(203 days)
For the qualitative determination of IgG antibodies to Helicobactor pylori antigen in human sera by indirect enzyme immunoasay. The H.pylori IgG assay may be used as an aid in the diagnosis of H. pylori infection in adult patients with gastrointestinal symptoms. The test can be performed either manually or in conjunction with the MAGO® PLUS Automated EIA Processor.
The & H. pylori IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies to H. pylori antigen in human serum.
This document describes the performance characteristics of the Is-H. pylori IgG ELISA Kit, an in vitro diagnostic (IVD) device used for the qualitative determination of IgG antibodies to Helicobacter pylori antigen in human sera.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the reported performance metrics, demonstrating the device's accuracy and precision.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Sensitivity (Biopsy GT) | High sensitivity (e.g., >85-90%) | 94.9% (95% CI: 89.3-98.1%) |
| Specificity (Biopsy GT) | High specificity (e.g., >85-90%) | 90.4% (95% CI: 83.8-94.9%) |
| Overall Agreement (Biopsy GT) | High overall agreement (e.g., >85-90%) | 92.6% (95% CI: 88.5-95.6%) |
| Relative Agreement (vs. Predicate ELISA) | High agreement (e.g., >95%) | 99.6% |
| Precision (Intra-assay CV%) | Low variability (e.g., <20% for positive, <40% for negative, these are approximate common ranges for ELISA tests) | Ranged from 2.16% to 37.22% for Site #1, 3.40% to 20.01% for Site #2, 2.08% to 19.99% for Site #3 (Manual) and 2.97% to 62.36% for MAGO Plus |
| Precision (Inter-assay CV%) | Low variability (e.g., <25% for positive, <50% for negative) | Ranged from 3.24% to 24.91% for Site #1, 4.93% to 18.56% for Site #2, 5.42% to 16.60% for Site #3 (Manual) and 5.19% to 57.40% for MAGO Plus |
| Correlation (Manual vs. MAGO Plus) | Strong positive correlation (e.g., r > 0.95) | Pearson Correlation Coefficient: 0.993 |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Sensitivity and Specificity Study (Section A): 249 patients.
- 121 sera characterized as positive for H. pylori.
- 128 sera characterized as negative for H. pylori.
- Sample Size for Relative Agreement Study (Section B): 249 patients (same samples as in Section A).
- Data Provenance: The sera were frozen retrospective samples from patients. The country of origin is not explicitly stated in the provided text.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth for characterizing H. pylori infection in the test set (Section A) was established using "biopsy with culture, stain and CLO results for H.pylori". While these are considered reference standard clinical tests, the document does not specify the number of experts (e.g., pathologists, microbiologists) who interpreted these results or their specific qualifications (e.g., years of experience as a pathologist). The interpretation of such tests inherently involves expert judgment, but the level of detail is not provided.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method (like 2+1 or 3+1) for resolving discrepancies in the biopsy, culture, stain, or CLO results that formed the ground truth. It states that "Based on the results of this testing, the patient sera were characterized." This implies that a consensus or a defined decision rule based on these multiple tests was used to establish the positive or negative status for each patient, but the specific adjudication process is not detailed. Equivocal results from the device under test were excluded from calculations, but this is a different kind of exclusion from an adjudication of ground truth.
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
No MRMC comparative effectiveness study was mentioned. This device is an immunoassay kit, not an AI-based image analysis or interpretation tool that would typically involve human readers and AI assistance for interpretation. Therefore, this section is not applicable.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
For the sensitivity and specificity study (Section A), the device (Is-H. pylori IgG Test Kit) was tested on sera, and its results were compared to the biopsy-based ground truth. This represents standalone performance, as the interpretation of the ELISA results would be direct based on the established cut-off, without a human "reader" making a subjective judgment in the same way a radiologist reads an image.
The section on "Correlation of Manual and MAGO Plus Results" (Section D) and "MAGO Plus Precision" (Section E) studies the performance of the device when used with an automated EIA processor. This also represents standalone performance of the device in either manual or automated modes, where the device directly produces a result.
7. The Type of Ground Truth Used
The primary ground truth used for the sensitivity and specificity study (Section A) was based on biopsy with culture, stain, and CLO results for H. pylori. These are objective laboratory and histopathological methods considered gold standards for H. pylori infection diagnosis.
