HardyDisk AST Rezafungin 5µg (RZF5)

K230827 · Hardy Diagnostics · JTN · Jun 1, 2023 · Microbiology

Device Facts

• Record ID: K230827
• Device Name: HardyDisk AST Rezafungin 5µg (RZF5)
• Applicant: Hardy Diagnostics
• Product Code: JTN · Microbiology
• Decision Date: Jun 1, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1620
• Device Class: Class 2

Indications for Use

HardyDisk™ AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby- Bauer). Standardized methods for agar diffusion testing have been described for Enterobacterales, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Candida spp., Haemophilus spp., Neisseria gonorrhoeae, Neisseria meningitidis and Streptococcus spp., including Streptococcus pneumoniae. Use of HardyDisk™ AST Rezafungin 5ug (RZF5) for in vitro agar diffusion susceptibility testing is indicated when there is the need to determine the susceptibility of microorganisms to Rezafungin. HardyDisk™ AST Rezafungin at concentration 5ug can be used to determine the zone diameter (mm) of Rezafungin against the following microorganisms for which Rezafungin has been shown to be active both clinically and in vitro. Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis.

Device Story

HardyDisk AST Rezafungin 5μg (RZF5) is a 6mm white filter paper disk impregnated with 5μg of the antifungal agent Rezafungin. Used in clinical microbiology laboratories for semi-quantitative in vitro susceptibility testing via the Kirby-Bauer agar diffusion method. The operator places the disk onto Mueller Hinton agar (supplemented with 2% glucose and 0.5μg/mL methylene blue) inoculated with a standardized yeast suspension (0.5 McFarland). Following 24-hour incubation at 35±2°C, the operator measures the zone of inhibition diameter (mm) around the disk. These measurements are compared against FDA-recognized interpretive criteria to determine the susceptibility of specific Candida species. This information assists clinicians in evaluating the susceptibility of microorganisms to Rezafungin.

Clinical Evidence

No clinical trials were performed. Substantial equivalence is supported by bench testing, including stability, quality control, and disk-to-MIC correlation studies conducted in accordance with CDER guidance. Breakpoints were established based on data evaluated by CDER and the FDA susceptibility test interpretive criteria (STIC) website.

Technological Characteristics

Paper disks impregnated with 5ug of Rezafungin. Operates via passive diffusion in agar media. Dimensions and form factor are standard for AST disks. Intended for use in clinical laboratory settings. No electronic components, software, or connectivity.

Indications for Use

Indicated for in vitro susceptibility testing of Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis to the antifungal agent Rezafungin using the agar diffusion (Kirby-Bauer) method.

Regulatory Classification

Identification

An antimicrobial susceptibility test disc is a device that consists of antimicrobic-impregnated paper discs used to measure by a disc-agar diffusion technique or a disc-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents. In the disc-agar diffusion technique, bacterial susceptibility is ascertained by directly measuring the magnitude of a zone of bacterial inhibition around the disc on an agar surface. The disc-broth elution technique is associated with an automated rapid susceptibility test system and employs a fluid medium in which susceptibility is ascertained by photometrically measuring changes in bacterial growth resulting when antimicrobial material is eluted from the disc into the fluid medium. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.

Predicate Devices

• HardyDisk AST Disks (K150665)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K230827

B Applicant

Hardy Diagnostics

C Proprietary and Established Names

HardyDisk AST Rezafungin 5μg (RZF5)

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| JTN | Class II | 21 CFR 866.1620 - Antimicrobial Susceptibility Test Disc | MI - Microbiology |

## II Submission/Device Overview:

A Purpose for Submission:

To obtain a substantial equivalence determination for Rezafungin Antimicrobial Susceptibility Test Disk

B Measurand:

Rezafungin 5μg

C Type of Test:

Antimicrobial Susceptibility Test Disks

## III Intended Use/Indications for Use:

A Intended Use(s):

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HardyDisk AST Disks are used for semi-quantitative *in vitro* susceptibility testing by the agar diffusion test procedure (Kirby-Bauer). Standardized methods for agar diffusion testing have been described for Enterobacterales, *Staphylococcus* spp., *Pseudomonas* spp., *Acinetobacter* spp., *Listeria monocytogenes*, *Enterococcus* spp., and by modified procedures, *Candida* spp., *Haemophilus* spp., *Neisseria gonorrhoeae*, *Neisseria meningitidis* and *Streptococcus* spp., including *Streptococcus pneumoniae*.

