FLEX Monoclonal Rabbitt Anti-Human Estrogen Receptor a, Clone EP1, Ready-to-Use (Link); FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use (Link)

K160922 · Dako North America, Inc. · MXZ · May 3, 2016 · Hematology

Device Facts

• Record ID: K160922
• Device Name: FLEX Monoclonal Rabbitt Anti-Human Estrogen Receptor a, Clone EP1, Ready-to-Use (Link); FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use (Link)
• Applicant: Dako North America, Inc.
• Product Code: MXZ · Hematology
• Decision Date: May 3, 2016
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 864.1860
• Device Class: Class 2

Intended Use

FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor α, Clone EP1, Ready-to-Use, (LINK), is intended for use in immunohistochemistry with EnVision FLEX, High pH visualization kit together with Autostainer Link 48 to semiquantitatively detect human estrogen in formalin-fixed, paraffin-embedded tissue sections of human breast cancer. The antibody labels estrogen receptor a-positive cells and is useful in the assessment of estrogen receptor status in human breast carcinomas. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist. FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link), is intended for use in immunohistochemistry together with EnVision FLEX+, High pH visualization kit together with Autostainer Link 48 instrument to semi-quantitatively detect human progesterone receptor in formalin-fixed, paraffin-embedded human breast carcinoma. This antibody labels progesterone receptor-positive cells and is useful in the assessment of progesterone receptor status in human breast carcinomas. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.

Device Story

Immunohistochemistry (IHC) reagents for breast cancer diagnostics; utilizes monoclonal antibodies (Clone EP1 for Estrogen Receptor α; Clone PgR 636 for Progesterone Receptor) to label receptor-positive cells in formalin-fixed, paraffin-embedded tissue sections. Used with EnVision FLEX/FLEX+ visualization kits and Autostainer Link 48 for automated staining. Modification adds Dako PT Link PT200 for automated epitope retrieval pre-treatment. Operated by laboratory technicians/pathologists in clinical settings. Pathologists evaluate stained tissue morphology to determine receptor status, informing clinical decision-making regarding breast cancer treatment. Benefits include standardized, semi-quantitative assessment of hormone receptor status.

Clinical Evidence

No clinical data provided; substantial equivalence established via design control activities and verification/validation of the modified epitope retrieval process (PT Link PT200).

Technological Characteristics

Immunohistochemistry (IHC) assay reagents; automated epitope retrieval via Dako PT Link PT200; fundamental scientific technology unchanged from predicate assays.

Indications for Use

Indicated for the qualitative detection of Estrogen Receptor α and Progesterone Receptor proteins in formalin-fixed, paraffin-embedded tissue sections via immunohistochemistry to aid in the assessment 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

• FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor α, Clone EP1, Ready-to-Use (Link) (K120663)
• FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use (Link) (K130861)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized graphic of three human profiles facing to the right, stacked on top of each other.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

May 2, 2016

Dako North America, Inc. Lasse Post Møller Team Lead - Regulatory Affairs 6392 Via Real Carpinteria, CA 93103

Re: K160922

| Trade/Device Name: | FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor α, Clone<br>EP1, Ready-to-Use (Link); FLEX Monoclonal Mouse Anti-Human<br>Progesterone Receptor, Clone PgR 636, Ready-to-Use (Link) |
|--------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Regulation Number: | 21 CFR 864.1860 |
| Regulation Name: | Immunohistochemistry reagents and kits |
| Regulatory Class: | II |
| Product Code: | MXZ, MYA |
| Dated: | March 31, 2016 |
| Received: | April 4, 2016 |

## Dear Mr. Møller:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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); good manufacturing practice requirements

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as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

# Reena Philip -S

Reena Philip, Ph.D. Director Division of Molecular Genetics and Pathology Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

## Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known) k160922

## Device Name

FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a. Clone EP1. Ready-to-Use (Link)

#### Indications for Use (Describe)

For in vitro diagnostic use.

FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor α, Clone EP1, Ready-to-Use, (LINK), is intended for use in immunohistochemistry with EnVision FLEX, High pH visualization kit together with Autostainer Link 48 to semiquantitatively detect human estrogen in formalin-fixed, paraffin-embedded tissue sections of human breast cancer. The antibody labels estrogen receptor a-positive cells and is useful in the assessment of estrogen receptor status in human breast carcinomas.

