Colibrí System by Copan WASP S.r.l.

The Collbri™ System is an in vitro diagnostic device comprised of the Collbri™ Preparation Station for use with the bioMérieux VITEK® MS or Bruker MALDI Biotyper® CA mass spectrometry systems for qualitative identification and with the bioMérieux VITEK® 2 Antimicrobial Susceptibility Testing (AST) system for qualitative testing of isolated colonies of gram-negative and gram-positive bacterial species grown on solid culture media. The Collbri™ System is a semi-automated pre-analytical processor that picks isolated colonies designated by the operator and uses a pipetting system to prepare MALDI-TOF MS (Matrix-Assisted Laser Desorption/Jonization-Time of Flight Mass Spectrometry) target slides for bacterial identification and microbial suspension at known concentration for Antimicrobial Susceptibility Testing and purity assessment.

The Colibrí software records the identity of each sample and its position on the target slide and communicates this information electronically to the MALDI-TOF MS analyzers.

Bacterial suspensions for AST and purity plates are identified by barcode label.

The Colibr™ System is intended for use by trained healthcare professionals in clinical laboratories in conjunction with other clinical and laboratory finding Gram staining, to aid in the diagnosis of bacterial infections.

The Collbri™ System has not been validated for use in the identification or processing of yeast species, Mocardia, or mycobacteria.

Device Description

The Copan Colibrí System is designed to be used as an accessory of the downstream MALDI-TOF MS and antimicrobial susceptibility testing (AST) analyzers automating various manual steps in the workflow for the preparation of samples for the identification of isolated colonies and for AST of isolated colonies of gram-negative and gram-positive bacterial species grown on solid culture media.

The Colibrí System automates the preparation of MALDI target slides for the bioMérieux VITEK MS or the Bruker MALDI Biotyper CA System that are used in clinical laboratories for identification (ID) of organisms grown on plated media by Matrix-Assisted Laser Desorption/Jonization Time-of Flight Mass Spectrometry (MALDI-TOF MS). The Colibri System automates the preparation of microbial suspensions at known concentration for bioMérieux VITEK 2 System that is used in clinical laboratories for AST analyses. Moreover, the Colibri System is used for Purity Plates preparation for purity assessments.

The Colibrí System comprises the Colibrí Vision System and Colibrí Preparation Station hardware modules and pipette tips, Primary Tubes, Spreader and nephelometer Verification Kit as consumables. After appropriate plate incubation, the operator using the graphical User Interface (Image Reading Interface) chooses the plates exhibiting adequate growth and selects the isolated colonies to be processed assigning the automatic ID or AST tasks. By using the Colibrí Vision System, specific colonies to be picked are designated by the operator on a digital plate. The Operator manually loads the plates in the Colibri Preparation Station where colonies are automatically picked, spotted on the target slide and overlayed with the matrix or suspended into the dedicated solution for the preparation of the microbial suspension for AST purposes (Secondary Tube).

When used in conjunction with the bioMérieux VITEK MS, the Colibrí System can prepare the 48spot target slides by performing the direct spotting of colonies. The calibrator used for quality control is manually applied by the operator at the end of the automated colony spotting. When used in conjunction with the Bruker MALDI Biotyper CA System, the Colibrí System can prepare either reusable 48-spot or disposable 96-spot targets by performing the Direct Transfer Sample Procedure. The BTS used for quality control is manually applied by the operator at the automated colony spotting.

When used in conjunction with the bioMérieux VITEK 2, the Colibrí System can prepare the microbial suspension at the proper concentration by direct colony suspension method. The onboard nephelometer allows the preparation of Secondary Tubes (AST suspensions) at the correct concentration and the Colibrí Spreader is used for Purity Plates preparation.

Copan WASP S.r.l., Traditional 510(k)- Colibrí System

The Colibrí software records the identity of each sample and its position on the target slide and communicates this information electronically to the MALDI-TOF MS analyzers.

The traceability of prepared Secondary Tube and Purity Plates is maintained by dedicated labels applications.

Colibri System requires four different calibrations, one on the nephelometer, three on the cameras. None of these calibration activities require user intervention if not in terms of periodical cleaning of the mechanical component as described in the dedicated section of the User Manual. The Set-up calibration of nephelometer and camera units positioned on the Colibrí Vision System and on the Colibrí Preparation Station are performed during the device initial setup. Auto-calibration is performed at the end of the initial set-up and periodically during the preventive maintenance to check that, in the Collbrí Preparation all the mechanical references can be found inside the positioning tolerances, that the I/Os are responsive. Run-time calibration is performed during the normal usage to automatically check the proper functioning of the Colibrí Vision System and the Colibrí Preparation Station.

Colibrí System requires a daily nephelometer verification to check the proper reading of suspensions at different turbidity values.

AI/ML Overview

The provided text describes the performance data for the Colibrí System, an in vitro diagnostic device. The acceptance criteria and performance are primarily focused on its ability to accurately prepare microbial suspensions for Antimicrobial Susceptibility Testing (AST) and for MALDI-TOF MS identification, compared to manual methods.

Here's an attempt to extract the requested information. Please note that the document is a 510(k) summary, which often provides summarized performance data rather than detailed study protocols. Therefore, some information might be explicitly stated as "not applicable" or inferred based on common practices for such device clearances.

1. A table of acceptance criteria and the reported device performance

The document outlines several analytical studies. While explicit "acceptance criteria" are not always presented as target percentages, the performance results are given, implying that these results met the internal pre-defined acceptance thresholds for substantial equivalence.

