WIELISA ANCA SCREENING KIT TEST SYSTEM

{0}------------------------------------------------ ## JUL 22 1998 Summary of Safety and Effectiveness Information ANCA Screening ELISA Test Kit I. Wieslab AB Ideon Research Park S-223 70 Lund Sweden Contact person: Dr. Jorgen Wieslander Telephone: 46-46-182840 Date of preparation: May 1, 1998 Description of Device: The Wielisa ANCA Screening Test Kit is an enzyme-linked II. immunosorbent assay (ELISA) for the qualitative detection of antibodies to Proteinase-3 (PR-3) and Myeloperoxidase (MPO) 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 systemic vasculitis, especially Wegener's granulomatosis (WG) and microcopic polyangiitis (MP). The assay is intended for use in patients with signs and symptoms consistent with systemic vasculitis. It is not intended for screening a healthy population. A positive result should always be confirmed by a semi-quantitative assay. The wells of the microtiter strips are coated with purified (Human Neutrophil source) proteinase 3, and MPO (Human Neutrophil source) antigen. 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 (Goat) 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 and the results are given as a ratio to the negative control. ## III. Predicate Device The ANCA Screening test is substantially equivalent to the Wielisa PR-3 ANCA ELISA Kit and the Wielisa MPO ANCA ELISA Kit. Equivalence is demonstrated by the following comparative results: {1}------------------------------------------------ | Control and<br>Disease groups | Total | Negative <3<br>PR3 MPO | Equivocal 3-4<br>PR3 MPO | Positive >4<br>PR3 MPO | |-------------------------------|-------|------------------------|--------------------------|------------------------| |-------------------------------|-------|------------------------|--------------------------|------------------------| | Table 1. Clinical sensitivity and specificity. A total of 288 frozen retrospective sera with clinical | | |-------------------------------------------------------------------------------------------------------|--| | characterisation were assayed. The following table summarises the results | | | Control and<br>Disease groups | Total | Negative +3 | | Equivocal +? | | Positive +? | | |-------------------------------|-------|-------------|-----|--------------|-----|-------------|-----| | | | PR3 | MPO | PR3 | MPO | PR3 | MPO | | Blood donors: (NS) | 131 | 131 | 127 | 0 | 4 | 0 | 0 | | WG: | 42 | 3 | 37 | 0 | 1 | 39 | 4 | | MP: | 43 | 20 | 23 | 2 | 0 | 21 | 20 | | SLE: | 31 | 31 | 24 | 0 | 2 | 0 | *5 | | RA: | 41 | 41 | 40 | 0 | 1 | 0 | 0 | WG = Wegener's granulomatosis, MP = microscopic polyangiitis RA = rheumatoid arthritis SLE = systemic lupus erythematosus GBM = glomerular basement membrane *All samples were positive in the semi-quantitative MPO-ELISA. ## Clinical sensitivity (Equivocal samples not included in the calculations) | PR3-ANCA: | WG = 39/42 = 92.9 % | 95% CI = 84.9-100% | |-----------|---------------------|---------------------| | | MP = 21/41 = 51.2 % | 95% CI = 35.6-66.8% | | MPO-ANCA: | WG = 4/41 = 9.8 % | 95% CI = 4.9-19.0% | | | MP = 20/43 = 46.5 % | 95% CI = 31.3-61.7% | Clinical specificity (Equivocal samples not included in the calculations) | PR3-ANCA: SLE = 31/31 = 100 % | 95% CI = 90.4-100% | |--------------------------------|---------------------| | RA = 41/41 = 100 % | 95% CI = 92.7-100% | | NS = 131/131 = 100 % | 95% CI = 97.6-100% | | MPO-ANCA: SLE = 24/29 = 82.8 % | 95% CI = 68.7-96.8% | | RA = 40/40 = 100 % | 95% CI = 92.6-100% | | NS = 127/127 = 100 % | 95% CI = 97.6-100% | {2}------------------------------------------------ Table 2. Relative sensitivity and specificity of the Wielisa ANCA screen kit compared to an semi-quantitative ELISA. A total of 216 frozen retrospective sera were assayed. The following table summarises the results. | Wielisa ANCA screen | | | | | | | | |-------------------------|-----------|-------------|---------------|-------------|-----|----|----| | Semi-quantitative ELISA | | Negative <3 | Equivocal 3-4 | Positive >4 | | | | | | | PR3 | MPO | PR3 | MPO | | | | MPO-ANCA | Positive | 0 | 1 | 0 | 0 | 0 | 23 | | PR3-ANCA | Positive | 1 | 0 | 0 | 0 | 