(686 days)
Intended Use:
The ASTar System is intended to be used for the automated quantitative susceptibility testing for most clinically significant microorganisms. The ASTar System does not provide organism identification.
Indications for Use:
The ASTar System, comprised of the ASTar Instrument with the ASTar BC G- Kit (ASTar BC G- Consumable kit, ASTar BC G- Frozen insert, and ASTar BC G-Kit software), utilizes high-speed, time-lapse microscopy imaging of bacteria for the in vitro, quantitative determination of antimicrobial susceptibility of on-panel gram-negative bacteria. The test is performed directly on positive blood culture samples signaled as positive by a continuous monitoring blood culture system and confirmed to contain gram-negative bacilli by Gram stain. Organism identification is required for AST result interpretation and reporting.
Test results from the ASTar BC G- Kit should be interpreted in conjunction with other clinical and laboratory findings. Standard laboratory protocols for processing positive blood cultures should be followed to ensure availability of isolates for supplemental testing. Sub-culturing is necessary to support further testing for: bacteria and antimicrobials not on the ASTar BC G- panel, where inconclusive results are obtained, epidemiologic testing, recovery of organisms present in microbial samples, and susceptibility testing of bacteria in polymicrobial samples.
The ASTar BC G- Kit tests the following antimicrobial agents with the following bacterial species:
Amikacin: Citrobacter freundii, Enterobacter cloacae complex, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens
Ampicillin: Escherichia coli, Proteus mirabilis
Ampicillin-sulbactam: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris
Aztreonam: Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens
Cefazolin: Klebsiella pneumoniae
Cefepime: Citrobacter freundii, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens
Ceftazidime: Enterobacter cloacae complex, Escherichia oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens
Ceftazidime-avibactam: Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Klebsiella oxytoca, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens
Cefuroxime: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis
Ciprofloxacin: Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens
Gentamicin: Citrobacter freundii, Citrobacter koseri, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens
Levofloxacin: Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens
Meropenem: Acinetobacter baumannii, Citrobacter freundii, Citrobacter koseri, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens
Meropenem-vaborbactam: Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens
Piperacillin-tazobactam: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens
Tigecycline: Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Serratia marcescens
Tobramycin: Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens
Trimethoprim-sulfamethoxazole: Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus vulgaris
ASTar System is a fully automated system for antimicrobial susceptibility testing (AST). It consists of the ASTar Instrument which is used in combination with dedicated application kits. The ASTar BC G- Kit consists of the ASTar BC G- Consumable kit, ASTar BC G- Frozen insert, and ASTar BC G-Kit software which must be installed on the instrument to process the kit.
The system provides robust and consistent inoculum preparation for AST and utilizes high-speed, time-lapse microscopy imaging of pathogens in broth microdilution to determine minimum inhibitory concentration (MIC) and qualitative susceptibility results. Organism identification using an approved method is required to be entered into the ASTar Instrument for results to be reported.
The instrument is designed to carry out sample preparation of up to six samples in parallel, using a dedicated ASTar Cartridge consumable for each sample. In the subsequent AST culturing step, the instrument transfers the prepared sample into a second dedicated consumable, referred to as the ASTar Disc. Up to 12 Discs can be incubated simultaneously in the system. The processed samples can be in different stages of the processing protocol. New samples can be loaded in a random-access manner when there are available slots. Processing of loaded samples will, in most cases, start shortly after loading. If six samples are started at the same time limitations given by the sample scheduler will result in a queue. The operator interacts with the instrument via the touchscreen display by which the operator controls the instrument.
ASTar BC G- Kit is used for in vitro determination of antimicrobial susceptibility testing of commonly isolated bacteria derived from positive blood culture samples confirmed positive for Gram-negative bacteria by Gram stain. The antimicrobial and organism combinations are listed in Table 1. Reportable ranges for each antimicrobial are listed in Table 2.