Performance Metric	Acceptance Criteria (Implied/Direct)	Reported Device Performance
Nephelometer Calibration Verification	Accurate preparation of microbial suspensions at specific concentrations (0.25, 0.5, 1.0, 2.0, 3.0 McFarland) with acceptable accuracy and nominal microbial content (e.g., 1-2 × 10⁸ CFU/mL for 0.5 McFarland E. coli).	Overall, 100% of suspensions contained the correct concentration of bacteria.
Pipettor Trueness and Precision	Trueness and reproducibility for four volumes (50uL, 100uL, 500uL, 900uL) within acceptance criteria.	Trueness and reproducibility varied according to the volume under testing but always within the acceptance criteria.
E. coli Suspensions Preparation Verification	Correct management of Primary Tubes according to turbidity value, and expected number of colonies based on McFarland standard (e.g., 1-2 × 10⁸ CFU/mL for 0.5 McFarland E. coli).	All Primary Tubes were correctly managed by Colibrí System according to the turbidity value. 100% of suspensions over the entire working range contained the expected number of colonies.
Colony Picking Accuracy & Microbial Suspension Preparation (Purity Check)	Accurate picking of designated colonies from culture plates without contamination from other microorganisms, demonstrating monomicrobial suspensions. High percentage of prepared suspensions with microbial concentration within acceptable limits.	100% of colonies designated by the operator were picked correctly by the Colibrí System (both whole plates and bi-plates). 100% of Purity Plates showed no evidence of microbial contamination. The percentage of prepared suspension with microbial concentration within the acceptable limits was 99.2%, and for each instrument, the result was always >98%. No statistically significant difference among instruments.
AST Challenge Test (Agreement with Manual Preparation)	High agreement (Essential Agreement and Category Agreement) with MICs obtained by VITEK 2 using manual sample preparation. Target percentages for EA and CA for comparability (typically >90% or >95% for Essential Agreement and >90% for Category Agreement and low major/very major error rates as per CLSI guidelines).	Overall Essential Agreement (EA) of evaluable MIC results was >99.9%. Overall Category Agreement (CA) was 99.3%. Notably low error rates: 0 Very Major Errors, 1 Major Error (for Cefepime, Non-fermenters), and 49 Minor Errors across all tested combinations. 1882/1883 evaluable MIC results were within one doubling dilution of the comparator method. 5947/5991 SIR categorizations were in agreement.
Reproducibility (MIC Results)	MIC results considered reproducible if they fell within one doubling dilution from the modal value of each combination.	Generally very high reproducibility. The "worst case" percentages, representing MIC values that were not within one doubling dilution, were generally very low (e.g., lowest was 96.3% for Tobramycin, Instrument 1/3, and Ciprofloxacin, Instrument 2; lowest combined was 97.5% for Tobramycin and Oxacillin), meaning that a very high percentage were within the acceptable limit. The values provided for "Best case" were often 100%.
Purity Plate Growth	100% of purity plates correctly processed and providing evidence of monomicrobial suspensions, demonstrating no cross-contamination.	2,364/2,364 (100%) purity plates were correctly processed, demonstrating that the Colibrí Preparation Station prepares monomicrobial suspensions and prevents cross-contamination.
QC Sample Preparation	100% in-range MIC values for QC organisms compared to established ranges. Purity of all suspensions confirmed.	100% in-range MIC values for QC organisms. Purity of all suspensions confirmed by Purity Plates.

2. Sample sizes used for the test set and the data provenance

Nephelometer Calibration Verification: 300 suspensions were prepared (20 suspensions for each of 5 concentrations, across 3 operators and 3 Colibrí systems, though the calculation isn't directly 2053*3).
Pipettor Trueness and Precision: 10 measurements for each of 4 volumes, across 3 Colibrí System pipettors (10 * 4 * 3 = 120 measurements).
E. coli Suspensions Preparation Verification: The exact number of suspensions isn't provided, but it states "A variable number of colonies was selected... to create different suspensions... Three Colibrí Systems run by three different operators were included."
Colony Picking and Microbial Suspensions for AST: 6 bacterial species (3 Gram-Negative and 3 Gram-Positive) grown in 2 polymicrobial mixtures on different culture media.
AST Challenge Test:
- Total Tested: 5991 (across various antibiotics and organism groups within the challenge test).
- Evaluated MIC results: 1883 evaluable MIC results.
- Organism groups: Enterobacterales (n=62 strains), Staphylococcus (n=16 strains), Streptococcus (n=30 strains), Enterococcus (n=16 strains), and non-fermenters (n=32 strains).
- Strains: Both susceptible and resistant strains, exhibiting a range of on-scale MIC values.
- Media: Trypticase Soy Agar + 5% Sheep Blood, MacConkey Agar, and Columbia agar + 5% sheep blood.
- Incubation times: Varied (e.g., 14h, 24h for Enterobacterales/Non-fermenters, 18h for Staphylococcus/Enterococcus/Streptococcus).
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, given it's a 510(k) submission for a medical device manufacturer (Copan WASP S.r.l., Italy), it's highly likely to be internal, prospective studies conducted at their facilities or collaborator sites.
Reproducibility Study: Each microorganism was tested with the appropriate antibiotic panel, with each condition tested in triplicate, for a total of 81 replicates for each combination strain-antimicrobial agent across three Colibrí Systems and three operators over three days.
Purity Plate Growth: 2,364 purity plates.
QC Sample Preparation: Conducted daily at the beginning of the working session on each instrument involved in the Analytical Studies.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not explicitly provided in the document.
For the AST Challenge Test, the "ground truth" (or comparator method) was the MICs obtained by the bioMérieux VITEK 2 using manual sample preparation, interpreted according to FDA-Recognized Antimicrobial Susceptibility Test Interpretive Criteria. This implies the ground truth relies on established, validated laboratory methods and interpretations, rather than subjective expert consensus.
For other analytical studies (e.g., nephelometer accuracy, pipettor precision), the ground truth generally relies on quantitative measurements using calibrated instruments and standard protocols (e.g., viable cell counts for McFarland turbidity verification, gravimetric measurements for pipettor accuracy).

4. Adjudication method for the test set

This is not applicable in the context of this device's performance validation. The device automates a pre-analytical step. The performance is assessed by comparing its output (prepared microbial suspensions) to a reference method (manual preparation for VITEK 2). It's not a diagnostic AI system requiring expert adjudication of image interpretations or clinical diagnoses.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for AI systems that assist human readers in interpreting medical images (e.g., radiology AI). The Colibrí System is a laboratory automation device for preparing samples. It does not involve human "readers" of AI outputs in a diagnostic context that would require such a study design.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

The performance data are essentially standalone (algorithm/device only) in terms of its ability to perform the physical process of colonial picking and suspension preparation. The device's output is then fed into other IVD analyzers (VITEK 2, bioMérieux VITEK MS, Bruker MALDI Biotyper CA System) for identification and AST.
The comparison in the AST Challenge Test is between the Colibrí System's automated preparation and manual preparation which is the existing standard. So, it's comparing automated device output to a manual, human-executed process, where the subsequent analysis (VITEK 2) is the same. The data provided (EA, CA, error rates) represent the performance of the Colibrí system's prepared samples, which is a form of standalone performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

Comparatative Ground Truth/Reference Method: For the AST Challenge Test, the ground truth was derived from the MICs obtained by the bioMérieux VITEK 2 using manual sample preparation, interpreted according to FDA-Recognized Antimicrobial Susceptibility Test Interpretive Criteria. This is a well-established and standardized laboratory reference method.
Quantitative Ground Truth: For other analytical studies, the ground truth was based on quantitative laboratory measurements, such as:
- Viable cell counts (CFU/mL) for confirming bacterial concentration for nephelometry.
- Gravimetric measurements for pipetting accuracy.
- Visual inspection of purity plates and accepted microbiological methods to ensure monomicrobial suspensions and absence of contamination.

