(102 days)
Monoclonal Mouse Anti-Human Estrogen Receptor, Clone 1D5 may be used in the semi-quantitative detection of human estrogen receptor in tissue sections of human breast cancer by immunohistochemistry. The information gained by this assay can aid in assessing the likelihood of response to therapy as well as in the prognosis and management of breast cancer patients.
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 having knowledge of all the potential antibody reactivities.
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Monoclonal Mouse Anti-Human Estrogen Receptor, Clone 1D5, Device Code No. M7047) is a mouse anti-human monoclonal antibody (Product) produced as a tissue culture supernatant. The antibody is supplied in Description: 0.05M Tris-HCl buffer, pH 7.2, containing fotal bovine serum and 15mM sodium azide. (1mL total volume).
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Monoclonal Mouse Anti-Human Estrogen Receptor. Clone 105 Ready-to-Use Antibody and Negative Control (Product Code No. N1576) consists of a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and pre-diluted in 0.05M Tris-HCI buffer, pH 7.6, containing fotal bovine serum and 15mM sodium azide (7mL total volume). The primary antibody is packaged with a negative control reagent consisting of a cocktail of purified mouse immunoglobulins (IgG, IgG, IgGz, IgGz, IgGz and IgM) in 0.05M Tris-HCI buffer, pH 7.6 and 15mM sodium azide (5mL total volume).
The provided text describes DAKO's Monoclonal Mouse Anti-Human Estrogen Receptor, Clone 1D5 (anti-ER, 1D5) and its comparison to a predicate device, Abbott ER-ICA Monoclonal, clone H222. The studies performed focused on demonstrating substantial equivalence, rather than establishing specific quantitative acceptance criteria for the anti-ER, 1D5 device alone against predefined thresholds.
However, based on the comparative effectiveness studies presented, we can infer performance and the methods used to demonstrate the device's utility.
Here's an analysis based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly state quantitative "acceptance criteria" for the anti-ER, 1D5 antibody against a specific clinical outcome. Instead, it demonstrates performance by comparing it to an already approved predicate device (Abbott ER-ICA H222) and by citing published studies on its use. The primary goal was to establish substantial equivalence.
The table below summarizes the reported performance of anti-ER, 1D5 and its comparison to the predicate device and clinical outcomes, where available.
| Metric (Inferred Acceptance Criterion based on predicate comparison or clinical relevance) | Reported Device Performance (anti-ER, 1D5) |
|---|---|
| Normal Tissue Reactivity (Expected specific staining, no non-specific staining) | Expected positive staining in breast, cervix, and uterus. No reactivity in ER-negative tissues. Weak cytoplasmic staining considered non-specific. |
| Reproducibility (Consistent results within and between runs) | Consistent results with intra- and inter-run testing. |
| Specificity vs. Predicate (H222) | Varied from 51% to 79% (across different studies). One study reported 79.2% specificity. Another reported 88% specificity with H222 frozen and 64.90% with H222 paraffin. |
| Sensitivity vs. Predicate (H222) | Varied from 89% to 100% (across different studies). One study reported 94.6% sensitivity. Another reported 91.95% sensitivity with H222 paraffin and 100% with H222 frozen. |
| Positive Predictive Value vs. Predicate (H222) | One study reported 64%. |
| Negative Predictive Value vs. Predicate (H222) | One study reported 92%. |
| Correlation with Outcome (Tamoxifen Response) | Predictive information for selecting patients benefiting from hormonal treatment. Strong predictor of favorable primary response in 89% of 72 cases in one study. |
| Correlation with Overall Survival (OS) | Significant for DFS (p = 0.01) and OS (p = 0.01) in one study (for 3+ intensity). |
| Correlation with Relapse-Free Survival (RFS) | Prognostically relevant for predicting relapse-free survival in node-positive cases. |
| Correlation with H222 frozen (R value, if reported) | R=0.7, with p |
§ 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.