(54 days)
The & MPO IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) For the qualitative detection and semi-quantitation of antibodies against the Myeloperoxidase antigen in serum as an aid in the diagnosis of Microscopic polyangiitis. The test can be performed either manually or in conjunction with the Mago Plus automated EIA processor.
The & MPO IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to Myeloperoxidase in human serum.
Here's an analysis of the provided text regarding the anti-MPO IgG ELISA Kit, focusing on acceptance criteria and study details:
Device: anti-MPO IgG ELISA Kit
Intended Use: Qualitative detection and semi-quantitation of antibodies against Myeloperoxidase antigen in serum as an aid in the diagnosis of Microscopic polyangiitis. Can be performed manually or with the Mago Plus automated EIA processor.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the relative sensitivity, specificity, or clinical performance. Instead, it reports the calculated performance characteristics. However, based on the presentation and the context of a 510(k) submission, the reported values serve as the de facto "met" criteria for demonstrating substantial equivalence to a predicate device. For precision, the document reports the CV% values. For the correlation study, a Pearson coefficient of 0.983 is reported, which is indicative of a strong correlation.
| Performance Metric | Acceptance Criteria (Inferred/Implicit) | Reported Device Performance (Manual) | Reported Device Performance (MAGO Plus) |
|---|---|---|---|
| Relative Sensitivity (vs. Other ELISA) | Demonstrated high sensitivity | 95.7% (95% CI: 78.0-99.9) | Not directly reported |
| Relative Specificity (vs. Other ELISA) | Demonstrated high specificity | 99.5% (95% CI: 97.4-100.0) | Not directly reported |
| Overall Agreement (vs. Other ELISA) | Demonstrated high agreement | 99.2% (95% CI: 97.0-99.9) | Not directly reported |
| Clinical Specificity (Normals) | Demonstrated high specificity | 98.9% (95% CI: 95.9-99.9) | Not directly reported (Manual implied) |
| Clinical Specificity (Wegener's Granulomatosis) | Demonstrated high specificity | 94.6% (95% CI: 81.8-99.3) | Not directly reported (Manual implied) |
| Clinical Sensitivity (Microscopic Polyangiitis) | Demonstrated sufficient sensitivity | 45.0% (95% CI: 29.3-61.5) | Not directly reported (Manual implied) |
| Intra-Assay Precision (CV%) | Low variability | Site 1: 4.49-194.37%Site 2: 3.23-100.23% | 8.15-105.41% (Positive results significantly lower) |
| Interassay Precision (CV%) | Low variability | Site 1: 7.31-136.93%Site 2: 9.57-100.23% | 15.88-100.98% (Positive results significantly lower) |
| Correlation: Manual vs. MAGO Plus | Strong correlation | Pearson Correlation Coefficient: 0.983 | N/A (this is the correlation test itself) |
Note on Precision CV%: The CV% for negative samples (E and F) is very high (e.g., 194.37%, 161.02%, 100.23%). This is common for values close to zero, where small absolute variations lead to large percentage changes. The CV% for positive samples is much lower and generally acceptable (e.g., 4.49-19.90%).
2. Sample Size Used for the Test Set and Data Provenance
- Relative Sensitivity and Specificity Study:
- Sample Size: 264 frozen retrospective sera from patients.
- Data Provenance: Not explicitly stated, but common for such studies in 510(k) submissions to be from a single or few clinical sites within the country of the applicant (USA, based on address). The term "retrospective sera" indicates samples collected in the past.
- Clinical Sensitivity and Specificity Study:
- Sample Size: 256 frozen retrospective, clinically characterized sera.
- Data Provenance: Not explicitly stated, but "retrospective, clinically characterized" implies samples from a clinical setting.
- Correlation of Manual and MAGO Plus Results:
- Sample Size: 100 serum samples.
- Data Provenance: Not specified, but likely from the same clinical context as the other studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- Relative Sensitivity and Specificity Study: The ground truth was established by another "Other ELISA" kit. There is no mention of human experts defining the ground truth for this comparison.