8. The sample size for the training set

The document describes performance validation studies, not product development or AI model training. Therefore, information about a "training set" (in the context of machine learning) is not applicable or provided. This device automates a physical process, not a machine learning model that needs training data in the traditional sense. The "training" of the device likely refers to physical calibration and quality control.

9. How the ground truth for the training set was established

As per point 8, the concept of a "training set" for an AI/machine learning model is not applicable to the description of this device's validation. The device's mechanics and software are validated against established engineering and microbiology standards.

Summary

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October 5, 2022

Copan WASP S.r.l. Chiara Congiu Regulatory Affairs Via A. Grandi, 32 Brescia, Brescia 25125 Italy

Re: K220546

Trade/Device Name: Colibrí System Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System Regulatory Class: Class II Product Code: LON, QQV, QBN Dated: February 18, 2022 Received: February 25, 2022

Dear Chiara Congiu:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 Part

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

For: Uwe Scherf, Ph.D. Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K220546

Device Name Colibrí System

Indications for Use (Describe)

The Colibri™ software records the identity of each sample and its position on the target slide and communicates this information electronically to the MALDI-TOF MS analyzers.

Bacterial suspensions for AST and purity plates are identified by barcode label.

The Collbri™ System has not been validated for use in the identification or processing of yeast species, Mocardia, or mycobacteria.

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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I. Submitter

Applicant Name:	Copan WASP SrlVia A. Grandi 3225125 Brescia, Italy+39 030 2687211copan.regulatory@copangroup.com
Contact Person	Chiara CongiuCopan WASP SrlVia A. Grandi 3225125 Brescia, Italy+39 338 6904942copan.regulatory@copangroup.com
Establishment Registration Number:	3009288740
Date Prepared:	February 18, 2022

II. Device Name

Proprietary Name	Colibrí System
Common/Usual Name	Colibrí System
Classification Name	Fully automated short-term incubation cycle antimicrobial susceptibility system (21 CFR 866. 1645)Clinical mass spectrometry microorganism identification and differentiation system (21 CFR 866.3378) [Cleared, K193138]
Device Class	II
Product Code	LON
Panel	QQV, QBN [Cleared, K193138]Microbiology

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III. Legally Marketed Predicate Device

Device Name	VITEK 2 Gram Negative Imipenem & VITEK 2Systems (PC) 5.02 Software
510(K) Number	K103752

No reference Devices were used in this submission.

IV. Device Description

Copan WASP S.r.l., Traditional 510(k)- Colibrí System

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The Colibrí software records the identity of each sample and its position on the target slide and communicates this information electronically to the MALDI-TOF MS analyzers.

The traceability of prepared Secondary Tube and Purity Plates is maintained by dedicated labels applications.

Colibrí System requires a daily nephelometer verification to check the proper reading of suspensions at different turbidity values.

V. Intended Use / Indications For Use

The Colibrí System is an in vitro diagnostic device comprised of the Colibrí Vision System and Colibrí Preparation Station for use with the bioMérieux VITEK MS or Bruker MALDI Biotyper CA mass spectrometry systems for qualitative identification and with the bioMérieux VITEK 2 Antimicrobial Susceptibility Testing (AST) system for qualitative testing of isolated colonies of gram-negative and gram-positive bacterial species grown on solid culture media. The Colibrí System is a semi-automated pre-analytical processor that picks isolated colonies designated by the a pipetting system to prepare operator and uses MALDI-TOF MS (Matrix-Laser Desorption/Ionization- Time Of Flight Mass Spectrometry) target slides for Assisted bacterial identification and microbial suspension at known concentration for Antimicrobial Susceptibility Testing and purity assessment.

The Colibrí software records the identity of each sample and its position on the target slide and communicates this information electronically to the MALDI-TOF MS analyzer.

Bacterial suspensions for AST and Purity Plates are identified by barcode label.

The Colibrí System is intended for use by trained healthcare professionals in clinical laboratories in conjunction with other clinical and laboratory findings, including Gram staining, to aid in the diagnosis of bacterial infections.

The Colibrí System has not been validated for use in the identification or processing of yeast species, molds, Nocardia, or mycobacteria.

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VI. Comparison to Predicate

Colibrí System is designed to automatize the standard manual workflow for the preparation of microbial suspension for AST via direct colony suspension method and purity assessment decreasing the risk of cross-contamination among colonies grown on the culture plate, the risk of scratching from the media plate surface and the risk to use AST suspensions at improper concentration. Specifically, the Colibrí Vision System aids the operator in selecting single, well-isolated colonies. The Colibrí Preparation Station allows the automatic picking of the preselected colonies and their suspension into the saline solution of the Primary Tube. The Primary Tube turbidity is checked by the on-board nephelometer to assure it is in the proper working range, allowing the preparation of a Secondary Tube at a precise concentration. The Colibri Preparation Station labels the Secondary Tube and the Purity Plate, optionally prepared, for traceability.

With reference to the sample preparation workflow for AST testing, comparison with the Predicate Device is provided in the following tables:

Similarities
Item	New Device	Predicate Device
Device Name(K number)	Colibrí System(K220546)	VITEK 2 Gram Negative Imipenem &VITEK 2 Systems (PC) 5.02 Software(K103752)
Device Classification	Class II (special controls)	Class II (special controls)
Regulation Number	21 CFR 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system	21 CFR 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system
Product Code	LON System, Test, Automated, Antimicrobial Susceptibility, Short Incubation	LON System, Test, Automated, Antimicrobial Susceptibility, Short Incubation
Indications for Use	The Colibrí System is an in vitro diagnostic device comprised of the Colibrí Vision System and Colibrí Preparation Station for use with the bioMérieux VITEK MS or Bruker MALDI Biotyper CA mass spectrometry systems for qualitative identification and with the bioMérieux VITEK 2 Antimicrobial Susceptibility Testing (AST) system for qualitative testing of isolated colonies of Gram-Negative and Gram-Positive bacterial species grown on solid culture media. The Colibrí System is a semi-automated pre-analytical processor that picks isolated colonies designated by the operator and uses a pipetting system to prepare MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry) target slides and microbial suspension at known concentration for Antimicrobial Susceptibility Testing and purity assessment.The Colibrí software records the identity of each sample and its position on the target slide and communicates this information electronically to the MALDI-TOF MS analyzer.Bacterial suspensions for AST and Purity Plates are identified by barcode label.The Colibrí System is intended for use by trained healthcare professionals in clinical laboratories in conjunction with other clinical and laboratory findings, including Gram staining, to aid in the	VITEK 2 GN Imipenem is designed for antimicrobial susceptibility testing of Gram-Negative bacilli. VITEK 2 GN Imipenem is a quantitative test intended for use with the VITEK 2 and VITEK 2 Compact Systems using VITEK 2 Systems 5.02 Software as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Imipenem has been shown to be active both in vitro and in clinical infections against most strains of the following microorganisms according to the FDA label for the antimicrobial.Active in vitro and in clinical infections:Acinetobacter spp.Citrobacter spp.Enterobacter aerogenesEscherichia coliKlebsiella spp.Active in vitro but clinical significance unknown:Providencia stuartiiThe VITEK 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK 2
		Morganella morganiiProteus vulgarisProvidencia rettgeriPseudomonas aeruginosaSerratia marcescens

