(56 days)
Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636 is intended for use in the qualititative detection of human progesterone receptor in tissue sections of human breast cancer by immunohistochemistry. The assay is intended for use as an aid in selecting patients most likely to benefit from hormonal therapy as well as an aid in the prognosis and management of breast cancer.
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Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, (Product Code No. M3569) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant. The antibody is supplied in 0.05M Tris-HCl buffer, pH 7.2, containing fetal bovine serum and 15mM sodium azide. (0.2 mL and 1 mL total volume).
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Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use Antibody (Product Code No. N1630) consists of a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and pre-diluted in 0.05M Tris-HCl buffer, pH 7.6, containing fetal bovine serum and 15mM sodium azide (7mL and 11 mL sizes).
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Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use Antibody (Product Code No. NP008) consists of a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and pre-diluted in 0.05M Tris-HCl buffer, pH 7.6, containing fetal bovine serum and 15mM sodium azide (7mL total volume).
Here's an analysis of the provided text, focusing on the acceptance criteria and the study that proves the device meets those criteria:
Device: DAKO Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636 (M3569, N1630, NP008)
Intended Use: Qualitative detection of human progesterone receptor (PgR) in tissue sections of human breast cancer by immunohistochemistry. Aid in selecting patients most likely to benefit from hormonal therapy and in the prognosis and management of breast cancer.
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria (Inferred from Predicate Equivalence) | Reported Device Performance (vs. Abbott PR-EIA) |
|---|---|
| Overall Concordance: High agreement with predicate device (implied by "substantial equivalence") | 90.7% |
| Sensitivity: High detection of positive cases (implied) | 87.2% |
| Specificity: High detection of negative cases (implied) | 94% |
| Kappa Statistic: Strong agreement (implied) | 0.8139 (almost perfect correlation) |
| Tissue Reactivity (Normal Tissues): Specific staining patterns as expected (implied by "Guidance for Submissions of Immunohistochemistry Applications to the FDA") | As per Table 1 (Breast, Cervix, Pituitary, Prostate, Uterus positive; other tissues negative) |
| Tumor Reactivity: Appropriate staining of known tumor types (implied) | Breast cancer (5/11), uterine (2/2), ovarian (2/6), endometrial (2/2) carcinomas stained strongly; Medullary thyroid (1/2), testicular yolk sac positive; melanoma, lymphoma, neuroendocrine, neural tumors negative. |
| Western Blot Reactivity: Specific binding to PR-A and PR-B without significant cross-reactivity (implied) | Reacted strongly with PR-A and PR-B from T47D cells; little/no cross-reactivity with other proteins; reacted equally with unliganded and liganded PR; epitope within amino terminal domain (aa 165-533). |
Note: The document explicitly states the "Concordance calculation showed concordance = 88 / 97 = 90.7% in this trial. Using the PR-ElA as the predicate device, sensitivity was determined to be 41/47 = 87.2% while specificity was determined to be 47/50, = 94%. The Kappa statistic indicated a 0.8139 kappa, which corresponds to an almost perfect correlation for the qualitative assessment." These values are direct performance metrics against the predicate. The criteria are indirectly inferred as the targets needed to demonstrate substantial equivalence.
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size for Comparison Study: 97 breast carcinoma specimens were successfully evaluated for comparison with the Abbott PR-EIA. (Initially, 106 tests were performed on 101 specimens, but 2 had too little tumor tissue and 2 lacked corresponding PR-EIA results, reducing the comparison set to 97).
- Data Provenance: Not explicitly stated, but it's a comparison to the Abbott PR-EIA which is a predicate device, likely indicating retrospective use of existing archived samples with known PR-EIA results. The country of origin is not specified, but given DAKO's location (USA) and the FDA submission, it's reasonable to assume the data is from the US or a region with comparable standards.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications:
- Not explicitly stated for the comparison study. The ground truth for the comparison study was established by the Abbott PR-EIA, which is itself a laboratory assay. Therefore, the "ground truth" for this specific comparison was the result generated by the predicate device, rather than a panel of human experts reviewing the slides.
- For the immunohistochemistry (IHC) on normal and tumor tissues, the evaluation of staining patterns and intensities ("3+ staining intensity," "2+ staining intensity") would have been performed by qualified pathologists or laboratory personnel with expertise in IHC interpretation. However, the exact number and qualifications are not mentioned.
4. Adjudication Method for the Test Set:
- Not applicable in the context of the comparison study, as the ground truth was the result from the predicate Abbott PR-EIA assay. The DAKO device's result was compared directly against this predicate result.
- For the initial normal and tumor tissue reactivity studies, the evaluation of staining was reported as findings. There is no mention of an adjudication process (e.g., 2+1, 3+1) for interpreting IHC results in the document; typically, this would be handled by a single qualified individual or through internal quality control mechanisms.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement:
- No, an MRMC comparative effectiveness study was not done. The study presented is a direct comparison of the DAKO device's output against a predicate device's output (Abbott PR-EIA) on breast cancer specimens. It does not involve human readers' interpretation with and without AI assistance to measure improvement.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
- This device is an antibody reagent for immunohistochemistry (IHC). IHC is inherently a "standalone" assay in the sense that the antibody binds to the target protein in the tissue, and the staining is then visually interpreted.
- The "performance" described here is the ability of this antibody to produce staining results that correlate with a predicate assay for progesterone receptor. There is no "algorithm" or "AI" involved, nor is there a "human-in-the-loop" component beyond the standard interpretation of an IHC slide by a pathologist. This is a traditional IVD reagent, not an AI-powered diagnostic device.
7. The Type of Ground Truth Used:
- For the comparison study: The ground truth was results from the predicate device, Abbott PR-EIA.
- For the normal and tumor tissue reactivity studies: The ground truth was based on expected biological expression of progesterone receptor in various normal and tumor tissues, evaluated by presumably qualified laboratory personnel/pathologists through visual interpretation of IHC staining.
8. The Sample Size for the Training Set:
- Not applicable / not provided. This is an antibody reagent, not a machine learning algorithm. Therefore, there is no "training set" in the computational sense. The antibody's specificity and reactivity are inherent to its molecular properties and laboratory development, not trained on data.
9. How the Ground Truth for the Training Set Was Established:
- Not applicable. As stated above, there is no training set for this type of device. The development of the antibody (Clone PgR 636) and confirmation of its binding characteristics (e.g., in Western blot described) are part of its development, but not "training" in the context of an AI/ML algorithm.
§ 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.