WIELISA PR-3 ANCA TEST SYSTEM

{0}------------------------------------------------ K974167 ### Summary of Safety and Effectiveness Information PR-3 ANCA Test Kit # FEB 17 1998 Wieslab AB Ideon Research Park S-223 70 Lund Sweden Contact person: Dr. Jorgen Wieslander Telephone: 46-46-182840 Date of preparation: Jan 19, 1998 【. Description of Device: The Wielisa PR-3 ANCA Test Kit is an enzyme-linked immunosorbent 11. assay (ELISA) for the detection and semi-quantitation of lgG antibodies to Proteinase-3 (PR-3) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Wegener's granulomatosis. FOR IN VITRO DIAGNOSTIC USE. The wells of the microtiter strips are coated with purified proteinase 3. During the first incubation, specific antibodies in diluted serum, will bind to the antigen coating, The wells are then washed to remove unbound antibodies and other components. A conjugate of alkaline phosphatase-labeled antibodies to human IgG binds to the antibodies in the wells in this second incubation. After a further washing step, detection of specific antibodies is obtained by incubation with substrate solution. The amount of bound antibodies correlates to the color intensity and is measured in terms of absorbance (optical density (OD)). The absorbance is then calculated against a calibrator curve and the results are given in arbitrary units. #### 111. Predicate Device The PR-3 ANCA test is substantially equivalent to the Immunoscan PR-3 ANCA ELISA Kit. Equivalence is demonstrated by the following comparative results: {1}------------------------------------------------ Table 1. Clinical Sensitivity and Specificity A total of 364 frozen retrospective sera with clinical characterization were assayed. The following table summarizes the data. | Control and<br>Disease groups | Total<br>number | Negative<br><10 units | Equivocal<br>10-20 units | Positive<br>>20 units | |-------------------------------|-----------------|-----------------------|--------------------------|-----------------------| | Healthy Normals: | 120 | 120 | 0 | 0 | | WG: | 70 | 5 | 0 | 65 | | MP: | 55 | 26 | 3 | 26 | | SLE: | 40 | 38 | 1 | 1 | | RA: | 17 | 17 | 0 | 0 | | Anti-GBM nephritis: | 62 | 58 | 0 | 4 | GBM = glomerular basement membrane WG = Wegener's granulomatosis, SLE = systemic lupus erythematosus MP = microscopic polyangiitis RA = rheumatoid arthritis Clinical Sensitivity (Equivocal samples excluded from calculations) | WG = 65/70 = 92.9% | 95% confidence interval = 86.7-99.0% | |--------------------|--------------------------------------| | MP = 26/52 = 50.0% | 95% confidence interval = 36.1-63.9% | ### Clinical Specificity (Equivocal samples excluded from calculations) | SLE | = 38/39 | = 97.4% | 95% confidence interval = 92.4-100% | |---------|-----------|---------|--------------------------------------| | RA | = 17/17 | = 100% | *95% confidence interval = 82.7-100% | | GBM | = 58/62 | = 93.6% | 95% confidence interval = 87.3-99.8% | | Normals | = 120/120 | = 100% | *95% confidence interval = 97.5-100% | The 95% confidence intervals were calculated using the normal method. *The 95% confidence intervals were calculated assuming one false positive. {2}------------------------------------------------ Table 2 A total of 245 frozen retrospective sera were assayed on the Wielisa PR-3 ANCA ELISA and IFA. The following Table summarizes the relative sensitivity and specificity. ### Relative Sensitivity and Specificity of the Wielisa PR-3 ANCA Compared to C-ANCA IFA | | | Positive | Equivocal | Negative | Total | |---------------|----------|----------|-----------|----------|-------| | C-ANCA<br>IFA | Positive | 78 | 0 | 3 | 81 | | | Negative | 13 | 3 | 148 | 164 | | | Total | 91 | 3 | 151 | 245 | Sera falling in the equivocal range were excluded from the following calculations | | | | 95% Confidence Interval | |----------------------|-----------|----------|-------------------------| | Relative Sensitivity | = 78/81 | = 96.3 % | 92.1 - 100.0 % | | Relative Specificity | = 148/161 | = 91.9 % | 87.6 - 96.2 % | | Relative Accuracy | = 226/242 | = 93.4 % | 90.2 - 96.6 % | {3}------------------------------------------------ Table 3 A total of 120 frozen retrospective sera were assayed by the Wielisa PR-3 ANCA ELISA and by an alternate commercial ELISA. The following table summarizes the relative sensitivity and specificity of the assay. ### Relative Sensitivity and Specificity of the Wielisa PR-3 Kit Compared to an Alternate ELISA .