← Product Code [JWY](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY) · K231988

# Sensititre 20-24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Dalbavancin in the dilution range of 0.0005-2µg/ml (K231988)

_Thermo Fisher Scientific · JWY · Aug 30, 2023 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K231988

## Device Facts

- **Applicant:** Thermo Fisher Scientific
- **Product Code:** [JWY](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY.md)
- **Decision Date:** Aug 30, 2023
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1640
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The Sensititre 20-24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of fastidious isolates. This 510(k) is for dalbavancin in the dilution range of 0.0005 - 2µg/ml with new FDA breakpoints for testing fastidious Streptococcus spp. on the Sensititre 20 - 24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System. Dalbavancin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Streptococcus agalactiae Streptococcus pyogenes Streptococcus anginosus group (S. anginosus, S. constellatus and S. intermedius)

## Device Story

The Sensititre 20-24-hour system is an in vitro diagnostic device used in clinical laboratories for antimicrobial susceptibility testing. It utilizes microbroth dilution to determine the Minimum Inhibitory Concentration (MIC) or breakpoint of dalbavancin against fastidious Streptococcus species. The system provides quantitative susceptibility results, which assist clinicians in selecting appropriate antibiotic therapy for patients with bacterial infections. The device is operated by laboratory personnel in a clinical setting. Results are interpreted by the healthcare provider to guide clinical decision-making regarding antibiotic treatment, potentially improving patient outcomes by ensuring targeted therapy.

## Clinical Evidence

No clinical data provided. The submission relies on bench testing to demonstrate performance for antimicrobial susceptibility testing of the specified organisms.

## Technological Characteristics

Microbroth dilution susceptibility system. Utilizes pre-filled microtiter plates containing varying concentrations of dalbavancin (0.0005-2ug/ml). Designed for 20-24 hour incubation. In vitro diagnostic use.

## 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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FDA U.S. FOOD & DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K231988

B Applicant

Thermo Fisher Scientific

C Proprietary and Established Names

Sensititre 20-24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Dalbavancin in the dilution range of 0.0005-2μg/ml

D Regulatory Information

|  Product Code(s) | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  JWY | Class II | 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder | MI - Microbiology  |
|  LRG | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology  |
|  LTT | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology  |

## II Submission/Device Overview:

### A Purpose for Submission:

To obtain clearance for the Sensititre 20-24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Dalbavancin in the dilution range of 0.0005-2μg/ml with updated FDA-recognized breakpoints for S. pyogenes, S. agalactiae and S. anginosus as well as expand claims to include species within the S. anginosus group (S. anginosus, S. intermedius and S. constellatus).

Previously obtained QC and reproducibility data are applicable to this reevaluation.

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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B Measurand:

Dalbavancin in the dilution range 0.0005 to 2 µg/mL

C Type of Test:

Quantitative antimicrobial susceptibility test (AST), growth-based fluorescence

III Intended Use/Indications for Use:

A Intended Use(s):

See Indications for Use below.

B Indication(s) for Use:

The Sensititre 20-24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of fastidious isolates.

This 510(k) is for dalbavancin in the dilution range of 0.0005 - 2µg/ml with new FDA breakpoints for testing fastidious Streptococcus spp. on the Sensititre 20 - 24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System.

Dalbavancin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label:

Streptococcus agalactiae

Streptococcus pyogenes

Streptococcus anginosus group (S. anginosus, S. constellatus and S. intermedius)

C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

According to the FDA approved pharmaceutical antimicrobial agent package insert, polysorbate-80 should be used for testing freshly prepared or frozen microtiter trays with Dalbavancin. Dalbavancin 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 Dalbavancin with Streptococcus spp. was performed using the AIM autoinoculator. The use of an alternative inoculation system when testing Dalbavancin has not been evaluated.

The ability of the Sensititre system to detect resistance or non-susceptibility to antimicrobics 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.

K231988 - Page 2 of 12

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Sensititre Dalbavancin MIC values for Streptococcus species tended to be one doubling dilution higher than the reference method.

