NEW YORK – After the successful completion of its preclinical trial, Accelerate Diagnostics is preparing to submit its new Wave antimicrobial susceptibility testing platform to the US Food and Drug Administration for regulatory approval this fall, with a commercial launch to follow.
The firm, which currently markets the Pheno system and Arc Module, reported earlier this month that its preclinical trial for the Wave platform achieved its goals of essential and categorical agreement with broth microdilution of approximately 95 percent. Essential agreement, which is whether the minimum inhibitory concentration matches the reference method within one microdilution, was between 93 percent and 99 percent for all of the antibiotic classes tested, while categorical agreement — whether Wave agrees with the reference method when categorizing an antibiotic as susceptible or resistant — ranged between 93 percent and 100 percent.
The trial included 1,570 test results and looked at carbapenems, b-lactam combos, aminoglycosides, cephalosporins, fluoroquinolones, monobactams, sulfonamides, and penicillin.
According to Accelerate Chief Strategy Officer John Meduri, the new platform delivers AST results directly from positive blood culture and bacterial isolated colonies within about 4.5 hours and uses digital holographic microscopy.
One of the key drivers to develop Wave, he said, was the need for rapid antibiotic susceptibility results that could be paired with existing rapid microbial identification platforms to arrive at more thorough clinical decisions. "With the proliferation of rapid positive blood culture identification assays … which provide same-shift microbial identification, the stakeholders are asking, 'Where the heck are the AST results?'" With Wave, AST results can be reported during the same shift as results from rapid microbial identification systems, such as syndromic molecular tests, he said.
Holographic microscopy is lens-free and uses a laser to image through the entirety of the broth in a well, enabling "more superior resolution" and an ability to see the "minute" morphologic changes that indicate an organism's response to a drug sooner, Meduri said.
Sample preparation on the Wave is included within the test card, which has 96 wells that contain dried sample preparation and lysing reagents. Once a positive blood culture is added and the card is inoculated, the system's vacuum pump draws the bacterial suspension into the card, where it is analyzed using digital holographic microscopy.
The technology allows the platform to measure the volumetric sample suspension in 3D with a higher resolution, which "enables direct observation of phenotypic responses of individual bacterial cells in a short time period," Meduri said. The system images every well every 10 minutes and analyzes growth characteristics and morphologic changes, as well as motility of organisms, to provide results.
The fully automated platform is scalable, as each module has 10 bays and can do between one and 10 isolated colony tests and between one and five positive blood cultures per module. Up to five modules can be interfaced together, and it can be run either on demand or in batch mode, Meduri noted.
The company is continuing to move forward with further validation after its preclinical trial, which was conducted in a subset of its clinical trial sites. The preclinical trial's end goals were to show accuracy of above 90 percent compared to the reference method, reach a time to result of 4.5 hours on average, and ensure ease of use for customers — all of which were met. The system's performance "exceeds FDA's requirements," and the company feels "comfortable that the system is performing as designed," Meduri said. Accelerate's goal is to submit for 510(k) clearance this autumn once its clinical trials are completed, and the clinical trials are intended to further build out its data for FDA submission and ensure accuracy, time to result, and ease of use are consistent.
The firm plans to submit the platform with its Gram-negative positive blood culture assay, and it is also developing a Gram-positive positive blood culture assay and isolating colony assays, Meduri said.
Because Accelerate already has a built-in instrument base with the Pheno system, the firm plans to target those customers after it launches Wave and encourage them to upgrade to Wave once it has received FDA clearance, he said, adding the majority of Pheno customers are under long-term contracts with innovation clauses that will allow them to easily transition to Wave if they choose.
The firm's experience with Pheno, which received de novo approval from the FDA in 2017, has helped it gain "significant market insights," Meduri said, such as customers' desire for the ability to do positive blood culture and colony isolation AST on one platform and their reliance on rapid molecular syndromic pathogen identification methods.
Wave addresses additional needs of Accelerate's customers beyond what Pheno can provide, Meduri said. While Pheno has pathogen identification capabilities, laboratories can get faster and more extensive identification with molecular systems, and those labs want their AST results to be fast to match. Wave has sped up the time to result compared to Pheno and has a higher throughput, as Pheno can only do one test at a time, Meduri noted.
Also, Pheno is an "incremental system," meaning it is a separate purchase that labs need to make to get positive blood culture AST results in addition to their existing AST system for isolated colonies. Wave, however, is able to do both, which Meduri said appeals to customers that use traditional AST systems like BioMérieux's Vitek 2 or Becton Dickinson's Phoenix.
The rapid pathogen identification and AST market has recovered as the focus on COVID-19 testing has waned, with multiple companies developing rapid AST systems and bringing them to market in the past two years. Earlier this year, Boston-based startup Selux Diagnostics raised $48 million to commercialize its FDA-cleared rapid phenotypic AST system that delivers results in five to seven hours from both positive blood cultures and isolated bacterial colonies. Microbiology giant BioMérieux's Vitek Reveal rapid AST system, which returns results in about six hours, received FDA approval in June, and Pattern Bioscience raised $28.7 million in funding last year to commercialize its rapid AST system.
Meduri said that no other companies' systems use the same holographic microscopy technology. For example, some use digital microscopy, which requires a lens and takes a bit longer to see an organism's response to antibiotics. Meduri couldn't speak to why other companies haven't utilized holographic microscopy but noted that Accelerate has patented its novel methodology, so other firms would not have access to its application of holography.
In Meduri's view, the increasing number of rapid AST systems will be a boon to Accelerate, as the proliferation will allow companies to "collectively remind hospital systems and clinicians and antimicrobial stewardship teams as to the importance of rapid AST systems and the many benefits … that they can have on patient care and hospital economics."