(91 days)
Ready-to-Use Format
For in vitro diagnostic use.
BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) is a monoclonal antibody intended to the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-III systems. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells.
Progesterone Receptor Clone (16) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. 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.
Progesterone Receptor Clone (16) is optimized for use on the Leica Biosystems automated BOND-MAX or BOND-III systems using the BOND Polymer Refine Detection kit.
Concentrated Liquid Antibody Format
For in vitro diagnostic use.
Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone (16) (Concentrated Liquid Antibody Format) is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. Progesterone Receptor Clone (10) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells.
Progesterone Receptor Clone (16) Monoclonal Antibody (Concentrated Liquid Antibody Format) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. 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.
Progesterone Receptor (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant. This antibody is utilized to perform a qualitative immunohistochemical (IHC) assay to identify Progesterone Receptor expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination.
Progesterone Receptor (PGR) Clone 16 Primary Antibody is provided in a Ready-to-Use (RTU) and a concentrated liquid format. The RTU format is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative and is provided in two volumes (7 mL and 30 mL). The total protein concentration is approximately 10 mg/mL and the total antibody concentration is greater than or equal to 1 mg/L as determined by ELISA. The RTU format is optimally diluted for use on the automated BOND-MAX and BOND-III instrument staining platforms in combination with BOND Polymer Refine Detection (DS9800). The concentrated liquid format is provided so that customers may utilize manual staining protocols. The concentrated liquid format is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative. The total protein concentration is determined on a per batch basis and is described on the vial label, and the antibody concentration is greater than or equal to 324.0 mg/L as determined by ELISA.
The BOND-MAX and BOND-III instruments are fully automated slide stainers that perform automated deparaffinization (dewaxing), antigen retrieval, immunohistochemistry (IHC) staining/in situ hybridization (ISH) staining, and counterstaining. The major components of the BOND staining platforms are the processing module, computer (BOND controller), handheld ID scanner, and slide label printer. The BOND staining platforms are composed of a number of discrete software components including the BOND application software, BOND instrument/processing module software, BOND service software, and Laboratory interface system - integration package (LIS-IP).
Here's a breakdown of the acceptance criteria and study details based on the provided text:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state numerical acceptance criteria for immunoreactivity or stability beyond "met acceptance criteria". However, the repeatability and reproducibility sections do provide numerical agreements and state that they met criteria. The method comparison also provides numerical agreements and states it met acceptance criteria.
| Performance Metric | Acceptance Criteria (Implicit from "met acceptance criteria") | Reported Device Performance |
|---|---|---|
| Intra-run Repeatability | "met acceptance criteria" | Overall Percent Agreement (OPA): 96.2% (51/53; 95% CI: 87.2% to 99.0%) |
| Positive Percent Agreement (PPA): 96.3% (26/27; 81.7% - 99.3%) | ||
| Negative Percent Agreement (NPA): 96.2% (25/26; 81.1% - 99.3%) | ||
| Inter-day Repeatability | "met acceptance criteria" | OPA: 98.8% (479/485; 95% CI: 97.3% - 99.4%) |
| PPA: 100% (198/198; 98.1% - 100%) | ||
| NPA: 97.9% (281/287; 95.5% - 99.0%) | ||
| Inter-instrument Repeatability | "met acceptance criteria" | OPA: 98.8% (479/485; 95% CI: 97.3% - 99.4%) |
| PPA: 100% (198/198; 98.1% - 100%) | ||
| NPA: 97.9% (281/287; 95.5% - 99.0%) | ||
| Inter-lot Repeatability | "met acceptance criteria" | OPA: 98.8% (479/485; 95% CI: 97.3% - 99.4%) |
| PPA: 100% (198/198; 98.1% - 100%) | ||
| NPA: 97.9% (281/287; 95.5% - 99.0%) | ||
| Inter-laboratory Reproducibility | "met acceptance criteria" | Average Positive Agreement (APA): 96.2% (95% CI: 94.5% - 97.6%) |
| Average Negative Agreement (ANA): 95.7% (95% CI: 93.9% - 97.3%) | ||
| Average Overall Agreement (AOA): 95.9% (95% CI: 94.3% - 97.4%) (Across 3 labs) | ||
| Inter-pathologist Reproducibility | "met acceptance criteria" | Average Positive Agreement (APA): 94.1% (95% CI: 92.0% - 95.8%) |
| Average Negative Agreement (ANA): 93.4% (95% CI: 91.1% - 95.3%) | ||
| Average Overall Agreement (AOA): 93.7% (95% CI: 91.7% - 95.5%) (Across 3 pathologists) | ||
| Method Comparison (Subject vs. Predicate) | "met acceptance criteria" | Positive Percent Agreement: 95.5% (95% CI: 91.9%-97.5%) |
| Negative Percent Agreement: 95.7% (95% CI: 92.2%-97.6%) | ||
| Overall Percent Agreement: 95.6% (95% CI: 93.3%-97.1%) | ||
| Stability | "met acceptance criteria" | Product shelf-life is conservatively set at 18 months, unchanged from the predicate device. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Intra-run Repeatability: 6 unique breast tumor tissue cases.
- Inter-day, Inter-instrument, Inter-lot Repeatability: 27 unique breast tumor tissue cases.
- Reproducibility (Inter-laboratory & Inter-pathologist): 135 unique FFPE breast tumor tissue cases.
- Method Comparison: A total of 455 cases (implied from the table total).
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It only mentions "human progesterone receptor in formalin-fixed, paraffin-embedded tissue" and "breast tumor tissue cases."
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
- Reproducibility (Inter-laboratory & Inter-pathologist): 3 pathologists were involved in scoring the slides, one per site. Their qualifications are not specified beyond "pathologist."
- Other studies (Repeatability, Method Comparison): The document does not explicitly state the number of experts used for establishing ground truth or their qualifications for these studies. The scoring for repeatability likely involved expert assessment, and method comparison relied on comparing the subject device to a predicate device, which would also implicitly rely on established expert assessment standards.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The document does not describe an explicit adjudication method (like 2+1 or 3+1) for resolving discrepancies. For the reproducibility studies, agreements are calculated between observers, suggesting individual pathologist assessments were compared rather than being subjected to a specific adjudication process to establish a single "ground truth" per case.
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
This document describes the performance of an immunohistochemistry reagent/antibody, not an AI-assisted diagnostic device. Therefore, an MRMC comparative effectiveness study involving human readers improving with AI assistance is not applicable and was not performed. The studies focus on the analytical performance and reproducibility of the staining process and the antibody's interpretation by pathologists.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is an immunohistochemistry reagent, not an algorithm. Therefore, a standalone algorithm-only performance study is not applicable and was not performed. The performance is intrinsically linked to its use in a laboratory setting by human interpretation.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the evaluations appears to be based on pathology assessments by qualified pathologists, specifically following ASCO/CAP guidelines (≥1% cut-off) for determining PR status in breast cancer tissue. This is indicated by phrases like "scored according to ASCO/CAP guidelines" and "clinical interpretation of any staining or its absence should be complemented by morphological studies... by a qualified pathologist."
8. The sample size for the training set
The document describes performance studies, not the development or training of an AI model. Therefore, there is no mention of a "training set" or its sample size.
9. How the ground truth for the training set was established
As this is not an AI model, there is no training set and thus no ground truth establishment process described for one. The "training" of the antibody is inherent to its development and optimization for specific antigen binding, which is evaluated through immunoreactivity and analytical performance studies.
§ 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.