(309 days)
The Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer are in vitro diagnostic devices intended for detection of fluorescently-labeled human genomic deoxyribonucleic acid (DNA) nucleotides by capillary electrophoresis.
The Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer are indicated for sequencing and fragment analysis using FDA- cleared or approved assays.
The Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer are fluorescence-based DNA analysis instruments that use capillary electrophoresis technology with 8 and 24 capillaries, respectively.
The 8-capillary system and the 24-capillary system include the following components:
- 8-capillary or 24-capillary array and POP™ polymer .
- . Consumables for system qualification
- Computer workstation and monitor
- Integrated software for instrument control, data collection, quality control, . basecalling and sizecalling of samples
The following consumables (branded with the Applied Biosystems name) are required to operate the Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer.
- . 50cm Capillary Array: enable the labeled DNA fragments to migrate from the cathode toward the anode for detection
- POP-6TM Polymer: used as a separation matrix to separate DNA fragments by size ● during electrophoresis for sequencing
- POP-7TM Polymer: used as a separation matrix for separating DNA fragments by size during electrophoresis for fragment analysis
- Hi-Di™ Formamide: sample re-suspension solution used for electrokinetic ● injection and denaturing the DNA
- Sequencing Standard v1.1: used for spectral calibration of the instrument and instrument performance check
- Cathode Buffer Container: pre-filled with running buffer which maintains a source . of ions and the correct pH for electrophoresis
- Anode Buffer Container: pre-filled with running buffer which maintains a source ● of ions and the correct pH for electrophoresis
- Conditioning Reagent: pre-filled pouch used for priming the polymer pump, ● washing the pump between polymer type changes, and during instrument shutdown
- DS-30 Matrix Standard Dx: used for spectral calibration ●
- DS-33 Matrix Standard - Dx: used for spectral calibration
- DS-33 GeneScan™ Install Kit Dx: used for instrument operational qualification ●
- GeneScan™ 600 LIZ® Size Standard v2.0 Dx: used as a ladder for sizing DNA ● fragments
- Other accessories (e.g. sample plate holders, plate retainers, septa) .
The provided text describes the Applied Biosystems™ 3500 Dx Genetic Analyzer and Applied Biosystems™ 3500xL Dx Genetic Analyzer, which are in vitro diagnostic devices. It details their intended use, comparison to a predicate device, and supporting performance studies.
Here's an analysis of the acceptance criteria and study information provided:
1. Table of Acceptance Criteria and Reported Device Performance
The document states that for both non-clinical and clinical performance studies, "all pre-established acceptance criteria were met." However, it does not explicitly list the quantitative acceptance criteria themselves.
| Performance Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Non-Clinical | Not explicitly stated (e.g., specific thresholds for accuracy, precision, reproducibility) | "The pre-established acceptance criteria were met." |
| Clinical | Not explicitly stated (e.g., specific thresholds for clinical accuracy, sensitivity, specificity) | "All pre-established performance criteria were met." |
2. Sample Size Used for the Test Set and Data Provenance
- Non-Clinical Study: "a reproducibility study using a representative fragment analysis assay. The reproducibility study was performed across multiple sites, using different instruments, multiple operators, and across several days."
- Sample Size: Not specified.
- Data Provenance: Implied to be prospective, collected across multiple sites for the study. Country of origin not specified, but the device is manufactured by Life Technologies Holdings Pte Ltd in Singapore and the submission is to the US FDA.
- Clinical Study: "Clinical performance studies were conducted across 3 US clinical laboratory sites, with multiple instruments using a representative fragment analysis assay and an appropriate method comparison assay."
- Sample Size: Not specified.
- Data Provenance: Prospective, conducted across 3 US clinical laboratory sites.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not mention the use of experts to establish ground truth. The studies appear to be focused on the analytical performance of the instrument using "a representative fragment analysis assay and an appropriate method comparison assay," rather than clinical diagnosis by human experts.
4. Adjudication Method for the Test Set
Not applicable, as ground truth was not established by human experts 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
This section is not applicable. The device described is a genetic analyzer (an instrument for detecting fluorescently-labeled DNA nucleotides). It is not an AI-based diagnostic tool designed to assist human readers or clinicians in interpreting images or other data that typically involve MRMC studies.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done
The device itself is a standalone instrument (analyzer) with integrated software for control, data collection, quality control, basecalling, and sizecalling. The performance studies evaluate the instrument's (algorithm's) ability to perform these functions. Therefore, the non-clinical and clinical performance data effectively describe the standalone performance of the instrument.
7. The Type of Ground Truth Used
The ground truth for the non-clinical and clinical studies appears to be based on the analytical results obtained from "a representative fragment analysis assay and an appropriate method comparison assay." This implies that the ground truth is established by the expected results of these assays or comparison to a reference method, rather than pathology, expert consensus, or outcomes data.
8. The Sample Size for the Training Set
The document does not provide information about a separate "training set" in the context of machine learning or AI. This device is an instrument, and its software (Data Collection Software 3 IVD v3.2) controls its operations and processes data. While software development involves testing, the concept of a "training set" as used in machine learning for algorithm development is not addressed here.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no mention of a traditional machine learning "training set" with established ground truth outlined in the document. The device's functionality is based on established principles of capillary electrophoresis and DNA analysis.
§ 862.2570 Instrumentation for clinical multiplex test systems.
(a)
Identification. Instrumentation for clinical multiplex test systems is a device intended to measure and sort multiple signals generated by an assay from a clinical sample. This instrumentation is used with a specific assay to measure multiple similar analytes that establish a single indicator to aid in diagnosis. Such instrumentation may be compatible with more than one specific assay. The device includes a signal reader unit, and may also integrate reagent handling, hybridization, washing, dedicated instrument control, and other hardware components, as well as raw data storage mechanisms, data acquisition software, and software to process detected signals.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems.” See § 862.1(d) for the availability of this guidance document.