← Product Code [JWY](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY) · K241967

# The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC or Breakpoint Susceptibility System with ceftriaxone in the dilution range of 0.015 - 2 ug/ml. (K241967)

_Thermo Fisher Scientific · JWY · Oct 1, 2024 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K241967

## Device Facts

- **Applicant:** Thermo Fisher Scientific
- **Product Code:** [JWY](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY.md)
- **Decision Date:** Oct 1, 2024
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1640
- **Device Class:** Class 2
- **Review Panel:** Microbiology
- **Attributes:** PCCP

## Indications for Use

The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus species.

## Device Story

Sensititre 20-24 hour HP MIC or Breakpoint Susceptibility System is an in vitro diagnostic device for quantitative antimicrobial susceptibility testing (AST). The system uses 96-well microtiter plates pre-dosed with dried, stabilized ceftriaxone (0.015–2 µg/mL). Clinical isolates are inoculated into the plates using the Sensititre AIM Autoinoculator. Plates are incubated for 20-24 hours at 34-36°C. Bacterial growth is detected either visually via the VIZION digital viewing device or automatically via the ARIS/OptiRead system, which uses fluorescence technology to monitor surface enzyme activity. The MIC is determined as the lowest concentration of ceftriaxone inhibiting visible growth. Results assist clinicians in selecting appropriate antibiotic therapy for fastidious bacterial infections. The device is intended for use in clinical laboratory settings.

## Clinical Evidence

Bench testing only. Performance evaluated using 410 clinical and 188 challenge Streptococcus isolates. Essential Agreement (EA) and Categorical Agreement (CA) were calculated against CLSI reference methods. For S. pneumoniae (meningitis breakpoints), EA was 94.7% and CA was 92.9% (ARIS HiQ). For S. pyogenes/S. agalactiae, EA was 99.0% and CA was 99.5%. Reproducibility was >95% for most conditions. No clinical data provided.

## Technological Characteristics

Multi-well plastic microtiter plates containing dried, stabilized ceftriaxone. Principle: microbroth dilution. Energy source: electrical (for incubation and automated reading). Connectivity: standalone or networked (ARIS/OptiRead). Reading methods: fluorescence-based automated detection (OptiRead) or visual digital imaging (VIZION). Inoculation: Sensititre AIM Autoinoculator required. Sterilization: not specified.

## 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)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
> Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/).

{0}

FDA U.S. FOOD & DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K241967

B Applicant

Thermo Fisher Scientific

C Proprietary and Established Names

The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC or Breakpoint Susceptibility System with Ceftriaxone in the dilution range of 0.015 - 2 µg/ml.

D Regulatory Information

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

## II Submission/Device Overview:

### A Purpose for Submission:

To obtain substantial equivalence determination for the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC or Breakpoint Susceptibility System with Ceftriaxone in the dilution range of 0.015 – 2 µg/mL with updated FDA-recognized breakpoints for Streptococcus spp. and an expanded dilution range from 0.06 – 2 µg/mL cleared in K062681.

Breakpoints for Haemophilus influenzae (also indicated for use with this device) remain unchanged.

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

{1}

B Measurand:

Ceftriaxone in the dilution range of 0.015 - 2 µg/mL

C Type of Test:

Quantitative Antimicrobial Susceptibility Test (AST) growth-based detection

III Intended Use/Indications for Use:

A Intended Use(s):

The Sensititre Haemophilus influenzae/Streptococcus pneumoniae plates are in vitro diagnostic products for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus species.

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 ceftriaxone in the dilution range of 0.015 - 2 µg/ml for testing fastidious isolates on the Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System.

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

Streptococcus pneumoniae

Streptococcus pyogenes

Streptococcus spp. Viridans Group

Haemophilus influenzae

Ceftriaxone has been shown to be active in vitro only against the following organisms of the FDA drug label:

Streptococcus agalactiae

C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

Bold text was used to indicate updates to the limitations to include ceftriaxone.

