Predicate Devices

Not Found

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device is a reagent (antibody cocktail) used for immunohistochemistry and does not involve any computational analysis or image processing that would utilize AI/ML. The performance studies describe the biological reactivity of the reagent, not the performance of an algorithm.

Therapeutic

No

This device is designed for aiding in the identification of human cells of lymphoid origin through light microscopy, which is a diagnostic purpose, not a therapeutic one.

Diagnostic

Yes
The device is described as aiding in the identification of human cells of lymphoid origin in normal and pathologic tissues, which is a diagnostic purpose.

SaMD (Software as a Medical Device)

No

The device description clearly states the device is comprised of a mixture of two mouse monoclonal antibodies, which are biological/chemical components, not software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use is to "qualitatively aid in the identification by light microscopy of human cells of lymphoid origin... in normal and pathologic paraffin embedded tissues". This clearly indicates the device is used to examine specimens derived from the human body for the purpose of providing information for diagnosis.
Device Description: The device is a mixture of monoclonal antibodies designed to react with a specific antigen (LCA/CD45) present on human leukocytes. This is a typical component of an in vitro diagnostic assay.
Input Imaging Modality: Light microscopy is a common method for examining stained tissue samples in diagnostic pathology.
Anatomical Site: The device is used on human tissues.
Intended User / Care Setting: The device is intended for laboratory use and interpretation by a pathologist, which aligns with the typical use of IVDs in a clinical laboratory setting.
Performance Studies: The document describes reproducibility and immunoreactivity studies performed on human tissue specimens, which are standard types of performance evaluations for IVDs.
Key Metrics: While not all standard metrics are provided, sensitivity and information about specificity (through non-reactivity) are included, which are relevant to the performance of a diagnostic assay.

Based on the intended use, the nature of the device (antibodies for tissue staining), and the context of its use in a laboratory for aiding in identification of cells in human tissue, it fits the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

FOR IN VITRO DIAGNOSTIC USE.
ChemMate™ LCA (CD45; Clones PD7/26/16 and B11) is intended for laboratory use to qualitatively aid in the identification by light microscopy of human cells of lymphoid origin, by recognizing Leukocyte Common Antigen (LCA), in normal and pathological paraffin embedded tissues processed in interpreted by a pathologist within the context of clinical data, gross and microscopic morphological data and multiple chemical and immunohistochemical stains.

For the LCA primary antibodyreagent:
To qualitatively aid in the identification by light microscopy of human cells of lymphoid orgin, by recognizing Leukocyte Common Antigen (LCA) in normal and pathologic paraffin embedded tissues processed in neutral buffered formalin, B5, or Bouin's fixative.

For the Ancillary Reagents:
To aid in the performance of immunohistochemical tests

Product codes (comma separated list FDA assigned to the subject device)

DEH

Device Description

The ChemMate™ LCA (CD45) is comprised of a mixture of two mouse monoclonal antibodies, clones PD7/26/16 and 2B11; each is of the IgG1 class of immunoglobulins. Each clone reacts with a different epitope of a family of membrane glycoproteins present on most human leukocytes known as the leukocyte common antigen (LCA). Tissues analyzed were either frozen or were embedded in paraffin and fixed with one of the following fixatives: formol saline, neutral buffered formalin, zinc sulfate [1%] formalin, B5, Bouin's, or acetic acid [2%] formol saline. The LCA family consists of five to eight glycoproteins (molecular weight 180 to 220 kD). The clone PD7/26/16, included in the Fourth International Workshop on Human Leukocyte Differentiation Antigens (Vienna, 1989), was confirmed to react with an epitope expressed on three of the glycoproteins in the LCA family (MW 190, 205, and 220 kD) and has been designated as CD45RB. The clone 2B11, included in the Third International Workshop on Human Leukocyte Differentiation Antigens (Oxford, 1986), was confirmed to react with epitopes on four of the LCA glycoproteins (MW 180, 190, 205, and 220 kD).

Additionally, the prediluted ChemMate™ LCA (CD45) antibody as well as Peroxdase/DAB kits have been optimized for use with the TechMate™ for automated immunohistochemical staining.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Light microscopy

Anatomical Site

Human cells of lymphoid origin, in normal and pathological paraffin embedded tissues.

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Laboratory use. Diagnoses are to be interpreted by a pathologist.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Performance Characteristics:
Reproducibility: ChemMate™ LCA (CD45), and Negative Control Reagent have been tested on serial sections of 271 tissue specimens (both normal and tumor specimens were included in the study; see Tables IB and V). Runs were performed a total of three times, with each run being performed on a different day. Consistent staining results were obtained.

Immunoreactivity: The following immunoreactivities have been demonstrated in paraffin-embedded tissues. The secondary staining systems were either ABC peroxidase or Indirect secondary antibody labeled peroxidase. The lists provided below (see Tables IA, II - IV) are not exhaustive but characterize the types of immunoreactivity reported in the literature for clones contained in the monoclonal antibody cocktail of ChemMate™ LCA (CD45). Tables IIB and V are summaries of the immunoreactivity studies performed by BioTek Solutions using ChemMate™ LCA (CD45) and the ChemMate™ Secondary Detection -Peroxidase/DAB Kit.

