(58 days)
The Trinity Biotech Captia™ Chlamydia IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative detection of IgG antibodies in human serum to Chlamydia for the determination of immunological experience.
The Chlamydia IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative detection of IgG antibodies inhuman serum to Chlamydia for the determination of immunological experience.
The Chlamydia IgG ELISA test is an enzyme linked immunosorbent assay to detect IgG antibodies to Chlamydia. Purified Chlamydia antigen (strain LGV II) 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. If antibody is preset 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 an analysis of the provided text, focusing on the acceptance criteria and the study proving the device meets them:
Acceptance Criteria and Device Performance for Trinity Biotech Chlamydia IgG ELISA Test Kit
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the reported performance relative to a predicate device and established precision standards.
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Comparative Agreement | - % Agreement Positive: High agreement with predicate IFA kit. - % Agreement Negative: High agreement with predicate IFA kit. - % Agreement: High overall agreement with predicate IFA kit. | % Agreement Positive: 92.1% (95% CI: 86.3% - 97.8%) % Agreement Negative: 98.0% (95% CI: 96.2% - 99.8%) % Agreement: 96.5% (95% CI: 94.5% - 98.5%) |
| Precision | Coefficient of Variation (CV) < 15% for intra- and inter-assay, and inter-site precision. | Intra-Assay CV: Ranged from 2.57% to 19.95% (Study 1), 1.69% to 53.59% (Study 2, some outliers). Inter-Assay CV: Ranged from 5.42% to 17.75% (Study 1), 3.41% to 46.90% (Study 2, some outliers). Inter-Site CV: Ranged from 4.63% to 78.91% (some outliers). Note: While some individual results exceed 15% CV, the summary states "With appropriate technique the user should obtain precision of < 15% CV," suggesting these represent expected user performance rather than strict pass/fail for every single test point in the study. |
| Paired Serum Analysis | Demonstrate seroconversion in a reasonable percentage of cases when the predicate (CF) shows a 4-fold increase or seroconversion. | % Agreement positive when CF showed seroconversion was 44% (4/9). |
| Reproducibility | High correlation between different sites and high percent agreement of expected results. | Pearson correlation coefficients >0.989 between sites. 97.1% (133/137) agreement between three sites (excluding equivocals). |
2. Sample Size Used for the Test Set and Data Provenance
- Comparative Agreement Study (Table 1):
- Test Set Sample Size: 355 sera (86 positive by IFA, 16 equivocal by IFA, 253 negative by IFA).
- Data Provenance: Retrospective. Sera were from "normal individuals of various ages, gender, and geographical areas." The studies were conducted at R&D laboratories of commercial companies located in Maryland and New York, affiliated with the manufacturer.
- Precision Studies (Tables 2, 3, 4):
- Test Set Sample Size: 7 sera, each assayed 10 times in 3 different assays at 2 different sites (total 60 tests per sera for inter-site precision, 30 tests per sera for inter-assay precision within each site).
- Data Provenance: Retrospective (sera likely selected for different activity levels), performed at 2 sites affiliated with the manufacturer.
- Paired Serum Analysis:
- Test Set Sample Size: 9 serum pairs.
- Data Provenance: Retrospective, serum pairs showing changes in Complement Fixation (CF) titer.
- Reproducibility Study:
- Test Set Sample Size: 50 different sera.
- Data Provenance: Retrospective, conducted at three different sites: two R&D laboratories at commercial companies (Maryland and New York, affiliated with the manufacturer) and one large clinical laboratory (Pennsylvania).
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
There is no mention of "experts" in the context of establishing ground truth in the traditional sense (e.g., medical professionals reviewing cases).
- For the Comparative Agreement Study: The "ground truth" for comparison was the results of a commercial IFA kit. The document states, "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." This clarifies that the IFA kit was the reference standard, not a true clinical ground truth established by experts.
4. Adjudication Method for the Test Set
Not applicable. The ground truth was established by a single predicate device (commercial IFA kit) or by the device itself for precision and reproducibility. There was no human adjudication process described. Equivocal results from the predicate IFA were excluded from agreement calculations, but this is not an adjudication process.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance
Not applicable. This device is an in-vitro diagnostic ELISA kit, not an AI-assisted diagnostic tool that requires human readers for interpretation in the manner typically associated with MRMC studies in medical imaging. The comparison is between two laboratory assays.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
This is an inherently standalone device as it is an ELISA kit. Its performance is measured directly through its reaction with serum samples, producing a measurable color intensity that is read photometrically. The results are quantitative and then interpreted qualitatively (positive/negative/equivocal) based on pre-defined cut-offs. There is no "human-in-the-loop" once the assay is performed and read by the instrument, beyond potentially interpreting the final qualitative result.
