K Number
K941170
Date Cleared
1997-04-22

(1135 days)

Product Code
Regulation Number
866.5550
Panel
IM
Reference & Predicate Devices
N/A
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

Ventana Medical Systems' Anti-Human Melanosome(Clone HMB45) may be used to aid in the identification of abnormal cells of melanocytic lineage as an aid in diagnosis of anaplastic tumors.

Device Description

Ventana Medical Systems' Anti-Human Melanosome(Clone HMB45) contains a mouse monoclonal antibody directed against a 10kD neuraminidase sensitive sialylated glycoconjugate present in immature melanosomes.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and study information for the Ventana Medical Systems' Anti-Human Melanosome(Clone HMB45) device:

1. Table of Acceptance Criteria and Reported Device Performance

The original document does not explicitly state pre-defined acceptance criteria with numerical targets. Instead, it describes general desired performance characteristics (specificity, sensitivity, reproducibility) and then presents the results. Therefore, the "acceptance criteria" presented below are inferred from the desired characteristics mentioned and the "reported device performance" are the results provided.

Acceptance Criteria (Inferred)Reported Device Performance
Specificity: No staining of normal cells.Specific: No staining of normal cells (75 normal tissues). Confined to neoplastic melanocytic cells in adults, except for specific reactivities in "activated" melanocytes (junctional nevi, Spitz nevi, cellular blue nevi, junctional components of compound nevi) and very rarely in angiolipomas. Note: The document highlights limitations where HMB45 is not useful for distinguishing benign from malignant proliferation due to reactivity with junctional nevi, Spitz tumors, and atypical melanocytic hyperplasia.
Sensitivity: Consistent staining of melanoma tumors.Sensitive: Consistent staining of 19 out of 20 melanoma tumors. This agrees with external reports (Gowan and associates: 60 of 62 melanomas positive). Note: Sensitivity is stated to be dependent on tissue processing and slide preparation.
Negative Control Performance: Negative results.Negative Control: Negative results for negative controls run with each tissue.
Inter-run Reproducibility: Consistent positive staining and similar intensity across multiple runs.Inter-run Reproducibility: 16 out of 16 samples of the same tissue stained positively across 16 different instrument runs. All slides had similar staining intensity.
Intra-run Reproducibility: Consistent positive staining and equivalent intensity within a single run.Intra-run Reproducibility: 10 out of 10 samples of the same tissue stained positively within one run. All slides stained with equivalent staining intensity.
Appropriate Staining: Staining only in abnormal cells of melanocytic lineage, not inappropriate tissues.Appropriate Staining: Staining occurred in the cytoplasm of melanoma cells. No inappropriate staining of tissues in the study. Does not react with non-melanocytic tissues (epithelial, lymphoreticular, glial, mesenchymal origin), with rare exceptions like myoid component of RAML and angiomyolipoma. Note: The document mentions early evidence of unexpected reactivity in RAML and angiomyolipoma, which seem like potential "inappropriate" staining but are described as related antigen or regular expression.

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

  • Test Set Sample Size:
    • Specificity: 75 normal tissues, an unspecified number of "melanoma tumors" for the initial specificity check, and an unspecified number of "pathologic samples" in the comparative study.
    • Sensitivity: 20 melanoma tumors.
    • Reproducibility: 16 samples (for inter-run), 10 samples (for intra-run).
    • Total for overall comparative study: "Formalin fixed paraffin embedded preparations from normal and pathologic samples". The exact count is not provided for the full comparative study beyond the specific breakdowns for specificity, sensitivity, and reproducibility.
  • Data Provenance: 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 Their Qualifications

  • Number of Experts: One ("a qualified pathologist").
  • Qualifications: "a qualified pathologist". No further specific details (e.g., years of experience, subspecialty) are provided.

4. Adjudication Method for the Test Set

  • Adjudication Method: None explicitly stated as a multi-reader consensus process. The evaluation was performed by "a qualified pathologist." It appears to be a single-reader assessment.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

  • No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described. The study focused on the performance of the antibody in staining tissues, evaluated by a single pathologist. There is no mention of human readers improving with or without AI assistance, as AI is not a component of this device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

  • This question is not applicable. The device is an immunohistochemical reagent (an antibody), not an algorithm or AI system. Its performance is inherently "standalone" in the sense that it's the chemical's reaction, which is then interpreted by a human.

7. The Type of Ground Truth Used

  • Type of Ground Truth: Pathological diagnosis. The samples were "pathologic and normal tissues." The evaluation was done by a "qualified pathologist" who assessed "specific staining intensity and background staining." The inherent assumption is that the pre-existing diagnosis of "melanoma" or "normal tissue" served as the ground truth against which the antibody's staining was compared.

8. The Sample Size for the Training Set

  • This device is an antibody, not a machine learning model, so there is no "training set." The antibody was developed through a process involving immunization and hybridoma screening.
  • For the development of the antibody: The immunogen was "Melanoma metastases from axillary lymph node finely minced in phosphate buffered saline." Hybridomas were screened by immunocytochemistry on "Carnoy's fixed, paraffin-embedded sections of the same melanoma that was used as an immunogen." The exact number of screens/samples used in this development phase (analogous to a training set for an AI) is not specified.

9. How the Ground Truth for the Training Set Was Established

  • This question is not applicable in the context of an antibody's development as an AI training set.
  • For the development of the antibody: The "ground truth" during development was the ability of the antibody to react with the target antigen in melanoma cells, specifically the "oncofetal antigen present within immature melanosomes." This was confirmed by the screening process using the same melanoma tissue that served as the immunogen, indicating a direct confirmation of its binding to the intended target.

§ 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).