VITEK REVEAL GN AST Assay and VITEK REVEAL AST System

K230675 · Specific Diagnostics, LLC · SAN · Jun 20, 2024 · Microbiology

Device Facts

• Record ID: K230675
• Device Name: VITEK REVEAL GN AST Assay and VITEK REVEAL AST System
• Applicant: Specific Diagnostics, LLC
• Product Code: SAN · Microbiology
• Decision Date: Jun 20, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1650
• Device Class: Class 2

Indications for Use

The VITEK® REVEAL™ AST System is an automated system for quantitative and qualitative antimicrobial susceptibility testing (AST) of organisms direct from positive blood culture. The VITEK® REVEAL™ AST System does not provide organism identification. The VITEK® REVEAL™ AST System is an automated system that uses an array of sensors to detect volatile organic compounds emitted by growing bacteria for the in vitro diagnostic quantitative and qualitative determination of antimicrobial susceptibility. The VITEK® REVEAL™ GN AST Assay is indicated for susceptibility testing direct from positive blood culture samples signaled positive by a continuous monitoring blood culture system and confirmed to contain gram-negative bacilli by Gram stain. Organism identification is required for the AST result interpretation and reporting. This test is performed by laboratory health professionals in a clinical diagnostic setting. Results may be used as an aid to clinicians in determining appropriate antimicrobial therapy. Test results from the VITEK® REVEAL™ AST System 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. Subculturing is necessary to support further testing for: bacteria and antimicrobials not on the VITEK® REVEAL™ GN AST Assay panel, inconclusive results, epidemiologic testing, recovery of organisms present in positive blood cultures samples, and susceptibility testing of bacteria in polymicrobial samples.

Device Story

The VITEK REVEAL AST System is an automated platform for phenotypic AST of Gram-negative bacteria directly from positive blood culture samples. The system uses broth microdilution principles; it utilizes an array of proprietary chemical Small Molecule Sensors (SMS) printed on a sensor panel to detect volatile organic compounds (VOCs) emitted by growing bacteria. The system monitors color changes in the SMS array every 10 minutes during incubation to assess bacterial growth in the presence of various antibiotic concentrations. The system compares growth in antibiotic-containing wells to control wells to determine the Minimum Inhibitory Concentration (MIC) and categorical interpretation (SIR). The system is used in clinical laboratories by health professionals. It provides rapid AST results (approximately 8 hours or less), aiding clinicians in selecting appropriate antimicrobial therapy. The system is modular and scalable, consisting of a sealer, instrument, and master controller computer.

Clinical Evidence

Clinical performance was evaluated across seven US sites using 1,115 samples (424 fresh prospective, 101 clinical stock, 590 challenge). Performance was compared to reference frozen broth microdilution (BMD) per CLSI M07. Overall essential agreement (EA) and categorical agreement (CA) were high, meeting acceptance criteria for most antimicrobial agents. Trending analyses were performed to identify systematic MIC differences. Reproducibility, bottle equivalency, sample stability (up to 16 hours), and interference studies were conducted to support performance claims.

Technological Characteristics

The system utilizes colorimetric Small Molecule Sensors (SMS) to detect VOCs emitted by bacterial metabolism. It includes a sealer, instrument, and master controller. The assay uses broth microdilution in a 96-well format. Connectivity is via a touchscreen interface/master controller. Software performs real-time growth monitoring and MIC calculation. Sterilization and material standards are not explicitly detailed beyond the use of proprietary SMS arrays.

Indications for Use

Indicated for qualitative and quantitative antimicrobial susceptibility testing (AST) of Gram-negative bacilli directly from positive blood culture samples. For use by laboratory professionals in clinical diagnostic settings. Requires organism identification from an FDA-cleared method for result interpretation.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• Accelerate Pheno System, Accelerate PhenoTest BC Kit (DEN160032)

Submission Summary (Full Text)

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June 20, 2024

Specific Diagnostics, LLC % Katie Hahnemann Regulatory Affairs Specialist MDC Associates 180 Cabot Street Beverly, Massachusetts 01915

# Re: K230675

Trade/Device Name: VITEK REVEAL GN AST Assay and VITEK REVEAL AST System Regulation Number: 21 CFR 866.1650 Regulation Name: A Cellular Analysis System For Multiplexed Antimicrobial Susceptibility Testing Regulatory Class: Class II Product Code: SAN, LON Dated: June 4, 2024 Received: June 4, 2024

# Dear Katie Hahnemann:

We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Natasha Griffin

o.b.o. Ribhi Shawar, Ph.D. (ABMM) Branch Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

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# Indications for Use

510(k) Number (if known) K230675

Device Name VITEK REVEAL GN AST Assay and VITEK REVEAL AST System

#### Indications for Use (Describe)

The VITEK REVEAL AST System is an automated system for qualitative antimicrobial susceptibility testing (AST) of organisms direct from positive blood culture. The VITEK REVEAL AST System does not provide organism identification.

