← Product Code [JWY](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY) · K143288

# Sensititre Susceptibility plates (K143288)

_Thermo Fisher Scientific · JWY · Apr 1, 2015 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K143288

## Device Facts

- **Applicant:** Thermo Fisher Scientific
- **Product Code:** [JWY](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY.md)
- **Decision Date:** Apr 1, 2015
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1640
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The Sensititre® MIC and Breakpoint Susceptibility system is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious Gram negative isolates, comprising of Enterobacteriaceae, Pseudomonas aeruginosa, and other non-Enterobacteriaceae and of non-fastidious Gram positive isolates, comprising of Staphylococcus sp., Enterococcus sp., and Beta haemolytic Streptococci other than S. pneumoniae. The Sensititre® ESBL confirmatory test plate is an in vitro diagnostic product for detection of ESBLs in clinical isolates of Klebsiella pneumoniae, Klebsiella oxytoca and Escherichia coli. MIC and ESBL plates can either be read manually or automatically on the Sensititre Autoreader® / OptiRead® and/or ARIS®. TREK Diagnostic Systems products have only been validated with TREK manufactured broths.

## Device Story

Sensititre susceptibility plates are 96-well microtiter plates pre-dosed with antimicrobial agents (Oritavancin 0.0005-8 µg/mL) and fluorogenic substrates. Clinical laboratory workflow: bacterial isolates are inoculated into plates using the Sensititre AIM Autoinoculator; plates are incubated for 18-24 hours. Principle of operation: bacterial surface enzymes cleave fluorogenic substrates, releasing a fluorophore; fluorescence intensity correlates with bacterial growth. Results are read automatically via OptiRead/ARIS or manually via Vizion. Output: Minimum Inhibitory Concentration (MIC) values. Healthcare providers use MIC results to determine antimicrobial susceptibility, guiding antibiotic therapy decisions for patients with Gram-positive infections. The device provides quantitative susceptibility data to assist in clinical management of non-fastidious Gram-positive organisms.

## Clinical Evidence

No clinical data provided; substantial equivalence is based on bench testing of the antimicrobial susceptibility system.

## Technological Characteristics

In vitro diagnostic susceptibility test system; utilizes MIC panels with Oritavancin (0.0005-8 ug/mL). Designed for non-fastidious Gram-positive organisms. Platform-based testing.

## Regulatory Identification

An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. 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 ASSAY ONLY TEMPLATE

A. 510(k) Number:
K143288

B. Purpose for Submission:
Addition of Oritavancin to the Sensititre 18-24 hour MIC susceptibility system for testing non-fastidious Gram positive organisms

C. Measurand:
Oritavancin in the dilution range of 0.0005-8 µg/mL

D. Type of Test:
Quantitative Antimicrobial Susceptibility Test (AST), growth based fluorescence.

E. Applicant:
Thermo Fisher Scientific

F. Proprietary and Established Names:
Sensititre Susceptibility plates

G. Regulatory Information:
1. Regulation section:
21 CFR 866.1640 Antimicrobial Susceptibility Test Powder
2. Classification:
Class II
3. Product code(s):
JWY - Manual Antimicrobial Susceptibility Test Systems
LRG - Instrument for Auto Reader & Interpretation of overnight susceptible systems

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LTT – Panels, Test, Susceptibility, Antimicrobial

4. Panel:
83 - Microbiology

H. Intended Use:

1. Intended use(s):

The Sensititre® MIC and Breakpoint Susceptibility system is an *in vitro* diagnostic product for clinical susceptibility testing of non-fastidious Gram negative isolates, comprising of *Enterobacteriaceae*, *Pseudomonas aeruginosa*, and other non-*Enterobacteriaceae* and of non-fastidious Gram positive isolates, comprising of *Staphylococcus* sp., *Enterococcus* sp., and Beta haemolytic *Streptococci* other than *S. pneumoniae*. The Sensititre® ESBL confirmatory test plate is an *in vitro* diagnostic product for detection of ESBLs in clinical isolates of *Klebsiella pneumoniae*, *Klebsiella oxytoca* and *Escherichia coli*. MIC and ESBL plates can either be read manually or automatically on the Sensititre Autoreader® / OptiRead® and/or ARIS®. TREK Diagnostic Systems products have only been validated with TREK manufactured broths.