For the "Relative Agreement Versus Another ELISA" study (Section B), the "ground truth" was the results from "another commercially available kit for H. pylori IgG antibodies." However, the notice explicitly states: "Please be advised that 'relative' refers to the comparison of the 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's accuracy to predict disease." This clarifies that the predicate ELISA was used for relative performance comparison, not as a true gold standard for disease presence.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning. This device is an immunoassay kit (ELISA), which is a biochemical test, not an algorithm that requires a separate training set. The various studies described (Sensitivity/Specificity, Relative Agreement, Precision) are all validation studies for the device's performance.
9. How the Ground Truth for the Training Set Was Established
As this is an immunoassay and not an AI/ML algorithm requiring a training set, this question is not applicable. The device itself produces a result based on a biochemical reaction and predefined interpretation rules.
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510k Summary of Safety and Effectiveness
SEP , 3 1999
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is:
Applicant Information:
| Date Prepared: | |
|---|---|
| Name: | Columbia Bioscience, Inc. |
| Address: | 8775 M Centre Park Drive, #559Columbia, MD 21045 |
| Contact Person: | Norman Jenkins |
|---|---|
| PhoneNumber. | 410-995-1278 |
| Fax Number. | 410-995-0508 |
Device Information:
| Trade Name: | Image: Logo H. pylori IgG ELISA Kit |
|---|---|
| Common Name. | H. pylori IgG EIA Test |
| Classification Name; | H. pylori IgG Serological Reagent |
Equivalent Device:
Wampole H. pylori IgG ELISA
Device Description: The & H. pylori IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies to H. pylori antigen in human serum.
Intended Use: For the qualitative determination of IgG antibodies to Helicobactor pylori antigen in human sera by indirect enzyme immunoasay. The H.pylori IgG assay may be used as an aid in the diagnosis of H. pylori infection in adult patients with gastrointestinal symptoms. The test can be performed either manually or in conjunction with the MAGO® PLUS Automated EIA Processor.
Principle of Procedure:
Purified H. pylori antigen is bound to microwells. Diluted patient sera, Cut-Off Calibrator and controls are placed in the microwells and incubated. Anti-H. pylori IgG antibodies, if present, will bind to the antigen forming antibody complexes. Residual sample is eliminated by aspirating and washing. Conjugate (norseradish peroxidase-labeled anti-human IgG) is added and will bind to these complexes. Unbound conjugate is removed by aspiration and washing. Substrate is then added and incubated. In the presence of bound enzyme the substrate is converted to an end product. The absorbance of this end product can be read spectrophotometrically at 450 nm (reference 600-630 nm) and is directly proportional to the concentration of IgG antibodies to H. pylori present in the sample.
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Performance Characteristics
A. Sensitivity and Specificity Using Characterized Sera
Frozen retrospective sera from two hundred forty-nine patients were characterized using biopsy with culture, stain and CLO results for H.pylori. Based on the results of this testing, the patient sera were characterized as follows :
-
- 121 sera were characterized as positive. These were positive for H. pylori by biopsy.
-
- 128 sera were characterized as negative. These were negative for H. pylori by biopsy.
The sera were tested on the 1s-H, pylori IgG Test Kit at a clinical commercial laboratory. The data is summarized in Table 2.
TABLE 2
Is-H. pylori IgG
| POSITIVE | *EQUIVOCAL | NEGATIVE | |||
|---|---|---|---|---|---|
| H. pylori | POSITIVE | 112 | 3 | 6 | |
| Clinical Status(Biopsy) | INEGATIVE | 12 | 3 | 113 | |
| SensitivitySpecificityOverall Agreement = | ll | 112/118 = 94.9%113/125 = 90.4%225/243 = 92.6% | 95% Cl89.3-98.1%83.8-94.9%88.5-95.6% |
*Equivocal results were excluded from the above calculations.
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B. Relative Agreement Versus Another ELISA
Frozen retrospective sera from two hundred forty-nine patients (same samples from Table 2) were tested at a clinical commercial laboratory using the 1s-H, pylori 1gG Test Kit and another commercially available kit for H. pylori IgG antibodies. The data in Table 3 illustrates the relative aggrement of the 1s-H. pylori lgG Test Kit versus another commercial ELISA.