The VITEK REVEAL AST System is an automated system that uses an array of sensors to detect volatile organic compounds emitted by growing bacteria for the in vitro quantitative determination of antimicrobial susceptibility. The VITEK REVEAL GN AST Assay is indicated for susceptibility testing direct from positive blood culture samples signaled as positive by a continuous monitoring blood culture system and confirmed to contain gramnegative bacilli by Gram stain. Organism identification is required for AST result interpretation and reporting.

This test is performed by laboratory health professionals in a clinical diagnostic setting. Results may be used as an aid to clinicians in determining appropriate antimicrobial therapy. Test results from the VITEK REVEAL AST System 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 VITEK REVEAL GN AST Assay panel, inconclusive results, epidemiologic testing, recovery of organisms present in positive blood cultures samples, and susceptibility testing of bacteria in polymicrobial samples.

The VITEK REVEAL GN AST Assay tests the following antimicrobial agents with the specific target organisms identified below:

Amikacin: Acinetobacter baumannii-calcoaceticus complex, Citrobacter freundii (including Citrobacter freundii complex), Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens

Amoxicillin/clavulanate: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis

Ampicillin/sulbactam: Escherichia coli, Klebsiella oxytoca, Proteus mirabilis

Aztreonam: Citrobacter freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Pseudomonas aeruginosa

Cefepime: Citrobacter koseri (syn. C. diversus), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella species (including K. pneumoniae group and K. aerogenes), Klebsiella oxytoca, Pseudomonas aeruginosa

Cefotaxime: Acinetobacter baumanni-calcoaceticus complex, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

Ceftazidime: Acinetobacter baumannii-calcoaceticus complex, Citrobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

Ceftazidime/avibactam: Citrobacter freundii complex, Citrobacter cloacae (including E. cloacae

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complex), Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Pseudomonas aeruginosa

Ceftolozane/tazobactam: Citrobacter koseri, Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa

Ceftriaxone: Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis

Cefuroxime: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae group, Klebsiella oxytoca, Proteus mirabilis

Ciprofloxacin: Citrobacter freundit complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Ertapenem: Escherichia coli, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris

Gentamicin: Citrobacter freundii complex, Citrobacter koseri, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Imipenem: Acinetobacter baumannii-calcoaceticus complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Pseudomonas aeruginosa, Serratia marcescens

Levofloxacin: Citrobacter koseri, Citrobacter freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Meropenem: Acinetobacter baumannii-calcoaceticus complex, Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Meropenem/vaborbactam: Citrobacter freundii (incluidng C. freundii complex), Citrobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis

Piperacillin/tazobactam: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae group), Proteus vulgaris

Tetracycline: Acinetobacter baumannii-calcoaceticus complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group

Tobramycin: Citrobacter freundii complex, Citrobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens

Trimethoprim/sulfamethoxazole: Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae group

| ESBL Confirmation test: | Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group |
|-------------------------|-------------------------------------------------------------------|
|-------------------------|-------------------------------------------------------------------|

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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# 510(k) Summary VITEK® REVEAL™ AST System and VITEK® REVEAL™ GN AST Assay

The summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

# Contact Details

| Sponsor: | Specific Diagnostics, LLC<br>130 Baytech Drive<br>San Jose, CA 95134 |
|----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Correspondent: | MDC Associates, Inc.<br>Katie Hahnemann, Ph.D.<br>48 Dunham Ridge Road<br>Beverly, MA 01915<br>Phone: [phone]<br>[e-mail] |
| Date Prepared: | June 20, 2024 |
| Device | |
| Device Trade Name: | VITEK® REVEAL™ GN AST Assay and VITEK® REVEAL™ AST System |
| Common Name: | VITEK® REVEAL™ GN AST Assay and VITEK® REVEAL™ AST System |
| Classification Name: | A cellular analysis system for multiplexed antimicrobial susceptibility<br>testing in a multiplex qualitative and/or quantitative in vitro device<br>intended for the identification and determination of the antimicrobial<br>susceptibility results of organisms detected in samples from patients<br>with suspected microbial infections. This device is intended to aid in the<br>determination of antimicrobial susceptibility or resistance when used in<br>conjunction with other laboratory findings. |
| Regulation Number: | 866.1650 |
| Product Code: | SAN (primary), LON |
| Predicate Device: | Accelerate Pheno System, Accelerate PhenoTest BC Kit, DEN160032,<br>Product Code: PRH, NSU, LON, PEO, PEN, PAM |

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No reference devices were used in this submission.

