(29 days)
For In Vitro Diagnostic Use. The Prostate-63 Cancer Diagnostic Test features a mouse monoclonal antibody, clone 4A4, that recognizes the human p63 protein in the nucleus of prostatic basal cells and urothelial tissues. This test is intended for laboratory use to qualitatively identify by immunohistochemistry the p63 antigen in histological sections from formalin-fixed paraffin-embedded tissue of normal and/or pathological prostate tissue obtained by needle biopsy or surgical procedures. The presence or absence of p63 staining aids the pathologist in the differential diagnosis of prostate cancer in conjunction with morphological findings seen with hematoxylin and eosin staining complemented by proper controls. The clinical interpretation of any staining or its absence should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
The Prostate-63 Cancer Diagnostic Test features a mouse monoclonal antibody, clone 4A4, that recognizes the human p63 protein in the nucleus of prostatic basal cells and urothelial tissues. The 4A4 anti-p63 monoclonal antibody is provided at a working dilution in a buffer containing 50 mM Tris-HCl, pH 7.2, and 15 mM sodium azide. The immunogen is p63 recombinant protein comprising amino acids 1-205 of the N-terminal portion of human △Np63 protein.
The provided text describes the intended use and background of the Prostate-63 Cancer Diagnostic Test, as well as a list of references to relevant studies. However, it does not contain a dedicated section detailing specific acceptance criteria or an explicit study proving the device meets those criteria in a structured manner typical of a regulatory submission.
Instead, the performance characteristics are discussed by referencing several scientific publications. The acceptance of this device by the FDA (as indicated by the 510(k) clearance letter) implies that the provided data (including these referenced studies) were deemed sufficient to demonstrate substantial equivalence to a predicate device.
Based on the provided text, here's what can be extracted and inferred:
1. Table of Acceptance Criteria and Reported Device Performance:
Since explicit acceptance criteria are not stated, the table below will summarize the implied performance based on the claims and references provided. The "acceptance criteria" here are interpreted as the expected performance of a basal cell marker for prostate cancer diagnosis.
| Acceptance Criteria (Inferred from clinical utility) | Reported Device Performance (as per references cited) |
|---|---|
| Stains prostatic basal cells of normal glands in needle biopsies with high sensitivity. | Sensitivity approaching 100% (Wu et al., 2004). |
| Stains benign glands derived from TURP. | Positive in 11 of 12 (95%) sections (Shah et al., 2002). |
| Does not stain neuroendocrine or luminal, secretory cells of the prostate. | Signoretti et al., 2000. |
| Basal cells are absent from invasive prostate carcinoma. | Hedrick and Epstein, 1995 (cited in a longer version of the extract not provided in full in the prompt) / General understanding of prostate carcinoma pathology. |
| Offers advantages over traditional basal cell markers (e.g., diffuse cytoplasmic stain vs. distinct nuclear stain). | Dark nuclear staining pattern (Shah et al., 2002). |
| Recognizes all known p63 protein isoforms on western blots and shows strong nuclear staining in relevant cells. | Yang et al., 1998. |
| Recognizes basal cells in mouse tissues (skin, breast, prostate, urothelia) but not in p63-deficient embryos. | Yang et al., 1999. |
2. Sample Size Used for the Test Set and Data Provenance:
The document primarily references external studies rather than detailing a single "test set" for this specific 510(k) submission. Therefore, the sample sizes and provenance would be varied across the referenced papers.
- Wu et al., 2004: "100 consecutive prostate carcinoma diagnosed by needle biopsies." (Implies retrospective data, likely from a single institution, but country of origin not specified).
- Shah et al., 2002: "11 of 12 (95%) sections derived from transurethral resection of the prostate (TURP)." (Small sample, likely retrospective, country of origin not specified).
- Other cited studies (Signoretti et al., 2000; Weinstein et al., 2002; Shah et al., 2004; Davis et al., 2002; Yang et al. publications) would have their own sample sizes and methodologies, which are not detailed in this summary.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:
This information is not provided in the 510(k) summary. Given that the references are peer-reviewed publications, it's highly probable that pathologists were involved in establishing diagnoses and ground truth, but their number and specific qualifications are not stated in this document.
4. Adjudication Method:
This information is not provided in the 510(k) summary.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No MRMC study is explicitly mentioned as part of the 510(k) submission. The document discusses the utility of the antibody in facilitating diagnosis and offers advantages over other markers, implying improved effectiveness for pathologists, but a formal MRMC study calculating an effect size of human readers with vs. without AI assistance (which is not applicable here as it's an antibody, not an AI) is not presented.
6. Standalone (Algorithm Only) Performance:
This is not an AI/algorithm-based device, but rather an immunohistochemical reagent. Therefore, the concept of "standalone performance" for an algorithm is not applicable. The performance is inherently tied to human interpretation by a pathologist.
7. Type of Ground Truth Used:
The ground truth for the referenced studies and the intended use of this diagnostic test is based on pathology findings (morphological findings seen with hematoxylin and eosin staining, and the specific characteristics of prostate cancer identified by qualified pathologists).
8. Sample Size for the Training Set:
The document describes the origin and specificity of the antibody (Immunogen: p63 recombinant protein, tested on BHK cells, mouse tissues), but it does not describe a "training set" in the context of machine learning or an algorithm. The development of the antibody involved biological and laboratory research, which would implicitly include various experiments and testing but not a formal "training set" as understood for AI.
9. How the Ground Truth for the Training Set Was Established:
Again, for an antibody reagent, there isn't a "training set" with established ground truth in the AI sense. The antibody's specificity and reactivity were established through:
- Immunogen: p63 recombinant protein.
- Testing on BHK cells expressing p63 cDNAs vs. control vectors.
- Immunohistochemistry in mouse tissues, comparing staining in p63-positive tissues with those from p63-deficient embryos (Yang et al., 1999).
- Western blot analysis for recognition of p63 protein isoforms (Yang et al., 1998).
These methods established the biological specificity and performance characteristics of the 4A4 anti-p63 monoclonal antibody.
§ 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.