(33 days)
The Verigene® Gram-Positive Blood Culture Nucleic Acid Test (BC-GP) performed using the sample-to-result Verigene System is a qualitative, multiplexed in vitro diagnostic test for the simultaneous detection and identification of potentially pathogenic gram-positive bacteria which may cause bloodstream infection (BSI). BC-GP is performed directly on blood culture bottles identified as positive by a continuousmonitoring blood culture system and which contain gram-positive bacteria. BC-GP detects and identifies the following bacterial genera and species: Staphylococcus spp., Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Enterococcus faecalis, Enterococcus faecium, Streptococcus spp., Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Listeria spp.
In addition. BC-GP detects the mecA resistance marker, inferring mecA-mediated methicillin resistance, and the vanA and vanB resistance markers, inferring vanA/vanB-mediated vancomycin resistance. In mixed growth, BC-GP does not specifically attribute van-mediated vancomycin resistance to either E. faecalis or E. faecium, or mecAmediated methicillin resistance to either S. aureus or S. epidermidis.
BC-GP is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections; however, is not to be used to monitor these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for susceptibility testing, identification of organisms not detected by BC-GP, differentiation of mixed growth, association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing.
The Verigene® Gram-Positive Blood Culture Nucleic Acid Test (BC-GP) is a molecular assay which relies on detection of specific nucleic acid targets in a microarray format. For each of the bacterial nucleic acid sequences detected by the BC-GP test. Capture and Mediator olizonucleotides are utilized for gold nanoparticle probe-based endpoint detection. The Canture oligonucleotides bind to a specific portion of the nucleic acid target and are themselves bound onto a substrate in the microarray. The Mediator oligonucleotides bind to a different portion of the same nucleic acid target and allow binding of a gold nanoparticle probe to a portion complementary to a gold nanoparticle probe. Specific silver enhancement of the bound gold nanoparticle probes at the capture sites results in gold-silver aggregates that scatter light with high efficiency.
The BC-GP test is performed on the Verigene System, a "sample-to-result", fully automated, bench-top molecular diagnostics workstation. The Verigene System consists of two components: the Verigene Reader and the Verigene Processor SP. The BC-GP test utilizes single-use disposable test consumables and a self-contained Verigene Test Cartridge for each sample tested. For the BC-GP test, the Verigene System allows automated nucleic acid extraction from grampositive bacteria-containing blood culture specimens and target detection of bacteria-specific DNA.
The Reader is the Verigene System's user interface, which serves as the central control unit for all aspects of test processing and results generation. The Reader's graphical user interface guides the user through test processing and test results using a barcode scanner. The user inserts the Test Cartridge into the Verigene Processor SP, which executes the test procedure, automating the steps of ( ) Sample Preparation - Cell lysis and magnetic bead-bacterial DNA isolation from blood culture samples and (2) Hybridization - Detection and identification of bacterialspecific DNA in a microarray format by using gold nanoparticle probe-based technology.
After test processing is complete, to obtain the test results the user removes the Test Cartridge from the Processor SP, removes the reagent pack from the substrate holder, and inserts the substrate holder into the Reader for analysis. Light scatter from the capture spots is imaged by the Reader and intensities from the microarray spots are used to make decisions regarding the presence (Detected) or absence (Not Detected) of a bacterial nucleic acid sequence/analyte.
The user is asking for information about the acceptance criteria and study data for the "Verigene® Gram-Positive Blood Culture Nucleic Acid Test (BC-GP)".
Here's a breakdown of the requested information based on the provided text:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state "acceptance criteria" in a tabular format with corresponding "reported device performance" for this specific 510(k) submission (K122514). This submission is an expansion of the intended use for a previously cleared device (K113450) and largely refers back to the original submission for detailed performance characteristics.
