the presence of seroconversions of IgG as an aid in the diagnosis of Herpes simplex virus infection.
The Herpes Group IgG ELISA test is an enzyme linked immunosorbent assay to detect IgG antibodies to Herpes simplex virus. Purified Herpes Group antigen is attached to a solid phase microtiter well. Diluted test sera are 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 IgG is added to each 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 and indirect measurement of specific antibody in the patient specimen.
The Trinity Biotech Herpes Group IgG ELISA Test Kit was evaluated for its agreement with predicate devices (Clark HSV 1 and HSV 2 ELISA assays) and for precision, cross-reactivity, and paired serum study performance.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state acceptance criteria in terms of predefined thresholds that the device must meet for approval. Instead, it presents performance characteristics (agreement percentages and precision) observed in comparison to predicate devices and other studies. The approval from the FDA indicates that the device's performance, as demonstrated, was deemed substantially equivalent to existing predicate devices. We can infer that the reported percentages of agreement and precision values were considered acceptable by the regulatory body for demonstrating substantial equivalence.
Based on the cumulative data from the four comparison studies with the predicate device, the key performance metrics are:
| Metric | Acceptance Criteria (Inferred from FDA Approval for Substantial Equivalence) | Reported Device Performance (Cumulative across 4 studies) |
|---|---|---|
| % Agreement Positive | Performance demonstrated substantial equivalence to predicate device | 98.9% (95% CI: 97.9% - 100%) |
| % Agreement Negative | Performance demonstrated substantial equivalence to predicate device | 96.7% (95% CI: 94.2% - 99.1%) |
| % Total Agreement | Performance demonstrated substantial equivalence to predicate device | 98.1% (95% CI: 97.0% - 99.2%) |
| Precision (Intersite CV) | < 15% (for appropriate technique), as stated for user expectation | From 9.08% to 15.1% for positive sera (Sera #1-5) |
| 121% and 150% for negative sera (Sera #6-7) | ||
| Paired Serum Study (Seroconversion) | 100% agreement expected for evaluable pairs | 100% agreement (for 11 evaluable pairs) |
| Cross-Reactivity | No cross-reactivity with EBV, CMV, VZV | No cross-reactivity observed with tested sera |
| CDC Panel Total Agreement | Performance demonstrated substantial equivalence to predicate device | 96.9% (excluding 2 equivocals) |
| CDC Panel Positive Agreement | Performance demonstrated substantial equivalence to predicate device | 95.7% |
| CDC Panel Negative Agreement | Performance demonstrated substantial equivalence to predicate device | 100% |
2. Sample Sizes Used for the Test Set and Data Provenance
The primary test set for comparison with the predicate device involved sera tested across four different sites.
- Study 1 (Maryland R&D lab): 187 frozen sera (normals aged 12-83, various gender and geographical areas). Retrospective.
- Study 2 (New York R&D lab): 152 frozen sera (normals aged 17-59, various gender and geographical areas). Retrospective.
- Study 3 (Pennsylvania clinical lab): 176 prospective samples sent for Herpes antibody testing. Prospective.
- Study 4 (Wisconsin clinical lab): 88 frozen random normal samples. Retrospective.
- Total Sample Size for Primary Comparison: 603 sera (cumulative across all four studies).
- CDC Panel: A masked, characterized serum panel (details on total number not explicitly stated, but 72% positive and 28% negative samples, with 2 equivocals excluded). The origin is the Centers for Disease Control (CDC), implying a well-characterized and respected source.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This study does not involve human readers interpreting results or establishing ground truth based on expert consensus. The "ground truth" for the comparative studies is the result obtained from the predicate device, the Clark HSV 1 and HSV 2 ELISA assays. For the CDC panel, the "ground truth" is the CDC's characterization of the panel samples. No human experts in the traditional sense (e.g., radiologist) are described as establishing ground truth in this context; instead, the comparator assays serve this role.
4. Adjudication Method for the Test Set
Not applicable. The study compares the new device's results directly against a predicate device. There is no mention of human adjudication for discrepancies between the new device and the predicate device or a clinical outcome.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This type of study is typically done for diagnostic imaging tests or similar assessments where human readers interpret results, and the AI's impact on their performance is evaluated. The device in question is an ELISA kit, which produces quantitative results, not interpretations by human readers in the style of imaging.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, the studies presented are standalone performance evaluations of the Trinity Biotech Herpes Group IgG ELISA kit. The results are generated solely by the device (the assay) and compared against a predicate device or a characterized panel. There is no human "in the loop" impacting the diagnostic output of the device itself.
