(52 days)
The Cepheid Xpert® C. difficile/Epi Control Panel is intended for use as external assayed positive and negative quality controls to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Clostridioides (Clostridium) difficile performed with the Cepheid Xpert® C. difficile/Epi assay on the GeneXpert® Dx System. The controls comprise cultured and inactivated Clostridioides (Clostridium) difficile 027-NAP1-B1 as the positive control and Clostridium sordellii as the negative control.
The Cepheid Xpert® C. difficile/Epi Control Panel is not intended to replace manufacturer controls provided with the device.
The Cepheid Xpert® C. difficile/Epi Control Panel to monitor DNA extraction, amplification and detection of the Cepheid Xpert® C. difficile/Epi assay. The Cepheid Xpert® C. difficile/Epi Control Panel contains cultured microorqanisms inactivated by heat treatments. Each Cepheid Xpert® C. difficile/Epi Control Panel consists of 6 individually packaged positive control swabs and 6 individually wrapped negative control swabs. Each positive control swab contains cultured and inactivated Clostridioides difficile at a target level that is designed to provide reproducible performance above the limit of detection of the Cepheid Xpert® C. difficile/Epi assay. The positive control swab is expected to produce positive results for each of the genes targeted by the Cepheid Xpert® C. difficile/Epi assay: toxin B (tcdB), binary toxin (CDT) and the variant requlator gene, tcdC. Each negative control swab contains Clostridium sordelli. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.
Here's an analysis of the provided text to fulfill your request regarding acceptance criteria and the study proving device performance:
Device Name: Cepheid Xpert C. difficile/Epi Control Panel
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a codified manner for a diagnostic accuracy study (e.g., target sensitivity, specificity). Instead, it presents the results of a precision and reproducibility study to demonstrate the performance of the control panel itself. The implicit acceptance criterion for a control panel is 100% agreement with the expected result (positive controls yield positive results, negative controls yield negative results).
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Positive Controls: 100% agreement with expected positive results | Clostridioides difficile: 91/91 (100%) agreement |
| Negative Controls: 100% agreement with expected negative results | Clostridium sordellii: 91/91 (100%) agreement |
| Consistent Ct values (low %CV) across sites and operators | Mean Ct (%CV) for tcdB: 29.5 (2.2) |
| Mean Ct (%CV) for Binary Toxin: 28.9 (2.2) | |
| Mean Ct (%CV) for tcdC: 28.8 (2.2) | |
| Mean Ct (%CV) for SPC (Negative Controls): 32.5 (2.0) |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 91 positive control tests and 91 negative control tests.
- For the positive control: 30 at Site 1, 31 at Site 2, 30 at Site 3.
- For the negative control: 30 at Site 1, 31 at Site 2, 30 at Site 3.
- Data Provenance: The document does not specify the country of origin. The study was conducted as a "precision and reproducibility study," which is typically prospective, designed to evaluate product consistency.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
Not applicable. This study evaluates a quality control panel, not a diagnostic device's ability to identify disease in patient samples. The "ground truth" for the test set is established by the known composition of the control panel itself (i.e., the positive control contains C. difficile, and the negative control contains C. sordellii). There are no human experts classifying images or results for ground truth in this context.
4. Adjudication Method for the Test Set
Not applicable. As noted above, the "ground truth" is inherent in the design of the control panel. The performance is assessed against the expected molecular detection profile of the contained microorganisms.
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
Not applicable. This is a study for a quality control panel, not an AI-powered diagnostic device. No human readers or AI assistance are involved in interpreting the results beyond standard laboratory procedures for running the GeneXpert® Dx System.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The study inherently evaluates the "standalone" performance of the control panel in conjunction with the Cepheid Xpert® C. difficile/Epi assay on the GeneXpert® Dx System. The control panel is a reagent designed to monitor the assay's performance. The results (presence/absence of targets, Ct values) are generated directly by the GeneXpert system without further human interpretation beyond confirming the system's output.
7. The Type of Ground Truth Used
The ground truth is based on the known composition of the manufactured control materials. The positive control contains cultured and inactivated Clostridioides difficile, and the negative control contains Clostridium sordellii. The expected results are therefore known beforehand based on the microbial content.
8. The Sample Size for the Training Set
Not applicable. This device is a quality control panel, not an algorithm or AI system that requires a "training set." The study evaluated the performance of the manufactured controls.
9. How the Ground Truth for the Training Set Was Established
Not applicable (as described in point 8).
§ 866.3920 Assayed quality control material for clinical microbiology assays.
(a)
Identification. An assayed quality control material for clinical microbiology assays is a device indicated for use in a test system to estimate test precision or to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. This type of device consists of single or multiple microbiological analytes intended for use with either qualitative or quantitative assays.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation and information concerning the composition of the quality control material, including, as appropriate:
(i) Analyte concentration;
(ii) Expected values;
(iii) Analyte source;
(iv) Base matrix;
(v) Added components;
(vi) Safety and handling information; and
(vii) Detailed instructions for use.
(2) Premarket notification submissions must include detailed documentation, including line data as well as detailed study protocols and a statistical analysis plan used to establish performance, including:
(i) Description of the process for value assignment and validation.
(ii) Description of the protocol(s) used to establish stability.
(iii) Line data establishing precision/reproducibility.
(iv) Where applicable, assessment of matrix effects and any significant differences between the quality control material and typical patient samples in terms of conditions known to cause analytical error or affect assay performance.
(v) Where applicable, identify or define traceability or relationship to a domestic or international standard reference material and/or method.
(vi) Where applicable, detailed documentation related to studies for surrogate controls.
(3) Premarket notification submissions must include an adequate mitigation (e.g., real-time stability program) to the risk of false results due to potential modifications to the assays specified in the device's 21 CFR 809.10 compliant labeling.
(4) Your 21 CFR 809.10 compliant labeling must include the following:
(i) The intended use of your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following:
(A) Assayed control material analyte(s);
(B) Whether the material is intended for quantitative or qualitative assays;
(C) Stating if the material is a surrogate control; and
(D) The system(s), instrument(s), or test(s) for which the quality control material is intended.
(ii) The intended use in your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following statement: “This product is not intended to replace manufacturer controls provided with the device.”
(iii) A limiting statement that reads “Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.”