2. Indication(s) for use:

The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System is an *in vitro* diagnostic product for clinical susceptibility testing of non-fastidious isolates.

This 510 (k) is for the newly approved Oritavancin, in the dilution range of 0.0005-8 µg/mL for testing non-fastidious gram positive organisms on the Sensititre 18-24 hour MIC panel.

The approved primary “Indications for Use” and clinical significance for non-fastidious Gram positive isolates:

*Staphylococcus aureus* (including methicillin-resistant [MRSA] and methicillin susceptible (MSSA) isolates)

*Enterococcus faecalis* (vancomycin-susceptible isolates only)

3. Special conditions for use statement(s):

Prescription use only

The ability of the Sensititre® system to detect resistance or non-susceptibility to antimicrobials as shown below is unknown because an insufficient number of resistant or non-susceptible strains were available at the time of comparative testing. If such a strain is observed, it should be submitted to a reference laboratory for further testing.

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The performance of Oritavancin with S. aureus and E. faecalis was performed using the AIM Autoinoculator. The use of an alternative inoculation system when testing Oritavancin has not been evaluated.

Due to the lack of intermediate and resistant interpretations for Oritavancin, there is a potential very major error rate. There were 3 isolates out of 9 non-susceptible isolates that reported one doubling dilution lower than the reference. Use an alternative testing method prior to reporting results for Enterococcus faecalis and Staphylococcus aureus with Oritavancin when the Sensititre MIC is 0.12 µg/mL (breakpoint) if critical to patient care".

4. Special instrument requirements:

The Sensititre Autoinoculator/AIM

The Sensititre Optiread System

The Sensititre Vizion

I. Device Description:

Each plate is dosed with antimicrobial agents at appropriate dilutions. Results can be read manually by visual reading of growth or automatically on an ARIS® / Autoreader® / OptiRead® using fluorescence. The Sensititre Autoreader/OptiRead® system utilizes fluorescence technology. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a non-fluorescent (fluorogenic) substrate. The non-fluorescent substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond, which prevents fluorescence. The fluorophore is then said to be quenched. Enzymatic action of the bacterial surface enzymes on the specific substrates cleaves this bond releasing the fluorophore, which is now capable of fluorescence. The amount of fluorescence detected is directly related to the activity of the bacterial surface enzymes and, therefore, to the bacterial growth.

J. Substantial Equivalence Information:

1. Predicate device name(s):

MicroScan® Dried Gram-Negative and Gram Positive MIC/Combo Panels.

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

k010159

3. Comparison with predicate:

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Table 1. Comparison of the Sensititre  ${18} - {24}\mathrm{\;h}$  with the Predicate Device

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Test Panel | Each 96 well plate is precision dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate | Antimicrobial agents are precision dosed into 96 wells and combined with culture media in the panel then dried. The bacterial standardized suspension is used to rehydrate the panel.  |
|  Intended Use | The Sensititre MIC or Breakpoint Susceptibility system is an in vitro diagnostic product for clinical susceptibility testing. | MicroScan panels are designed for use in determining antimicrobial agent susceptibility for gram positive isolates, gram negative isolates.  |
|  Test Organisms | Non-fastidious gram positive isolates from culture | Non-fastidious gram positive and gram negative isolates  |
|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Product Name | Sensititre™ 18-24 hour Susceptibility System S. aureus, E. faecalis Oritavancin | MicroScan®, Dried Gram Negative and Gram-Positive MIC/Combo Panels K010159  |
|  Antibiotic/Assay | Oritavancin | Gatifloxacin  |
|  Incubation | 18-24 hours | 16-20 hours  |
|  Reading method | Automated OptiRead by detection of fluorescence. Or by reading of growth on the Vizion. | Organism growth read visually or by MicroScan instrumentation  |
|  Instrumentation | Each plate is dosed with antimicrobial agents at appropriate dilutions and inoculated with standardized organism suspension. Results can be read automatically on ARIS®/Autoreader®/OptiRead® using fluorescence or manually on the Vizion or a manual viewer, by visual reading of growth. | MicroScan®, Dried Gram-Negative and Gram-Positive MIC/Combo panel is inoculated with a standardized organism suspension, incubated in a non-CO2 incubator, and visually read or read by MicroScan instrumentation  |

