SUSCEPTIBILITY TEST PLATE FOR ERTAPENEM 0.002-16UG/ML FOR GRAM NEGATIVE. SUSCEPTIBILITY TEST PLATE FOR ERTAPENEM 0.015-

K060621 · Tds Holdings, Inc. · JWY · Apr 21, 2006 · Microbiology

Device Facts

• Record ID: K060621
• Device Name: SUSCEPTIBILITY TEST PLATE FOR ERTAPENEM 0.002-16UG/ML FOR GRAM NEGATIVE. SUSCEPTIBILITY TEST PLATE FOR ERTAPENEM 0.015-
• Applicant: Tds Holdings, Inc.
• Product Code: JWY · Microbiology
• Decision Date: Apr 21, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1640
• Device Class: Class 2

Indications for Use

The Sensititre 18 - 24 hour MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of gram positive and gram negative organisms. This 510(k) is for the addition of Ertapenem in the dilution range of 0.002 -16 ug/ml for gram negative organisms and 0.015-64ug/ml for gram positive organisms to the Sensititre 18 - 24 hour MIC panel for testing gram positive and gram negative isolates. The approved primary "Indications for Use" and clinical significance of Ertapenem is for: Staphylococcus species (methicillin-susceptible strains), Streptococcus agalactiae, Steptococcus pyogenes, Escherichia coli, and Klebsiella pneumoniae. In vitro data, without clinical correlation is provided for: Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Klebsiella oxytoca, Morganella morganii, Proteus mirabilis, Proteus vulgaris, and Serratia marcescens.

Device Story

Sensititre 18-24 hour MIC or Breakpoint Susceptibility System; in vitro diagnostic device for antimicrobial susceptibility testing. Device utilizes microdilution panels containing Ertapenem (0.002-16 ug/ml for gram-negative; 0.015-64 ug/ml for gram-positive). Used in clinical laboratories by trained personnel to determine minimum inhibitory concentrations (MIC) of antibiotics against bacterial isolates. Results assist clinicians in selecting appropriate antibiotic therapy for patients. System provides standardized, automated or manual reading of bacterial growth inhibition to guide clinical decision-making.

Clinical Evidence

Bench testing only. Performance evaluated across 3 sites using clinical and challenge isolates. Gram-positive panels (MSSS, Beta-hemolytic Strep) showed 99.3% Essential Agreement (EA) and 95% Category Agreement (CA). Gram-negative panels (Enterobacteriaceae) showed 98.7% EA and 100% CA. Reproducibility >95% for both automated and manual read methods. Quality control isolates met CLSI ranges.

Technological Characteristics

Multi-well plastic microtitre plates; dried, stabilized antimicrobics. Fluorescence-based growth detection (enzymatic substrate) or manual visual turbidity/deposit assessment. Incubation: 34-36°C. Connectivity: Compatible with Sensititre Autoreader, ARIS, manual viewer, or SensiTouch. Software: Automated reading algorithms for fluorescence intensity analysis.

Indications for Use

Indicated for clinical susceptibility testing of gram-positive and gram-negative organisms. Specifically for Staphylococcus species (methicillin-susceptible), Streptococcus agalactiae, Streptococcus pyogenes, Escherichia coli, and Klebsiella pneumoniae. In vitro data provided for Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Klebsiella oxytoca, Morganella morganii, Proteus mirabilis, Proteus vulgaris, and Serratia marcescens.

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 ASSAY ONLY TEMPLATE

A. 510(k) Number:
K060621

B. Purpose for Submission:
Submission of the antibiotic ertapenem at concentrations of 0.002 - 16 µg/mL for Gram Negative organisms and at concentrations of 0.015-64 µg/mL for Gram Positive organisms to the Sensititre 18-24 hour MIC panels.