## D Special Instrument Requirements:

Sensititre AIM for device inoculation

Digital reading device Sensititre Vizion, ARIS/OptiRead (AutoReader)

## IV Device/System Characteristics:

### A Device Description:

The Sensititre Haemophilus influenzae/Streptococcus pneumoniae MIC Susceptibility Plate System is a micro-version of the classic broth dilutions method and can provide both qualitative and quantitative susceptibility results in a dried microtiter plate format. Each micro-broth dilution plate is dosed with antimicrobial agents at specific dilutions and then dried. The organism to be tested must be in pure culture and identified as a Streptococcus species. A standardized suspension is prepared from colonies and inoculated into the microtiter plate using the Sensititre AutoInoculator/AIM instrument (AutoInoculator). After the indicated hours of incubation, the microtiter plate is examined for growth to determine the MIC either automatically on an ARIS/Autoreader/OptiRead using fluorescence or by visual reading of growth either on the Vizion digital reading device or on a manual viewer.

### B Principle of Operation:

The Sensititre Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC Susceptibility plates are multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read using the digital reading device (Vizion) or by use of an automated reader (ARIS/OptiRead).

The digital reading device (Vizion) allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 20 to 24 hours incubation. 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 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 enzymatic action of the bacterial surface enzymes on the bound non-fluorescent substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to the activity of bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The non-fluorescent (fluorogenic) substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or the plates can be prepared with the substrate already added to each micro-well.

Streptococcus spp. plates can either be read automatically on an ARIS/Autoreader/OptiRead using fluorescence or by visual reading of growth either on the Vizion digital reader or on a manual viewer.

K231988 - Page 3 of 12

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V Substantial Equivalence Information:

A Predicate Device Name(s):
Sensititre Susceptibility Plates

B Predicate 510(k) Number(s):
K143381

C Comparison with Predicate(s):

|  Device & Predicate Device(s): | Device: K231988 | Predicate: K143381  |
| --- | --- | --- |
|  Device Trade Name | Sensititre 20-24-hour
Haemophilus influenzae/
Streptococcus pneumoniae
MIC or Breakpoint
Susceptibility System with
Dalbavancin in the dilution
range of 0.0005-2μg/ml | Sensititre Haemophilus /
Streptococcus pneumoniae
(HP) MIC Plates with
Dalbavancin at a
concentration of 0.0005 -
2μg/ml  |
|  General Device Characteristic Similarities |  |   |
|  Indications for Use | The Sensititre 20-24-hour
Haemophilus influenzae/Streptococcus
pneumoniae MIC or
Breakpoint Susceptibility
System is an in vitro
diagnostic product for
clinical susceptibility testing
of fastidious isolates.

This 510(k) is for
dalbavancin in the dilution
range of 0.0005 - 2μg/ml
with new FDA breakpoints
for testing fastidious
Streptococcus spp. on the
Sensititre 20 - 24-hour
Haemophilus influenzae/Streptococcus
pneumoniae MIC or
Breakpoint Susceptibility
System.

Dalbavancin has been shown
to be active both clinically
and in vitro against the
following organisms
according to the FDA drug
label: | The Sensititre HP MIC
Susceptibility plate is an in
vitro diagnostic product for
clinical susceptibility
testing of fastidious
isolates. This 510(k) is for
the addition of newly
approved Dalbavancin for
the dilution range of
0.0005–2μg/ml to the
Sensititre HP MIC
Susceptibility plate for
testing Streptococcus
species. The approved
primary “Indications for
Use” and clinical
significance for
Streptococcus spp.:
Streptococcus pyogenes
Streptococcus agalactiae
Streptococcus anginosus  |

K231988 - Page 4 of 12

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|   | Streptococcus agalactiae
Streptococcus pyogenes
Streptococcus anginosus group (S. anginosus, S. constellatus and S. intermedius) |   |
| --- | --- | --- |
|  Test Panel | 96 well plate is 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. | Same  |
|  Instrument | Results can be read automatically on an ARIS/Autoreader/OptiRead using fluorescence or by visual reading of growth either on the Vizion digital device or on a manual viewer. | Same  |
|  Reading Method | Fluorescence or organism growth | Same  |
|  Incubation Temperature | 34-36°C | Same  |
|  Incubation Atmosphere | Ambient air | Same  |
|  Incubation Time | 20-24 hours | Same  |
|  Antibiotic and Dilution Range | Dalbavancin 0.0005 - 2μg/ml | Same  |
|  General Device Characteristic Differences |  |   |
|  Breakpoints | ≤0.25 | ≤0.12  |
|  Indicated Organisms | Streptococcus pyogenes
Streptococcus agalactiae
Streptococcus anginosus group (S. anginosus, S. constellatus and S. intermedius) | Streptococcus pyogenes
Streptococcus agalactiae
Streptococcus anginosus  |