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

1. Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucmO71462.pdf

2. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, Approved Standard-9th Edition, Document M07-A9

3. Performance Standards for Antimicrobial Susceptibility Testing - 24th Informational Supplement, M100-S24 (QC parameters only)

L. Test Principle:

Sensititre susceptibility plates are multi-well plastic microtiter plates that contain doubling dilutions of antibacterial agents. Each plate is dosed with antimicrobial agents at appropriate dilutions. Results can be read manually by visual reading of growth or automatically on an Autoreader® using fluorescence. The Sensititre Autoreader system utilizes fluorescence technology which involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a non-fluorescent (fluorogenic) substrate. The substrate can be added to the inoculum broth and dispensed into the test plates at the same time as the test organism or the plates can be prepared with the substrate already added to the plate. The nonfluorescent substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond, which prevents fluorescence (i.e. the fluorophore is quenched in this state). Enzymatic action of the bacterial surface enzymes on the specific substrates cleaves this bond releasing the fluorophore which is now capable of fluorescence. The amount of fluorescence detected is directly related to the activity of the bacterial surface enzymes and, therefore, to bacterial growth.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

A reproducibility study was conducted at three study sites Non-fastidious Gram positive isolates (37) were tested at each site on the Sensititre18-24 hour Susceptibility System only. Due to insufficient reproducibility isolates tested, based on "Indications for Use" as per the FDA, two studies labeled study 1 and study 2 were included as recommended by the pre-submission (Q141181). Study 1, consisted of 15 gram positive organisms (9 S. aureus, 6 E. faecalis) and study 2 consisted 22 gram positive organisms (13 S. aureus, 9 E. faecalis). Testing was performed using Sensititre plates only, read manually and automatically (18-20 hours). Staphylococcus aureus (including methicillin-resistant (MRSA) and methicillin-susceptible (MSSA)

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isolates), Enterococcus faecalis (Vancomycin-susceptible isolates only).

Results were read by the automated read [Study 1 (AutoReader), Study 2 (OptiRead)] and by reading on the Vizion.

Reproducibility was calculated as the percent of results for the combined sites which were within +/- one doubling dilution of the mode MIC value for all sites.

For the sake of reproducibility calculations, off-scale values are handled in two ways; "best case" and "worst case" scenarios. Best case calculation for reproducibility assumes the off-scale result is within one well from the mode MIC value. Worst case calculation for reproducibility assuming the off-scale result is greater than one well from the mode MIC value. There were no off-scale results in this study. So, only one value for overall reproducibility is reported for each reading method.

For reading on the Vizion, the reproducibility in study 1 was 97.7%, and 95.4% in study 2. The overall reproducibility combined in Study 1 and Study 2 (supplemental study) was 96.4% for both S. aureus and E. faecalis.

For the automated read the AutoReader was utilized in Study 1 with a reproducibility of 97.7% and the OptiRead was utilized in Study 2 with a reproducibility of 95.4% for both S. aureus and E. faecalis.

The results were acceptable.

b. Linearity/assay reportable range:

Not applicable

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The FDA (CDER) and CLSI recommended QC isolates were tested on every test occasion with the reference method and the Sensititre. The reference method QC results were in range for every day tested. The Sensititre Susceptibility plate was tested a sufficient number of times to demonstrate that the system can produce QC results in the recommended range.

Quality Control was performed at all sites using the Sensititre Autoinoculator/AIM for inoculation, read by the Vizion and the automated (i.e. OptiRead) read methods. Table 2 below represents the frequency of the results and all results were in acceptable range.

