DIAMEDIX IS-ENA-6 SCREEN TEST SYSTEM

{0}------------------------------------------------ # 510(k) Summary of Safety and Effectiveness This 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: K980759 #### Applicant Information: | Date Prepared: | April 10, 1998 | |----------------|-----------------------------------------| | Name: | Diamedix Corporation | | Address: | 2140 N. Miami Avenue<br>Miami, FL 33127 | | Contact Person: | Dr. Lynne Stirling | |-----------------|--------------------| | Phone Number: | 305-324-2354 | | Fax Number: | 305-324-2585 | #### Device Information: | Trade Name: | Is-ENA-6 Screen Test System | |----------------------|--------------------------------------------------------------------------------| | Common Name: | ENA Screening Test | | Classification Name: | Antinuclear Antibody Immunological Test System<br>(866.5100), product code LLL | #### Equivalent Device: Zeus Scientific ENA Screen, ELISA Test System Device Description: The Is-ENA-6 Screen Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to six extractable nuclear antigens (ENAs), in human serum. Intended Use: The assay is intended for use in detecting IgG antibodies to ENA's (SSA, SSB, Sm, Sm/RNP, Scl-70 and Jo-1 in one well) in a single human serum sample. The results of the assay can be used as an aid in the diagnosis of autoimmune disorders. #### Principle of the Procedure: The Is-ENA-6 Screen Test System is an enzyme-linked immunosorbent assay to detect IgG to six ENAs in human serum. Purified antigens are attached to a solid phase microtiter well. Diluted test sera are added to each well. If antibodies which recognize the antigens are present in the patient sample they will bind to the antigens in the well. After incubation, the wells are washed to remove unbound antibody. An enzyme labeled anti-human immunoglobulin (conjugate) is added to each test well. If antibody is present the enzyme-linked antibody will bind to it. After incubation, the wells are washed to remove unbound conjugate. A substrate solution is then added to each well. If enzyme is present from prior step, the reaction is stopped and the color intensity is measured photometrically producing an indirect measure of the specific antibodies present in the patient sample. {1}------------------------------------------------ # Performance Characteristics ### A. Comparison Testing The Diamedix Is-ENA-6 Screen Test Kit was evaluated relative to another commercially available ENA Screen test kit. One hundred and fifty sera from normal blood donors and eighty-eight sera from clinical patients were tested by the Is-ENA-6 Screen Test Kit and the comparative method. Testing was performed manually and using the MAGO and MAGO PLUS Automated Processors. The results obtained are shown in Table 1. | | Manual | | | MAGO | | | MAGO PLUS | | | |----------------------|-----------|------|-----------|-----------|------|-----------|-----------|------|-----------| | TABLE 1. | # of Sera | % | 95%CI | # of Sera | % | 95% CI | # of Sera | % | 95% CI | | Relative Sensitivity | 81/88 | 92.0 | 84.3-96.7 | 82/89 | 92.1 | 84.5-96.8 | 82/89 | 92.1 | 84.5-96.8 | | Relative Specificity | 143/146 | 97.9 | 94.1-99.6 | 142/146 | 97.2 | 93.1-99.2 | 143/146 | 97.9 | 94.1-99.6 | | Overall Agreement | 224/234* | 95.7 | 92.3-97.9 | 224/235** | 95.3 | 91.8-97.6 | 225/235** | 95.7 | 92.3-97.9 | * Four equivocal samples were exluded from calculations; ** Three equivocal samples were excluded from calculations. Ten sera were discordant in the manual and MAGO PLUS testing; an additional sample was discordant in the MAGO testing. All discordant samples were tested in 6 specific commercially available ENA test kits for anti-SSA, -SSB, -Sm, -Sm/RNP, Scl-70 and Jo-1. The resolution of discordant samples is summarized in Table 2. #### TABLE 2. | Sample # | Is-ENA-6 Screen<br>Result | Other ENA Screen<br>Result | Resolution | |--------------|---------------------------|----------------------------|---------------------------------| | 82-normal | POS | NEG | NEG in all 6 specific ENA tests | | 84-normal | NEG | POS | NEG in all 6 specific ENA tests | | 90-normal* | POS | NEG | NEG in all 6 specific ENA tests | | 91-normal | NEG | POS | NEG in all 6 specific ENA tests | | 112-clinical | POS | NEG | POS for anti-SSA | | 128-clinical | NEG | POS | NEG in all 6 specific ENA tests | | 138-clinical | NEG | POS | POS for anti-Jo-1 | | 140-clinical | NEG | POS | NEG in all 6 specific ENA tests | | 173-clinical | POS | NEG | POS for anti-SSA | | 205-normal | NEG | POS | NEG in all 6 specific ENA tests | | 225-normal | NEG | POS | NEG in all 6 specific ENA tests | * This sample was a weak positive (Index 1.2) during MAGO testing only. ### B. Precision The precision of the Is-ENA-6 Screen test kit was determined by testing six different sera (2 negative and 4 positive) and the kit calibrator and controls in triplicate in two different runs on three different days. Precision was evaluated manually and using the MAGO and MAGO PLUS Processors. The intra- and interassay precision is shown in Table3. | TABLE 3. | Overall | MANUAL | | MAGO | | MAGO PLUS | | |----------|-----------|-----------|-----------|-----------|-----------|-----------|-----------| | SERUM | Mean Abs. | Intra-CV% | Inter CV% | Intra-CV% | Inter-CV% | Intra-CV% | Inter-CV% | | A (NEG) | 0.024 | 10.3 | 15.1 | 44.8 | 47.0 | 26.1 | 25.1 | | B (NEG) | 0.044 | 4.7 | 9.3 | 10.1 | 28.6 | 