#### Device Description Summary

The VITEK® REVEAL™ AST System is an in vitro diagnostic (IVD) automated platform for phenotypic Antimicrobial Susceptibility Testing (AST) of bacterial samples, directly from positive blood cultures. The System utilizes broth microdilution (BMD) principles to quickly and accurately determine Minimum Inhibitory Concentrations (MIC) for the drugs on the VITEK® REVEAL™ GN AST Assay, and in combination with species identification (obtained from an FDA-cleared rapid ID method), will provide a Susceptible / Intermediate / Resistant (SIR) determination, or a Positive/Negative (POS/NEG) determination for the ESBL Confirmation screen test, for the species tested. The VITEK® REVEAL™ AST System is indicated for susceptibility testing of specific Gramnegative bacteria commonly associated with bacteremia (Table 1).

Sample preparation for testing in the VITEK® REVEAL™ AST System is fast, simple, and requires minimal skill. After a blood culture sample is identified as positive by a validated, automated blood culture system, a Gram stain is performed to confirm positivity and to determine whether the sample is Gram-positive, Gram-negative, or yeast. Samples determined by Gram stain to be monomicrobial for Gram-negative bacteria are diluted in Pluronic water and dispensed into VITEK® REVEAL™ Antibiotic Panels, containing serial dilutions of antibiotics and dried media. A VITEK® REVEAL™ Sensor Panel is sealed atop an inoculated VITEK® REVEAL™ Antibiotic Panel using the VITEK® REVEAL™ Sealer in an AST disposable assembly comprising a VITEK® REVEAL™ GN AST Assay.

The VITEK® REVEAL™ AST System detects bacterial growth using an array of proprietary chemical Small Molecule Sensors (SMS), which change color in the presence of various metabolic gases (volatile organic compounds) emitted by growing bacteria during incubation. The SMS arrays, printed onto the VITEK® REVEAL™ Sensor Panel, are positioned atop each well of the VITEK® REVEAL™ Antibiotic Panel. The sealed VITEK® REVEAL™ GN AST Assay is placed in the VITEK® REVEAL™ Instrument, which functions as an incubator for the samples being tested and optically monitors and tracks the change in sensor colors as the bacteria grow. These color changes are monitored by a scan every 10 minutes, allowing a real-time assessment of growth as a function of antibiotic concentration. A real-time algorithm detects sensor array responses indicating the volatile-compound emissions that are associated with bacterial population growth. Each antimicrobial agent-containing well is then compared to the response in control wells (the positive control well containing no antimicrobial agent, and the negative containing no growth media). Bacterial growth (indicating resistance) or inhibition of growth (indicating susceptibility) relative to these controls is determined for each antimicrobial agent-concentration pair. The MIC is defined as the lowest concentration of antimicrobial agent that inhibits growth. Categorical interpretation (SIR result) is furnished based on current FDA or FDA-recognized CLSI breakpoints for each antimicrobial. Species identification by an FDA-cleared test method may be entered at any time during the AST run or after the AST run.

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The VITEK® REVEAL™ AST System includes a VITEK® REVEAL™ Sealer, a VITEK® REVEAL™ Instrument, and a master controller computer (MCC)/touch screen monitor. The system is scalable, and up to eight (8) VITEK® REVEAL™ Instruments can be controlled by one user-friendly, touchscreen interface. The VITEK® REVEAL™ AST System is also modular, avoiding the risk of a single instrument failure causing an interruption in laboratory testing. Each VITEK® REVEAL™ Instrument has two independently loadable drawers with each drawer able to hold two (2) GN AST Assays. A single VITEK® REVEAL™ Sealer can support multiple VITEK® REVEAL™ instruments since each sealing step takes less than a minute with a one-button operation.