- Clinical Sensitivity and Specificity Study: The samples were "clinically characterized." This implies that patient diagnoses (Normals, Wegener's Granulomatosis, Microscopic Polyangiitis) were established through standard clinical evaluation, which would involve medical professionals (e.g., physicians, specialists). However, the number and qualifications of these experts are not mentioned in the document.
- Training Set Ground Truth: No specific "training set" or "ground truth for training set" details are provided, as this is a traditional ELISA kit, not an AI/machine learning device. The design and validation of ELISAs rely on established biochemical principles and purified antigens/antibodies, rather than iterative machine learning training.
4. Adjudication Method for the Test Set
- Relative Sensitivity and Specificity Study: The ground truth was based on the results of an "Other ELISA" kit. There was no human adjudication process described. "Equivocal results were excluded from calculations."
- Clinical Sensitivity and Specificity Study: The samples were "clinically characterized." This implies a clinical diagnosis process, which often involves multiple clinicians or a consensus, but no specific adjudication method (e.g., 2+1, 3+1) is detailed in the document. "Equivocal results were excluded from calculations."
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) assay, and such studies are typically performed for imaging devices or AI-assisted diagnostic tools where human readers interpret results. The "MAGO Plus" is an automated processor, not a human reader. The correlation study between manual and MAGO Plus results assesses the equivalence of the method of processing, not the improvement of human readers.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the device operates as a standalone assay for detecting MPO IgG antibodies. The "algorithm" in this context refers to the chemical reactions and spectrophotometric measurement, not a computational algorithm. The performance of the test, both manually and with the MAGO Plus automated EIA processor, is the standalone performance of the assay to detect the target analyte.
7. The Type of Ground Truth Used
- Relative Sensitivity and Specificity Study:
- Ground Truth: Results from a "similar assay" (other ELISA).
- Clinical Sensitivity and Specificity Study:
- Ground Truth: "Clinically characterized" patient diagnoses (e.g., Normals, Wegener's Granulomatosis, Microscopic Polyangiitis). This is effectively a form of clinical diagnosis/outcomes data as established by medical professionals.
8. The Sample Size for the Training Set
The concept of a "training set" as understood in artificial intelligence and machine learning is not applicable to this traditional immunoassay device. ELISA kits are developed based on established biochemical principles (antigen-antibody binding) and calibrated using standards and controls, not trained on vast datasets of patient samples in the same way an AI model would be. Therefore, there is no discrete "training set" in the context of this device.
9. How the Ground Truth for the Training Set was Established
As noted above, there is no "training set" in the context of AI/ML for this device. The development and calibration of the ELISA kit would involve a different process:
- Antigen and Antibody Validation: Ensuring the MPO antigen used is pure and reactive, and the anti-human IgG conjugate is specific.
- Assay Optimization: Determining optimal reagent concentrations, incubation times, wash steps, and developing cut-offs or calibration curves using known positive and negative control materials. These controls and calibrators serve a role analogous to "ground truth" for assay performance characterization, but it's fundamentally different from training an ML algorithm.
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510k Summary of Safety and Effectiveness
his 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:
Applicant Information:
| Date Prepared: | Sept 2, 1998 |
|---|---|
| Name: | Columbia Bioscience, Inc. |
| Address: | 8775 M Centre Park Drive, #559 |
| Columbia, MD 21045 |
| Contact Person: | Norman Jenkins |
|---|---|
| PhoneNumber. | 410-995-0450 |
| Fax Number. | 410-995-0448 |
Device Information:
| Trade Name: | anti-MPO IgG ELISA Kit |
|---|---|
| Common Name. | MPO IgG EIA Test |
| Classification Name; | MPO Serological Reagent |
Juivalent Device: ELIAS MPO Kit
Device Description: The & MPO IgG ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to Myeloperoxidase in human serum.
Intended Use: The & MPO IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) For the qualitative detection and semi-quantitation of antibodies against the Myeloperoxidase antigen in serum as an aid in the diagnosis of Microscopic polyangiitis. The test can be performed either manually or in conjunction with the Mago Plus automated EIA processor.
Principle of Procedure:
MPO antigen is bound to microwells. Diluted patient sera, Calibrators and controls are placed inthe microwells and incubated. Anti-MPO IgG antibodes, if present, will bind to the antigen forming 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 ਾroduct. The absorbance of this end product can be read spectrophotometrically at 450 nm (reference 600-630
)) and is directly proportional to the concentration of IgG antibodies to MPO present in the sample.