5.8 | 15.3 | | C (POS) | 0.600 | 7.0 | 8.4 | 7.3 | 12.0 | 5.9 | 11.6 | | D (POS) | 0.927 | 4.0 | 10.4 | 7.1 | 11.0 | 6.3 | 8.3 | | E (POS) | 1.004 | 3.0 | 9.3 | 6.6 | 9.9 | 6.7 | 9.9 | | F (POS) | 1.488 | 4.9 | 8.5 | 6.7 | 10.4 | 4.9 | 7.9 | | c/o CAL | 0.368 | 6.6 | 11.2 | 3.7 | 9.2 | 3.3 | 5.0 | | POS | 0.487 | 3.1 | 7.7 | 5.6 | 9.1 | 3.6 | 7.0 | | NEG | 0.060 | 9.0 | 12.9 | 18.1 | 23.0 | 10.7 | 13.7 | {2}------------------------------------------------ ### C. Expected Values The expected value for a normal patient is a negative result. However, positive results for autoantibodies may be found in some apparently healthy individuals. Patient sera containing autoantibodies to those antigens represented in the Is-ENA-6 Screen test will give positive results which can be further evaluated in specific tests. The number of positive samples detected is dependent upon the populations being tested. The expected values in a normal S. Florida blood donor population were evaluated by assaying 150 sera both manually and using the MAGO and MAGO PLUS Automated Processors. Figures 1, 3 and 5 show the distribution of results in this normal population. For manual and MAGO PLUS testing 98.6% of the normals gave negative results; for MAGO 98% gave negative results. Two normal samples positive in the Is-ENA-6 Screen were subsequently shown to be strongly positive for SSA antibodies. In the present studies 88 sera obtained from patients with an autoimmune disease or with a known autoantibody reactivity were evaluated in the Is-ENA-6 Screen. Figures 2, 4 and 6 show the distribution of results for this population. Image /page/2/Figure/3 description: The image contains six line graphs comparing expected values of normal and clinical samples using different methods: Manual, MAGO, and MAGO PLUS. Figures 1, 3, and 5 show the expected values for normal samples using Manual, MAGO, and MAGO PLUS methods, respectively, with a noticeable spike in index values towards the end of the sample range. Figures 2, 4, and 6 depict the expected values for clinical samples using the same methods, showing a gradual increase in index values as the number of samples increases. {3}------------------------------------------------ # D. Correlation of Manual, MAGO and MAGO PLUS Results Correlation of manual, MAGO and MAGO PLUS Index Values for the 238 samples tested in the Is-ENA-6 Screen Test Kit is shown in Figures 7, 8 and 9. Image /page/3/Figure/2 description: This image is a scatter plot titled "Figure 7. Manual vs MAGO Correlation". The x-axis is labeled "Mago" and ranges from 0.0 to 7.0, while the y-axis is labeled "Manual" and ranges from 0.0 to 9.0. A trend line is plotted through the data points, and the R-squared value is 0.9707. Image /page/3/Figure/3 description: The image is a scatter plot comparing "Manual" and "Mago Plus" measurements. The x-axis represents "Mago Plus" values ranging from 0.0 to 8.0, while the y-axis represents "Manual" values ranging from 0.0 to 10.0. A linear trendline is fitted to the data points, indicating a strong positive correlation between the two measurement methods. The R-squared value is 0.9799, suggesting a high degree of variance explained by the linear model. Figure 8. Manual vs MAGO PLUS Correlation Image /page/3/Figure/4 description: The image is a scatter plot titled "Figure 9. MAGO vs MAGO PLUS Correlation". The x-axis represents the MAGO index, and the y-axis represents the MAGO Plus Index. The scatter plot shows a strong positive correlation between the two indices, with an R-squared value of 0.988. Mago Index Figure 9. MAGO vs MAGO PLUS Correlation {4}------------------------------------------------ Image /page/4/Picture/2 description: The image is a black and white seal for the Department of Health & Human Services USA. The seal is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is a stylized image of three faces in profile, stacked on top of each other. The faces are connected by a flowing ribbon-like shape. APR 23 1998 Food and Drug Administration 2098 Gaither Road Rockville MD 20850 Lynne Stirling, Ph.D. Diamedix Corporation 2140 N. Miami Avenue Miami, Florida 33127 Re : K980759 Diamedix Is-ENA-6 Screen Test System Trade Name: Regulatory Class: II Product Code: LLL February 26, 1998 Dated: Received: February 27, 1998 Dear Dr. Stirling: 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 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 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. {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 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}------------------------------------------------ ## Appendix G. Indications for Use Statement # INDICATIONS FOR USE STATEMENT # 510(K) NUMBER : K980759 ### DEVICE NAME : Is-ENA-6 Screen Test System Indications for Use : For the qualitative screening of human IgG antibodies to extractable nuclear antigens (ENA) in human serum by indirect enzyme immunoassay as an aid in the diagnosis of certain autoimmune disorders. This test system screens for antibodies to Sm, Sm/RNP, SSA, SSB, Scl-70 and Jo-1 in one well. Positive samples should be evaluated further using tests designed for each ENA antibody. These reagents can be used either manually or in conjunction with the MAGO® or MAGO® PLUS Automated EIA Processors. prescription use ✓ in 4/23/98 Peter E. Makison (Division S... Ort) Division ...ical Laboratory Devices 510(k) Number k980759