To start an analysis approximately 1 mL of a positive blood culture, confirmed Gram-negative by Gram stain is pipetted into the ASTar Cartridge by the operator and loaded into the system, from which the system purifies and quantifies the bacterial concentration is adjusted to the appropriate inoculum concentration and produces an inoculum for analysis of non-fastidious organisms. The bacterial suspensions are transferred automatically to the ASTar Disc and antimicrobial susceptibility testing is performed based on a defined short-term protocol. Results are available within approximately six hours. Bacterial growth and response to relevant concentrations of different antimicrobial drugs are measured throughout the incubation period, using a high-performance optical detection system in combination with image analysis algorithms. The system generates an MIC and further qualitative susceptibility results (i.e., S, I, R) for the tested antimicrobials when applicable. The qualitative results are determined based on established breakpoints stipulated by applicable authorities, i.e., FDA, CLSI or EUCAST. FDA Susceptibility Testing Interpretive Criteria (STIC), aka "breakpoints" are found in Table 3.
The provided text describes the performance characteristics of the ASTar BC G- Kit and ASTar Instrument, primarily focusing on its antimicrobial susceptibility testing (AST) capabilities. While it details various studies, it does not describe an AI/ML device that utilizes a test set with ground truth experts. Instead, it describes a medical device for in vitro quantitative determination of antimicrobial susceptibility based on time-lapse microscopy imaging.
Therefore, many of the requested points, such as "number of experts used to establish ground truth," "adjudication method," "MRMC comparative effectiveness study," "standalone (algorithm only) performance," and "sample size for the training set" (for an AI model), are not applicable to this document as it does not describe an AI/ML-driven diagnostic device in the traditional sense.
However, I will extract relevant information about the device's acceptance criteria and studies to the best of my ability, interpreting "acceptance criteria" as performance metrics for this type of medical device.
Key Information from the Document:
The ASTar System is an automated system for antimicrobial susceptibility testing (AST) that uses high-speed, time-lapse microscopy imaging of bacteria to determine Minimum Inhibitory Concentration (MIC) and qualitative susceptibility results (S, I, R).
1. A table of acceptance criteria and the reported device performance
The document defines acceptance criteria primarily through performance metrics like Essential Agreement (EA) and Category Agreement (CA) compared to a reference method (frozen Broth Micro-Dilution, BMD), along with rates for Very Major (VMJ) discordant results, Major (MAJ) discordant results, and Minor (MIN) discordant results.
While a single explicit "acceptance criteria table" is not provided with specific pass/fail percentages before results, the overall performance table (Table 16) implicitly represents the success or failure against internal performance goals. The FDA's Special Controls guidance (referenced in 8.5.8) would typically outline such criteria. Based on the "Conclusions" section, the device was deemed "substantially equivalent," implying these metrics were acceptable.
Here's a summary of the reported device performance from Table 16, which reflects the met acceptance criteria for the clinical study:
Table: Reported Device Performance (Summary from Table 16)
| Antimicrobial Combination (Example) | Measured EA % | Measured CA % | VMJ | MAJ | MIN |
|---|---|---|---|---|---|
| Amikacin (Enterobacterales) | 94.78 | 98.91 | 0 | 0 | 5 |
| Amikacin (Pseudomonas aeruginosa) | 92.19 | 96.88 | 0 | 0 | 2 |
| Ampicillin (Enterobacterales) | 97.46 | 97.88 | 0 | 2 | 3 |
| Ampicillin-sulbactam (Enterobacterales) | 97.53 | 89.66 | 0 | 1 | 45 |
| Aztreonam (Enterobacterales) | 96.55 | 96.86 | 4 | 0 | 16 |
| Cefazolin (Klebsiella pneumoniae) | 96.43 | 87.86 | 1 | 1 | 15 |
| Cefepime (Enterobacterales) | 95.09 | 96.2 | 0 | 2 | 22 |
| Cefepime (Pseudomonas aeruginosa) | 93.75 | 89.06 | 4 | 3 | 0 |
