DAKOCYTOMATION ER/PR PHARMDX KIT

K042884 · Dakocytomation California, Inc. · MXZ · Feb 15, 2005 · Hematology

Device Facts

• Record ID: K042884
• Device Name: DAKOCYTOMATION ER/PR PHARMDX KIT
• Applicant: Dakocytomation California, Inc.
• Product Code: MXZ · Hematology
• Decision Date: Feb 15, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.1860
• Device Class: Class 2

Intended Use

The DakoCytomation ER/PR pharmDx™ assay is an immunohistochemical (IHC) kit system to identify human estrogen receptor (ER) and human progesterone receptor (PR) expression in breast cancer tissues routinely processed and paraffin-embedded for histological evaluation. ER/PR pharmDx specifically detects the ER alpha protein as well as the PR located in the cell nucleus of ER and/or PR-expressing cells. ER/PR pharmDx is indicated as an aid in identifying patients eligible for treatment with antihormonal or aromatase inhibitor therapies, as well as an aid in the prognosis and management of breast cancer. The DakoCytomation Monoclonal Mouse Anti-Human Progesterone Receptor, clone PgR 1294, is intended for laboratory use as a semi-quantitative detection of progesterone receptor by light microscopy in routinely processed normal and pathological human paraffinembedded tissue. This antibody is indicated for use as an aid in the management, prognosis and prediction of outcome of breast cancer. The clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual.

Device Story

IHC kit system identifies ER and PR expression in formalin-fixed, paraffin-embedded breast tissue; utilizes monoclonal mouse anti-human ER cocktail (clones 1D5/ER-2-123) and PR antibody (clone PgR 1294). Two-step staining procedure uses dextran-based reagent linked to secondary goat anti-mouse antibodies and horseradish peroxidase; enzymatic conversion of chromogen creates visible reaction product at antigen site. Performed manually or on Dako Autostainer in clinical laboratories by pathologists. Results interpreted via light microscopy using Allred scoring method (PS + IS > 2 = positive). Assists clinicians in determining patient eligibility for endocrine therapies and predicting disease-free/overall survival.

Clinical Evidence

Bench testing only. Performance characteristics evaluated include specificity, sensitivity, reproducibility, and concordance. Concordance testing between the DakoCytomation ER/PR pharmDx kit and the reference Allred method demonstrated 99% concordance.

Technological Characteristics

Immunohistochemical (IHC) kit system; utilizes monoclonal mouse anti-human antibodies (Clone PgR 1294). Detection via immunoenzymatic staining for light microscopy visualization. Optimized for manual and automated staining platforms. Semi-quantitative detection of nuclear protein expression.

Indications for Use

Indicated for patients with breast cancer to identify eligibility for antihormonal or aromatase inhibitor therapies and as an aid in prognosis and management. Used on routinely processed, paraffin-embedded tissue samples.

Regulatory Classification

Identification

Immunohistochemistry test systems (IHC's) are in vitro diagnostic devices consisting of polyclonal or monoclonal antibodies labeled with directions for use and performance claims, which may be packaged with ancillary reagents in kits. Their intended use is to identify, by immunological techniques, antigens in tissues or cytologic specimens. Similar devices intended for use with flow cytometry devices are not considered IHC's.

Special Controls

(2) Class II (special control, guidance document: “FDA Guidance for Submission of Immunohistochemistry Applications to the FDA,” Center for Devices and Radiologic Health, 1998). These IHC's are intended for the detection and/or measurement of certain target analytes in order to provide prognostic or predictive data that are not directly confirmed by routine histopathologic internal and external control specimens. These IHC's provide the pathologist with information that is ordinarily reported as independent diagnostic information to the ordering clinician, and the claims associated with these data are widely accepted and supported by valid scientific evidence. Examples of class II IHC's are those intended for semiquantitative measurement of an analyte, such as hormone receptors in breast cancer.

