(185 days)
The BioGenex Mouse Monoclonal Anti-Progesterone Receptor Antibody (Clone PR88) is an immunohistochemical (IHC) assay and is intended for laboratory use to qualitatively identify by light microscopy human progesterone receptor in normal and/or pathological paraffin-embedded, formalin-fixed tissues. The PR88 antibody specifically binds to antigens located in the nucleus of cell populations that express progesterone receptor in normal and abnormal tissues. This antibody is indicated as an aid in assessing patient response to hormonal therapy and as an aid in the prognosis and management of breast cancer patients. 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.
BioGenex PR88 is a monoclonal antibody, which specifically binds to progesterone Dreceptor antigen located in the nuclear region of a variety of normal and abnormal tissues. It is a mouse monoclonal anti-progesterone receptor antibody from mouse ascites fluid diluted in phosphate buffered saline pH 7.6 containing bovine serum albumin as carrier and on and 0.09% sodium azide as preservative. The antibody is available in concentrated proximand 0.5970 bounds ready to use form (AM328-5M and AM328-10M). Refer to package insert for details.
This document appears to be a 510(k) summary for a medical device, the BioGenex Mouse Monoclonal Anti-Progesterone Receptor Antibody (Clone PR88). It does not contain explicit "acceptance criteria" in the format typically used for performance studies with predefined thresholds for success (e.g., a specific sensitivity or specificity target to be met). Instead, it describes a "performance data" section to demonstrate substantial equivalence to a predicate device and a reference method.
Therefore, the response below will present the reported device performance and infer the "acceptance criteria" based on the described concordance and the overall conclusion of substantial equivalence.
Here's a breakdown of the requested information:
1. A table of acceptance criteria and the reported device performance
| Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|
| Substantial equivalence to predicate device (Ventana K990618) and reference DCC technique | Verified by comparison of features and performance study results. |
| Specificity with normal human tissues | PR88 antibody demonstrated negative immunoreactivity with most normal human tissues. Positive immunoreactivity observed in specific normal tissues (Langerhans islet cells of pancreas, endometrium of uterus, stromal cells of cervix, parenchymal cells of ovary, convoluted and collecting tubes of kidney, epithelial cells of colon, adenohypophysis of pituitary). |
| Intra-run (within-run) reproducibility | No significant variation among slides of the same tissue stained in a single run. |
| Inter-run (run-to-run) reproducibility | No significant variation among slides of the same tissue stained in different runs. |
| Agreement between instrumental vs. manual runs | No significant variation between slides stained manually and by the automated process. |
| Concordance with reference DCC assay for PR | Overall binary concordance of 74% (99/134) with a 2-sided 95% confidence interval of 66% - 81% (p10% of positive tumor cells was used to score a slide as positive or negative. The document reports a single concordance figure, implying agreement or a method not detailed. |
5. 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, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly conducted as described in the context of human readers improving with AI assistance. This device is an immunohistochemical antibody, not an AI software. The study compared the IHC staining (read by pathologists) against a biochemical assay (DCC).
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- No, a standalone algorithm-only performance assessment was not performed, as this is not an AI device. The device itself is an antibody reagent, and its performance (IHC staining) is evaluated by human pathologists. The "specificity" and "reproducibility" sections effectively describe the standalone performance of the antibody and staining system.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- For the Sensitivity (DCC Comparison) Test Set: The primary ground truth for comparison was the dextran-coated charcoal (DCC) technique, described as a biochemical assay and "considered the gold standard for PR assay" at the time. Pathologists' readings of IHC slides were then compared against this DCC ground truth.
8. The sample size for the training set
- This document does not describe a "training set" in the context of machine learning or AI. This is a traditional IVD device (antibody). The development and optimization of the antibody and staining protocols would have involved various internal tests, but these are not referred to as a "training set" in the provided text.
9. How the ground truth for the training set was established
- As there is no mention of a "training set" in the context of an AI/ML algorithm, this question is not applicable to the provided document. The ground truth for the performance evaluation (test set) was established by the DCC assay.
§ 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.