## B Indication(s) for Use:

HardyDisk AST Disks are used for semi-quantitative *in vitro* susceptibility testing by the agar diffusion test procedure (Kirby-Bauer). Standardized methods for agar diffusion testing have been described for Enterobacterales, *Staphylococcus* spp., *Pseudomonas* spp., *Acinetobacter* spp., *Listeria monocytogenes*, *Enterococcus* spp., and by modified procedures, *Candida* spp., *Haemophilus* spp., *Neisseria gonorrhoeae*, *Neisseria meningitidis* and *Streptococcus* spp., including *Streptococcus pneumoniae*.

Use of HardyDisk AST Rezafungin 5 µg (RZF5) for *in vitro* agar diffusion susceptibility testing is indicated when there is the need to determine the susceptibility of microorganisms to Rezafungin.

HardyDisk AST Rezafungin at concentration 5 µg can be used to determine the zone diameter (mm) of Rezafungin against the following microorganisms for which Rezafungin has been shown to be active both clinically and *in vitro*: *Candida albicans*, *Candida glabrata*, *Candida parapsilosis*, and *Candida tropicalis*.

## C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

## D Special Instrument Requirements:

Not applicable.

## IV Device/System Characteristics:

### A Device Description:

HardyDisk AST Rezafungin 5 µg (RZF5) is a high quality 6mm diameter white filter paper disk that is impregnated with 5 µg Rezafungin. The disks are clearly marked on both sides with RZF5, designating the agent and the drug content. The disks are supplied in plastic cartridges containing 50 disks each. HardyDisk AST Rezafungin 5 µg (RZF5) is intended to be used for *in vitro* agar diffusion susceptibility testing.

### B Principle of Operation:

The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that

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are placed onto the test medium surface. Mueller Hinton (MH) agar supplemented with 2% glucose and 0.5 µg/mL methylene blue dye is recommended for agar diffusion testing of yeasts. Five distinct colonies (approximately 1 mm in diameter) are transferred to 5 mL of a diluent such as sterile saline (0.85%). The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. Alternatively, the inoculum can be standardized photometrically to facilitate adjustment of rapidly growing microorganisms.

Within 15 minutes of inoculum preparation, the MH agar plate supplemented with 2% glucose and 0.5 µg/mL methylene blue dye is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 24 hours.

After incubation, the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested.

V Substantial Equivalence Information:

A Predicate Device Name(s):

Hardy Disk Ast Tigecycline 15µg

B Predicate 510(k) Number(s):

K062245

C Comparison with Predicate(s):

| Device & Predicate Device(s): | Device: K230827 | Predicate: K062245 |
| --- | --- | --- |
| Device Trade Name | HardyDisk AST Rezafungin 5µg (RZF5) | Hardy Disk Ast Tigecycline 15µg |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Antimicrobial Susceptibility Test Disks are used for in vitro susceptibility testing by standardized agar diffusion test procedures. | Same |
| Test Method | Antimicrobial Susceptibility testing using paper disks impregnated with an antimicrobial agent | Same |
| Methodology | Kirby-Bauer Disk Diffusion | Same |

