What is the regulatory pathway for FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EPI, RTU (Dako Onmis)?

510(k) clearance (submission type: Traditional).

Who can help prepare an FDA 510(k) submission like FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EPI, RTU (Dako Onmis)?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EPI, RTU (Dako Onmis)

Q: Who is the manufacturer of FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EPI, RTU (Dako Onmis)?

Dako Denmark A/S filed the 510(k) submission for FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EPI, RTU (Dako Onmis) (K170028).

Q: What is the FDA product code for FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EPI, RTU (Dako Onmis)?

MYA. It is classified under 21 CFR 864.1860 as a Class 2 device in the Hematology panel.

K170028 · Dako Denmark A/S · MYA · Dec 21, 2017 · Hematology

Device Facts

Record ID	K170028
Device Name	FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EPI, RTU (Dako Onmis)
Applicant	Dako Denmark A/S
Product Code	MYA · 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 Rabbit Anti-Human Estrogen Receptor α, Clone EP1, 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 estrogen receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer. The antibody binds estrogen receptor α expressing 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. This antibody is intended to be used after the primary diagnosis of tumor has been made by conventional histopathology using non-immunologic histochemical stains.

Device Story

IHC assay using monoclonal rabbit anti-human estrogen receptor alpha (clone EP1) antibody; detects ER expression in formalin-fixed, paraffin-embedded breast cancer tissue. Used on Dako Omnis instrument; utilizes dynamic gap staining with active slide lids for reagent distribution via capillary force. Reagent applied at 32°C; automated deparaffinization, antigen retrieval, and visualization. Pathologist evaluates stained slides via light microscopy; positive result defined as ≥1% positive staining of breast cancer cells. Complements morphological studies and clinical history for breast cancer prognosis. Benefits include standardized, automated assessment of ER status to guide clinical decision-making.

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

Ready-to-use liquid antibody (15 µg/mL) in buffer with stabilizing protein and 0.015 mol/L sodium azide. Immunohistochemistry principle; automated staining on Dako Omnis instrument. Features dynamic gap staining with active slide lids. Temperature controlled at 32°C ± 2°C. Compatible with EnVision FLEX visualization system. Software-controlled automated slide staining process.

Indications for Use

Indicated for qualitative detection of human estrogen receptor α in formalin-fixed, paraffin-embedded (FFPE) breast cancer tissue sections to assess ER status in patients diagnosed with breast carcinoma.

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 (RTU) antibody (K120663)

Related Devices

K110215 — CONFIRM ANTI-ESTROGEN RECEPTOR (SP1) RABBIT MONOCLONAL PRIMARY ANTIBODY · Ventana Medical Systems, Inc. · Dec 17, 2012

Submission Summary (Full Text)