The evaluation of Tedizolid and Dalbavancin, with Streptococcus spp. (Streptococcus pyogenes, S. agalactiae, and S. anginosus), Delafloxacin with Streptococcus pyogenes, S. agalactiae, S. anginosus, S. pneumoniae and H. influenzae, Imipenem-relebactam with H. influenzae, Imipenem with S. pneumoniae, Ceftolozane-tazobactam with H. influenzae, and the evaluation

K241967 - Page 2 of 12

{2}

of Oritavancin with Streptococcus spp. (Streptococcus pyogenes, S. agalactiae, S. dysgalactiae, and S. anginosus), Ceftriaxone with Streptococcus pneumoniae, Streptococcus spp. (Streptococcus pyogenes and S. agalactiae), Streptococcus spp. Viridans Group was performed using the AIM autoinoculator. The use of an alternative inoculation system when testing Tedizolid, Dalbavancin, Delafloxacin, Oritavancin Imipenem-Relebactam, Imipenem, Ceftriaxone and Ceftolozane-tazobactam has not been evaluated.

Due to a lack of interpretive criteria other than susceptible for ceftriaxone, isolates of S. pyogenes yielding MIC results other than Susceptible should be submitted to a reference laboratory for further testing.

## D Special Instrument Requirements:

- Sensititre AIM Autoinoculator for device inoculation
- Sensititre VIZION for plate reading

## IV Device/System Characteristics:

### A Device Description:

The device is an antimicrobial susceptibility test. Each plate is dosed with dried, stabilized antimicrobial agents at appropriate dilutions. It is a micro-version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34-36°C for 20-24 hours and examined for bacterial growth.

### 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 nonfluorescent 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.

K241967 - Page 3 of 12

{3}

Streptococcus spp. plates can either be read automatically on an ARIS/Autoreader/OptiRead using fluorescence or by visual reading of growth on the VIZION digital viewing device.

## V Substantial Equivalence Information:

### A Predicate Device Name(s):

The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC or Breakpoint Susceptibility System with Imipenem in the dilution range of 0.015 - 4 µg/ml

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

K240445

### C Comparison with Predicate(s):

|  Device & Predicate Device(s): | Device: K241967 | Predicate: K240445  |
| --- | --- | --- |
|  Device Trade Name | The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC or Breakpoint Susceptibility System with Ceftriaxone in the dilution range of 0.015 - 2 µg/ml. | The Sensititre 20 - 24 hour Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC or Breakpoint Susceptibility System with Imipenem in the dilution range of 0.015 - 4 µg/ml.  |
|  General Device Characteristic Similarities  |   |   |
|  Intended Use | The Sensititre Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC Susceptibility plate is an in vitro diagnostic product for clinical susceptibility testing of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species | Same  |
|  Test Panel | 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. | Same  |
|  Incubation | 20–24 hours | Same  |

K241967 - Page 4 of 12

{4}

|  Reading Method | Results can be read using the ARIS HiQ/OptiRead or VIZION (digital viewing device) | Same  |
| --- | --- | --- |
|  General Device Characteristic Differences  |   |   |
|  Test Organisms | Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus spp. Viridans Group and Haemophilus influenzae | Haemophilus influenzae and Streptococcus pneumoniae  |
|  Antibiotic and Dilution Range | Ceftriaxone 0.015 - 2 μg/mL | Imipenem 0.015 - 4 μg/mL  |

## VI Standards/Guidance Documents Referenced:

CLSI M07, "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard - Eleventh Edition", (January 2018)

CLSI M100, "Performance Standards for Antimicrobial Susceptibility Testing; 33rd Edition", (March 2023)

Class II Special Control Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, August 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 Ceftriaxone in the dilution range of 0.015-2 μg/ml was performed at three sites using 16 Streptococcus isolates [Streptococcus pneumoniae (6), Streptococcus pyogenes (1), Streptococcus agalactiae (2), Streptococcus anginosus (1), Streptococcus anginosus group (1), Streptococcus sanguinis (3), Streptococcus salivarius (2)] for a total of four hundred thirty-two (432) data points read automatically with the ARIS HiQ (OptiRead) as well as using the digital viewing/reading device (VIZION). The Sensititre AIM inoculator was used for Sensititre plate inoculation. The mode MIC value was determined, and the reproducibility was calculated based on MIC values falling within ±1 dilution of the mode MIC value. Best-case reproducibility was greater than 95% for Streptococcus spp. read using the autoread method, and 94.9% for Streptococcus spp. read with VIZION, and the worst-case reproducibility was 94.7% for Streptococcus spp. read using the autoread method.