TABLE IA Note: A total of 45 tissues were fixed in either 10% neutral buffered formalin, B5, or Zenker's acetic acid solution. Three specimens were fixed in multiple fixatives (B5, Zenker's, formalin, and Bouin's). Tissues were embedded in paraffin, and the secondary staining systems were either ABC peroxidase or Indirect secondary antibody labeled peroxidase. The tissues evaluated included: bone marrow [6], dermatopathic lymphadenitis [4], lymph nodes (nonspecific reactive hyperplasia) [10], normal skin [2], prostate (severe chronic prostatitis) [1], salivary gland (benign lymphoepithelial lesion) [1], spleen (hyperplastic changes) [5], sarcoidosis [5], thymus [3], talc granuloma [1], toxoplasmic lymphadenitis [4], thyroid (Hashimoto's thyroiditis) [3].

Table IB Note: In studies performed by BioTek Solutions, a total of 126 normal tissues were fixed in 10% neutral buffered formalin, embedded in paraffin, immunostained with ChemMate™LCA-CD45 and the ChemMate™ Secondary Detection - Peroxidase/DAB Kit. All tissues were stained using the TechMate™ Automated Staining System. The tissues evaluated included: adrenal [3], brain [7], breast [50], heart [3], kidney [5], large intestine [2], liver [5], lung [5], ovary [5], pancreas [5], prostate [5], skin [2], small intestine [2], spleen [3], squamous epithelial [2], stomach [1], striated muscle [2], testis [5], thyroid [6], tonsil [3], uterus [5].

Table II Note: A total of 80 specimens were fixed in either formalin (25 specimens), B5 (48 specimens), or Zenker's solution (2). Five specimens were fixed in multiple fixatives (B5, formalin, Zenker's, and Bouin's). The specimens were embedded in paraffin, and the secondary staining systems were either ABC peroxidase or indirect secondary antibody labeled peroxidase.

Table III Note: A total of 51 specimens were fixed in either formalin (2 spleens, 1 lymph node, and 1 skin specimen), B5 (9 spleens, 5 lymph nodes, and 1 soft tissue mass), or Zenker's acetic acid solution (32 bone marrow specimens). The specimens were embedded in paraffin, and the secondary staining systems were either ABC peroxidase or indirect secondary antibody labeled peroxidase.

Table IV Note: A total of 162 tissues were fixed in either formol saline, neutral buffered formalin, 10% neutral buffered formalin. B5. Zenker's acetic acid solution, acetic acid (2%) formol saline, or Bouin's. Six specimens were fixed in multiple fixatives (B5, Zenker's, formalin, and Bouin's). Tissues were embedded in paraffin, and the secondary staining systems were either ABC peroxidase or indirect secondary antibody labeled peroxidase.

Table V Note: In studies performed by BioTek Solutions, a total of 145 pathological tissues were fixed in 10% neutral buffered formalin, embedded in paraffin, immunostained with ChemMate™ LCA-CD45 and the ChemMate™ Secondary Detection - Peroxidase/DAB Kit. All tissues were stained using the TechMate™ Automated Staining System. The tissues evaluated included: breast carcinoma [65], lymphoma [45], carcinoid [4], colonic carcinoma [3], gastric carcinoma [2], hepatocellular carcinoma [3], lung carcinoma [2], ovarian carcinoma [1], prostatic carcinoma [6], thyroid carcinoma [1], endodermal sinus carcinoma [1], melanoma [6], placental tumor [1], sarcoma, Ewing's [1], sarcoma, fibro [1], seminoma [2], teratoma [1].

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Performance Characteristics:
Reproducibility: ChemMate™ LCA (CD45), and Negative Control Reagent have been tested on serial sections of 271 tissue specimens (both normal and tumor specimens were included in the study; see Tables IB and V). Runs were performed a total of three times, with each run being performed on a different day. Consistent staining results were obtained.

Immunoreactivity:
Tables IA, II, III, IV, and V summarize the immunoreactivity results for various normal and pathological tissues.

For B-CELL Lymphoplasmacytic Follicular center cell:
-small cleaved: 4/4 reactive (100%), 95% Confidence Interval: 39.8-100%
-large cleaved: 15/15 reactive (100%), 95% Confidence Interval: 78.2-100%
-mixed small and large: 4/6 reactive (66.7%), 95% Confidence Interval: 22-95%
-small non-cleaved: 5/5 reactive (100%), 95% Confidence Interval: 48-100%
-large non-cleaved: 5/5 reactive (100%), 95% Confidence Interval: 48-100%
Immunoblastic sarcoma: 11/12 reactive (91.7%), 95% Confidence Interval: 62.5-99.7%

For T-CELL:
Mycosis fungoides: 1/1 reactive (100%)
Immunoblastic sarcoma: 10/11 reactive (90.9%), 95% Confidence Interval: 58-99.5%
Lymphoblastic: 2/4 reactive (50%), 95% Confidence Interval: 9.0-91%
Unclassified: 3/3 reactive (100%), 95% Confidence Interval: 29.2-100%

