(58 days)
The Trinity Biotech Captia™ Legionella pneumophila IgG/IgM ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative detection of total antibodies (IgG and IgM) to serogroups 1-6 in serum from patients with clinical suspicion of Legionella Disease. The assay is not intended to differentiate between the serotypes of Legionella pneumophila.
The Legionella pneumophila IgG/IgM ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative detection of total antibodies (IgG and IgM) to Legionella pneumophila serogroups 1-6 in serum from patients with clinical suspicion of Legionella Disease.
The Legionella pneumophila IgG/IgM ELISA test is an enzyme linked immunosorbent assay to detect IgG/IgM antibodies to legionella. Purified Legionella pneumophila antigen (serogroups 1, 2, 3, 4, 5, 6) 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 IgG/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 study details for the Trinity Biotech Legionella pneumophila IgG/IgM ELISA Test Kit, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state pre-defined acceptance criteria in terms of numerical thresholds for sensitivity, specificity, or agreement. Instead, it presents the results of a comparative study against a predicate device (Legionella IFA) and implicitly suggests that these results demonstrate substantial equivalence. The precision study evaluates consistency rather than diagnostic accuracy.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Site 1) | Reported Device Performance (Site 2) |
|---|---|---|---|
| % Agreement Positive (compared to IFA positive) | Demonstrate substantial agreement with predicate device (IFA) | 90.00% (95% CI: 79.0% - 100%) | 98.53% (95% CI: 95.6% - 100%) |
| % Agreement Negative (compared to IFA negative) | Demonstrate substantial agreement with predicate device (IFA) | NA (no IFA negative samples) | 98.57% (95% CI: 95.7% - 100%) |
| Precision (Intra-assay CV) | Not explicitly stated, but common industry practice aims for low CVs (e.g., <15-20%) | Max observed: 14.8% (Sera #4, Assay 1, Site 1) | Max observed: 12.3% (Sera #4, Assay 1, Site 2) |
| Precision (Inter-assay CV) | Not explicitly stated, but common industry practice aims for low CVs (e.g., <15-20%) | Max observed: 15.9% (Sera #7, Inter-Assay, Site 1) | Max observed: 11.9% (Sera #4, Inter-Assay, Site 2) |
| Precision (Inter-site CV) | Not explicitly stated, but common industry practice aims for low CVs (e.g., <15-20%) | Max observed: 19.2% (Sera #6, Inter-Site) | Not applicable (inter-site combines both) |
| Seroconversion Detection | Demonstrate agreement in detecting seroconversion compared to IFA | 93.5% agreement | Not applicable (CDC panel results) |
2. Sample Sizes Used for the Test Set and Data Provenance
- Comparative Performance Study (Site 1 - Maryland):
- Sample Size: 33 single IFA positive sera.
- Data Provenance: Retrospective. Samples were "from an outbreak and samples routinely submitted for Legionella testing" at a commercial R&D lab in Maryland.
- Comparative Performance Study (Site 2 - Pennsylvania):
- Sample Size: 72 prospective serum samples.
- Data Provenance: Prospective. Samples were "routinely submitted for Legionella testing" at a clinical laboratory in Pennsylvania.
- IFA Paired Serum Analysis (CDC Panel):
- Sample Size: 31 serum pairs (total of 62 samples, though the analysis focuses on the 31 seroconversions).
- Data Provenance: Presumed retrospective, from samples "submitted to CDC for titer confirmation." Origin of patients not specified, but the CDC is a US federal agency.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth for the test sets was established using Legionella IFA (Immunofluorescence Assay).
- The document implies that the IFA results were the established "truth" for comparison. It does not explicitly mention human experts establishing this ground truth for each individual sample, but rather relies on the accepted methodology of the IFA itself, likely performed by trained laboratory personnel.
- For the CDC Panel, the serum pairs were "confirmed to be serologically positive for an increase in titer" by IFA at the CDC. This suggests that the CDC's internal lab procedures and personnel established this confirmation. Specific qualifications of the CDC personnel are not provided.
4. Adjudication Method for the Test Set
There was no multi-expert adjudication method described for the test sets. The results of the Trinity Biotech ELISA were directly compared to the results of the Legionella IFA.
- Equivocal results from the Trinity Biotech ELISA were excluded from the agreement calculations.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This study focuses on the performance of the device itself (an ELISA kit) compared to a predicate device (IFA), not on human reader performance with or without AI assistance.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
This is a standalone study of the ELISA kit. The ELISA kit is a laboratory test with a defined output; there isn't an "algorithm" in the sense of AI that could operate without human involvement in running the test. The test results are read photometrically, and interpretation of those results to classify as positive, negative, or equivocal is inherent to the kit's design, rather than being an AI-driven interpretation.