K241967 - Page 5 of 12

{5}

2. Linearity: Not applicable

Analytical Specificity/Interference: Not applicable

3. Assay Reportable Range: Not applicable

4. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

The quality control strain recommended by CLSI, namely S. pneumoniae ATCC 49619, was tested with ceftriaxone at three sites. The QC strain was tested a minimum of 20 times per site and read automatically with the ARIS HiQ and visually using the digital reading device (VIZION). The QC strain was also tested with the reference method. The results demonstrate that the Sensititre Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC Susceptibility plates with ceftriaxone produced quality control results in the recommended range of  $0.03 - 0.12\mu \mathrm{g / mL} > 95\%$  of time (Table 1).

Table 1. QC Results for S. pneumoniae with Ceftriaxone Compared to the Reference Method with the ARIS HiQ and the Digital Reading Device (VIZION)

|  QC Organism | Expected Range (μg/mL) | Concentration (μg/mL) | Reference | Sensititre ARIS HiQ (Autoread) | Sensititre Digital Reading Device  |
| --- | --- | --- | --- | --- | --- |
|  S. pneumoniae ATCC 49619 | 0.03-0.12 μg/mL | ≤0.015 |  |  |   |
|   |   |  0.03 | 3 |  | 3  |
|   |   |  0.06 | 63 | 77 | 66  |
|   |   |  0.12 | 5 | 5 | 13  |
|   |   |  ≥0.25 | 1 | 1 | 1  |

Inoculum Density: Inoculum density checks were performed for all QC, reproducibility and challenge isolates and clinical isolates tested.

Purity Checks: Purity checks were performed each day for each clinical, challenge, reproducibility and QC strain tested. Only results from pure cultures were reported.

Growth Failure: There were two growth failures for S. pneumoniae, one growth failure for S. pyogenes, eight growth failures for Streptococcus spp. Viridans Group, and one growth failure for S. agalactiae.

5. Detection Limit: Not applicable

6. Assay Cut-Off: Not applicable

K241967 - Page 6 of 12

{6}

# B Comparison Studies:

1. Method Comparison with Predicate Device:

Testing of the Sensititre *Haemophilus influenzae/Streptococcus pneumoniae* MIC Susceptibility plates with ceftriaxone was performed at two external sites and one internal site. Results were compared to results obtained with the frozen CLSI broth microdilution reference panel containing ceftriaxone. Sensititre panels were inoculated using only the AIM Autoinoculator and results were interpreted using the ARIS HiQ (Optiread) and using the digital reading device (VIZION). Reference panels were inoculated according to recommendations in the CLSI M07 document and results were interpreted manually using a mirrored reader.

No inoculation system other than the AIM Autoinoculator was used in the comparative study. To address the inoculation method limitation, an existing method limitation was modified in the device labeling to include testing *Streptococcus pneumoniae*, *Streptococcus* spp. β-Hemolytic Group (*Streptococcus pyogenes* and *S. agalactiae*), *Streptococcus* spp. Viridans Group with Ceftriaxone (modifications in bold font):

The evaluation of *Tedizolid* and *Dalbavancin*, with *Streptococcus* spp. (*Streptococcus pyogenes*, *S. agalactiae*, and *S. anginosus*), *Delafloxacin* with *Streptococcus pyogenes*, *S. agalactiae*, *S. anginosus*, *S. pneumoniae* and *H. influenzae*, *Imipenem-relebactam* with *H. influenzae*, *Imipenem* with *S. pneumoniae*, *Ceftolozane-tazobactam* with *H. influenzae*, and the evaluation of *Oritavancin* with *Streptococcus* spp. (*Streptococcus pyogenes*, *S. agalactiae*, *S. dysgalactiae*, and *S. anginosus*), *Ceftriaxone* with *Streptococcus pneumoniae*, *Streptococcus* spp. (*Streptococcus pyogenes* and *S. agalactiae*), *Streptococcus* spp. Viridans Group was performed using the AIM autoinoculator. The use of an alternative inoculation system when testing *Tedizolid*, *Dalbavancin*, *Delafloxacin*, *Oritavancin* Imipenem-Relebactam, *Imipenem*, *Ceftriaxone* and *Ceftolozane-tazobactam* has not been evaluated.

