VITEK 2 AST-ST CEFOTAXIME

• K Number: K121863
• Device Name: VITEK 2 AST-ST CEFOTAXIME
• Manufacturer: BIOMERIEUX, INC.
• Date Cleared: 2012-08-16 ( 51 days)
• Product Code: LON
• Regulation Number: 866.1645

Intended Use

VITEK® 2 AST - ST Cefotaxime is designed for antimicrobial susceptibility testing of Streptococcus species. VITEK® 2 AST - ST Cefotaxime is a quantitative test intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Cefotaxime has been shown to be active against most strains of the microorganism listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Streptococcus pneumoniae. Streptococcus pyogenes (Group A betahemolytic streptococci), Streptococcus spp. The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 and VITEK 2 Compact Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli. Staphylococcus spp., Enterococcus spp., Streptococcus agalactiae, and S. pneumoniae.

Device Description

The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card. The VITEK® 2 AST - ST Cefotaxime for Streptococcus species has the following concentrations in the card: 0.25, 0.5, 1, and 2 ug/ml (equivalent standard method concentration by efficacy in uq/ml). The MIC result range for the VITEK 2 card is ≤ 0.125 ~ ≥ 8 µg/ml.

Predicate Devices

K063597

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on a traditional automated microbiological method for determining MIC values based on growth in wells with varying antibiotic concentrations. There is no mention of AI, ML, or advanced computational analysis beyond automated data collection and reporting of MIC and interpretive categories.

Therapeutic

No.
This device is an in vitro diagnostic device used as a laboratory aid to determine antimicrobial susceptibility, not for direct therapeutic intervention on a patient.

Diagnostic

Yes

The input explicitly states that the device is "designed for antimicrobial susceptibility testing" and is "a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents." This indicates its use in providing information to aid in diagnosis and treatment decisions.

SaMD (Software as a Medical Device)

No

The device description clearly details a physical AST card with wells containing media and antibiotics, which is a hardware component. The system also involves automated or manual filling, sealing, incubation, and reading, indicating significant hardware interaction.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

• Intended Use: The intended use explicitly states it is a "laboratory aid in the determination of in vitro susceptibility to antimicrobial agents." "In vitro" means "in glass" or "in the lab," referring to tests performed outside of a living organism.
• Device Description: The device description details how it tests bacterial isolates (obtained from clinical specimens) in a laboratory setting using culture media and antimicrobial agents within a card. This is a classic description of an in vitro diagnostic test.
• Performance Studies: The performance studies describe testing "clinical isolates" and comparing the results to a "CLSI broth microdilution reference method," which is another in vitro diagnostic technique.

The device is designed to provide information about the susceptibility of microorganisms to antibiotics, which is crucial for guiding treatment decisions for patients. This falls squarely within the definition of an in vitro diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

VITEK® 2 AST - ST Cefotaxime is designed for antimicrobial susceptibility testing of Streptococcus species. VITEK® 2 AST - ST Cefotaxime is a quantitative test intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Cefotaxime has been shown to be active against most strains of the microorganism listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections: Streptococcus pneumoniae. Streptococcus pyogenes (Group A betahemolytic streptococci), Streptococcus spp.

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 and VITEK 2 Compact Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli. Staphylococcus spp., Enterococcus spp., Streptococcus agalactiae, and S. pneumoniae.
For prescription use only.

Product codes (comma separated list FDA assigned to the subject device)

LON

Device Description

The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

The VITEK® 2 AST - ST Cefotaxime for Streptococcus species has the following concentrations in the card: 0.25, 0.5, 1, and 2 ug/ml (equivalent standard method concentration by efficacy in uq/ml). The MIC result range for the VITEK 2 card is ≤ 0.125 ~ ≥ 8 µg/ml.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

A reproducibility study was conducted at three external clinical sites. Nine isolates of Streptococcus pneumoniae and one isolate of Streptococcus mitis were tested at each site and testing was performed in triplicate over three days with the VITEK® 2 AST - ST Cefotaxime card resulting in a total of 270 test results. The testing was performed using both the manual dilution method and the automated dilution method. Testing was conducted on the VITEK® 2 instrument.

Performance was established through a clinical study which was conducted at four external study sites. A total of 1425 clinical isolates were tested by VITEK® 2 AST - ST Cefotaxime with the VITEK® 2 System. The majority of the isolates were recently recovered from clinical specimens. Four hundred sixty-five of the 1425 clinical isolates tested were stock isolates (32.6%). Nine of the isolates failed to grow in the VITEK® card giving a no growth rate of 0.6% (9/1425). Therefore, the total number of viable clinical isolates evaluated was 1416.