7. Type of Ground Truth Used
The ground truth used was comparison to a predicate device (Legionella IFA).
- For the comparative performance studies, the IFA results (titer ≥ 256 for positive, < 256 for negative) served as the reference standard.
- For the CDC Panel, "seroconversion" as determined by a greater than 4-fold increase in IFA titer was the ground truth.
8. Sample Size for the Training Set
The document does not provide information about a specific "training set" or "validation set" in the context of machine learning. This is a traditional IVD device submission, where studies are designed to demonstrate performance against a reference method rather than training a model. Therefore, no explicit training set size is mentioned.
9. How the Ground Truth for the Training Set Was Established
As no distinct training set is described for an AI/algorithm, this question is not applicable to the provided document. The performance studies described are essentially validation studies against established clinical (IFA) or commercial (R&D lab) reference points.
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NOV 2 6 2003
K033a51
Summary of Safety and Effectiveness Information Legionella pneumophila IgG/IgM 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 Legionella pneumophila IgG/IgM ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative detection of total antibodies (IgG and IgM) to Legionella pneumophila serogroups 1-6 in serum from patients with clinical suspicion of Legionella Disease.
The Legionella pneumophila IgG/IgM ELISA test is an enzyme linked immunosorbent assay to detect IgG/IgM antibodies to legionella. Purified Legionella pneumophila antigen (serogroups 1, 2, 3, 4, 5, 6) 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 IgG/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 Legionella pneumonphila IgG/IgM ELISA test is substantially equivalent to BioWhittaker's Legionella STAT test. Equivalence is demonstrated by the following comparative results:
Performance Characteristics
% Agreement Positive and % Agreement Negative
The Trinity Biotech Legionella pneumophila IgG/IgM ELISA was evaluated relative to Legionella IFA at two different sites. The first site was a commercial R&D lab located in Marvland. Thirty-three single IFA positive sera, from an outbreak and samples routinely submitted for Legionella testing, were tested. The results of the study are summarized in Table 3.
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Table 3 Comparison of Trinity Biotech Legionella pneumophila IgG/IgM ELISA and Legionella IFA Trinity Biotech Legionella pneumophila IgG/IgM ELISA
| + | eq | - | Total | |
|---|---|---|---|---|
| + ≥ 256 | 27 | 3 | 3 | 33 |
| IFA - < 256 | 0 | 0 | 0 | 0 |
| Total | 27 | 3 | 3 | 33 |
| % Agreement positive | $27/30 = 90.00%$ | 95% Confidence interval = $79.0% - 100%$ |
|---|---|---|
| % Agreement negative | NA | 95% Confidence interval = NA |
Equivocals were not included in the above calculations. The 95% confidence intervals were calculated using the normal method.
Please be advised that "% agreement positive" and "% agreement negative" refer to the 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.
The second site was a clinical laboratory in Pennsylvania. Seventy-two prospective serum for Legionella testing were tested. The results of the study are summarized in Table 4.
Table 4 Comparison of Trinity Biotech Legionella pneumophila IgG/IgM ELISA and Legionella IFA
Trinity Biotech Legionella pneumophila IgG/IgM ELISA
| + | eq | - | Total | ||
|---|---|---|---|---|---|
| IFA | + ≥256 | 2 | 0 | 0 | 2 |
| - <256 | 1 | 2 | 67 | 70 | |
| Total | 3 | 2 | 67 | 72 |
% Agreement positive = 67/68 = 98.53% 95% Confidence Interval = 95.6% - 100% % Agreement negative = 69/70 = 98.57% 95% Confidence Interval = 95.7% - 100%
Equivocals were not included in the above calculations.
The 95% confidence intervals were calculated using the normal method.
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Precision
Seven different sera were assayed at two different sites to determine the precision of the assay. An additional three sera were tested at site 1. Each sera was tested ten times each, on three different days at each of the two study sites. The intra- and inter-assay precision for each site is presented in Tables 5 and 6. The inter-site coefficient of variation (CV) for each serum is presented in Table 7.
