(875 days)
Ventana Medical Systems, Inc. developed the Ventana Keratin Primary Antibody for use on the Ventana 320 automated immunohistochemistry system.
Ventana Keratin Primary Antibody for use on the Ventana 320 automated immunohistochemistry system.
Here's an analysis of the provided text regarding the Ventana Keratin Primary Antibody, structured according to your request:
Device: Ventana Keratin Primary Antibody (clone 5D3) for use on the Ventana 320 automated immunohistochemistry system.
Description of Acceptance Criteria and Study:
The primary acceptance criteria for the Ventana Keratin Primary Antibody (clone 5D3) is its substantial equivalence to a commercially available anti-human cytokeratin (clone CAM 5.2). This equivalence is demonstrated through a comparative study evaluating staining patterns, intensity, specificity, and sensitivity in various tissue samples.
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria Category | Specific Metric | Acceptance Threshold (Implied) | Reported Device Performance |
|---|---|---|---|
| Equivalence to Comparator | Staining in Epithelial Cancers | ~100% agreement with comparator | 91% agreement with comparator in epithelial line cancers |
| Specificity (Non-Epithelial Cancers) | No staining in non-epithelial cancers | 0% staining | Neither antibody stained any non-epithelial type cancers |
| Normal Tissue Staining | Appropriate staining patterns | Qualitative assessment of appropriateness | Staining patterns of normal tissues considered appropriate |
| Staining Intensity | No statistically significant difference from comparator | p < 0.01 (Wilcoxon matched pairs) | No difference in performance (p < 0.01) |
| Specificity (Origin Based) | Staining of epithelial origin cells and no staining of mesodermal/endodermal origin cells | Qualitative assessment of appropriate staining | Appropriate staining of epithelial origin cells and no staining of mesodermal or endodermal origin cells |
| Sensitivity (Epithelial Cancers) | Comparable sensitivity to comparator | Similar number of positive cases out of 37 | Ventana: 30/37; Comparator: 31/37 |
| Reproducibility (Inter-Run) | Identical to comparator | Identical staining results across runs | Identical for both antibodies on 16 runs |
| Reproducibility (Intra-Run) | Identical to comparator | Identical staining results within a run | Identical for both antibodies on 10 samples within one run |
| Staining Intensity (Reproducibility) | Mean intensity and SD identical to comparator | Mean intensity and SD identical | Mean intensity and SD of 2.5 ± 0.00 for both antibodies |
2. Sample size used for the test set and the data provenance:
- Test Set Sample Size:
- Epithelial Line Cancers: 37 cases for sensitivity comparison.
- Non-Epithelial Type Cancers: Number not explicitly stated, but "any of the nonepithelial type cancers" implies a set of such samples were used.
- Normal Tissues: Breast, ureter, thyroid, skin, small intestine, stomach, liver, adrenal, muscle, prostate, tonsil, pituitary, thymus, esophagus, ovary, testes, pancreas, cardiac muscle, spinal cord, spleen, adenoid, kidney, connective tissue and salivary gland (number of samples for each not specified, but multiple types).
- Overall: "Paraffin embedded preparations from normal and pathologic samples" were used. The total number of individual samples across all categories is not explicitly provided, but is greater than 37.
- Data Provenance: The data is retrospective. Samples were "obtained from excess tissues obtained for reasons other than the present study." The country of origin is not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The text does not explicitly state the number of experts used.
- It mentions that slides were "evaluated on a blind basis for specific staining intensity and background staining." While this implies expert evaluation, no specific qualifications for these evaluators (e.g., "radiologist with 10 years of experience") are provided. The term "evaluated" suggests trained personnel, likely pathologists or histotechnicians with expertise in immunohistochemistry interpretation.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- The text does not describe an explicit adjudication method (like 2+1 or 3+1) for resolving discrepancies. It only states that slides were "evaluated on a blind basis." This suggests individual evaluations, but doesn't detail how agreement was reached or conflicts resolved if multiple evaluators were involved.
5. 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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study compares two antibodies against each other, not a human reader's performance with and without AI assistance. The "device" in this context is the antibody, not an AI system.
