VENTANA CEA PRIMARY ANTIBODY by VENTANA MEDICAL SYSTEMS, INC.

Ventana Medical Systems, Inc. developed the Ventana CEA Primary Antibody for use on the Ventana ES automated slide staining system. Ventana CEA Primary Antibody (clone TF 3H8-1) is substantially equivalent to a commercially available anti-human cytokeratin (clone CAM 5.2) in that they both stain antigens on cells of epithelial origin.

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Here's an analysis of the provided text, focusing on acceptance criteria and the study details:

The provided text, K94034J, is a 510(k) Summary of Safety and Effectiveness for the Ventana CEA Primary Antibody. This document describes a comparative study to demonstrate substantial equivalence to a commercially available anti-human cytokeratin antibody.

Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state quantitative acceptance criteria in a pass/fail format with specific thresholds. Instead, it focuses on demonstrating "substantially equivalent" performance to a predicate device in terms of staining patterns and specificity. The key performance indicators evaluated are:

Acceptance Criteria (Inferred from study goals)	Reported Device Performance (Ventana CEA Primary Antibody)
Staining Pattern Equivalency to Predicate (CAM 5.2) on Epithelial Tissues	Stained the same epithelial cells (normal breast, anexal glandular cells of skin, glandular cells of stomach, prostate, pancreas) as the predicate.
Specificity (No Inappropriate Staining)	No inappropriate staining of tissue observed.
Agreement with Predicate for Epithelial Line Cancers	Stained the same tissues as the predicate 78% of the time for epithelial line cancers.
Absence of Staining for Non-Epithelial/Non-Mesothelial Cancers	Did not stain any non-epithelial or non-mesothelial type cancers (same as predicate).
Appropriate Staining of Cells of Epithelial Origin	Showed appropriate staining of cells of epithelial origin.
No Staining of Cells of Endodermal Origin	Showed no staining of cells of endodermal origin.
Sensitivity for Known Positive Tissues	Consistent staining of 9 of 10 breast malignancies and 10 of 10 colon malignancies. Appropriate staining of normal epithelial tissue.
Negative Control Performance	Negative results observed with negative controls, with one exception attributed to tissue interference (1+ background).
Inter-run Reproducibility	Equivalent staining across 16 different instrument runs using samples of the same tissue.
Intra-run Reproducibility	Equivalent staining for 10 samples of the same tissue within one run.

Study Details

Sample size used for the test set and the data provenance:
- Sample Size:
  - "Paraffin embedded preparations from normal and pathologic samples" were used. The exact number of samples is not specified, but it encompassed various normal tissues (breast, skin, stomach, prostate, pancreas, brain, pituitary, kidney) and pathologic samples (epithelial line cancers, breast malignancies (10 cases), colon malignancies (10 cases), non-epithelial/non-mesothelial cancers).
  - For reproducibility: 16 samples of the same tissue for inter-run; 10 samples of the same tissue for intra-run.
- Data Provenance: "Samples were obtained from excess tissues obtained for reasons other than the present study." This indicates a retrospective collection of samples, likely from a pathology archive. The country of origin is not specified.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Number of Experts: One ("a qualified pathologist").
- Qualifications of Experts: Desc

Summary

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K94034J

DEC 2 3 1996

510(k) Summary of Safety and Effectiveness

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 the Ventana CEA Primary Antibody and a commercially available anti-human cytokeratin. Samples were obtained from excess tissues obtained for reasons other than the present study. Pathologic and normal tissues were examined. Slides were processed on the Ventana ES Automated Slide Stainer, prepared for examination, and evaluated by a qualified pathologist on a blinded basis for specific staining intensity and background staining.

Results

Staining with both antibodies occurred in the epithelial cells of normal breast, anexal glandular cells of skin, glandular cells of stomach, prostate and pancreas.

Cytokeratin stained brain, glandular cells of pituitary and tubular cells of kidney. CEA did not stain these tissues. Since the antigens are different, it would not be expected to have 100% concordance. There was however, no inappropriate staining of tissue by either of the antibodies.

When compared with the commercially available anti-human cytokeratin antibody, Ventana CEA Primary Antibody stained the same tissues 78% of the time for enithelial line cancers. Neither Ventana CEA Primary Antibody nor the commercially available cytokeratin antibody stained any of the non-epithelial or non-mesothelial type cancers.

Specificity of both antibodies was shown with appropriate staining of cells of enithelial origin and no staining of cells of endodermal origin. In addition, the specificity seen in this study agrees with the data published by (Verstijnen et al., Anticancer Research 6:97-104. 1986).

The sensitivity of this antibody was shown by consistent staining of 9 of 10 breast and 10 of 10 colon malignancies, and appropriate staining of normal epithelial tissue. As with any immunohistochemical reagent, the sensitivity is dependent on fixation, tissue processing, and slide preparation parameters.

The negative control which was run with each tissue gave negative results with one exception. In this case, the negative control gave the same score as the non-specific

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background (1+) which indicates that there was some inteference due to the tissue and not the specific antibody.

Inter-run reproducibility was determined based on samples of the same tissue on 16 different instrument runs with equivalent staining in all 16 slides. Intra-run reproducibility was determined based on 10 samples of the same tissue within one run with equivalent staining in all ten slides.

Regulation Number and Section

§ 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).