A total of 301 clinical isolates of Streptococcus pneumoniae were tested and the performance data was analyzed using the meningitis and non-meningitis breakpoints for Cefotaxime. None of the isolates failed to grow in the VITEK® 2 AST card. One hundred fifty one of the 301 clinical isolates tested were stock isolates (50.2%).

A challenge set consisting of 207 isolates (Streptococcus species) and 50 isolates for Streptococcus pneumonia (non-meningitis breakpoint) was also evaluated with VITEK® 2 AST - ST Cefotaxime at one external site. The challenge set was tested with both of the VITEK® 2 System card inoculation options, automatic dilution and manual dilution.

Testing of clinical isolates was performed using the automated method of inoculation and the challenge organisms were tested with both the manual dilution and automatic dilution. Each isolate was tested by the VITEK® 2 AST - ST Cefotaxime and the CLSI broth microdilution reference method. The inoculum was prepared with direct colony suspension.

Performance of the VITEK® 2 Compact was evaluated as a secondary procedural option. The evaluation was conducted using the same 207 isolates (Streptococcus species), and 50 isolates of Streptococcus pneumoniae challenge set tested in the VITEK® 2 system.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Precision/Reproducibility Study:

• Study Type: Reproducibility study
• Sample Size: 9 isolates of Streptococcus pneumoniae and 1 isolate of Streptococcus mitis, tested in triplicate over three days per site for a total of 270 test results.
• Key Results: Overall reproducibility was > 95% with +/- one dilution observation for both VITEK® 2 and VITEK® 2 Compact systems.
  • VITEK® 2 (Auto Dilution): Best Case 100%, Worst Case 100%
  • VITEK® 2 (Manual): Best Case 100%, Worst Case 100%
  • VITEK® 2 Compact (Manual): Best Case 100%, Worst Case 100%

Method Comparison with Predicate Device (Clinical Study):

• Study Type: Clinical study comparing VITEK® 2 AST - ST Cefotaxime to CLSI broth microdilution reference method.
• Sample Size:
  • Clinical isolates: 1416 viable clinical isolates (out of 1425 total, 9 failed to grow). 301 clinical isolates of Streptococcus pneumoniae.
  • Challenge set: 207 isolates (Streptococcus species) and 50 isolates (Streptococcus pneumoniae, non-meningitis breakpoint).
• Key Results:
  • Streptococcus pneumoniae (non-meningitis breakpoint):
    • Combined (Clinical and Challenge, n=351): Essential Agreement (EA) Total 98.6%, Evaluable EA 96.6%, Category Agreement (CA) 89.7%. 1 major error, 35 minor errors. No very major errors.
  • Streptococcus pneumoniae (meningitis breakpoint):
    • Combined (Clinical and Challenge, n=351): EA Total 98.6%, Evaluable EA 96.6%, CA 89.5%. 2 major errors, 35 minor errors. No very major errors.
  • Streptococcus pyogenes:
    • Combined (Clinical and Challenge, n=310): EA Total 100%, CA 100%. No errors.
  • All Streptococcus species including S. pneumoniae (meningitis breakpoint):
    • Combined (Clinical and Challenge, n=1623): EA Total 99.0%, Evaluable EA 97.1%, CA 96.5%. 3 major errors, 54 minor errors. No very major errors.

Manual Dilution (VITEK® 2) - Challenge:

• Study Type: Performance evaluation of manual dilution for challenge isolates on VITEK® 2.
• Sample Size: 50 Streptococcus pneumoniae (non-meningitis breakpoint), 50 Streptococcus pneumoniae (meningitis breakpoint), 207 Streptococcus species including S. pneumoniae (meningitis breakpoint).
• Key Results:
  • S. pneumoniae (non-meningitis breakpoint): EA Total 100%, Evaluable EA 100%, CA 92.0%. 4 minor errors. No major/very major errors.
  • S. pneumoniae (meningitis breakpoint): EA Total 100%, Evaluable EA 100%, CA 90.0%. 5 minor errors. No major/very major errors.
  • All Streptococcus species: EA Total 100%, Evaluable EA 100%, CA 96.6%. 7 minor errors. No major/very major errors.