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Similarities
Item	New Device	Predicate Device
Device Name(K number)	Colibrí System(K220546)	VITEK 2 Gram Negative Imipenem &VITEK 2 Systems (PC) 5.02 Software(K103752)
	diagnosis of bacterial infections.The Colibrí System has not been validated foruse in the identification or processing of yeastspecies, molds, Nocardia or mycobacteria.	System for the automated quantitative orqualitative susceptibility testing of isolatedcolonies for the most clinically significantaerobic Gram-Negative bacilli, Staphylococcusspp., Enterococcus spp., Streptococcusagalactiae, S. pneumoniae and clinicallysignificant yeast. The VITEK 2 Systems (PC)5.02 Software is intended for use with VITEK 2and VITEK 2 Compact Systems.
Method of testing	Direct testing from isolated colonies.	Direct testing from isolated colonies.
Sample/Media Type	Isolated bacterial colonies from any patientsource.	Isolated bacterial colonies from any patientsource.
	Acceptable media:1. Trypticase soy agar with 5% sheep blood2. MacConkey agar3. Columbia blood agar with 5% sheep bloodas whole plate or bi-plate	Acceptable media:1. Trypticase soy agar with 5% sheep blood2. MacConkey agar3. Columbia blood agar with 5% sheep blood
Solution for SuspensionPreparation	Aqueous 0.45% NaCl Saline Solution (pH 4.5 to7.0)3mL volume in the Secondary Tube	Aqueous 0.45% NaCl Saline Solution (pH 4.5 to7.0)3mL volume in the Secondary Tube
Inoculum density check	The accuracy of the inoculum preparation isverified by an on-boarding nephelometer.	The accuracy of the inoculum preparation isverified by a nephelometer.
Quality control	Suspension of reference strains to be used asquality control should be prepared manuallyaccording to the instruction for use of the usedVITEK 2 card.	Suspension of reference strains to be used asquality control should be prepared manuallyaccording to the instruction for use of the usedVITEK 2 card.
AST resultsinterpretation	MIC and categorization of results are providedby VITEK 2	MIC and categorization of results are providedby VITEK 2

Differences
Item	New Device	Predicate Device
Device Name(K number)	Colibrí System(K220546)	VITEK 2 Gram Negative Imipenem &VITEK 2 Systems (PC) 5.02 Software(K103752)
Colony Selection	The colony to be picked is selected by anoperator on a digital plate using the GraphicalUser Interface of a Vision System.	The colony to be picked be picked is manuallyselected by an operator on a real plate throughthe visual inspection.
Media Type	Colibrí System is not validated for ChromID CPS	Acceptable media:1. ChromID CPS
Method of ColonyPicking	Colibrí System has been validated for automaticpicking of colonies using a sterile pipette tip.	The colonies to be picked are manuallytransferred using a sterile stick or swab.
Sample Traceability	On each Secondary Tube prepared by the ColibríSystem, a barcode label is applied includingfollowing data: the sample identification, thehour of the preparation and the Gramclassification associated to the processed isolate.Label data are used for sample traceability forfurther processing on the VITEK 2.	The sample identification is recorded directlyin the Cassette Docking Station softwaremanually or scanning the barcode of theculture media plate from which the colonieswere collected during the preparation of themicrobial suspension.
Method of ASTsuspension preparation	Using a pipetting system, a predefined numberof morphologically similar colonies aretransferred into Primary Tube containing salinesolution (0.45% NaCl Saline Solution pH 4.5 to7.0). A homogenous heavy suspension oforganisms is prepared and checked by using on-	Using a sterile stick or swab, a sufficientnumber of morphologically similar coloniesare transferred to a saline tube (0.45% NaCl,Saline Solution pH 4.5 to 7.0). A homogenoussuspension with a density equivalent to the 0.5McFarland is prepared and checked with the

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	Differences
Item	New Device	Predicate Device
Device Name(K number)	Colibrí System(K220546)	VITEK 2 Gram Negative Imipenem &VITEK 2 Systems (PC) 5.02 Software(K103752)
	board Colibrí nephelometer. In the SecondaryTube containing 3.0mL of the same salinesolution, a variable aliquot of the heavysuspension is automatically transferred to obtainthe final microbial concentration according toIVD package insert indications. The suspensionsprepared by Colibrí System must be tested inMANUAL MODE on the VITEK 2.	nephelometer. In a second tube containing3.0mL of saline, a predetermined aliquot of 0.5McFarland is transferred according to IVDpackage insert indications (MANUALMODE).Alternatively, the 0.5 McFarland suspensionis loaded on the VITEK 2 that automaticallyprepares the Secondary Tube at properconcentration (AUTO DILUTION MODE).

These differences do not affect substantial equivalence of Colibrí System and the Predicate Device. Both Systems are intended for the AST of microorganisms cultured from human specimens

VII. Performance Data

The following performance data were provided in support of the substantial equivalence determination.

Analytical Studies

The Analytical studies performed with the Colibri System support its use for the preparation of microbial suspension used in conjunction with the bioMérieux VITEK 2 AST analyzer. The Analytical studies demonstrated that the Device can automatically prepare the microbial suspensions at appropriate concentrations, starting from gram-negative and ram-positive bacterial colonies grown on solid culture media, which can be used to hydrate VITEK 2 cards for the determination of susceptibility of organisms to certain drugs. The used methodology (direct colony suspension) and claimed prerequisites for sample preparation are in line with the IVD analyzer manufacturer IFU.

Nephelometer Calibration Verification

To verify the accuracy of the onboard Colibrí System nephelometer in preparing microbial suspensions at specific concentrations within the calibration range, isolated colonies of E. coli (ATCC 25922) grown on non-selective medium were used to manually prepare suspensions at determined concentrations (0.25, 0.5, 1.0, 2.0, 3.0 McFarland), representing the calibration points. For each concentration, 20 suspensions were prepared from three operators in rotation, and the process was repeated on 3 Colibrí Systems calibrated with 3 different lots of suspensions at known concentrations. For each suspension, ten-fold dilutions were prepared and plated in triplicate; to perform viable cell count to calculate the initial tube concentration.