Other Hematopoietic Neoplasms - Reactive:
Chronic Lymphocytic Leukemia - B-cell Type: lymphoid cells: 3/3 (100%), 95% CI: 29.2-100%
Chronic Lymphocytic Leukemia - T-cell Type: lymphoid cells: 3/3 (100%), 95% CI: 29.2-100%
Acute Lymphoblastic Leukemia - lymphoblasts: 3/8 (37.5%), 95% CI: 8.5-75.5%
Prolymphocytic (B-cell) Leukemia - prolymphocytes: 1/1 (100%)
Hairy Cell Leukemia - Hairy Cells: 5/5 (100%), 95% CI: 48-100%
Monocytic Leukemia - monoblasts: 1/1 (100%)
Multiple Myeloma - plasma cells: 10/10 (100%), 95% CI: 68.5-100%
Systemic Mast Cell Disease - mast cells: 3/3 (100%), 95% CI: 29.2-100%

Other Hematopoietic Neoplasms - Nonreactive (100% nonreactive):
Acute Myelogenous Leukemia - myeloid cells (sample size 7)
Chronic Myelogenous Leukemia - myeloblasts (sample size 2)
Erythroleukemia - erythroblasts (sample size 2)
Polycythemia Vera - erythroid cells (sample size 2)
Extramedullary Hematopoiesis - myeloid cells (sample size 3)
Extramedullary Hematopoiesis - megakaryocytes (sample size 3)
Plasma Cell Leukemia - plasma cells (sample size 1)

Nonreactive Non-Lymphoid Pathological Tissues (100% nonreactive):
Squamous cell carcinoma (sample size 4)
Nasopharyngeal squamous cell carcinoma (sample size 1)
Adenocarcinoma (sample size 54)
Ovarian serous cystadenocarcinoma (sample size 1)
Transitional cell carcinoma (sample size 2)
Bladder-invasive transitional cell carcinoma (sample size 1)
Metastatic carcinoma (sample size 5)
Basal-cell carcinoma (sample size 1)
Breast-infiltrating lobular carcinoma (sample size 2)
Small cell anaplastic lung carcinoma (sample size 10)
Breast-infiltrating ductal carcinoma (sample size 2)
Pulmonary large-cell undiff. carcinoma (sample size 1)
Pulmonary small-cell undiff. carcinoma (sample size 2)
Nasopharyngeal undiff. carcinoma (sample size 7)
Laryngeal undiff. carcinoma (sample size 1)
Medullary carcinoma, thyroid (sample size 1)
Thymoma (epithelial) (sample size 4)
Amelanocytic malignant melanoma (sample size 5)
Malignant melanoma (sample size 3)
Alveolar rhabdomyosarcoma (sample size 3)
Ewing's sarcoma (sample size 9)
Neuroblastoma (sample size 2)
Soft-tissue fibrosarcoma (sample size 1)
Soft-tissue malignant fibrous histiocytoma (sample size 4)
Eosinophilic granuloma (sample size 1)
Granular cell tumor (sample size 1)
Adrenal Pheochromocytoma (sample size 2)
Adrenal neuroblastoma (sample size 3)
Glioblastoma (sample size 1)
Neurofibroma/neuroma (sample size 6)
Oligodendroglioma (sample size 1)
Cerebellar astrocytoma (sample size 1)
Meningioma (sample size 1)
Chordoma (sample size 1)
Skeletal giant cell tumor (sample size 1)
Carcinoid, lung (sample size 1)
Ileal carcinoid tumor (sample size 2)
Colonic carcinoid carcinoma (sample size 1)
Wilm's tumor (sample size 1)
Germ cell tumor (sample size 7)
Meduloblastoma (sample size 1)
Ependymoma (sample size 1)
Testicular embryonal carcinoma (sample size 1)
Testicular spermatocytic seminoma (sample size 1)
Testicular seminoma (sample size 1)

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

Not Found

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

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).

Summary

0

14343

SEP 2 5 1997

510(k) SUMMARY

September 22, 1997 Date:

VENTANA MEDICAL SYSTEMS, INC. 3865 North Business Center Drive Tucson, Arizona 85705

Telephone: (520) 887-2155 (520) 887-2558 Facsimile:

Stephen A. Tillson, Ph.D. Contact: Vice President Scientific Affairs/ Quality Assurance
Registration # : 2028492

ChemMate™ LCA (CD45) Trade Name:

Class II

FOR IN VITRO DIAGNOSTIC USE. Intended Use:

ChemMate™ LCA (CD45; Clones PD7/26/16 and B11) is intended for laboratory use to qualitatively aid in the identification by light microscopy of human cells of lymphoid origin, by recognizing Leukocyte Common Antigen (LCA), in normal and pathological paraffin embedded tissues processed in interpreted by a pathologist within the context of clinical data, gross and microscopic morphological data and multiple chemical and immunohistochemical stains.

This mouse monoclonal antibody has been optimally prediluted for use with the ChemMate™ SDK605 and SDK305 Secondary Detection -Peroxidase/DAB kits. Additionally, the prediluted ChemMate™ LCA (CD45) antibody as well as Peroxdase/DAB kits have been optimized for use with the TechMate™ for automated immunohistochemical staining.