Table 5 Trinity Biotech Legionella pneumophila IgG/IgM ELISA Intra- and Inter-Assay Precision Study 1
| Assay 1 (n=10) | Assay 2 (n=10) | Assay 3 (n=10) | Inter-Assay(n=30) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sera# | X | SD | CV | X | SD | CV | X | SD | CV | X | SD | CV |
| 1 | 3.17 | 0.138 | 4.35% | 3.55 | 0.235 | 6.62% | 3.41 | 0.349 | 10.2% | 3.42 | 0.305 | 8.92% |
| 2 | 2.44 | 0.244 | 10.0% | 2.66 | 0.267 | 10.0% | 2.41 | 0.127 | 5.27% | 2.50 | 0.247 | 9.88% |
| 3 | 2.49 | 0.322 | 12.9% | 2.78 | 0.240 | 8.63% | 2.81 | 0.332 | 11.8% | 2.70 | 0.327 | 12.1% |
| 4 | 1.22 | 0.180 | 14.8% | 1.36 | 0.131 | 9.63% | 1.16 | 0.125 | 10.8% | 1.25 | 0.164 | 13.1% |
| 5 | 0.50 | 0.051 | 10.2% | 0.56 | 0.042 | 7.50% | 0.53 | 0.041 | 7.74% | 0.53 | 0.050 | 9.43% |
| 6 | 0.18 | 0.025 | 13.9% | 0.21 | 0.023 | 11.0% | 0.20 | 0.031 | 15.5% | 0.20 | 0.030 | 15.0% |
| 7 | 0.28 | 0.039 | 13.9% | 0.34 | 0.046 | 13.5% | 0.33 | 0.048 | 14.6% | 0.32 | 0.051 | 15.9% |
| 8 | 1.02 | 0.051 | 5.00% | 1.13 | 0.039 | 3.45% | 1.19 | 0.044 | 3.70% | 1.11 | 0.084 | 7.57% |
| 9 | 0.85 | 0.053 | 6.24% | 0.92 | 0.025 | 2.72% | 0.99 | 0.043 | 4.34% | 0.92 | 0.069 | 7.50% |
| 10 | 0.96 | 0.067 | 6.98% | 1.05 | 0.056 | 5.33% | 1.11 | 0.094 | 8.47% | 1.03 | 0.122 | 11.20% |
| HPC* | 3.64 | .0402 | 11.05% | |||||||||
| CAL** | 1.44 | 0.122 | 8.44% | |||||||||
| LPC* | 1.49 | 0.195 | 13.11% | |||||||||
| NC* | 0.18 | 0.052 | 28.97% |
- n = 17 ** n = 51
Table 6
Trinity Biotech Legionella pneumophila IgG/IgM ELISA Intra- and Inter-Assay Precision
Study 2
| Assay 1 (n=10) | Assay 2 (n=10) | Assay 3 (n=10) | Inter-Assay(n=30) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sera# | X | SD | CV | X | SD | CV | X | SD | CV | X | SD | CV | |
| 1 | 2.80 | 0.246 | 8.79% | 2.66 | 0.165 | 6.20% | 3.08 | 0.245 | 7.95% | 2.85 | 0.272 | 9.54% | |
| 2 | 3.10 | 0.343 | 11.1% | 3.05 | 0.276 | 9.05% | 3.14 | 0.259 | 8.25% | 3.10 | 0.293 | 9.45% | |
| 3 | 3.31 | 0.392 | 11.8% | 3.17 | 0.220 | 6.94% | 3.38 | 0.214 | 6.33% | 3.31 | 0.289 | 8.73% | |
| 4 | 1.10 | 0.135 | 12.3% | 1.15 | 0.131 | 11.4% | 1.18 | 0.142 | 12.0% | 1.16 | 0.138 | 11.9% | |
| 5 | 0.56 | 0.060 | 10.7% | 0.58 | 0.053 | 9.14% | 0.59 | 0.036 | 6.10% | 0.58 | 0.050 | 8.62% | |
| 6 | 0.28 | 0.016 | 5.71% | 0.26 | 0.013 | 5.00% | 0.29 | 0.020 | 6.90% | 0.28 | 0.020 | 7.14% | |
| 7 | 0.29 | 0.018 | 6.21% | 0.28 | 0.020 | 7.14% | 0.31 | 0.023 | 7.42% | 0.29 | 0.023 | 7.93% | |
| HPC* | 3.16 | 0.092 | 2.91% | ||||||||||
| CAL** | 1.45 | 0.060 | 4.11% | ||||||||||
| LPC* | 1.68 | 0.190 | 11.29% | ||||||||||
| NC* | 0.35 | 0.121 | 34.44% | ||||||||||
| * n = 5 |
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Table 7
Trinity Biotech Legionella pneumophila IgG/IgM ELISA Inter-Site Precision Study Inter Site (n=60)
| Sera # | X | SD | CV | # positive | #equivocal | #negative |
|---|---|---|---|---|---|---|
| 1 | 3.13 | 0.406 | 13.0% | 60 | 0 | 0 |
| 2 | 2.80 | 0.403 | 14.4% | 60 | 0 | 0 |
| 3 | 3.00 | 0.431 | 14.4% | 60 | 0 | 0 |
| 4 | 1.21 | 0.158 | 13.1% | 43 | 16 | 1 |
| 5 | 0.56 | 0.055 | 9.82% | 0 | 0 | 60 |
| 6 | 0.24 | 0.046 | 19.2% | 0 | 0 | 60 |
| 7 | 0.30 | 0.040 | 13.3% | 0 | 0 | 60 |
| 8* | 1.11 | 0.084 | 7.57% | 19 | 11 | 0 |
| 9* | 0.92 | 0.069 | 7.50% | 0 | 20 | 10 |
| 10* | 1.03 | 0.122 | 11.20% | 8 | 20 | 2 |
| HPC** | 3.42 | 0.401 | 11.75% | 9 | 0 | 0 |
| CAL*** | 1.45 | 0.069 | 4.77% | 27 | 0 | 0 |
| LPC** | 1.56 | 0.240 | 15.46% | 9 | 0 | 0 |
| NC** | 0.27 | 0.124 | 45.68% | 0 | 0 | 9 |
-
