(27 days)
The & PR-3 IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) For the qualitative detection and semi-quantitation of antibodies against the Proteinase-3 antigen in serum as an aid in the diagnosis of Wegeners granulomatosis. The test can be performed either manually or in conjunction with the Mago Plus automated EIA processor.
The & PR-3 IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to Proteinase-3 in human serum.
Here's a breakdown of the acceptance criteria and the study details for the Columbia Bioscience, Inc. & PR-3 IgG ELISA Kit based on the provided 510(k) summary:
Acceptance Criteria and Device Performance
The acceptance criteria are implied by the results presented in the performance studies, showing that the device achieved these values. Explicit pre-defined acceptance thresholds are not directly stated in the summary, but the reported performance serves as the basis for substantial equivalence.
Table 1: Acceptance Criteria (Implied) and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Relative Sensitivity | High (e.g., >90%) | 100.0% (95% CI: 93.7-100%) |
| Relative Specificity | High (e.g., >95%) | 97.9% (95% CI: 94.7-99.4) |
| Overall Agreement | High (e.g., >95%) | 98.4% (95% CI: 95.9-99.6) |
| Clinical Specificity (Normals) | High (e.g., >95%) | 98.3% (95% CI: 95.0-99.6) |
| Clinical Sensitivity (Wegener's Granulomatosis) | High (e.g., >90%) | 95.0% (95% CI: 83.1-91.4) |
| Clinical Sensitivity (Microscopic Polyangiitis) | Acceptable (Specific target not clear, but 55.3% is reported) | 55.3% (95% CI: 38.3-71.4) |
| Correlation (Manual vs. MAGO Plus) | Strong positive correlation | Pearson Correlation Coefficient: 0.983 |
| Precision (Intra-assay CV%) | Low variability (e.g., <20%) | Site 1: POS sera: 5.94-15.86%, NEG sera: 15.17-57.92% Site 2: POS sera: 5.27-29.87%, NEG sera: 12.95-31.44% |
| Precision (Inter-assay CV%) | Low variability (e.g., <20%) | Site 1: POS sera: 8.60-22.56%, NEG sera: 38.89-50.84% Site 2: POS sera: 7.04-29.87%, NEG sera: 17.26-31.44% |
| MAGO Plus Precision (Intra-assay CV%) | Low variability (e.g., <20%) | POS sera: 7.59-23.20%, NEG sera: 24.00-78.26% |
| MAGO Plus Precision (Inter-assay CV%) | Low variability (e.g., <20%) | POS sera: 10.61-23.50%, NEG sera: 44.80-44.89% |
Note on Acceptance Criteria: For diagnostic kits like ELISA, typical acceptance criteria for sensitivity and specificity are often high (e.g., >90% or >95%), and for precision, Coefficient of Variation (CV%) values are expected to be low (e.g., <20% for positive samples, although negative samples can have higher CV% due to values close to zero). The provided document doesn't explicitly state the pre-defined acceptance criteria but presents the achieved performance as a demonstration of suitability.
Study Details
This submission describes standalone performance studies for the & PR-3 IgG ELISA Kit. It does not appear to involve a multi-reader multi-case (MRMC) comparative effectiveness study, nor does it explicitly mention human readers or AI assistance. The device is an in-vitro diagnostic (IVD) kit for antibody detection.
2. Sample Size and Data Provenance
-
Test Set (Relative Sensitivity and Specificity):
- Sample Size: 256 frozen retrospective sera.
- Data Provenance: Not explicitly stated, but the mention of "frozen retrospective sera" suggests samples collected from various sources over time. No country of origin is specified.
- Retrospective/Prospective: Retrospective.
-
Test Set (Clinical Sensitivity and Specificity):
- Sample Size: 256 frozen retrospective, characterized sera.
- Data Provenance: Not explicitly stated.
- Retrospective/Prospective: Retrospective.
-
Test Set (Precision):
- Sample Size: Six sera (four positive, two negative) assayed ten times each in three different runs. This represents 180 individual tests per site (6 samples * 10 reps * 3 runs).
- Data Provenance: Not specified.
- Retrospective/Prospective: Prospective (lab-based testing of selected sera).