C. Measurand:
Ertapenem at 0.002 - 16 µg/mL and at 0.015-64 µg/mL

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

E. Applicant:
TREK Diagnostic Systems, Inc.

F. Proprietary and Established Names:
Sensititre® 18-24 hours Susceptibility 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

4. Panel:
83 Microbiology

H. Intended Use:

1. Intended use(s):
For the addition of Ertapenem at concentrations of 0.002 - 16 µg/mL for Enterobacteriaceae, (Gram Negative organisms), and at concentrations of 0.015-64 µg/mL for Methicillin susceptible Staphylococcus species, and Beta hemolytic Streptococcus, (Gram Positive organisms) to the Sensititre 18-24 hour MIC panels for testing gram positive and gram negative isolates.

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The Sensititre® 18-24 hour MIC Susceptibility system is an in vitro diagnostic product for clinical susceptibility testing of Gram negative and Gram positive organisms.

2. **Indication(s) for use:**
Addition of the antibiotic ertapenem at concentrations of 0.002 - 16 µg/mL for Gram Negative organisms and at concentrations of 0.015-64 µg/mL for Gram Positive organisms to the Sensititre® 18-24 hour MIC panels.

3. **Special condition for use statement(s):**
The ability of the Sensititre® 18-24 hour susceptibility system to detect resistance with: *Streptococcus spp* and Ertapenem is unknown because these strains have not yet been detected and should be retested. If the non-susceptible result is confirmed the strain should be sent to a reference laboratory for further testing.

Prescription Use Only

4. **Special instrument Requirements:**
Not Applicable

I. **Device Description:**
Sensititre® MIC Susceptibility plate MIC panels are multi-well plastic microtitre plates, precision dosed with dried, stabilized antimicrobics. This is a modification of the classic broth dilution methods and can provide both qualitative and quantitative susceptibility results in a dried plate format. Inoculum is prepared in Mueller-Hinton broth for testing gram negative and gram positive organisms. After inoculation, plates are sealed with an adhesive seal, incubated at 34-36°C for 18-24 hours and the contents of the wells are examined for bacterial growth.

The 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):**
Pasco Laboratories, Inc. MIC and MIC/ID panels

2. **Predicate K number(s):**
K041776

3. **Comparison with predicate:**

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended use | an in vitro diagnostic product for clinical susceptibility testing of indicated organisms | an in vitro diagnostic product for clinical susceptibility testing of indicated organisms |
| Inoculum | Prepared from colonies | Prepared from colonies |

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| | using the direct inoculation method | using the direct inoculation method |
| --- | --- | --- |
| Inoculation method | Direct equated to a 0.5 McFarland | Direct equated to a 0.5 McFarland |
| | Differences | |
| Item | Device | Predicate |
| Antibiotic | Ertapenem | Different antibiotic and concentrations |
| Type panel | antimicrobial agent serially diluted then dried | frozen |
| Technology | Fluorescence detection of growth for automated reading, growth for manual read method. | Visual growth |

K. Standard/Guidance Document Referenced (if applicable):
“Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA”; Clinical and Laboratory Standards Institute (CLSI) M7 (M100-S16) “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 form 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.

Alternatively, after incubation for 18-24 hours, the Sensititre viewer enables the user to read the panel manually for growth based on turbidity, haziness, or a deposit of cells at the bottom of a well. The MIC is recorded as the lowest concentration of antimicrobic that inhibits visible growth. The growth control well should be read first. If the growth control well does not exhibit growth, the test is considered invalid.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility
Testing was performed using the Sensititre 18-24 hour Susceptibility System. The 25 gram negative and 25 gram positive isolate study described in the guidance document was used. (25 organisms tested 1 time at 3 sites). The study demonstrated >95% reproducibility

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using either the automated read method or the manual method of reading.