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Table 2. Summary of Quality Control Results for Oritavancin for Non-Fastidious Organisms

|  ORGANISMS | Oritavancin (μg/mL) | Reference Manual Read | Sensititre- Read Method  |   |
| --- | --- | --- | --- | --- |
|   |   |   |  Optiread | Vizion  |
|  S. aureus ATCC 29213
0.015-0.12μg/mL | 0.008 | 0 | 0 | 0  |
|   |  0.015 | 5% (3/60) | 0 | 0  |
|   |  0.03 | 70% (42/60) | 1.6% (1/60) | 6.6% (4/60)  |
|   |  0.06 | 16.6% (10/60) | 76.6% (46/60) | 78.3% (47/60)  |
|   |  0.12 | 8.3%(5/60) | 21.6% (13/60) | 15% (9/60)  |
|   |  0.25 | 0 | 0 | 0  |
|  E. faecalis ATCC 29212
0.008-0.03μg/mL | 0.004 | 0 | 0 | 0  |
|   |  0.008 | 65% (39/60) | 55% (33/60) | 65% (39/60)  |
|   |  0.015 | 30% (18/60) | 30% (18/60) | 21.6% (13/60)  |
|   |  0.03 | 5% (3/60) | 15% (9/60) | 13.3% (8/60)  |
|   |  0.06 | 0 | 0 | 0  |

Quality Control (QC) results for the Sensititre Susceptibility System using either reading methods demonstrated that the system could produce the expected quality control results. The QC results with S. aureus ATCC 29213 were within the expected range >95% of the time but an upward MIC trend of Sensititre 18-24 hours was observed compared to the reference method. For the Vizion read (the primary method used in the clinical study) almost 70% of the QC reference MIC results are at 0.03μg/mL, while 78.3% of the Sensititre 18-24 hours manual read QC results are at 0.06μg/mL. For the automated read method 76.7% of the QC reference MIC results are at 0.06μg/mL. This MIC trend was addressed by adding a footnote in the labeling.

The QC results are acceptable.

d. Detection limit:

Not applicable

e. Analytical specificity:

Not applicable

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f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

Performance was established through a clinical study which was conducted at three sites. Studies have been conducted with the Sensititre dried susceptibility plates containing Oritavancin to test susceptibility Gram positive isolates (Sensititre 18-24 hour susceptibility plate). The CLSI microdilution reference methods with 0.002% Polysorbate 80 containing the same antimicrobial in the same dilutions were used for a comparison and evaluation of performance. Sensititre panels were prepared using an alternative method that was developed to provide comparable results to the reference method containing polysorbate-80.

The following footnote was added to the Performance Information insert of the device labeling:

"According to the FDA approved pharmaceutical antimicrobial agent package insert, polysorbate-80 should be used for testing freshly prepared or frozen microtiter trays with Oritavancin. Oritavancin on the Sensititre panel has been developed with an alternative method to provide equivalent performance to the reference method that contained polysorbate-80."

The performance of Oritavancin with Gram positive non-fastidious organisms was performed using the Aim Autoinoculator. The inoculum was prepared using the Sensititre Nephelometer which was calibrated at the start of each test. Plates were inoculated and incubated at 35° C. The reading was done on the automated read (OptiRead) and manually using the Vizion at 18-24 hours.

The device labeling indicates that the 18-24 hour MIC panels Susceptibility System can be manually inoculated. However, this procedural option was not utilized for testing either the clinical isolates or the challenge isolates.

Therefore, the sponsor was asked to include a limitation in the device package insert stating the following:

"The performance of Oritavancin with S. aureus and E. faecalis was performed using the AIM Autoinoculator. The use of an alternative inoculation system when testing Oritavancin has not been evaluated."

For both manual read and automated read, clinical testing was performed on 300 Gram positive isolates (179 S. aureus and 121 vancomycin susceptible Enterococcus faecalis). All were freshly collected clinical isolates. In addition, testing was

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performed on 75 Gram positive stock challenge isolates (40 S. aureus and 35 vancomycin susceptible Enterococcus faecalis, VSE)

The clinical study included 89 Methicillin Susceptible Staphylococcus aureus (MSSA) and 90 Methicillin Resistant Staphylococcus aureus (MRSA); the challenge set was comprised of 20 MSSA and 20 MRSA resulting 109 MSSA and 110 MRSA.