6. If a standalone (i.e. algorithm only, without human-in-the-loop performance) was done:
- Yes, this was a standalone study in the sense that the performance of the antibody (the "device") was assessed directly through its staining characteristics on tissue samples. There is no "algorithm" or "human-in-the-loop" interaction in the context of an antibody's performance. The automatic component is the Ventana 320 automated immunohistochemistry system that processes the slides, but the evaluation of the stained slides is a distinct step.
7. The type of ground truth used:
- The ground truth was established through a combination of:
- Expert Consensus/Pathology: Implicitly, the classification of tissues as "epithelial line cancers," "non-epithelial type cancers," or specific "normal tissues" would be based on prior pathological diagnosis.
- Comparative Analysis: The "ground truth" for the Ventana antibody's performance was its comparison to a "commercially available anti-human cytokeratin" (clone CAM 5.2), which served as the reference standard. The appropriateness of staining patterns was also likely based on expert pathological knowledge.
8. The sample size for the training set:
- The text does not mention a training set. This is a comparative study of two diagnostic reagents (antibodies), not a machine learning model that requires a training phase.
9. How the ground truth for the training set was established:
- Not applicable, as no training set was used.
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MAR 22 1999
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510(k) Summary of Safety and Effectiveness
Ventana Medical Systems, Inc. developed the Ventana Keratin Primary Antibody for use on the Ventana 320 automated immunohistochemistry system. Ventana Keratin Primary Antibody (clone 5D3) is substantially equivalent to a commercially available anti-human cytokeratin (clone CAM 5.2).
Comparative Study
Supporting data for the equivalence statement is shown by the following study. Paraffin embedded preparations from normal and pathologic samples were tested using Ventana Keratin Primary Antibody and a commercially available anti-human cytokeratin. Samples were obtained from excess tissues obtained for reasons other than the present study. Pathologic tissues evaluated for staining included colon carcinomas, breast carcinomas, prostatic carcinomas, adenocarcinoma, squamous cell carcinomas and nonepithelial cancers. Normal tissues examined were breast, ureter, thyroid, skin, small intestine, stomach, liver, adrenal, muscle, prostate, tonsil, pituitary, thymus, esophagus, ovary, testes, pancreas, cardiac muscle, spinal cord, spleen, adenoid, kidney, connective tissue and salivary gland. Slides were processed on the Ventana 320 Automated Slide Stainer and prepared for examination, then evaluated on a blind basis for specific staining intensity and background staining.
Results
When compared with a commercially available anti-human cytokeratin antibody. Ventana Keratin Primary Antibody stained the same tissues 91% of the time in epithelial line cancers. Neither Ventana Keratin Primary Antibody nor the commercially available antibody stained any of the nonepithelial type cancers. The staining patterns of the normal tissues were considered to be appropriate.
Staining intensity was scored on a scale of 0 - 4+. Non parametric analysis of the staining intensity results (Wilcoxon matched pairs) shows no difference in the performance of the two antibodies tested, even at the .01 level of significance.
Specificity of both antibodies was proven with appropriate staining of cells of epithelial origin and no staining of cells of mesodermal or endodermal origin. Sensitivity of keratin antibodies, based on comparison of 37 epithelial line cancers. showed that Ventana Keratin Primary Antibody stained 30 of 37 and the commercially available anti-human cytokeratin antibody stained 31 of 37.
Inter-run reproducibility, based on samples of the same tissue on 16 different instrument runs, and intra-run reproducibility, based on 10 samples of the same tissue within one run, were identical for both antibodies. The mean staining intensity and standard deviation of each antibody was 2.5 ± 0.00.
§ 866.5550 Immunoglobulin (light chain specific) immunological test system.
(a)
Identification. An immunoglobulin (light chain specific) immunological test system is a device that consists of the reagents used to measure by immunochemical techniques both kappa and lambda types of light chain portions of immunoglobulin molecules in serum, other body fluids, and tissues. In some disease states, an excess of light chains are produced by the antibody-forming cells. These free light chains, unassociated with gamma globulin molecules, can be found in a patient's body fluids and tissues. Measurement of the various amounts of the different types of light chains aids in the diagnosis of multiple myeloma (cancer of antibody-forming cells), lymphocytic neoplasms (cancer of lymphoid tissue), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus.(b)
Classification. Class II (performance standards).