Manual Dilution (VITEK® 2 Compact) - Challenge:

• Study Type: Performance evaluation of manual dilution for challenge isolates on VITEK® 2 Compact.
• Sample Size: Same as Manual Dilution (VITEK® 2) - Challenge.
• Key Results:
  • S. pneumoniae (non-meningitis breakpoint): EA Total 100%, Evaluable EA 100%, CA 88.0%. 6 minor errors. No major/very major errors.
  • S. pneumoniae (meningitis breakpoint): EA Total 100%, Evaluable EA 100%, CA 86.0%. 7 minor errors. No major/very major errors.
  • All Streptococcus species: EA Total 99.0%, Evaluable EA 98.0%, CA 94.7%. 11 minor errors. No major/very major errors.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Essential Agreement (EA), Category Agreement (CA), Major discrepancies (maj), Very Major discrepancies (vmj), Minor discrepancies (min).

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K063597

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.

(a)
Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”

Summary

0

1863

510(k) SUMMARY

AUG 16 2012

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VITEK® 2 AST- ST Cefotaxime

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	100 Rodolphe Street
Durham, NC 27712
Contact Person:	Elizabeth (Betty) Landon
Staff Regulatory Affairs Specialist
Phone Number:	919-620-2329
Fax Number:	919-620-2548
Date of Preparation:	June 25, 2012

A. 510(k) Number:

K121863

B. Purpose for Submission:

Substantial equivalence determination for the addition of Cefotaxime to the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems for testing of Streptococcus species.

C. Measurand:

Cefotaxime concentrations of 0.25, 0.5, 1, and 2 µg/ml. The MIC result range of the card is ≤ 0.125 -- ≥ 8 µg/ml.

D. Type of Test:

The minimum inhibitory concentration (MIC) is determined using qualitative growth based detection algorithm according to a predetermined growth threshold.

E. Applicant:

bioMérieux, Inc.

F. Proprietary and Established Names:

VITEK® 2 AST - ST Cefotaxime

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G. Requlatory Information:

| roduct | 411010 | CONSULTION CONSULTION CONSULTER COLLECTION COLLECTION COLLECTION COLLECTION COLLECTION COLLECTION COLLECTION COLLEGION COLLEGION COLLECTION CONSULTION CONSULTION CONSULTION C
.
Requiation >>
ection | |
|--------|------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------|
| 1 | 900
A - 100 - 1000 - 1000 - 100 | ----------------------------------------
164 | Alcronininov |

H. Intended Use:

1. Intended use:

VITEK® 2 AST - ST Cefotaxime is designed for antimicrobial susceptibility testing of Streptococcus species. VITEK® 2 AST - ST Cefotaxime is a quantitative test intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Cefotaxime has been shown to be active against most strains of the microorganism listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections: Streptococcus pneumoniae. Streptococcus pyogenes (Group A betahemolytic streptococci), Streptococcus spp.

• 2. Indication(s) for use:
     VITEK® 2 AST - ST Cefotaxime is designed for antimicrobial susceptibility testing of Streptococcus species. VITEK® 2 AST - ST Cefotaxime is a quantitative test intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Cefotaxime has been shown to be active against most strains of the microorganism listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections:

Streptococcus pneumoniae. Streptococcus pyogenes (Group A betahemolytic streptococci), Streptococcus spp.

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 and VITEK 2 Compact Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli. Staphylococcus spp., Enterococcus spp., Streptococcus agalactiae, and S. pneumoniae.

• 3. Special conditions for use statement(s):
     For prescription use only.

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4. Special instrument requirements:

For use with the VITEK® 2 and VITEK® 2 Compact Systems.

I. Device Description:

The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

The VITEK® 2 AST - ST Cefotaxime for Streptococcus species has the following concentrations in the card: 0.25, 0.5, 1, and 2 ug/ml (equivalent standard method concentration by efficacy in uq/ml). The MIC result range for the VITEK 2 card is ≤ 0.125 ~ ≥ 8 µg/ml.