1

510K SUMMARY OF SAFETY AND EFFECTIVENESS

SUMMARY AND EXPLANATION

The ChemMate™ LCA (CD45) is comprised of a mixture of two mouse monoclonal antibodies, clones PD7/26/16 and 2B11; each is of the IgG1 class of immunoglobulins.1 Please refer to Warnke, et. al.1 for a description of the cultivation, characterization and selection of these two clones. Each clone reacts with a different epitope of a family of membrane glycoproteins present on most human leukocytes known as the leukocyte common antigen (LCA). Tissues analyzed were either frozen or were embedded in paraffin and fixed with one of the following fixatives: formol saline, neutral buffered formalin, zinc sulfate [1%] formalin, B5, Bouin's, or acetic acid [2%] formol saline. 13 The LCA family consists of five to eight glycoproteins (molecular weight 180 to 220 kD)4-6.19 The clone PD7/26/16, included in the Fourth International Workshop on Human Leukocyte Differentiation Antigens (Vienna, 1989), was confirmed to react with an epitope expressed on three of the glycoproteins in the LCA family (MW 190, 205, and 220 kD) and has been designated as CD45RB.8 The clone 2B11, included in the Third International Workshop on Human Leukocyte Differentiation Antigens (Oxford, 1986), was confirmed to react with epitopes on four of the LCA glycoproteins (MW 180, 190, 205, and 220 kD).4 For additional information of the CD45 isoforms, see Knapp, et al.6

A unique feature of the ChemMate™ LCA (CD45) is it's ability to recognize epitopes on lymphocytes that survive the rigors of processing and fixation. The resultant advantage in the use of this antibody is its applicability with formalin-fixed specimens.1 Excessive exposure of tissue to formalin beyond what is required for adequate fixation will result in increased cross linking and loss of many reactive epitopes. For example, in fresh (frozen) tissue, cross linking is eliminated hence antigenic reactivity is well preserved. It is in such frozen specimens that reactivity with the clones PD7/26/16 and 2B11 is not only demonstrated among lymphoid cell populations but may also be rarely demonstrated in some myeloid populations.3

In paraffin-embedded, fixed specimens, the strongest labeling is seen on lymphoid cells, where it is most intense on the cell surface and less marked within the cytoplasm. Weaker membranous and/ or cytoplasmic staining is seen on macrophages and histiocytes, while other myeloid cells variably demonstrate even weaker staining or are frequently unreactive.17 ChemMate™ LCA (CD45) may be of value in assisting in the recognition of certain neoplasms, since neoplastic cells may, in a proportion of cases, fail to display the usual morphologic features of normal leukocytes in H & E sections, or may display atypical morphologic features. 810 Studies have also demonstrated LCA reactivity in many lymphomas and other hematopoietic neoplasms of Ivmphoid

2

type while neoplasms of epithelial, mesenchymal, or neural derivation remain unreactive. 137,11 The antibody is reactive with most, but not all neoplastic B and T cells in non-Hodgkin's lymphomas and leukemias of B and T cell type, malignant lymphoma of the thyroid, and hairy cells. 72-16 In a study of non-Hodgkin's lymphomas that compared genotypic analysis with immunophenotyping in paraffin-embedded tissue sections (fixed in B5 or 10% buffered formalin), LCA was positive in 42 of 44 cases (95%).24 Rare Reed-Sternberg cells and their variants have been reported to reveal membrane staining for LCA. although most Reed-Sternberg cells appeared negative or indeterminant due to the presence of adjacent strongly LCA positive reactive Ivmphoid cells. Among neoplastic diseases of non-lymphocvtic leukocvtic origin. (monocytic, myeloid and histiocytic neoplasms) staining is less frequent. less sensitive and more variable involving both a membranous and cytoplasmic pattern. A summary of immunoreactivity found in paraffinembedded cells/tissues and neoplasms (from references 1 and 7) may be found in Tables I-V of Performance Characteristics in this insert.

The antibody has been nonreactive with most carcinomas and tissues of epithelial, mesenchymal, and neural origin, as well as malignant melanomas, rhabdomyosarcomas and Ewing's sarcoma 17. These observations are also borne out in the immunoreactivity profiles of Table IV and V in this insert. It should however be noted that the interpretation of any positive LCA staining or its absence should be complemented by morphological studies and proper controls and should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified individual.

Product Specific Limitations:

1. In poorly fixed tissue specimens, nonspecific staining of non-lymphoid tissues may be observed. particularly epithelium and smooth muscle.
1. Association between lymphocytes and secretory ductal epithelium in the production of immunoglobulin is well known. LCA staining may be exhibited in the epithelium of both fibroadenoma and fibrocystic disease of the breast.20 Although LCA reactivity has not been extensively studied in maliqnancies of the breast such as secretory carcinoma, signet ring cell lobular or ductal carcinoma, or for cystosarcoma phylloides, it is possible that LCA staining may also occur in some of these conditions. LCA reactions in breast tissues should not present differential difficulties in that histologic patterns in normal and abnormal breast tissues should be recognizable. Additionally, LCA is generally employed in a panel typically including cytokeratins and other markers (e.g., vimentin, S100).
1. It has been reported that the sensitivity of clones PD7/26/16 and 2B11 is 90- . 93% for non-Hodgkin's lymphomas. False negative results have been seen

3

in acute lymphoblastic leukemia.722,24 It is recommended that a panel of antibodies be used to rule out lymphoid tumors.23

1. Among neoplastic diseases of non-lymphocytic leukocytic origin, (monocytic, myeloid and histiocytic neoplasms) staining is less frequent, less sensitive and more variable involving both a membranous and cytoplasmic pattern.
1. LCA positive lymphocytes closely apposed to carcinoma cells give the appearance of membrane reactivity to the latter cells'.
1. To avoid false positive interpretations, cytoplasmic staining unaccompanied bv membrane staining should not be considered a positive result.