VI Standards/Guidance Documents Referenced:

M07-A9 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Ninth Edition, 2012

M100-S33 Performance Standards for Antimicrobial Susceptibility Testing; 33rd Edition, 2023

K231988 - Page 5 of 12

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Guidance for Industry and FDA: Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems, August 28, 2009

## VII Performance Characteristics (if/when applicable):

### A Analytical Performance:

1. **Precision/Reproducibility:**

A reproducibility study of the Sensititre 20-24-hour *Haemophilus influenzae/Streptococcus pneumoniae* MIC or Breakpoint Susceptibility System with Dalbavancin in the dilution range of 0.0005-2 µg/ml was previously performed in support of K143381. No additional data were reviewed in the current submission.

The reproducibility studies for both the Vizion and AutoRead methods demonstrated acceptable performance of 98.7% and 100%, respectively.

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):**

Quality Control (QC) testing, growth failure rate, purity check plates, and inoculum density check were previously evaluated during review of K143381 and were determined acceptable. No additional data were reviewed in the current submission.

6. **Detection Limit:**

Not applicable.

7. **Assay Cut-Off:**

Not applicable.

### B Comparison Studies:

1. **Method Comparison with Predicate Device:**

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The Sensititre 20-24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Dalbavancin in the dilution range of 0.0005-2μg/ml which was originally cleared in K143381, included indications for Streptococcus agalactiae, Streptococcus pyogenes and Streptococcus anginosus (Viridans Group) read with the Vizion digital reader or using the ARIS/Autoreader/OptiRead (AutoReader) and compared to the CLSI broth microdilution reference method.

The performance of the Sensititre 20-24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Dalbavancin in the dilution range of 0.0005-2μg/ml with S. agalactiae, S. pyogenes and S. anginosus group (S. anginosus, S. constellatus and S. intermedius) using revised criteria currently recognized by FDA was evaluated in the current submission using the original data obtained in support of K143381.

Since there was no change in the design or the dilution range of the Sensititre 20-24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Dalbavancin, the performance evaluation was achieved via re-analysis of the MIC data of the original 510(k) submission (K143381). For this review, the current Dalbavancin interpretive criteria are applied to S. agalactiae, S. pyogenes and S. anginosus group (S. anginosus, S. constellatus and S. intermedius) according to the FDA STIC webpage.

Results obtained with the Thermo Fisher Sensititre dried MIC susceptibility panels with Dalbavancin were compared to results obtained using the reference frozen broth microdilution panel (which was prepared in the original studies according to CLSI M07-A9 guidelines and included 0.002% polysorbate-80). 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 Dalbavancin. Dalbavancin on the Sensititre panel has been developed with an alternative method to provide equivalent performance to the reference method that contained polysorbate-80.

All isolates were tested using the same 13 two-fold dilutions of Dalbavancin in both the Sensititre and reference panels. Dilutions tested were appropriate for the interpretive breakpoints established for the drug.

Test inocula were standardized using a spectrophotometric method; Sensititre panels were inoculated using the Autoinoculator and incubated at 34 to 36°C. Sensititre panels were read using the both the Vizion and the AutoRead methods. Reference panels were inoculated as outlined in the CLSI M07-A9 document and were read manually.

The device labeling indicates that the Haemophilus influenzae/Streptococcus pneumoniae MIC panels can be manually inoculated. However, this procedural option was not utilized for testing either the clinical isolates or the challenge isolates. Therefore, the following limitation was added to the device package insert: "The performance of Dalbavancin with

K231988 - Page 7 of 12

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Streptococcus spp. was performed using the AIM autoinoculator. The use of an alternative inoculation system when testing Dalbavancin has not been evaluated."