| | Reportable range on<br>VITEK® REVEAL™ | Breakpoints<br>(FDA STIC ≤S, I, ≥R) | | |
|-------------------------------|---------------------------------------|-------------------------------------|---------------|---------------|
| Antimicrobial | (µg/mL) | Enterobacterales | P. aeruginosa | Acinetobacter |
| Amikacin | ≤0.5->128 | 16, 32, 64 | 16, 32, 64 | 16, 32, 64 |
| Amoxicillin/clavulanate | ≤2/1->64/32 | 8, 16, 32 | - | - |
| Ampicillin/sulbactam | ≤2/1->64/32 | 8, 16, 32 | - | - |
| Aztreonam | ≤0.25->64 | 4, 8, 16 | 8, 16, 32 | - |
| Cefepime | ≤0.125->64 | 2, 4-8*, 16 | 8, --, 16 | - |
| Cefotaxime | ≤0.25->128 | 1, 2, 4 | - | 1, 2, 4 |
| Ceftazidime | ≤0.125->64 | 4, 8, 16 | - | 8, 16, 32 |
| Ceftazidime/avibactam | ≤0.0625/4->32/4 | 8, --, 16 | 8, --, 16 | - |
| Ceftolozane/tazobactam | ≤0.0625/4->32/4 | 2, 4, 8 | 4, 8, 16 | - |
| Ceftriaxone | ≤0.25->16 | 1, 2, 4 | - | - |
| Cefuroxime | ≤1->32 | 8, --, 16 | - | - |
| Ciprofloxacin | ≤0.0625->8 | 0.25, 0.5, 1 | 0.5, 1, 2 | - |
| Ertapenem | ≤0.125->16 | 0.5, 1, 2 | - | - |
| Gentamicin | ≤0.25->32 | 4, 8, 16 | 4, 8, 16 | - |
| Imipenem | ≤0.25->16 | 1, 2, 4 | 2, 4, 8 | 2, 4, 8 |
| Levofloxacin | ≤0.125->16 | 0.5, 1, 2 | 1, 2, 4 | - |
| Meropenem | ≤0.0625->32 | 1, 2, 4 | 2, 4, 8 | 2, 4, 8 |
| Meropenem/vaborbactam | ≤0.0625/8->32/8 | 4, 8, 16 | - | - |
| Piperacillin/tazobactam | ≤2/4->256/4 | 8, 16, 32 | - | - |
| Tetracycline | ≤1->64 | 4, 8, 16 | - | 4, 8, 16 |
| Tobramycin | ≤0.125->32 | 4, 8, 16 | 4, 8, 16 | - |
| Trimethoprim/sulfamethoxazole | ≤0.5/9.5->64/1216 | 2, --, 4 | - | - |
| ESBL Confirmation | POS/NEG | - | - | - |

Table 1: Reportable MIC Ranges and Breakpoints for Antimicrobials Included in VITEK® REVEAL™ GN AST Assay

NEG=Negative; POS=Positive

*SDD per US FDA STIC website

#### Intended Use/Indications for Use

The VITEK® REVEAL™ AST System is an automated system for quantitative and qualitative antimicrobial susceptibility testing (AST) of organisms direct from positive blood culture. The VITEK® REVEAL™ AST System does not provide organism identification.

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The VITEK® REVEAL™ AST System is an automated system that uses an array of sensors to detect volatile organic compounds emitted by growing bacteria for the in vitro diagnostic quantitative and qualitative determination of antimicrobial susceptibility. The VITEK® REVEAL™ GN AST Assay is indicated for susceptibility testing direct from positive blood culture samples signaled positive by a continuous monitoring blood culture system and confirmed to contain gram-negative bacili by Gram stain. Organism identification is required for the AST result interpretation and reporting.

This test is performed by laboratory health professionals in a clinical diagnostic setting. Results may be used as an aid to clinicians in determining appropriate antimicrobial therapy. Test results from the VITEK® REVEAL™ AST System 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. Subculturing is necessary to support further testing for: bacteria and antimicrobials not on the VITEK® REVEAL™ GN AST Assay panel, inconclusive results, epidemiologic testing, recovery of organisms present in positive blood cultures samples, and susceptibility testing of bacteria in polymicrobial samples.

