SENSITITRE HAEMOPHILUS/STREPTOCOCCUS PNEUMONIAE (HP) MIC PLATES

K040846 · Trek Diagnostic Systems, Inc. · JWY · Apr 26, 2004 · Microbiology

Device Facts

• Record ID: K040846
• Device Name: SENSITITRE HAEMOPHILUS/STREPTOCOCCUS PNEUMONIAE (HP) MIC PLATES
• Applicant: Trek Diagnostic Systems, Inc.
• Product Code: JWY · Microbiology
• Decision Date: Apr 26, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1640
• Device Class: Class 2

Indications for Use

The Sensititre® Haemophilus/Streptococcus pneumoniae (HP) MIC plates are in vitro diagnostic product for clinical susceptibility testing of Haemophilus influenzae and Streptococcus pneumoniae. This will include ertapenem in the dilution range of 0.008 - 16 ug/mL to the Sensititre® Haemophilus/Streptococcus pneumoniae (HP) MIC susceptibility plate for testing Haemophilus influenzae and Streptococcus pneumoniae isolates.

Device Story

Sensititre® HP MIC plates are multi-well plastic microtitre plates containing dried, stabilized antimicrobics for broth microdilution susceptibility testing. Inoculum prepared in Haemophilus Test medium (H. influenzae) or 2–5% lysed horse blood (S. pneumoniae). Plates are sealed, incubated at 34–36°C for 20–24 hours. Growth is detected via fluorescence (automated) or turbidity (manual). Automated reading uses Sensititre® AutoReader® or ARIS®; manual reading uses viewer or SensiTouch®. Output is Minimum Inhibitory Concentration (MIC) and categorical interpretation (SIR). Used in clinical microbiology laboratories to guide antibiotic therapy decisions for patients with H. influenzae or S. pneumoniae infections.

Clinical Evidence

No clinical data provided. The submission relies on in vitro data demonstrating the performance of the Sensititre HP MIC Susceptibility plate for Ertapenem testing against specified bacterial strains.

Technological Characteristics

Multi-well plastic microtitre plates; dried, stabilized antimicrobics. Sensing principle: fluorescence detection of bacterial growth (automated) or visual turbidity (manual). Energy source: electrical (for automated readers). Connectivity: standalone or networked (ARIS®). Sterilization: not specified. Software: automated growth detection algorithm.

Indications for Use

Indicated for clinical susceptibility testing of H. influenzae and S. pneumoniae isolates. Specifically for Ertapenem testing: S. pneumoniae (penicillin-susceptible strains) and H. influenzae (beta-lactamase negative strains). In vitro data provided for S. pneumoniae (penicillin-intermediate strains) and H. influenzae (beta-lactamase positive strains).

Regulatory Classification

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
DEVICE ONLY TEMPLATE

A. 510(k) Number:
k040846

B. Purpose for Submission
Addition of ertapenem to the Sensititre® Haemophilus/Streptococcus pneumoniae (HP) MIC Susceptibility Plates

C. Analyte:
Ertapenem (0.008 - 16 ug/mL) AST

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

E. Applicant:
TREK Diagnostic Systems, Inc.

F. Proprietary and Established Names:
Sensititre® Haemophilus/Streptococcus pneumoniae (HP) MIC Plates

G. Regulatory Information:
1. Regulation section:
866.1640 Antimicrobial Susceptibility Test Powder
2. Classification:
II
3. Product Code:
JWY-manual readings of AST testing of >16 hour incubation
LRG-Automated readings of AST of >16 hour incubation.
4. Panel:
83 Microbiology

H. Intended Use:
1. Intended use(s):
The Sensititre® Haemophilus/Streptococcus pneumoniae (HP) MIC plates are in vitro diagnostic product for clinical susceptibility testing of Haemophilus influenzae and Streptococcus pneumoniae.
2. Indication(s) for use:
This will include ertapenem in the dilution range of 0.008 - 16 ug/mL to the Sensititre® Haemophilus/Streptococcus pneumoniae (HP) MIC susceptibility plate for testing Haemophilus influenzae and Streptococcus pneumoniae isolates.
3. Special condition for use statement(s):
H. influenzae is a manual read only.
Prescription use only
4. Special instrument Requirements:

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Automated readings are performed for *S. pneumoniae* only on the Sensititre® AutoReader or ARIS®.

## I. Device Description:

Sensititre® Haemophilus/Streptococcus pneumoniae (HP) Susceptibility plates are multi-well plastic microtitre plates, precision dosed with dried, stabilized antimicrobics. This is a microversion of the classic broth dilution methods and can provide both qualitative and quantitative susceptibility results. *H. influenzae* inoculum is prepared in Haemophilus Test medium and *S. pneumoniae* inoculum is prepared in 2 – 5% lysed horse blood. After inoculation, plates are sealed with an adhesive seal, incubated at 34 -36°C for 20 – 24 hours and examined for bacterial growth.

AST results may be read automatically using the Sensititre® AutoReader® or Sensititre® ARIS® or manually using the Sensititre manual viewer or SensiTouch®.