The performance evaluations are shown in tables 3-6 below.

Footnotes for Tables 3-6:
a There are no intermediate or resistant interpretive criteria for Oritavancin. The current absence of resistant isolates precludes defining any results other than "Susceptible."
b The number of potential major errors.
c These isolates would be considered potential very major errors (i.e. false susceptible)

Table 3. Overall Performance of Clinical and Challenge Isolates, Automated Read Method (OptiRead)

|   | Tot | No. EA | EA % | Eval Tot | No. Eval EA | Eval EA % | No. CA | CA % | No. NS | No. S | mina | majab | vmjc  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Clinical | 300 | 292 | 97.3 | 292 | 300 | 97.3 | 294 | 98.0 | 4 | 296 | N/A | 3 | 2  |
|  Challenge | 75 | 75 | 100 | 75 | 75 | 100 | 73 | 97.3 | 5 | 70 | N/A | 2 | 1  |
|  Combined | 375 | 367 | 97.9 | 367 | 375 | 97.9 | 367 | 97.9 | 9 | 366 | N/A | 5 | 3  |

Table 4. Trek Oritavancin Performance of Clinical and Challenge Isolates by Species Automated Read (OptiRead)

|   | EA TOT | EA N | EA % | Eval EA Tot | Eval EAN | Eval EA % | CA N | CA % | No. NS | mina | majab | vmjc  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  MSSA  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 89 | 86 | 96.6 | 89 | 86 | 96.6 | 86 | 96.6 | 2 | N/A | 2 | 1  |
|  Challenge | 20 | 20 | 100 | 20 | 20 | 100 | 19 | 95 | 1 | N/A | 0 | 1  |
|  MRSA  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 90 | 89 | 98.9 | 90 | 89 | 98.9 | 89 | 98.9 | 2 | N/A | 1 | 0  |
|  Challenge | 20 | 20 | 100 | 20 | 20 | 100 | 20 | 100 | 0 | N/A | 0 | 0  |
|  S. aureus (MRSA + MSSA)  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 179 | 175 | 97.8 | 179 | 175 | 97.8 | 175 | 97.8 | 4 | N/A | 3 | 1  |
|  Challenge | 40 | 40 | 100 | 40 | 40 | 100 | 39 | 97.5 | 1 | N/A | 0 | 1  |
|  Combined | 219 | 217 | 99.1 | 218 | 217 | 99.5 | 219 | 100 | 5 | N/A | 3 | 2  |
|  Enterococcus faecalis (vancomycin susceptible isolates only)  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 121 | 117 | 96.7 | 117 | 121 | 96.7 | 119 | 98.3 | 0 | N/A | 2 | 0  |
|  Challenge | 35 | 35 | 100 | 35 | 35 | 100 | 34 | 97.1 | 4 | N/A | 0 | 1  |
|  Combined | 156 | 152 | 97.4 | 152 | 156 | 97.4 | 153 | 98.1 | 4 | N/A | 2 | 1  |

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Table 5. Overall Performance of Clinical and Challenge Isolates, Vizion Read Method

|   | Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | No. NS | No. S | \( \text{min}^{\text{a}} \) | \( \text{maj}^{\text{a,b}} \) | \( \text{vmj}^{\text{c}} \)  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Clinical | 300 | 293 | 97.7 | 293 | 300 | 97.7 | 294 | 98 | 4 | 296 | N/A | 5 | 1  |
|  Challenge | 75 | 75 | 100 | 75 | 75 | 100 | 73 | 97.3 | 5 | 70 | N/A | 0 | 1  |
|  Combined | 375 | 368 | 98.1 | 375 | 368 | 98.1 | 367 | 97.9 | 9 | 366 | N/A | 5 | 2  |

