IS-ANTI-PR3 IGG ELISA TEST SYSTEM

{0}------------------------------------------------ K983740 #### 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, {1}------------------------------------------------ # 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 | |----------------------|------------|-------------------|-----------|---------------------| | Other<br>ELISA | POSITIVE | 57 | 0 | 0 | | | EQUIVOCAL* | 1 | 0 | 0 | | | NEGATIVE | 4 | 7 | 187 | | Relative Sensitivity | | $57/57 = 100.0%$ | | 95% CI<br>93.7-100% | | 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. {2}------------------------------------------------ ### 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 | | |---------|-------------------|-------|-------------------|-------|-------------------|-------|---------------|-------| | | MEAN<br>EU/ml | CV% | MEAN<br>EU/ml | CV% | MEAN<br>EU/ml | CV% | MEAN<br>EU/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 | | |---------|-------------------|-------|-------------------|-------|-------------------|-------|---------------|-------| | | MEAN<br>EU/ml | CV% | MEAN<br>EU/ml | CV% | MEAN<br>EU/ml | CV% | MEAN<br>EU/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 {3}------------------------------------------------ ### 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 {4}------------------------------------------------ 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. {5}------------------------------------------------ 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 {6}------------------------------------------------ Page I of I K983740 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)