(77 days)
The assay is intended for use in detecting antibodies to SSB (La) antigen in a single human serum sample. The results of the assay are to be used as an aid in the diagnosis of autoimmune disorders.
The Is-anti-SSB Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to SSB (La) antigen in human serum.
Here's a breakdown of the acceptance criteria and study information for the Diamedix Is-anti-SSB Test System, based on the provided text:
Acceptance Criteria and Reported Device Performance
| Criteria | Acceptance Criteria (Implied) | Reported Device Performance (Manual) | Reported Device Performance (MAGO) |
|---|---|---|---|
| Relative Sensitivity | High sensitivity for detecting autoantibodies (e.g., ≥ 80-90%) | 95% (38/40 sera) | 95% (38/40 sera) |
| Relative Specificity | High specificity to avoid false positives (e.g., ≥ 95%) | 100% (124/124 sera) | 100% (124/124 sera) |
| Agreement | High concordance with a predicate device (e.g., ≥ 95%) | 99% (162/164 sera) | 99% (162/164 sera) |
| Linearity | Strong linear relationship between dilution and absorbance | R² = 0.9829 (Manual) | R² = 0.9874 (MAGO) |
| Precision | Low intra- and inter-assay variability (e.g., CV% < 20%) | Ranges from 2.5-10.3% (Intra-CV%) and 5.3-30.0% (Inter-CV%) across samples, calibrator and controls | Ranges from 3.0-53.0% (Intra-CV%) and 8.3-50.0% (Inter-CV%) across samples, calibrator and controls |
| Cross-reactivity | Minimal cross-reactivity with other auto-specificities | No cross-reactivity with SSA, Sm, RNP, Jo-1, Scl-70 (20/24 samples negative) | Not explicitly reported for MAGO, but implied similar to manual. |
| Correlation (Manual vs. MAGO) | High correlation between manual and automated methods (e.g., ≥ 0.90) | N/A | 0.91 (Pearson) for 165 samples |
Note on Acceptance Criteria: The document directly states the reported performance but does not explicitly define numerical acceptance criteria that were set before the study. The implied criteria are derived from typical expectations for diagnostic assays and the results themselves.
Study Details
-
Sample size used for the test set and the data provenance:
- Sample Size:
- Comparison Testing: 165 sera (100 normal blood donors + 65 autoimmune patients).
- Precision Testing: 6 different sera, kit Calibrator, and controls.
- Cross-reactivity: 24 sera.
- Expected Values: 100 normal donor sera + 65 clinically characterized sera (total 165 sera).
- Correlation (Manual vs. MAGO): 165 samples.
- Data Provenance:
- Normal Donor Sera: Collected in South Florida (USA).
- Autoimmune Patients Sera: "Clinically characterized sera" - no specific geographic origin or retrospective/prospective nature is stated for these.
- The study is likely retrospective as samples are "clinically characterized" and already available for testing against two methods.
- Sample Size:
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number of experts or their qualifications.
- It mentions "clinically characterized sera" for autoimmune patients, implying medical professionals or a diagnostic process established their status, but details are not provided.
- For normal blood donors, the "normal" status serves as a baseline ground truth.
-
Adjudication method for the test set:
- The document mentions: "Upon retest by a referee method, one of the sera was positive, the other was negative" for two discrepant samples in the comparison testing. This indicates a form of adjudication by a referee method for discordant results, but the specific process (e.g., number of referees, consensus rules) is not detailed.
- For the initial ground truth of "clinically characterized sera," the adjudication method is not described.
-
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This is a diagnostic device (ELISA kit) for detecting antibodies, not an AI-powered system designed to assist human readers (like radiologists interpreting images). Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed. The "MAGO" system mentioned is likely an automated instrument for running the ELISA, not an AI interpretation tool.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, in essence. The "device" itself (the Is-anti-SSB Test System) operates as a standalone diagnostic tool. Its performance (sensitivity, specificity) is measured by how accurately it detects antibodies in patient samples, independent of human interpretation of the result beyond reading the final photometric value. The MAGO system further automates this, effectively representing a "standalone" automated assay.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Clinical Characterization: For the 65 autoimmune patients, the ground truth was established by their "clinically characterized" status, implying a diagnosis based on clinical symptoms, other diagnostic tests, and potentially expert medical opinion.
- Normal Status: For the 100 normal blood donors, the ground truth was their status as "normal."
- Referee Method: For discrepant results, a "referee method" was used as the ground truth.
-
The sample size for the training set:
- This document describes performance validation studies, not the development or training of an algorithm (like an AI model). Therefore, there is no "training set" in the context of machine learning. The ELISA kit itself is a biochemical assay.