The MIC ranges, interpretive criteria and equivalent concentrations are as follows:

| VITEK® 2
AST- ST | Equivalent
Standard Method
Concentration by
Efficacy in µg/ml | Organism
(Infection) | MIC Ranges and
FDA/CLSI Categories*
MIC in µg/ml: | | |
|---------------------|------------------------------------------------------------------------|-------------------------------------------|---------------------------------------------------------|---|-----|
| | | | S | I | R |
| Cefotaxime | 0.25, 0.5, 1, and
2 | S. pneumoniae
(non-meningitis)
CLSI | ≤ 1 | 2 | ≥ 4 |
| | | S. pneumoniae
(meningitis)
FDA | ≤ 0.5 | 1 | ≥ 2 |
| | | Streptococcus
Species
FDA | ≤ 0.5 | 1 | ≥ 2 |

• S = Susceptible; I = Intermediate; R = Resistant

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J. Substantial Equivalence Information:

• 1. Predicate device name(s):
     VITEK® 2 AST - GP Amoxicillin for S. pneumoniae
• 2. Predicate K number(s):
     K063597
• 3. Comparison with predicate:

Item	Device	Predicate
Intended Use	Determining quantitative and qualitative susceptibility to antimicrobial agents	Same
Inoculation and test organism	Isolated colonies of Streptococcus pneumoniae	Same
Instrument	Test are run on both the VITEK® 2 and VITEK® 2 Compact Systems	Same
Test Card	VITEK® 2 card, including base broth	Same
Test Method	Automated quantitative Antimicrobial susceptibility test to determine the in vitro susceptibility of Streptococcus pneumoniae	Same

Differences
Item	Device	Predicate
Antibiotic	Cefotaxime-specific
concentrations	Amoxicillin-specific
concentrations
Reading algorithm	Unique to Cefotaxime	Unique to Amoxicillin
Test organisms	Streptococcus pyogenes
(Group A beta-hemolytic
streptococci), and
Streptococcus spp. in
addition to S. pneumoniae	S. pneumoniae

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

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

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http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidanc e/GuidanceDocuments/ucm071462.pdf

Clinical and Laboratory Standards Institute (CLSI) Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. Approved Standard -8th Edition, Document M7-A8.

CLSI Performance Standards for Antimicrobial Susceptibility Testing -Twenty-first Informational Supplement, M100-S21.

L. Test Principle:

Automated growth based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK® 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a "rapid" read but may be extended to 18 hours in some instances. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic on the card.

The VITEK® 2 AST - ST Cefotaxime for Streptococcus species has the following concentrations in the card: 0.25, 0.5, 1, and 2 µg/ml (equivalent standard method concentration by efficacy in ug/ml). The MIC result range for the VITEK® 2 card is ≤ 0.125 - ≥ 8 µg/ml.

M. Performance Characteristics (if/when applicable):

• 1. Analytical performance:
  • a. Precision/Reproducibility:

A reproducibility study was conducted at three external clinical sites. Nine isolates of Streptococcus pneumoniae and one isolate of Streptococcus mitis were tested at each site and testing was performed in triplicate over three days with the VITEK® 2 AST - ST Cefotaxime card resulting in a total of 270 test results. The testing was performed using both the manual dilution method and the automated dilution method. Testing was conducted on the VITEK® 2 instrument.

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For the sake of reproducibility calculations, off-scale values are handled in two ways; "best case" and "worst case" scenarios. Best case calculation for reproducibility assumes the off-scale result is within one well from the mode MIC value. Worst case calculation for reproducibility assuming the off-scale result is greater than one well from the mode MIC value.

The overall reproducibility was > 95% with +/- one dilution observation for the VITEK® 2 and the VITEK® 2 Compact system. Only Manual Dilution testing was conducted since the VITEK® 2 Compact system does not have a functionality to support automatic dilution to inoculate the card. Results were as follows:

| VITEK® System | Inoculation
Method | Best Case | Worst Case |
|------------------|-----------------------|-----------|------------|
| VITEK® 2 | Auto Dilution | 100% | 100% |
| | Manual | 100% | 100% |
| VITEK® 2 Compact | Manual | 100% | 100% |

• b. Linearity/assay reportable range:
  Not applicable

• c. Traceability, Stability, Expected values (controls, calibrators, or methods):
  The recommended Streptococcus pneumonia QC organism was tested on every test occasion with the reference method and the VITEK® 2 System.

The reference method QC results were in range for every day tested. The VITEK® 2 was tested a sufficient number of times to demonstratethat the system can produce QC results in the recommended range.

Quality Control was performed during the studies using both the Autodilution and the manual method of diluting the organisms on the VITEK® 2 System. Results demonstrated that methods were comparable.