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A total of 300 suspensions were prepared: overall, 100% of suspensions contained the correct concentration of bacteria considering that a 0.5 McFarland suspension of E. coli has a nominal microbial content of 1-2 × 10° CFU/mL+. The study demonstrated acceptable accuracy.

Pipettor Trueness and Precision

The accuracy and reproducibility of the on-board Colibrí System pipettor was determined gravimetrically. Appropriate vessels were weighted before and after the dispensations of four volumes (50uL, 100 uL, 500uL, 900uL) representing the 5%, 10%, 50% and 90% of the nominal volume of the tip used for the AST preparation. Three Colibrí System pipettors were included in the examination: for each volume, 10 measurements were performed using saline solution (aqueous 0.45%, pH 4.5 to 7.0) and the trueness and reproducibility were calculated. As expected, trueness and reproducibility vary according to the volume under testing but always within the acceptance criteria.

E. coli Suspensions Preparation Verification Study

To assess the ability of the Colibri System to prepare and manage Primary Tubes at various concentrations, isolated colonies of the E. coli ATCC® 25922 were used to automatically prepare Primary Tubes at various turbidities.

A variable number of colonies was selected on the plates images to create different suspensions at increasing turbidity values. Three Colibrí Systems run by three different operators were included in the test.

All the Primary Tubes were correctly managed by Colibrí System according to the turbidity value.

100% suspensions over the entire working range contained the expected number of colonies, estimated considering that the 0.5 McFarland has a nominal content of 1-2 × 108 CFU/mL for E. coli'.

Validation of Colony Picking and Preparation of Microbial Suspensions for AST

The accuracy of colony picking and preparation of the microbial suspension was demonstrated by purity check and bacterial concentration determination of the Primary Tubes.

Three Colibrí Systems were used to prepare Primary Tubes and the respective subculture (Purity Plate) from isolated colonies of 6 bacterial species (3 Gram-Negative and 3 Gram-Positive) grown in 2 polymicrobial mixtures on different types of culture medium in whole and biplates at various incubation time. To confirm nephelometer accuracy, bacterial concentration of the Primary Tube was determined by viable cell count and compared to the theorical concentration, estimated considering that the 0.5 McFarland has a nominal content of 1-2 × 108 CFU/mL for E. coli¹.

1 CLSI guideline M07. 11th ed Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. Wayne, PA: Clinical and Laboratory Standards Institute, 2018.

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100% of colonies designated by the operator were picked correctly by the Colibrí System both on whole plates and bi-plates and 100% of Purity Plates showed no evidence of microbial contamination, demonstrating that the Colibrí System accurately picks microbial colonies, without contamination from other microorganisms grown on the same culture plate.

The percentage of prepared suspension with microbial concentration within the acceptable limits was 99.2% and, for each instrument, the result was always >98%. The percentage suspension within acceptable limits has been compared between each instrument with y-test, resulting in no statistically significant difference among the instruments. The results provided evidence that the microbial concentration is accurately measured by the Colibri nephelometer through its turbidity.

AST Challenge Test

The accuracy of MICs obtained by bioMérieux VITEK 2 using Colibrí System for microbial suspensions preparation was evaluated using representative isolates of different species of Enterobacterales (n=62), Staphylococcus (n=16), Streptococcus (n=30), Enterococcus (n=16) and non-fermenters (n=32). The strains included in this study were both susceptible and resistant strains, exhibiting a range of on-scale MIC values toward at least 4 antibiotics representative for the major classes of drugs. Each strain was grown on different agar media (Trypticase Soy Agar + 5% Sheep Blood, MacConkey Agar and Columbia agar+5% sheep blood) at specific incubation times and then processed on three Colibrí System in comparison with the manual preparation.

Microbial suspensions were prepared by Colibrí Preparation Station and processed by the bioMérieux VITEK 2 using the appropriate antibiotic panel. The MICs obtained by bioMérieux VITEK 2 using Colibri System were compared to the MICs obtained by bioMérieux VITEK 2 using manual sample preparation and the SIR category was reported according to the FDA- Recognized Antimicrobial Susceptibility Test Interpretive Criteria. Essential Agreement (EA) of the MICs and Category Agreement (CA) were calculated. The discrepant SIR results were categorized as Very Major Category Error, Major Category Error and Minor Category Error.

