(74 days)
The Solana® Strep Complete Assay is a rapid in vitro diagnostic test, using isothermal amplification technology (helicase-dependent amplification, HDA), for the qualitative detection of Streptococcus pyogenes (Group A B-hemolytic Streptococcus) and Streptococcus dysgalactiae (pyogenic Group C and G ß-hemolytic Streptococus) nucleic acids isolated from throat swab specimens obtained from patients with signs and symptoms of pharyngitis, such as sore throat. The Solana® Strep Complete Assay is intended for use only with the the Solana® instrument.
The Solana Strep Complete Assay amplifies, detects and differentiates Streptococcus pyogenes DNA and Streptococcus dysgalactiae 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 S. pyogenes (GAS) and S. dysgalactiae (C/G) 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 two Reaction Tubes, GAS Reaction Tube and Strep C/G Reaction Tube. GAS Reaction Tube contains white lyophilized HDA reagents, dNTPs, primers and probes specific for the amplification and detection of S. pyogenes target sequence, while C/G Reaction Tube contains blue lyophilized HDA reagents, dNTPs, primers and probes specific for the amplification and detection of S. dysgalactiae target sequence. Once rehydrated with the diluted sample, the Reaction Tubes are placed in a Solana Instrument for amplification and detection of the target sequences. In Solana, the target sequences are amplified by specific primers and detected by a specific fluorescence probe included in each Reaction Tube. Two competitive process controls (PRCs) are included in the Lysis Tube to monitor sample processing, inhibitory substances in clinical samples, reagent failure or device failure for each target. PRCs are amplified by the target-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. Upon annealing to target or PRC amplicons, the fluorescence signal increases due to physical separation of the fluorophore from the quencher. Solana measures and interprets the fluorescent signal for each Reaction Tube, using on-board method-specific algorithms. Solana then reports the test results for each Reaction Tube to the user on its display screen, and optionally prints out the results via a printer.
Here's a summary of the acceptance criteria and study details for the Solana® Strep Complete Assay, based on the provided text:
Solana® Strep Complete Assay Acceptance Criteria and Performance Study
| Acceptance Criteria Category | Specific Metric | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|---|
| Clinical Performance | GAS Sensitivity | Not explicitly stated, but typically high for medical devices. | 98.8% (95% CI: 97.3% to 99.4%) |
| GAS Specificity | Not explicitly stated, but typically high for medical devices. | 98.9% (95% CI: 98.3% to 99.2%) | |
| S. dysgalactiae Sensitivity | Not explicitly stated, but typically high for medical devices. | 100% (95% CI: 95.3% to 100%) | |
| S. dysgalactiae Specificity | Not explicitly stated, but typically high for medical devices. | 99.5% (95% CI: 99.1% to 99.7%) | |
| Analytical Sensitivity (LOD) | S. pyogenes LOD | Lowest concentration at which 95% of replicates tested positive. | 8.5 x 10^4 CFU/mL |
| S. dysgalactiae LOD | Lowest concentration at which 95% of replicates tested positive. | 7.1 x 10^5 CFU/mL | |
| Reproducibility | Consistent results across sites, operators, and instruments for positive and negative controls/samples. | Demonstrated reproducible results across three sites. | |
| Cross-Reactivity | No cross-reactivity with common interfering organisms from in silico BLAST analysis. | In silico analysis showed no evidence of cross-reactivity with 61 organisms. | |
| Negligible cross-reactivity with a panel of common throat microorganisms during wet lab testing. | Klebsiella pneumoniae, Serratia marcescens, and Enterococcus faecalis each cross-reacted once out of six times tested. | ||
| Interference | No interference from common biological and chemical substances found in throat samples. | None of the 28 tested substances interfered with the assay. | |
| Inclusivity | Detection of various strains of target organisms (S. pyogenes and S. dysgalactiae). | Detected 7 S. pyogenes strains and 25 S. dysgalactiae strains at LOD concentrations. | |
| Specimen Stability | Stability of collected specimens under specified storage conditions. | Specimens stable for 2 days at 25°C, then up to 6 days at 2-8°C, or up to 32 days at ≤-15°C or ≤-70°C. |
Study Details:
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Sample Size for Test Set and Data Provenance:
- Clinical Study: 2688 fresh throat swab specimens.
- Provenance: Prospective study conducted from February to July 2016 at four (4) external and one (1) internal laboratories across the United States.
- Additional data for reproducibility (analytical performance): 540 specimens (including controls) tested across three sites for reproducibility.
- Clinical Study: 2688 fresh throat swab specimens.
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Number of Experts Used to Establish Ground Truth and Qualifications:
- The document does not explicitly state the number or qualifications of experts used to establish ground truth for the clinical test set. It mentions that "Cultured isolates were typed by latex agglutination" and "species were determined using an FDA-cleared MALDI TOF assay." It also states, "A specimen was recorded as positive for either Streptococcus pyoqenes or Streptococcus dysgalactiae if either the culture or the FDA-cleared NAAT was positive, respectively." This suggests that laboratory personnel performing these standard diagnostic methods established the ground truth, but specific expert qualifications (e.g., radiologist with 10 years of experience) are not provided as this is a molecular diagnostic assay.
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Adjudication Method for the Test Set:
- For the clinical study, the ground truth was established by a composite reference method. A specimen was considered positive if either the culture result or an FDA-cleared Nucleic Acid Amplification Test (NAAT) was positive. This acts as a form of retrospective adjudication based on multiple gold standards.
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Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly described in the provided text. The study focused on the performance of the device itself against established laboratory methods, not on how human readers' performance might improve with AI assistance.
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Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:
- Yes, the clinical performance study evaluated the "Solana® Strep Complete Assay" (the device/algorithm) against a composite reference standard (culture + FDA-cleared NAAT). The results presented are for the device's standalone performance in identifying the target pathogens. The device has an "on-board method-specific algorithms" that measures and interprets the fluorescent signal and reports results.
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Type of Ground Truth Used:
- Composite Reference Standard: For the clinical study, the ground truth was established by combining the results of:
- Directly cultured patients' throat swabs (followed by latex agglutination and FDA-cleared MALDI TOF for speciation).
- Another FDA-cleared Nucleic Acid Amplification Test (NAAT) performed on leftover swab transport fluid.
- Composite Reference Standard: For the clinical study, the ground truth was established by combining the results of:
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Sample Size for the Training Set:
- The document does not specify a sample size for a training set. The descriptions provided are for analytical validation (LOD, reproducibility, cross-reactivity, interference, inclusivity) and a clinical performance study (test set). For molecular diagnostic assays, manufacturers typically perform extensive in-house development and optimization, which would involve internal training/validation sets, but these are not usually detailed in 510(k) summaries as separate "training sets" in the context of AI/ML device submissions.
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How the Ground Truth for the Training Set Was Established:
- As no specific "training set" is detailed in the document, how its ground truth was established is not explicitly mentioned. For the analytical and clinical studies, ground truth was established using standard microbiological techniques (culture, latex agglutination, MALDI TOF) and comparison to another FDA-cleared NAAT.
§ 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.