Data from a total of 418 (clinical and challenge) Streptococcus spp. isolates that were tested using the AutoRead Method was reanalyzed using the current breakpoints in this submission. The isolates included 358 clinical isolates and 60 challenge isolates.

Results of the re-analyzed 418 Streptococcus spp. clinical and challenge isolates (including 189 Streptococcus pyogenes (Group A Beta-Hemolytic streptococci), 184 Streptococcus agalactiae (Group B Beta-Hemolytic streptococci) and 45 Streptococcus anginosus group are summarized in Table 1. There were no non-susceptible isolates tested based on the revised breakpoints and the potential very major error rate could not be determined.

Based on the lack of non-susceptible isolates, the following statement was applied to Dalbavancin testing in the device package insert: The ability of the Sensititre system to detect resistance or non-susceptibility to antimicrobics 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.

Data from a total of 424 (clinical and challenge) Streptococcus spp. isolates that were tested using the Vizion digital reader was reanalyzed using the current breakpoints in this submission. The isolates included 364 clinical isolates and 60 challenge isolates. Results of the re-analyzed 424 Streptococcus spp. clinical and challenge isolates (including 189 Streptococcus pyogenes (Group A Beta-Hemolytic streptococci), 190 Streptococcus agalactiae (Group B Beta-Hemolytic streptococci) and 45 Streptococcus anginosus are summarized in Table 2.

Table 1: Performance of Clinical and Challenge Isolates by Species, AutoRead Method

|   | Total | #EA | %EA | Eval EA Total | Eval EA # | Eval EA % | #CA | %CA | #NS | #S | mina | majab | vmja  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  S. pyogenes and S. agalactiae (Beta-Hemolytic streptococci) ≤0.25 (S)  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 323 | 311 | 96.3 | 323 | 311 | 96.3 | 323 | 100.0 | 0 | 323 | N/A | 0 | N/A  |
|  Challenge | 50 | 46 | 92.0 | 50 | 46 | 92.0 | 49 | 98.0 | 0 | 50 | N/A | 1 | N/A  |
|  Combined | 373 | 357 | 95.7 | 373 | 357 | 95.7 | 372 | 99.7 | 0 | 373 | N/A | 1 | N/A  |
|  S. anginosus groupa (Viridans) ≤0.25 (S)  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 35 | 35 | 100.0 | 35 | 35 | 100.0 | 35 | 100.0 | 0 | 35 | N/A | 0 | N/A  |
|  Challenge | 10 | 10 | 100.0 | 10 | 10 | 100.0 | 10 | 100.0 | 0 | 10 | N/A | 0 | N/A  |
|  Combined | 45 | 45 | 100.0 | 45 | 45 | 100.0 | 45 | 100.0 | 0 | 45 | N/A | 0 | N/A  |
|  All Streptococcus species  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 358 | 346 | 96.6 | 358 | 346 | 96.6 | 358 | 100.0 | 0 | 358 | N/A | 0 | N/A  |
|  Challenge | 60 | 56 | 93.3 | 60 | 56 | 93.3 | 59 | 98.3 | 0 | 60 | N/A | 1 | N/A  |
|  Combined | 418 | 402 | 96.2 | 418 | 402 | 96.2 | 417 | 99.8 | 0 | 418 | N/A | 1 | N/A  |

N/A, Not applicable
aThere are no intermediate or resistant interpretive criteria for Dalbavancin. The current absence of resistant isolates precludes defining any results other than "susceptible."
bThese isolates would be considered potential major errors (a non-susceptible result obtained for a susceptible organism)
aIncluding the following species: S. anginosus (28), S. constellatus (9), S. intermedius (8).

