(322 days)
This antibody is intended for in vitro diagnostic (IVD) use. CONFIRM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal (IgG) Primary Antibody is intended for laboratory use for the qualitative detection of progesterone receptor (PR) antigen in sections of formalin-fixed, paraffin-embedded tissue on a VENTANA automated slide stainer with VENTANA detection kits and ancillary reagents. CONFIRM anti-PR (1E2) is directed against an epitope present on human progesterone receptor protein located in the nucleus of PR positive normal and neoplastic cells. CONFIRM anti-PR (1E2) 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.
Ventana's CONFIRM anti-Progesterone Receptor (1E2) Rabbit Monoclonal Primary Antibody specifically binds to progesterone receptor antigen located in the nuclear region of a variety of normal and neoplastic tissues. The antibody is diluted in 0.05 M Tris-HCl with 2% carrier protein, and 0.1% 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 10 mg/mL. Specific antibody concentration is approximately 1 µg/mL. CONFIRM anti-PR (1E2) is a rabbit monoclonal antibody produced as a cell culture supernatant.
The provided text describes the 510(k) summary for the CONFIRM anti-Progesterone Receptor (1E2) Rabbit Monoclonal Primary Antibody. This document focuses on demonstrating substantial equivalence to a predicate device, rather than defining and proving against specific acceptance criteria for a novel device. Therefore, the information typically requested for acceptance criteria and a study proving a device meets those criteria is not explicitly presented in the same way as for a de novo device or a device with new performance claims.
Instead, the study aims to show agreement between the new device and the predicate device. The acceptance criteria, therefore, are implicitly related to achieving a high level of agreement.
Here's an interpretation based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
Implicit Acceptance Criteria for Substantial Equivalence:
| Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Agreement with Predicate) |
|---|---|---|
| Positive Agreement | High level of agreement with the predicate device (implied > 85%) | CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%. |
| CONFIRM anti-PR (1E2) on BenchMark XT vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%. | ||
| CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. CONFIRM anti-PR (1E2) on BenchMark XT: Greater than 85%. | ||
| Negative Agreement | High level of agreement with the predicate device (implied > 85%) | CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%. |
| CONFIRM anti-PR (1E2) on BenchMark XT vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%. | ||
| CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. CONFIRM anti-PR (1E2) on BenchMark XT: Greater than 85%. | ||
| Overall Agreement | High level of agreement with the predicate device (implied > 85%) and between different platforms of the new device (implied > 85%) | CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%. |
| CONFIRM anti-PR (1E2) on BenchMark XT vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%. | ||
| CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. CONFIRM anti-PR (1E2) on BenchMark XT: Greater than 85%. |
Note: The document states "greater than 85%" for agreement rates, implying this was the threshold for acceptable performance for substantial equivalence to the predicate.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: Approximately 120 negative and 216 positive cases of breast cancer (total = 336 cases).
- Data Provenance: Not explicitly stated, but the study design suggests retrospective use of archived breast cancer tissue samples, representing a "clinical range of the assay." The cases were "randomly assigned to three study sites," which implies that the data was collected at multiple institutions. Country of origin is not mentioned.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts used to establish the ground truth for the test set. It mentions that "This product should be interpreted by a qualified pathologist in conjunction with histological examination, relevant clinical information, and proper controls." However, for the study to compare performance, it's not detailed how the initial classification of positive/negative cases was done or if an independent panel established a reference standard for the test set. Given it's a comparison study to a predicate, it's possible that the "ground truth" was established by the predicate device's results as an established standard, or by routine pathology reports prior to the study.
4. Adjudication Method for the Test Set
The adjudication method for establishing the ground truth of the test set is not explicitly mentioned. The study design focuses on comparing the staining performance of the new device against the predicate device. It does not detail a process for resolving discrepancies in initial diagnosis or a separate ground truth establishment.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, and Effect Size
Yes, a multi-site, multi-reader study was conducted.
- Type of Study: "A randomized, multi-site, multi-reader study was conducted to compare the staining performance of the CONFIRM anti-PR (1E2) on the BenchMark ULTRA instrument and on the BenchMark XT instrument to that of the Dako FLEX Monoclonal Mouse Anti-Human Progesterone Receptor Clone PgR 636 Ready-To-Use (FLEX anti-PgR (636)) on the Dako Autostainer Plus."
- Effect Size of Human Readers with vs. without AI Assistance: This information is not applicable here. This study is for an immunohistochemistry (IHC) antibody, which is a diagnostic reagent, not an AI or software device that assists human readers. The readers (pathologists) interpret the stained slides, but there is no "AI assistance" component described in this context. The study compares the performance of different reagents/platforms as interpreted by human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
This information is not applicable. The device is an antibody (reagent) for immunohistochemistry, which requires a human pathologist for interpretation. There is no algorithm or standalone performance without human interpretation.
7. The Type of Ground Truth Used
The type of ground truth used is not explicitly stated as a separate, independently established reference standard. Given the nature of a substantial equivalence study for an IHC antibody, the "ground truth" for comparison is likely the performance or results obtained using the predicate device (Dako FLEX Monoclonal Mouse Anti-Human Progesterone Receptor Clone PgR 636) or potentially prevailing clinical consensus based on established pathological diagnosis of the breast cancer cases included in the study. The study measures agreement with the predicate.
8. The Sample Size for the Training Set
No training set is mentioned or applicable for this type of device. The CONFIRM anti-PR (1E2) is a monoclonal antibody (a biological reagent), not a machine learning model that requires training data. Non-clinical performance data included testing on a "required panel of normal tissues" for tissue specificity, but this is not a "training set" in the context of an AI/ML device.
9. How the Ground Truth for the Training Set was Established
Not applicable as there is no training set for this type of device.
§ 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.