MONOCLONAL RABBIT ANTI HUMAN ESTROGEN RECEPTOR ALPHA ANTIBODY CLONE SP1, MODEL M3634

K081286 · Dako North America, Inc. · MYA · May 8, 2009 · Hematology

Device Facts

• Record ID: K081286
• Device Name: MONOCLONAL RABBIT ANTI HUMAN ESTROGEN RECEPTOR ALPHA ANTIBODY CLONE SP1, MODEL M3634
• Applicant: Dako North America, Inc.
• Product Code: MYA · Hematology
• Decision Date: May 8, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.1860
• Device Class: Class 2

Intended Use

Monoclonal Rabbit Anti-Human Estrogen Receptor α (ER α) antibody, Clone SP1, may be used in the semi-quantitative detection of human estrogen receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer by immunohistochemistry. The information gained by this assay can aid in assessing the likelihood of response to therapy as well as in the prognosis and management of breast cancer patients. Clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist.

Device Story

Monoclonal Rabbit Anti-Human Estrogen Receptor a (Clone SP1) is an immunohistochemical (IHC) assay; identifies ER expression in formalin-fixed, paraffin-embedded breast cancer tissue. Operates via antibody-antigen binding to nuclear estrogen receptors; requires detection chemistry for visualization. Used in clinical pathology laboratories; interpreted by qualified pathologists. Output provides semi-quantitative staining results; assists clinicians in determining breast cancer prognosis and potential response to endocrine therapy.

Clinical Evidence

Clinical performance supported by a published study (Cheang et al., 2006) evaluating 4,150 breast cancer samples. Study demonstrated SP1 positivity rate of 69.5% vs 63.1% for 1D5. Ten-year Breast Cancer Specific Survival (BCSS) for SP1 ≥ 1% nuclear staining was 76.5% (95% CI: 73.9-79.0%) vs 65% (95% CI: 62.6-68%) for < 1% staining. A bridging study (n=27) confirmed 100% agreement between the publication's protocol and the Dako SP1 protocol. Analytical performance included precision/reproducibility studies showing 100% agreement across sites.

Technological Characteristics

Semi-quantitative IHC assay; utilizes monoclonal rabbit anti-human ERα antibody (Clone SP1) in concentrated liquid form with 0.015mol/L sodium azide. Detection system uses dextran-polymer backbone conjugated with secondary goat anti-rabbit antibody and horseradish peroxidase. Requires Dako Autostainer for processing. Results interpreted via light microscopy.

Indications for Use

Indicated for the semi-quantitative detection of estrogen receptor in formalin-fixed, paraffin-embedded breast cancer tissue sections to aid in therapy response assessment, prognosis, and management of breast cancer patients.

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

• Monoclonal Mouse ER 1D5/ER-2-123 in the Dako ER/PR pharmDx™ Kit (K042884)

Submission Summary (Full Text)

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# MAY - 8 2009

## 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92 (c).

The assigned 510(k) number is: K081286

| Submitter: | Dako North America, Inc.<br>6392 Via Real<br>Carpinteria, CA 93013<br>PH. 805.566.6655 FX. 805.566.0866<br>Establishment registration number: 2022180 |
|------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Kelly Miller<br>Manager, Regulatory Affairs<br>PH. 805.566.6655 ext. 5330<br>Fax: [phone] |
| Date Summary Prepared: | April 8, 2009 |
| Device Name(s): | Monoclonal Rabbit Anti-Human Estrogen Receptor a antibody,<br>Clone SP1<br>(Code M3634) |
| Device Classification: | Class II (21 CFR 864.1860) |
| Predicate Device: | Monoclonal Mouse ER 1D5/ER-2-123 in the Dako ER/PR<br>pharmDx™ Kit (K042884) |

## Device Description:

Dako Monoclonal Rabbit Anti-Human Estrogen Receptor a antibody, Clone SP1 is a semiquantitative immunohistochemical (IHC) kit assay to identify estrogen receptor (ER) expression in normal and neoplastic tissues routinely processed and paraffin-embedded.

## Intended Use:

For in vitro diagnostic use.

Monoclonal Rabbit Anti-Human Estrogen Receptor a (ER a) antibody, Clone SP1, may be used in the semi-quantitative detection of human estrogen receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer by immunohistochemistry. The information gained by this assay can aid in assessing the likelihood of response to therapy as well as in the prognosis and management of breast cancer patients.

Clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made

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within the context of the patient's clinical history and other diagnostic tests by a qualified pahtologist.

## Substantial Equivalence:

Dako Estrogen Receptor Clone SP1 immunohistochemical assay is substantially equivalent to Monoclonal Mouse ER 1D5/ER-2-123 in the Dako ER/PR pharmDx™ Kit. Both 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.

## Performance Characteristics:

Performance characteristics evaluated for the Estrogen Receptor Clone SP1 IHC assay include results on analytical specificity and sensitivity, precision, reproducibility and method comparison testing. Results of all testing conducted substantial equivalence to the predicate device listed above.

Based on the information provided in this premarket notification, Dako concludes that Monoclonal Rabbit Anti-Estrogen Receptor a, Clone SP1 is substantially equivalent to the predicate device and is safe and effective for its intended use.

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Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services, USA. The logo features a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES, USA" is arranged in a circular pattern around the eagle. The logo is black and white and appears to be a scanned image.

Public Health Service

Food and Drug Administration 2098 Gailher Road Rockville MD 20850

MAY - 8 2009

Dako North America, Inc. c/o Kelly Miller Manager RA 6392 Via Real Carpinteria, CA 93013

Re: k081286

Trade/Device Name: Dako Monoclonal Rabbit Anti-Human Estrogen Receptor, Clone SP1 Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Code: MYA Dated: May 4, 2009 Received: May 5, 2009

Dear Ms. Miller:

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter

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Page 2 - Ms. Kelly Miller

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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Viro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at [phone]. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at [phone]. For more information regarding the reporting of adverse events, please go to http://www.fda.gov/cdrh/mdr/.

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 vours.

Mana M. Chan

Maria Chan, PhD Division Director Division of Immunology and Hematology Devices 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): K081286

Device Name: Dako Monoclonal Rabbit Estrogen Receptor a, Clone SP1

#### Indications For Use:

For in vitro diagnostic use.

Monoclonal Rabbit Anti-Human Estrogen Receptor a (ER a) antibody, Clone SP1, may be used in the semi-quantitative detection of human estrogen receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer by immunohistochemistry. The information gained by this assay can aid in assessing the likelihood of response to therapy as well as in the prognosis and management of breast cancer patients.

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 pathologist.

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

# Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use J (Per 21 CFR 801.109)

OR
*Maris M Chan*

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Division Sign-Off

Over-The-Counter Use (Per 21 CFR 801.110)

IVD Use_______________________________________________________________________________________________________________________________________________________________________ (Per 21 CFR 801.119) Office of in Vitro Dlagnostic Device Evaluation and Safety

Proprietary and confidential

8-Apr-09

510kl

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