(263 days)
The Cepheid Xpert®Respiratory Control Panel is intended for use as an external assayed positive and negative quality control to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Influenza A (H1N1) virus, Influenza A (H3N2) virus, Influenza B virus and Respiratory Syncytial Virus A performed with the Cepheid Xpert® Xpress Flu/RSV assay on the GeneXpert® Instrument System. The controls comprise cultured and inactivated Influenza A (H1N1) virus, Influenza A (H3N2) virus, Influenza B virus and Respiratory Syncytial Virus A as the positive control and Coxsackie virus B1 as the negative control.
The Cepheid Xpert®Respiratory Control Panel is not intended to replace manufacturer controls provided with the device.
The Cepheid Xpert® Respiratory Control Panel is used to monitor RNA extraction, amplification of the Cepheid Xpert® Xpress Flu/RSV assay. The Cepheid Xpert® Respiratory Control Panel contains cultured viruses inactivated by chemical or radiological treatments. Each Cepheid Xpert® Respiratory Control Panel consists of 6 individually packaged positive control swabs and 6 individually wrapped negative control swabs. Each positive control swab contains Influenza A (H1N1) virus, Influenza A (H3N2) virus, Influenza B virus and Respiratory syncytial virus A. Each negative control swab contains Coxsackie B1 virus. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.
The acceptance criteria and study proving the device meets them are described below for the Cepheid Xpert® Respiratory Control Panel.
1. Acceptance Criteria and Reported Device Performance
The core acceptance criterion for the Cepheid Xpert® Respiratory Control Panel, as demonstrated by the provided data, is 100% agreement between the expected and observed results for both positive and negative analytes.
| Analyte | Acceptance Criteria (Agreement %) | Reported Device Performance (Agreement %) |
|---|---|---|
| Positive Analytes | ||
| Influenza A (H1N1) | 100% | 100% (90/90) |
| Influenza A (H3N2) | 100% | 100% (90/90) |
| Influenza B | 100% | 100% (90/90) |
| Respiratory Syncytial Virus A | 100% | 100% (90/90) |
| Negative Analytes | ||
| Coxsackievirus B1 | 100% | 100% (91/91) |
It's important to note that the acceptance criteria are inferred from the demonstrated performance, as explicit numerical acceptance criteria for agreement percentages are not directly stated but consistently met at 100%.
2. Sample Size Used for the Test Set and Data Provenance
- Positive Controls: The test set included 90 individual tests for each positive analyte (Influenza A (H1N1), Influenza A (H3N2), Influenza B, and Respiratory Syncytial Virus A), resulting in a total of 360 positive control tests. This was broken down into 30 tests per analyte at each of the three sites.
- Negative Controls: The test set included 91 individual tests for the negative analyte (Coxsackievirus B1). This was broken down into 30 tests at Site 1, 30 tests at Site 2, and 31 tests at Site 3.
- Data Provenance: The study was conducted from three different production lots, at three different sites, using three different GeneXpert® Instrument Systems, and involved six different users. This suggests a prospective, multi-site study design intended to demonstrate real-world performance. The country of origin is not explicitly stated, but the applicant (Microbiologics, Inc.) is based in the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document describes the performance of an assayed quality control material for clinical microbiology assays. For such devices, the "ground truth" is inherent to the known composition of the control material (i.e., presence or absence of specific inactivated viruses). Therefore, no human experts or their qualifications are mentioned for establishing the ground truth of the control panel itself, as it's a manufactured standard. The "ground truth" is defined by the components of the control panel.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1 or 3+1) are typically used when there is ambiguity or disagreement in human interpretation of results, often in image analysis or diagnostic readings. For a quality control material like the Cepheid Xpert® Respiratory Control Panel, the result is an objective output from the GeneXpert® Instrument System (e.g., positive or negative for a specific virus). Therefore, an adjudication method for the test set is not applicable and not mentioned in the document.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. This type of study assesses how AI assistance impacts human reader performance, which is not relevant for an assayed quality control material designed to objectively monitor instrument performance rather than assist human interpretation of diagnostic images or clinical cases.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Study was Done
Yes, the study described is essentially a standalone performance evaluation of the quality control material itself when processed by the GeneXpert® Instrument System. The purpose is to verify that the control panel consistently yields the expected objective results when run through the assay, demonstrating its suitability for monitoring the RNA extraction, amplification, and detection stages of the assay. While humans operate the system and record results, the performance being assessed is that of the QC material and the GeneXpert system, without human "interpretation" of the QC result itself beyond confirming the expected positive/negative output.
7. The Type of Ground Truth Used
The ground truth used is the known composition of the manufactured control panel.
- For positive controls, the ground truth is the confirmed presence of specific inactivated viruses (Influenza A (H1N1), Influenza A (H3N2), Influenza B, and Respiratory Syncytial Virus A) at concentrations expected to be detected by the Cepheid Xpert® Xpress Flu/RSV assay.
- For the negative control, the ground truth is the confirmed presence of a non-target virus (Coxsackie B1) that should not be detected by the Cepheid Xpert® Xpress Flu/RSV assay.
8. The Sample Size for the Training Set
The document does not provide information about a "training set" because this device is a quality control material, not a machine learning algorithm that requires training data. Its performance is evaluated based on its ability to produce expected results when tested, not by learning from a dataset.
9. How the Ground Truth for the Training Set Was Established
As mentioned above, there is no training set for this type of device. The ground truth for the performance evaluation (test set) is intrinsically defined by the known biological composition and manufacturing specifications of the control panel itself.
§ 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.”