TABLE 3
Is-H. pylori IgG
Another ELISA
| POSITIVE | * EQUIVOCAL | NEGATIVE | |
|---|---|---|---|
| POSITIVE | 122 | 3 | 0 |
| *EQUIVOCAL | 1 | 1 | 3 |
| NEGATIVE | 1 | 2 | 116 |
· Of the 125 sera positive on the alternate ELISAtested, 122 were positive for Is-H. pylori IgG, none were negative, and 3 were equivocal
· Of the 119 sera negative on the alternate ELISAtested, 1 was positive for Is-H. pylori IgG, 116 were negative, and 2 were equivocal
· Of the 5 sera equivocal on the alternate ELISAtested, 1 was positive for Is-H, pylori IgG, 1 was negative, and 3 were equivocal
- · Overall Relative Agreement = 238/239 = 99.6%
- Equivocal results were excluded from calculations
NOTE : Please be advised that 'relative' relers to the comparison of the 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's accuracy to predict disease.
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C. Precision
To determine the precision of the Is-H. pyleri IgG Test Kit, four positive sera were assayed ten times each in thee different runs at three different sites included: the manufacturer, a research & development laboratory, and a clinical commercial laboratory. The intra- and interassay precision obtained at each site is shown in Tables 4,5, and 6.
| SERUM | INTRA-ASSAY RUN 1 | INTRA-ASSAY RUN 2 | INTRA-ASSAY RUN 3 | INTERASSAY | |||||
|---|---|---|---|---|---|---|---|---|---|
| MEANINDEX | CV% | MEANINDEX | CV% | MEANINDEX | CV% | MEANINDEX | CV% | ||
| A (POS) | 1.51 | 3.85 | 1.47 | 5.05 | 1.45 | 4.97 | 1.47 | 4.80 | |
| B (POS) | 2.60 | 2.16 | 2.58 | 4.20 | 2.59 | 3.69 | 2.59 | 3.35 | |
| C (POS) | 2.23 | 3.66 | 2.23 | 3.65 | 2.20 | 2.98 | 2.22 | 3.39 | |
| D (POS) | 1.73 | 3.82 | 1.72 | 2.19 | 1.70 | 3.57 | 1.71 | 3.24 | |
| E (NEG) | 0.19 | 10.81 | 0.16 | 13.54 | 0.14 | 36.64 | 0.17 | 23.60 | |
| F (NEG) | 0.36 | 37.22 | 0.32 | 16.08 | 0.34 | 11.54 | 0.34 | 24.91 |
TABLE 4 : Site #1 - Intra-Assay and Interassay Precision
TABLE 5 : Site #2- Intra-Assay and Interassay Precision
| SERUM | INTRA-ASSAY RUN 1 | INTRA-ASSAY RUN 2 | INTRA-ASSAY RUN 3 | INTERASSAY | ||||
|---|---|---|---|---|---|---|---|---|
| MEANINDEX | CV% | MEANINDEX | CV% | MEANINDEX | CV% | MEANINDEX | CV% | |
| A (POS) | 1.34 | 4.92 | 1.32 | 5.00 | 1.38 | 4.39 | 1.35 | 4.93 |
| B (POS) | 2.25 | 5.85 | 2.27 | 5.17 | 2.45 | 6.18 | 2.33 | 6.78 |
| C (POS) | 1.97 | 3.40 | 1.96 | 4.24 | 2.11 | 4.83 | 2.01 | 5.41 |
| D (POS) | 1.46 | 6.27 | 1.45 | 4.52 | 1.62 | 4.02 | 1.51 | 6.93 |
| E (NEG) | 0.18 | 12.48 | 0.17 | 11.70 | 0.22 | 10.28 | 0.19 | 15.39 |
| F (NEG) | 0.40 | 11.01 | 0.35 | 20.01 | 0.47 | 12.50 | 0.41 | 18.56 |
TABLE 6 : Site #3 - Intra-assay and Interassay Precision
| SERUM | INTRA-ASSAY RUN 1 | INTRA-ASSAY RUN 2 | INTRA-ASSAY RUN 3 | INTERASSAY | ||||
|---|---|---|---|---|---|---|---|---|
| MEANINDEX | CV% | MEANINDEX | CV% | MEANINDEX | CV% | MEANINDEX | CV% | |
| A (POS) | 1.41 | 7.59 | 1.30 | 5.70 | 1.27 | 4.60 | 1.33 | 7.64 |
| B (POS) | 2.54 | 4.41 | 2.30 | 3.74 | 2.19 | 2.52 | 2.34 | 7.31 |
| C (POS) | 2.13 | 5.91 | 1.96 | 4.89 | 1.90 | 3.43 | 2.00 | 6.94 |
| D (POS) | 1.56 | 6.16 | 1.50 | 4.59 | 1.45 | 2.08 | 1.50 | 5.42 |
| E (NEG) | 0.16 | 19.99 | 0.18 | 6.38 | 0.16 | 6.25 | 0.17 | 13.77 |
| F (NEG) | 0.34 | 10.92 | 0.34 | 13.65 | 0.27 | 15.74 | 0.32 | 16.60 |
D. Correlation of Manual and MAGO Plus Results
The Is-H. pylori IgG Test Kit has been developed for automated as . To demonstrate the equivalence of the manual and MAGO Plus procedures, the results of 100 serum samples tested by both methods were plotted. A scattergram and regression line of the results obtained with 95% confidence intervals is shown in Figure 3. The data indicate good correlation with a Pearson Correlation Coefficient of 0.993.