The testing conditions for the reference method consisted of the following:

- Media: per CLSI M07 guidelines for *Streptococcus* spp.
- Inoculum: Inoculated per CLSI M07 guidelines
- Incubation: 34 - 36°C in a non-CO₂ incubator for 20 to 24 hours

*Streptococcus* spp.

- Media: cation-adjusted Mueller Hinton broth with TES buffer (CAMHBT) and cation-adjusted Mueller Hinton broth with TES buffer and lysed horse blood (CAMHBT+LHB, CP-114).
- Inoculum: A suspension approximating a 0.5 McFarland standard was prepared with *Streptococcus* spp. in 5 mL CAMHBT. A volume of 50 μL of the standardized suspension was added to 11 mL of HTM. Susceptibility panels were inoculated with 100 μL of the final organism suspension using the Sensititre AIM.
- Incubation: 34 - 36°C in a non-CO₂ incubator for 20 to 24 hours.

A total of 410 *Streptococcus* clinical isolates and 188 challenge isolates were evaluated using the ARIS HiQ (OptiRead) in this study and the results are provided in Table 2. Using meningitis breakpoints for *S. pneumoniae* read using the ARIS HiQ, the combined clinical and challenge

K241967 - Page 7 of 12

{7}

results (226 isolates) were acceptable at 94.7% and 92.9% for EA and CA, respectively. There were 15 minor errors, one major (1/187 = 0.53%) and no very major errors. Using non-meningitis breakpoints for S. pneumoniae read using the ARIS HiQ (OptiRead), the combined clinical and challenge results (226 isolates) were acceptable at 94.7% and 96.0% for EA and CA, respectively. There were 8 minor errors, one major (1/211 = 0.47%) and no very major errors. For Streptococcus spp. β-Hemolytic Group read using the ARIS HiQ (OptiRead), the combined clinical and challenge results (94 S. pyogenes and 111 S. agalactiae isolates) were acceptable at 99.0% and 99.5% for EA and CA, respectively. There were no potential major errors and one potential very major error (1/1 = 100%) for S. pyogenes. A limitation to address the unacceptable error rate is described below. For Streptococcus spp. Viridans Group read using the ARIS HiQ (OptiRead), the combined clinical and challenge results (167 isolates) were acceptable at 96.4% and 97.6% for EA and CA, respectively. There were 4 minor errors and no major or very major errors.

Table 2. Ceftriaxone Performance of S. pneumoniae, Streptococcus spp. β-Hemolytic Group, and Streptococcus spp. Viridans Group Read by ARIS HiQ (Autoread)

|   | Tot | EA N | EA % | Eval Tot | Eval EA N | Eval EA % | CA Tot | CA % | No. R/N S | No.S | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  S. pneumoniae [≤ 0.5 (S), 1 (I), ≥2 (R)] meningitis breakpoints  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 154 | 151 | 98.1 | 152 | 149 | 96.5 | 98.0 | 95.5 | 6 | 138 | 6 | 1 | 0  |
|  Challenge | 72 | 63 | 87.5 | 69 | 60 | 89.0 | 63 | 87.5 | 9 | 49 | 9 | 0 | 0  |
|  Total | 226 | 214 | 94.7 | 221 | 209 | 94.6 | 210 | 92.9 | 15 | 187 | 15 | 1 | 0  |
|  S. pneumoniae [≤ 1 (S), 2 (I), ≥4 (R)] non-meningitis breakpoints  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 154 | 151 | 98.1 | 152 | 149 | 98.0 | 149 | 96.8 | 2 | 148 | 4 | 1 | 0  |
|  Challenge | 72 | 63 | 87.5 | 69 | 60 | 87.0 | 68 | 94.4 | 3 | 63 | 4 | 0 | 0  |
|  Total | 226 | 214 | 94.7 | 221 | 209 | 94.6 | 217 | 96.0 | 5 | 211 | 8 | 1 | 0  |
|  S. pyogenes and S. agalactiae (Streptococcus spp. β-Hemolytic Group) [≤ 0.5 (S)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 148 | 147 | 99.3 | 148 | 147 | 99.3 | 147 | 99.3 | 1 | 148 | 0 | 0 | 1  |
|  Challenge | 57 | 56 | 98.3 | 57 | 56 | 98.3 | 57 | 100 | 0 | 57 | 0 | 0 | 0  |
|  Total | 205 | 203 | 99.0 | 205 | 203 | 99.0 | 204 | 99.5 | 1 | 204 | 0 | 0 | 1  |
|  Streptococcus spp. Viridans Groupa [≤ 1 (S), 2 (I), ≥4 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 108 | 107 | 99.1 | 108 | 107 | 99.1 | 107 | 99.1 | 0 | 108 | 1 | 0 | 0  |
|  Challenge | 59 | 54 | 91.5 | 56 | 51 | 91.1 | 56 | 94.9 | 3 | 51 | 3 | 0 | 0  |
|  Total | 167 | 161 | 96.4 | 164 | 158 | 96.3 | 163 | 97.6 | 3 | 159 | 4 | 0 | 0  |

