HardyDisk AST Omadacycline 30µg (OMC30)

K183298 · Hardy Diagnostics · JTN · Jan 18, 2019 · Microbiology

Device Facts

• Record ID: K183298
• Device Name: HardyDisk AST Omadacycline 30µg (OMC30)
• Applicant: Hardy Diagnostics
• Product Code: JTN · Microbiology
• Decision Date: Jan 18, 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.

Device Story

HardyDisk AST Omadacycline 30μg consists of 6-mm filter paper disks impregnated with 30μg Omadacycline; used in clinical microbiology laboratories. Principle: Kirby-Bauer agar diffusion. Process: Inoculum prepared from pure bacterial colonies to 0.5 McFarland turbidity; streaked onto Mueller Hinton agar (or with 5% sheep blood for Streptococcus); disks applied; incubated 16-18 hours at 35°C. Output: Zone of inhibition measured in millimeters. Healthcare providers compare measured zone diameters against established interpretive criteria to categorize bacteria as susceptible, intermediate, or resistant. Results guide antibiotic selection for patients with bacterial infections.

Clinical Evidence

No clinical trials performed. Evidence based on analytical disk-to-MIC correlation studies and quality control data evaluated by CDER to establish breakpoints. Performance characteristics derived from microbiology studies supporting the spectrum of activity for Omadacycline.

Technological Characteristics

The device is a paper disc impregnated with 30μg of omadacycline. It functions via the disk diffusion method (Kirby-Bauer) to create a zone of inhibition on agar media. It is a standalone, non-electronic, manual diagnostic tool.

Indications for Use

Indicated for semi-quantitative in vitro susceptibility testing of rapidly growing and fastidious bacteria to Omadacycline. Patient population includes those with infections caused by S. aureus (MRSA/MSSA), S. lugdunensis, E. faecalis, S. anginosus group, S. pyogenes, H. influenzae, H. parainfluenzae, E. cloacae, K. pneumoniae, and S. pneumoniae. Not active against Morganella, Proteus, or Providencia spp.

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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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
K183298

B. Purpose for Submission:
To obtain a substantial equivalence determination for Omadacycline Antimicrobial Susceptibility Test Disk

C. Measurand:
Omadacycline 30μg

D. Type of Test:
Antimicrobial Susceptibility Test Disks

E. Applicant:
Hardy Diagnostics

F. Proprietary and Established Names:
HardyDisk AST Omadacycline 30μg (OMC30)

G. Regulatory Information:

1. Regulation section:
21 CFR 866.1620 Antimicrobial Susceptibility Test Disc

2. Classification:
Class II

3. Product code:
JTN

4. Panel:

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83, Microbiology

H. Intended Use:

1. 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*.

2. 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 Omadacycline 30μg (OMC30) for *in vitro* agar diffusion susceptibility testing is indicated when there is the need to determine the susceptibility of bacteria to Omadacycline.

HardyDisk AST Omadacycline at concentration 30μg can be used to determine the zone diameter (mm) of Omadacycline against the following bacteria for which Omadacycline has been shown to be active both clinically and *in vitro*:

- *Staphylococcus aureus* (methicillin-susceptible and resistant isolates)
- *Staphylococcus lugdunensis*
- *Enterococcus faecalis*
- *Streptococcus anginosus* group (includes *S. anginosus*, *S. intermedius*, and *S. constellatus*)
- *Streptococcus pneumoniae*
- *Streptococcus pyogenes*
- *Haemophilus influenzae*
- *Haemophilus parainfluenzae*
- *Enterobacter cloacae*
- *Klebsiella pneumoniae*

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3. Special conditions for use statement(s):

For prescription use only

4. Special instrument requirements:

Not applicable.

I. Device Description:

HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 30μg Omadacycline. The disks are marked with the code OMC30, 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.