7. The Type of Ground Truth Used
- For the primary comparison: The predicate device's results (Clark HSV 1 and HSV 2 ELISA assays) served as the "ground truth" or reference standard against which the new device's qualitative agreement (% agreement positive, negative, and total) was measured.
- For the paired serum study: The complement fixation (CF) method was used to determine seroconversion, serving as the ground truth.
- For the cross-reactivity study: The presence of IgG antibodies to specific viruses (EBV, CMV, VZV) was likely determined by established ELISA or other serological methods for those viruses, acting as the ground truth for non-cross-reactivity.
- For the CDC panel: The CDC's characterization of the masked serum panel served as the ground truth.
It is important to note that the document explicitly states: "There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be made on the comparison assay's accuracy to predict disease." This clarifies that the ground truth is primarily based on concordance with another assay, not directly on clinical pathology or patient outcomes.
8. The Sample Size for the Training Set
The document does not describe a "training set" in the context of an algorithm or AI development. ELISA kits are laboratory tests with defined chemical reactions and optical detection methods; they are not typically "trained" in the way AI models are. The development and optimization of the test kit itself would involve internal studies and reagent validation, but these are distinct from a typical AI training/validation set paradigm.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" for an algorithm described, this point is not applicable. The development of the ELISA test kit relies on established biochemical principles and validation procedures to ensure the reagents and protocol accurately detect the target antibodies.
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Summary of Safety and Effectiveness Information Herpes Group IgG ELISA Test Kit
- I. Trinity Biotech 2823 Girts Road Jamestown, NY 14701 Contact person: Bonnie B. DeJoy Telephone: 716-483-3851 Date of preparation: Nov. 20, 2003
II. Description of Device
The Herpes Group IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative determination of IgG antibodies in human serum to Herpes simplex virus. The Herpes Group IgG ELISA kit may be used to evaluate paired sera for the presence of seroconversions of IgG as an aid in the diagnosis of Herpes simplex virus infection.
The Herpes Group IgG ELISA test is an enzyme linked immunosorbent assay to detect IgG antibodies to Herpes simplex virus. Purified Herpes Group antigen is attached to a solid phase microtiter well. Diluted test sera are 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 IgG is added to each 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 and indirect measurement of specific antibody in the patient specimen.
III. Predicate Device
The Herpes Group IgG ELISA test is substantially equivalent to Clark Laboratories, Inc. (Clark) HSV I and HSV II ELISA tests. Equivalence is demonstrated by the following comparative results:
Performance Characteristics
- % Agreement Positive and % Agreement Negative. Four different sites compared the Trinity Biotech Herpes Group IgG ELISA test relative to Clark HSVI ELISA assays. The first site was a R&D laboratory at a commercial company located in Maryland. The frozen sera were from normals with ages from 12-83, with various gender and geographical areas. The results of the study are compiled and summarized in Table 1.
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Please be advised the "% agreement positive" and "% agreement negative" refers to the Note: comparison of this assay's results to that of a similar assay. There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be made on the comparison assay's accuracy to predict disease.
Table 1 Comparison of Herpes Group IgG ELISA and Clark HSV 1 and HSV 2 Study 1
Trinity Biotech Herpes Group IgG ELISA
| + | eq | - | Total | ||
|---|---|---|---|---|---|
| ClarkHSV 1 &HSV 2 | +* | 104 | 1 | 1 | 106 |
| eq* | 3 | 0 | 0 | 3 | |
| -*** | 4 | 2 | 72 | 78 | |
| Total | 111 | 3 | 73 | 187 |
| % Agreement positive = 104/105 = 99.1% | 95% Confidence interval = 97.2% - 100% |
|---|---|
| % Agreement negative = 73/76 = 94.7% | 95% Confidence interval = 89.6% - 99.9% |
| % Agreement = 176/181 = 97.2% | 95% Confidence interval = 94.8% - 100% |
Equivocals were not included in the above calculations. The 95% confidence intervals were calculated using the normal method.
- Indicates positive on Clark HSV 1 and/or Clark HSV 2.
** Indicated equivocal on Clark HSV 1 and/or Clark HSV 2.
*** Indicates negative on both Clark HSV 1 and Clark HSV 2.
The second site was a R&D laboratory at a commercial company located in New York. The frozen sera were from normals with ages from 17-59, with various fender and geographical areas. The results of the study are compiled and summarized in Table 2.