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Agent	Organism group	Total tested	# EA	% EA	Total Evaluable	# EA of Evaluable	% EA of Evaluable	Total cat.	# CA	% CA	# S	# R	# vmj	# maj	# min
Amikacin	Enterobacterales	186	186	100%	81	81	100%	186	182	97.8%	141	39	0	0	4
Amikacin	Non-fermenters	81	81	100%	39	39	100%	81	79	97.5%	66	6	0	0	2
Ampicillin	Enterococcus	48	48	100%	4	4	100%	48	48	100%	36	12	0	0	0
Ampicillin	Streptococcus	90	90	100%	0	0	N/A	90	90	100%	90	0	0	0	0
Ampicillin / Sulbactam	Enterobacterales	111	111	100%	9	9	100%	111	111	100%	21	90	0	0	0
Ampicillin / Sulbactam	Non-fermenters	24	24	100%	5	5	100%	24	23	95.8%	15	6	0	0	1
Aztreonam	Enterobacterales	186	185	99.5%	54	54	100%	186	185	99.5%	57	123	0	0	1
Cefepime	Enterobacterales	186	186	100%	58	58	100%	186	185	99.5%	93	54	0	0	1
Cefepime	Non-fermenters	81	81	100%	50	50	100%	81	80	98.8%	48	33	0	1	0
Cefotaxime	Streptococcus	90	90	100%	0	0	N/A	90	90	100%	90	0	0	0	0
Cefoxitin	Enterobacterales	186	186	100%	42	42	100%	186	184	98.9%	36	132	0	0	2
Ceftazidime	Enterobacterales	180	180	100%	43	43	100%	180	179	99.4%	33	132	0	0	1
Ceftazidime	Non-fermenters	105	105	100%	68	68	100%	105	105	100%	57	36	0	0	0
Ceftriaxone	Enterobacterales	186	185	99.5%	31	30	96.8%	186	185	99.5%	36	144	0	0	1
Ceftriaxone	Streptococcus	90	90	100%	0	0	N/A	90	90	100%	90	0	0	0	0
Ciprofloxacin	Non-fermenters	81	81	100%	28	28	100%	81	80	98.8%	51	18	0	0	1
Ciprofloxacin	Staphylococcus	48	48	100%	6	6	100%	48	48	100%	33	12	0	0	0
Clindamycin	Enterococcus	48	48	100%	30	30	100%	48	47	97.9%	27	12	0	0	1
Clindamycin	Streptococcus	90	90	100%	2	2	100%	90	89	98.9%	54	33	0	0	1
Ertapenem	Enterobacterales	186	186	100%	22	22	100%	186	184	98.9%	102	81	0	0	2
Erythromycin	Staphylococcus	48	48	100%	9	9	100%	48	47	97.9%	21	24	0	0	1
Erythromycin	Enterococcus	48	48	100%	15	15	100%	48	48	100%	6	30	0	0	0
Erythromycin	Streptococcus	90	90	100%	29	29	100%	90	90	100%	54	36	0	0	0
Agent	Organism group	Total tested	# EA	% EA	Total Evaluable	# EA of Evaluable	% EA of Evaluable	Total cat.	# CA	% CA	# S	# R	# vmj	# maj	# mi
Gentamicin	Enterobacterales	186	186	100%	40	40	100%	186	185	99.5%	108	66	0	0	1
Gentamicin	Non-fermenters	81	81	100%	27	27	100%	81	81	100%	54	21	0	0	0
Imipenem	Staphylococcus	48	48	100%	6	6	100%	48	48	100%	27	21	0	0	0
Imipenem	Non-fermenters	105	104	99.0%	54	54	100%	105	105	100%	72	33	0	0	0
Levofloxacin	Enterobacterales	186	186	100%	47	47	100%	186	183	98.4%	69	99	0	0	3
Levofloxacin	Non-fermenters	81	81	100%	63	63	100%	81	79	97.5%	42	27	0	0	2
Levofloxacin	Staphylococcus	33	33	100%	14	14	100%	33	32	97.0%	27	6	0	0	1
Levofloxacin	Enterococcus	48	48	100%	41	41	100%	48	47	97.9%	27	6	0	0	1
Linezolid	Streptococcus	90	90	100%	90	90	100%	90	90	100%	87	0	0	0	0
Linezolid	Staphylococcus	48	48	100%	48	48	100%	48	48	100%	48	0	0	0	0
Linezolid	Enterococcus	48	48	100%	48	48	100%	48	47	97.9%	45	0	0	0	1
Linezolid	Streptococcus	90	90	100%	0	0	N/A	90	90	100%	90	0	0	0	0
Meropenem	Enterobacterales	186	186	100%	26	26	100%	186	184	98.9%	111	72	0	0	2
Meropenem	Non-fermenters	105	105	100%	64	64	100%	105	105	100%	72	27	0	0	0
Moxifloxacin	Staphylococcus	48	48	100%	12	12	100%	48	48	100%	39	6	0	0	0
Nitrofurantoin	Enterobacterales	186	186	100%	134	134	100%	186	184	98.9%	51	90	0	0	2
Nitrofurantoin	Staphylococcus	48	48	100%	2	2	100%	48	48	100%	48	0	0	0	0
Oxacillin	Enterococcus	48	48	100%	27	27	100%	48	47	97.9%	24	15	0	0	1
Oxacillin	Staphylococcus	48	48	100%	13	13	100%	48	48	100%	21	27	0	0	0
Penicillin (Benzyl-penicillin)	Enterococcus	48	48	100%	38	38	100%	48	48	100%	33	15	0	0	0
Penicillin (Benzyl-penicillin)	Streptococcus	90	90	100%	25	25	100%	90	90	100%	90	0	0	0	0
Piperacillin / Tazobactam	Staphylococcus	48	48	100%	11	11	100%	48	48	100%	12	36	0	0	0
Piperacillin / Tazobactam	Enterobacterales	177	177	100%	29	29	100%	177	176	99.4%	60	111	0	0	1
Piperacillin / Tazobactam	Non-fermenters	105	105	100%	52	52	100%	105	103	98.1%	57	30	0	0	2
Quinupristin / Dalfopristin	Staphylococcus	48	48	100%	16	16	100%	48	48	100%	45	3	0	0	0
Agent	Organism group	Total tested	# EA	% EA	Total Evaluable	# EA of Evaluable	% EA of Evaluable	Total cat.	# CA	% CA	# S	# R	# vmj	# maj	# min
Tetracycline	Enterobacterales	186	186	100%	54	54	100%	186	184	98.9%	90	87	0	0	2
	Staphylococcus	48	48	100%	7	7	100%	48	48	100%	30	18	0	0	0
	Enterococcus	48	48	100%	0	0	N/A	48	48	100%	15	33	0	0	0
	Streptococcus	42	42	100%	0	0	N/A	42	42	100%	39	3	0	0	0
Tigecycline	Enterobacterales	186	186	100%	104	104	100%	186	183	98.4%	144	18	0	0	3
	Staphylococcus	33	33	100%	0	0	N/A	33	33	100%	33	0	0	0	0
	Enterococcus	21	21	100%	0	0	N/A	21	21	100%	21	0	0	0	0
	Streptococcus	90	90	100%	2	2	100%	90	90	100%	90	0	0	0	0
Tobramycin	Enterobacterales	186	186	100%	42	42	100%	186	185	99.5%	51	108	0	0	1
	Non-fermenters	81	81	100%	1	1	100%	81	80	98.8%	57	24	0	0	1
Trimethoprim / Sulfamethoxazole	Enterobacterales	186	186	100%	3	3	100%	186	186	100%	63	123	0	0	0
Vancomycin	Staphylococcus	48	48	100%	35	35	100%	48	48	100%	45	0	0	0	0
	Enterococcus	48	48	100%	18	18	100%	48	48	100%	30	18	0	0	0
	Streptococcus	90	89	98.9%	65	65	100%	90	90	100%	90	0	0	0	0

AST Challenge Study summary of results, antimicrobial agent

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Group	Incub. time	Totaltested	# EA	% EA	TotalEvaluable	# EA ofEvaluable	% EA ofEvaluable	Totalcat.	# CA	% CA	# S	# R	# maj	# min
Enterobacterales	14 h	1383	1382	99.9%	361	361	100%	1383	1373	99.3%	561	735	0	10
	24 h	1689	1688	99.9%	458	457	99.8%	1689	1672	99.0%	705	834	0	17
Non-fermenters	14 h	420	420	100%	200	200	100%	420	416	99.0%	252	126	0	4
	24 h	510	509	99.8%	251	251	100%	510	504	98.8%	339	135	1	5
Staphylococcus	18 h	594	594	100%	179	179	100%	594	592	99.7%	429	153	0	2
Enterococcus	18 h	453	453	100%	221	221	100%	453	449	99.1%	264	141	0	4
Streptococcus	18 h	942	941	99.9%	213	213	100%	942	941	99.9%	864	72	0	1

AST Challenge Study summary of results, organism group

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MICs obtained using Colibrí System for microbial suspensions preparation showed very high agreement with the manual preparation for all the microorganisms group; overall, 1882/1883 evaluable MIC results were within one doubling dilution of the comparator method result and 5947/5991SIR categorizations were in agreement. The overall Essential Agreement of the evaluable MIC results was > 99.9% and the Category Agreement was 99.3%.