Performance Characteristics:

Reproducibility: ChemMate™ LCA (CD45), and Negative Control Reagent have been tested on serial sections of 271 tissue specimens (both normal and tumor specimens were included in the study; see Tables IB and V). Runs were performed a total of three times, with each run being performed on a different day. Consistent staining results were obtained.

Immunoreactivity: The following immunoreactivities have been demonstrated in paraffin-embedded tissues. The secondary staining systems were either ABC peroxidase or Indirect secondary antibody labeled peroxidase. The lists provided below (see Tables IA, II - IV) are not exhaustive but characterize the types of immunoreactivity reported in the literature for clones contained in the monoclonal antibody cocktail of ChemMate™ LCA (CD45). Tables IIB and V are summaries of the immunoreactivity studies performed by BioTek Solutions using ChemMate™ LCA (CD45) and the ChemMate™ Secondary Detection -Peroxidase/DAB Kit.

4

TABLE IA TABLE TA

REACTIVE AND NONREACTIVE NORMAL TISSUES/CELLS*,7,17,18,21

| REACTIVE CELLS | VARIABLY REACTIVE
CELLS | NONREACTIVE
CELLS |
|--------------------------------------|-------------------------------------------------------------|--------------------------------------------------------------------------------|
| Follicular center
lymphoid cells | Interfollicular transformed
lymphoid cells immunoblasts) | Polymorphonuclear leukocytes,
rare myeloid precursors with
weak staining |
| Follicular mantle zones | Epithelioid histiocytes | Erythroid cells |
| Interfollicular small
lymphocytes | Sinus histiocytes | Megakaryocytes |
| Perisinusoidal cells | Plasma cells | Tingible body macrophages with
occasional small cytoplasmic
granules |
| Splenic white pulp | Monocytes
Macrophages | Interdigitating reticulum cells
with rare, weak membrane
• staining |
| Splenic red pulp
lymphoid cells | | Splenic macrophages and sinus
lining cells |
| Thymic lymphocytes | | Thymic epithelial cells |
| Mast cells | | Epithelium |
| Osteoclast | | Langerhans' cells, skin
Connective tissue |

Table IA Note: A total of 45 tissues were fixed in either 10% neutral buffered formalin, B5, or Zenker's acetic acid solution. Three specimens were fixed in multiple fixatives (B5, Zenker's, formalin, and Bouin's). Tissues were embedded in paraffin, and the secondary staining systems were either ABC peroxidase or Indirect secondary antibody labeled peroxidase. The tissues evaluated included:

bone marrow [6]	dermatopathic lymphadenitis [4]
lymph nodes (nonspecific reactive hyperplasia) [10]	normal skin [2]
prostate (severe chronic prostatitis) [1]
salivary gland (benign lymphoepithelial lesion) [1]	spleen (hyperplastic changes) [5]
sarcoidosis [5]	thymus [3]
talc granuloma [1]	toxoplasmic lymphadenitis [4]
thyroid (Hashimoto's thyroiditis) [3]

5

TABLE IB REACTIVE AND NONREACTIVE NORMAL TISSUES/CELLS

REACTIVE	VARIABLY REACTIVE	NONREACTIVE
CELLS	CELLS	CELLS
lymphocytes		adrenal glandular epithelium
		breast epithelium & stroma
		neurons
		glia
		squamous epithelium
		heart muscle
		colonic epithelium
		small intestinal epithelium
		renal epithelium
		hepatocytes / liver bile ducts
		alveolar epithelium
		striated muscle
		ovarian stroma & epithelium
		pancreatic epithelium
		prostate epithelium
		gastric epithelium
		testicular & interstitial epithelium
		thyroid epithelium
		uterine epithelium, muscle & stroma

Table IB Note: In studies performed by BioTek Solutions, a total of 126 normal tissues were fixed in 10% neutral buffered formalin, embedded in paraffin, immunostained with ChemMate™LCA-CD45 and the ChemMate™ Secondary Detection - Peroxidase/DAB Kit. All tissues were stained using the TechMate™ Automated Staining System. The tissues evaluated included:

adrenal [3]	skin [2]
brain [7]	small intestine [2]
breast [50]	spleen [3]
heart [3]	squamous epithelial [2]
kidney [5]	stomach [1]
large intestine [2]	striated muscle [2]
liver [5]	testis [5]
lung [5]	thyroid [6]
ovary [5]	tonsil [3]
pancreas [5]	uterus [5]
prostate[5]