The VITEK® REVEAL™ GN AST Assay tests the following antimicrobial agents with the specific target organisms identified below:

Amikacin: Acinetobacter baumannii-calcoaceticus complex, Citrobacter freundii (including Citrobacter freundii complex), Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens

Amoxicillin/clavulanate: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis:

Ampicillin/sulbactam: Escherichia coli, Klebsiella oxytoca, Proteus mirabilis

Aztreonam.: Citrobacter freundii (including C. freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Pseudomonas aeruginosa

Cefepime: Citrobacter koseri (syn. C. diversus), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella species (including K. pneumoniae group and K. aerogenes), Klebsiella oxytoca, Pseudomonas aeruginosa

Cefotaxime: Acinetobacter baumannii-calcoaceticus complex, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

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Ceftazidime: Acinetobacter baumannii-calcoaceticus complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

Ceftazidime/avibactam: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Pseudomonas

Ceftolozane/tazobactam: Citrobacter koseri, Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa

Ceftriaxone: Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis

Cefuroxime: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae group, Klebsiella oxytoca, Proteus mirabilis

Ciprofloxacin: Citrobacter freundii (including C. freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Ertapenem: Escherichia coli, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris

Gentamicin: Citrobacter freundii complex, Citrobacter koseri, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens Imipenem: Acinetobacter baumanniicalcoaceticus complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Pseudomonas aeruginosa, Serratia marcescens

Levofloxacin: Citrobacter koseri, Citrobacter freundii (including C. freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Meropenem: Acinetobacter baumannii-calcoaceticus complex, Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

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Meropenem/vaborbactam: Citrobacter freundii (incluidng C. freundii complex), Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis

Piperacillin/tazobactam: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae (including K. pneumoniae group), Proteus vulgaris

Tetracycline: Acinetobacter baumannii-calcoaceticus complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

Tobramycin: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens

Trimethoprim/sulfamethoxazole: Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae group

ESBL Confirmation test: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group

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| Description | Specific Diagnostics<br>Subject Device | Accelerate Diagnostics, Inc.<br>Predicate Device |
|-----------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | VITEK® REVEAL™ AST System and<br>VITEK® REVEAL™ GN AST Assay | Accelerate Pheno System and<br>PhenoTest BC Kit<br>K192665 |
| Similarities | | |
| Intended Use | The VITEK® REVEAL™ AST System is an automated system for quantitative and qualitative antimicrobial susceptibility testing (AST) of organisms direct from positive blood culture. The VITEK® REVEAL™ AST System does not provide organism identification. | The Accelerate PhenoTest BC kit is a multiplexed <i>in vitro</i> diagnostic test utilizing both qualitative nucleic acid fluorescence <i>in situ</i> hybridization (FISH) identification and quantitative, antimicrobial susceptibility testing (AST) methods and is intended for use with the Accelerate Pheno system. The Accelerate PhenoTest BC kit is capable of simultaneous detection and identification of multiple microbial targets followed by susceptibility testing of the appropriate detected bacterial organisms. The Accelerate PhenoTest BC kit is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system. Results are intended to be interpreted in conjunction with Gram stain results. |
| Type of Test | Automated incubation and reading | Automated incubation and reading |
| Indicated Organisms | Gram-negative organisms | Gram-negative organisms |
| Sample | Dilution from positive blood culture | Aliquot from positive blood culture as identified by a continuous monitoring blood culture system |
| Inoculum Methods | Manual: Pipetting 25 µL positive blood culture into 25 mL of Pluronic water | Manual: Aliquot of positive blood culture into sample vial |
| Differences | | |
| AST Panel Preparation | Manual: Pipetting the inoculum into the antibiotic panel and sealing it to the sensor panel using the VITEK® REVEAL™ Sealer | Automated: User loads an aliquot of the positive blood culture into the sample vial, then places the test cassette, reagent cartridge and sample vial into an Accelerate Pheno System module and starts the run. The remaining panel preparation steps are automated |
| Technology | Automated growth based, using detection of emission of volatiles by colorimetric sensors to detect and monitor organism growth | Morphokinetic cellular analysis (MCA), such as cell morphology and light intensity of a growing clone over time, are used for analysis |
| Time to AST Result | Approximately 8 hours or less (directly)<br>Approximately 7 hours<br>from positive blood cultures) | |
| Results | Report results as minimum inhibitory<br>concentration (MIC) and categorical<br>interpretation (SIR) for antimicrobials<br>and Positive/Negative (POS/NEG) for<br>the ESBL Confirmation screen test | Report results as minimum inhibitory<br>concentration (MIC) and categorical<br>interpretation (SIR) |
| Antimicrobial Agents | | For use with Gram negative organisms |
| | Amikacin | Amikacin |
| | Amoxicillin/clavulanate | Ampicillin/sulbactam |
| | Ampicillin/sulbactam | Aztreonam |
| | Aztreonam | Cefepime |
| | Cefepime | Ceftazidime |
| | Cefotaxime | Ceftriaxone |
| | Cefotaxime/clavulanate | Ciprofloxacin |
| | Ceftazidime | Ertapenem |
| | Ceftazidime/avibactam | Gentamicin |
| | Ceftazidime/clavulanate | Meropenem |
| | Ceftolozane/tazobactam | Piperacillin/tazobactam |
| | Ceftriaxone | Tobramycin |
| | Cefuroxime | |
| | Ciprofloxacin | |
| | Ertapenem | |
| | Gentamicin | |
| | Imipenem | |
| | Levofloxacin | |
| | Meropenem | |
| | Meropenem/vaborbactam | |
| | Piperacillin/tazobactam | |
| | Tetracycline | |
| | Tobramycin | |
| | Trimethoprim/sulfamethoxazole | |