-
Test Set (Correlation of Manual and MAGO Plus Results):
- Sample Size: 90 serum samples.
- Data Provenance: Not specified.
- Retrospective/Prospective: Not specified, but likely prospective testing on a set of existing samples.
-
Test Set (MAGO Plus Precision):
- Sample Size: Six sera assayed ten times each in three different runs. This represents 180 individual tests.
- Data Provenance: Not specified.
- Retrospective/Prospective: Prospective (lab-based testing of selected sera).
3. Number of Experts and Qualifications for Ground Truth
- Relative Sensitivity and Specificity: The "ground truth" for this section was another commercially available ELISA for anti-PR-3 antibodies. No human experts were involved in establishing this "ground truth" as it compares one test kit against another.
- Clinical Sensitivity and Specificity: The "ground truth" was established by "characterized sera" which were classified into "Normals," "Wegener's Granulomatosis," and "Microscopic Polyangiitis" patient groups. The summary does not specify the number of experts, their qualifications, or the method by which these characterizations were made. It's likely these were clinically diagnosed and confirmed cases based on established medical criteria, but details are absent.
4. Adjudication Method for the Test Set
Not applicable. The concept of adjudication by human experts typically applies to image interpretation or clinical diagnosis scenarios where multiple experts review and reconcile differences. For this ELISA kit, the "ground truth" was either another commercial ELISA kit or pre-characterized patient groups.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not conducted. This refers to comparing human reader performance with and without AI assistance, which is not relevant to this IVD (ELISA) kit.
6. Standalone Performance Study (Algorithm Only)
Yes, a standalone study was performed. The entire performance evaluation focuses on the performance of the & PR-3 IgG ELISA Kit itself, either manually or in conjunction with the MAGO Plus automated EIA processor. There is no human-in-the-loop component being evaluated in the reported performance metrics.
7. Type of Ground Truth Used
- Relative Sensitivity and Specificity: The ground truth was based on the results of a "similar assay" (another commercially available ELISA).
- Clinical Sensitivity and Specificity: The ground truth was based on "characterized sera" representing patient groups (Normals, Wegener's Granulomatosis, Microscopic Polyangiitis). This implies a form of clinical diagnosis/classification rather than direct pathology or outcome data, although pathology would likely be part of the diagnosis for these conditions.
8. Sample Size for the Training Set
The document does not describe a "training set" in the context of an algorithm or AI model development. This ELISA kit is a biochemical assay, not a machine learning algorithm. The samples described are for performance validation (test set).
9. How Ground Truth for the Training Set Was Established
Not applicable, as there is no training set described for an algorithm.
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NOV 1 8 1998 510k Summary of Safety and Effectiveness
s 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: | Oct 20, 1998 |
|---|---|
| Name: | Columbia Bioscience, Inc. |
| Address: | 8775 M Centre Park Drive, #559 Columbia, MD 21045 |
| Contact Person: | Norman Jenkins |
|---|---|
| PhoneNumber. | 410-995-0450 |
| Fax Number. | 410-995-0448 |
Device Information:
| Trade Name: | 78 anti-PR-3 IgG ELISA Kit |
|---|---|
| Common Name. | PR-3 lgG EIA Test |
| Classification Name; PR-3 Serological Reagent |
aivalent Device: ELIAS PR-3 Kit
Device Description: The & PR-3 IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to Proteinase-3 in human serum.
Intended Use: The & PR-3 IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) For the qualitative detection and semi-quantitation of antibodies against the Proteinase-3 antigen in serum as an aid in the diagnosis of Wegeners granulomatosis. The test can be performed either manually or in conjunction with the Mago Plus automated EIA processor.