7. The Type of Ground Truth Used
- For Comparative Agreement, Paired Serum Analysis: The ground truth was the results of a predicate commercial IFA kit (for agreement) or a Complement Fixation (CF) titer (for seroconversion) for Chlamydia. It is explicitly stated that there was no attempt to correlate the assay's results with disease presence or absence, and therefore, no true clinical or pathological ground truth was established in these comparative studies.
- For Precision and Reproducibility: "Expected results" for reproducibility were derived from "previous Trinity Biotech ELISA testing of the samples." For precision, the study aimed to evaluate the consistency of the device's own measurements.
8. The Sample Size for the Training Set
Not applicable. This is a traditional in-vitro diagnostic kit, not a machine learning model. There is no concept of a "training set" in the context of developing this device. The development process would involve iterative optimization of assay components and protocols, rather than training an algorithm on a dataset.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for this type of device.
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NOV 26 2003
Image /page/0/Picture/1 description: The image shows a sequence of handwritten alphanumeric characters. The sequence reads 'K033079'. The characters are written in a dark ink, and the image has a slightly grainy texture.
Summary of Safety and Effectiveness Information Chlamydia 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 Chlamydia IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative detection of IgG antibodies inhuman serum to Chlamydia for the determination of immunological experience.
The Chlamydia IgG ELISA test is an enzyme linked immunosorbent assay to detect IgG antibodies to Chlamydia. Purified Chlamydia antigen (strain LGV II) 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. If antibody is preset 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 Chlamydia IgG ELISA test is substantially equivalence is demonstrated by the following comparative results:
Performance Characteristics
- % Agreement Positive and % Agreement Negative. Two different sites compared the Trinity Biotech Chlamydia IgG ELISA test relative to a commercial IFA kit. The two sites were R&D laboratories at commercial companies located in Maryland and New York, and affiliated with the manufacturer of the kit. The sera were from normal individuals of various ages, gender, and geographical areas. The results of the studies are compiled and summarized in Table 1. None of the performance characteristics were established with specimens from patients having documented chlamydia infections.
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Table 1 Comparison of Chlamydia IgG ELISA and IFA
Trinity Biotech Chlamydia IgG ELISA
| + | eq | - | Total | ||
|---|---|---|---|---|---|
| + > 1:8 | 81 | 7 | 7 | 95 | |
| ChlamydiaIFA | - < 1:8 | 5 | 9 | 246 | 260 |
| Total | 86 | 16 | 253 | 355 |
| % Agreement positive = 81/88 = 92.1% | 95% Confidence Interval = 86.3% - 97.8% |
|---|---|
| % Agreement negative = 246/251 = 98.0% | 95% Confidence Interval = 96.2% - 99.8% |
| % Agreement = 327/239 = 96.5% | 95% Confidence Interval = 94.5% - 98.5% |
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.
- Precision. Seven sera were assayed ten times each on three different assays at two different sites. Both sites were affiliated with the manufacturer of the kit. The inter and intra assay precision for each site is presented in Tables 2 and 3 and the inter-site precision is shown in Table 4. With appropriate technique the user should obtain precision of < 15% CV.
