(237 days)
The Spartan RX CYP2C19 System is a qualitative in vitro diagnostic test for the identification of a patient's CYP2C19 *2, *3 and *17 genotype determined from genomic DNA obtained from a buccal swab sample. For prescription use only.
Spartan RX CYP2C19 Assay - The Spartan RX CYP2C19 System is indicated for use as an aid to clinicians in determining therapeutic strategies for therapeutics that are metabolized by the Cytochrome P450 2C19 gene product, and that are specifically affected by the *2, *3, and *17 alleles. The Spartan RX CYP2C19 Assay will be run on the Spartan RX CYP2C19 Platform from the buccal sample collected with a buccal swab. The Spartan RX CYP2C19 Assay is not indicated to be used to predict drug response or non-response.
Spartan RX CYP2C19 Platform - The Spartan RX CYP2C19 System is indicated for use as an aid to clinicians in determining therapeutic strategies for therapeutics that are metabolized by the Cytochrome P450 2C19 gene product, and that are specifically affected by the *2, *3, and *17 alleles. The Spartan RX CYP2C19 Platform will be used to run the Spartan RX CYP2C19 Assay.
The Spartan RX CYP2C19 System is a sample-to-result DNA testing system that uses proprietary technology to integrate DNA extraction and amplification. Genotypes are determined using PCR and fluorescent probe detection. The Spartan RX CYP2C19 System is comprised of the Spartan RX liadrooom prable a and Spartan RX CYP2C19 Assays. The Spartan RX CYP2C19 Assays are run on the Spartan RX CYP2C19 Platform.
The Spartan RX CYP2C19 System is based on the following processes:
- Buccal swab collection i.
- ii. DNA extraction
- PCR-based amplification of the target gene lii.
- Detection of the *2, *3, and *17 alleles using fluorescent-probes iv.
- Fluorescent signal detection and analysis V.
- Genotype determination vi.
The Spartan RX CYP2C19 System integrates and automates steps ii to vi. Results are presented to the end user as genotype calls. The system also has integrated controls that monitor performance of a run and automatically inform the user of any anomalies in the instrument or reagents.
The system detects the CYP2C19 *2, *3, and *17 genotypes in separate reagent tubes. The operator collects buccal swab samples from a patient; inserts each sample into a reagent tube; and then inserts the reagent tubes into a Spartan RX Analyzer instrument.
The Spartan RX CYP2C19 System is a qualitative in vitro diagnostic test for the identification of a patient's CYP2C19 *2, *3, and *17 genotype from buccal swab samples. The system comprises the Spartan RX Platform (instrumentation) and Spartan RX CYP2C19 Assays (consumables). It integrates DNA extraction, PCR-based amplification, fluorescent probe detection, and genotype determination.
Acceptance Criteria and Reported Device Performance
| Study Parameter | Acceptance Criteria (Implicit) | Reported Device Performance (First Pass) | Reported Device Performance (Second Pass) |
|---|---|---|---|
| Limit of Detection (LOD) | High percentage of correct calls, especially with typical or low DNA input. | 84.6% (5 pooled swabs), 100.0% (2 pooled swabs), 98.1% (Normal Swab), 98.1% (1 Half Stroke), 84.6% (Inside Mouth Touch) | 98.1% (5 pooled swabs), 100.0% (2 pooled swabs), 100.0% (Normal Swab), 100.0% (1 Half Stroke), 100.0% (Inside Mouth Touch) |
| Method Comparison | High percentage of agreement with bi-directional sequencing. | 98.8% correct call rate (overall) | 100.0% correct call rate (overall) |
| Inter-Laboratory Reproducibility | High percentage of correct calls across different sites and operators. | 98.9% correct call rate (overall) | 99.8% correct call rate (overall) |
| Reagent Lot-to-Lot Reproducibility | Consistent performance across different reagent lots. | Lot 1: 97% correct, Lot 2: 100% correct, Lot 3: 100% correct | Lot 1: 100% correct, Lot 2: 100% correct, Lot 3: 100% correct |
| Exogenous and Endogenous Interfering Substances | High percentage of correct calls in presence of common interfering substances. | 91.5% correct call rate (overall), with some variation depending on substance (e.g., toothpaste 31.3%) | 99.55% correct call rate (overall) |
Note: The acceptance criteria are implicitly inferred from the reported performance results, which consistently show very high percentages of correct calls and agreement. A lower limit of detection study indicates an acceptable first pass correct call rate of 84.6% at input levels lower than 0.1 swabs per test.
