PASCO MIC AND MIC/ID PANELS

K033119 · Pasco Laboratories, Inc. · JWY · Nov 18, 2003 · Microbiology

Device Facts

• Record ID: K033119
• Device Name: PASCO MIC AND MIC/ID PANELS
• Applicant: Pasco Laboratories, Inc.
• Product Code: JWY · Microbiology
• Decision Date: Nov 18, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1640
• Device Class: Class 2

Indications for Use

Pasco™ panels are used for quantitatively measuring the susceptibility of rapidly growing aerobic and facultative anaerobic bacterial pathogens to a battery of antimicrobial agents and determining the biochemical identification of these organisms. The indication is for including the antibiotic daptomycin at concentrations of 0.06-8 ug/mL to Pasco™ Panels for testing Staphylococcus spp. and Enterococcus spp. on the gram positive panels.

Device Story

Pasco™ MIC panels are frozen microdilution plates containing two-fold dilutions of antimicrobial agents. Panels are thawed, inoculated with bacterial samples (Staphylococcus spp. or Enterococcus spp.) using either Direct Turbidity Standard or Director™ Inoculation System, and incubated for 16-24 hours at 35°C. Growth is assessed manually via indirect lighted background viewer. The minimum inhibitory concentration (MIC) is defined as the lowest concentration showing no visible growth. Used in clinical microbiology laboratories to determine antibiotic susceptibility. Results guide clinicians in identifying susceptible bacterial pathogens; however, as only a 'susceptible' category exists, non-susceptible results require reference laboratory confirmation.

Clinical Evidence

Bench testing performed comparing Pasco methodology to reference methodology. Study included 413 Staphylococcus spp. and 365 Enterococcus spp. isolates. Essential Agreement (EA) was 99.6%. Reproducibility testing (10 organisms, three sites, three days, triplicate) showed 100% inter-site and intra-site reproducibility. Quality control using S. aureus ATCC 29213 and E. faecalis ATCC 29212 met acceptance criteria.

Technological Characteristics

Microdilution panels containing two-fold dilutions of antimicrobial agents. Manual or visual interpretation of growth/color change. No electronic sensing or energy source required for the panel itself. Standard incubation (16-24 hours).

Indications for Use

Indicated for susceptibility testing of rapidly growing aerobic and facultative anaerobic bacterial pathogens, specifically Enterococcus faecalis (vancomycin-susceptible), Staphylococcus aureus (including MRSA), and in vitro activity against Enterococcus faecalis (vancomycin-resistant), Enterococcus faecium (including VRE), Staphylococcus epidermidis (including MRSE), and Staphylococcus haemolyticus.

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

• Pasco MIC Panels (K032259)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
k033119

B. Analyte:
Daptomycin – 0.06-8 ug/mL AST

C. Type of Test:
Quantitative – broth based growth detected by turbidity

D. Applicant:
Pasco Laboratories -BD Diagnostic Systems

E. Proprietary and Established Names:
Pasco™ MIC and MIC/ID Panels

F. Regulatory Information:
1. Regulation section:
866.1640 - Antimicrobial Susceptibility Test Powder
2. Classification:
II
3. Product Code:
JWY - Manual Antimicrobial Test Systems
4. Panel:
83 - Microbiology

G. Intended Use:
1. Intended use(s):
Pasco™ panels are used for quantitatively measuring the susceptibility of rapidly growing aerobic and facultative anaerobic bacterial pathogens to a battery of antimicrobial agents and determining the biochemical identification of these organisms.
2. Indication(s) for use:
The indication is for including the antibiotic daptomycin at concentrations of 0.06-8 ug/mL to Pasco™ Panels for testing Staphylococcus spp. and Enterococcus spp. on the gram positive panels.
3. Special condition for use statement(s):
The ability to detect resistance is unknown since there is no category but susceptible. Any result other than susceptible should be submitted to a reference laboratory.
4. Special instrument Requirements:
Manual reading only

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H. Device Description:

Various concentrations of antimicrobial agents (usually in two-fold dilutions) are dispensed into the Pasco microdilution panels and the panels are then frozen. Panels are thawed prior to use, inoculated with the test organisms, incubated the traditional 16-24 hours at 35° in a non-CO₂ incubator and panels are then observed for visible growth or color changes (ID portion). The lowest concentration of each antimicrobial agent with no apparent visible growth of the test organism is recorded as the minimum inhibitory concentration (MIC). Only manual readings are performed using an indirect lighted background viewer.

Inoculation procedures include the Direct Turbidity Standard method and Stationary Phase methods which use a spectrophotometer to equate the suspension to a 0.5 McFarland and the Director™ Inoculation System which does not use a spectrophotometer.

I. Substantial Equivalence Information:

1. Predicate device name(s): Pasco MIC Panels
2. Predicate K number(s): K032259
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Type panel | 100 μl/well frozen | 100 μl/well frozen |
| Inoculum | 5 μl | 5 μl |
| Inoculation method | Direct equated to a 0.5 McFarland or Director™ Inoculator | Direct equated to a 0.5 McFarland or Director™ Inoculator |
| Incubation | 16-24 hours | 16-24 hours |
| Reading method | Visual growth | Visual growth |
| Differences | | |
| Item | Device | Predicate |
| Antibiotic | Daptomycin | Gatifloxacin |

J. Standard/Guidance Document Referenced (if applicable):

"Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA"; NCCLS Standard M7 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard; M100 Performance Standards for Antimicrobial Susceptibility Testing.