Principle of Procedure:
PR-3 antigen is bound to microwells. Diluted patient sera, Calibrators and controls are placed inthe microwells and incubated. Anti-PR-3 IgG antibodes, if present, will bind to the antigen forming antigen-antibody complexes. Residual sample is eliminated by aspirating and washing. Conjugate (horseradish peroxidase-labeled anti-human lgG) 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 repduct. The absorbance of this end product can be read spectrophotometrically at 450 nm (reference 600-630
and is directly proportional to the concentration of IgG antibodies to PR-3 present in the sample,
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Performance Characteristics
A. Relative Sensitivity and Specificity
Frozen retrospective sera from two hundred and fifty-six patients were tested on the Is-anti-PR-3 IgG Test Kit and another commercially available ELISA for anti-PR-3 antibodies. Based on the results of this testing, the relative sensitivity and specificity were calculated. The results obtained are shown in Table 2:
TABLE 2
Is-anti-PR-3 IgG
| POSITIVE | EQUIVOCAL | NEGATIVE | ||
|---|---|---|---|---|
| OtherELISA | POSITIVE | 57 | 0 | 0 |
| EQUIVOCAL* | 1 | 0 | 0 | |
| NEGATIVE | 4 | 7 | 187 | |
| Relative Sensitivity | $57/57 = 100.0%$ | 95% CI93.7-100% | ||
| Relative Specificity | $187/191 = 97.9%$ | 94.7-99.4 | ||
| Overall Agreement | $244/248 = 98.4%$ | 95.9-99.6 |
- Equivocal results were excluded from calculations.
NOTE : Please be advised that "relative" refers to 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 discase.
B. Clinical Sensitivity and Specificity Using Characterized Sera
A total of 256 frozen retrospective, characterized sora were assayed using the Is-anti-PR-3 IgG Test Kit. The results obtained are shown in Table 3.
| Patient Group: | Positive | Equivocal* | Negative | Total |
|---|---|---|---|---|
| Normals | 3 | 5 | 168 | 176 |
| Wegener's Granulomatosis | 38 | 0 | 2 | 40 |
| Microscopic Polyangiitis | 21 | 2 | 17 | 40 |
| Clinical Specificity: | 95% CI | |||
| Normals | $168/171 = 98.3%$ | 95.0-99.6 | ||
| Clinical Sensitivity: | 95% CI | |||
| Wegener's Granulomatosis | $38/40 = 95.0%$ | 83.1-91.4 | ||
| Microscopic Polyangiitis | $21/38 = 55.3%$ | 38.3-71.4 |
| TABLE 3 | |
|---|---|
| --------- | -- |
- Equivocal results were excluded from calculations.
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C. Precision
To determine the precision of the Is-anti-PR-3 IgG Test Kit, four positive sera were assayed ten times cach in three different runs at two different sites. The intra- and interassay precision obtained at each site is shown in Tables 4 and 5.
| SERUM | INTRA-ASSAY RUN 1 | INTRA-ASSAY RUN 2 | INTRA-ASSAY RUN 3 | INTERASSAY | ||||
|---|---|---|---|---|---|---|---|---|
| MEANEU/ml | CV% | MEANEU/ml | CV% | MEANEU/ml | CV% | MEANEU/ml | CV% | |
| A (POS) | 43.3 | 12.60 | 43.7 | 7.34 | 35.5 | 9.71 | 40.8 | 13.65 |
| B (POS) | 65.1 | 12.86 | 55.5 | 8.10 | 48.8 | 9.35 | 56.5 | 15.86 |
| C (POS) | 20.9 | 14.19 | 17.8 | 11.46 | 13.2 | 12.18 | 17.3 | 22.56 |
| D (POS) | 30.6 | 5.94 | 27.7 | 8.11 | 27.1 | 6.74 | 28.4 | 8.60 |
| E (NEG) | 0.5 | 20.18 | 0.3 | 33.99 | 0.2 | 57.92 | 0.3 | 50.84 |
| F (NEG) | 0.5 | 15.17 | 0.4 | 38.33 | 0.3 | 43.90 | 0.4 | 38.89 |
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 | ||||
|---|---|---|---|---|---|---|---|---|
| MEANEU/ml | CV% | MEANEU/ml | CV% | MEANEU/ml | CV% | MEANEU/ml | CV% | |
| A (POS) | 44.8 | 8.70 | 46.4 | 5.91 | 48.5 | 8.01 | 46.6 | 8.07 |
| B (POS) | 67.3 | 5.27 | 66.1 | 7.52 | 68.7 | 8.15 | 67.4 | 7.04 |
| C (POS) | 15.2 | 12.28 | 27.4 | 8.18 | 16.4 | 10.52 | 19.7 | 29.87 |
| D (POS) | 26.1 | 10.71 | 35.1 | 5.10 | 28.2 | 7.80 | 29.8 | 15.11 |
| E (NEG) | 0.5 | 29.22 | 0.4 | 16.64 | 0.4 | 20.20 | 0.4 | 31.44 |
| F (NEG) | 0.5 | 21.74 | 0.5 | 17.89 | 0.5 | 12.95 | 0.5 | 17.26 |
1 D. Correlation of Manual and MAGO Plus Results
The Is-anti-PR-3 IgG Test Kit has been developed for automated as well as manual use. To demonstrate the equivalence of the manual and MAGO Plus procedures, the results of 90 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 0.983.
