(352 days)
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.
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.
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.
§ 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.