FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis)

K170005 · Dako Denmark A/S · MXZ · Dec 21, 2017 · Hematology

Device Facts

• Record ID: K170005
• Device Name: FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis)
• Applicant: Dako Denmark A/S
• Product Code: MXZ · Hematology
• Decision Date: Dec 21, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.1860
• Device Class: Class 2

Intended Use

For in vitro diagnostic use. FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis), is intended for use in immunohistochemistry with the EnVision FLEX visualization system together with the Dako Omnis instrument to qualitatively detect human progesterone receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer. The antibody binds progesterone receptor-expressing 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. This antibody is intended to be used after the primary diagnosis of tumor has been made by conventional histopathology using nonimmunologic histochemical stains.

Device Story

Device is an immunohistochemical (IHC) assay using monoclonal mouse anti-human progesterone receptor (Clone PgR 1294) antibody. Input is formalin-fixed, paraffin-embedded (FFPE) human breast cancer tissue sections on glass slides. Processed on Dako Omnis instrument; utilizes automated deparaffinization, heat-induced epitope retrieval, and incubation with HRP-linked visualization reagent. Enzymatic conversion of DAB+ chromogen creates visible reaction product at antigen sites. Operated by qualified pathology laboratory professionals. Output is stained tissue slide visualized via light microscope. Pathologist interprets staining (positive defined as ≥1% nuclear staining). Assists in determining progesterone receptor status for clinical decision-making in breast cancer management.

Clinical Evidence

Bench testing only. Performance evaluated via analytical specificity in normal tissues and reproducibility studies (intra-run, inter-lot, inter-laboratory, inter-observer). Concordance study established equivalence to predicate device. All performance metrics met acceptance criteria.

Technological Characteristics

IHC reagent; monoclonal mouse IgG antibody (Clone PgR 1294) in buffer with stabilizing protein and 0.015 mol/L sodium azide. Designed for Dako Omnis instrument; utilizes dynamic gap capillary staining. Temperature controlled at 32°C ± 2°C. Onboard stability 80 hours. Automated deparaffinization, heat-induced epitope retrieval (30 min), and EnVision FLEX visualization.

Indications for Use

Indicated for the qualitative detection of human progesterone receptor in formalin-fixed, paraffin-embedded breast cancer tissue sections to assess progesterone receptor status in patients diagnosed with breast carcinoma. For prescription use only.

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 Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link) (K130861)

Submission Summary (Full Text)

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December 21, 2017

Dako Denmark A/S Lasse Post Møller Pathology Regulatory Affairs Manager Produktionsvej 42 DK-2600 Glostrup, Denmark

Re: K170005

Trade/Device Name: FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis) Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Code: MXZ Dated: December 28, 2017 Received: January 3, 2017

Dear Lasse Post 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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR

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Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

# 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

Enclosure

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# Indications for Use

510(k) Number (if known) K170005

#### Device Name

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis)

#### Indications for Use (Describe)

For in vitro diagnostic use.

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis), is intended for use in immunohistochemistry with the En Vision FLEX visualization system together with the Dako Omnis instrument to qualitatively detect human progesterone receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer. The antibody binds progesterone receptor-expressing 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. This antibody is intended to be used after the primary diagnosis of tumor has been made by conventional histopathology using nonimmunologic histochemical stains.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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#### 5. 510(k) Summary

Traditional Premarket Notification Submission (510(k)) Summary Prepared in accordance with 21 CFR 807.92

#### Submitter Information

Dako Denmark A/S

Produktionsvej 42

2600 Glostrup, Denmark

Establishment registration No: 9610099

### Contact Information

Lasse Post Møller Dako Denmark A/S Produktionsvej 42 2600 Glostrup, Denmark Telephone: [phone] Telefax: [phone] Email: [e-mail]

# Date Summary Prepared

December 21, 2017

# Device Name(s)

| Trade name(s) | FLEX Monoclonal Mouse Anti-Human Progesterone<br>Receptor, Clone PgR 1294, Ready-to-Use (Dako<br>Omnis) |
|-------------------|---------------------------------------------------------------------------------------------------------|
| Product code: | GA090 |
| Common name | Anti-Human PR, Clone PgR 1294 (Dako Omnis) |
| Classification: | Class II (21 CFR 864.1860) |
| FDA Product Code: | MXZ |

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### Predicate Device:

| Trade name(s): | FLEX Monoclonal Mouse Anti-Human<br>Progesterone Receptor, Clone PgR 636, Ready-to-<br>Use, (Link) |
|---------------------------------------------------|----------------------------------------------------------------------------------------------------|
| Product code: | IR068 |
| Classification: | Class II (21 CFR 864.1860) FDA Product Code: MXZ |
| Device cleared in Premarket notification K130861. | |

#### Device Description

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Readyto-Use (Dako Omnis) is utilized to perform a qualitative immunohistochemical (IHC) assay to identify progesterone receptor (PR) expression in formalin fixed human breast cancer tissues routinely processed and paraffin-embedded for histological examination. The proposed device is a variant of FLEX Monoclonal Mouse Anti-Human Progesterone Receptor intended for use with the automated slide staining instrument Dako Omnis.