aIncluding the following species: S. anginosus (39), S. anginosus group (18), S. constellatus (12), S. intermedius (7), S. mitis (34), S. oralis (2), S. salivarius (19), S. sanguinis (18), and Viridans group streptococci (18).

EA - Essential Agreement

CA - Categorical Agreement

S - Susceptible

NS - Non-susceptible

Maj - Major Discrepancies

EVAL - Evaluable MICs

R - Resistant

min - Minor Discrepancies

vmj - Very Major Discrepancies

Essential agreement (EA) occurs when the result of the reference method and that of the Sensititre panel are within plus or minus one serial two-fold dilution of the antibiotic. Evaluable results are those that are on scale for both the reference method and the Sensititre panel or those in which an off-scale result is at least two doubling dilutions from the on-scale result. Category agreement (CA) occurs when the interpretation of the result of the reference method agrees exactly with the interpretation of the Sensititre panel.

K241967 - Page 8 of 12

{8}

A total of 412 Streptococcus clinical isolates and 188 challenge isolates were evaluated using the digital viewing device (VIZION), in this study and the results are provided in Table 3. Using meningitis ceftriaxone breakpoints, for S. pneumoniae read using the digital viewing device (VIZION), the combined clinical and challenge results (227 isolates) were acceptable at 98.7% and 94.3% for EA and CA, respectively. There were 13 minor errors, and no major or very major errors. Using non-meningitis breakpoints for S. pneumoniae read using the digital viewing device (VIZION), the combined clinical and challenge results (227 isolates) were acceptable at 98.7% and 97.8% for EA and CA, respectively. There were 5 minor errors, and no major or very major errors. For Streptococcus spp. β-Hemolytic Group read using the digital viewing device (VIZION), the combined clinical and challenge results (94 S. pyogenes and 111 S. agalactiae isolates) were acceptable at 99.0% and 99.5% for EA and CA, respectively. There were no potential major errors and one potential very major error (1/1 = 100%). For Streptococcus pyogenes, there was 1 potential very major error using both the VIZION read method and autoread method (potential errors since no other category is defined other than "susceptible only"). Due to the lack of non-susceptible isolates evaluated, the following limitation will be added to the device labeling:

Due to a lack of interpretive criteria other than susceptible for ceftriaxone, isolates of S. pyogenes yielding MIC results other than Susceptible should be submitted to a reference laboratory for further testing.

Due to the lack of non-susceptible isolates evaluated, the potential VMJ error is considered random the following performance footnote will be added to the device labeling:

The 1 potential very major error observed was considered a random error due to the limited number of non-susceptible isolates tested for S. pyogenes.

For Streptococcus spp. Viridans Group read using the digital viewing device (VIZION), the combined clinical and challenge results (168 isolates) were acceptable at 99.4% and 97.6% for EA and CA, respectively. There were 4 minor errors and no major or very major errors.

