(14 days)
The AmpliChip CYP450 test is intended to identify a patient's CYP2C19 genotype from genomic DNA extracted from a whole blood sample. Information about CYP2C19 genotype may be used as an aid to clinicians in determining therapeutic strategy and treatment dose for therapeutics that are metabolized by the CYP2C19 gene product.
The AmpliChip CYP450 Test is based on five major processes: PCR amplification of purified DNA: fragmentation and labeling of the amplified products; hybridization of the amplified products to a microarray and staining of the bound products; scanning of the microarray; and determination of the CYP450 genotype and predicted phenotype.
The AmpliChip CYP450 Test is designed to identify specific nucleic acid sequences and query for the presence of known sequence polymorphisms through analysis of the pattern of hybridization to a series of probes that are specifically complementary either to wildtype or mutant sequences. Microarrays of oligonucleotide probes synthesized on a glass substrate are utilized for the analysis.
The provided document describes the performance of the AmpliChip CYP450 Test for CYP2C19. Here's an analysis based on your request:
Acceptance Criteria and Device Performance
The document doesn't explicitly state "acceptance criteria" as a separate section with predefined thresholds. Instead, it presents performance data from non-clinical studies (Limit of Detection, Specificity, Genotype Detection, Whole System Failure, Cross Contamination, Reproducibility, Interference Studies) and implicitly demonstrates that the device meets the expected performance for a diagnostic tool of this nature. The "Percent Agreement" values (often ≥99%) and "Positivity Rate" (100% at relevant DNA concentrations) serve as de facto performance targets that the device achieved.
Here's a table summarizing the reported device performance, with implicit acceptance criteria derived from the presented results:
| Performance Metric | Implicit Acceptance Criteria (Achieved) | Reported Device Performance |
|---|---|---|
| Limit of Detection (LoD) | ≥95% positivity rate for correct genotype detection at 25 ng DNA/mL. | 100% positivity rate at 50 ng DNA/mL (144/144 correct calls). 100% positivity rate at 25 ng DNA/mL (144/144 correct calls). 93.1% positivity rate at 2.5 ng DNA/mL (134/144 correct calls). The lowest level for ≥95% was considered 25 ng and 2.5 ng (the document states "25 and 2.5 ng" without further clarification, but the table shows 100% for 25ng and 93.1% for 2.5ng). |
| Specificity | 100% correct identification of wild-type samples. | 100% (270/270 correct calls for *1/*1 genotype). |
| Genotype Detection | High agreement (e.g., ≥99%) with sequencing for individual alleles and overall genotype call rate. | Sequencing Concordance (Alleles): Overall agreement: 99.6% (245/246 correct calls). Individual allele agreement: *1 (100%), *2 (98.7%), *3 (100%). Overall Genotype Call Rate: 99.7% for all 399 tested samples. Overall Percent Agreement: 99.7% for all 399 tested samples. |
| Whole System Failure | Low failure rate (e.g., |
§ 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.