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.

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.

AI/ML Overview

This document describes the Dako FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor α, Clone EP1, Ready-to-Use (Dako Omnis) Immunohistochemistry (IHC) reagent system, referred to as GA084, and its equivalence to a predicate device (IR084).

Here's an analysis of the acceptance criteria and study findings based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document states that "All results from performance studies confirm that GA084 meets its acceptance criteria and is substantial equivalent to its predicate device IR084." However, it does not explicitly list the numerical acceptance criteria for each performance characteristic. Instead, it broadly indicates that the device met these criteria. The performance characteristics evaluated were:

Performance Characteristic	Reported Device Performance (GA084)	Acceptance Criteria
Analytical Specificity	Met criteria	Not explicitly stated (implied specific staining of ER in normal tissues)
Reproducibility (Intra-run)	Met criteria	Not explicitly stated (implied consistent results within a run)
Reproducibility (Inter-lot)	Met criteria	Not explicitly stated (implied consistent results across different manufacturing lots)
Reproducibility (Inter-laboratory)	Met criteria	Not explicitly stated (implied consistent results across different laboratories)
Reproducibility (Inter-observer)	Met criteria	Not explicitly stated (implied consistent results between different pathologists)
Concordance with Predicate Device (IR084)	Demonstrated equivalence	Not explicitly stated (implied high agreement with predicate)

2. Sample Size Used for the Test Set and Data Provenance

The document does not specify the exact sample size used for the test set in the performance studies. It mentions that concordance studies were performed to establish equivalence.

The data provenance is not explicitly stated regarding country of origin or whether it was retrospective or prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The document does not specify the number of experts used or their qualifications for establishing ground truth specifically for the test set. It mentions that clinical interpretation "should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist." This implies that qualified pathologists are involved in interpretation but doesn't detail their role in establishing ground truth for the study.

4. Adjudication Method for the Test Set

The document does not specify the adjudication method used for the test set.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance.

This device is an immunohistochemistry (IHC) reagent system, not an AI or imaging device. Therefore, an MRMC comparative effectiveness study involving AI assistance for human readers is not applicable and was not reported. The focus is on the performance of the staining reagent itself.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done.

As stated above, this is an IHC reagent system. There is no algorithm involved that operates in a standalone manner. The device's performance is inherently tied to the staining process and subsequent human interpretation by a pathologist.

7. The Type of Ground Truth Used

The type of ground truth used is expert evaluation by qualified pathologists of the stained tissue sections. 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." The antibody is intended to be used "after the primary diagnosis of tumor has been made by conventional histopathology using nonimmunologic histochemical stains." This implies that the 'ground truth' for whether a tumor is present and for the ER status would ultimately rely on comprehensive pathological assessment.

8. The Sample Size for the Training Set

The document does not mention a training set as this is not an algorithm-based device.

9. How the Ground Truth for the Training Set Was Established

As there is no training set for this type of device, this question is not applicable.

Summary

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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: 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

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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 (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

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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.

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

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:

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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

Intended Use:

For in vitro diagnostic use.

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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 EstrogenReceptor 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 stainingbreast cancer cells	Same

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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 withDako Omnis	Pre-diluted Ready-to-usewith Autostainer Link 48
TemperatureControl/IncubationTemperature	Temperature controlled at32°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 anddistributed across slide viaactive slide lids which enablecapillary force spreading	Open slide staining: Reagentis applied and distributedacross slide via gravitationalspreading
Vial	Dako Omnis Large Vial, 30 mL	Automation Vial, 25mL
Cap	Dako Omnis Closure includingseptum	White Nalgene Cap
Deparaffinization	On-board Dako Omnis withClearify	EnVision FLEX High pH onexternal PT Module
Pre-Treatment (AntigenRetrieval)	EnVision FLEX High pH (30minute heat-induced Epitoperetrieval)	EnVision FLEX High pH (20minute heat-induced Epitoperetrieval)
Visualization	EnVision FLEX (Chromogen 5minutes)	EnVision FLEX (Chromogen 2x 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

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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.

Regulation Number and Section

§ 864.1860 Immunohistochemistry reagents and kits.

(a)
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.(b)
Classification of immunohistochemistry devices. (1) Class I (general controls). Except as described in paragraphs (b)(2) and (b)(3) of this section, these devices are exempt from the premarket notification requirements in part 807, subpart E of this chapter. This exemption applies to IHC's that provide the pathologist with adjunctive diagnostic information that may be incorporated into the pathologist's report, but that is not ordinarily reported to the clinician as an independent finding. These IHC's are used after the primary diagnosis of tumor (neoplasm) has been made by conventional histopathology using nonimmunologic histochemical stains, such as hematoxylin and eosin. Examples of class I IHC's are differentiation markers that are used as adjunctive tests to subclassify tumors, such as keratin.(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.
(3) Class III (premarket approval). IHC's intended for any use not described in paragraphs (b)(1) or (b)(2) of this section.
(c)
Date of PMA or notice of completion of a PDP is required. As of May 28, 1976, an approval under section 515 of the Federal Food, Drug, and Cosmetic Act is required for any device described in paragraph (b)(3) of this section before this device may be commercially distributed. See § 864.3.