Table 3. Ceftriaxone Performance of S. pneumoniae, Streptococcus spp. β-Hemolytic Group, and Streptococcus spp. Viridans Group Read by Digital Viewing Device (VIZION)

|   | Tot | EA N | EA % | Eval Tot | Eval EA N | Eval EA % | CA Tot | CA % | No. R/ NS | No.S | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  S. pneumoniae [≤ 0.5 (S), 1 (I), ≥2 (R)] meningitis breakpoints  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 155 | 155 | 100 | 68 | 68 | 100 | 150 | 96.8 | 6 | 139 | 5 | 0 | 0  |
|  Challenge | 72 | 69 | 93.3 | 45 | 42 | 93.3 | 64 | 88.9 | 9 | 49 | 8 | 0 | 0  |
|  Total | 227 | 224 | 98.7 | 222 | 219 | 97.3 | 214 | 94.3 | 15 | 188 | 13 | 0 | 0  |
|  S. pneumoniae [≤ 1 (S), 2 (I), ≥4 (R)] non-meningitis breakpoints  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 155 | 155 | 100 | 153 | 153 | 100 | 153 | 98.7 | 2 | 149 | 2 | 0 | 0  |
|  Challenge | 72 | 69 | 95.8 | 69 | 66 | 95.7 | 69 | 95.8 | 3 | 63 | 3 | 0 | 0  |
|  Total | 227 | 224 | 98.7 | 222 | 219 | 98.6 | 222 | 97.8 | 5 | 212 | 5 | 0 | 0  |
|  S. pyogenes and S. agalactiae (Streptococcus spp. β-Hemolytic Group) [≤ 0.5 (S)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 148 | 147 | 99.3 | 148 | 147 | 99.3 | 147 | 99.3 | 1 | 147 | 0 | 0 | 1  |
|  Challenge | 57 | 56 | 98.3 | 57 | 56 | 98.5 | 57 | 100 | 0 | 57 | 0 | 0 | 0  |
|  Total | 205 | 203 | 99.0 | 205 | 203 | 99.0 | 204 | 99.5 | 1 | 204 | 0 | 0 | 1  |
|  Streptococcus spp. Viridans Group* [≤ 1 (S), 2 (I), ≥4 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 109 | 108 | 99.1 | 109 | 108 | 99.1 | 107 | 98.2 | 0 | 109 | 2 | 0 | 0  |

K241967 - Page 9 of 12

{9}

|   | Tot | EA N | EA % | Eval Tot | Eval EA N | Eval EA % | CA Tot | CA % | No. R/ NS | No.S | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Challenge | 59 | 59 | 100 | 56 | 56 | 100 | 57 | 96.6 | 3 | 51 | 2 | 0 | 0  |
|  Total | 168 | 167 | 99.4 | 165 | 164 | 96.3 | 163 | 97.6 | 3 | 160 | 4 | 0 | 0  |

aIncluding the following species: S. anginosus (39), S. anginosus group (18), S. constellatus (12), S. intermedius (8), S. mitis (34), S. oralis (2), S. salivarius (19), S. sanguinis (18), and Viridans group streptococci (18).

EA - Essential Agreement

CA - Categorical Agreement

S-Susceptible

NS - Non-susceptible

Maj - Major Discrepancies

EVAL - Evaluable MICs

R - Resistant

min - Minor Discrepancies

vmj - Very Major Discrepancies

Essential agreement (EA) occurs when the result of the reference method and that of the Sensititre panel are within plus or minus one serial two-fold dilution of the antibiotic. Evaluable results are those that are on scale for both the reference method and the Sensititre panel or those in which an off-scale result is at least two doubling dilutions from the on-scale result. Category agreement (CA) occurs when the interpretation of the result of the reference method agrees exactly with the interpretation of the Sensititre panel.

# Trending

A trending analysis was conducted using the combined data (clinical and challenge) obtained for both the ARIS HiQ (OptiRead) and the digital viewing device (VIZION) for S. pneumoniae, Streptococcus spp.  $\beta$ -Hemolytic Group, and Streptococcus spp. Viridans Group. This trending calculation takes into account MIC values that are determined to be one or more doubling dilutions lower or higher than the reference method irrespective of whether the device MIC values are on-scale or not. Results that are not clearly 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.

