(251 days)
The xTAG® Cystic Fibrosis 39 kit v2 is a device used to simultaneously detect and identify a panel of mutations and variants in the cystic fibrosis transmembrance regulator (CFTR) gene in human blood specimens. The panel includes mutations and variants currently recommended by the American College of Medical Genetics and American College of Obstetricians and Gynecologists (ACMG/ACOG), plus some of the worlds most common and North Americanprevalent mutations. The xTAG Cystic Fibrosis 39 kit v2 is a qualitative genotyping test which provides information intended to be used for carrier testing in adults of reproductive age, as an aid in newborn screening, and in confirmatory diagnostic testing in newborns and children.
The kit is not indicated for use in fetal diagnostic or pre-implantation testing. This kit is also not indicated for stand-alone diagnostic purposes.
The xTAG CFTR 39 kit v2 includes the following components:
- PCR Primer Mix v2 including dNTPs designed to simultaneously produce 23 amplimers of the CFTR gene (24 in the presence of CFTR del 2, 3).
- ASPE Mix A v2 including dNTPs contains primers designed to hybridize to either wild-type or mutant alleles ◆ with proprietary sequences at their 5' ends designed to specifically hybridize to complementary sequences coupled to a given bead population in Bead Mix A.
- Bead Mix A v2 contains spectrally distinguishable populations of polystyrene beads internally dyed with red and . infrared fluorochromes coupled to proprietary DNA sequences designed to specifically hybridize to complementary sequences on the ASPE primers in ASPE Mix A v2.
- 10X Buffer
- Platinum® TFI DNA Polymerase .
- Platinum® TFI Reaction Buffer .
- TFI MgCl2 .
- Shrimp Alkaline Phosphatase .
- Exonuclease I .
- Strepavidin-Phycoerythrin Conjugate .
- xTAG Data Analysis Software (TDAS) CFTR .
Here's a breakdown of the acceptance criteria and study details for the xTAG® Cystic Fibrosis 39 kit v2, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the "overall accuracy" and "agreement with comparator" percentages, which were consistently 100% or very close to it across various sample types and individual alleles, especially after any allowed reruns.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (After allowable reruns) |
|---|---|---|
| Overall Accuracy per Sample (all exons) | At or near 100% | 100.00% (327/327 samples) |
| % Agreement with Comparator (per allele) | At or near 100% | 100.00% for most alleles; 99.57% for dF508 |
| Reproducibility (across sites, operators, lots) | > 99.54% | > 99.54% |
2. Sample Sizes Used for Test Set and Data Provenance
- Test Set Sample Size:
- Clinical Samples: 319 independent clinical samples.
- Cell Lines: 8 cell lines.
- Plasmids: Number of plasmids tested is not explicitly stated for the accuracy study calculation, but they were used to supplement samples.
- Per Allele Reproducibility: Varied per allele, ranging from 6 to 468 total calls across all sites (e.g., 36 calls for G85E, 468 for dF508).
- Data Provenance: The majority of samples consisted of left-over, anonymized, banked whole-blood specimens. These were supplemented with genomic DNAs from EBV-transformed lymphoid cell lines and custom-designed plasmids. Archived clinical genomic DNA samples were obtained from a variety of sources. The document does not specify the country of origin, but study sites included Hartford Hospital, Connecticut, USA; Luminex Molecular Diagnostics, Toronto, Canada; and Hospital for Sick Children, Toronto, Canada, suggesting a North American provenance. The nature of the samples (archived clinical genomic DNA, banked specimens) indicates a retrospective study design.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The document does not explicitly mention the use of "experts" to establish ground truth in the traditional sense of medical image interpretation or clinical diagnosis. Instead, the ground truth was established by comparison with a predicate device. The "FDA cleared xTAG Cystic Fibrosis Kit (K043011 and K060627)" was used as the comparator for all clinical specimens. No human experts are described as part of ground truth establishment for the test set.
4. Adjudication Method for the Test Set
Not applicable. The ground truth was established by comparison with a predicate device, not by human expert consensus requiring adjudication. The study mentions "allowable re-runs" for device performance, but this is an internal process, not an adjudication of a human expert ground truth.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This type of study is typically performed for AI systems that aid human readers in diagnostic tasks, such as medical image interpretation. The xTAG® Cystic Fibrosis 39 kit v2 is a laboratory diagnostic test for gene mutation detection, which does not involve human readers interpreting images with or without AI assistance.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, this was a standalone study of the device. The device, which includes "xTAG Data Analysis Software (TDAS) CFTR," processes MFI signals from the Luminex instrument to "provide a final qualitative genotype for the sample." The performance evaluation focuses on the accuracy and reproducibility of this automated process against a comparator device, without human intervention in the interpretation phase for the reported performance metrics.
7. Type of Ground Truth Used
The ground truth was established by comparison with a predicate device ("FDA cleared xTAG Cystic Fibrosis Kit (K043011 and K060627)"). This indicates that the established genotypes of the samples (both positive and negative for various mutations/variants) were determined using another FDA-cleared CFTR mutation detection system.
8. Sample Size for the Training Set
The document does not provide details on a separate "training set" or its size. This is common for traditional in vitro diagnostic (IVD) kits, where performance is typically validated through studies demonstrating accuracy, precision, and reproducibility, rather than through machine learning model training. The device uses "proprietary software," but the development and validation process is likely based on established molecular diagnostics principles and analytical validation rather than a machine learning training/validation split.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as a distinct training set (in the machine learning sense) and its ground truth establishment are not discussed in the provided document. The device's performance evaluation focuses on its accuracy against a predicate device and its internal reproducibility.
§ 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.