Table 2 Trinity Biotech Chlamydia IgG 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 | 2.86 | 0.152 | 5.32% | 2.97 | 0.076 | 2.57% | 3.13 | 0.115 | 3.69% | 2.99 | 0.162 | 5.42% |
| 2 | 1.71 | 0.101 | 5.91% | 1.88 | 0.098 | 5.20% | 1.90 | 0.092 | 4.89% | 1.83 | 0.129 | 7.05% |
| 3 | 1.74 | 0.107 | 6.15% | 1.87 | 0.071 | 3.78% | 1.95 | 0.072 | 3.67% | 1.85 | 0.121 | 6.50% |
| 4 | 1.78 | 0.126 | 7.07% | 1.92 | 0.053 | 2.77% | 2.03 | 0.075 | 3.72% | 1.91 | 0.135 | 7.06% |
| 5 | 1.06 | 0.051 | 4.83% | 1.12 | 0.034 | 3.00% | 1.16 | 0.049 | 4.24% | 1.11 | 0.060 | 5.42% |
| 6 | 0.34 | 0.032 | 9.59% | 0.32 | 0.042 | 13.06% | 0.37 | 0.052 | 14.25% | 0.34 | 0.046 | 13.55% |
| 7 | 0.30 | 0.061 | 19.95% | 0.29 | 0.056 | 19.43% | 0.33 | 0.043 | 12.81% | 0.31 | 0.054 | 17.75% |
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| Table 3 |
|---|
| Trinity Biotech Chlamydia IgG 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 | 3.08 | 0.052 | 1.69% | 3.11 | 0.106 | 3.40% | 3.00 | 0.117 | 3.91% | 3.06 | 0.104 | 3.41% |
| 2 | 1.77 | 0.085 | 4.80% | 1.78 | 0.073 | 4.10% | 1.75 | 0.094 | 5.38% | 1.77 | 0.084 | 4.75% |
| 3 | 1.86 | 0.062 | 3.35% | 1.85 | 0.086 | 4.63% | 1.86 | 0.083 | 4.46% | 1.86 | 0.076 | 4.08% |
| 4 | 1.81 | 0.060 | 3.30% | 1.84 | 0.112 | 6.12% | 1.84 | 0.102 | 5.52% | 1.83 | 0.091 | 4.98% |
| 5 | 0.93 | 0.051 | 5.46% | 0.93 | 0.071 | 7.69% | 0.94 | 0.053 | 5.61% | 0.93 | 0.058 | 6.19% |
| 6 | 0.04 | 0.014 | 31.17% | 0.03 | 0.018 | 53.59% | 0.06 | 0.024 | 39.50% | 0.05 | 0.022 | 46.90% |
| 7 | 0.05 | 0.016 | 35.60% | 0.05 | 0.015 | 32.60% | 0.07 | 0.032 | 47.62% | 0.05 | 0.024 | 45.41% |
Table 4
Trinity Biotech Chlamydia IgG ELISA Inter-Site Precision Study
| Inter-Site (n = 60) | |||
|---|---|---|---|
| Sera # | X | SD | CV |
| 1 | 3.03 | 0.140 | 4.63% |
| 2 | 1.80 | 0.112 | 6.24% |
| 3 | 1.86 | 0.100 | 5.37% |
| 4 | 1.87 | 0.121 | 6.46% |
| 5 | 1.02 | 0.110 | 10.73% |
| 6 | 0.19 | 0.153 | 78.91% |
| 7 | 0.18 | 0.137 | 75.20% |
X = Mean
SD = standard deviation
CV = coefficient of variation = SD/X x 100
The methods in NCCLS EP5 were utilized for precision parameters.
3. Paired Serum Analysis
Nine serum pairs showing a greater than 4-fold increase in Complement Fixation (CF) titer or seroconversions by CF were assayed on the Trinity Biotech Chlamydia IgG ELISA assay. Each serum pair was evaluated to determine a seroconversion in antibody (acute negative and convalescent positive). Four pairs demonstrated a seroconversion by ELISA. Therefore the assay showed a % agreement positive of 44% (4/9) in demonstrating a seroconversion when the CF showed a 4-fold increase or a seroconversion.
4. Reproducibility Study
Fifty different sera with various levels of activity were assayed at three different sites. Two sites were R&D laboratories at commercial companies located in Maryland and New York. The third site was a large clinical laboratory located in Pennsylvania. The data from the three sites show good correlation with ISR values with Pearson product moment correlation coefficients of >0.989 between the sites. Excluding equivocals (n = 13), four determinations varied from their expected results for a positive specimen) giving a percent agreement of expected results between the three sites of 97.1% (133/137). The expected results were derived from previous Trinity Biotech ELISA testing of the samples.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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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: K033079
Trade/Device Name: Captia Chlamydia IgG ELISA Regulation Number: 21 CFR 866.3120 Regulation Name: Chlamydia serological reagents Regulatory Class: Class I Product Code: LJC 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 (QS) 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). 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 Putman
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: K033079
Device Name: Trinity Biotech Captia™ Chlamydia IgG ELISA
Indications For Use: The Trinity Biotech Captia™ Chlamydia IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for qualitative detection of IgG antibodies in human serum to Chlamydia for the determination of immunological experience.
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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)
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Office of In Vitro Diagnostic Device Office of in-ond Safety
510(k) K033079
§ 866.3120 Chlamydia serological reagents.
(a)
Identification. Chlamydia serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to chlamydia in serum. Additionally, some of these reagents consist of chlamydia antisera conjugated with a fluorescent dye used to identify chlamydia directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusChlamydia and provides epidemiological information on these diseases. Chlamydia are the causative agents of psittacosis (a form of pneumonia), lymphogranuloma venereum (a venereal disease), and trachoma (a chronic disease of the eye and eyelid).(b)
Classification. Class I (general controls).