59 | 0 | | | Negative | 152 | 182 | 2 | 4 | 0 | 0 | | | Equivocal | 1 | 4 | 0 | 1 | 1 | 1 | | | Total | 154 | 187 | 2 | 5 | 60 | 24 | Sera falling in the equivocal range were are not including in the calculations: | Relative sensitivity PR3-ANCA = 59/60 = 98.3 % | 95% CI = 95.0-100% | |-------------------------------------------------|--------------------| | Relative sensitivity MPO-ANCA = 23/24 = 95.8 % | 95% CI = 87.7-100% | | Relative specificity PR3-ANCA = 152/152 = 100 % | 95% CI = 98.0-100% | | Relative specificity MPO-ANCA = 182/182 = 100 % | 95% CI = 98.4-100% | . {3}------------------------------------------------ | Sample<br>PR3 | Mean<br>OD ratio | SD | CV % | Sample<br>MPO | Mean<br>OD ratio | SD | CV % | |---------------|------------------|-----|------|---------------|------------------|-----|------| | 2 | 34.5 | 1.0 | 3 | 3 | 16.3 | 3.9 | 24 | | 5 | 19.8 | 2.2 | 11 | 6 | 27.8 | 2.1 | 7 | | 8 | 33.8 | 1.5 | 4 | 9 | 23 | 2.9 | 13 | Table 3. Batch to batch variation was determined by testing three different samples. Results were obtained for 4 different batches. Table 4. Inter-assay precision was determined by testing one sample. Results were obtained for six different runs. | Sample | OD<br>ratio | SD | CV % | Sample<br>MPO | Mean<br>OD ratio | SD | CV % | |--------|-------------|-----|------|---------------|------------------|------|------| | PK | 27.3 | 2.9 | 11 | PK | 17.3 | 3.8 | 21 | | K5 | 12.1 | 1.2 | 10 | K6 | 16.5 | 0.84 | 5 | Table 5. Intra-assay precision was determined by testing one sample in 22 wells. | Sample | Mean<br>OD | SD | CV % | Sample | Mean<br>OD | SD | CV % | |--------|------------|------|------|--------|------------|------|------| | PK | 1.3 | 0.07 | 6 | PK | 1.9 | 0.06 | 3 | | K5 | 1.3 | 0.06 | 5 | K6 | 1.46 | 0.07 | 5 | {4}------------------------------------------------ Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three lines representing its body and wings. The eagle is positioned to the right of a circular border containing the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA". The text is arranged around the circumference of the circle. JUL 2 2 1998 Food and Drug Administration 2098 Gaither Road Rockville MD 20850 Weislab AB c/o William L. Boteler, Jr. IMMUNO PROBE, INC. 1306 Bailes Lane, Suite F Frederick, MD 21701 K981748 Re: Trade Name: Wielisa ANCA Screening Test Kit Regulatory Class: II Product Code: MOB Dated: May 3, 1998 Received: May 18, 1998 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, Druq, 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 reqistration, 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 Existing major regulations affecting your device additional controls. 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 requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General requlation (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 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. {5}------------------------------------------------ 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 Sutman 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 K981748 510(k) Number: Not known Device Name: Wielisa ANCA Screening Test Kit Indications For Use: The Wielisa ANCA Screening Test Kit is an enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of antibodies to Proteinase-3 (PR-3) and Myeloperoxidase (MPO) 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 systemic vasculitis, especially Wegener's granulomatosis (WG) and : microcopic polyangiitis (MP). The assay is intended for use in patients with signs and symptoms consistent with systemic vasculitis. It is not intended for screening a healthy population. A positive result should always be confirmed by a semi-quantitative assay. ## PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) _____________________________________________________________________________________________________________________________________________________________________________ Concurrence of CDRH, Office of Device Evaluation (ODE) 11 Prescription Use (Per 21 CFR 801.109) OR Over-The Counter Use (Optional Format 1-2-96) Ji Ma (Division Sign-Off) Divotlinical Laboratory Devices K98,748 510(k) Number