(69 days)
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.
The & TPO IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to thyroid peroxidase in human serum.
Acceptance Criteria and Study for Is-anti-TPO IgG ELISA Test Kit
This document describes the acceptance criteria and the studies performed to demonstrate the safety and effectiveness of the Is-anti-TPO IgG ELISA Kit.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Relative Sensitivity | Not explicitly stated, but compared to a commercially available ELISA kit. | 100% (71/71) when equivocal results are excluded. |
| Relative Specificity | Not explicitly stated, but compared to a commercially available ELISA kit. | 97.1% (167/172) when equivocal results are excluded. |
| Overall Agreement | Not explicitly stated, but compared to a commercially available ELISA kit. | 97.9% (238/243) when equivocal results are excluded. |
| Clinical Specificity (Normals) | Not explicitly stated, but assessed in normal patient group. | 91.4% (160/175) with a 95% CI of 86.3-95.1%. |
| Clinical Sensitivity (Grave's Disease) | Not explicitly stated, but assessed in Grave's Disease patient group. | 64.3% (9/14) with a 95% CI of 35.1-87.2%. |
| Clinical Sensitivity (Hashimoto's Disease) | Not explicitly stated, but assessed in Hashimoto's Disease patient group. | 75.0% (12/16) with a 95% CI of 47.6-92.7%. |
| Intra-Assay Precision (CV%) | Desired to be low for consistent results within a single assay run. | Site #1 (Manual): Range from 4.96% to 14.37% for positive sera, and 36.15% to 316.23% for negative sera (higher CV% for very low values is expected).Site #2 (Manual): Range from 6.31% to 19.84% for positive sera, and 6.35% to 15.90% for negative sera.MAGO Plus: Range from 8.42% to 20.61% for all sera. |
| Interassay Precision (CV%) | Desired to be low for consistent results across different assay runs. | Site #1 (Manual): Range from 5.89% to 11.04% for positive sera, and 41.92% to 161.76% for negative sera.Site #2 (Manual): Range from 8.29% to 21.47% for positive sera, and 43.97% to 55.73% for negative sera.MAGO Plus: Range from 11.43% to 48.32% for all sera. |
| Correlation of Manual and MAGO Plus Results | Demonstrate equivalence between manual and automated methods. | Pearson Correlation Coefficient of 0.977 (indicated good correlation). |
2. Sample Size and Data Provenance (Test Set)
- Relative Sensitivity and Specificity Study: 255 frozen retrospective sera.
- Clinical Sensitivity and Specificity Study: 207 frozen retrospective, characterized sera.
- Precision Study: 4 positive sera and 2 negative sera, each assayed 10 times in 3 different runs at 2 different sites. For MAGO Plus precision, 6 sera were assayed 10 times each in 3 different runs.
- Correlation of Manual and MAGO Plus Results: 104 serum samples.
Data Provenance: All data appears to be retrospective. The country of origin of the data is not explicitly stated in the provided text, but given the context of a US regulatory submission, it is likely the data was collected in the USA or a region with comparable clinical practices.
3. Number of Experts and Qualifications for Ground Truth (Test Set)
The document does not explicitly state the number of experts used to establish the ground truth for the test set, nor their specific qualifications (e.g., radiologist with X years of experience).
- For the "Relative Sensitivity and Specificity" study, a "commercially available ELISA kit for TPO antibodies" was used as the comparator, implying its results served as the reference for ground truth in that comparison.
- For the "Clinical Sensitivity and Specificity" study, "characterized sera" were used. This suggests that the ground truth for these samples (e.g., normal, Grave's Disease, Hashimoto's Disease) was previously established through clinical diagnosis, but the method and expert involvement are not detailed.
4. Adjudication Method (Test Set)
The document does not describe an adjudication method for the test set, such as 2+1 or 3+1. The ground truth appears to be based on results from a comparative device or pre-characterized clinical diagnoses.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned. The device is an in-vitro diagnostic (ELISA kit), not an imaging or AI-assisted diagnostic tool that typically involves human readers. Therefore, the concept of human readers improving with or without AI assistance is not applicable here.
6. Standalone Performance Study
Yes, a standalone performance study was conducted. The "Relative Sensitivity and Specificity" and "Clinical Sensitivity and Specificity" sections, along with the "Precision" studies, evaluate the performance of the "Is-anti-TPO IgG Test Kit" as a standalone device. The correlation study with the MAGO Plus demonstrates the performance of the kit both manually and when integrated with an automated processor, but these are still evaluations of the algorithm/kit itself.
7. Type of Ground Truth Used
- Relative Sensitivity and Specificity Study: The "ground truth" was established by the results of a commercially available ELISA kit for TPO antibodies. This is a form of comparative reference standard.
- Clinical Sensitivity and Specificity Study: The "ground truth" was based on characterized clinical diagnoses (Normals, Grave's Disease, Hashimoto's Disease). This can be categorized as clinical diagnosis/outcomes data, although the specific methods of characterization are not detailed.
8. Sample Size for the Training Set
The document does not mention a "training set" or "validation set" in the context of device development. The studies described are performance evaluations of the final device. This type of in-vitro diagnostic development typically focuses on analytical and clinical performance studies rather than machine learning model training.
9. How Ground Truth for Training Set Was Established
As no training set is described, the method for establishing its ground truth is not applicable or provided.
{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, #559Columbia, 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 | ||||
|---|---|---|---|---|---|---|---|---|
| MEANIU/ml | CV% | MEANIU/ml | CV% | MEANIU/ml | CV% | MEANIU/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)
§ 866.5870 Thyroid autoantibody immunological test system.
(a)
Identification. A thyroid autoantibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the thyroid autoantibodies (antibodies produced against the body's own tissues). Measurement of thyroid autoantibodies may aid in the diagnosis of certain thyroid disorders, such as Hashimoto's disease (chronic lymphocytic thyroiditis), nontoxic goiter (enlargement of thyroid gland), Grave's disease (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid.(b)
Classification. Class II (performance standards).