(366 days)
For in vitro diagnostic use.
Monoclonal Rabbit Anti-Human Estrogen Receptor a (ER a) antibody, Clone SP1, may be used in the semi-quantitative detection of human estrogen receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer by immunohistochemistry. The information gained by this assay can aid in assessing the likelihood of response to therapy as well as in the prognosis and management of breast cancer patients.
Clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Dako Monoclonal Rabbit Anti-Human Estrogen Receptor a antibody, Clone SP1 is a semiquantitative immunohistochemical (IHC) kit assay to identify estrogen receptor (ER) expression in normal and neoplastic tissues routinely processed and paraffin-embedded.
The provided text describes the Dako Monoclonal Rabbit Anti-Human Estrogen Receptor a antibody, Clone SP1, an immunohistochemical (IHC) assay. The document is a 510(k) summary and associated FDA correspondence, which focuses on demonstrating substantial equivalence to a predicate device rather than presenting specific acceptance criteria and detailed study results for a novel device.
Therefore, much of the requested information regarding detailed acceptance criteria, specific performance metrics, sample sizes, ground truth establishment, and MRMC studies is not explicitly present in the provided text.
Here's an analysis of what can be extracted based on the document's content:
1. Table of Acceptance Criteria and Reported Device Performance:
The document states that "Performance characteristics evaluated for the Estrogen Receptor Clone SP1 IHC assay include results on analytical specificity and sensitivity, precision, reproducibility and method comparison testing." It then states: "Results of all testing conducted substantial equivalence to the predicate device listed above."
This implies that the acceptance criterion was achieving substantial equivalence to the predicate device, especially across these performance characteristics. However, specific numerical targets for these characteristics are not provided.
| Acceptance Criteria (Implied) | Reported Device Performance (Implied) |
|---|---|
| Demonstrate substantial equivalence to predicate device (Monoclonal Mouse ER 1D5/ER-2-123 in Dako ER/PR pharmDx™ Kit) for: | Substantial equivalence achieved. |
| - Analytical specificity | Met |
| - Analytical sensitivity | Met |
| - Precision | Met |
| - Reproducibility | Met |
| - Method comparison | Met |
2. Sample size used for the test set and data provenance:
- Sample size: The document does not specify the sample size (number of cases or samples) used for the testing that established substantial equivalence.
- Data provenance: Not explicitly stated. The document refers to "testing conducted," but provides no details on the origin, retrospective, or prospective nature of the data.
3. Number of experts used to establish the ground truth for the test set and their qualifications:
- Number of experts: Not specified.
- Qualifications: "Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist." This indicates that pathologists are involved in interpretation but does not detail their role in establishing a ground truth for testing.
4. Adjudication method for the test set:
- Not specified.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, and its effect size:
- An MRMC study is not mentioned. The focus is on the device's performance against a predicate device, not direct human reader improvement with or without the device.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- This device is an IHC antibody, which is a reagent used in a laboratory setting for manual or automated staining, subsequently interpreted by a pathologist. It is not an "algorithm" in the sense of AI. Therefore, the concept of "standalone performance" for an algorithm without a human-in-the-loop is not applicable in this context. The assay itself requires human interpretation.
7. The type of ground truth used:
- The document implies that the ground truth for comparing the new device against the predicate device would be based on the established accuracy of the predicate device and potentially agreement with clinical and morphological findings. The statement "Clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls" suggests that the ultimate ground truth incorporates pathological and clinical evaluation, but the specific method for establishing a gold standard for the comparison study is not detailed.
8. The sample size for the training set:
- This device is a biological reagent (antibody), not a machine learning algorithm that requires a "training set" in the conventional sense. Therefore, the concept of a training set size is not applicable.
9. How the ground truth for the training set was established:
- As explained above, the concept of a training set is not applicable to this type of device.
In summary:
The provided document is a regulatory submission focused on demonstrating substantial equivalence of a new IHC reagent to an existing one. It does not provide the detailed study design, acceptance criteria, specific performance metrics, or ground truth establishment methods that would be expected for a novel diagnostic algorithm or AI device as the questions imply. The study described is primarily a comparative study to establish equivalency to a predicate, rather than a de novo performance validation with detailed acceptance criteria.
§ 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.