- n = 30 ** n = 9 *** n = 27 X = Mean SD = Standard Deviation CV = Coefficient of Variation = SD/X x 100
The methods in NCCLS EP5 were utilized for precision parameters.
- n = 30 ** n = 9 *** n = 27 X = Mean SD = Standard Deviation CV = Coefficient of Variation = SD/X x 100
IFA Paired Serum Analysis (CDC Panel)
The following information is from a serum panel tested at the Centers for Disease Control (CDC) by IFA and confirmed to be serologically positive for an increase in titer from <1:256 to >1:256. The sera were submitted to CDC for titer confirmation. The results are presented as a means to convey further information on the performance of this assay with a masked serum panel. This does not imply an endorsement of the assay by the CDC.
The panel consisted of thirty-one serum pairs showing a greater than 4-fold increase in IFA titer. Each serum pair was evaluated on the Trinity Biotech Legionella pneumophila IgG/IgM ELISA assay to determine a seroconversion in antibody. Twenty nine pairs had a seroconversion, thus giving a % agreement positive of 29/31 = 93.5% in detecting seroconversions.
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Image /page/4/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, which is a traditional symbol of medicine and healthcare.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV 26 2003
Ms. Bonnie B. DeJoy Director, Quality Systems Trinity Biotech USA P.O. Box 1059 Jamestown, NY 14702-1059
Re: K033051
Trade/Device Name: Legionella pneumophila IgG/IgM ELISA Regulation Number: 21 CFR 866.3300 Regulation Name: Haemophilus spp. serological reagents Regulatory Class: Class II Product Code: MJH 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. Iisting 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 (QS) regulation (21 CFR Part 820).
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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). You may obtain other general information on your responsibilities under the Act 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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510(k) Number: K033051
Device Name: Trinity Biotech Captia™ Legionella pneumophila IgG/IgM ELISA
Indications For Use: The Trinity Biotech Captia™ Legionella pneumophila IgG/IgM ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative detection of total antibodies (IgG and IgM) to serogroups 1-6 in serum from patients with clinical suspicion of Legionella Disease. The assay is not intended to differentiate between the serotypes of Legionella pneumophila.
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Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use V (Per 21 XFR 801.109)
OR
Over-The-Counter Use (Optional Format 1-2-96)
Thomas J. O'Brien for SYH
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K033051
§ 866.3300
Haemophilus spp. serological reagents.(a)
Identification. Haemophilus spp. serological reagents are devices that consist of antigens and antisera, including antisera conjugated with a fluorescent dye, that are used in serological tests to identifyHaemophilus spp. directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusHaemophilus and provides epidemiological information on diseases cause by these microorganisms. Diseases most often caused byHaemophilus spp. include pneumonia, pharyngitis, sinusitis, vaginitis, chancroid venereal disease, and a contagious form of conjunctivitis (inflammation of eyelid membranes).(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.