## J. Substantial Equivalence Information:

1. Predicate device name(s):
MicroScan® MICroSTREP plus™ Panel
2. Predicate K number(s):
K021037
3. Comparison with predicate:

| Item | Device | Predicate |
| --- | --- | --- |
| | Similarities | |
| Intended use | an in vitro diagnostic product for clinical susceptibility testing of Haemophilus influenzae and Streptococcus pneumoniae. | an in vitro diagnostic product for clinical susceptibility testing of streptococci including Streptococcus pneumoniae. |
| Type panel | Dried antibiotics | Same |
| Inoculation method | Direct equated to a 0.5 McFarland | Same |
| Results | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | Same |
| | Differences | |
| Reading method | Visual growth and Auto read by instrumentation | Visual growth only |
| Technology | Fluorescence detection of growth | Growth based |

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

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"Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA"; NCCLS M7 (M100-S14)
"Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard"

L. Test Principle:
The Sensititre® Autoread System utilizes fluorescence technology to read 18-24 hour plates. The technology involves the detection of bacterial growth which is determined by generating a fluorescent product from a non-fluorescent substrate. The non-fluorescent substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The substrate is added to the inoculum broth and dispensed into the test plates at the same time as the test organism. 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 manual reading is based solely in visualization of growth as turbidity.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:
a. Precision/Reproducibility:
Reproducibility testing was performed on 25 gram-positive isolates appropriate for testing with ertapenem. These were tested 1 time at each of the three sites on each reading method. This demonstrated >95% reproducibility using either the automated read method or the manual read method.
b. Linearity/assay reportable range:
Not applicable
c. Traceability (controls, calibrators, or method):
The recommended QC isolates were tested daily with acceptable results with the reference method. Quality control was performed at all sites. For the QC organism, S. pneumoniae ATCC 49619, both the manual read method and the Autoread method were used. The Sensititre® results demonstrated that the system can produce QC results in the recommended range for both the manual read and the automated read methods. For the QC organism, H. influenzae ATCC 49766, only the manual read method was used.

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| ORGANISM | Conc ug/mL | Reference | Sensititre® Autoread | Sensititre® manual |
| --- | --- | --- | --- | --- |
| S. pneumoniae
ATCC 49619
Expected Range:
0.03 – 0.25 μg/mL | <0.03 | | 1 | |
| | 0.03 | | 1 | |
| | 0.06 | 28 | 6 | 5 |
| | 0.12 | 38 | 58 | 61 |
| | | | | |
| H. influenzae
ATCC 49766
Expected Range:
0.016 – 0.06 μg/mL | <0.016 | 1 | | |
| | 0.016 | 11 | | 3 |
| | 0.03 | 46 | | 52 |
| | 0.06 | 2 | | 5 |
| | | | | |

Nephelometer was used at each site to standardize the inoculum and it was calibrated each time it was switched on. Colony counts were also performed at each site to demonstrate that colony counts were in the expected range in most occasions.

d. Detection limit:
Not applicable

e. Analytical specificity:
Not applicable

f. Assay cut-off:
Not applicable

2. Comparison studies:

a. Method comparison with predicate device:
Broth reference panels prepared according to the recommendations of the NCCLS standards were used to compare to the Sensititre® panel results. Testing was performed at 3 sites and included fresh and stock clinical isolates and a set of challenge organisms.

The following are the comparative results for the manual read method for H. influenzae.

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | Min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 303 | 300 | 99% | 277 | 274 | 99% | 303 | 100% | 0 | N/A | 0 | 0 |
| Challenge | 53 | 53 | 100% | 47 | 47 | 100% | 53 | 100% | 0 | N/A | 0 | 0 |
| Combined | 356 | 353 | 99% | 324 | 321 | 99% | 356 | 100% | 0 | N/A | 0 | 0 |

NA – No intermediate range therefore no minor errors possible

There were no vmj errors or maj errors in the H. influenzae study. The overall EA% of 99.0 and CA% of 100.0 are both very good. Since only susceptible category exists for H. influenzae, NCCLS recommends repeating of results that are not susceptible.

The percent no growth rate for the H. influenzae group is 0%.

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The following are the comparative results for the manual read method for S. pneumoniae.

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 309 | 309 | 100% | 297 | 297 | 100% | 283 | 92% | 1 | 26 | 0 | 0 |
| Challenge | 53 | 53 | 100% | 52 | 52 | 100% | 48 | 91% | 1 | 5 | 0 | 0 |
| Combined | 362 | 362 | 100% | 349 | 349 | 100% | 331 | 91% | 2 | 31 | 0 | 0 |

The following are the comparative results for the Automated Read method.

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | Min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 309 | 309 | 100% | 293 | 293 | 100% | 290 | 94% | 1 | 19 | 0 | 0 |
| Challenge | 53 | 53 | 100% | 52 | 52 | 100% | 50 | 94% | 1 | 3 | 0 | 0 |
| Combined | 362 | 362 | 100% | 345 | 345 | 100% | 340 | 94% | 2 | 22 | 0 | 0 |

EA-Essential Agreement
CA-Category Agreement
R-resistant isolates

maj-major discrepancies
vmj-very major discrepancies
min- minor discrepancies

EA is when there is agreement between the reference method and the Sensititre panel within plus or minus one serial two-fold dilution of antibiotic. Category agreement (CA) is when the Sensititre® panel result interpretation agrees exactly with the reference panel result interpretation. The EA% is acceptable when compared to the reference method as described in the FDA guidance document, "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA".

Autoread results for S. pneumoniae were very similar to the manual readings with no observable trending. Although the number of resistant isolates tested was not that many, there was sufficient number of evaluable isolates tested. There were 31 min errors for the manual read method and 22 min errors for the autoread method. All min errors were in essential agreement. No vmj errors and maj errors were encountered in this group. The overall EA% of 100.0 and eval EA% of 100.0 for the manual read and overall EA% of 100.0 and eval EA% of 100.0 for the Autoread methods were both very good.

The percent no growth in the manual read method was 0% and the Autoread method was 0%.

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):

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Not applicable

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
H. influenzae ≤ 0.5
S. pneumoniae ≤1(S), 2(I), ≥4 (R)
The Interpretative criteria, QC isolates and the expected ranges are the same as recommended by the NCCLS. All values will be included in the package insert.

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