SENSITIVE HAEMOPHILUS INFLUENZAE, STREPTOCOCCUS PNEUMONIA, (HP) MIC SUSCEPTIBILITY PLATES

K093741 · Trek Diagnostic Systems, Ltd. · JWY · Feb 25, 2010 · Microbiology

Device Facts

• Record ID: K093741
• Device Name: SENSITIVE HAEMOPHILUS INFLUENZAE, STREPTOCOCCUS PNEUMONIA, (HP) MIC SUSCEPTIBILITY PLATES
• Applicant: Trek Diagnostic Systems, Ltd.
• Product Code: JWY · Microbiology
• Decision Date: Feb 25, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1640
• Device Class: Class 2

Intended Use

The Sensititre® Haemophilus influenza/Streptococcus pneumoniae (HP) MIC susceptibility plates and Justone are in vitro diagnostic products for quantitatively and or qualitative susceptibility testing of isolated colonies of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus species from clinical specimens. Plates can either be read manually or automatically on the Sensititre Autoreader and/or ARIS with Streptococcus pneumoniae and Streptococcus species and manually with H. influenzae. The JustOne® strip can only be read manually. This 510(k) is for the addition of Tigecycline in the dilution range of 0.004 - 8 µg/ml for testing Streptococcus pneumoniae isolates on the Sensititre® (HP) MIC susceptibility system. The additional approved primary "Indications for Use" and clinical significance of Tigecycline is for: Aerobic facultative Gram-positive microorganisms Streptococcus pneumoniae (Penicillin susceptible stains only)

Device Story

Sensititre® HP MIC plates are multi-well microtiter plates containing dried, stabilized antimicrobial dilutions; used for quantitative antimicrobial susceptibility testing (AST). Device accepts bacterial isolates as input; utilizes broth microdilution method. Principle of operation involves fluorescence technology: bacterial growth generates fluorescent product from non-fluorescent substrate; fluorescence intensity correlates with growth. MIC determined by lowest antimicrobial dilution inhibiting growth. Plates read manually or automatically via Sensititre® AutoReader or ARIS®. Used in clinical laboratories by trained personnel. Output provides MIC values and categorical interpretations (SIR) to assist clinicians in selecting appropriate antibiotic therapy for patients with bacterial infections.

Clinical Evidence

Bench testing only. Performance was evaluated by comparing the Sensititre MIC system results to a reference method for the determination of Tigecycline susceptibility in Streptococcus pneumoniae. No clinical trial data was required for this 510(k) submission.

Technological Characteristics

Multi-well plastic microtiter plates; dried, stabilized antimicrobics. Fluorescence-based growth detection. Dimensions: microtiter format. Connectivity: compatible with Sensititre® AutoReader/ARIS® for automated reading. Software: automated analysis of fluorescence signals. Sterilization: not specified.

Indications for Use

Indicated for quantitative/qualitative antimicrobial susceptibility testing of isolated colonies of Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus species from clinical specimens. Specifically for Tigecycline testing of Streptococcus pneumoniae (penicillin-susceptible 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.

Predicate Devices

• Siemens’ Microscan®, Dried Gram-Negative and Gram-Positive MIC/Combo Panels (k010159)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k093741

B. Purpose for Submission:
To add S. pneumoniae to tigecycline on the Sensititre® Haemophilus/Streptococcus pneumoniae (HP) MIC plates

C. Measurand:
Tigecycline 0.004 – 8 µg/mL

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

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:
Class II
3. Product code:
JWY-manual readings of AST testing of >16 hour incubation
LRG Automated readings of AST of >16 hour incubation

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4. Panel:
83 Microbiology

H. Intended Use:

1. Intended use(s):
Sensititre® Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC plates are in vitro diagnostic products for clinical susceptibility testing of H. influenzae, Streptococcus pneumoniae and Streptococcus species.

2. Indication(s) for use:
The Sensititre® HP Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of fastidious organisms.

Plates can either be read manually or automatically on the Sensititre Autoreader and/or ARIS with Streptococcus pneumoniae and Streptococcus species and manually with H. influenzae. The JustOne® strip can only be read manually.

This 510(k) is for the addition of Tigecycline in the dilution range of 0.004 - 8 µg/mL for testing Streptococcus pneumoniae isolates on the Sensititre® (HP) MIC susceptibility system. The additional approved primary "Indications for Use" and clinical significance of Tigecycline is for:
Aerobic facultative Gram-positive microorganisms
Streptococcus pneumoniae (Penicillin susceptible stains only)

3. Special conditions for use statement(s):
Prescription use only

The current absence of resistant isolates precludes defining any results other than "Susceptible." Isolates yielding MIC results suggestive of "Nonsusceptible" category should be submitted to reference laboratory for further testing.

The only method of inoculation used for this drug/bug combination is Autoinoculator. Any other method of inoculation should be validated before use.