Image /page/2/Figure/8 description: This image is a scatter plot that compares MAGO Plus EU/ML values to MANUAL EU/ML values. The x-axis represents MANUAL EU/ML values, ranging from 0 to 70, while the y-axis represents MAGO Plus EU/ML values, ranging from -20 to 100. The plot shows a strong positive correlation between the two sets of values, with data points clustered around a regression line. The correlation coefficient, r, is 0.983, indicating a very strong linear relationship.
FIGURE 3 : Manual and MAGO Plus Result Correlation
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E. MAGO Plus Precision
The precision of the Is-anti-PR-3 IgG Test Kitwhen performed on the MAGO Plus Automated EIA Processor was determined by assaying six sera ten times cach in three different runs. Table 6 shows the intra-and interassay precision obtained using the MAGO Plus Automated EIA Processor.
| SERUM | INTRA-ASSAY RUN 1 | INTRA-ASSAY RUN 2 | INTRA-ASSAY RUN 3 | INTERASSAY | ||||
|---|---|---|---|---|---|---|---|---|
| MEAN | CV% | MEAN | CV% | MEAN | CV% | MEAN | CV% | |
| EU/ml | EU/ml | EU/ml | EU/ml | |||||
| A (POS) | 34.9 | 15.47 | 41.2 | 11.44 | 51.8 | 13.68 | 42.9 | 20.55 |
| B (POS) | 53.9 | 17.30 | 71.9 | 23.20 | 80.8 | 11.19 | 69.4 | 23.50 |
| C (POS) | 19.5 | 25.46 | 25.2 | 7.59 | 25.1 | 7.66 | 23.3 | 17.82 |
| D (POS) | 32.1 | 13.83 | 36.0 | 5.40 | 32.7 | 8.37 | 33.6 | 10.61 |
| E (NEG) | 0.4 | 78.26 | 0.5 | 27.43 | 0.5 | 24.00 | 0.4 | 44.80 |
| F (NEG) | 0.7 | 74.05 | 0.7 | 23.22 | 0.7 | 22.81 | 0.7 | 44.89 |
TABLE 6 : Site #2- Intra-Assay and Interassay Precision - MAGO Plus
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Image /page/4/Picture/2 description: The image is a black and white 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 image of a human figure with three overlapping profiles, suggesting a sense of community or interconnectedness.
NOV 1 8 1998
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Norman Jenkins President Columbia Bioscience, Inc. 8775 M Centre Park Drive, #559 Columbia, Maryland 21045
Re: K983740 Is-Anti PR-3 IqG ELISA Test System Trade Name: Requlatory Class: II Product Code: MOB Dated: October 21, 1998 Received: October 22, 1998
Dear Mr. Jenkins:
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, qood manufacturing practice, labeling, and prohibitions aqainst 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 Requlations, 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 QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation 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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Page 2
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 leqally 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 requlation (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 (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/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 I of I
510(k) Number: Not Known
Device Name: & PR-3 IgG ELISA
Indications For Use: The & PR-3 IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) For the qualitative detection and semi-quantitation of antibodies against the Proteinase-3 (PR-3) antigen in serum as an aid in the diagnosis of Wegener's granulomatosis. The test can be performed either manually or in conjunction with the Mago Plus automated EIA processor.
Peta E. Madison
PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use i (Per 21 CFR 801.109)
OR
Over-The Counter Use (Optional Format 1-2-96)
§ 866.5660 Multiple autoantibodies immunological test system.
(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).