Table 6. Trek Oritavancin Performance of Clinical and Challenge Isolates by Species, Vizion Read Method

|   | EA TOT | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | No. NS | \( \text{min}^{\text{a}} \) | \( \text{maj}^{\text{a,b}} \) | \( \text{vmj}^{\text{c}} \)  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  MSSA  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 89 | 86 | 96.6 | 89 | 86 | 96.6 | 85 | 95.5 | 2 | N/A | 3 | 1  |
|  Challenge | 20 | 20 | 100 | 20 | 20 | 100 | 19 | 95 | 1 | N/A | 0 | 1  |
|  MRSA  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 90 | 89 | 98.9 | 90 | 89 | 98.9 | 90 | 100 | 2 | N/A | 0 | 0  |
|  Challenge | 20 | 20 | 100 | 20 | 20 | 100 | 20 | 100 | 0 | N/A | 0 | 0  |
|  S. aureus (MRSA + MSSA)  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 179 | 175 | 97.8 | 179 | 175 | 97.8 | 175 | 97.8 | 4 | N/A | 3 | 1  |
|  Challenge | 40 | 40 | 100 | 40 | 40 | 100 | 39 | 97.5 | 1 | N/A | 0 | 1  |
|  Combined | 219 | 215 | 98.2 | 219 | 215 | 98.2 | 214 | 97.7 | 5 | N/A | 3 | 2  |
|  Enterococcus faecalis (vancomycin susceptible only)  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 121 | 118 | 97.5 | 118 | 121 | 97.5 | 119 | 98.3 | 0 | N/A | 2 | 0  |
|  Challenge | 35 | 35 | 100 | 35 | 35 | 100 | 34 | 97.1 | 0 | N/A | 0 | 0  |
|  Combined | 156 | 153 | 98.1 | 153 | 156 | 98.1 | 153 | 98.1 | 0 | N/A | 2 | 0  |

EA-Essential Agreement CA-Category Agreement NS-not susceptible

Essential agreement (EA) is when the Sensititre panels agree with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the Sensititre panel result interpretation agrees exactly with the reference panel result interpretation. Evaluable EA is when the MIC result is on scale for both the Sensititre and the reference and have on-scale EA.

The EA% is acceptable when compared to the reference method as described in the FDA guidance document, "Class I1 Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA".

EA and CA for all organisms were greater than  $90\%$  as shown in Table 7 below.

Table 7. Performance of Sensititre Panels Read on the Vizion and Automatically on the OptiRead

|  ORGANISMS | Number of isolates tested | % EA | % CA  |
| --- | --- | --- | --- |
|  Optiread  |   |   |   |
|  S. aureus | 219 | 99.1 | 100  |
|  E. faecalis | 156 | 97.4 | 98.1  |
|  Vizion  |   |   |   |
|  S. aureus | 219 | 98.2 | 97.7  |
|  E. faecalis | 156 | 98.1 | 98.1  |

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For manual reading method in combined clinical and challenge study; there are 8 categorical errors; three of which were  $E$  faecalis, five were  $S$  aureus.

For the automated read method in combined clinical and challenge study; there are 8 categorical errors; three of which were  $E$  faecalis and five were  $S$  aureus.

There are no intermediate or resistance interpretative criteria for Oritavancin. The data was analyzed for major (maj) and very major (vmj) errors only, considering any false susceptible as vmj error and any false non-susceptible as maj error. An analysis was conducted to calculate the vmj error (i.e. false susceptible) as described in Table 8 below.

Table 8. Analysis of False Susceptible Results

|  Organism | Total # of NS by reference method | # vmj (false susceptible) | % of false susceptible | # within EA  |
| --- | --- | --- | --- | --- |
|  OptiRead  |   |   |   |   |
|  |   |   |   |   |
|  E. faecalis | 4 | 1 | 25 | 1  |
|  S. aureus | 5 | 2 | 40 | 2  |
|  Vizion  |   |   |   |   |
|  E. faecalis | 4 | 1 | 25 | 1  |
|  S. aureus | 5 | 2 | 40 | 2  |

We observed that there is a high rate of false susceptible in  $E$  faecalis and  $S$  aureus both Vizion and OptiRead methods. Using the data provided by the sponsor in the diagonal table format recommended in the AST Guidance, the majority of the vmj error (i.e. false susceptible) were observed when the Sensititre MIC is at  $0.12\mu \mathrm{g / mL}$  and the reference method is at one double doubling dilution (MIC  $0.25\mu \mathrm{g / mL}$ ). Due to the lack of an intermediate interpretation for this drug, there is a high potential for occurrence of very major error for  $S$  aureus and  $E$  faecalis that could otherwise be considered minor errors if an intermediate category existed. Any  $S$  aureus and  $E$  faecalis isolates that yield MIC results  $0.12\mu \mathrm{g / mL}$  for Oritavancin should be submitted to a reference laboratory for additional testing.

