(89 days)
The GenePOC CDiff assay performed on the revogene instrument is a qualitative in vitro diagnostic test that utilizes automated sample processing and real-time polymerase chain reaction (PCR) to detect the toxin B (tcdB) gene of toxigenic Clostridium difficile( C. difficile) in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The GenePOC CDiff assay is intended to aid in the diagnosis of CDI.
The GenePOC™ CDiff assay is a single-use test for the qualitative detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile (C. difficile) in unformed (liquid or soft) stool specimens. The GenePOC™ CDiff assay kit is comprised of the disposable CDiff microfluidic cartridges (PIE), Disposable Transfer Loops (DTL), Sample Buffer Tubes (SBT), and Disposable Transfer Tools (DTT; pipette). These components are used to suspend the sample, extract, amplify, and detect C. difficile nucleic acid. A Process Control (PrC) is also incorporated into each PIE to verify sample processing and amplification steps. The PrC allows for the verification of potential inhibitor substances as well as microfluidic, instrument or reagent failure. The GenePOC™ CDiff assay is designed to be used on the revogene™. The revogene™ is an instrument that automates sample homogenization, sample dilution, cells lysis, DNA amplification and detection of the amplified PCR products.
Each GenePOC™ CDiff assay kit provides components for 24 tests. User intervention is required for sample preparation, transferring the stool specimen with the DTL into the SBT, using the DTT to transfer the sample into the PIE, and loading/unloading the PIE into the revogene™ carousel. Each PIE is a completely integrated closed device in which a sample is dispensed and processed through different microfluidic chambers and channels that allow for the sample processing and subsequent real-time PCR steps.
Upon completion of a run, the results are computed by the revogene™ from measured fluorescent signals and embedded calculation algorithms. The output results include positive, negative, indeterminate, and unresolved. Upon completion of a run, the user removes the used cartridges and disposes of them in normal biological waste. Results may be viewed, printed, transferred, and/or stored by the user.
The provided document describes the regulatory submission for the GenePOC CDiff assay, a diagnostic test for Clostridium difficile infection (CDI). The document focuses on the analytical and clinical performance of the device to demonstrate its substantial equivalence to a predicate device.
Here's a breakdown of the acceptance criteria and study details based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in a formal table. However, the performance characteristics sections imply the criteria for various analytical and clinical aspects. The reported performance is presented in the tables and text within the document.
Let's infer the acceptance criteria from the reported results, especially concerning agreement percentages and confidence intervals. Typically, for in vitro diagnostics, high sensitivity and specificity are desired, often above certain thresholds (e.g., 85% or 90% for sensitivity, and 95% or more for specificity). For reproducibility, high agreement is also expected (e.g., >95%).
| Metric | Acceptance Criterion (Implied) | Reported Device Performance (GenePOC CDiff) |
|---|---|---|
| Analytical Performance | ||
| Reproducibility | ||
| Between-Laboratory Reproducibility: | ||
| Low Positive Samples (Overall Agreement) | High agreement (e.g., >90%) | 97.2% (95% CI: 93.6-99.1%) |
| Moderate Positive Samples (Overall Agreement) | High agreement (e.g., >90%) | 98.3% (95% CI: 95.2-99.7%) |
| True Negative Samples (Overall Agreement) | Very high agreement (e.g., >95%) | 100% (95% CI: 97.5-100%) |
| CVs for Ct Values | Low variability (e.g., 90%) | 95.0% (95% CI: 90.7-97.7%) |
| Moderate Positive Samples (Overall Agreement) | High agreement (e.g., >90%) | 98.3% (95% CI: 95.2-99.7%) |
| True Negative Samples (Overall Agreement) | Very high agreement (e.g., >95%) | 100% (95% CI: 97.5-100%) |
| Within-Laboratory Precision: | ||
| Low Positive Samples (Overall Agreement) | High agreement (e.g., >90%) | 94.4% (95% CI: 89.3-97.6%) |
| Moderate Positive Samples (Overall Agreement) | High agreement (e.g., >90%) | 96.5% (95% CI: 92.1-98.9%) |
| True Negative Samples (Overall Agreement) | Very high agreement (e.g., >95%) | 100% (95% CI: 96.9-100%) |
| Detection Limit (LoD) | Lowest concentration for 95%+ detection | 1,500 CFU/mL of SB for C. difficile strains (95% or greater detection) |
| Analytical Inclusivity | All strains detected at 2-3xLoD | All 20 toxigenic C. difficile strains detected at 3,750 CFU/mL SB (2-3xLoD) |
| Analytical Specificity | Minimal to no false positives | Limited specific false positives at high concentrations for some Clostridium species. No reactivity at lower concentrations. One case of false positive for Enterococcus faecalis at high concentration. |
| Interference | No interference | No interference from 30 tested organisms; interference from Tums and Stomaax at high concentrations; no interference from 5 endogenous agents. |
| Carry-Over & Cross-Contamination | Absence of carry-over/cross-contamination | Demonstrated absence. |
| Clinical Performance | ||
| Sensitivity (Fresh Specimens) | High sensitivity (e.g., >80%) | 80.5% (95% CI: 72.0-87.4%) |
| Specificity (Fresh Specimens) | High specificity (e.g., >95%) | 97.1% (95% CI: 95.5-98.2%) |
| Sensitivity (Frozen Specimens) | High sensitivity (e.g., >80%) | 87.3% (95% CI: 82.1-91.4%) |
| Specificity (Frozen Specimens) | High specificity (e.g., >95%) | 97.3% (95% CI: 96.3-98.1%) |
| Unresolved Rate (After Repeat Testing) | Low rate (e.g., |
§ 866.3130 Clostridium difficile toxin gene amplification assay.
(a)
Identification. AClostridium difficile toxin gene amplification assay is a device that consists of reagents for the amplification and detection of target sequences inClostridium difficile toxin genes in fecal specimens from patients suspected of havingClostridium difficile infection (CDI). The detection of clostridial toxin genes, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of CDI caused byClostridium difficile. (b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Toxin Gene Amplification Assays for the Detection ofClostridium difficile; Guideline for Industry and Food and Drug Administration Staff.” See § 866.1(e) for information on obtaining this document.