VENTANA ANTI-CD5 PRIMARY ANTIBODY by VENTANA MEDICAL SYSTEMS, INC.

The provided text describes a study for the Ventana Anti-CD5 (clone L17F12/Leu-1) for use on the Ventana ES automated immunohistochemistry system. However, it does not explicitly define acceptance criteria in a quantitative table format or state precise performance metrics as acceptance thresholds. Instead, the study aims to demonstrate substantial equivalence to previously reported antibodies by showing appropriate staining and reactivity consistent with established literature.

Here's an attempt to extract the information based on the provided text, with an acknowledgment of the missing explicit quantitative acceptance criteria:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Inferred from study goal)	Reported Device Performance
Appropriate staining of normal cells of lymphoid origin (e.g., tonsil, thymus, blood)	Demonstrated appropriate positive staining of lymphoid cells in normal tonsil, thymus, and blood.
Reactivity consistent with literature for T-cell lymphomas	Reactivity shown in 8 of 9 T-cell lymphomas.
Lack of reactivity (or minimal) in B-cell lymphomas	Reactivity shown in 0 of 11 B-cell lymphomas.
Lack of reactivity (or minimal) in Hodgkin's lymphomas	Reactivity shown in 0 of 11 Hodgkin's lymphomas.
Absence of "inappropriate staining" (e.g., non-lymphoid cells, non-specific background)	"There was no inappropriate staining of the specimens in this study."
Negative control antibody produced negative results	"The negative control antibody which was run with each tissue produced negative results."
Inter-run reproducibility (consistent positive staining of CD5 antigen)	All ten slides stained positively for CD5 antigen during ten different instrument runs.
Intra-run reproducibility (consistent positive staining of CD5 antigen)	All ten slides stained positively for CD5 antigen within one run.

2. Sample size used for the test set and the data provenance

Test Set Sample Sizes:
- Normal samples: Number not explicitly stated, but included tonsil, thymus, cytospins, and blood smears.
- Pathological samples: 9 T-cell lymphomas, 11 B-cell lymphomas, 11 Hodgkin's lymphomas.
- Reproducibility samples: 10 samples for inter-run, 10 samples for intra-run (all from the same frozen tonsil tissue).
Data Provenance:
- Country of Origin: Not specified.
- Retrospective or Prospective: "Samples were obtained from excess tissues and specimens obtained for reasons other than the present study." This indicates the data was retrospective.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Number of Experts: One ("evaluated by a qualified independent pathologist").
Qualifications of Experts: "A qualified independent pathologist." Specific years of experience or sub-specialty were not detailed, but 'qualified' implies appropriate expertise in pathology and immunohistochemistry interpretation.

4. Adjudication method for the test set

Adjudication Method: None. The evaluation was performed by a single pathologist.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done

No, an MRMC comparative effectiveness study was not explicitly described. The study compares the device's performance to literature reports and the negative control, not to human readers with and without AI assistance.

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

Yes, this was a standalone study of the device (antibody and automated stainer). The pathologist evaluated the slides produced by the automated system, effectively assessing the algorithm's (or system's) output.

7. The type of ground truth used

The ground truth was based on:
- Pathology/Clinical Diagnosis: For the lymphoma specimens (T-cell, B-cell, Hodgkin's).
- Tissue Type/Anatomical Location: For normal samples (tonsil, thymus, blood smears, cytospins).
- Literature Reports: The results were compared to established knowledge and published data by Engleman et. al. and Chan et. al. to confirm appropriate, expected staining patterns.

8. The sample size for the training set

The text does not mention a training set in the context of an algorithm. This device is an antibody and an automated staining system, not an AI/ML algorithm that requires a separate training set. The "Comparative Study" section describes the evaluation of the final product.

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

As no training set for an algorithm was described, this question is not applicable.

Summary

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K941782 SEP 10 1996

510(k) Summary of Safety and Effectiveness

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 the Ventana Anti-CD5 (clone L17F12/Leu-1) for use on the Ventana ES automated immunohistochemistry system. Ventana's Anti-CD5 (clone L17F12/Leu-1) is substantially equivalent to antibodies detecting cellular elements of lymphocytic origin as reported by E. G. Engleman et. al. and J. K. C. Chan et. al.2

Comparative Study

Supporting data for the equivalence statement is shown by the following study. Frozen tissue preparations from normal and pathologic samples as well as cytospins and blood smears from normal subjects were tested using the Ventana Anti-CD5 (clone L17F12/Leu-1). Samples were obtained from excess tissues and specimens obtained for reasons other than the present study. Pathologic tissues examined were lymphoma specimens. Normal specimens examined were tonsil, thymus, cytospins and blood smears. Slides were processed on the Ventana ES Automated Slide Stainer, prepared for examination and evaluated by a qualified independent pathologist for specific staining intensity and background staining. These results were compared to literature reports.

Results

L17F12/Leu-1 detects an antigen present on 95-100% of human peripheral T lymphocytes, the majority of thymocytes and acute lymphocytic leukemia T cells' and less than 5% of peripheral blood B lymphocytes, 54-87% of T cell lymphomas, most all B cell chronic lymphocytic leukemia and centrocytic (mantle cell) lymphomas2.3.

In Ventana's testing, the antibody showed appropriate staining of normal cells of lymphoid origin from normal tonsil, thymus and blood. For example, in tonsil a majority of lymphocytes in the interfollicular areas (T cell predominant) stain positive. Scattered cells in the mantle zone (B cell predominant), germinal centers (dendritic rich), subepithelial and perivascular regions also stain positively. Staining of cells of nonlymphoid origin was not undertaken nor reported. There was no inappropriate staining of the specimens in this study. In addition, this study agrees with the data published by Engleman, et.al.1 and Chan, et.al. 3

The reactivity of this antibody was shown by consistent staining of lymphoid cells in 8 of 9 T cell lymphomas, 0 of 11 B cell lymphomas and 0 of 11 Hodgkins lymphomas. As with any immunohistochemical reagent, the sensitivity is dependent on tissue processing and slide preparation parameters. The negative control antibody which was run with each tissue produced negative results.

Inter-run reproducibility was determined based on samples of the same frozen tonsil tissue on ten different instrument runs using Ventana DAB Detection Kit. All ten slides stained positively for CD5 antigen.

Intra-run reproducibility was determined based on ten samples of the same frozen tonsil tissue within one run. All ten slides stained positively for CD5 antigen.

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'Engleman EG, Warnke R, Fox RI, Dilley J, Benike CJ and Levy R: Studies of a human T lymphocyte antigen recognized by a monoclonal antibody. Proc Natl Acad Sci, USA 1981, 78:1791-1795.

3Chan JKC, Ng CS and Hui PK: A simple guide to the terminology and application of leucocyte monoclonal antibodies. Histopathology 1988, 12:461-480.

3Zukerberg LR, Medeiros LJL, Ferry JA, Harris NL. Diffuse low-grade B cell lymphomas. Four clinically distinct subtypes defined by a combination of morphologic and immunophenotypic features. Am J Clin Path 1993; 100:373-385.

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).