Quality Control Results with the VITEK® 2 System for Cefotaxime were as follows:

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| Organism | Cefotaxime
Concentration
(µg/ml) | Auto Dilution | | Manual Dilution | |
|--------------------------------------------------|----------------------------------------|---------------|----------|-----------------|----------|
| | | Reference | VITEK® 2 | Reference | VITEK® 2 |
| Streptococcus
pneumonia
ATCC 49619 | 0.016 | 1 | | 1 | |
| | 0.03 | | | | |
| | 0.06 | 128 | | 126 | |
| | 0.12* | 53 | 182 | 52 | 178 |
| Acceptable MIC
range:
0.06-0.25 (FDA) | 0.25* | | | | |
| | 0.5* | | | | 1 |
| | 1* | | | | |
| | 2* | | | | |
| | 4* | | | | |
| | 8* | | | | |

• VITEK® Card Result Range is ≤ 0.125 - ≥ 8.

Results for the VITEK® 2 AST - ST Cefotaxime were within the expected QC results range > 95% of the time for both the automatic and manual dilution options of the VITEK® 2.

A similar QC study was conducted to evaluate the VITEK® 2 Compact System. Results were within the expected FDA QC ranges. Quality Control results for the VITEK® 2 System using either inoculation dilution method demonstrated that the VITEK® 2 System could produce the expected quality control results.

Inoculum density control was monitored using the DensiChek2 instrument. This was standardized weekly with all results recorded and in the expected range.

• d. Detection limit:
  Not applicable.

• e. Analytical specificity:
  Not applicable.

• f. Assay cut-off:
  Not applicable.

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2. Comparison studies:

a. Method comparison with predicate device:

Performance was established through a clinical study which was conducted at four external study sites. A total of 1425 clinical isolates were tested by VITEK® 2 AST - ST Cefotaxime with the VITEK® 2 System. The majority of the isolates were recently recovered from clinical specimens. Four hundred sixty-five of the 1425 clinical isolates tested were stock isolates (32.6%). Nine of the isolates failed to grow in the VITEK® card giving a no growth rate of 0.6% (9/1425). Therefore, the total number of viable clinical isolates evaluated was 1416.

A total of 301 clinical isolates of Streptococcus pneumoniae were tested and the performance data was analyzed using the meningitis and non-meningitis breakpoints for Cefotaxime. None of the isolates failed to grow in the VITEK® 2 AST card. One hundred fifty one of the 301 clinical isolates tested were stock isolates (50.2%).

A challenge set consisting of 207 isolates (Streptococcus species) and 50 isolates for Streptococcus pneumonia (non-meningitis breakpoint) was also evaluated with VITEK® 2 AST - ST Cefotaxime at one external site. The challenge set was tested with both of the VITEK® 2 System card inoculation

options, automatic dilution and manual dilution.

Testing of clinical isolates was performed using the automated method of inoculation and the challenge organisms were tested with both the manual dilution and automatic dilution. Each isolate was tested by the VITEK® 2 AST - ST Cefotaxime and the CLSI broth microdilution reference method. The inoculum was prepared with direct colony suspension. A comparison was provided to the reference method with the agreement shown in the following tables.

There is only one set of breakpoints [≤ 0.5 (S), 1 (I), ≥ 2 (R)] for Streptococcus spp in the FDA drug label for Cefotaxime. The performance data for Streptococcus species and S. pneumoniae were analyzed using the FDA breakpoints for Streptococcus spp.

Another analysis was conducted using CLSI breakpoints for S. pneumoniae. As stated in CLSI M100-S22, Vol 32, No. 3, January 2012, Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement, CLSI breakpoints for S. pneumoniae meningitis are the same as FDA breakpoints for

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Streptococcus species [≤ 0.5 (S), 1 (I), ≥ 2 (R)]. Therefore, the clinical trial performance data was analyzed by combining Streptococcus species and the CLSI S. pneumoniae meningitis breakpoint. Because the CLSI breakpoints the S. pneumoniae non-meningitis ([≤ 1 (S), 2 (I), ≥ 4 (R)] are different, this performance data is presented separately.