K231988 - Page 8 of 12

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EA - Essential Agreement

CA - Category Agreement

EVAL - Evaluable isolates

NS - Non-susceptible

maj - major discrepancies

vmj - very major discrepancies

min - minor discrepancies

S - Susceptible

Table 2: Performance of Clinical and Challenge Isolates by Species, Vizion

|   | Total | #EA | %EA | Eval EA Total | Eval EA # | Eval EA % | #CA | %CA | #NS | #S | \( \text{min}^{\text{a}} \) | \( \text{maj}^{\text{a,b}} \) | \( \text{vmj}^{\text{a}} \)  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  S. pyogenes and S. agalactiae (Beta-Hemolytic streptococci) ≤0.25 (S)  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 329 | 317 | 96.4 | 329 | 317 | 96.4 | 328 | 99.7 | 0 | 329 | N/A | 1 | N/A  |
|  Challenge | 50 | 46 | 92.0 | 50 | 46 | 92.0 | 49 | 98.0 | 0 | 50 | N/A | 1 | N/A  |
|  Combined | 379 | 363 | 95.8 | 379 | 363 | 95.8 | 377 | 99.5 | 0 | 379 | N/A | 2 | N/A  |
|  S. anginosus \( group^a \) (Viridans) ≤0.25 (S)  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 35 | 35 | 100.0 | 35 | 35 | 100.0 | 35 | 100.0 | 0 | 35 | N/A | 0 | N/A  |
|  Challenge | 10 | 10 | 100.0 | 10 | 10 | 100.0 | 10 | 100.0 | 0 | 10 | N/A | 0 | N/A  |
|  Combined | 45 | 45 | 100.0 | 45 | 45 | 100.0 | 45 | 100.0 | 0 | 45 | N/A | 0 | N/A  |
|  All Streptococcus species  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 364 | 352 | 96.7 | 364 | 352 | 96.7 | 363 | 99.7 | 0 | 364 | N/A | 1 | N/A  |
|  Challenge | 60 | 56 | 93.3 | 60 | 56 | 93.3 | 59 | 98.3 | 0 | 60 | N/A | 1 | N/A  |
|  Combined | 424 | 408 | 96.2 | 424 | 408 | 96.2 | 422 | 99.5 | 0 | 424 | N/A | 2 | N/A  |

N/A, Not applicable
aThere are no intermediate or resistant interpretive criteria for Dalbavancin. The current absence of resistant isolates precludes defining any results other than "susceptible."
bThese isolates would be considered potential major errors (a non-susceptible result obtained for a susceptible organism)
cIncluding the following species: S. anginosus (28), S. constellatus (9), S. intermedius (8).

EA - Essential Agreement

CA-Category Agreement

EVAL-Evaluable isolates

NS - Non-susceptible

maj - major discrepancies

vmj - very major discrepancies

min - minor discrepancies

S - Susceptible

When applying the new breakpoint of  $\leq 0.25$  (S), the overall performance of Streptococcus spp. using the Autoread method demonstrated an EA of  $96.2\%$  and a CA of  $99.8\%$ . When evaluating Beta-Hemolytic streptococci (S. pyogenes and S. agalactiae), performance was acceptable with an EA of  $95.7\%$  and a CA of  $99.7\%$ . There was one potential major error  $(0.54\%)$  for S. agalactiae. With S. anginosus group isolates, the combined EA and CA was  $100\%$ . The performance based on combined clinical and challenge data was acceptable. The overall performance when using the AutoRead method is shown in Table 1.

When applying the new breakpoint of  $\leq 0.25$  (S), the overall performance of Streptococcus spp. using the Vizion digital reader demonstrated an EA of  $96.2\%$  and a CA of  $99.5\%$ . When evaluating Beta-Hemolytic streptococci (S. pyogenes and S. agalactiae), performance was acceptable with an EA of  $95.8\%$  and a CA of  $99.5\%$ . There were two potential major errors  $(1.05\%)$  for S. agalactiae. With S. anginosus group isolates, the combined EA and CA was  $100\%$ . The performance based on combined clinical and challenge data was acceptable. The overall performance when using the Vizion digital reader is shown in Table 2.

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# MIC Trending

An analysis of trending was conducted using the combined clinical and challenge data for each organism group. This trending calculation considers MIC values that are determined to be one or more doubling dilutions lower or higher compared to the reference method regardless of whether the device MIC values are on-scale. Results that are not clearly determined to be at least one dilution lower, at least one dilution higher or in exact agreement with the CLSI reference method are not considered in the trending analysis. Trending results were stratified by species to assess species-related trends. Species for which the difference between the percentage of isolates with higher or lower readings was $\geq 30$ with a statistically significant confidence interval were considered to show evidence of trending.

