(148 days)
Ventana Medical Systems' PGR Primary Antibody (Clone 1A6) may be used in immunohistochemical methods to aid in the identification of progesterone receptor (PGR) antigen in normal and neoplastic cells as an aid in the diagnosis of PGR positive tumors. The anti-PGR is intended for laboratory use to qualitatively stain PGR antigen in sections of formalin fixed, paraffin embedded tissue on a Ventana automated slide staining device. Detection chemistries used by Ventana to detect PGR are DAB, AEC, Alkaline phosphatase red and blue. Light microscopy is used to detect the staining of cell components. It is indicated for use as an aid in the management, prognosis and prediction of therapy outcome of breast cancer.
Ventana's PGR Primary Antibody (clone 1A6) is a monoclonal antibody which specifically binds to progesterone receptor antigen located in the nuclear region of a variety of normal and neoplastic tissues. The dispenser contains approximately 5 µg (50 test) or 25 µg (250 test) of mouse anti-human PGR monoclonal antibody. The total protein concentration of the reagent is approximately 10 mg/ml. Specific antibody concentration is approximately 1 ug/ml. Clone 1A6 is immunoglobulin class IgG, light chain kappa. There is no known irrelevant antibody in the preparation.
The provided text is a 510(k) summary for the Ventana PGR Primary Antibody (Clone 1A6). It details the device's purpose, comparison to a predicate device, and performance data from a validation study.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical targets in the document. Instead, the study aims to demonstrate substantial equivalence to the predicate device and satisfactory performance relative to an FDA-approved reference method (SBA/DCC). The "best agreement" with the reference method, particularly at a specific cutoff, implies the acceptance criteria.
| Acceptance Criteria (Implied) | Reported Device Performance (at ≥ 11% cutoff) |
|---|---|
| Best agreement/concordance with SBA/DCC | Concordance: 78% (76/98) with 95% CI of 68-85% |
| Acceptable sensitivity relative to SBA/DCC | Relative Sensitivity: 67.9% (36/53) with 95% CI of 54-80% |
| Acceptable specificity relative to SBA/DCC | Relative Specificity: 88.9% (40/45) with 95% CI of 76-96% |
| Appropriate tissue specificity (expected staining patterns) | Staining considered appropriate, with minor explanations for exceptions in normal tissues. Neoplastic tissue staining was expected. |
2. Sample size used for the test set and the data provenance
- Sample Size for Test Set: 100 breast cancer cases were initially chosen. After exclusions, 98 cases were analyzed.
- Data Provenance: Retrospective study, using archived formalin-fixed, paraffin-embedded breast carcinoma biopsies from a single investigative site. The country of origin is not explicitly stated but can be inferred as the USA, given the FDA submission context.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Number of Experts: The document explicitly mentions "The pathologist scoring the IHC was masked to the results of the PGR SBA/DCC." This indicates at least one qualified pathologist was involved in scoring the IHC slides. It does not specify if multiple pathologists independently scored or if consensus was reached among multiple pathologists for the IHC results.
- Qualifications of Experts: Assumed to be "qualified pathologist" as stated in the text and expected for this type of test. No further specific qualifications like years of experience are provided for the IHC scoring pathologist. The study also refers to a "qualified pathologist" evaluating the neoplastic tissues for specificity studies.
4. Adjudication method for the test set
- Primary Ground Truth: The SBA/DCC (Serum Binding Assay/Dextran Coated Charcoal) assay for PGR was the independent reference method used for comparison. The IHC test's performance was evaluated relative to this FDA-approved chemical cytosol receptor assay.
- IHC Scoring Adjudication: The document states that "Scoring of the benign elements was also performed to aid in discrepancy resolution."
- "Resolved" Data for Discrepancies: "Because SBA/DCC cannot distinguish between positivity of pathological and benign elements, the protocol allowed for the resolution of false negative PGR IHC to true negative if benign elements were positive and pathological elements did not stain. The results of these analyses are noted as 'Resolved'." This implies a form of adjudication or re-evaluation based on the pathologist's assessment of benign vs. pathological elements when there was a discrepancy between IHC and SBA/DCC. It's not a standard "+1" scheme; rather, it's a rule-based re-categorization for specific discrepancy types.
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 MRMC study was done. This study evaluates the performance of the Ventana PGR Primary Antibody (an IVD reagent), not an AI system. Therefore, there's no mention of human readers improving with or without AI assistance.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- This is a standalone test in the context of an IVD reagent. The Ventana PGR Primary Antibody is a reagent (antibody) for immunohistochemistry (IHC) performed on an automated staining device. Its performance is evaluated independently against a reference assay (SBA/DCC). It is not an AI algorithm and does not inherently involve a human-in-the-loop performance study in the way AI systems are typically evaluated. The "human" element is the pathologist's interpretation of the stained slides.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- The primary ground truth for validation was an FDA-approved chemical cytosol receptor assay for PGR: Serum Binding Assay/Dextran Coated Charcoal (SBA/DCC).
- Pathologist interpretation was used to score the IHC slides and for the resolution of discrepancies (distinguishing pathological from benign elements).
8. The sample size for the training set
- The document describes a validation study on a test set (98 cases). There is no explicit mention of a separate training set for the development of "Ventana PGR Primary Antibody (Clone 1A6)" itself, as it is a monoclonal antibody (reagent), not a machine learning algorithm that requires a training set in the conventional sense. The "development" of the antibody would involve biological processes and optimization, not data-driven training.
9. How the ground truth for the training set was established
- As noted above, there is no conventional "training set" in the context of this IVD reagent's development in the document. The ground truth (SBA/DCC results) was used for the validation (test) set to assess the antibody's performance.
§ 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.