However, the document describes a study to support the expanded use (analytical testing of additional culture bottles) and reports the performance of the device in that study. I can create a table based on the findings of this specific study as it relates to the suitability of the additional bottle types.
| Acceptance Criteria Category | Reported Device Performance (for additional bottle types) |
|---|---|
| Overall Performance for Additional Bottle Types | Demonstrated acceptable performance for all six new bottle types with representative strains. |
| Detection of Expected Targets | Expected targets detected for all tests performed with two exceptions. |
| Exceptions | a) Two of twenty-one replicates of MRSE in BACTEC Lytic/10 Anaerobic/F bottles were positive for Staphylococcus spp. but negative for S. epidermidis and mecA. |
| b) One replicate of Listeria monocytogenes in a VersaTREK REDOX 2 EZ DRAW/Anaerobic (Trek N) bottle detected Staphylococcus spp. in addition to the Listeria spp. target. | |
| Product Labeling Action for Exceptions | Product labeling includes information regarding detection of MRSE in BACTEC Lytic/10 Anaerobic/F bottles and the potential cross-reactivity of Listeria species with BC-GP Staphylococcus species probes. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size for Test Set: For the analytical testing of additional culture bottles, the study inoculated each of the six additional bottle types with representative strains into seven replicates each.
- Data Provenance: The document does not specify the country of origin of the data, nor does it explicitly state whether the study was retrospective or prospective. Given it involved controlled inoculations into specific bottle types to test performance, it would be considered a prospective analytical study within a lab setting rather than clinical data provenance.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
The document does not mention the use of experts or their qualifications for establishing ground truth in this analytical study. Ground truth in this context (testing specific bacterial strains in culture bottles) would typically be established by controlled inoculation of known bacterial strains, confirmed by standard microbiological identification methods, rather than expert consensus on interpretation.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The document does not mention any adjudication method. For an analytical study involving known bacterial inoculations, adjudication by experts for ground truth is generally not applicable in the same way it would be for interpreting complex clinical images or diagnoses.
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
- Was an MRMC study done? No. This device is an in vitro diagnostic test for detecting nucleic acid sequences of bacteria directly from blood cultures, not an imaging device requiring human readers or AI assistance in interpretation in the context of an MRMC study.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
- Standalone performance: Yes, the performance described in the document is for the standalone device (Verigene® BC-GP test on the Verigene System). The system is a "sample-to-result, fully automated" system with "automated nucleic acid extraction... and target detection," and interpretation by "Diagnostic Software/Decision Algorithm." This indicates it operates without human-in-the-loop performance for result generation. The results are "Detected" or "Not Detected" for specific analytes based on signal intensity read by the system.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
For the analytical testing of additional culture bottles, the ground truth was established by controlled inoculation of known bacterial strains. The presence or absence of specific bacterial targets was predetermined by the strains inoculated.
8. The sample size for the training set
The document does not provide information about a "training set" for the BC-GP test. This type of molecular diagnostic device is typically developed based on known genetic sequences and optimized through analytical studies, rather than machine learning models that require a distinct training set in the conventional sense. The "Performance Characteristics" section refers to K113450 for the full analytical and clinical performance data, indicating that the core technology and algorithm were established in the previous submission.
9. How the ground truth for the training set was established
As there's no mention of a "training set" in the context of machine learning, ground truth establishment for such a set is not applicable here. The establishment of the assay's detection capabilities would have been through rigorous analytical validation using characterized bacterial cultures and nucleic acid controls.
§ 866.3365 Multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures.
(a)
Identification. A multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures is a qualitative in vitro device intended to simultaneously detect and identify microorganism nucleic acids from blood cultures that test positive by Gram stain or other microbiological stains. The device detects specific nucleic acid sequences for microorganism identification as well as for antimicrobial resistance. This device aids in the diagnosis of bloodstream infections when used in conjunction with other clinical and laboratory findings. However, the device does not replace traditional methods for culture and susceptibility testing.(b)
Classification. Class II (special controls). The special control for this device is FDA's guideline document entitled “Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures.” For availability of the guideline document, see § 866.1(e).