| Ceftazidime (Enterobacterales) | 89.44 | 96.72 | 2 | 2 | 14 |
| Ceftazidime-avibactam (Enterobacterales) | 92.58 | 99.13 | 1 | 1 | 0 |
| Ceftazidime-avibactam (Pseudomonas aeruginosa) | 100 | 100 | 0 | 0 | 0 |
| Cefuroxime (Enterobacterales) | 94.38 | 96.49 | 3 | 12 | 0 |
| Ciprofloxacin (Enterobacterales) | 97.55 | 96.25 | 2 | 6 | 18 |
| Ciprofloxacin (Pseudomonas aeruginosa) | 96.43 | 82.14 | 0 | 0 | 5 |
| Gentamicin (Enterobacterales) | 95.28 | 97.11 | 0 | 1 | 10 |
| Gentamicin (Pseudomonas aeruginosa) | 93.75 | 96.88 | 0 | 0 | 2 |
| Levofloxacin (Enterobacterales) | 98.24 | 95.02 | 2 | 3 | 29 |
| Levofloxacin (Pseudomonas aeruginosa) | 92.86 | 82.14 | 0 | 0 | 5 |
| Meropenem (Acinetobacter baumannii) | 95.65 | 93.48 | 0 | 0 | 3 |
| Meropenem (Enterobacterales) | 90.29 | 98.24 | 3 | 0 | 3 |
| Meropenem (Pseudomonas aeruginosa) | 91.67 | 100 | 0 | 0 | 0 |
| Meropenem-vaborbactam (Enterobacterales) | 96.98 | 98.94 | 0 | 0 | 7 |
| Piperacillin-tazobactam (Enterobacterales) | 93.32 | 94.33 | 3 | 5 | 20 |
| Tigecycline (Enterobacterales) | 96.03 | 97.46 | 2 | 0 | 14 |
| Tobramycin (Enterobacterales) | 92.66 | 92.37 | 2 | 1 | 24 |
| Trimethoprim-sulfamethoxazole (Enterobacterales) | 95.94 | 98.89 | 1 | 5 | 0 |
*Note: Some "poor performance" combinations (EA 95% of MIC values within ±1 doubling dilution of the mode MIC of initial samples (loaded 95% pass rate as compared to control samples without interfering antibiotics.
Interfering Antibiotics Performance (Table 13):
- All six evaluated antibiotic/BCB-combinations had overall pass rates of 96.2% to 100%. Some individual combinations fell below 90% (e.g., Cefotaxime / BACTEC: Trimethoprim-sulfamethoxazole 77.8%), but the overall criterion (per combination type) was met.
Carry Over and Cross Contamination Acceptance Criteria: (Implicitly, close to 100% pass rate expected)
- MIC for the susceptible isolate for each antimicrobial must be within ±1 doubling dilution of the control mode MIC to pass.
Carry Over and Cross Contamination Performance:
- 99.7% pass rate (307/308) for susceptible isolate MIC value. No carry over or cross contamination observed.
Set Inoculum for AST Acceptance Criteria:
- For starting bacterial concentration >5 x 10^7 CFU/mL, assess and adjust successfully at high rate, producing an inoculum within acceptance ranges.
- For concentrations 5 x 10^7 CFU/mL: 95.8% (23/24) completed concentration adjustment, and 100% (23/23) of those produced an inoculum within acceptance ranges.
- For samples with starting bacterial concentration 5 x 10^6 to
§ 866.1650 A cellular analysis system for multiplexed antimicrobial susceptibility testing.
(a)
Identification. A cellular analysis system for multiplexed antimicrobial susceptibility testing is a multiplex qualitative and/or quantitative in vitro diagnostic device intended for the identification and determination of the antimicrobial susceptibility results of organisms detected in samples from patients with suspected microbial infections. This device is intended to aid in the determination of antimicrobial susceptibility or resistance when used in conjunction with other laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) Detailed device description documentation, including the device components, ancillary reagents required but not provided, a detailed explanation of the methodology, including primer/probe sequence, design, rationale for sequence selection, and details of the antimicrobial agents, as applicable.
(ii) Detailed documentation from the following analytical and clinical performance studies: limit of detection, inclusivity, precision, reproducibility, interference, cross-reactivity, carryover, and cross-contamination, quality control and additional studies, as applicable to specimen type and assay intended use.
(iii) Detailed documentation from an appropriate 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.
(iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) Limitations and protocols regarding the need for correlation of results by standard laboratory procedures, as applicable.
(ii) A detailed explanation of the interpretation of results and acceptance criteria.
(iii) A detailed explanation of the principles of operation and procedures for assay performance and troubleshooting.