The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.

Type of Use (Select one or both, as applicable)

| <div> <span> <svg height="16" width="16"> <rect fill="white" height="16" stroke="black" stroke-width="1" width="16"></rect> <path d="M2,2 L14,14 M14,2 L2,14" stroke="black" stroke-width="2"></path> </svg> </span> Prescription Use (Part 21 CFR 801 Subpart D) </div> | <div> <span> <svg height="16" width="16"> <rect fill="white" height="16" stroke="black" stroke-width="1" width="16"></rect> </svg> </span> Over-The-Counter Use (21 CFR 801 Subpart C) </div> |
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CONTINUE ON A SEPARATE PAGE IF NEEDED

| 2016 May 03 <div> <img alt="Dako Logo" height="50" src="dako_logo.png" width="50"/> Dako Dako Denmark A/S Produktionsvej 42 DK-2600 Glostrup </div> |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
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## This section applies only to requirements of the Paperwork Reduction Act of 1995,

## *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff [e-mail]

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

## Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known) k160922

#### Device Name

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PGR 636, Ready-To-Use (LINK)

#### Indications for Use (Describe)

For in vitro diagnostic use.

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link), is intended for use in immunohistochemistry together with EnVision FLEX+, High pH visualization kit together with Autostainer Link 48 instrument to semi-quantitatively detect human progesterone receptor in formalin-fixed, paraffin-embedded human breast carcinoma. This antibody labels progesterone receptor-positive cells and is useful in the assessment of progesterone receptor status in human breast carcinomas.

The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.

Signature

ko Denmark oduktionsvei 42 K-2600 Glostrup

Type of Use (Select one or both, as applicable)

> Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

#### CONTINUE ON A SEPARATE PAGE IF NEEDED.

## This section applies only to requirements of the Paperwork Reduction Act of 1995.

#### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff [e-mail]

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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## SPECIAL 510(k): Device Modification OIR Decision Summary

RE: DOCUMENT NUMBER To: THE FILE K160922

This 510(k) submission contains information/data on modifications made to the SUBMITTER'S own Class II, Class III or Class I devices requiring 510(k). The following items are present and acceptable:

- 1. The name and 510(k) number of the SUBMITTER'S previously cleared device:
- a. K120663 FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor «, Clone EP1, Ready-to-Use (Link)
- b. K130861 -FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use (Link)
- 2. Submitter's statement that the INDICATION/INTENDED USE of the modified device as described in its labeling HAS NOT CHANGED along with the proposed labeling which includes instructions for use, package labeling, and, if available, advertisements or promotional materials (labeling changes are permitted as long as they do not affect the intended use).
- 3. A description of the device MODIFICATION(S), including clearly labeled diagrams, engineering drawings, photographs, user's and/or service manuals in sufficient detail to demonstrate that the FUNDAMENTAL SCIENTIFIC TECHNOLOGY of the modified device has not changed.

This change was for the addition of the new Dako PT Link PT200 as recommended equipment for automated epitope retrieval pre-treatment, and the addition of the Dako PT Link PT200 product code number in the Instructions For Use for the two Immunohistochemistry antibody assays.

- 4. Comparison Information (similarities and differences) to applicant's legally marketed predicate device including labeling, intended use, physical characteristics, and user-software interface.
- 5. A Design Control Activities Summary which includes:
- a) Identification of Risk Analysis method(s) used to assess the impact of the modification on the device and its components, and the results of the analysis.
- b) Based on the Risk Analysis, an identification of the verification and/or validation activities required, including methods or tests used and acceptance criteria to be applied.

The labeling for this modified subject device has been reviewed to verify that the indication/intended use for the device is unaffected by the modification. In addition, the submitter's description of the particular modification(s) and the comparative information between the modified and unmodified devices demonstrate that the fundamental scientific technology has not changed. The submitter has provided the design control information as specified in The New 510(k) Paradigm and on this basis, I recommend the device be determined substantially equivalent to the previously cleared (or their preamendment) device.