Reproducibility Study

The Reproducibility Study was performed to demonstrate consistency of AST results given by bioMérieux VITEK 2 on microbial suspensions prepared by different Colibrí Systems in different test days.

Culture media showing isolated colonies of different Gram-Positive and Gram-Negative strains were processed on three Colibrí Systems run by three operators over 3 days. Each microorganism was tested with the appropriate antibiotic panel following the analyzer's instructions for use. Each condition was tested in triplicate for a total number of 81 replicates for each combination strainantimicrobial agent.

The MIC results were considered reproducible if they fell within one doubling dilution from the modal value of each combination strain-antimicrobial agent

The results were reproducible for each antimicrobial agent between instruments, operators and days.

Antibiotic	Colibrí System	Best caseª (%)	Worst case (%)
Ampicillin-Sulbactam	Instrument 1	27/27 (100%)	27/27 (100%)
	Instrument 2	27/27 (100%)	27/27 (100%)
	Instrument 3	27/27 (100%)	27/27 (100%)
	Combined	81/81 (100%)	81/81 (100%)
Piperacillin/Tazobactam	Instrument 1	134/135 (99.3%)	133/135 (98.5%)
	Instrument 2	133/135 (98.5%)	132/135 (97.8%)
	Instrument 3	135/135 (100%)	133/135 (98.5%)
	Combined	402/405 (99.3%)	398/405 (98.3%)
Cefoxitin	Instrument 1	81/81 (100%)	79/81 (97.5%)
	Instrument 2	81/81 (100%)	80/81 (98.8%)
	Instrument 3	80/81 (98.8%)	79/81 (97.5%)
	Combined	242/243 (99.6%)	238/243 (97.9%)
Ceftazidime	Instrument 1	187/189 (98.9%)	186/189 (98.4%)
	Instrument 2	189/189 (100%)	189/189 (100%)
	Instrument 3	188/189 (99.5%)	188/189 (99.5%)
	Combined	564/567 (99.5%)	563/567 (99.3%)
Ceftriaxone	Instrument 1	27/27 (100%)	27/27 (100%)
	Instrument 2	27/27 (100%)	27/27 (100%)
	Instrument 3	27/27 (100%)	27/27 (100%)
	Combined	81/81 (100%)	81/81 (100%)
Cefepime	Instrument 1	162/162 (100%)	162/162 (100%)
	Instrument 2	162/162 (100%)	162/162 (100%)

			Summary of reproducibility results - Gram-negatives Organisms Stratified by Antibiotic

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Antibiotic	Colibrí System	Best caseª (%)	Worst caseᵇ (%)
Aztreonam	Instrument 1	81/81 (100%)	81/81 (100%)
	Instrument 2	81/81 (100%)	81/81 (100%)
	Instrument 3	81/81 (100%)	81/81 (100%)
	Combined	243/243 (100%)	243/243 (100%)
Meropenem	Instrument 1	108/108 (100%)	108/108 (100%)
	Instrument 2	108/108 (100%)	108/108 (100%)
	Instrument 3	108/108 (100%)	108/108 (100%)
	Combined	324/324 (100%)	324/324 (100%)
Amikacin	Instrument 1	189/189 (100%)	189/189 (100%)
	Instrument 2	189/189 (100%)	189/189 (100%)
	Instrument 3	188/189 (99.5%)	188/189 (99.5%)
	Combined	566/567 (99.8%)	566/567 (99.8%)
Gentamicin	Instrument 1	81/81 (100%)	81/81 (100%)
	Instrument 2	81/81 (100%)	81/81 (100%)
	Instrument 3	81/81 (100%)	81/81 (100%)
	Combined	243/243 (100%)	243/243 (100%)
Tobramycin	Instrument 1	27/27 (100%)	26/27 (96.3%)
	Instrument 2	27/27 (100%)	27/27 (100%)
	Instrument 3	27/27 (100%)	26/27 (96.3%)
	Combined	81/81 (100%)	79/81 (97.5%)
Levofloxacin	Instrument 1	81/81 (100%)	81/81 (100%)
	Instrument 2	80/81 (98.8%)	80/81 (98.8%)
	Instrument 3	80/81 (98.8%)	80/81 (98.8%)
	Combined	241/243 (99.2%)	241/243 (99.2%)
Tetracycline	Instrument 1	54/54 (100%)	54/54 (100%)
	Instrument 2	54/54 (100%)	54/54 (100%)
	Instrument 3	54/54 (100%)	54/54 (100%)
	Combined	162/162 (100%)	162/162 (100%)
Tigecycline	Instrument 1	81/81 (100%)	80/81 (98.8%)
	Instrument 2	81/81 (100%)	80/81 (98.8%)
	Instrument 3	81/81 (100%)	80/81 (98.8%)
	Combined	243/243 (100%)	240/243 (98.8%)
Nitrofurantoin	Instrument 1	135/135 (100%)	135/135 (100%)
	Instrument 2	135/135 (100%)	134/135 (99.3%)
	Instrument 3	134/135 (99.3%)	134/135 (99.3%)
	Combined	404/405 (99.8%)	403/405 (99.5%)
Imipenem	Instrument 1	27/27 (100%)	27/27 (100%)
	Instrument 2	27/27 (100%)	27/27 (100%)
	Instrument 3	27/27 (100%)	27/27 (100%)
	Combined	81/81 (100%)	81/81 (100%)
Ciprofloxacin	Instrument 1	27/27 (100%)	27/27 (100%)
	Instrument 2	27/27 (100%)	26/27 (96.3%)
	Instrument 3	27/27 (100%)	27/27 (100%)
	Combined	81/81 (100%)	80/81 (98.8%)
Antibiotic	Colibrí System	Best case (%)	Worst case (%)
Levofloxacin	Instrument 1	243/243 (100%)	243/243 (100%)
	Instrument 2	241/243 (99.2%)	241/243 (99.2%)
	Instrument 3	241/243 (99.2%)	241/243 (99.2%)
	Combined	725/729 (99.5%)	725/729 (99.5%)
Tetracycline	Instrument 1	27/27 (100%)	27/27 (100%)
	Instrument 2	27/27 (100%)	26/27 (96.3%)
	Instrument 3	27/27 (100%)	27/27 (100%)
	Combined	81/81 (100%)	80/81 (98.8%)
Tigecycline	Instrument 1	27/27 (100%)	27/27 (100%)
	Instrument 2	27/27 (100%)	27/27 (100%)
	Instrument 3	27/27 (100%)	27/27 (100%)
	Combined	81/81 (100%)	81/81 (100%)
Nitrofurantoin	Instrument 1	54/54 (100%)	54/54 (100%)
	Instrument 2	54/54 (100%)	54/54 (100%)
	Instrument 3	54/54 (100%)	54/54 (100%)
	Combined	162/162 (100%)	162/162 (100%)
Ciprofloxacin	Instrument 1	81/81 (100%)	81/81 (100%)
	Instrument 2	81/81 (100%)	81/81 (100%)
	Instrument 3	81/81 (100%)	81/81 (100%)
	Combined	243/243 (100%)	243/243 (100%)
Penicillin(Benzylpenicillin)	Instrument 1	162/162 (100%)	160/162 (98.8%)
	Instrument 2	162/162 (100%)	159/162 (98.1%)
	Instrument 3	161/162 (99.4%)	159/162 (98.1%)
	Combined	485/486 (99.8%)	478/486 (98.4%)
Ampicillin	Instrument 1	27/27 (100%)	27/27 (100%)
	Instrument 2	27/27 (100%)	27/27 (100%)
	Instrument 3	27/27 (100%)	27/27 (100%)
	Combined	81/81 (100%)	81/81 (100%)
Oxacillin	Instrument 1	27/27 (100%)	27/27 (100%)
	Instrument 2	27/27 (100%)	26/27 (96.3%)
	Instrument 3	27/27 (100%)	26/27 (96.3%)
	Combined	81/81 (100%)	79/81 (97.5%)
Erythromycin	Instrument 1	108/108 (100%)	107/108 (99.1%)
	Instrument 2	108/108 (100%)	108/108 (100%)
	Instrument 3	108/108 (100%)	107/108 (99.1%)
	Combined	324/324 (100%)	322/324 (99.4%)
Quinupristin/Dalfopristin	Instrument 1	54/54 (100%)	52/54 (96.3%)
	Instrument 2	54/54 (100%)	53/54 (98.1%)
	Instrument 3	54/54 (100%)	54/54 (100%)
	Combined	162/162 (100%)	159/162 (98.1%)
Linezolid	Instrument 1	108/108 (100%)	108/108 (100%)
	Instrument 2	108/108 (100%)	108/108 (100%)
	Instrument 3	108/108 (100%)	108/108 (100%)
	Combined	324/324 (100%)	324/324 (100%)
Vancomycin	Instrument 1	189/189 (100%)	188/189 (99.5%)
	Instrument 2	189/189 (100%)	188/189 (99.5%)
	Instrument 3	189/189 (100%)	188/189 (99.5%)
	Combined	567/567 (100%)	564/567 (99.5%)
Antibiotic	Colibrí System	Best case (%)	Worst case (%)
	Instrument 3	189/189 (100%)	188/189 (99.5%)
	Combined	567/567 (99.2%)	564/567 (99.5%)