Species for which the difference between the percentage of isolates with higher vs. lower readings was  $>30\%$  and for which the confidence interval was determined to be statistically significant were considered to show evidence of trending. Trending that shows higher or lower MIC values compared to the reference is addressed in the labeling.

Evaluation of results for S. pneumoniae, Streptococcus spp.  $\beta$ -Hemolytic Group and Streptococcus spp. Viridans Group and ceftriaxone using either the autoread method (ARIS HiQ) and the digital viewing device (VIZION) did not indicate trending for these organisms (Tables 4 and 5).

K241967 - Page 10 of 12

{10}

Table 4. Trending Analysis for S. pneumoniae, Streptococcus spp. β-Hemolytic Group, and Streptococcus spp. Viridans Group with Ceftriaxone Read by Sensititre ARIS HiQ (Autoread)

|  Organism | Total Evaluable for Trending | ≥ 1 Dilution lower No. (%) | Exact No. (%) | ≥ 1 Dilution Higher No. (%) | Percent Difference (95% CI) | Trending Noted  |
| --- | --- | --- | --- | --- | --- | --- |
|  S. pneumoniae | 221 | 16 (7.2%) | 145 (65.6%) | 60 (27.1%) | 20% (13% to 27%) | No  |
|  β-Hemolytic Streptococcus spp. | 205 | 14 (6.8%) | 150 (73.2%) | 41 (20.0%) | 13% (7% to 20%) | No  |
|  Streptococcus spp. Viridans Group | 164 | 46 (28.1) | 90 | 28 (17.1) | -11% (-20 to -2%) | No  |

Table 5. Trending Analysis S. pneumoniae, Streptococcus spp. β-Hemolytic Group, and Streptococcus spp. Viridans Group Isolates Read by Digital Viewing Device (VIZION)

|  Organism | Total Evaluable for Trending | ≥ 1 Dilution lower No. (%) | Exact No. (%) | ≥ 1 Dilution Higher No. (%) | Percent Difference (95% CI) | Trending Noted  |
| --- | --- | --- | --- | --- | --- | --- |
|  S. pneumoniae | 222 | 53 (23.9%) | 139 (62.6%) | 30 (13.5%) | -10% (-18.0% -to -3%) | No  |
|  Streptococcus spp. β-Hemolytic Group | 205 | 11 (5.4%) | 142 (69.3%) | 29 (14.1%) | 14% (7% to 21%) | No  |
|  Streptococcus spp. Viridans Group | 165 | 30 (18.2) | 97 | 38 (23.0) | 5% (-4% to 14%) | No  |

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 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

K241967 - Page 11 of 12

{11}

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:

Table 6. FDA-Recognized Interpretive Criteria for Ceftriaxone

|  Organism | Interpretive Criteriaa for Ceftriaxone  |   |   |
| --- | --- | --- | --- |
|   |  Susceptible | Intermediate | Resistant  |
|  S. pneumoniae (meningitis) | ≤0.5 | 1 | ≥2  |
|  S. pneumoniae (non-meningitis) | ≤1 | 2 | ≥4  |
|  Streptococcus spp. β- Hemolytic Group | ≤0.5 | - | -  |
|  Streptococcus spp. Viridans Group | ≤1 | 2 | ≥4  |
|  Haemophilus influenzae | ≤0.25 | - | -  |

aAccording to the FDA STIC Webpage

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.

To support the implementation of changes to FDA-recognized susceptibility test interpretive criteria (i.e., breakpoints), this submission incorporated by reference a breakpoint change protocol that was reviewed and accepted by FDA in submission K231994 cleared on August 25, 2023. This referenced 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 referenced protocol outlined the specific procedures and acceptance criteria that Thermo Fisher Scientific intends to use to evaluate the Sensititre 20-24-hour Haemophilus influenzae/Streptococcus pneumoniae MIC or Breakpoint Susceptibility System with Ceftriaxone when revised breakpoints for ceftriaxone are published on the FDA STIC webpage. The breakpoint change protocol included with the submission indicated that if specific criteria are met, Thermo Fisher Scientific will update the ceftriaxone 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.

K241967 - Page 12 of 12

---

**Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K241967](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K241967)

**Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact).

**Cite:** Innolitics at https://innolitics.com