SENSITITRE HAEMOPHILUS/STREPTOCOCCUS PNEUMONIAE (HP) MIC PLATES

K040619 · Trek Diagnostic Systems, Inc. · JWY · Apr 7, 2004 · Microbiology

Device Facts

• Record ID: K040619
• Device Name: SENSITITRE HAEMOPHILUS/STREPTOCOCCUS PNEUMONIAE (HP) MIC PLATES
• Applicant: Trek Diagnostic Systems, Inc.
• Product Code: JWY · Microbiology
• Decision Date: Apr 7, 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, Streptococcus pneumoniae and other fastidious organisms. This will include clindamycin in the dilution range of 0.016 - 8 ug/mL to the Sensititre® Haemophilus/Streptococcus pneumoniae (HP) MIC susceptibility plate for testing Streptococcus pneumoniae isolates. Not routinely reported on isolates from the urinary tract Prescription use only

Device Story

Sensititre® HP MIC plates are multi-well plastic microtitre plates containing dried, stabilized antimicrobics; used for quantitative antimicrobial susceptibility testing (AST). Inoculum prepared in 2–5% lysed horse blood; plates sealed and incubated at 34–36°C for 20–24 hours. Device detects bacterial growth to determine Minimum Inhibitory Concentration (MIC). Automated reading performed via Sensititre® AutoReader® or ARIS® using fluorescence technology; manual reading performed via viewer or SensiTouch® based on turbidity. Fluorescence detection involves generating a fluorescent product from a non-fluorescent substrate conjugated to enzyme substrates; fluorescence intensity correlates with bacterial growth. Results provide MIC and categorical interpretation (SIR) to guide antimicrobial therapy for fastidious organisms. Used in clinical microbiology laboratories.

Clinical Evidence

Bench testing only. The submission relies on performance validation of the Sensititre MIC plate for the specific antibiotic-organism combination (Clindamycin/Streptococcus pneumoniae) compared to reference broth microdilution methods. No clinical trial data provided.

Technological Characteristics

Multi-well plastic microtitre plates; dried, stabilized antimicrobics. Fluorescence-based growth detection (automated) or turbidity-based (manual). Inoculum standardized via nephelometer. Connectivity via Sensititre® AutoReader® or ARIS®. Software-assisted reading of MIC values.

Indications for Use

Indicated for in vitro clinical susceptibility testing of Haemophilus and Streptococcus pneumoniae isolates to Clindamycin (0.016-8μg/ml).

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:
k040619

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

C. Analyte:
Clindamycin (0.016 - 8 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, Streptococcus pneumoniae and other fastidious organisms.
2. Indication(s) for use:
This will include clindamycin in the dilution range of 0.016 - 8 ug/mL to the Sensititre® Haemophilus/Streptococcus pneumoniae (HP) MIC susceptibility plate for testing Streptococcus pneumoniae isolates.
3. Special condition for use statement(s):
Not routinely reported on isolates from the urinary tract
Prescription use only

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4. Special instrument Requirements:
Automated readings are performed 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. 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, Streptococcus pneumoniae and other fastidious organisms. | 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 clindamycin. 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 method of reading.

b. Linearity/assay reportable range:

Not applicable

c. Traceability (controls, calibrators, or method):

The recommended QC isolate was tested daily with acceptable results with the reference method. Quality control was also performed at all sites using both the manual read method and the Autoread method. The Sensititre® results demonstrated that the system can produce QC results in the recommended range for both the manual method of reading and the automated read method.

| ORGANISM | Conc ug/mL | Reference | Sensititre® Autoread | Sensititre® manual |
| --- | --- | --- | --- | --- |
| S. pneumoniae ATCC 49619
Expected Range 0.03 – 0.12 ug/ml | <0.06 | 65 | 65 | 65 |
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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.

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 309 | 305 | 98.7 | 231 | 227 | 98.3 | 308 | 99.7 | 76 | 1 | 0 | 0 |
| Challenge | 53 | 53 | 100.0 | 40 | 40 | 100.0 | 53 | 100.0 | 14 | 0 | 0 | 0 |
| Combined | 362 | 358 | 98.9 | 271 | 267 | 98.5 | 361 | 99.7 | 90 | 1 | 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 | 305 | 98.7 | 228 | 224 | 98.2 | 309 | 100.0 | 76 | 0 | 0 | 0 |
| Challenge | 53 | 53 | 100.0 | 40 | 40 | 100.0 | 53 | 100.0 | 14 | 0 | 0 | 0 |
| Combined | 362 | 358 | 98.9 | 268 | 264 | 98.5 | 362 | 100.0 | 90 | 0 | 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 $\% \mathrm{EA}$ 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 were very similar to the manual readings with no observable trending. There was one min error for the manual read method which was in essential agreement. No vmj errors and maj errors were encountered in the study.

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The overall EA% of 99.4 and CA% of 99.9 for the manual read and overall EA% of 99.4 and CA% of 100.0 for the Autoread methods were both very good.

The percent no growth in the manual reading 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):
Not applicable

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
≤ 0.25 (S), 0.5 (I), ≥1 (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.