(119 days)
The DakoCytomation ER/PR pharmDx™ assay is an immunohistochemical (IHC) kit system to identify human estrogen receptor (ER) and human progesterone receptor (PR) expression in breast cancer tissues routinely processed and paraffin-embedded for histological evaluation. ER/PR pharmDx specifically detects the ER alpha protein as well as the PR located in the cell nucleus of ER and/or PR-expressing cells.
ER/PR pharmDx is indicated as an aid in identifying patients eligible for treatment with antihormonal or aromatase inhibitor therapies, as well as an aid in the prognosis and management of breast cancer.
The DakoCytomation Monoclonal Mouse Anti-Human Progesterone Receptor, clone PgR 1294, is intended for laboratory use as a semi-quantitative detection of progesterone receptor by light microscopy in routinely processed normal and pathological human paraffinembedded tissue. This antibody is indicated for use as an aid in the management, prognosis and prediction of outcome of breast cancer. The clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual
The DakoCytomation ER/PR pharmDx™ assay is a semi-quantitative immunohistochemical (IHC) kit system to identify estrogen receptor (ER) and progesterone receptor (PR) expression in normal and neoplastic tissues routinely processed and paraffin-embedded for histological expressing cells respectively.
ER/PR pharmDx assay is available in two configurations, both manual and automated and is optimized for use with DakoCytomation detection systems.
The DakoCytomation Monoclonal Mouse Anti-Human Progesterone Receptor, clone PgR 1294, is a component of the ER/PR pharmDx kit, which will also be commercially available as a concentrate.
Here's an analysis of the provided 510(k) summary, specifically focusing on the acceptance criteria and study proving device performance for the DakoCytomation ER/PR pharmDx™ Kit and the Monoclonal Mouse Anti-Human Progesterone Receptor, clone PgR 1294:
Acceptance Criteria and Device Performance
The document does not explicitly present a table of numerical acceptance criteria with corresponding reported device performance values. Instead, it describes performance characteristics that were evaluated and states that the results demonstrated "a substantial degree of equivalency to the predicate devices" and "substantially equivalent staining results" to a reference method.
The primary acceptance criteria appear to be substantial equivalence to predicate devices and high concordance with a recognized reference method.
Table of Acceptance Criteria and Reported Device Performance (Inferred)
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Concordance | Substantial equivalency (e.g., >95% or similar) with predicate devices and reference methods. | 99% concordance with the reference Allred method. |
| Specificity | Demonstrates appropriate specificity compared to predicate devices. | Demonstrated specificity; results deemed substantially equivalent to predicate devices. |
| Sensitivity | Demonstrates appropriate sensitivity compared to predicate devices. | Demonstrated sensitivity; results deemed substantially equivalent to predicate devices. |
| Reproducibility | Demonstrates appropriate reproducibility compared to predicate devices. | Demonstrated reproducibility; results deemed substantially equivalent to predicate devices. |
Study Description and Details:
The summary refers to a single study that encompassed evaluations of specificity, sensitivity, reproducibility, and concordance testing.
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Sample Size and Data Provenance:
- Test Set Sample Size: Not explicitly stated for any of the performance characteristics.
- Data Provenance: Not specified (e.g., country of origin, retrospective/prospective).
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Number of Experts and Qualifications for Ground Truth:
- The document does not provide information on the number of experts used to establish ground truth or their specific qualifications.
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Adjudication Method:
- The document does not specify any adjudication method used for the test set.
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Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No MRMC comparative effectiveness study is mentioned. The comparison is between the new device and predicate devices/reference methods, not an assessment of human reader improvement with or without AI assistance.
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Standalone Performance (Algorithm Only):
- Yes, the performance characteristics (specificity, sensitivity, reproducibility, and concordance) are described for the device itself (the IHC kit and its components) when used according to its intended purpose. This represents a standalone assessment of the assay's performance.
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Type of Ground Truth Used:
- The ground truth for the concordance testing was established using the "Allred method." The Allred score is a semi-quantitative scoring system for ER/PR expression in breast cancer, combining the proportion of positive cells and the staining intensity. This can be considered a type of expert consensus/established semi-quantitative scoring method based on histopathology. For specificity, sensitivity, and reproducibility, the ground truth would also be based on established histopathological evaluation or comparison to the predicate devices, which are already considered validated.
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Training Set Sample Size:
- Not specified. The document primarily focuses on the validation study demonstrating substantial equivalence. It does not provide details about any internal development or training data used in the creation of the assay itself, as this would typically be a chemical/biological assay rather than a machine learning algorithm requiring a separate "training set" in the computational sense.
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How Ground Truth for Training Set was Established:
- Not applicable as this is not a machine learning device and no "training set" is described. The development of such IHC kits typically involves chemical formulation, antibody selection, and optimization against known positive and negative tissue samples, but these are not referred to as a "training set" in the context of this document.
§ 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.