(32 days)
The Progenika A1AT genotyping kit is a quantitative, polymerase chain reaction (PCR) and hybridization-based in vitro diagnostic test to be used with the Luminex 200 instrument (with xPONENT software) for the simultaneous detection and identification of 14 allelic variants and their associated alleles found in the Alpha-1 antitrypsin (A1AT) codifying gene SERPINA1. The test intended for use with genomic DNA extracted from human whole blood samples collected as dry blood spot (DBS) or in K2-EDTA or from human saliva samples collected as buccal swabs using ORAcollect Dx model OCD-100. The A1AT allelic variant genotypes and associated allele results, when used in conjunction with clinical findings and other laboratory tests, are intended as an aid in the diagnosis of individuals with A1AT deficiency (A1ATD). The kit is indicated for prescription use only.
Alpha 1 antitrypsin (A1AT) Genotyping Test utilizes Luminex xMAP technology. Genomic DNA is extracted from DBS or from human EDTA anticoagulated whole blood or from human saliva samples collected as buccal swabs using ORAcollect-Dx model OCD-100. Extracted DNA is amplified and biotinylated by multiplex PCR and PCR products are denatured and hybridized to oligonucleotide probes coupled to color-coded beads. Hybridized DNA is labeled with a fluorescent conjugate and the resulting signal is detected with a Luminex® 200 system. Raw data obtained is processed with the A1AT Genotyping Test ANALYSIS SOFTWARE in order to obtain the final report. The A1AT Genotyping Test ANALYSIS SOFTWARE algorithm converts the allelic variant genotypes into associated alleles, based on the current literature.
The A1AT Genotyping Test Kit is composed of 4 reagent components (A1AT PCR Master Mix, A1AT Beads Master Mix, SAPE, SAPE Dilution Buffer) required to perform all the above mentioned processing steps, and a CD containing the A1AT Genotyping Test ANALYSIS SOFTWARE and other necessary files. Two kit configurations are available: for 48 or for 192 tests (different amounts of the same reagent components are provided in each case).
Here’s a summary of the acceptance criteria and study details for the A1AT Genotyping Test, as extracted from the provided FDA 510(k) submission.
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly list "acceptance criteria" in a separate section with specific numerical thresholds for each performance metric. Instead, the study aims to demonstrate "100% concordance" with bi-directional Sanger sequencing for accuracy. The "Performance specifications" section outlines the areas tested, and the "Comparison Data" section reports the accuracy.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (Saliva Samples) |
|---|---|---|
| Accuracy (Concordance) | 100% concordance with bi-directional Sanger sequencing | 100% |
| Precision/Reproducibility | Not explicitly stated in terms of acceptance criteria, refers to previous submission (K171868) | Referred to K171868 - assumed acceptable |
| Reagent Stability | Not explicitly stated in terms of acceptance criteria, refers to previous submission (K171868) | Up to 24 months at 2-8ºC, up to 9 months after opening |
| Specimen Stability | Not explicitly stated in terms of acceptance criteria, refers to previous submission (K171868) and for saliva to K152464 | Saliva (ORAcollect Dx model OCD-100): up to 60 days at ambient temperature |
| Lower Limit of Detection (LoD) | Not explicitly stated in terms of acceptance criteria, refers to previous submission (K171868) | Referred to K171868 - assumed acceptable |
| DNA Extraction Variability | All results correct | All results correct (12 samples tested with 3 methods by 2 operators on 3 days) |
| Cross-reactivity/Cross-contamination | No inhibition/interference | No inhibition observed for tested microbes. Potentially interfering variants listed with information included in assay limitations. |
| Interfering Substances | No inhibition of the assay | No inhibition observed for α-amylase, hemoglobin, IgA, total protein. Saliva samples should be collected at least 30 minutes after activities (eating, drinking, smoking, chewing gum, mouth washing, brushing teeth). |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Accuracy Test Set: 147 DNA samples.
- 140 archived left-over clinical genomic DNA samples obtained from human saliva (buccal swabs using ORAcollect Dx model OCD-100).
- 3 genomic DNA samples extracted from cell lines.
- 4 synthetic DNA samples.
- Data Provenance: The 140 clinical samples were "archived left-over clinical genomic DNA samples," suggesting a retrospective collection of samples from clinical practice. The country of origin for the clinical samples is not specified in the provided text.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable. The ground truth was established by bi-directional Sanger sequencing, which is a laboratory method, not human expert interpretation.
4. Adjudication Method for the Test Set
Not applicable, as the ground truth was based on a laboratory method (bi-directional Sanger sequencing) rather than expert review requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This device is a genotyping test, not an image-based AI-assisted diagnostic tool for human readers. It provides direct genetic results.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
A standalone performance study was done for the device, where its results were compared directly against bi-directional Sanger sequencing (the ground truth). The A1AT Genotyping Test ANALYSIS SOFTWARE algorithm processes raw data to obtain the final report, effectively representing the "algorithm only" performance against the comparator.
7. The Type of Ground Truth Used
The ground truth used for the accuracy study was bi-directional Sanger sequencing.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" for the device itself in the context of an AI/ML algorithm. This device is a PCR and hybridization-based assay with associated analysis software. The performance data presented refers to the evaluation of this assay. If the "ANALYSIS SOFTWARE" incorporates machine learning, the training set details are not provided. However, given the nature of the device (genotyping test), it is unlikely to involve a dynamic machine learning model in the typical sense that would require a separate, distinct training set in the context of this submission. The software's algorithm converts allelic variants into associated alleles based on existing literature.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as a distinct training set (in the context of AI/ML) and its ground truth establishment are not discussed in the provided text. The "analysis software algorithm" is described as converting genotypes into alleles "based on the current literature," implying established scientific knowledge rather than a learned model from a specific training dataset.
§ 866.5130
Alpha -1-antitrypsin immunological test system.(a)
Identification. Analpha -1-antitrypsin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques thealpha -1-antitrypsin (a plasma protein) in serum, other body fluids, and tissues. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition,alpha -1-antitrypsin deficiency has been associated with pulmonary emphysema.(b)
Classification. Class II (performance standards).