• -• ## PR-3 Wielisa | | | Positive | Equivocal | Negative | Total | |--------------------|-----------|----------|-----------|----------|-------| | | Positive | 37 | 0 | 0 | 37 | | Alternate<br>ELISA | Equivocal | 1 | 0 | 1 | 2 | | | Negative | 2** | 0 | 79 | 81 | | | Total | 40 | 0 | 80 | 120 | Sera falling in the equivocal range were excluded from the following calculations | | | 95% Confidence Interval | |----------------------|--------------------|-------------------------| | Relative Sensitivity | = 37/37 = 100 % | 92.0 - 100 %* | | Relative Specificity | = 79/81 = 97.5 % | 94.1 - 100 % | | Relative Accuracy | = 116/118 = 98.3 % | 95.9 - 100 % | * One false negative was included in this caclulation. ** Both sera were from vasculitis patients {4}------------------------------------------------ ### Table 4. Batch to batch variation. Batch to batch variation was determined by testing 4 different samples in duplicate. Results were obtained for four different batches. | Sample | Mean value | SD | CV % | |--------|------------|-----|------| | 1 | 25 units | 2.3 | 9.1 | | 2 | 29 units | 4.1 | 14.3 | | 3 | 68 units | 8.7 | 12.7 | | 4 | 76 units | 6.7 | 8.9 | ### Table 5. Inter-assay precision. Inter-assay precision was determined by testing 2 different samples in duplicate. 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Intra-assay precision. Intra-assay precision was determined by testing one sample in 80 wells. | .<br>. 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Linearity . The values were determined for serial two-fold dilutions of seven positive sera. The values were compared to log2 of dilution by standard linear regression. The data in Table 7 indicates that the assay has a linear relationship with serum dilution. | Serum | Neat | 1:2 | 1:4 | 1:8 | 1:16 | 1:32 | 1:64 | r | |-------|------|-----|-----|-----|------|------|------|-------| | 1 | 168 | 95 | 57 | 34 | 15 | 5 | | 0.945 | | 2 | 84 | 43 | 23 | 13 | 5 | | | 0.942 | | 3 | 230 | 80 | 50 | 31 | 19 | 7 | | 0.851 | | 4 | 200 | 130 | 81 | 38 | 19 | 10 | 6 | 0.935 | | 5 | 269 | 146 | 64 | 34 | 20 | 9.5 | | 0.908 | | 6 | 276 | 75 | 46 | 26 | 12 | 8 | | 0.811 | | 7 | 141 | 73 | 50 | 30 | 16 | 8 | | 0.931 | {5}------------------------------------------------ Image /page/5/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle with three profiles of human faces incorporated into its design. 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 WEISLAB AB William L. Boteler c/o IMMUNO PROBE, INC. 1306 Bailes Lane, Suite F Frederick, MD 21701 FFB 17 1998 Re: K974167 Trade Name: Wielisa PR-3 ANCA Test System Regulatory Class: II Product Code: MOB 82 Dated: January 19, 1998 January 20, 1998 Received: 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 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 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 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 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations. {6}------------------------------------------------ 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 Putman 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 {7}------------------------------------------------ Page 1 of 1 510(k) Number: Not known ¥974167 Device Name: Wielisa PR-3 ANCA Test Kit Indications For Use: The Wielisa PR-3 ANCA Test Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of antibodies to Proteinase-3 (PR-3) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Wegener's granulomatosis. Peter E. Makin (Division Sign-Off) (Division of Clinical Laboratory Devices LG 74 16 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)