J. Substantial Equivalence Information:

1. Predicate device name(s):

HardyDisk Tigecycline 15μg

2. Predicate 510(k) number(s):

K062245

3. Comparison with predicate:

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Table 1: Comparison with the Predicate

| Similarities | | |
| --- | --- | --- |
| Item | Device
K183298
HardyDisk
Omadacycline 30μg | Predicate
K062245
HardyDisk
Tigecycline 15μg |
| 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 colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. | Same |
| Inoculation 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 according established interpretive criteria for the drug. | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Product Name | HardyDisk Omadacycline 30μg (OMC30) | HardyDisk Tigecycline |
| Antimicrobial Agent | Omadacycline | Tigecycline |
| Concentration | 30μg | 15μg |

K. Standard/Guidance Document Referenced (if applicable):

CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing

L. Test Principle:

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

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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.

## M. Performance Characteristics (if/when applicable):

Descriptive characteristics were sufficient for the HardyDisk Omadacycline 30μg (OMC30) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. 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 Omadacycline and as noted in the device's intended use.

Data obtained from reproducibility, quality control, and disk to MIC correlation studies was 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 broadly to the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. To address the unknown clinical utility of omadacycline to organisms outside of the drug's indication for use, the following statements are added as footnotes to the Omadacycline 30μg interpretative criteria table in the HardyDisk AST package insert:

- The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, E. faecalis, S. anginosus group, and S. pyogenes may or may not have been established in adequate and well-controlled

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clinical trials. The clinical significance of susceptibility information in such instances is unknown.

- The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Haemophilus spp. and Gram-positive organisms other than S. aureus (MSSA only) and S. pneumoniae may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown.
- Omadacycline is not active in vitro against Morganella spp., Proteus spp., and Providencia spp.

1. Analytical performance:
a. Precision/Reproducibility:
Not applicable
b. Linearity/assay reportable range:
Not applicable
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Not applicable
d. Detection limit:
Not applicable
e. Analytical specificity:
Not applicable
f. Assay cut-off:
Not applicable

2. Comparison studies:
a. Method comparison with predicate device:
Not applicable
b. Matrix comparison:

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Not applicable

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable

b. Clinical specificity:

Not applicable

c. Other clinical supportive data (when a. and b. are not applicable):

Not applicable

4. Clinical cut-off:

Not applicable

5. Expected values/Reference range:

The Omadacycline interpretative criteria for disk diffusion is shown in Table 2 and 3 below.

Table 2: Disk Diffusion Interpretative Criteria (Zone diameter in mm) for Omadacycline ${}^{a}$ - Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

| Organism(s) | Susceptible | Intermediate | Resistant |
| --- | --- | --- | --- |
| Enterobacteriaceaeb,c | ≥15 | 16-17 | ≤18 |
| S. aureus(including MRSA isolates) | ≥18 | 19-20 | ≤21 |
| S. lugdunensis | ≥25 | 26-28 | ≤29 |
| E. faecalis | ≥15 | 16-17 | ≤18 |
| S. anginosus groupd | ≥17 | 18-23 | ≤24 |
| S. pyogenes | ≥15 | 16-18 | ≤19 |

Table 3: Disk Diffusion Interpretative Criteria (Zone diameter in mm) for Omadacycline ${}^{a}$ - Community Acquired Bacterial Pneumoniae (CABP)

| Organism(s) | Susceptible | Intermediate | Resistant |
| --- | --- | --- | --- |
| Enterobacteriaceaee,c | ≥15 | 16-17 | ≤18 |
| S. aureus(MSSA isolates only) | ≥20 | 21-22 | ≤23 |
| Haemophilus spp.f | ≥16 | 17-19 | ≤20 |
| S. pneumoniae | ≥16 | 17-19 | ≤20 |

${}^{a}$ FDA-recognized Antimicrobial Susceptibility Test Interpretive Criteria Website

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https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm575163.htm. The QC strains and expected ranges are the same as recommended in CLSI M100 29th edition.

b K. pneumoniae and E. cloacae only.
c Omadacycline is not active in vitro against Morganella spp., Proteus spp., and Providentia spp.
d S. anginosus group includes S. anginosus, S. intermedius, and S. constellatus.
e K. pneumoniae only.
f Haemophilus spp. includes H. influenzae, and H. parainfluenza.

N. Proposed Labeling:

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

O. Conclusion:

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