ªCalculated assuming the off-scale results are within one well from the mode.

bCalculated assuming the off-scale results are greater than one well from the mode.

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Summary of reproducibility results – Gram-positives Organisms Stratified by Antibiotic

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a Calculated assuming the off-scale results are within one well from the mode. bCalculated assuming the off-scale results are greater than one well from the mode.

Purity Plate Growth

In total, 2,364 purity plates have been prepared by different Colibri™ Preparation Station throughout the analytical studies used to support the AST microbial suspension function of the Colibrí System, starting from Secondary Tubes of VITEK® 2, inoculated with various microbial strains. All the purity plates (2364/2364, 100%) were correctly processed and provided evidence of microbial contamination of the Secondary Tubes, demonstrating that Colibri™ Preparation Station is able to prepare monomicrobial suspensions by picking precisely the designated colonies from the culture plates and to prevent the cross-contamination between the specimens.

Sample preparation for Quality Control

The study was performed to demonstrate the reproducibility of MIC results for AST Quality Control organisms listed in CLSI M100 using the Colibrí System as suspension preparator.

The sample preparation for Quality Control was conducted daily at the beginning of the working session on each instrument involved in the Analytical Studies. All instruments were used to prepare bacterial suspensions then tested using the appropriate AST panel. MIC values for each drug/organism combination were compared to the established ranges reported in the AST analyzer labeling, resulting in 100% in-range MIC values. Purity of all the suspensions was confirmed by Purity Plates prepared by Colibrí System. The summary of results is in the table below.

Electrical safety and electromagnetic compatibility (EMC)

Electrical safety and EMC testing were conducted on the Colibrí System, consisting of Colibrí Vision System and Colibrí Preparation Station. The system complies with the IEC 61010-1: 2010, IEC 61010-2-081: 2015, IEC 61010-2-101: 2015 standards for safety and the IEC 61326-1: 2012, IEC 61326-2-6: 2012 and IEC 60601-1-2:2014 standards for EMC; test reports are included.

Laser Product

Colibrí System complies with the IEC 60825-1: 2007 standard; test report is included.

Software Verification and Validation Testing

Software verification and validation testing were conducted according to the internal Standard Operative Procedure in agreement with IEC 62304 Edition 1.1 2015-06 Consolidate version. Documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices"

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issued on May 11, 2005. The software for the Device was considered as a "Moderate" level of concern, since a failure or latent design flaw could directly through incorrect or delayed information or through the action of a care provider result in minor injury to the patient or operator.

Usability validation

Usability has been addressed for Colibri System following recommendations in the "Guidance for Industry and Food and Drug Administration Staff - Applying Human Factors and Usability Engineering to Medical Devices (February 3, 2016)" and in agreement with "IEC 62366-1:2015-02 Medical Devices - Part 1: Application Of Usability Engineering To Medical Devices [Including CORRIGENDUM 1 (2016)]".

The results of usability validation provided evidence that all the measurements implemented to prevent use errors, regarding the device design, labelling and training, are effective and the device can be used in a safe and effective way, establishing that all the risks included in the Risk Analysis have been mitigated and there are no Unacceptable residual risks.

VIII. Non-Clinical and/or Clinical Tests Summary & Conclusions

Conclusions:

All the necessary safety tests were performed and documented. We have verified and validated that the Copan Colibrí System meets its functional specifications and performance requirements, and complies with applicable international standards IEC 61010-1, IEC 61010-2:101, IEC 61010-2:081, IEC 60825-1, IEC 61326-1, IEC 61326-2:6, IEC 60601-1-2:2014, CLSI M100, CLSI M52, CLSI M52, IEC 62304 and IEC 62366-1.

The Analytical Studies results demonstrated that the Colibrí System when used in conjunction with its parental devices is as safe, as effective, and performs as well as the predicate device. The minor differences between the devices do not adversely affect safety and effectiveness. The used methodology (direct colony suspension) and claimed prerequisites for sample preparation are in line with the IVD analyzer manufacturer IFU and with the relevant CLSI guidance.

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.”