6

| | NO. REACTIVE/
NO. TESTED | % | 95% CONFIDENCE
INTERVAL |
|---------------------------------------------|-----------------------------|-------|----------------------------|
| A. TISSUE: B-CELL | | | |
| Lymphoplasmacytic
Follicular center cell | 4/4 | 100% | 39.8-100% |
| -small cleaved | 15/15 | 100% | 78.2-100% |
| -large cleaved | 4/6 | 66.7% | 22-95% |
| -mixed small and large | 5/5 | 100% | 48-100% |
| -small non-cleaved | 5/5 | 100% | 48-100% |
| -large non-cleaved | 11/12 | 91.7% | 62.5-99.7% |
| Immunoblastic sarcoma | 14/14 | 100% | 76.8-100% |
| B. TISSUE: T-CELL | | | |
| Mycosis fungoides | 1/1 | 100% | -- |
| Immunoblastic sarcoma | 10/11 | 90.9% | 58-99.5% |
| lymphoblastic | 2/4 | 50% | 9.0-91% |
| Unclassified | 3/3 | 100% | 29.2-100% |

TABLE II REACTIVE B- AND T- CELL NON-HODGKIN'S LYMPHOMA'

Table II Note: Confidence intervals were not calculated for those cases with a sample size of one. The reactivity however was included for anecdotal reference information.

A total of 80 specimens were fixed in either formalin (25 specimens), B5 (48 specimens), or Zenker's solution (2). Five specimens were fixed in multiple fixatives (B5, formalin, Zenker's, and Bouin's). The specimens were embedded in paraffin, and the secondary staining systems were either ABC peroxidase or indirect secondary antibody labeled peroxidase.

7

TABLE III OTHER HEMATOPOIETIC NEOPLASMS '

| TISSUE /RELEVANT CELL TYPE | NO. REACTIVE/
NO. TESTED | % | 95% CONFIDENCE
INTERVAL |
|----------------------------------------------|--------------------------------|-------|----------------------------|
| Chronic Lymphocytic Leukemia | | | |
| -B-cell Type: lymphoid cells | 3/3 | 100% | 29.2-100% |
| -T-cell Type: lymphoid cells | 3/3 | 100% | 29.2-100% |
| Acute Lymphoblastic Leukemia: | | | |
| -lymphoblasts | 3/8 | 37.5% | 8.5-75.5% |
| Prolymphocytic (B-cell) Leukemia: | | | |
| -prolymphocytes | 1/1 | 100% | -- |
| Hairy Cell Leukemia: | | | |
| -Hairy Cells | 5/5 | 100% | 48-100% |
| Acute Myelogenous Leukemia: | | | |
| - myeloid cells | 0/7 | 0% | 0-41% |
| Chronic Myelogenous Leukemia: | | | |
| - myeloblasts | 0/2 | 0% | 0-84.7% |
| Erythroleukemia: | | | |
| -erythroblasts | 0/2 | 0% | 0-84.7% |
| Monocytic Leukemia: | | | |
| -monoblasts | 1/1 | 100% | -- |
| Polycythemia Vera: | | | |
| -erythroid cells | 0/2 | 0% | 0-84.7% |
| Extramedullary Hematopoiesis: | | | |
| -myeloid cells | 0/3 | 0% | 0-70.8% |
| -megakaryocytes | 0/3 | 0% | 0-70.8% |
| Multiple Myeloma: | | | |
| -plasma cells | 10/10 | 100% | 68.5-100% |
| Plasma Cell Leukemia: | | | |
| -plasma cells | 0/1 | 0% | -- |
| Systemic Mast Cell Disease: | | | |
| -mast cells | 3/3 | 100% | 29.2-100% |
| TISSUE | NO. NONREACTIVE/
NO. TESTED | % | 95% CONFIDENCE
INTERVAL |
| Squamous cell carcinoma | 4/4 | 100% | 39.8-100% |
| Nasopharyngeal squamous cell carcinoma | 1/1 | 100% | -- |
| Adenocarcinoma | 54/54 | 100% | 93-100% |
| Ovarian serous cystadenocarcinoma | 1/1 | 100% | -- |
| Transitional cell carcinoma | 2/2 | 100% | 15.8-100% |
| Bladder-invasive transitional cell carcinoma | 1/1 | 100% | -- |
| Metastatic carcinoma | 5/5 | 100% | 48-100% |
| Basal-cell carcinoma | 1/1 | 100% | -- |
| Breast-infiltrating lobular carcinoma | 2/2 | 100% | 15.8-100% |
| Small cell anaplastic lung carcinoma | 10/10 | 100% | 68.5-100% |
| Breast-infiltrating ductal carcinoma | 2/2 | 100% | 15.8-100% |
| Pulmonary large-cell undiff. carcinoma | 1/1 | 100% | -- |
| Pulmonary small-cell undiff. carcinoma | 2/2 | 100% | 15.8-100% |
| Nasopharyngeal undiff. carcinoma | 7/7 | 100% | 59-100% |
| Laryngeal undiff. carcinoma | 1/1 | 100% | -- |
| Medullary carcinoma, thyroid | 1/1 | 100% | -- |
| Thymoma (epithelial) | 4/4 | 100% | 39.8-100% |
| Amelanocytic malignant melanoma | 5/5 | 100% | 48-100% |
| Malignant melanoma | 3/3 | 100% | 29.2-100% |
| Alveolar rhabdomyosarcoma | 3/3 | 100% | 29.2-100% |
| Ewing's sarcoma | 9/9 | 100% | 66-100% |
| Neuroblastoma | 2/2 | 100% | 15.8-100% |
| Soft-tissue fibrosarcoma | 1/1 | 100% | -- |
| Soft-tissue malignant fibrous histiocytoma | 4/4 | 100% | 39.8-100% |
| Eosinophilic granuloma | 1/1 | 100% | -- |
| Granular cell tumor | 1/1 | 100% | -- |
| Adrenal Pheochromocytoma | 2/2 | 100% | 15.8-100% |
| Adrenal neuroblastoma | 3/3 | 100% | 29.2-100% |
| Glioblastoma | 1/1 | 100% | -- |
| Neurofibroma/neuroma | 6/6 | 100% | 54.1-100% |
| Oligodendroglioma | 1/1 | 100% | -- |
| Cerebellar astrocytoma | 1/1 | 100% | -- |
| Meningioma | 1/1 | 100% | -- |
| Chordoma | 1/1 | 100% | -- |
| Skeletal giant cell tumor | 1/1 | 100% | -- |
| Carcinoid, lung | 1/1 | 100% | -- |
| Ileal carcinoid tumor | 2/2 | 100% | 15.8-100% |
| Colonic carcinoid carcinoma | 1/1 | 100% | -- |
| Wilm's tumor | 1/1 | 100% | -- |
| Germ cell tumor | 7/7 | 100% | 59-100% |
| Meduloblastoma | 1/1 | 100% | -- |
| Ependymoma | 1/1 | 100% | -- |
| Testicular embryonal carcinoma | 1/1 | 100% | -- |
| Testicular spermatocytic seminoma | 1/1 | 100% | -- |
| Testicular seminoma | 1/1 | 100% | -- |

