HardyDisk AST Cefiderocol 30µg (FDC30)

K241060 · Hardy Diagnostics · JTN · Jul 18, 2024 · Microbiology

Device Facts

• Record ID: K241060
• Device Name: HardyDisk AST Cefiderocol 30µg (FDC30)
• Applicant: Hardy Diagnostics
• Product Code: JTN · Microbiology
• Decision Date: Jul 18, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1620
• Device Class: Class 2
• Attributes: PCCP

Indications for Use

HardyDisk™ AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacterales, Staphylococus spp., Acinetobacter spp., Listeria monocytogenes, Enterocccus spp., and by modified procedures, Candida spp., Neisseria gonorrhoeae, Neisseria meningitidis and Streptococcus spp., including Streptococcus pneumoniae. Use of HardyDisk™ AST Cefiderocol 30μg (FDC30) for in vitro agar diffusion susceptibility testing is indicated when there is the need to determine the susceptibility of microorganisms to Cefiderocol. HardyDisk™ AST Cefiderocol at concentration 30μg can be used to determine the zone diameter (mm) of Cefiderocol against the following microorganisms. Active both in vitro and clinical infections against: Gram-negative bacteria Escherichia coli Enterobacter cloacae complex Proteus mirabilis Pseudomonas aeruginosa Acinetobacter baumannii complex Klebsiella pneumoniae Serratia marcescens Active in vitro against: Gram-negative bacteria Citrobacter freundii complex Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca Morganella morganii Proteus vulgaris Providencia rettgeri

Device Story

HardyDisk AST Cefiderocol 30μg (FDC30) is an antimicrobial susceptibility test (AST) disk; used for semi-quantitative in vitro susceptibility testing via Kirby-Bauer agar diffusion method. Device consists of paper disks impregnated with 30μg of Cefiderocol. Used in clinical microbiology laboratories by trained personnel. Input: bacterial culture samples; process: disk diffusion on agar media; output: zone of inhibition diameter (mm). Results assist clinicians in determining susceptibility of specific Gram-negative pathogens to Cefiderocol, guiding antibiotic therapy decisions. Benefits include standardized assessment of bacterial resistance profiles to inform treatment of clinical infections.

Clinical Evidence

No clinical data. Evidence based on bench testing, including stability, quality control, and disk-to-MIC correlation studies conducted in accordance with CDER guidance. Data supported by right of reference to NDA 209445 and alignment with FDA-recognized susceptibility test interpretive criteria.

Technological Characteristics

Antimicrobial susceptibility test disk; 30μg Cefiderocol concentration; Kirby-Bauer agar diffusion principle; manual or automated zone measurement; in vitro diagnostic use.

Indications for Use

Indicated for semi-quantitative in vitro susceptibility testing of rapidly growing and fastidious bacterial pathogens, specifically to determine susceptibility to Cefiderocol. Target organisms include Gram-negative bacteria: Escherichia coli, Enterobacter cloacae complex, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Acinetobacter baumannii complex, Serratia marcescens, Citrobacter freundii complex, Citrobacter koseri, Klebsiella aerogenes, Klebsiella oxytoca, Morganella morganii, Proteus vulgaris, and Providencia rettgeri.

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.

Submission Summary (Full Text)

{0}

FDA

U.S. FOOD & DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K241060

B Applicant

Hardy Diagnostics

C Proprietary and Established Names

HardyDisk AST Cefiderocol 30μg (FDC30)

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:

1. To obtain a substantial equivalence determination for cefiderocol antimicrobial susceptibility test disk.
2. Establish a Pre-Determined Change Control Plan (PCCP) to address future revisions to device labeling in response to breakpoint changes that are recognized on the FDA STIC webpage.

### B Measurand:

Cefiderocol 30μg

### C Type of Test:

Antimicrobial Susceptibility Test Disks

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

{1}

K241060 - Page 2 of 8

## III Intended Use/Indications for Use:

### A Intended Use(s):

HardyDisk AST Disks are used for semi-quantitative *in vitro* susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. 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) of rapidly growing and certain fastidious bacterial pathogens. 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 Cefiderocol 30μg (FDC30) for *in vitro* agar diffusion susceptibility testing is indicated when there is the need to determine the susceptibility of microorganisms to Cefiderocol.

HardyDisk AST Cefiderocol at concentration 30μg can be used to determine the zone diameter (mm) of Cefiderocol against the following microorganisms.

### Active both *in vitro* and clinical infections against:

- Gram-negative bacteria
- Escherichia coli
- Enterobacter cloacae complex
- Klebsiella pneumoniae
- Proteus mirabilis
- Pseudomonas aeruginosa
- Acinetobacter baumannii complex
- Serratia marcescens

{2}

Active in vitro against:

- Gram-negative bacteria
- Citrobacter freundii complex
- Citrobacter koseri
- Klebsiella aerogenes
- Klebsiella oxytoca
- Morganella morganii
- Proteus vulgaris
- Providencia rettgeri

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 Cefiderocol 30μg (FDC30) is a high quality 6 mm diameter white filter paper disk that is impregnated with 30μg Cefiderocol. The disks are clearly marked on both sides with FDC30, designating the agent and the drug content. The disks are supplied in plastic cartridges containing 50 disks each. HardyDisk AST Cefiderocol 30μg (FDC30) 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 are placed onto the test medium surface. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically.