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health and Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue. December 21, 2017 Dako Denmark A/S Lasse Post Møller Pathology Regulatory Affairs Manager Produktionsvej 42 DK-2600 Glostrup, Denmark Re: K170028 Trade/Device Name: FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EP1, Readyto-Use (Dako Omnis) Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Code: MYA 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 {1}------------------------------------------------ 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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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 {2}------------------------------------------------ ## Indications for Use 510(k) Number (if known) K170028 #### Device Name FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EP1, Ready-to-Use (Dako Omnis) Indications for Use (Describe) For in vitro diagnostic use. FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EP1, 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 estrogen receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer. The antibody binds estrogen receptor a expressing 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. 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) #### 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 PRAStaff@fda.hhs.gov "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." {3}------------------------------------------------ #### 5. 510(k) Summary Traditional Premarket Notification Submission (510(k)) Summary Prepared in accordance with 21 CFR 807.92 ## Sponsor Name and Address Dako Denmark A/S Produktionsvej 42 2600 Glostrup, Denmark Establishment registration No: 9610099 ### Contact Lasse Post Møller Dako Denmark A/S Produktionsvej 42 2600 Glostrup, Denmark Telephone: +45 5167 6362 Telefax: +45 8830 5998 Email: lasse.moller@agilent.com #### Date Summary Prepared December 21, 2017 #### Device Name(s) | Trade name(s) | FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor α, Clone EP1, Ready-to-Use (Dako Omnis) | |-------------------|------------------------------------------------------------------------------------------------| | Product code: | GA084 | | Common name | Anti-Human ER a, Clone EP1 (Dako Omnis) | | Classification: | Class II (21 CFR 864.1860) | | FDA Product Code: | MYA | ## Predicate Device: {4}------------------------------------------------ | Trade name (s): | Dako Monoclonal Rabbit Anti-Human Estrogen Receptor α, | |-------------------|--------------------------------------------------------| | | Clone EP1, FLEX, Ready-to-Use (RTU) Link | | FDA Product code: | MYA | | Classification: | Class II (21 CFR 864.1860) | | | Device Cleared in Premarket notification K120663. | #### Device Description The FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EP1, Ready-to-Use (Dako Omnis) antibody is utilized to perform a qualitative immunohistochemical (IHC) assay to identify estrogen receptor (ER) expression in fixed human breast cancer tissues routinely processed and paraffin-embedded for histological examination. The design of the proposed device is based on the design of its predicate FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor α. Clone EP1, 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 antibody 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. FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EP1, 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 estrogen receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer. The antibody binds estrogen receptor a expressing cells and is useful in the assessment of estrogen receptor status in human breast carcinomas. {5}------------------------------------------------ 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 Rabbit Anti-Human Estrogen Receptor a, Clone EP1, Ready-to-Use (Dako Omnis), is claimed to be substantially equivalent to the predicate device FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a, Clone EP1, Ready-to-Use (Link), also referred to by its product code IR084. The predicate device is cleared for the US market in the premarket notification K120663. Both products specifically bind to estrogen receptor (ER) 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. Both products have the same intended use, staining steps and scoring guideline for interpretation. All differences between the proposed device GA084 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 Estrogen Receptor α Protein | same | | Antibody Type | Monoclonal, rabbit origin | Same | | Isotype | IgG | Same | | Clone | EP1 | Same | | Staining Pattern | Nuclear | Same | | Interpretation of results | Positive: ≥1% positive staining breast cancer cells | Same | {6}------------------------------------------------ | Similarities | | | |--------------|----------------------------------------------------|-----------| | Item | Device | Predicate | | Tissue Type | Formalin-fixed paraffin- embedded breast cancer | Same | | Technology | Immunohistochemistry | Same | | Storage | 2-8 °C | Same | | Differences | | | |--------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------| | Item | Device | Predicate | | Configuration | Pre-diluted Ready-to-use with Dako Omnis | Pre-diluted Ready-to-use with Autostainer Link 48 | | Temperature Control/Incubation Temperature | Temperature controlled at 32°C $\u00b1$ 2°C | No temperature control (ambient temperature) | | Antibody Concentration | 15 µg/mL | 3.7 µg/mL | | Antibody Incubation Time | 10 minutes | 20 minutes | | Staining | Dynamic gap staining: Reagent is applied and distributed across slide via active slide lids which enable capillary force spreading | Open slide staining: Reagent is applied and distributed across slide via gravitational spreading | | Vial | Dako Omnis Large Vial, 30 mL | Automation Vial, 25mL | | Cap | Dako Omnis Closure including septum | White Nalgene Cap | | Deparaffinization | On-board Dako Omnis with Clearify | EnVision FLEX High pH on external PT Module | | Pre-Treatment (Antigen Retrieval) | EnVision FLEX High pH (30 minute heat-induced Epitope retrieval) | EnVision FLEX High pH (20 minute heat-induced Epitope retrieval) | | Visualization | EnVision FLEX (Chromogen 5 minutes) | EnVision FLEX (Chromogen 2 x 5 minutes) | The proposed device is evaluated to be substantially equivalent to its predicate device and does not introduce any new issues for safety and effectiveness. ## Performance Characteristics Performance characteristics were evaluated to determine its analytical specificity for normal tissue and reproducibility to control intra run, inter lot, inter-laboratory and interobserver variations. The device was also evaluated in a concordance study to establish equivalence to the predicate device. All results from performance studies confirm that {7}------------------------------------------------ GA084 meets its acceptance criteria and is substantial equivalent to its predicate device IR084. Therefore, based on the information provided in this premarket notification, we conclude that, FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor α, Clone EP1, 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.