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| | Susceptibility Test Protocol require the user to determine categorical interpretations (S/I/R) using the measured zone diameters. | |
| --- | --- | --- |
| Inoculum | Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland. | Same |
| Inoculum Method | Dip a sterile swab into the prepared inoculums, and streak an appropriate agar plate’s surface three times. Add the disks impregnated with the antimicrobial agent to the surface of the plate. The temperature, atmospheric conditions and duration of incubation are dependent on the organism tested. | Same |
| Reading Method | The user will interpret the zone diameters according to established interpretive criteria for the drug. | Same |
| General Device Characteristic Differences | | |
| Product Name | HardyDisk AST Rezafungin 5μg (RZF5) | Hardy Disk Ast Tigecycline 15μg |
| Antibiotic | Rezafungin | Tigecycline |
| Concentration | 5μg | 15μg |

VI Standards/Guidance Documents Referenced:

- CLSI M27M44S 3rd ed. Performance Standards for Antifungal Susceptibility Testing of Yeasts (August 2022).
- CLSI M44-S3 Zone Diameter Interpretive Standards, Corresponding Minimal Inhibitory Concentration (MIC) Interpretive Breakpoints, and Quality Control Limits for Antifungal Disk Diffusion Susceptibility Testing of Yeasts (2018).

VII Performance Characteristics (if/when applicable):

The premarket submission for HardyDisk Rezafungin included a letter dated February 02, 2023 indicating the right of reference to NDA 217417. Descriptive characteristics were sufficient for

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the HardyDisk Rezafungin 5μg (RZF5) disk based on data from microbiology disk studies evaluated by CDER which were used to generate the breakpoints identified by FDA on the susceptibility test interpretive criteria webpage. In addition, CDER concurred with the disk QC ranges that were established by CLSI. The disk data used to support this submission included data from testing organisms shown to be active in vitro and in clinical infections within the spectrum of activity of Rezafungin and as noted in the device's intended use.

Data obtained from stability, quality control, disk to MIC correlation, reproducibility (from disk content optimization) studies were generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs-Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results.

For this review, the interpretive criteria are applied to Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis according to the FDA STIC website. As required under 511A(2)(2)(B) of the Federal Food, Drug and Cosmetic Act, the following statement is included in the Precautions section of the HardyDisk AST Rezafungin 5μg package insert:

Per the FDA-Recognized Susceptibility Test Interpretive Criteria website, the safety and efficacy of antimicrobial drugs, for which antimicrobial susceptibility is tested by this AST device, may or may not have been established in adequate and well-controlled clinical trials for treating clinical infections due to microorganisms outside of those found in the indications and usage in the drug label. The clinical significance of susceptibility information in those instances is unknown. The approved labeling for specific antimicrobial drugs provides the uses for which the antimicrobial drug is approved.

## A Analytical Performance:

1. Precision/Reproducibility:
N/A

2. Linearity:
N/A

3. Analytical Specificity/Interference:
N/A

4. Assay Reportable Range:
N/A

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
N/A

6. Detection Limit:

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N/A

7. Assay Cut-Off:

N/A

## B Comparison Studies:

1. Method Comparison with Predicate Device:

N/A

2. Matrix Comparison:

N/A

## C Clinical Studies:

1. Clinical Sensitivity:

N/A

2. Clinical Specificity:

N/A

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

N/A

## D Clinical Cut-Off:

N/A

## E Expected Values/Reference Range:

The FDA-identified susceptibility interpretive criteria for Rezafungin are listed below.

FDA-Identified Disk Diffusion Interpretive Criteria (zone diameter in mm) for Rezafungin

| Organisms | Susceptible | Intermediate | Resistant |
| --- | --- | --- | --- |
| Candida abicans | ≥13 | - | - |
| Candida glabrata | ≥15 | - | - |
| Candida parapsilosis | ≥9 | - | - |
| Candida tropicalis | ≥14 | - | - |

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Exception to the recognized standard of CLSI M27M44S as noted on the FDA STIC website

For the species listed below, susceptibility test interpretive criteria are not recognized at this time:
- Candida auris
- Candida dubliniensis
- Candida krusei

VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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