K241060 - Page 3 of 8

{3}

Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate 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 contact the agar surface. Agar plates are incubated in an ambient air incubator at $35 \pm 2^{\circ} \mathrm{C}$ for 16-18 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):

HardyDisk AST Sulbactam/Durlobactam 10/10μg (SUD20)

B Predicate 510(k) Number(s):

K231568

C Comparison with Predicate(s):

| Device & Predicate Device(s): | Device K241060 | Predicate K231568 |
| --- | --- | --- |
| Device Trade Name | HardyDisk AST Cefiderocol 30μg (FDC30) | HardyDisk AST Sulbactam/Durlobactam 10/10μg (SUD20) |
| General Device Characteristic Similarities | | |
| Intended Use | Semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. | Same |
| Test Method | Antimicrobial susceptibility testing using paper disks impregnated with an antimicrobial agent | Same |
| Methodology | Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. | Same |
| Inoculum | Prepared from pure isolated | Same |

K241060 - Page 4 of 8

{4}

| Device & Predicate Device(s): | Device K241060 | Predicate K231568 |
| --- | --- | --- |
| | colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. | |
| Inoculum Method | Dip a sterile swab into the prepared inoculum 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 is dependent on the organism tested. | Same |
| Reading Method | The user will interpret the zone diameters according to the established interpretive criteria for the drug. | Same |
| General Device Characteristic Differences | | |
| Antimicrobial Agent | Cefiderocol | Sulbactam/Durlobactam |
| Concentration | 30μg | 10/10μg |

VI Standards/Guidance Documents Referenced:

- CLSI M02-13th ed. Performance Standards for Antimicrobial Disk Susceptibility Tests (January 2018).
- CLSI M100-34th ed. Performance Standards for Antimicrobial Susceptibility Testing (February 2024).

VII Performance Characteristics (if/when applicable):

The premarket submission for HardyDisk Cefiderocol included a letter dated December 14, 2023, indicating the right of reference to NDA 209445. Descriptive characteristics were sufficient for the HardyDisk Cefiderocol 30μg (FDC30) 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/or in clinical infections within the spectrum of activity of Cefiderocol 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

K241060 - Page 5 of 8

{5}

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 Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex 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 Cefiderocol 30μg 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:
Not applicable.

2. Linearity:
Not applicable.

3. Analytical Specificity/Interference:
Not applicable.

4. Assay Reportable Range:
Not applicable.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Not applicable.

6. Detection Limit:
Not applicable.

7. Assay Cut-Off:
Not applicable.

## B Comparison Studies:

K241060 - Page 6 of 8

{6}

1. Method Comparison with Predicate Device:
Not applicable.

2. Matrix Comparison:
Not applicable.

## C Clinical Studies:

1. Clinical Sensitivity:
Not applicable.

2. Clinical Specificity:
Not applicable.

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

## D Clinical Cut-Off:

Not applicable.

## E Expected Values/Reference Range:

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

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

| Organisms | Interpretive Criteria | | |
| --- | --- | --- | --- |
| | Susceptible (S) | Intermediate (I) | Resistant I |
| Enterobacterales^{a,b} | ≥ 16 | 9 – 15 | ≤ 8 |
| Pseudomonas aeruginosa | ≥ 22 | 13 – 21 | ≤ 12 |
| Acinetobacter baumannii complex | ≥ 19 | 12 – 18 | ≤ 11 |

aClinical efficacy was shown for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae complex in patients with complicated urinary tract infections (cUTI).
bClinical efficacy was shown for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Serratia marcescens in patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).

## VIII Proposed Labeling:

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

K241060 - Page 7 of 8

{7}

IX Conclusion:

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

To support the implementation of changes to FDA-recognized susceptibility test interpretive criteria (i.e., breakpoints), this submission included a predetermined change control plan (PCCP) that was reviewed and accepted by FDA. This PCCP addresses future revisions to device labeling in response to breakpoint changes that are recognized on the FDA STIC webpage (https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm410971.htm). The PCCP outlined the specific procedures and acceptance criteria that Hardy Diagnostics intends to use to evaluate the HardyDisk AST Cefiderocol 30μg (FDC30) when revised breakpoints for cefiderocol are published on the FDA STIC webpage. The PCCP included with the submission indicated that if specific criteria are met, Hardy Diagnostics will update the HardyDisk AST Cefiderocol 30μg (FDC30) device label to include the new breakpoints.

K241060 - Page 8 of 8