(254 days)
For in Vitro Diagnostic Use:
QCS HER2 ImmunoControls, are intended for a laboratory to control semi-quantitative immunohistochemistry using different HER2/neu antibodies. Each QCS HER2 control slide contains four control sections prepared from breast cancer ccll lines that represent different levels of Her-2/neu protein expression. The cells are formalin-fixed and paraffin-embedded. These controls ensure that performance of immunohistochemical staining is consistent in one laboratory over time and also aids in correlation with the results of other laboratories.
QCS HER2 ImmunoControls: This product provides appropriate control for semi-quantitative immunohistochemistry using polyclonal or monoclonal HER2/neu antibodies. Each slide contains four control sections prepared from breast cancer cell lines that represent different levels of Her-2/neu protein expression (-, 1+, 2+, 3+). These cells are formalin-fixed and paraffin-embedded, the slide is positively charged.
Here's a breakdown of the acceptance criteria and study information for the QCS HER2 ImmunoControls, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance:
The document describes the device as a control with expected staining levels for different cell lines when tested with specific HER2 antibodies. The acceptance criteria are implicit in the "expected results" for the QCS HER2 Controls as presented in Table 1, which are compared directly to the predicate device, DAKO HER2 Controls.
| Acceptance Criteria (Expected Staining Level using listed Antibodies) | Reported Device Performance (QCS HER2 Controls) |
|---|---|
| When tested with CB11 (Cell Marque) antibody: | |
| MDA-361 cell line: 3+ | MDA-361 cell line: 3+ |
| MDA-453 cell line: 2+ | MDA-453 cell line: 2+ |
| MDA-175 cell line: 1+ | MDA-175 cell line: 1+ |
| MCF-7 cell line: - | MCF-7 cell line: - |
| When tested with HercepTest (DAKO) antibody: | |
| MDA-361 cell line: 3+ | MDA-361 cell line: 3+ |
| MDA-453 cell line: 2+ | MDA-453 cell line: 2+ |
| MDA-175 cell line: 1+ | MDA-175 cell line: 1+ |
| MCF-7 cell line: - | MCF-7 cell line: - |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size for Test Set: Not explicitly stated. The "Multiple studies" sentence suggests more than one evaluation, but no specific number of samples or experiments is provided beyond the cell lines themselves.
- Data Provenance: Not explicitly stated for the specific comparison shown in Table 1. However, the cell lines (MDA-361, MDA-453, MDA-175, MCF-7) are human breast cancer cell lines. The referenced studies (Rhodes et al., Taylor CR, Ruby SG & McNally AC) are published scientific articles, implying a general scientific/medical community provenance. The context of a 510(k) summary implies the data was generated or compiled for regulatory submission. It is retrospective in the sense that the data in Table 1 represents established characteristics of these cell lines, likely from previous research, rather than a new prospective clinical trial.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
- Number of Experts: Not specified.
- Qualifications of Experts: Not specified. The data in Table 1 reflects "expected results" which are typically established through extensive research by pathologists and other specialists skilled in immunohistochemistry. The external references imply a basis in published, peer-reviewed scientific literature, often involving expert consensus or established laboratory practices.
4. Adjudication Method for the Test Set:
- Adjudication Method: Not specified. The "expected results" suggest a prior determination of the staining levels, likely based on established laboratory protocols and expert evaluation, rather than an explicit adjudication process for this specific submission.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
- No, an MRMC comparative effectiveness study was NOT done. This device is a control slide for immunohistochemistry, not an AI diagnostic tool for interpreting images. The study focuses on demonstrating the control's intended performance (i.e., showing specific staining patterns) with standard antibodies, not on reader performance with or without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Not applicable. This device is a physical control slide, not an algorithm. Therefore, "standalone performance" in the context of an algorithm is not relevant.
7. The Type of Ground Truth Used:
- Ground Truth Type: Expert consensus/established biological characteristics. The "expected level of staining" for the cell lines, as recognized in the scientific community and presumably confirmed by the manufacturer's testing, serves as the ground truth. This is supported by the direct comparison to the "Expected level of staining for valid results on the DAKO cell line control slide, as given in the HercepTest protocol." This indicates that the ground truth is based on established, conventional laboratory understanding of these cell lines' HER2 expression.
8. The Sample Size for the Training Set:
- Not applicable. This product is a control device, not an AI algorithm that requires a training set. The cell lines themselves are the "samples" whose characteristics are being confirmed.
9. How the Ground Truth for the Training Set was Established:
- Not applicable. As this is not an AI algorithm, there is no "training set" in the conventional sense. The "ground truth" for the cell lines' HER2 expression levels would have been established through extensive research, molecular characterization, and immunhistochemical testing over time in research and diagnostic laboratories. The references provided (e.g., Rhodes et al.) highlight studies that contribute to establishing such control materials and their expected 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.