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Table 2 Comparison of Herpes Group IgG ELISA and Clark HSV 1 and Clark HSV 2 Study 2
Trinity Biotech Herpes Group IgG ELISA
| + | eq | - | Total | |||
|---|---|---|---|---|---|---|
| ClarkHSV 1 andHSV 2 | +* | 92 | 6 | 2 | 100 | |
| eq** | 1 | 0 | 0 | 1 | ||
| -*** | 0 | 0 | 51 | 51 | ||
| Total | 93 | 6 | 53 | 152 | ||
| % Agreement positive = 92/94 = 97.9% | 95% Confidence interval = 94.9% - 100% |
95% Confidence interval = 94.2% - 100% % Agreement negative = 51/51 = 100% % Agreement = 143/145 = 98.6% 95% Confidence interval = 96.7% - 100%
Equivocals were not included in the above calculations.
The 95% confidence intervals were calculated using the normal method.
The 95% confidence interval for % agreement positive was calculated assuming one false positive.
- Indicates positive on Clark HSV 1 and/or Clark HSV 2.
** Indicated equivocal on Clark HSV land/or Clark HSV 2.
*** Indicates negative on both Clark HSV 1 Clark HSV 2.
The third site was a clinical laboratory located in Pennsylvania. The sera were prospective samples sent in to the lab for Herpes antibody testing. The results of the studies are compiled and summarized in Table 3.
Table 3 Comparison of Herpes Group IgG ELISA and Clark HSV 1 and Clark HSV 2 Study 3
Trinity Biotech Herpes Group IgG ELISA
| + | eq | - | Total | ||
|---|---|---|---|---|---|
| +* | 112 | 0 | 1 | 113 | |
| ClarkHSV 1 andHSV 2 | eq** | 1 | 0 | 1 | 2 |
| -*** | 3 | 4 | 54 | 61 | |
| Total | 116 | 4 | 56 | 176 |
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| % Agreement positive = 112/113 = 99.1% | 95% Confidence interval = 97.4% - 100% |
|---|---|
| % Agreement negative = 54/57 = 94.7% | 95% Confidence interval = 88.8% - 100% |
| % Agreement = 166/170 = 97.7% | 95% Confidence interval = 95.3% - 100% |
Equivocals were not included in the above calculations. The 95% confidence intervals were calculated using the normal method.
The 95% confidence intervals were calculated using the normal method.
- Indicates positive on Clark HSV 1 and/or Clark HSV 2.
** Indicated equivocal on Clark HSV land/or Clark HSV 2.
*** Indicates negative on both Clark HSV 1 Clark HSV 2.
The fourth site was a clinical laboratory located in Wisconsin. The frozen sera were random normal samples. The results of the studies are compiled and summarized in Table 4.
Table 4 Comparison of Herpes Group IgG ELISA and Clark HSV 1 and Clark HSV 2 Study 4
Trinity Biotech Herpes Group IgG ELISA
| + | eq | - | Total | ||
|---|---|---|---|---|---|
| ClarkHSV 1 andHSV 2 | +* | 62 | 0 | 0 | 62 |
| eq** | 0 | 0 | 0 | 0 | |
| -*** | 1 | 0 | 25 | 26 | |
| Total | 63 | 0 | 25 | 88 |
| % Agreement positive = 62/62 = 100% | 95% Confidence interval = 95.3% - 100% |
|---|---|
| % Agreement negative = 25/26 = 96.2% | 95% Confidence interval = 96.2% - 100% |
| % Agreement = 87/88 = 98.9% | 95% Confidence interval = 98.9% - 100% |
Equivocals were not included in the above calculations.
The 95% confidence intervals were calculated using the normal method. The 95% confidence interval for % agreement positive was calculated assuming on false positive.
- Indicates positive on Clark HSV 1 and/or Clark HSV 2.
** Indicated equivocal on Clark HSV 1and/or Clark HSV 2.
*** Indicates negative on both Clark HSV 1 Clark HSV 2.
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The results of the four studies are compiled and summarized in Table 5.
Table 5 Comparison of Herpes Group IgG ELISA and Clark HSV 1 and Clark HSV 2
Trinity Biotech Herpes Group IgG ELISA
| + | eq | - | Total | ||
|---|---|---|---|---|---|
| ClarkHSV 1 andHSV 2 | +* | 370 | 7 | 4 | 381 |
| eq** | 5 | 0 | 1 | 6 | |
| -*** | 7 | 6 | 203 | 216 | |
| Total | 382 | 13 | 208 | 603 |
| % Agreement positive = 370/374 = 98.9% | 95% Confidence interval = 97.9% - 100% |
|---|---|
| % Agreement negative = 203/210 = 96.7% | 95% Confidence interval = 94.2% - 99.1% |
| % Agreement = 573/584 = 98.1% | 95% Confidence interval = 97.0% - 99.2% |
Equivocals were not included in the above calculations.
The 95% confidence intervals were calculated using the normal method.
- Indicates positive on Clark HSV 1 and/or Clark HSV 2.