The data demonstrated that there was an upward trend in the MIC of the Sensititre panel compared to the reference method. Re-analysis of the trending of results for the AutoRead Method indicated that $77.1\%$ of isolates gave Sensititre results that were $\geq 1$ MIC doubling dilution higher than the MIC determined using the reference method (containing $0.002\%$ polysorbate-80) (Table 3). For the Vizion Read Method, re-analysis of the results indicated that $79.5\%$ of isolates Sensititre results that were $\geq 1$ MIC doubling dilution higher than the MIC determined using the reference method. For most isolates, the higher MIC reading did not result in a change in the categorical interpretation (susceptible vs. non-susceptible).

The following statement is included in the device package insert as a footnote to the interpretation table: "Sensititre Dalbavancin MIC values for Streptococcus species tended to be one doubling dilution higher than the reference method".

The performance of the Sensititre panel for determination of MIC values for Dalbavancin was determined to be acceptable.

Table 3: Trending Re-analysis for Streptococcus spp. with Vizion and ARIS/Autoreader/OptiRead

|  Read Method | Organism | Total Evaluable for Trending | ≥1 Dilution Lower No. (%) | Exact No. (%) | ≥1 Dilution Higher No. (%) | Percent Difference (CI) | Trending Noted  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Vizion | S. pyogenes | 189 | 6 (3.2) | 33 (17.5) | 150 (79.4) | 76.2 | Yes High  |
|   |  S. agalactiae | 190 | 0 (0.0) | 32 (16.8) | 158 (83.2) | 83.2 | Yes High  |
|   |  S. anginosus group | 45 | 0 (0.0) | 16 (35.6) | 29 (64.4) | 64.4 | Yes High  |
|  Autoread | S. pyogenes | 189 | 5 (2.6) | 33 (17.5) | 151 (79.9) | 77.3 | Yes High  |
|   |  S. agalactiae | 184 | 0 (0.0) | 39 (21.2) | 145 (78.8) | 78.8 | Yes High  |
|   |  S. anginosus group | 45 | 1 (2.2) | 13 (28.9) | 31 (68.9) | 66.7 | Yes High  |

Testing/Reporting MICs for Non-indicated Species. For this review, the interpretive criteria are applied to the organisms/organism groups 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 Warnings and Precautions section of the device labeling to address testing and reporting of non-indicated species:

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

K231988 - Page 10 of 12

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specific antimicrobial drugs provides the uses for which the antimicrobial drug is approved.

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 and CLSI susceptibility interpretive criteria for Dalbavancin are listed in Table 4.

Table 4: FDA Recognized Interpretive Criteria for Dalbavancin

|   | Minimum Inhibitory Concentrations (μg/mL)a  |   |   |
| --- | --- | --- | --- |
|  Organisms | S | I | R  |
|  Streptococcus spp. β-Hemolytic Groupb | ≤0.25 | - | -  |
|  Streptococcus spp. Viridans Groupc | ≤0.25 | - | -  |

S = Susceptible; I = Intermediate; R = Resistant
$^{\mathrm{a}}$ FDA-Recognized Antimicrobial Susceptibility Test Interpretative Criteria Website
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm410971.htm
$^{\mathrm{b}}$ Report only on S. pyogenes, S. agalactiae and S. dysgalactiae
$^{\mathrm{c}}$ Report only on S. anginosus group (includes S. anginosus, S. intermedius and S. constellatus)

## VIII Proposed Labeling:

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

## IX Conclusion:

K231988 - Page 11 of 12

{11}

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 the breakpoint change protocol that was reviewed and accepted by FDA during review of K231988. This protocol 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 protocol outlined the specific procedures and acceptance criteria that Thermo Fisher intends to use to evaluate the Sensititre 20-24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Dalbavancin in the dilution range of 0.0005-2μg/ml when revised breakpoints for dalbavancin are published on the FDA STIC webpage. The breakpoint change protocol included in K231988 indicated that if specific criteria are met, Thermo Fisher will update the dalbavancin device label to include (1) the new breakpoints, (2) an updated performance section after re-evaluation of data in this premarket notification with the new breakpoints, and (3) any new limitations as determined by their evaluation.

K231988 - Page 12 of 12

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**Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K231988](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K231988)

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