A summary of the data is shown in the tables that follow.

| Organism
Group | EA
Tot | EA
N | EA
% | Eval
EA
Tot | Eval
EA
N | Eval
EA
% | CA
N | CA
% | #R | #
vmj | #
maj | #
min |
|-----------------------------------------------------------------------------------------|-----------|---------|---------|-------------------|-----------------|-----------------|---------|---------|----|----------|----------|----------|
| Streptococcus pneumoniae (non-meningitis breakpoint) | | | | | | | | | | | | |
| CLINICAL | 301 | 296 | 98.3 | 83 | 79 | 95.2 | 270 | 89.7 | 6 | 0 | 1 | 30 |
| CHALLENGE | 50 | 50 | 100 | 35 | 35 | 100 | 45 | 90.0 | 17 | 0 | 0 | 5 |
| COMBINED
(CLINICAL
AND
CHALLENGE) | 351 | 346 | 98.6 | 118 | 114 | 96.6 | 315 | 89.7 | 23 | 0 | 1 | 35 |
| Streptococcus pneumoniae (meningitis breakpoint) | | | | | | | | | | | | |
| CLINICAL | 301 | 296 | 98.3 | 83 | 79 | 95.2 | 270 | 89.7 | 29 | 0 | 2 | 29 |
| CHALLENGE | 50 | 50 | 100 | 35 | 35 | 100 | 44 | 88.0 | 25 | 0 | 0 | 6 |
| COMBINED
(CLINICAL
AND
CHALLENGE) | 351 | 346 | 98.6 | 118 | 114 | 96.6 | 314 | 89.5 | 54 | 0 | 2 | 35 |
| Streptococcus pyogenes | | | | | | | | | | | | |
| CLINICAL | 260 | 260 | 100 | 0 | 0 | N/A | 260 | 100 | 0 | 0 | 0 | 0 |
| CHALLENGE | 50 | 50 | 100 | 0 | 0 | N/A | 50 | 100 | 0 | 0 | 0 | 0 |
| COMBINED
(CLINICAL
AND
CHALLENGE) | 310 | 310 | 100 | 0 | 0 | N/A | 310 | 100 | 0 | 0 | 0 | 0 |
| All Streptococcus species including S. pneumoniae (meningitis breakpoint) | | | | | | | | | | | | |
| CLINICAL | 1416 | 1400 | 98.9 | 188 | 181 | 96.3 | 1367 | 96.5 | 50 | 0 | 3 | 46 |
| CHALLENGE | 207 | 207 | 100 | 55 | 55 | 100 | 199 | 96.1 | 31 | 0 | 0 | 8 |
| COMBINED
(CLINICAL
AND
CHALLENGE) | 1623 | 1607 | 99.0 | 243 | 236 | 97.1 | 1566 | 96.5 | 81 | 0 | 3 | 54 |

Auto Dilution (S. pneumonia and Streptococcus species)

EA-Essential Agreement: CA-Category Agreement; maj-major discrepancies vmj-very major discrepancies; min-minor discrepancies

Essential agreement (EA) is when the VITEK® 2 panels agree with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the VITEK® 2 panel result interpretation agrees exactly with the reference panel result interpretation. Evaluable (EA) is when the MIC result is on scale for both the VITEK® 2 and the reference and have on-scale EA.

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For the non-meningitis breakpoint for S. pneumoniae, 35 (10%) minor categorical errors were seen along with one maior error. A high agreement was observed with a total EA of 98.6%, evaluable EA of 96.6%, and a CA of 89.7%. Of 351 total isolates of S. pneumoniae, 23 isolates were considered resistant based on the Cefotaxime breakpoint for non-meningitis, but no very major errors occurred.

For the meningitis breakpoint for S. pneumoniae, 35 (10%) minor categorical errors were seen along with two major errors. A high agreement was observed with a total EA of 98.6%, evaluable EA of 96.6%, and a CA of 89.5%. Of 351 total isolates of S. pneumoniae, 54 isolates were considered resistant based on the Cefotaxime breakpoint for non-meningitis, but no very major errors occurred.

For combined Streptococci species and S. pneumoniae (meningitis breakpoint). 54 (3.3%) minor categorical errors were seen along with three major errors. A high agreement was observed with a total EA of 99.0%, evaluable EA of 97.1%, and a CA of 96.5%. Of 1623 total isolates of Streptococci, 81 isolates were considered resistant based on the Cefotaxime breakpoints of [≤ 0.5(S), 1 (I) . ≥ 2(R)], but no very major errors occurred.