Study Details
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Sample sizes used for the test set and data provenance:
- Limit of Detection (LOD):
- Part 1: 100 individual buccal swabs collected from 40 different individuals.
- Part 2: 52 samples were tested per condition (5 conditions, total 260 tests), collected from *1/*1, *2/*17, *17/*17, and *2/*3 individuals.
- Data Provenance: Not explicitly stated, but implies clinical samples possibly from Canada where the submitter is located. Retrospective or prospective is not explicitly mentioned for sample collection, but the samples were analyzed as part of a validation study.
- Method Comparison: 327 samples tested, with 325 included in the analysis.
- Data Provenance: Not explicitly stated, but implies clinical samples. Samples were de-identified.
- Inter-Laboratory Reproducibility: 960 tests performed (8 individuals * 2 operators * 2 sessions * 5 days * 3 sites).
- Data Provenance: Not explicitly stated, but implies clinical samples or samples with confirmed genotypes.
- Reagent Lot-to-Lot Reproducibility: 107 samples (Lot 1), 106 samples (Lot 2), 107 samples (Lot 3) in the first pass testing.
- Data Provenance: Not explicitly stated.
- Exogenous and Endogenous Interfering Substances: 16 samples tested for each of 14 substances (total 224 tests).
- Data Provenance: Buccal swab samples collected from *1/*1, *2/*17, *17/*17, and *2/*3 individuals where genotypes were confirmed.
- Limit of Detection (LOD):
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Number of experts used to establish the ground truth for the test set and their qualifications:
- The ground truth for all studies was established by bi-directional sequencing. This is a molecular biology technique, not a human expert interpretation. Geneticists or molecular biologists would be involved in performing and interpreting the sequencing results, but specific numbers and qualifications are not mentioned.
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Adjudication method for the test set:
- The study design employed a "second pass" re-test for samples that initially yielded "No calls." For the Method Comparison and Inter-Laboratory Reproducibility studies, if a first pass resulted in a "No call," the sample was re-tested. This serves as an internal adjudication or re-evaluation mechanism. No explicit "2+1" or "3+1" expert adjudication is described, as the ground truth is objective sequencing data.
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Multi-reader multi-case (MRMC) comparative effectiveness study:
- No MRMC comparative effectiveness study was done. The device is a diagnostic test that provides a genotype call, not an imaging device or aid to human interpretation that would typically involve human readers.
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Standalone (i.e., algorithm only without human-in-the-loop performance) study:
- Yes, the performance studies (Limit of Detection, Method Comparison, Inter-Laboratory Reproducibility, Reagent Lot-to-Lot Reproducibility, Exogenous and Endogenous Interfering Substances) represent standalone performance of the Spartan RX CYP2C19 System. The system integrates and automates the DNA testing process, and results are presented as genotype calls directly, indicating an algorithm-only performance assessment against sequencing-derived ground truth.
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Type of ground truth used:
- Bi-directional sequencing was used as the ground truth for all performance studies. This is a highly accurate and widely accepted method for confirming DNA sequences and, thus, genotypes.
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Sample size for the training set:
- The document does not explicitly mention a separate training set or its sample size. The reported studies primarily describe validation/test set performance. For molecular diagnostic devices, the development often involves internal optimization and algorithm tuning using various samples, but these are not typically referred to as a "training set" in the same way as machine learning models.
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How the ground truth for the training set was established:
- Since a distinct "training set" is not explicitly defined or discussed in the document for performance evaluation, the method for establishing its ground truth is also not detailed. However, it can be inferred that any samples used during the development and optimization phases would also likely have been characterized using highly accurate methods like bi-directional sequencing, similar to the test sets.
§ 862.3360 Drug metabolizing enzyme genotyping system.
(a)
Identification. A drug metabolizing enzyme genotyping system is a device intended for use in testing deoxyribonucleic acid (DNA) extracted from clinical samples to identify the presence or absence of human genotypic markers encoding a drug metabolizing enzyme. This device is used as an aid in determining treatment choice and individualizing treatment dose for therapeutics that are metabolized primarily by the specific enzyme about which the system provides genotypic information.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Drug Metabolizing Enzyme Genotyping Test System.” See § 862.1(d) for the availability of this guidance document.