Image /page/3/Figure/10 description: The image is a scatter plot that shows the correlation between MANUAL Index Values and MAGO PLUS Index Values. The x-axis represents the MANUAL Index Values, ranging from 0.0 to 4.0, while the y-axis represents the MAGO PLUS Index Values, ranging from -0.5 to 5.0. The scatter plot shows a strong positive correlation between the two variables, with a correlation coefficient of r = 0.993. A regression line is plotted through the data points.
FIGURE 3 : Manual and MAGO Plus Result Correlation
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E. MAGO Plus Precision
The precision of the assay when performed on the MAGO Plus Automated EIA Processor was determined by assaying six sera ten times each in three different runs. Table 7 shows the intra-and interassay precision obtained using the MAGO Plus.
| SERUM | INTRA-ASSAY RUN 1 | INTRA-ASSAY RUN 2 | INTRA-ASSAY RUN 3 | INTERASSAY | ||||
|---|---|---|---|---|---|---|---|---|
| MEANINDEX | CV% | MEANINDEX | CV% | MEANINDEX | CV% | MEANINDEX | CV% | |
| A (POS) | 1.19 | 8.36 | 1.02 | 15.19 | 1.25 | 5.66 | 1.15 | 12.83 |
| B (POS) | 2.12 | 4.87 | 2.20 | 9.34 | 2.27 | 2.97 | 2.20 | 6.71 |
| C (POS) | 1.97 | 4.18 | 1.89 | 5.82 | 1.90 | 4.96 | 1.92 | 5.19 |
| D (POS) | 1.37 | 6.01 | 1.45 | 4.88 | 1.54 | 7.62 | 1.45 | 7.82 |
| E (NEG) | 0.13 | 37.16 | 0.12 | 35.14 | 0.20 | 62.36 | 0.15 | 57.40 |
| F (NEG) | 0.32 | 24.65 | 0.34 | 24.80 | 0.34 | 15.19 | 0.33 | 21.33 |
TABLE 7 : Site #2- Intra-Assay and Interassay Precision - MAGO Plus
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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular arrangement of text surrounding a stylized symbol. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular fashion. The symbol in the center appears to be an abstract representation of a bird or a stylized human figure.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
SEP 3 1999
Mr. William Boteler Immunoprobe, Inc. 1306F Bailes Lane Frederick, Maryland 21701
Re: K990462 Trade Name: Helicobactor pylori IgG ELISA Regulatory Class: I Product Code: LYR Dated: June 15, 1999 Received: June 16, 1999
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 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 OS 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.
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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 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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510(k) Number:
Device Name: 20 H. pylori IgG ELISA
Indications For Use: For the qualitative determination of IgG antibodies to Helicobactor pylori antigen in human sera by indirect enzyme immunoassay. The H.pylori IgG assay may be used as an aid in the diagnosis of H. pylori infection in adult patients with gastrointestinal symptoms. The test can be performed either manually or in conjunction with the MAGO® PLUS Automated EIA Processor.
PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use (Per 21 CFR 801.109) OR
w===========================================================================================================================================================================
Over-The Counter Use (Optional Format 1-2-96)
Woody Dubaes
(Division Sign Off) Division of Clinical Laboratory Devices 510(k) Number_19
§ 866.3110
Campylobacter fetus serological reagents.(a)
Identification. Campylobacter fetus serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identifyCampylobacter fetus from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium and provides epidemiological information on these diseases.Campylobacter fetus is a frequent cause of abortion in sheep and cattle and is sometimes responsible for endocarditis (inflammation of certain membranes of the heart) and enteritis (inflammation of the intestines) in humans.(b)
Classification. Class I (general controls).