# b. Linearity/assay reportable range:

Not applicable

# c. Traceability, Stability, Expected values (controls, calibrators, or method)

The CLSI recommended QC isolates were 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 demonstrate 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. aureus ATCC 29213 Range 0.06-0.25 ug/ml | <0.06 | 0 | 0 | 0 |
| | 0.06 | 0 | 0 | 0 |
| | 0.12 | 48 | 38 | 43 |
| | 0.25 | 12 | 22 | 17 |
| | >0.25 | 0 | 0 | 0 |
| Total | | 60 | 60 | 60 |
| | | | | |
| Enterococcus faecalis ATCC 29212 Range 4-16 ug/ml | <4 | 0 | 3 | 0 |
| | 4 | 0 | 5 | 1 |
| | 8 | 56 | 52 | 59 |
| | 16 | 4 | 0 | 0 |
| | >16 | 0 | 0 | 0 |
| Total | | 60 | 60 | 60 |
| | | | | |
| E. coli ATCC 25922 Range 0.004-0.016 ug/ml | ≤0.004 | 1 | 0 | 0 |
| | 0.004 | 27 | 0 | 0 |
| | 0.008 | 32 | 60 | 55 |
| | 0.016 | | 0 | 5 |
| | >0.016 | | 0 | 0 |
| Total | | 60 | 60 | 60 |
| | | | | |
| P. aeruginosa ATCC 27853 Range 2-8 ug/ml | <2 | | | |
| | 2 | 12 | 3 | 13 |
| | 4 | 42 | 51 | 40 |
| | 8 | 5 | 6 | 7 |
| | >8 | 1 | | |
| Total | | 60 | 60 | 60 |

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Pseudomonas aeruginosa and Enterococcus faecalis were tested for QC purposes only.

Nephelometer was used at each site to standardize the inoculum and it was calibrated each time it was switched on. Colony counts were performed with a range of $8.6 \times 10^{5} - 1.1 \times 10^{5}$.

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 CLSI 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 gram positive panels for the automated read method only for the organisms indicated for use:

Gram Positive isolates= Methicillin Susceptible Staph species (MSSS), Beta hemolytic Streptococci

| Gpos | total | EA | %EA Total | Total evaluable | EA of evaluable | %EA eval | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 120 | 120 | 100 | 107 | 107 | 100 | 120 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 22 | 21 | 95.4 | 22 | 21 | 95.4 | 21 | 95.4 | 0 | 0 | 1 | 0 |
| Combined | 142 | 141 | 99.3 | 129 | 128 | 99.2 | 141 | 95 | 0 | 0 | 1 | 0 |

The following are the comparative results for the gram negative panels for the automated read method only:

Gneg=Enterobacteriaceae

| Gneg | total | EA | %EA Total | Total evaluable | EA of evaluable | %EA eval | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 245 | 242 | 98.8 | 245 | 242 | 98.8 | 245 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 58 | 57 | 98.3 | 57 | 56 | 98.2 | 58 | 100 | 0 | 0 | 0 | 0 |
| Combined | 303 | 299 | 98.7 | 302 | 298 | 98.7 | 303 | 100 | 0 | 0 | 0 | 0 |

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

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

Essential agreement (EA) is when the Sensititre 18-24 hour MIC panel results agree with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the Sensititre 18-24 hour MIC panel interpretative results, Sensitive, Intermediate, and Resistant (SIR) agrees exactly

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with the reference panel result interpretation. Evaluable (Eval) are results that are within the test range and are on scale.

The test device had a growth rate of &gt;95% and the performance data are acceptable.

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:
$$MSSS = \leq 2(S), 4(I), &gt;= 8(R)$$
*Beta hemolytic Strep spp. (BHS) = ≤1 (S)
Enterobacteriaceae = ≤2 (S), 4 (I), &gt;=8 (R)

*The ability of the Sensititre® 18-24 hour susceptibility system to detect resistance with: Streptococcus spp and Ertapenem is unknown because these strains have not yet been detected and should be retested. If the non-susceptible result is confirmed the strain should be sent to a reference laboratory for further testing.

The expected value range, interpretative criteria and QC are the same as recommended in CLSI and FDA.

N. Labeling
The expected value range, interpretive criteria and QC for ertapenem utilized in the gram negative panels and in the gram positive panels are included in the package insert. The labeling conforms to the requirements of 21 CRF Part 809.10.

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