| Organism
Group
(breakpoint) | EA
Tot | EA
N | EA
% | Eval
EA
Tot | Eval
EA
N | Eval
EA
% | CA
N | CA
% | #R | #
vmj | #
maj | #
min |
|-----------------------------------------------------------------------------------------|-----------|---------|---------|-------------------|-----------------|-----------------|---------|---------|----|----------|----------|----------|
| Streptococcus pneumoniae (non-meningitis breakpoint) | | | | | | | | | | | | |
| CHALLENGE
(non-
meningitis) | 50 | 50 | 100 | 33 | 33 | 100 | 46 | 92.0 | 17 | 0 | 0 | 4 |
| Streptococcus pneumoniae (meningitis breakpoint) | | | | | | | | | | | | |
| CHALLENGE
(meningitis) | 50 | 50 | 100 | 33 | 33 | 100 | 45 | 90.0 | 25 | 0 | 0 | 5 |
| All Streptococcus species including S. pneumoniae (meningitis breakpoint) | | | | | | | | | | | | |
| CHALLENGE | 207 | 207 | 100 | 53 | 53 | 100 | 200 | 96.6 | 31 | 0 | 0 | 7 |

Manual Dilution (VITEK® 2) - Challenge

Performance of the VITEK® 2 Compact was evaluated as a secondary procedural option. The evaluation was conducted using the same 207 isolates (Streptococcus species), and 50 isolates of Streptococcus pneumoniae challenge set tested in the VITEK® 2 system.

A comparison was provided to the reference method with the following agreement as shown here:

1 0

10

| Organism
Group
(breakpoint) | EA
Tot | EA
N | EA
% | Eval
EA
Tot | Eval
EA
N | Eval
EA
% | CA
N | CA
% | #R | #
vmj | #
maj | #
min |
|---------------------------------------------------------------------------|-----------|---------|---------|-------------------|-----------------|-----------------|---------|---------|----|----------|----------|----------|
| Streptococcus pneumoniae (non-meningitis breakpoint) | | | | | | | | | | | | |
| CHALLENGE
(non-
meningitis) | 50 | 50 | 100 | 34 | 34 | 100 | 44 | 88.0 | 17 | 0 | 0 | 6 |
| Streptococcus pneumoniae (meningitis breakpoint) | | | | | | | | | | | | |
| CHALLENGE
(meningitis) | 50 | 50 | 100 | 34 | 34 | 100 | 43 | 86.0 | 25 | 0 | 0 | 7 |
| All Streptococcus species including S. pneumoniae (meningitis breakpoint) | | | | | | | | | | | | |
| CHALLENGE | 207 | 205 | 99.0 | 50 | 49 | 98.0 | 196 | 94.7 | 31 | 0 | 0 | 11 |

Manual Dilution (VITEK® 2 Compact) - Challenge

• 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:
     The interpretive criteria and QC ranges are as recommended in the approved drug label. S. pneumoniae (non-meningitis) was also analyzed using CLSI interpretive criteria.

FDA: Streptococcus species and S. pneumoniae (meningitis): ≤ 0.5 (S), 1 (l), ≥ 2 (R)

CLSI: S. pneumoniae (non-meningitis): ≤ 1(S), 2 (I), ≥ 4 (R)

11

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/11/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized eagle with its wings spread, symbolizing protection and service. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle, indicating the department's name and national affiliation. The seal is in black and white and appears to be a scanned or digital representation.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

bioMérieux, Inc. c/o Elizabeth Landon Staff Regulatory Affairs Specialist 100 Rodolphe Street Durham, NC 27712

AUG 16 2012

Re: K121863

Trade Name: VITEK®2 AST- ST Cefotaxime Regulation Number: 21 CFR §866.1645 Regulation Name: Fully automated short-term incubation cycle antimicrobial susceptibility system. Regulatory Class: Class II Product Code: LON Dated: June 25, 2012 Received: July 13, 2012

Dear Ms. Landon:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000

12

510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97): For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Soy aitar

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

13

Indications for Use

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

K121863

Device Name: VITEK® 2 AST - ST Cefotaxime ( ≤ 0.125 - ≥ 8 µg/ml )

Indications For Use:

VITEK® 2 AST - ST Cefotaxime is designed for antimicrobial susceptibility testing of Streptococcus species. VITEK 2 AST - ST Cefotaxime is a quantitative test intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Cefotaxime has been shown to be active against most strains of the microorganism listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections

Streptococcus pneumoniae, Streptococcus pyogenes (Group A beta-hemolytic streptococi), Streptococcus spp.

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 and VITEK 2 Compact Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus agalactiae, and S. pneumoniae.

Prescription Use (Part 21 CFR 801 Subpart D) 1 AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Eualdi h. Poole

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K121863

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