(83 days)
The Solana™ GAS Assay is a rapid in vitro diagnostic test for the qualitative detection of Group A B-hemolytic Streptococus (Streptococcus pyogenes) nucleic acids isolated from throat swab specimens obtained from patients with signs and symptoms of pharyngitis, such as sore throat. The Solana™ GAS Assay is intended for use only with the Solana™ instrument.
The Solana™ GAS Assay amplifies and detects GAS DNA present in throat swab specimens obtained from symptomatic patients.
The assay consists of two major steps: 1) specimen preparation, and 2) amplification and detection of target sequence specific to GAS using isothermal Helicase-Dependent Amplification (HDA) in the presence of target-specific fluorescence probe.
Patient specimen on a throat swab is transferred to a Lysis Tube and subjected to heattreatment at 95°C for 5 minutes. The heat-treated sample is added to a Dilution Tube, and then transferred to a Reaction Tube. The Reaction Tube contains lyophilized HDA reagents, dNTPs, primers and probes. Once rehydrated with the diluted sample, the Reaction Tube is placed in Solana for amplification and detection of GAS-specific target sequence. In Solana, the target sequence is amplified by GAS specific primers and detected by a GAS specific fluorescence probe included in the Reaction Tube. A competitive process control (PRC) is included in the Lysis Tube to monitor sample processing, inhibitory substances in clinical samples, reagent failure or device failure. The PRC target is amplified by GAS specific primers and detected by a PRC specific fluorescence probe.
The target and PRC probes are labeled with a quencher on one end and a fluorophore on the other end. In addition, the target and PRC probes carry a ribonucleic acid. Upon annealing to GAS or PRC amplicons, the fluorescence probes are cleaved by RNaseH2 and the fluorescence signal increases due to physical separation of fluorophore from quencher. Solana measures and interprets the fluorescent signal, using on-board method-specific algorithms. Solana instrument will then report the test results to the user on its display screen, and it can print out the results via a printer.
The Solana™ GAS Assay is a rapid in vitro diagnostic test for the qualitative detection of Group A β-hemolytic Streptococcus (Streptococcus pyogenes) nucleic acids isolated from throat swab specimens obtained from patients with signs and symptoms of pharyngitis, such as sore throat. The assay is intended for use only with the Solana™ instrument.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implicit for predicate device)** | Reported Device Performance (Solana™ GAS Assay) |
|---|---|---|
| Clinical Sensitivity | 96.5% (95% CI: 91.3% - 98.6%)* | 98.2% (95% CI: 95.5% - 99.3%) |
| Clinical Specificity | 98.0% (95% CI: 97.0% - 98.6%)* | 97.2% (95% CI: 95.9% - 98.1%) |
| Analytical Sensitivity (LoD) | Not explicitly stated but expected to be comparable to predicate for substantial equivalence | 6.81 x 10⁴ CFU/mL |
*The predicate device's performance (Lyra™ Direct Strep Assay) in the "Comparison with predicate" section is used as a proxy for implicit acceptance criteria, as the submission aims to demonstrate substantial equivalence. Explicit acceptance criteria beyond this are not detailed in the provided text for the Solana™ GAS Assay's clinical performance.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 1082 fresh throat swab specimens.
- Data Provenance: Prospective study conducted from December 2014 to February 2015 at four distinct geographical sites across the United States.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly state the number of experts or their specific qualifications (e.g., radiologists with 10 years of experience). However, the ground truth was established by "conventional streak-stab culture technique onto a trypticase soy agar plate containing 5% horse red blood cells" and "typed as Lancefield group A by latex agglutination." This implies standard microbiology laboratory procedures and interpretation, which would typically be performed by trained clinical microbiologists or laboratory technologists.
4. Adjudication Method for the Test Set
The document describes discordant specimens. Of the 24 specimens that were Solana™ GAS Assay positive but Composite Culture negative, 16 were tested with an additional FDA-cleared molecular device, and 8 were negative. Of the 4 specimens that were Solana™ GAS Assay negative but Composite Culture positive, 3 were tested with an additional FDA-cleared molecular device. This indicates a form of secondary testing or adjudication for discordant results, though a formal 2+1 or 3+1 method is not explicitly named.
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
No, an MRMC comparative effectiveness study involving human readers and AI assistance was not done. This device is an in-vitro diagnostic test for qualitative detection of nucleic acids, not an imaging or diagnostic aid for human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the clinical performance study evaluated the Solana™ GAS Assay as a standalone device. The "Solana instrument measures and interprets the fluorescent signal, using on-board method-specific algorithms" and "report the test results to the user on its display screen."
7. The Type of Ground Truth Used
The ground truth used was composite bacterial culture. A specimen was considered positive if either the swab or the transport media was positive for β-hemolytic Streptococcus and typed as Lancefield group A by latex agglutination.
8. The Sample Size for the Training Set
The document does not explicitly mention a separate "training set" for the clinical performance evaluation. The clinical sensitivity and specificity were established using a prospective clinical study where 1082 fresh throat swab specimens were collected and tested. This dataset largely serves as the evaluation or test set. For analytical performance, various specified quantities of bacterial strains were used.
9. How the Ground Truth for the Training Set Was Established
Given that a specific "training set" for clinical performance with a separate ground truth establishment method is not described, the approaches described for the test set (composite bacterial culture as detailed in point 7) would apply if any training data were used from clinical samples. For analytical studies, ground truth was established by using quantified (CFU/mL) cultures of known bacterial strains.
§ 866.2680
Streptococcus spp. nucleic acid-based assay.(a)
Identification. AStreptococcus spp. nucleic acid-based assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify variousStreptococcus spp. nucleic acids extracted directly from clinical specimens. The device detects specific nucleic acid sequences for organism identification. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection.
(2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (Limit of Detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, and cross contamination.
(3) Premarket notification submissions must include detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods.
(4) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardware-based devices that incorporate software.
(5) Premarket notification submissions must include database implementation methodology, construction parameters, and quality assurance protocols, as appropriate.
(6) The device labeling must include limitations regarding the need for culture confirmation of negative specimens, as appropriate.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.
(8) Premarket notification submissions must include details on an end user device training program that will be offered while marketing the device, as appropriate.