(27 days)
The eSensor® Cystic Fibrosis Carrier Detection (CFCD) System is a device for the detection of carrier status for cystic fibrosis for all adult couples contemplating pregnancy, regardless of ethnicity. It is a qualitative genotyping assay that simultaneously detects mutations currently recommended by the American College of Medical Genetics and American College of Obstetricians and Gynecologists (ACMG/ACOG). The eSensor® CFCD System is not indicated for prenatal screening or for diagnostic purposes, and is for Rx only professional use within the confines of a licensed laboratory, as defined by the Clinical Laboratory Improvement Amminents (CLIA) of 1988.
The eSensor® Cystic Fibrosis Carrier Detection System is an in vitro diagnostic test for the detection and genotyping of a selected panel of 24 cystic fibrosis mutations from DNA isolated from human whole blood.
The CFCD System is a clinical multiplex genetic test system which includes reagents for polymerase chain reaction amplification, exonuclease digestion and hybridization of target DNA, instrumentation and software. The CFCD System uses electrochemical detection to determine the carrier status of patient blood specimens for the ACOG/ACMG recommended panel of 24 cystic fibrosis mutations. Sample preparation for genotyping involves converting each blood specimentions: "Bunp genomic DNA (gDNA); then using multiplex PCR amplification followed by exonuclease digestion to convert the gDNA into a set of single-stranded targets. The genotyping reaction is set up with the combination of the single-stranded targets with appropriate buffers containing allele-specific signal probes differentially labeled with electrochemical signaling molecules, called ferrocenes. This mixture is then loaded into cartridges that contain single-stranded capture probes bound to an array of electrodes, with each electrode containing capture probess specific for a single mutation. Cartridges are inserted into the eSensor 4800 Instrument where the single-stranded targets hybridize to the complementary sequences of the carture probes and signal probes. Detection of the target/probe complexes is achieved using alternating current voltammetry that generates specific electrical signals from the hybridized signal probes. The eSensor® DNA Detection System Application Software then classifies the signals from each mutation and generates a report for each specimen that describes the carrier or non-carrier status of each of the cystic fibrosis panel mutations.
The requested information is detailed below, based on the provided text:
Acceptance Criteria and Device Performance for eSensor® Cystic Fibrosis Carrier Detection System
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the entire system's performance metrics (e.g., a target percentage for overall agreement). However, it reports the performance observed in the studies. Given the context of a 510(k) submission, the "performance characteristics" section details the metrics used to demonstrate substantial equivalence. I will present the reported performance as if they implicitly represent the achieved acceptance criteria based on the clearance.
| Performance Metric | Reported Device Performance |
|---|---|
| Input DNA Requirements | |
| Accuracy with 10 ng gDNA | 99.0% (complete and accurate results) with a lower one-sided 95% confidence bound of 95.1% |
| Method Comparison (vs. DNA Sequencing) | |
| Per Sample Overall Agreement | 98.8% (479/486) |
| Per Sample Agreement (excluding no-calls) | 99.6% (479/481) |
| Per Mutation Overall Agreement | 98.9% (11,540/11,663) |
| Per Mutation Agreement (excluding no-calls) | 99.97% (11,540/11,543) |
| Reproducibility | |
| Overall Per-Sample Agreement (after re-testing no-calls) | 99.8% |
| Per-Sample No-Call Rate | 0.1% |
| Per-Sample Contradictory Call Rate | 0.1% |
| Overall Per-Mutation Agreement (after re-testing no-calls) | 99.9% |
| Per-Mutation No-Call Rate | 0.1% |
| Per-Mutation Contradictory Call Rate | 0.008% |
| System Failure (First-pass no-call rate in Clinical Trial) | |
| Initial First-Pass No-Call Rate | 3.3% |
| No-Call Rate (after no more than 2 repeat tests) | 1.0% |
2. Sample Size and Data Provenance for Test Set
- Sample Size for Test Set:
- Method Comparison: 486 samples (freshly collected and banked) were used.
- Reproducibility: Genomic DNA samples from one non-carrier cell line and 20 carrier cell lines (expressing all 23 panel mutations) were used. This set was tested repeatedly.
- Input DNA Requirements: 96 tests were performed with 10 ng gDNA samples.
- Data Provenance: The document does not explicitly state the country of origin of the data. It refers to "freshly collected and banked samples" for the method comparison, implying a retrospective component to the data collection, potentially combined with prospectively collected samples.
3. Number and Qualifications of Experts for Ground Truth
The document does not mention the number or specific qualifications of experts used to establish the ground truth.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for the test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned in the provided text. The device is for laboratory use, not image interpretation by human readers.
6. Standalone Performance Study
Yes, a standalone performance study was conducted. The "Method Comparison" section directly compares the CFCD System's results to DNA sequencing, which serves as the reference standard, demonstrating the algorithm's performance without direct human-in-the-loop intervention during the genotyping output.
7. Type of Ground Truth Used
The primary type of ground truth used for performance evaluation was DNA sequencing. This is considered a highly reliable and definitive method for genetic mutation detection.
8. Sample Size for the Training Set
The document does not explicitly state the sample size used for the training set. The performance data focuses on validation and comparison.
9. How Ground Truth for the Training Set Was Established
The document does not describe how ground truth was established for a training set, as a specific training set size is not mentioned. It is common for such systems to be developed and optimized using a variety of known samples, but the specifics are not provided in this summary. The ground truth for the validation test set was established by DNA sequencing.
§ 866.5900 Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation detection system.
(a)
Identification. The CFTR gene mutation detection system is a device used to simultaneously detect and identify a panel of mutations and variants in the CFTR gene. It is intended as an aid in confirmatory diagnostic testing of individuals with suspected cystic fibrosis (CF), carrier identification, and newborn screening. This device is not intended for stand-alone diagnostic purposes, prenatal diagnostic, pre-implantation, or population screening.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: CFTR Gene Mutation Detection System.” See § 866.1(e) for the availability of this guidance document.