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Performance Characteristics
A. Relative Sensitivity and Specificity
Frozen retrospective sera from two hundred sixty-four patients were tested on the Is-anti-MPO IgG Test Fridan retrospective sera from two maneres for you antibodies. Based on the results of this testing, the relative senstitivity and specificity was calculated. The results obtained are shown in Table 2:
TABLE 2
Is-anti-MPO IgG
| POSITIVE | * EQUIVOCAL | NEGATIVE | ||
|---|---|---|---|---|
| OtherELISA | POSITIVE | 22 | 0 | 1 |
| EQUIVOCAL* | 6 | 2 | 15 | |
| NEGATIVE | 1 | 3 | 214 | |
| Relative Sensitivity | 22/23 = 95.7% | 95% CI78.0-99.9 | ||
| Relative Specificity | 214/215 = 99.5% | 97.4-100.0 | ||
| Overall Agreement | 236/238 = 99.2% | 97.0-99.9 |
- Equivocal results were excluded from calculations
NOTE : Please be advised that 'relative' refers to the assay's results to that of a similar assay. There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be made on the comparison's accuracy to predict disease.
B. Clinical Sensitivity and Specificity Using Characterized Sera
A total of 256 frozen retrospective, clinically characterized using the Is-anti-MPO Test Kit. The results obtained are shown in Table 3.
| Patient Group: | Positive | Equivocal* | Negative | Total |
|---|---|---|---|---|
| Normals | 2 | 1 | 173 | 176 |
| Wegener's Granulomatosis | 2 | 3 | 35 | 40 |
| Microscopic Polyangiitis | 18 | 0 | 22 | 40 |
| Clinical Specificity: | 95% CI | |||
| Normals | $173/175 = 98.9%$ | 95.9-99.9 | ||
| Wegener's Granulomatosis | $35/37 = 94.6%$ | 81.8-99.3 | ||
| Clinical Sensitivity: | 95% CI | |||
| Microscopic Polyangiitis | $18/40 = 45.0%$ | 29.3-61.5 |
| TABLE | 3 |
|---|---|
| ------- | --- |
- Equivocal results were excluded from calculations
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C. Precision
To determine the precision of the Is-anti-MPO IgG Test Kit, four positive and two negative sera were essayed ten times each in three different runs at two different sites. The intra- and interassay precision obtained at cach site is shown in Tables 4 and 5.
| SERUM | INTRA-ASSAY RUN 1 | INTRA-ASSAY RUN 2 | INTRA-ASSAY RUN 3 | INTERASSAY | ||||
|---|---|---|---|---|---|---|---|---|
| MEAN | CV% | MEAN | CV% | MEAN | CV% | MEAN | CV% | |
| EU/ml | EU/ml | EU/ml | EU/ml | |||||
| A (POS) | 21.88 | 4.49 | 22.67 | 5.14 | 24.79 | 5.48 | 23.11 | 7.31 |
| B (POS) | 8.12 | 8.61 | 8.66 | 8.75 | 8.22 | 8.13 | 8.33 | 8.70 |
| C (POS) | 14.76 | 5.92 | 15.14 | 8.22 | 16.21 | 8.76 | 15.37 | 8.56 |
| D (POS) | 47.29 | 5.35 | 57.31 | 7.70 | 47.86 | 5.10 | 50.82 | 11.08 |
| E (NEG) | 0.13 | 96.28 | 0.06 | 161.02 | 0.05 | 194.37 | 0.08 | 136.93 |
| F (NEG) | 0.26 | 45.15 | 0.24 | 56.25 | 0.06 | 86.07 | 0.19 | 74.09 |
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 EU/ml | CV% | MEAN EU/ml | CV% | MEAN EU/ml | CV% | MEAN EU/ml | CV% | |
| A (POS) | 25.71 | 17.57 | 22.74 | 3.23 | 24.02 | 4.05 | 24.16 | 11.94 |
| B (POS) | 9.96 | 9.92 | 8.76 | 5.47 | 8.82 | 5.85 | 9.18 | 9.57 |
| C (POS) | 22.88 | 8.58 | 15.60 | 7.24 | 15.77 | 3.86 | 18.08 | 20.40 |
| D (POS) | 79.81 | 7.20 | 50.83 | 9.42 | 56.29 | 5.52 | 62.31 | 21.76 |
| E (NEG) | 0.71 | 32.83 | 0.17 | 28.41 | 0.07 | 96.42 | 0.32 | 100.23 |
| F (NEG) | 0.84 | 11.50 | 0.31 | 23.80 | 0.24 | 40.25 | 0.46 | 61.70 |
D. Correlation of Manual and MAGO Plus Results
The Is-anti-MPO IgG Test Kit has been developed for automated as well as manual use. To demonstrate the equivalence of the manual and MAGO Plus procedures, the results of 100 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 0.983.