Table III Note: Confidence intervals were not calculated for those cases with a sample size of one. The reactivity however was included for anecdotal reference information.

A total of 51 specimens were fixed in either formalin (2 spleens, 1 lymph node, and 1 skin specimen), B5 (9 spleens, 5 lymph nodes, and 1 soft tissue mass), or Zenker's acetic acid solution (32 bone marrow specimens). The specimens were embedded in paraffin, and the secondary staining systems were either ABC peroxidase or indirect secondary antibody labeled peroxidase.

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TABLE IV TABEE TV

NONREACTIVE NON-LYMPHOID PATHOLOGICAL TISSUES 17

Table IV Note: Confidence intervals were not calculated for those cases with a sample size of one. The reactivity however was included for anecdotal reference information.

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A total of 162 tissues were fixed in either formol saline, neutral buffered formalin, 10% neutral buffered formalin. B5. Zenker's acetic acid solution, acetic acid (2%) formol saline, or Bouin's. Six specimens were fixed in multiple fixatives (B5, Zenker's, formalin, and Bouin's). Tissues were embedded in paraffin, and the secondary staining systems were either ABC peroxidase or indirect secondary antibody labeled peroxidase.

TABLE V REACTIVE AND NONREACTIVE PATHOLOGICAL TISSUES/CELLS

REACTIVE	VARIABLY REACTIVE	NONREACTIVE
CELLS	CELLS	CELLS
lymphoma cells		breast epithelium & stroma
		carcinoid epithelium
		colonic carcinoma
		gastric carcinoma
		hepatocellular carcinoma
		lung carcinoma
		ovarian carcinoma
		prostatic carcinoma
		thyroid carcinoma
		endodermal sinus carcinoma
		melanocytes
		placental trophoblasts
		Ewing's sarcoma
		fibrosarcoma
		seminoma seminiferous epithelium
		teratoma epithelia & mesenchyme

Table V Note: In studies performed by BioTek Solutions, a total of 145 pathological tissues were fixed in 10% neutral buffered formalin, embedded in paraffin, immunostained with ChemMate™ LCA-CD45 and the ChemMate™ Secondary Detection - Peroxidase/DAB Kit. All tissues were stained using the TechMate™ Automated Staining System. The tissues evaluated included:

breast carcinoma [65] lymphoma [45] carcinoid [4] colonic carcinoma [3] gastric carcinoma [2] hepatocellular carcinoma [3] lung carcinoma [2] ovarian carcinoma [1] prostatic carcinoma [6]

ﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬﻬ

thyroid carcinoma [1] endodermal sinus carcinoma [1] melanoma [6] placental tumor [1] sarcoma, Ewing's [1] sarcoma, fibro [1] seminoma [2] teratoma [1]

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References:

