IS-ANTI-MPO IGG ELISA TEST SYSTEM

{0}------------------------------------------------ ### 510k Summary of Safety and Effectiveness his 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: | Sept 2, 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: | anti-MPO IgG ELISA Kit | |----------------------|-------------------------| | Common Name. | MPO IgG EIA Test | | Classification Name; | MPO Serological Reagent | Juivalent Device: ELIAS MPO Kit Device Description: The & MPO IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to Myeloperoxidase in human serum. Intended Use: The & MPO IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) For the qualitative detection and semi-quantitation of antibodies against the Myeloperoxidase antigen in serum as an aid in the diagnosis of Microscopic polyangiitis. The test can be performed either manually or in conjunction with the Mago Plus automated EIA processor. Principle of Procedure: MPO antigen is bound to microwells. Diluted patient sera, Calibrators and controls are placed inthe microwells and incubated. Anti-MPO 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 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 ਾroduct. 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 MPO present in the sample. {1}------------------------------------------------ # Performance Characteristics ## A. Relative Sensitivity and Specificity Frozen retrospective sera from two hundred sixty-four patients were tested on the Is-anti-MPO IgG Test Fridan retrospective sera from two maneres for you antibodies. Based on the results of this testing, the relative senstitivity and specificity was calculated. The results obtained are shown in Table 2: #### TABLE 2 #### Is-anti-MPO IgG | | | POSITIVE | * EQUIVOCAL | NEGATIVE | |----------------------|------------|----------|-----------------|---------------------| | Other<br>ELISA | POSITIVE | 22 | 0 | 1 | | | EQUIVOCAL* | 6 | 2 | 15 | | | NEGATIVE | 1 | 3 | 214 | | Relative Sensitivity | | | 22/23 = 95.7% | 95% CI<br>78.0-99.9 | | Relative Specificity | | | 214/215 = 99.5% | 97.4-100.0 | | Overall Agreement | | | 236/238 = 99.2% | 97.0-99.9 | * 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 disease. #### B. Clinical Sensitivity and Specificity Using Characterized Sera A total of 256 frozen retrospective, clinically characterized using the Is-anti-MPO Test Kit. The results obtained are shown in Table 3. | Patient Group: | Positive | Equivocal* | Negative | Total | |--------------------------|-------------------|------------|---------------|-------| | Normals | 2 | 1 | 173 | 176 | | Wegener's Granulomatosis | 2 | 3 | 35 | 40 | | Microscopic Polyangiitis | 18 | 0 | 22 | 40 | | Clinical Specificity: | | | <b>95% CI</b> | | | Normals | $173/175 = 98.9%$ | | 95.9-99.9 | | | Wegener's Granulomatosis | $35/37 = 94.6%$ | | 81.8-99.3 | | | Clinical Sensitivity: | | | <b>95% CI</b> | | | Microscopic Polyangiitis | $18/40 = 45.0%$ | | 29.3-61.5 | | | TABLE | 3 | |-------|---| |-------|---| * Equivocal results were excluded from calculations {2}------------------------------------------------ #### C. Precision To determine the precision of the Is-anti-MPO IgG Test Kit, four positive and two negative sera were essayed ten times each in three different runs at two different sites. The intra- and interassay precision obtained at cach site is shown in Tables 4 and 5. | 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) | 21.88 | 4.49 | 22.67 | 5.14 | 24.79 | 5.48 | 23.11 | 7.31 | | B (POS) | 8.12 | 8.61 | 8.66 | 8.75 | 8.22 | 8.13 | 8.33 | 8.70 | | C (POS) | 14.76 | 5.92 | 15.14 | 8.22 | 16.21 | 8.76 | 15.37 | 8.56 | | D (POS) | 47.29 | 5.35 | 57.31 | 7.70 | 47.86 | 5.10 | 50.82 | 11.08 | | E (NEG) | 0.13 | 96.28 | 0.06 | 161.02 | 0.05 | 194.37 | 0.08 | 136.93 | | F (NEG) | 0.26 | 45.15 | 0.24 | 56.25 | 0.06 | 86.07 | 0.19 | 74.09 | 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 EU/ml | CV% | MEAN EU/ml | CV% | MEAN EU/ml | CV% | MEAN EU/ml | CV% | | A (POS) | 25.71 | 17.57 | 22.74 | 3.23 | 24.02 | 4.05 | 24.16 | 11.94 | | B (POS) | 9.96 | 9.92 | 8.76 | 5.47 | 8.82 | 5.85 | 9.18 | 9.57 | | C (POS) | 22.88 | 8.58 | 15.60 | 7.24 | 15.77 | 3.86 | 18.08 | 20.40 | | D (POS) | 79.81 | 7.20 | 50.83 | 9.42 | 56.29 | 5.52 | 62.31 | 21.76 | | E (NEG) | 0.71 | 32.83 | 0.17 | 28.41 | 0.07 | 96.42 | 0.32 | 100.23 | | F (NEG) | 0.84 | 11.50 | 0.31 | 23.80 | 0.24 | 40.25 | 0.46 | 61.70 | ## D. Correlation of Manual and MAGO Plus Results The Is-anti-MPO 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 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 0.983. Image /page/2/Figure/8 description: The image is a scatter plot comparing MAGO Plus EU/ml values to MANUAL EU/ML values. The x-axis represents MANUAL EU/ML values, ranging from 0 to 100, while the y-axis represents MAGO Plus EU/ml values, ranging from 0 to 80. 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 given as 0.983, indicating a very strong linear relationship. FIGURE 3 : Correlation of Manual vs MAGO Plus Results {3}------------------------------------------------ #### E. MAGO Plus Precision -- - The precision of the Is-anti-MPO IgG Test Kit when performed on the MAGO Plus Automated EIA Processor was determined by assaying six sera ten times each in three different runs. Table 6 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 | | |---------|-------------------|--------|-------------------|-------|-------------------|-------|------------|--------| | | MEAN | CV% | MEAN | CV% | MEAN | CV% | MEAN | CV% | | | EU/ml | | EU/ml | | EU/ml | | EU/ml | | | A (POS) | 23.01 | 8.15 | 25.25 | 15.20 | 25.82 | 19.90 | 24.69 | 15.88 | | B (POS) | 9.74 | 16.92 | 10.66 | 11.56 | 11.62 | 18.50 | 10.67 | 17.17 | | C (POS) | 16.57 | 12.08 | 18.18 | 7.13 | 18.55 | 10.76 | 17.81 | 10.81 | | D (POS) | 46.89 | 10.76 | 47.86 | 18.45 | 59.31 | 25.50 | 51.35 | 22.71 | | E (NEG) | 0.10 | 105.41 | 0.45 | 68.09 | 0.32 | 99.70 | 0.29 | 100.98 | | F (NEG) | 0.33 | 37.93 | 0.99 | 45.03 | 0.48 | 59.58 | 0.60 | 69.62 | TABLE 6 : Site #2- Intra-Assay and Interassay Precision - MAGO Plus {4}------------------------------------------------ Image /page/4/Picture/2 description: The image shows the logo for the Department of Health & Human Services USA. The date "NOV 1 8 1998" is printed below the logo. The logo consists of a stylized eagle with three lines representing its wings and head. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle. 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: K983390 Is-Anti MPO IgG ELISA Test System Trade Name: Requlatory Class: II Product Code: MOB Dated: September 23, 1998 Received: September 25, 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 regulation 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}------------------------------------------------ Paqe 2 This letter will allow you to beqin 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 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 requlation 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 Autman 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 1 of 1 K983390 510(k) Number: Not Known Device Name: MPO IgG ELISA Indications For Use: The & MPO IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) For the qualitative detection and semi-quantitation of antibodies against the Myeloperoxidase (MPO) antigen in serum as an aid in the diagnosis of The test can be performed either manually or in microscopic polyangiitis. conjunction with the Mago Plus automated EIA processor. Peter E. Magrini PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use v (Per 21 CFR 801.109) OR Over-The Counter Use (Optional Format 1-2-96)