Search Results

The xTAG® Cystic Fibrosis 60 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 Genetics and American College of Obstetricians and Gynecologists (ACMG/ACOG) plus some of the world's most common and North American prevalent mutations. The xTAG Cystic Fibrosis 60 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.

Indication(s) for use: same as intended use.

The xTAG CFTR 60 kit v2 includes the following components:

• xTAG PCR Primer Mix v2
• . xTAG ASPE Mix A v2
• xTAG ASPE Mix B v2 .
• xTAG Bead Mix A v2 .
• . xTAG Bead Mix B.v2
• xTAG 10X Buffer .
• . Platinum® TFI Exo(-) DNA Polymerase
• Platinum® TFI Reaction Buffer, 5x .
• . TFI 50mM MgCl2
• xTAG Shrimp Alkaline Phosphatase .
• xTAG Exonuclease I .
• xTAG Strepavidin-Phycoerythrin Conjugate .

Here is an analysis of the provided text regarding the xTAG® Cystic Fibrosis 60 kit v2's acceptance criteria and studies:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily focuses on analytical performance characteristics rather than formally defined acceptance criteria with numerical targets. However, based on the results presented, "100% accuracy" and "precision of >99.99%" appear to be the overarching goals the device achieved.

2. Sample Size Used for the Test Set and Data Provenance

• Accuracy Study (Clinical Performance Characteristics):

  • Sample Size: 396 clinical samples. These samples contained a total of 488 mutant alleles. Some samples were compound heterozygotes or homozygous mutants.
  • 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 "several custom-designed plasmids engineered to contain 1-2 CFTR mutations each." "Archived clinical genomic DNA samples were obtained from a variety of sources." The origin (e.g., country) of these banked specimens is not explicitly stated. The study appears to be retrospective as it used archived and banked samples.

• Precision/Reproducibility Study:

  • Sample Size: Not explicitly stated as a single number, but involves multiple replicates. Each assay point was run in duplicate within a run.
    • For the overall precision study of all 60 mutations and wild-type: "Each set of samples representing all mutations and variants probed by the xTAG Cystic Fibrosis 60 kit v2."
    • For dF508mut reproducibility: 36 replicates of a sample.
    • For 2307insA allele reproducibility: 36 test points.
  • Data Provenance: Purified genomic DNAs extracted from clinical (whole blood) samples, purified genomic DNA extracted from lymphoid cell lines, and/or plasmids. The study was "multi-centre" (3 independent sites) and "multi-operator" (2 operators per site). The origin of these specific samples is not detailed, but it's reasonable to infer they are similar to the accuracy study samples. The study design implies a prospective collection and testing for the purpose of the study, even if the underlying samples were banked.

• Detection Limit and Range of Assay Study:

  • Sample Size: "Genomic DNA samples representing a subset of mutations in the CFTR 60 kit v2 test" (number not specified). Each sample was run in duplicate. For LoD determination: 22 replicates of each of 10 genomic DNAs, plus 8 negative controls.
  • Data Provenance: Genomic DNA samples used at various concentrations, plus wild-type positive control and negative controls.

• Interference Study:

  • Sample Size: Eight whole blood samples.
  • Data Provenance: Whole blood samples.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not explicitly state that experts were used to establish ground truth for the test samples in the typical sense of a diagnostic interpretation.

• For the accuracy study, the FDA-cleared xTAG Cystic Fibrosis Kit (predicate device) was used as the comparator for Panel A mutations, and dideoxy-sequencing was used for Panel B mutations. This implies that the ground truth for these samples was established by these reference methods, which are considered highly reliable for genetic variant detection.

• For the reproducibility and other analytical studies, the ground truth for the samples (e.g., presence or absence of specific mutations) would have been known from their characterization by reference methods or their design (e.g., custom-designed plasmids).

Therefore, there's no mention of a "number of experts" or their "qualifications" involved directly in adjudicating the ground truth in this context, as the ground truth was established by established genetic testing methodologies.

4. Adjudication Method for the Test Set

As the ground truth was established by reference methods (predicate device and dideoxy-sequencing), an "adjudication method" involving multiple human readers or experts to determine the ground truth for each case is not described or applicable to this type of genetic assay. The device's results were compared directly against the results from the reference methods.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. The xTAG® Cystic Fibrosis 60 kit v2 is a qualitative genotyping test. It does not involve human readers interpreting images or data in a way that an MRMC study (typically used for imaging diagnostics or complex diagnostic interpretations by humans) would be relevant. The "reader" in this context is the Luminex instrument and the xTAG Data Analysis Software (TDAS CFTR), which generate a definitive genotype output.

6. Standalone Performance Study

Yes. The entire performance evaluation reported (accuracy, precision, LoD, interference) describes the standalone performance of the xTAG® Cystic Fibrosis 60 kit v2. The kit's output, analyzed by its proprietary software, provides a final qualitative genotype. While the intended use notes it "is not indicated for stand-alone diagnostic purposes" in the clinical context (meaning clinicians integrate the result with other information), the technical performance studies presented are for the algorithm/device itself operating independently.

7. Type of Ground Truth Used

• For Panel A mutations (Accuracy Study): Results from the FDA cleared xTAG Cystic Fibrosis Kit (K043011 and K060627).
• For Panel B mutations (Accuracy Study): Dideoxy-sequencing.
• For other analytical studies (Precision, LoD, Interference): Pre-characterized genomic DNAs from clinical samples, lymphoid cell lines, and custom-designed plasmids where the presence/absence of mutations was known with high certainty through established genetic analysis methods. This effectively falls under a form of expert consensus on the genetic makeup of the samples, derived from gold-standard molecular techniques.

8. Sample Size for the Training Set

The document does not provide information on a separate "training set" or its sample size. This type of genetic assay, based on PCR and allele-specific primer extension, is designed based on known genetic sequences and variants. While there would be an inherent development and optimization phase (analogous to training for an AI model), the detailed data for such a phase is not presented in this 510(k) summary. The described studies are primarily for validation/verification of the final product.

9. How the Ground Truth for the Training Set Was Established

As no explicit "training set" and its size are mentioned, the method for establishing its ground truth is also not described. For such a molecular diagnostic, the "ground truth" for developing the assays would derive from established knowledge of CFTR gene mutations and their sequences, along with empirical testing and optimization using characterized samples (similar to those used in the validation, but within a developmental context).

Ask a specific question about this device