The design of the proposed device is developed to provide equivalent performance to its predicate FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link) with adaptation of the product configuration, to be used on the Dako Omnis Instrument instead of the Autostainer Link 48 Instrument.

The antibody is provided in liquid form in a buffer containing stabilizing protein and 0.015 mol/L sodium azide. The proposed device is intended for automated immunohistochemical (IHC) slide staining with the Dako Omnis Instrument and the software performing and controlling the automated slide staining process is validated for its intended use.

#### Intended Use:

For in vitro diagnostic use.

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FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Readyto-Use (Dako Omnis), is intended for use in immunohistochemistry with the EnVision FLEX visualization system together with the Dako Omnis instrument to qualitatively detect human progesterone receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer. The antibody binds progesterone receptor-expressing 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. This antibody is intended to be used after the primary diagnosis of tumor has been made by conventional histopathology using nonimmunologic histochemical stains.

# Substantial Equivalence

The proposed device, FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis) is claimed to be substantially equivalent to the predicate FLEX Monoclonal Mouse Anti- Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link). The predicate device IR068 is cleared for the US market in the premarket notification K130861.

Both products have the same intended use and specifically bind to progesterone receptor (PR) proteins located in the nuclei of cells. Both products require similar detection chemistry principles for visualization of antigens, and both aid in the prognosis of breast carcinoma.

All differences between the proposed device and its predicate are related to their use with different slide staining instruments, see details in the comparison table below.

| Similarities | | |
|---------------|---------------------------------------|-----------|
| Item | Device | Predicate |
| Intended Use | Detection of progesterone<br>receptor | Same |
| Antibody Type | Monoclonal, mouse origin | Same |

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| Isotype | IgG | Same |
|---------------------------|--------------------------------------------------------|------|
| Staining Pattern | Nuclear | Same |
| Positive Cell Type | Cells expressing<br>progesterone | Same |
| Interpretation of results | Positive: ≥1% positive<br>staining breast cancer cells | Same |
| Tissue Type | Formalin-fixed paraffin-<br>embedded breast cancer | Same |
| Technology | Immunohistochemistry | Same |
| Storage | 2-8 °C | Same |

| Differences | | |
|--------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------|
| Item | Device | Predicate |
| Clone | Clone PgR 1294 | Clone PgR 636 |
| Configuration | Pre-diluted-Ready-to-use<br>with Dako Omnis | Pre-diluted-Ready-to-use with<br>Autostainer Link 48 |
| Temperature<br>Control/Incubation<br>Temperature | Temperature controlled at<br>$32°C ± 2°C$ | No temperature<br>control (ambient<br>temperature) |
| Antibody Incubation<br>Time* | 10 minutes | 20 minutes |
| Onboard Stability | 80 hours | Not defined nor<br>applicable |
| Staining | Dynamic gap staining:<br>Reagent is applied and<br>distributed across slide via<br>active slide lids which<br>enable capillary force<br>spreading | Open slide staining:<br>Reagent is applied<br>and distributed<br>across slide via<br>gravitational<br>spreading |
| Vial | Dako Omnis Large Vial, 30<br>mL | Automation Vial,<br>25mL |
| Cap | Dako Omnis Closure<br>including septum | White Nalgene Cap |
| Deparaffinization | Onboard Dako Omnis with<br>Clearify | Envision FLEX<br>High pH on external<br>PT Module |
| Pre-Treatment (Antigen<br>Retrieval) | EnVision FLEX High pH<br>(30 minute heat-induced<br>epitope retrieval) | EnVision FLEX<br>High pH (20 minute<br>heat-induced epitope<br>retrieval) |
| Visualization | EnVision FLEX<br>(Chromogen 5 minutes) | EnVision FLEX<br>(Chromogen 2x5<br>minutes) |

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#### Performance Characteristics

Performance characteristics of the device were evaluated to determine its analytical specificity for normal tissue and reproducibility to control intra-run, inter-lot, inter-laboratory and inter-observer variations. The device was also evaluated in a concordance study to establish equivalence to the predicate device. All results from performance studies confirm that the device meets its acceptance criteria and is substantial equivalent to its predicate device.

Therefore, based on the information provided in this premarket notification, Dako concludes that the FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis) is safe, effective and substantially equivalent to the predicate device in the indication for use, device design, materials, operational principles, and intended use.