** Indicated equivocal on Clark HSV 1and/or Clark HSV 2.
*** Indicates negative on both Clark HSV 1 Clark HSV 2.
- Precision. Seven sera were assayed ten times each on three different assays at three different sites. The intersite precision is shown in Table 6. With appropriate technique the user should obtain precision of <15% CV.
Table 6 Herpes Group IgG ELISA inter Site Precision Study
| (n = 90) | |||
|---|---|---|---|
| Sera # | X | SD | CV |
| 1. | 3.81 | 0.351 | 9.21% |
| 2. | 2.03 | 0.255 | 12.6% |
| 3. | 3.16 | 0.287 | 9.08% |
| 4. | 2.01 | 0.272 | 13.5% |
| 5. | 1.31 | 0.198 | 15.1% |
| 6. | 0.09 | 0.109 | 121% |
| 7. | 0.03 | 0.045 | 150% |
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Paired Serum Study
Twenty serum pairs tested by CF from patients suspected of having acute Herpes simplex infection were assayed on the Trinity Biotech Herpes Group IgG ELISA assay. Each serum pair was evaluated to determine a seroconversion. Six serum pairs could not be evaluated due to the acute being positive. Three serum pairs could not be evaluated due to the convalescent being negative. The remaining eleven pairs all demonstrated a seroconversion thus giving a 100% agreement positive versus CF for showing a seroconversion in antibody for serum meeting the paired sera criteria.
Cross-Reactivity
Serum containing IgG antibody detectable by ELISA to Epstein Barr virus, Cytomegalovirus, and Varicella-zoster virus were assayed. The data summarized in Table 8 indicate that antibodies to these Herpes Viruses do not cross-react with the Trinity Biotech Herpes Group IgG ELISA kit.
Table 7
Cross-Reactivity
| SERUM | TrinityHerpes GroupIgG | EBV VCA | CMV | VZV |
|---|---|---|---|---|
| 1 | 0.17 | 2.6 | Negative | 2.7 |
| 2 | 0.05 | 2.3 | Negative | 1.6 |
| 3 | 0.00 | Negative | Negative | 2.2 |
| 4 | 0.00 | 1.8 | Negative | 2.0 |
| 5 | 0.14 | 6.3 | 1.2 | 2.1 |
| 6 | 0.08 | 2.4 | Negative | 3.3 |
| 7 | 0.09 | 1.1 | Negative | 2.1 |
| 8 | 0.12 | 7.2 | 1.1 | 3.2 |
| 9 | 0.18 | Negative | 2.9 | 3.0 |
Sera ≥ 1.10 were considered positive. Sera ≤ 0.90 were considered negative.
The following information is from a serum panel obtained from the Centers for Disease Control (CDC) and tested by the Trinity Biotech Herpes Group IgG ELISA. The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC.
The panel consists of 72% positive and 28% negative samples. Excluding two equivocals, the Trinity Biotech Herpes Group IgG ELISA demonstrated 96.9% total agreement with the CDC results. Of the results obtained by the Trinity Biotech Herpes Group IgG ELISA, there was 95.7% aggreement with the positive specimens, and 100% agreement with the negative specimens.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular emblem with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is a stylized image of a caduceus, a symbol often associated with medicine and healthcare, featuring a staff with a serpent entwined around it.
Public Health Service
NOV 26 2003
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Bonnie B. DeJoy Director, Quality Systems Trinity Biotech USA P.O. Box 1059 Jamestown. NY 14702-1059
Re: K033059
Trade/Device Name: Captia Herpes Group IgG ELISA Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus Serological Reagents Regulatory Class: Class III Product Code: LGC Dated: September 17, 2003 Received: September 29, 2003
Dear Ms. DeJoy:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21. Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Steven Sutman
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Page 1 of 1
510(k) Number: K033059
Device Name: Trinity Biotech Captia™ Herpes Group IgG ELISA
Indications For Use: The Trinity Biotech Captia™ Herpes Group IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative determination of IgG antibodies in human serum to Herpes simplex virus. The Herpes Group IgG ELISA kit may be used to determine serologic status in females of child bearing age, and to evaluate paired sera for the presence of a seroconversion of IgG as an aid in the diagnosis of Herpes simplex virus infection. It is not intended for determining the type of Herpes simplex virus.
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED
Concurrence of CDRH, Office of Device Evaluation (ODE)
| Prescription Use | ✓ | OR | Over-The-Counter Use ______ |
|---|---|---|---|
| (Per 21 XFR 801.109) | (Optional Format 1-2-96) |
Division Sign-Off
Office of In Vitro Diagnostic Device
Evaluation and Safety
510(k) K033059
§ 866.3305 Herpes simplex virus serological assays.
(a)
Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.(b)
Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).