# Technology Comparison with the Predicate Device

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Any differences between the subject device and the predicate device shown in the table above do not affect the safety and effectiveness of the subject device.

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## Performance Characteristics

## Reproducibility

The reproducibility study was designed to demonstrate the reproducibility of VITEK" REVEAL™ GN AST Assay results generated on the VITEK® REVEAL™ AST System from positive blood cultures when tested at different sites by different operators and on different days. A set of Gram-negative isolates were selected for reproducibility testing such that there were at least ten (10) on-scale MIC results for each antibiotic on the VITEK" REVEAL™ GN AST Assay. For each panel organism, testing on the VITEK® REVEAL™ AST System was performed at three (3) sites, in triplicate, on three (3) days, for a total of 27 results per sample. Each site utilized at least two (2) operators. Selected isolates were contrived in blood culture bottles with human blood added and incubated until positivity. Blinded positive blood culture aliquots were delivered to each of three testing sites (one internal and two external) on the same day and tested within 16 hours of positivity. Three inoculum dilutions were prepared from each positive blood culture aliquot and used to inoculate three VITEK® REVEAL™ Antibiotic Panels.

Reproducibility was calculated as the percentage of results that fall within one (1) dilution (+/-1) of the mode result. Both best-case (assumes that off-scale results are within one dilution of the mode) and worst-case (assumes that off-scale results are more than one dilution from the mode) reproducibility was calculated for each antibiotic for each site and across all sites.

Overall best-case reproducibility (assumes that off-scale results are within one dilution of the mode) for each antimicrobial was ≥96%, meeting the acceptance criteria of ≥95% (Table 2). Worst-case reproducibility for each antimicrobial was ≥91.7%, meeting the acceptance criteria of ≥89%.

| Antibiotic | Best case #<br>within +/-1<br>dilution / Total<br>tests | Best case<br>% | Worst case<br># within +/ -<br>1 dilution/<br>Total tests | Worst case<br>% |
|-------------------------|---------------------------------------------------------|----------------|-----------------------------------------------------------|-----------------|
| Amikacin | 891/891 | 100.0% | 870/891 | 97.6% |
| Amoxicillin/clavulanate | 324/324 | 100.0% | 323/324 | 99.7% |
| Ampicillin/sulbactam* | 269/270 | 99.6% | 266/270 | 98.5% |
| Aztreonam* | 287/296 | 97.0% | 287/296 | 97.0% |
| Cefepime | 371/377 | 98.4% | 360/377 | 95.5% |
| Cefotaxime | 342/351 | 97.4% | 342/351 | 97.4% |
| Ceftazidime* | 395/396 | 99.7% | 395/396 | 99.7% |
| Ceftazidime/avibactam* | 345/350 | 98.6% | 345/350 | 98.6% |
| Ceftolozane/tazobactam* | 564/565 | 99.8% | 564/565 | 99.8% |
| Ceftriaxone | 267/267 | 100.0% | 259/267 | 97.0% |
| Cefuroxime | 429/429 | 100.0% | 427/429 | 99.5% |

Table 2. VITEK® REVEAL™ Reproducibility Overall Results Summary

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| Antibiotic | Best case #<br>within +/-1<br>dilution / Total<br>tests | Best case<br>% | Worst case<br># within +/-<br>1 dilution/<br>Total tests | Worst case<br>% |
|-------------------------------|---------------------------------------------------------|----------------|----------------------------------------------------------|-----------------|
| Ciprofloxacin | 319/324 | 98.5% | 319/324 | 98.5% |
| Ertapenem* | 291/297 | 98.0% | 291/297 | 98.0% |
| Gentamicin | 538/538 | 100.0% | 523/538 | 97.2% |
| Imipenem | 397/397 | 100.0% | 364/397 | 91.…