Predicate Devices

• Ventana ER, clone 6F11 (K984567)
• DakoCytomation ER, clone 1D5 (K993957)
• Dako Cytomation PR, clone PgR 636 (K020023)

Submission Summary (Full Text)

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# FEB 1 5 2005

### 510(k) Summary

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.

The assigned 510(k) number is: _______K042884

| Submitter: | DakoCytomation California, Inc.<br>6392 Via Real<br>Carpinteria, CA 93013<br>PH. 805.566.6655 FX. 805.566.0866<br>Establishment registration number: 2022180 |
|------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Tiffany D. Almeroth, RAC<br>Sr. Regulatory Affairs Specialist<br>PH. 805.566.3041 |
| Date Summary Prepared: | September 30, 2004 |
| Device Name(s): | DakoCytomation ER/PR pharmDx™ Kit.<br>Immunohistochemistry kit.<br>(Code K1903/K1904) |
| | DakoCytomation Monoclonal Mouse Anti-Human Progesterone<br>Receptor, clone PgR 1294.<br>Antibody for immunoenzymatic staining.<br>(Code M3568) |
| Device Classification: | Class II, for prognostic immunohistochemical staining reagents<br>21 CFR 864.1860 |
| Panel: | Hematology and Pathology Devices Panel<br>Division of Clinical Laboratory Devices. |
| Predicate Devices: | Estrogen Receptor<br>• DakoCytomation Monoclonal Mouse Anti-Human<br>Estrogen Receptor, Clone 1D5, (K993957)<br>• Ventana ER clone 6F11, (K984567)<br>Progesterone Receptor<br>• DakoCytomation Monoclonal Mouse Anti-Human<br>Progesterone Receptor, Clone PgR 636, (K020023) |

Device Description:

The DakoCytomation ER/PR pharmDx™ assay is a semi-quantitative immunohistochemical (IHC) kit system to identify estrogen receptor (ER) and progesterone receptor (PR) expression in normal and neoplastic tissues routinely processed and paraffin-embedded for histological expressing cells respectively.

ER/PR pharmDx assay is available in two configurations, both manual and automated and is optimized for use with DakoCytomation detection systems.

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The DakoCytomation Monoclonal Mouse Anti-Human Progesterone Receptor, clone PgR 1294, is a component of the ER/PR pharmDx kit, which will also be commercially available as a concentrate.

Intended Use:

#### For In Vitro Diagnostic Use

The DakoCytomation ER/PR pharmDx™ assay is an immunohistochemical (IHC) kit system to identify human estrogen receptor (ER) and human progesterone receptor (PR) expression in breast cancer tissues routinely processed and paraffin-embedded for histological evaluation. ER/PR pharmDx specifically detects the ER alpha protein as well as the PR located in the cell nucleus of ER and/or PR-expressing cells.

ER/PR pharmDx is indicated as an aid in identifying patients eligible for treatment with antihormonal or aromatase inhibitor therapies, as well as an aid in the prognosis and management of breast cancer.

The DakoCytomation Monoclonal Mouse Anti-Human Progesterone Receptor, clone PgR 1294, is intended for laboratory use as a semi-quantitative detection of progesterone receptor by light microscopy in routinely processed normal and pathological human paraffinembedded tissue. This antibody is indicated for use as an aid in the management, prognosis and prediction of outcome of breast cancer. The clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual

#### Substantial Equivalence:

The DakoCytomation anti-estrogen receptor reagent cocktail. clones 1D5 and ER-2-123. is substantially equivalent to the Ventana ER clone 6F11 and DakoCytomation monoclonal mouse anti-human ER, clone 1D5 in that these products specifically bind to estrogen receptor proteins located in the nuclei of cells. These products require similar detection chemistry principles for visualization of the product, and both aid in the prognosis of breast carcinoma. The difference in visualization does not introduce new issues of safety and effectiveness.