1. Warnke RA, et al. Diagnosis of human lymphoma with monoclonal antileukocyte antibodies. N Enq J Med 1983; 309:1275
1. Pulido R, et al. Comparative biochemical and tissue distribution study of four distinct CD45 antigen specificities. J Immun 1988; 140:3851
1. Warnke RA, Rouse RV. Limitations encountered in the application of tissue section immunodiagnosis to the study of lymphomas and related disorders. Human Path 1985; 16:326
1. Cobbold S, et al. Non-lineage, LFA-1 family and leuycocyte common antigens: new and previously defined clusters. In: McMichael AJ, et al., Eds. Leukocyte Typing III. White cell differentiation antigens. Oxford University Press, New York; 1987; 788
1. Knapp W, et al., eds. Leukocyte Typing IV. White cell differentiation antigens. Oxford University Press., 1989
1. Streuli M, Morimoto C, Schrieber M, Schlossman SF, and Saito H. Characterization of CD45 and CD45R monoclonal antibodies using transfected mouse cell lines that express individual human leukocyte common antigens. J Immunology 1988; 141:3910-3914
1. Kurtin PJ, Pinkus GS. Leukocyte common antigen-a diagnosis discriminant between hematopoietic and nonhematopoietic neoplasms in paraffin sections using monoclonal antibodies. Human Path 1985;16:353
1. Taylor CR. Kledzik G. Immunohistologic techniques in surgical pathologya spectrum of "new" special stains. Hum Pathol 1981; 12:590
1. Rosai J. Borderline epithelial lesions of the breast. Am J Surg Pathol. 1991; 15:209-221
1. Van Ginneken AM. Van der Lei J. Understanding differential diagnostic disagreement in pathology. Proc Annu Symp Comput Appl Med Care. 1991: 99-103
1. Gatter KC, et al. The differential diagnosis of routinely processed anaplastic tumors using monoclonal antibodies. Am J Clin Path 1984;82-83
1. Meis JM. et al. A comparative marker study of large cell lymphoma. Hodqkin's disease, and true histiocytic lymphoma in paraffin-embedded tissue. Am J Clin Pathol 1986:86-591
1. Hall PA, et al. Paraffin section immunohistochemistry. I. Non-Hodgkin's Ivmphoma. Histopathology 1988:13:149
1. Faure P, et al. Diagnostic features of primary malignant lymphomas of the thyroid with monoclonal antibodies. Cancer 1988; 61:1852
1. Shvero J, et al. Anaplastic thyroid carcinoma.. A clinical, histologic, and immunohistochemical study. Cancer 1988; 62:319
1. Michie SA, et al. A panel approach to the evaluation of the sensitivity and specificity of antibodies for the diagnosis of routinely processed histologically undifferentiated human neoplasms. Am J Clin Pathol 1987: 88:457

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1. Hall PA, et al. Demonstration of lymphoid antigens in decalcified bone marrow trephines. J Clin Pathol 1987; 40:870
1. Athanasou NA. et al. Leucocyte common antigen is present on osteoclasts. J. Pathol 1987; 153:121
1. Kiernan JA. Histological and histochemical Methods: Theory and Practice. New York: Pergamon Press 1981
1. Herman. GE. Elfont E. Aberrant CD45 (Leukocyte Common Antigen) Staining of Non-Malignant Breast Lesions in Zinc Formalin Fixed Tissue. J Histotechnology 1993; 16(2):151
1. Athanasou NA, Puddle B, Quinn J, Woods CG. Use of Monoclonal Antibodies to Recognise Osteoclasts in Routinely Processed Bone Biopsy Specimens. J Clin Pathol 1991; 44:664
1. Wieczorek R. Buck D. Bindl. J and Knowles. DM. Monoclonal Antibody Leu-22 (L60) Permits the Demonstration of Some Neoplastic T Cells in Routinely Fixed and Paraffin-Embedded Tissue Sections. Hum Pathol 1988; 19:1434
1. Cartun, RW, Coles FB, and Pastuszak WT. Utilization of Monoclonal Antibody L26 in the Identification and Confirmation of B-Cell Lymphomas. Am J Pathol 1987; 129:415
1. Elghetany MT, Kurec AS, Schuehler K, Forbes BA, Duggan DB, and Davey FR. Immunophenotyping of Non-Hodgkin's Lymphomas in Paraffin-Embedded Tissue Sections. A Comparison with Genotypic Analysis. Am J Clin Pathol 1991; 95:517

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Image /page/12/Picture/2 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three swooping lines representing its body and wings. The eagle's head is facing left. Encircling the eagle is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Stephen A. Tillson, Ph.D. Vice President Scientific Affairs/Quality Assurance Ventana Medical Systems, Inc. 3865 North Business Center Drive Tucson, Arizona 85705

K973393 Re: Trade Name: ChemMate™ LCA (CD45) Regulatory Class: II Product Code: DEH Dated: June 27, 1997 Received: July 1, 1997

SEP 2 5 1997

Dear Dr. Tillson:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in requlatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. this response to your premarket notification Please note: submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

13

Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling requlation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page_1 of 1

510(k) Number (if known):K 973393

Device Namel LCA(leukocyte common antigen) ChemMate: includes ChemMate secondary detection kits peroxidase DAB SDK 605 & 305;ChemMate Negative Control reagent; ChemMate standard secondary buffer kit

Indications For Use:

For the LCA primary antibodyreagent:

To qualitatively aid in the identification by light microscopy of human cells of lymphoid orgin, by recognizing Leukocyte Common Antigen (LCA) in normal and pathologic paraffin embedded tissues processed in neutral buffered formalin, B5, or Bouin's fixative.

For the Ancillary Reagents:

To aid in the performance of immunohistochemical tests

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluat

Petur E. Massi

(Division Sign-Off) Division of Clinical Laborator 510(k) Number _

Prescription Use
(Per 21 CFR 801.109)

OR

Over-The-Counter. Use_

(Optional Format 1-2-96)

O