K. Test Principle:

The test panels are dependent on the growth of the organisms in the presence of the antibiotics. The lowest concentration of each antimicrobial agent with no apparent

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visible growth of the test organism is recorded as the minimum inhibitory concentration (MIC).

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

# 1. Analytical performance:

# a. Precision/Reproducibility:

Ten isolates with on-scale results were tested at three sites. These were evaluated for site to site reproducibility and inter site reproducibility using the ten isolate study described in the guidance document (10 organisms tested 3 times on 3 days at 3 sites).

This study was performed on both the turbidity standard method and the Director™ Inoculation System method. Both were reproducible at $>95\%$ for intra site and inter site testing.

# b. Linearity/assay reportable range:

Not applicable

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

The recommended QC isolate was tested a sufficient number of times with acceptable results with the reference method. The Pasco results demonstrate that the system can produce QC results in the recommended range for both the Direct and the Director methods of inoculation. The reference and the Director method of inoculation had the same mode while the turbidity method of inoculation has a mode that was one well more susceptible.

| ORGANISM | conc | Reference | Pasco™ turbidity | Pasco™ Director |
| --- | --- | --- | --- | --- |
| | | | | |
| S. aureus ATCC 29213 Range 0.25-1 ug/mL | 0.12 | | | |
| | 0.25 | 24 | 117 | 4 |
| | 0.5 | 113 | 21 | 102 |
| | 1 | 1 | | 4 |
| | 2 | | | |
| | | | | |
| E. faecalis ATCC 29212 Range 1-8 ug/mL | 0.5 | | | |
| | 1 | 5 | 15 | 4 |
| | 2 | 103 | 109 | 85 |
| | 4 | 30 | 14 | 11 |
| | 8 | | | |
| | >8 | | | |

Inoculum Density Check- An internal study was performed to verify the colony counts (CC) that would be obtained with each method of inoculation. CC demonstrated that the $\mathrm{Pasco}^{\mathrm{TM}}$ direct turbidity inoculation method results in a slightly less concentration of organisms than the reference method. The Director appeared to have a slightly

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wider range of results. Clinical site inoculum density checks were also performed on QC isolates with the Director Inoculation method and the Turbidity method demonstrating acceptable performance.

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 were used to compare to the Pasco results. The concentration of calcium on the Mueller Hinton Broth was adjusted to 50 ug/mL as recommended by the NCCLS and FDA. Testing was performed at 3 sites and included fresh (78%) and stock (22%) clinical isolates and a set of challenge organisms. The comparison resulted in the following performance evaluations for the gram positive panel. Category agreement is not determined since there is only a susceptible interpretative category.

The following are the comparative results for the Staphylococcus spp.

| | total | EA | %EA | Total evaluable | EA of evaluable | %EA |
| --- | --- | --- | --- | --- | --- | --- |
| Clinical | 349 | 348 | 99.7 | 346 | 345 | 99.7 |
| Challenge | 64 | 63 | 98.4 | 64 | 63 | 98.4 |
| Combined | 413 | 411 | 99.5 | 410 | 408 | 99.5 |

The following are the comparative results for the Enterococcus spp.

| | total | EA | %EA | Total evaluable | EA of evaluable | %EA |
| --- | --- | --- | --- | --- | --- | --- |
| Clinical | 318 | 316 | 99.4 | 311 | 309 | 99.4 |
| Challenge | 47 | 47 | 100 | 47 | 47 | 100 |
| Combined | 365 | 363 | 99.4 | 358 | 356 | 99.4 |

EA-Essential Agreement

There is a trend for the direct turbidity method of inoculation with the Pasco™ panel to produce results that are more susceptible than the reference method result.

EA is when there is agreement between the reference method and the Pasco panel within plus or minus one serial two-fold dilution of antibiotic. The %EA is acceptable when compared to the reference method as described in the FDA guidance document, "Class II

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Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA".

Testing of the challenge set was also performed using the Director™ Inoculation System method of inoculation demonstrating little difference between the two methods of inoculation. Summary table of the Director™ Inoculation System from two sites follows:

**Staphylococcus spp.**

| | total | EA | %EA | Total evaluable | EA of evaluable | %EA |
| --- | --- | --- | --- | --- | --- | --- |
| Challenge | 128 | 128 | 100 | 128 | 128 | 100 |

**Enterococcus spp.**

| | total | EA | %EA | Total evaluable | EA of evaluable | %EA |
| --- | --- | --- | --- | --- | --- | --- |
| Challenge | 94 | 94 | 100 | 93 | 93 | 100 |

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:**
**Staphylococcus spp. ≤ 1 (S)**
**Enterococcus spp. ≤ 4 (S)**
The Interpretative criteria, QC isolates and the expected ranges are the same as recommended by the NCCLS and the FDA. All values will be included in the package insert

**M. Conclusion:**
Data analysis when analyzed as recommended in the “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” demonstrates that the Pasco™ Panel with daptomycin is substantially equivalent to the Pasco™ Panels with other antibiotics for the testing of appropriate organisms.