Image /page/2/Figure/8 description: The image is a scatter plot comparing MAGO Plus EU/ml values to MANUAL EU/ML values. The x-axis represents MANUAL EU/ML values, ranging from 0 to 100, while the y-axis represents MAGO Plus EU/ml values, ranging from 0 to 80. The plot shows a strong positive correlation between the two sets of values, with data points clustered around a regression line. The correlation coefficient, r, is given as 0.983, indicating a very strong linear relationship.
FIGURE 3 : Correlation of Manual vs MAGO Plus Results
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E. MAGO Plus Precision
The precision of the Is-anti-MPO IgG Test Kit when performed on the MAGO Plus Automated EIA Processor was determined by assaying six sera ten times each in three different runs. Table 6 shows the intra-and interassay precision obtained using the MAGO Plus.
| SERUM | INTRA-ASSAY RUN 1 | INTRA-ASSAY RUN 2 | INTRA-ASSAY RUN 3 | INTERASSAY | ||||
|---|---|---|---|---|---|---|---|---|
| MEAN | CV% | MEAN | CV% | MEAN | CV% | MEAN | CV% | |
| EU/ml | EU/ml | EU/ml | EU/ml | |||||
| A (POS) | 23.01 | 8.15 | 25.25 | 15.20 | 25.82 | 19.90 | 24.69 | 15.88 |
| B (POS) | 9.74 | 16.92 | 10.66 | 11.56 | 11.62 | 18.50 | 10.67 | 17.17 |
| C (POS) | 16.57 | 12.08 | 18.18 | 7.13 | 18.55 | 10.76 | 17.81 | 10.81 |
| D (POS) | 46.89 | 10.76 | 47.86 | 18.45 | 59.31 | 25.50 | 51.35 | 22.71 |
| E (NEG) | 0.10 | 105.41 | 0.45 | 68.09 | 0.32 | 99.70 | 0.29 | 100.98 |
| F (NEG) | 0.33 | 37.93 | 0.99 | 45.03 | 0.48 | 59.58 | 0.60 | 69.62 |
TABLE 6 : Site #2- Intra-Assay and Interassay Precision - MAGO Plus
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Image /page/4/Picture/2 description: The image shows the logo for the Department of Health & Human Services USA. The date "NOV 1 8 1998" is printed below the logo. The logo consists of a stylized eagle with three lines representing its wings and head. 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
Mr. Norman Jenkins President Columbia Bioscience, Inc. 8775 M Centre Park Drive, #559 Columbia, Maryland 21045
Re: K983390 Is-Anti MPO IgG ELISA Test System Trade Name: Requlatory Class: II Product Code: MOB Dated: September 23, 1998 Received: September 25, 1998
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, qood manufacturing practice, labeling, and prohibitions aqainst 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 requlatory 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.
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Paqe 2
This letter will allow you to beqin 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 requlation (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 requlation 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 Autman
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
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Page 1 of 1
510(k) Number: Not Known
Device Name: MPO IgG ELISA
Indications For Use: The & MPO IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) For the qualitative detection and semi-quantitation of antibodies against the Myeloperoxidase (MPO) antigen in serum as an aid in the diagnosis of The test can be performed either manually or in microscopic polyangiitis. conjunction with the Mago Plus automated EIA processor.
Peter E. Magrini
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)
§ 866.5660 Multiple autoantibodies immunological test system.
(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).