HardyDisk AST Lefamulin 20µg (LMU20)

K192326 · Hardy Diagnostics · JTN · Sep 19, 2019 · Microbiology

Device Facts

• Record ID: K192326
• Device Name: HardyDisk AST Lefamulin 20µg (LMU20)
• Applicant: Hardy Diagnostics
• Product Code: JTN · Microbiology
• Decision Date: Sep 19, 2019
• 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) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. Use of HardyDisk AST Lefamulin 20μg (LMU20) for in vitro agar diffusion susceptibility testing is indicated when there is the need to determine the susceptibility of bacteria to Lefamulin. HardyDisk AST Lefamulin at concentration 20μg can be used to determine the zone diameter (mm) of Lefamulin against the following bacteria for which Lefamulin has been shown to be active both clinically and in vitro: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae.

Device Story

HardyDisk AST Lefamulin 20μg (LMU20) is an antimicrobial susceptibility test (AST) disc used for in vitro testing of bacterial susceptibility to the antibiotic lefamulin. The device consists of paper discs impregnated with a specific concentration of lefamulin. It is intended for use by clinical microbiology laboratories to determine the zone of inhibition around the disc when placed on inoculated agar plates, following standardized procedures. The resulting zone diameter is measured and interpreted to categorize the organism as susceptible, intermediate, or resistant to lefamulin, aiding clinicians in selecting appropriate antibiotic therapy for patients with bacterial infections.

Clinical Evidence

No clinical data. Performance supported by disk-to-MIC correlation, stability, and quality control data generated in accordance with CDER guidance for antimicrobial susceptibility testing devices. Interpretive criteria established based on CDER-evaluated microbiology disk studies.

Technological Characteristics

Paper discs impregnated with 20μg of lefamulin. Used for disk diffusion antimicrobial susceptibility testing. Class II device (21 CFR 866.1620).

Indications for Use

Indicated for semi-quantitative in vitro susceptibility testing of S. pneumoniae, S. aureus (methicillin-susceptible), and H. influenzae to Lefamulin using agar diffusion (Kirby-Bauer).

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)

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Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K192326

B Applicant

Hardy Diagnostics

C Proprietary and Established Names

HardyDisk AST Lefamulin 20μg (LMU20)

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 Lefamulin (LMU20) Antimicrobial Susceptibility Test Disk

B Measurand:

Lefamulin 20μg

C Type of Test:

Antimicrobial Susceptibility Test Disks

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## 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 Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. 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 Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae.

Use of HardyDisk AST Lefamulin 20μg (LMU20) for in vitro agar diffusion susceptibility testing is indicated when there is the need to determine the susceptibility of bacteria to Lefamulin.

HardyDisk AST Lefamulin at concentration 20μg can be used to determine the zone diameter (mm) of Lefamulin against the following bacteria for which Lefamulin has been shown to be active both clinically and in vitro:

- Streptococcus pneumoniae
- Staphylococcus aureus (methicillin-susceptible isolates)
- Haemophilus influenzae

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

Rx - For Prescription Use Only

For S. pneumoniae, H. influenzae, and S. aureus, the current absence of resistant isolates precludes defining any results other than "Susceptible". No resistance or intermediate interpretive criteria have been established. Isolates yielding MIC results other than "Susceptible" should be submitted to a reference laboratory for further testing.

### D Special Instrument Requirements:

N/A

### IV Device/System Characteristics:

#### A Device Description:

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HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20μg Lefamulin. The disks are marked with the code LMU20, on both sides.

HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant.

## 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. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. 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.

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 make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO₂, as recommended in the CLSI M02 approved standard document.

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 15 μg

### B Predicate 510(k) Number(s):

K062245

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# C Comparison with Predicate(s):

Table 1: Comparison with Predicate

| Device & Predicate Device(s): | Device: K192326 | Predicate: K062245 |
| --- | --- | --- |
| Device Trade Name | HardyDisk AST Lefamulin 20μg (LMU20) | HardyDisk Tigecycline 15μg |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | Semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. | 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 colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. | Same |
| 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. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16-18 hours. | Same |
| Reading Method | The user will interpret the zone diameters | Same |

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| | according established interpretive criteria for the drug. | |
| --- | --- | --- |
| General Device Characteristic Differences | | |
| Antimicrobial Agent | Lefamulin | Tigecycline |
| Concentration | 20μg | 15μg |

VI Standards/Guidance Documents Referenced:

CLSI M100-29th ed. Performance Standards for Antimicrobial Susceptibility Testing (January 2019).

VII Performance Characteristics (if/when applicable):

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:
N/A

7. Assay Cut-Off:
N/A

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B Comparison Studies:

1. Method Comparison with Predicate Device:

Descriptive characteristics were sufficient for the HardyDisk Lefamulin 20μg (LMU20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints. In addition, CDER concurred with the QC ranges that were established by CLSI of which QC data obtained for this subject device were deemed acceptable. 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 Lefamulin 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 interpretative criteria are applied to S. aureus (methicillin-susceptible), S. pneumoniae, and H. influenzae according to the FDA STIC website. Testing has been expanded to include isolates of similar genus or organism group and is not limited only to the indicated species. To address the unknown clinical utility of lefamulin for organisms outside of the drug’s indication for use, the following statements are added as footnotes to the Lefamulin 20μg interpretative criteria table in the HardyDisk AST 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.

2. Matrix Comparison:

N/A

C Clinical Studies:

1. Clinical Sensitivity:

N/A

2. Clinical Specificity:

N/A

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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 Lefamulin interpretative criteria for disk diffusion is shown in Table 2 below.

Table 2: FDA Identified Disk Diffusion Interpretative Criteria (Zone diameter in mm for Lefamulin)

| Organism(s) | Susceptible* | Intermediate | Resistant |
| --- | --- | --- | --- |
| Staphylococcus. aureus (methicillin-susceptible isolates) | ≥23 | - | - |
| Streptococcus pneumoniae | ≥17 | - | - |
| Haemophilus influenzae | ≥17 | - | - |

*The current absence of resistant isolates precludes defining any results other than "Susceptible". Isolates yielding MIC results other than "Susceptible" should be submitted to a reference laboratory for further testing.

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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