(719 days)
This antibody is intended for in vitro diagnostic (IVD) use.
CONFIRM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody is intended for laboratory use for the qualitative detection of estrogen receptor (ER) antigen in sections of formalin-fixed, paraffin-embedded breast tissue on a Ventana automated slide stainer with Ventana detection kits and ancillary reagents. CONFIRM anti-ER (SP1) is directed against an epitope present on human ER alpha protein located in the nucleus of ER positive normal and neoplastic cells. CONFIRM anti-ER (SP1) is indicated as an aid in the management, prognosis, and prediction of hormone therapy for breast carcinoma.
This product should be interpreted by a qualified pathologist in conjunction with histological examination, relevant clinical information, and proper controls.
Prescription use only.
CONFIRM anti-ER (SP1) binds to human estrogen receptor alpha (ER) in paraffin embedded tissue sections. The antibody is diluted in 0.05 M Tris-HCl with 2% carrier protein, and 0.10% ProClin 300, a preservative. There is trace (~0.2%) fetal calf serum of U.S. origin from the stock solution. Total protein concentration of the reagent is approximately 20 mg/mL. Specific antibody concentration is approximately 1 ug/mL. CONFIRM anti-ER (SP1) is a rabbit monoclonal antibody produced as a cell culture supernatant.
CONFIRM anti-ER (SP1) is optimized for use on the BenchMark XT and BenchMark ULTRA automated slides stainers using iView DAB and ultraView DAB detection chemistries.
Here's a breakdown of the acceptance criteria and the study details for the CONFIRM anti-Estrogen Receptor (SP1) Rabbit Monoclonal Primary Antibody, based on the provided text:
Acceptance Criteria and Device Performance
| Acceptance Criterion | Reported Device Performance | Study Type |
|---|---|---|
| Method Comparison: Overall Percent Agreement (OPA) for ER status between BenchMark XT and BenchMark ULTRA instruments | 90.9% (95% CI: 86.2-94.1%) | Comparison of current device on two different automated stainers (BenchMark XT vs. BenchMark ULTRA) |
| Equivalence to Predicate: Overall Percent Agreement (OPA) for ER status between CONFIRM anti-ER (SP1) and FLEX anti-ER (SP1) | 97.8% (95% CI: 96.2-98.8%) | Comparison of current device (CONFIRM anti-ER (SP1)) with predicate device (FLEX anti-ER (SP1)) |
| Equivalence to Predicate: Comparison against patient outcome (median survival times in tamoxifen treated patients) | Identical median survival times (101.6 months in ER+ patients vs 47.2 months in ER- patients) for both assays. Log-rank test showed statistically significant difference between ER+/ER- relative to survival (P 0.999). | Comparison of current device and predicate device against a preceding technology (LBA) |
| Equivalence to Predicate: Negative Percent Agreement (NPA) with Ligand Binding Assay (LBA) for ER- cases | CONFIRM anti-ER (SP1): 27.6% | |
| FLEX anti-ER (SP1): 34.5% | ||
| Difference not statistically significant (McNemar's exact test p-value = 0.500). | Comparison of current device and predicate device against a preceding technology (LBA) |
Study Details
-
Sample size used for the test set and the data provenance:
- Method Comparison Study (BenchMark XT vs. BenchMark ULTRA): 120 ER negative and 132 ER positive breast cancer cases (total 252 cases). Data provenance is not explicitly stated in terms of country of origin but is presumed to be retrospective clinical samples. It is a prospective study in terms of evaluating the newly stained slides.
- Equivalence to Predicate Study (CONFIRM vs. FLEX and LBA): 820 invasive breast cancer cases in the clinical cohort, from which 594 breast cancer cases with primary tumor underwent IHC staining on 1907 tissue microarray cores. The study is described as having "available from the cohort database," suggesting retrospective data for patient outcome and LBA, but the IHC staining and evaluation of the tissue microarrays were performed as part of this study. The origin is implied to be a clinical cohort, but specific country is not mentioned.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Method Comparison Study: Evaluated by "pathologists" for determining the percentage of stained tumor cells. The exact number of pathologists per case is not specified beyond "multi-reader study", nor are their qualifications.
- Equivalence to Predicate Study: Evaluated by "three independent pathologists" who determined the percentage of stained tumor cells. Their specific qualifications (e.g., years of experience, subspecialty) are not provided.
-
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- The document implies that pathologists independently evaluated the slides and their interpretations were used to determine ER status. There is no explicit mention of an adjudication method for discordant reads (e.g., 2+1 rule). For the "Equivalence to Predicate Study," three independent pathologists evaluated the slides, but it's not stated how disagreements were resolved for the final ER status used in the analysis.
-
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This is not a multi-reader multi-case (MRMC) comparative effectiveness study evaluating human readers improvement with or without AI assistance. This study evaluates the performance of an immunohistochemistry (IHC) antibody (CONFIRM anti-ER (SP1)) as a diagnostic reagent, comparing it to an existing predicate device and patient outcomes. The "multi-reader" aspect refers to multiple pathologists reading the slides to generate the initial data, not to an AI-assisted workflow.
-
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- No. This device is an immunohistochemistry antibody reagent, not an algorithm or AI product. Its performance is assessed through the staining of tissue samples, which are then interpreted by human pathologists. Therefore, a "standalone algorithm performance" study is not applicable.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For ER status determination on stained slides: The immediate "ground truth" used for calculating agreement percentages (OPA) was the interpretation by pathologists based on the percentage of stained tumor cells.
- For comparing against clinical relevance: Progression-free survival outcome data in tamoxifen-treated patients and Ligand Binding Assay (LBA) data were used as ground truth comparators for the "Equivalence to Predicate" study to assess the clinical utility and biological agreement of the IHC assays.
-
The sample size for the training set:
- This document describes a performance study for an antibody reagent, not a machine learning model. Therefore, there is no "training set" in the context of an algorithm. The antibody itself is "optimized" for use on specific instruments, which implies internal development and testing, but not a dataset-driven training process in the AI sense.
-
How the ground truth for the training set was established:
- As there is no training set for an AI/algorithm, this question is not applicable. The antibody's specificity and reactivity are inherent to its design and manufacturing process, and its performance is validated in clinical studies like the ones described.
§ 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.