IS ANTI-TPO IGG ELISA TEST SYSTEM

{0}------------------------------------------------ #### FEB 2 1999 ## 510k 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. 1984228 The assigned 510(k) number is: #### Applicant Information: | Date Prepared: | Nov 24, 1998 | |----------------|------------------------------------------------------| | Name: | Columbia Bioscience, Inc. | | Address: | 8775 M Centre Park Drive, #559<br>Columbia, MD 21045 | | Contact Person: | Norman Jenkins | |-----------------|----------------| | PhoneNumber: | 410-995-0450 | | Fax Number: | 410-995-0448 | #### Device Information: | Trade Name: | anti-TPO IgG ELISA Kit | |----------------------|-------------------------| | Common Name: | TPO IgG EIA Test | | Classification Name: | TPO Serological Reagent | #### Equivalent Device: ELIAS TPO Kit Device Description: The & TPO IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to thyroid peroxidase in human serum. Intended Use: The TPO IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) For the qualitative detection and quantitation of antibodies against the thyroid peroxidase antigen in serum as an aid in the diagnosis of thyroid autoimmune disease. The test can be performed either manually or in conjunction with the Mago Plus automated EIA processor. ### Principle of Procedure: TPO antigen is bound to microwells. Diluted patient sera, Calibrators and controls are placed inthe microwells and incubated. Anti-TPO IgG antibodes, if present, will bind to the 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 product. The absorbance of this end product can be read spectrophotometrically at 450 nm (reference 600-630 nm) and is directly proportional to the concentration of IgG antibodies to TPO present in the sample. {1}------------------------------------------------ # Performance Characteristics # A. Relative Sensitivity and Specificity Frozen retrospective sera from two hundred fifty-five patients were tested on the Is-anti-TPO IgG TestKit and a commercially available ELISA kit for TPO antibodies. Based on the results of this testing, the relative sensitivity and specificity was calculated. The results obtained are shown in Table 2: #### TABLE 2 ## Is-anti-TPO IgG | | Other | | |---|-------|--| | Ü | ાટે પ | | : | | POSITIVE | * EQUIVOCAL | NEGATIVE | |----------------------|-----------------|-------------|-----------| | POSITIVE | 71 | 0 | 0 | | EQUIVOCAL* | 6 | 0 | 2 | | NEGATIVE | 5 | 4 | 167 | | Relative Sensitivity | 71/71 = 100% | | 94.9-100 | | Relative Specificity | 167/172 = 97.1% | | 93.3-99.1 | | Overall Agreement | 238/243 = 97.9% | | 95.3-99.3 | * Equivocal results were excluded from calculations NOTE : Please be advised that 'relative' refers to the comparison of the assay's results to that of a similar assay. There was not an attempt to correlate the assuy'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 207 frozen retrospective, characterized sera were assayed using the Is-anti-TPO IgG Test Kit. The results obtained are shown in Table 3. | Patient Group: | Positive | Equivocal* | Negative | Total | |-----------------------|----------|-------------------|-----------|-------| | Normals | 15 | 1 | 160 | 176 | | Grave's Disease | 9 | 1 | 5 | 15 | | Hashimoto's Disease | 12 | 0 | 4 | 16 | | Clinical Specificity: | | | 95% CI | | | Normals | = | $160/175 = 91.4%$ | 86.3-95.1 | | | Clinical Sensitivity: | | | 95% CI | | | Grave's Disease | = | $9/14 = 64.3%$ | 35.1-87.2 | | | Hashimoto's Disease | = | $12/16 = 75.0%$ | 47.6-92.7 | | TABLE 3 * Equivocal results were excluded from calculations {2}------------------------------------------------ #### C. Precision To determine the precision of the Is-anti-TPO IgG Test Kit, four positive sera were assayed ten times each 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 IU/ml | CV% | MEAN IU/ml | CV% | MEAN IU/ml | CV% | MEAN IU/ml | CV% | | A (POS) | 49.2 | 12.19 | 46.8 | 8.76 | 46.6 | 8.80 | 47.5 | 10.10 | | B (POS) | 99.8 | 14.37 | 91.5 | 7.28 | 91.5 | 7.57 | 94.2 | 11.04 | | C (POS) | 209.5 | 11.70 | 205.4 | 4.98 | 205.3 | 4.96 | 206.7 | 7.73 | | D (POS) | 257.5 | 5.16 | 246.5 | 5.97 | 246.2 | 5.93 | 250.1 | 5.89 | | E (NEG) | 0.6 | 316.23 | 0.2 | 133.13 | 0.1 | 135.53 | 0.1 | 161.76 | | F (NEG) | 2.4 | 36.15 | 2.6 | 46.33 | 2.6 | 46.08 | 2.5 | 41.92 | 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 IU/ml | CV% | MEAN IU/ml | CV% | MEAN IU/ml | CV% | MEAN IU/ml | CV% | | A (POS) | 53.5 | 12.64 | 52.3 | 9.65 | 46.0 | 9.93 | 50.6 | 21.47 | | B (POS) | 105.6 | 19.84 | 93.2 | 9.49 | 87.3 | 6.31 | 95.4 | 15.91 | | C (POS) | 233.9 | 7.09 | 210.0 | 14.91 | 229.3 | 10.99 | 224.4 | 11.78 | | D (POS) | 123.1 | 7.10 | 246.6 | 7.51 | 244.2 | 9.30 | 240.6 | 8.29 | | E (NEG) | 8.8 | 6.35 | 7.8 | 11.40 | 1.5 | 12.17 | 6.0 | 55.73 | | F (NEG) | 13.1 | 11.21 | 11.7 | 10.67 | 4.0 | 15.90 | 9.6 | 43.97 | #### D. Correlation of Manual and MAGO Plus Results The Is-anti-TPO IgG Test Kit has been developed for automated as well as manual use. To demonstrative equivalence of the manual and MAGO Plus procedures, the results of 104 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 0.977. Image /page/2/Figure/9 description: The image is a title that reads "FIGURE 3 : Correlation of Manual vs MAGO Plus Results". The title is written in a bold, sans-serif font. The words are all capitalized. The title is centered on the image. Image /page/2/Figure/10 description: This image is a scatter plot comparing MAGO Plus IU/ml to MANUAL IU/ml. The x-axis represents MANUAL IU/ml, ranging from 0 to 1000, while the y-axis represents MAGO Plus IU/ml, ranging from -200 to 1200. The plot shows a positive correlation between the two variables, with data points scattered around a regression line, and the correlation coefficient (r) is 0.977. {3}------------------------------------------------ ## E. MAGO Plus Precision The precision of the Is-anti-TPO IgC Test Kit when performed on the MAGO Plus Automated EIA Processor was dctermined by assaying six sera ten times cach in three different runs. Table 6 shows the intra-and interassy precision obtained using the MAGO Plus. | SERUM | INTRA-ASSAY RUN 1 | | INTRA-ASSAY RUN 2 | | INTRA-ASSAY RUN 3 | | INTERASSAY | | |---------|-------------------|-------|-------------------|-------|-------------------|-------|---------------|-------| | | MEAN<br>IU/ml | CV% | MEAN<br>IU/ml | CV% | MEAN<br>IU/ml | CV% | MEAN<br>IU/ml | CV% | | A (POS) | 76.4 | 14.13 | 71.0 | 11.92 | 75.7 | 13.26 | 74.3 | 13.15 | | B (POS) | 147.1 | 13.08 | 124.7 | 8.42 | 156.6 | 12.01 | 142.8 | 14.75 | | C (POS) | 284.6 | 10.39 | 251.8 | 9.95 | 266.7 | 11.35 | 267.7 | 11.43 | | D (POS) | 321.0 | 16.29 | 320.7 | 17.74 | 351.4 | 20.61 | 331.1 | 16.90 | | E (NEG) | 1.1 | 36.81 | 2.3 | 16.64 | 1.1 | 49.66 | 1.5 | 48.32 | | F (NEG) | 7.7 | 33.81 | 6.1 | 20.62 | 6.0 | 19.59 | 6.6 | 29.15 | #### TABLE 6 : Site #2- Intra-Assay and Interassay Precision - MAGO Plus {4}------------------------------------------------ Public Health Service 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 features a stylized caduceus symbol, which is a staff with two snakes coiled around it. The symbol is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a circular arrangement. The text is written in a simple, sans-serif font. #### EEB 2 1999 Food and Drug Administration 2098 Gaither Road Rockville MD 20850 Norman Jenkins COLUMBIA BIOSCIENCE, INC. 8775 M Centre Park Drive, #559 21045 Columbia, MD K984228 Re: Trade Name: Is-anti-TPO IgG ELISA Test System Requlatory Class: II Product Code: JZO November 24, 1998 Dated: November 25, 1998 Received: 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, 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 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 In addition, FDA may publish further regulatory action. 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 (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html". Sincerely yours. Steven Dutman 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 1 510(k) Number .. Device Name: 7 TPO IgG ELISA Indications For Use: The TPO IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative detection and quantitation of antibodies against the Thyroid Peroxidase (TPO) antigen in serum as an aid in the diagnosis of thyroid autoimmune disease. The test can be performed either manually or in conjunction with the Mago Plus automated EIA processor. Peter E. Mapes | Labels | Values | |---------------|---------| | 510(k) Number | k984228 | 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)