-
How the ground truth for the training set was established:
- Not applicable as there is no training set for an algorithm. The "training" of the assay kit would pertain to its biochemical formulation and optimization during its development, not a data-driven training process in the AI sense.
{0}------------------------------------------------
510(k) Summary of Safety and Effectiveness
This summary of 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: | January 15, 1997 |
|---|---|
| Name: | Diamedix Corporation |
| Address: | 2140 N. Miami AvenueMiami, FL 33127 |
| Contact Person: | Dr. Lynne Stirling |
| Contact Person: | Dr. Lynne Stirling |
| Phone Number: | 305-324-2354 |
| Fax Number: | 305-324-2585 |
Device Information:
Trade Name: Is-(immunosimplicity)-anti-SSB Test System Common Name: Anti-SSB EIA Test Classification Name: Extractable Antinuclear Antibody
Equivalent Device:
Helix Diagnostics Enzyme Immunoassav Anti-SS-B/La Antibody Test Kit
Device Description: The Is-anti-SSB Test Kit System is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG to SSB (La) antigen in human serum.
Intended use: The assay is intended for use in detecting antibodies to SSB (La) antigen in a single human serum sample. The results of the assay are to be used as an aid in the diagnosis of autoimmune disorders.
Comparison to Predicate Device:
The Is-anti-SSB Test System is an enzyme-linked immunosorbent assay to detect IgG to SSB (La) in human serum. Purified SSB (La) antigen is attached to a solid phase microtiter well. Diluted test sera are added to each well. If antibodies which recognize the SSB antigen are present in the patient sample, they will bind to the antigen 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 the prior step, the substrate will be converted to produce a colored product. The reaction is stopped and the color intensity is measured photometrically providing an indirect measure of the specific antibody present in the patient sample.
{1}------------------------------------------------
Summary of Safety and Effectiveness
Performance Characteristics
A. Comparison Testing
The Diamedix Is-anti-SSB Test Kit was evaluated relative to another commercially available anti-SSB ELISA test kit using clinically characterized sera. One hundred sera from normal blood donors and 65 sera from autoimmune patients were tested by Is-anti-SSB and a commercially obtained anti-SSB ELISA test kit. The results are summarized in Table 1. below.
| Table 1 | Manual | MAGO | ||||
|---|---|---|---|---|---|---|
| Number of Sera | % | 95% Confidence | Number of Sera | % | 95% Confidence | |
| Relative Sensitivity | 38/40 | 95 | 83-99 | 38/40 | 95 | 83-99 |
| Relative Specificity | 124/124 | 100 | 97-100 | 124/124 | 100 | 97-100 |
| Agreement | 162/164* | 99 | 96-100 | 162/164* | 99 | 96-100 |
- One borderline sample was excluded from the calculation.
Two sera were negative in Is-anti-SSB and positive in the comparative method (manual and MAGO). Upon retest by a referee method, one of the sera was positive, the other was negative.
B. Linearity
Figures 1 and 2 show typical examples of Is-anti-SSB Test Kit linearity. The figures depict the results of the Calibrator tested by Is-anti-SSB after a serial two-fold manual dilution in Sample Diluent. Separate dilutions were tested both manually and with MAGO. The results demonstrate a high degree of linearity for the Is-anti-SSA Test Kit throughout the testing range.
Image /page/1/Figure/9 description: The image contains two line graphs titled "Is anti-SSB Calibrator Linearity". Both graphs show the relationship between dilution and absorbance. The first graph has an R-squared value of 0.9829, while the second graph has an R-squared value of 0.9874, indicating a strong positive correlation between dilution and absorbance in both graphs.
Figurel. Manual Linearity
Figure 2. MAGO Linearity
000208
■
{2}------------------------------------------------
C. Precision
The precision of the Is-anti-SSB Test Kit was determined by testing six different sera and kit Calibrator and controls in two runs on three different days. The intra- and inter assay precision is shown in Table 2.