The potential for occurrence of vmj error(s) for Oritavancin when testing S. aureus and E. faecalis was addressed by adding the following limitation in labeling:

"Due to the lack of intermediate and resistant interpretations for Oritavancin, there is a potential very major error rate. There were 3 isolates out of 9 non-susceptible isolates that reported one doubling dilution lower than the reference. Use an alternative testing method prior to reporting results for Enterococcus faecalis and Staphylococcus aureus with Oritavancin when the Sensititre MIC is  $0.12\mu \mathrm{g} / \mathrm{mL}$  (breakpoint) if critical to patient care".

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# MIC Trend Analysis:

Using the data provided by the sponsor in the diagonal table format recommended in the AST Guidance, an analysis was conducted to check for trending in MIC values.

A higher reading trend was observed in the overall performance of S. aureus in both manual and automated read methods compared to the CLSI broth micro-dilution method, which raises concerns for potential major errors as summarized in Table 9 and 10 below.

Table 9. Trending of Results by Automated Read Method in Combined Clinical and Challenge Study

|  Organism | Difference in MIC as Compared to the CLSI Reference Method  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|   |  -3 | -2 | -1 | 0 | +1 | ≥2  |
|  MRSA | 0 | 0 | 8.2% (9/110) | 30% (33/110) | 60.9% (67/110) | 0.9% (1/110)  |
|  MSSA | 0 | 0 | 5.5% (6/109) | 27.5% (30/109) | 64.2% (70/109) | 1.8% (3/109)  |
|  Total | 0 | 0 | 6.8% (15/219) | 28.7% (63/219) | 62.5% (137/219) | 1.8% (4/219)  |

Table 10. Trending of Results by Vizion Read Method in Combined Clinical and Challenge Study

|  Organism | Difference in MIC as Compared to the CLSI Reference Method  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|   |  -3 | -2 | -1 | 0 | +1 | ≥2  |
|  MRSA | 0 | 0 | 7.3% (8/110) | 33.6% (37/110) | 58.2% (64/110) | 0.9% (1/110)  |
|  MSSA | 0 | 0 | 5.5% (6/109) | 29.4% (32/109) | 62.4% (68/109) | 0.9% (3/109)  |
|  Total | 0 | 0 | 6.4% (14/219) | 31.5% (69/219) | 60.2% (132/219) | 1.8% (4/219)  |

This trending and the potential for occurrence of major errors(s) for Orivancin when testing S.aureus was addressed in labeling. This was addressed by adding the following footnote in the interpretation table in labeling:

"Sensititre Oritavancin MIC values for non-fastidious gram positive organisms tended to be one doubling dilution higher in S. aureus Manual and AutoRead compared to reference broth micro-dilution. S. aureus with an interpretation of non-susceptible for Oritavancin is uncommon in most institutions or may result from technical errors. Verify AST if this phenotype has not been previously encountered from this patient or institution".

{12}

# Growth Rate:

In the manual and automated read the no growth rate was  $0.3\%$  (1/313) MSSA

The growth rate for the manual and automated read methods was greater than  $90\%$ ; this meets the acceptance criteria of  $\leq 10\%$  non-growth of organisms tested.

b. Matrix comparison:

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:

Table 11. FDA Interpretive Criteria for Oritavancin

|  Organism | Interpretive Criteria (Oritavancin MIC in μg/mL)  |   |   |
| --- | --- | --- | --- |
|   |  S | I | R  |
|  S. aureus (MSSA, MRSA) | ≤0.12 | - | -  |
|  E. faecalis (VSE only) | ≤0.12 | - | -  |

Currently, there are no intermediate or resistance interpretative criteria for Oritavancin

# N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

# O. Conclusion:

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

---

**Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K143288](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K143288)

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