VENTANA ANTI-CD8 PRIMARY ANTIBODY by VENTANA MEDICAL SYSTEMS, INC.

Here's an analysis of the provided text regarding the acceptance criteria and study for Ventana Anti-CD8 (Clone SFC121Thy2D3), structured as requested:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Specific Staining Intensity	Staining occurred on the surface of lymphoid cells from normal tonsil, thymus, and blood. 9 of 9 T cell lymphomas, and appropriate staining of normal lymphoid tissues (9 of 9 blood smears, 4 of 4 peripheral blood lymphocyte cytospins, 4 of 4 thymus tissues and 10 of 10 tonsil tissues) stained positively.
Background Staining	Negative control tissue was all negative. No inappropriate staining of tissues. The negative control run with each tissue gave negative results.
Sensitivity (Appropriate staining of lymphoid origin cells)	Appropriate staining of cells of lymphoid origin.
Specificity (No staining of non-lymphoid origin cells)	No staining of cells of non-lymphoid origin.
Inter-run Reproducibility (Consistent staining across different runs)	All ten slides (using frozen tonsil as positive control) stained positively for CD8 antigen across 10 different instrument runs.
Intra-run Reproducibility (Consistent staining within a single run)	All ten slides (using same frozen tonsil tissue) stained positively for CD8 antigen within one run.
Equivalence to existing antibodies/published data	The Ventana data in this study agrees with the data published by Reinherz et.al. and Deegan.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size:
- T cell lymphomas: 9
- Normal blood smears: 9
- Peripheral blood lymphocyte cytospins: 4
- Thymus tissues: 4
- Tonsil tissues: 10
- Negative control tissue: (Number not specified, but stated as "all negative")
- Inter-run reproducibility: 10 (frozen tonsil)
- Intra-run reproducibility: 10 (frozen tonsil)
Data Provenance: Samples were "obtained from excess tissues obtained for reasons other than the present study." This indicates a retrospective collection of samples. The country of origin is not specified.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

Number of Experts: 1
Qualifications: "a qualified pathologist" (specific experience level not provided).

4. Adjudication Method for the Test Set

The text describes evaluation by "a qualified pathologist," implying a single reader's assessment. There is no mention of an adjudication method such as 2+1 or 3+1.

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, an MRMC comparative effectiveness study was not done. This study evaluates an immunohistochemistry reagent, not an AI system or device intended for a human-in-the-loop diagnostic process. The reported study focuses on the performance of the antibody in staining tissues, not on human reader performance with or without assistance.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, a standalone study was done. The device being evaluated is an anti-CD8 antibody used on an automated immunohistochemistry system. The study assesses the performance of this reagent (antibody + automated system) in staining tissues, which is a standalone function where the "algorithm" is the biochemical reactivity of the antibody and the automation of the system. The evaluation by the pathologist is to assess the staining, not to use the device as a diagnostic aid in a human-in-the-loop scenario.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth was established by pathological evaluation of the tissue samples by a qualified pathologist, assessing "specific staining intensity and background staining." The text also refers to existing published literature and previous knowledge (Reinherz et al., Deegan) as part of the understanding of what constitutes "appropriate staining" for CD8.

8. The sample size for the training set

This information is not provided. The study described here is evaluating the performance of the antibody; there is no mention of a "training set" in the context of machine learning or algorithm development. The antibody's specificity and reactivity would have been developed through prior R&D, but the details of that are not in this summary.

9. How the ground truth for the training set was established

This information is not provided as there is no training set described.

Summary

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KQ41784

510(k) Summary of Safety and Effectiveness

FEB 1 4 1997

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.

Ventana Medical Systems. Inc. developed Ventana Anti-CD8 (Clone SFC121Thy2D3) for use on the Ventana ES automated immunohistochemistry system. Ventana Anti-CD8 (Clone SFCI21Thy2D3) is substantially equivalent to antibodies detecting cellular elements of lymphocytic origin as reported by Reinherz, et al.1

Comparative Study

Supporting data for the equivalence statement is shown by the following study. Frozen preparations from normal and pathologic samples were tested using Ventana Anti-CD8 (Clone SFCI21Thv2D3). 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 for specific staining intensity and background staining.

Results

Staining occurred on the surface of lymbhoid cells from normal tonsil, thymus and blood. Negative control tissue was all negative. There was no inappropriate staining of the tissues in this study.

Sensitivity of the antibody was shown with appropriate staining of cells of lymphoid origin and no staining of cells of non-lymphoid origin. In addition, the Ventana data in this study agrees with the data published by Reinherz et.al. and Deegan2.

The reactivity of this antibody was shown by consistent staining of 9 of 9 T cell lymphomas, and appropriate staining of normal lymphoid tissues (9 of 9 blood smears, 4 of 4 peripheral blood lymphocyte cytospins, 4 of 4 thymus tissues and 10 of 10 tonsil tissues). As with any immunohistochemical reagent, the sensitivity is dependent on tissue processing and slide preparation parameters. The negative control which was run with each tissue gave negative results.

Inter-run reproducibility was determined by using the same positive control (frozen tonsil) on each of 10 different instrument runs. All ten slides stained positively for CD8 antigen.

Intra-run reproducibility was determined based on ten same frozen tonsil tissue within one run. All ten slides stained positively for CD8 antigen.

'Reinherz EL, Hussey RE, Fitzgerald K, Snow P, Terhorst C and Schlossman SF: Antibody directed at a surface structure inhibits cytolytic but not suppressor function of human T lymphocytes. Nature 1981, 294:168-170,

"Deegan Michael J: Membrane antigen analysis in the diagnosis of lymphomas. Arch Pathol Lab Med 1989, 113:606-618.

Revised on December 10, 1996

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).