| Table 2 | anti-SSB PRECISION | ||||
|---|---|---|---|---|---|
| OVERALL | MANUAL | MAGO | |||
| SERUM | MEANEU/ml | INTRA-CV% | INTER-CV% | INTRA-CV% | INTER-CV% |
| 1 (NEG) | 1.4 | 10.1 | 21.4 | 27.3 | 30.8 |
| 2 (NEG) | 1.4 | 4.3 | 6.3 | 13.9 | 16.7 |
| 3 (POS) | 37.5 | 4.5 | 11.2 | 8.2 | 11.2 |
| 4 (POS) | 29.7 | 4.1 | 10.4 | 4.1 | 9.2 |
| 5 (POS) | 55.4 | 4.0 | 8.0 | 4.0 | 8.3 |
| 6 (POS) | 96.9 | 3.5 | 5.3 | 3.0 | 8.7 |
| CAL | 100.8 | 4.2 | 6.5 | 5.6 | 10.1 |
| POS CTRL | 39.8 | 2.5 | 8.5 | 4.5 | 11.3 |
| NEG CTRL | 0.9 | 10.3 | 30.0 | 53.0 | 50.0 |
D. Crossreactivity
Twenty-four sera positive for the six autoimmune specificities were tested in Is-anti-SSB Test Kit. The results are shown in Table 3
| Sample | Is-anti-SSB EU/ml | Interp | Specificity |
|---|---|---|---|
| 1 | 5.5 | Neg | SSA |
| 2 | 3.7 | Neg | SSA |
| 3 | 0.9 | Neg | SSA |
| 4 | 1.6 | Neg | SSA |
| 5 | 236.2 | Pos | SSB |
| 6 | 48.3 | Pos | SSB |
| 7 | 148.3 | Pos | SSB |
| 8 | 128.4 | Pos | SSB |
| 9 | 6.3 | Neg | Sm |
| 10 | 1.4 | Neg | Sm |
| 11 | 1.1 | Neg | Sm |
| 12 | 1.6 | Neg | Sm |
| 13 | 3.7 | Neg | RNP |
| 14 | 2.1 | Neg | RNP |
| 15 | 2.3 | Neg | RNP |
| 16 | 3.3 | Neg | RNP |
| 17 | 1.4 | Neg | Jo-1 |
| 18 | 4.5 | Neg | Jo-1 |
| 19 | 1.5 | Neg | Jo-1 |
| 20 | 1.7 | Neg | Jo-1 |
| 21 | 2.1 | Neg | Scl-70 |
| 22 | 2.5 | Neg | Scl-70 |
| 23 | 2.3 | Neg | Scl-70 |
| 24 | 1.8 | Neg | Scl-70 |
厚手
| Table 3 | Crossreactivity | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| -- | -- | --------- | -- | -- | -- | -- | -- | ----------------- | -- | -- | -- | -- |
{3}------------------------------------------------
E. Expected Values
The expected values in the normal population were determined by assaying 100 normal donor sera collected in South Florida. Figures 3 and 5 show the distribution of SSB results in the normal population performed manually and on MAGO respectively.
The distribution of EU/ml values for 65 clinically characterized sera along with the 100 normal donor sera are shown in Figures 4 and 6 performed manually and on MAGO respectively.
Image /page/3/Figure/3 description: The image is a graph titled "Is anti-SSB Normals". The x-axis is labeled "Number of Sera" and ranges from 0 to 100. The y-axis is labeled "EU/ml" and ranges from 0.0 to 30.0, with a horizontal line at 20.0. There is a line plot that starts near 0.0 and gradually increases to just under 10.0 at the end of the x-axis.
Image /page/3/Figure/4 description: The image is a graph titled "Is anti-SSB Expected Values". The x-axis is labeled "Number of Sera" and ranges from 0 to 160. The y-axis is labeled "EU/ml" and ranges from 0.0 to 250.0. The graph shows a line that is relatively flat until the x-axis reaches approximately 120, at which point the line increases sharply.
Figure 3. Manual Normals
Figure 4. Manual Expected Values
Image /page/3/Figure/7 description: The image is a graph titled "Is anti-SSB Normals". The x-axis is labeled "Number of Sera" and ranges from 0 to 100. The y-axis is labeled "EU/ml" and ranges from 0.0 to 30.0. A horizontal line is drawn at the 20.0 mark, and a curve is plotted that starts near 0.0 and increases to around 7.0 at the 100 mark.
Image /page/3/Figure/8 description: The image is a graph that shows the EU/ml on the y-axis and the number of sera on the x-axis. The y-axis ranges from 0.0 to 250.0, and the x-axis ranges from 0 to 150. The graph shows a horizontal line at around 10 EU/ml until the number of sera reaches around 120, then the graph increases sharply to around 170 EU/ml at 160 sera.
Figure 5 MAGO Normals
Figure 6. MAGO Expected Values
F. Correlation of Manual and MAGO Results
Numerical comparison of EU/ml values, between manual and MAGO results for 165 samples in the Is-anti-SSB Test Kit showed a correlation of 0.91 (Pearson).
토
§ 866.5100 Antinuclear antibody immunological test system.
(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).