The DakoCytomation PgR 1294 antibody is substantially equivalent to the DakoCytomation PgR 636 antibody, in that these products both bind to progesterone receptor proteins located in the nuclei of breast cancer cells, and use similar detection chemistry principles for visualization.

#### Performance Characteristics:

Performance characteristics evaluated in support of the ER/PR pharmDx™ IHC kit and components include results on specificity, sensitivity, reproducibility, and concordance testing. Results of all testing conducted have demonstrated a substantial degree of equivalency to the predicate devices listed above. Further, concordance testing between the DakoCytomation ER/PR pharmDx kit and the reference, Allred method, demonstrated

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substantially equivalent staining results (99% concordance).

Therefore, based on the information provided in this premarket notification, DakoCytomation concludes that the devices listed above are safe, effective and substantially equivalent to their respective predicate devices in their indications for use, device design, materials, operational principles, and intended use.

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FEB 1 5 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Tiffany D. Almeroth, RAC Senior, Regulatory Affairs Specialist DakoCytomation California, Inc. 6392 Via Real Carpinteria, California 93013

k042884 Re:

Trade/Device Name: DakoCytomation ER/PR pharmDxTM Kit Regulation Number: 21 CFR § 864.1860 Regulation Name: Immunohistochemistry Reagents and Kits Regulatory Class: II Product Code: MYA, MXZ Dated: January 3, 2005 Received: January 6, 2005

Dear Ms. Almeroth:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 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.

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Page 2 -

If you desire specific information about the application of labeling requirements to your device, rr you stions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

lobatz Beckerh

Robert L. Becker, Jr., MD, PH. Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## 510(k) Number (if known): __K042884

Monoclonal Mouse Anti-Human Progesterone Receptor, Clone: Device Name: PgR 1294 (DakoCytomation Code No. M3568)

#### Indications For Use:

The DakoCytomation Monoclonal Mouse Anti-Human Progesterone Receptor, clone PgR 1294, is intended for laboratory use as a semi-quantitative detection of progesterone receptor by light microscopy in routinely processed normal and or progotical human paraffin-embedded tissue. This antibody is indicated for use as an aid in the management, prognosis and prediction of outcome of breast cancer. The clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

| Prescription Use | | OR | Over-The-Counter Use |
|----------------------|--|----|--------------------------|
| (Per 21 CFR 801.109) | | | (Per 21 CFR 801.110 |
| IVD Use | | | |
| (Per 21 CFR 801.119 | | | (Optional Format 1-2-96) |

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

| 510(k) | K042884 |
|--------|---------|
|--------|---------|

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# 510(k) Number (if known):__K042884

DakoCytomation ER/PR pharmDx™ Device Name: (DakoCytomation Code No. K1903)

### Indications For Use:

The DakoCytomation ER/PR pharmDx™ assay is a semi-quantitative immunohistochemical (IHC) kit system to identify estrogen receptor (ER) and progesterone receptor (PR) expression in normal and neoplastic tissues routinely processed and paraffin-embedded for histological evaluation. ER/PR pharmDx specifically detects the ER alpha protein as well as the PR protein located in the cell nucleus of ER and PR-expressing cells respectively.

ER/PR pharmDx is indicated as an aid in identifying patients eligible for treatment with anti-hormonal or aromatase inhibitor therapies, as well as an aid in the prognosis and management of breast cancer.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

| Prescription Use | <div> <span style="text-decoration: underline;">✓</span> </div> (Per 21 CFR 801.109) | OR | Over-The-Counter Use | <span style="text-decoration: underline;"></span> (Per 21 CFR 801.110) |
|------------------|--------------------------------------------------------------------------------------|----|----------------------|------------------------------------------------------------------------|
| IVD Use | <span style="text-decoration: underline;"></span> (Per 21 CFR 801.119 | | | |

Division Sign-Off

(Optional Format 1-2-96)

Office of In Vitro Diagnostic Device Evaluation and Safety

| 510(k) | K042884 |
|--------|---------|
|--------|---------|