4. Special instrument requirements:
Automated readings are performed on the Sensititre® AutoReader or Sensititre® ARIS®.

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I. Device Description:

Sensititre® MIC Susceptibility plate MIC panels are multi-well plastic microtiter plates, precision dosed with dried, stabilized antimicrobics. This is a micro version of the classic broth dilution methods and can provide both qualitative and quantitative susceptibility results.

JustOne® STRIPS:

Refer to the format (in configuration sheet enclosed separately) before using the strips. The JustOne® strip is a single row of 12 wells containing the antimicrobial dilutions along with one positive control well. The positive control wells on each strip contain no antimicrobic and are used to check for satisfactory growth in the broth system used. The JustOne® strip is equal to one row of the Sensititre MIC susceptibility plate and can only be read manually.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Siemens’ Microscan®, Dried Gram-Negative and Gram-Positive MIC/Combo Panels

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

k010159

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | an in vitro diagnostic product for clinical susceptibility testing of gram negative and gram positive organisms. | Microscan panels are designed for use in determining antimicrobial agent susceptibility for gram positive isolates, gram negative isolates, and Streptococcus spp. |
| Inoculum | Prepared from colonies using the direct inoculation method | Prepared from colonies using the direct inoculation method |
| Inoculation method | Direct equated to a 0.5 McFarland | Direct equated to a 0.5 McFarland |
| Technology | Growth based | Growth based |
| Results | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Components | Tigecycline | Different concentrations depending on the antibiotic |

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| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Test organism | S. pneumoniae | Varies according to the antibiotic |

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

Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA”; CLSI M7 (M100-S19) “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.

## M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

A reproducibility study was performed on 10 S. pneumoniae and 15 Streptococcus species (spp.) for testing with tigecycline. These were tested once at each of the three sites on the automated and manual read method demonstrating >95% reproducibility for both read methods.

b. Linearity/assay reportable range:

Not Applicable

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

The QC performance was within the expected ranges as shown in the table below. Quality control was also performed at all sites using both manual and autoread methods. The Sensititre® results demonstrated that the system can produce QC results in the recommended range for both manual and automated read methods.

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Quality Control Table

| ORGANISM | Conc ug/mL | Sensititre® Autoread | Sensititre® manual | Reference |
| --- | --- | --- | --- | --- |
| | | | | |
| S. pneumoniae | 0.008 | | | |
| ATCC 49619 | 0.015 | 40 | 39 | 33 |
| Expected Range : | 0.03 | 30 | 31 | 37 |
| 0.015 – 0.12 ug/ml | 0.06 | | | |
| | | | | |

A Nephelometer was used at each site to standardize the inoculum and it was calibrated each time it was switched on. A colony count from the QC ATCC source was performed using the direct inoculum method and the mean result was within the minimum and maximum ranges.

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:
The broth dilution reference panel was prepared according to CLSI recommendation. Clinical testing was performed on 227 Streptococcus isolates which included fresh and stock clinical isolates and a set of challenge organisms. The broth reference panel for Streptococcus pneumoniae was set up on a cation adjusted MH broth with 2% to 5% lysed horse blood and incubated at 35°C; ambient air for 20 – 24 hours as recommended by CLSI. The comparison resulted in the following performance evaluations as reflected below.

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Summary Table (Manual Read Method)

| Organism Group | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #NS | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 151 | 148 | 99.3 | 150 | 147 | 99.3 | 151 | 100 | N/A | 0 | 0 | 0 |
| Challenge | 76 | 76 | 100 | 76 | 76 | 100 | 76 | 100 | N/A | 0 | 0 | 0 |
| Combined | 227 | 224 | 98.7 | 226 | 223 | 98.7 | 227 | 100 | N/A | 0 | 0 | 0 |

Summary Table (Automated Read Method)

| Organism Group | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #NS | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 151 | 147 | 98.7 | 149 | 146 | 99.3 | 151 | 100 | N/A | 0 | 0 | 0 |
| Challenge | 76 | 76 | 100 | 76 | 76 | 100 | 76 | 100 | N/A | 0 | 0 | 0 |
| Combined | 227 | 223 | 98.2 | 223 | 222 | 99.6 | 227 | 100 | N/A | 0 | 0 | 0 |

EA-Essential Agreement
CA-Category Agreement
N/A – not applicable
NS – Not Susceptible Isolates

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. Evaluable EA is when the MIC result is on scale for both the Sensititre® and the reference and have on-scale EA. The EA% is acceptable when compared to the reference method as described in the FDA guidance document, “Class 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. The growth rate for Streptococcus pneumoniae is greater than 90%.

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

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4. Clinical cut-off:
Not Applicable

5. Expected values/Reference range:
S. pneumoniae ≤0.06*
* Limitation statement: The current absence of resistant isolates precludes defining any category other than "Susceptible". Isolates yielding MIC results suggestive of "Nonsusceptible" category should be submitted to a reference laboratory for further testing.

N. Proposed Labeling:
The expected range, interpretive criteria and QC are included in the package insert. The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10.

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

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