Colibri System by COPAN WASP S.r.l.

The Colibrí System is an in vitro diagnostic device comprised of the Colibrí Vision System and Collbrí Preparation Station for use with the bioMérieux VITEK MS or Bruker MALDI Biotyper CA mass spectrometry systems for qualitative identification of isolated colonies of Gram-negative bacterial species grown on solid culture media. The Collbri System is a semi-automated pre-analytical processor that picks isolated 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. 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 analyzer.

The Colibrí 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 Colibrí System has not been validated for use in identification of yeast species.

Device Description

The Copan Colibrí System is designed to be used as an accessory of the downstream MALDI-TOF analyzers automating various manual steps in the workflow for the preparation of samples for the identification of isolated colonies of microorganisms cultured from the human body.

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 and differentiation of organisms grown on plated media by Matrix-Assisted Laser Desorption/Ionization Time-of Flight Mass Spectrometry (MALDI-TOF MS). The system comprises the Colibrí Vision System and Colibrí Preparation Station and pipette tips 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 tasks. By using the Collbrí 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.

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 and of the automated colony spotting.

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.

Colibri System requires three different calibrations. 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. Set-up calibration is performed during the device initial setup for the camera units positioned on the Colibrí Vision System and on the Colibrí Preparation Station. Auto-calibration is performed at the end of the initial set-up and periodically during the preventive maintenance to check that, in the Colibri Preparation Station, 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 Colibri Preparation Station.

AI/ML Overview

The provided text describes the performance data for the Colibrí System, an in vitro diagnostic device. The acceptance criteria are implicitly defined by the performance observed in various analytical studies, with the goal of demonstrating substantial equivalence to predicate devices for qualitative identification of isolated colonies of Gram-negative and Gram-positive bacterial species.

Here's an analysis of the acceptance criteria and study proving the device meets them:

1. Table of Acceptance Criteria (Implicit) and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in a dedicated table with specific thresholds. However, based on the studies conducted, the implicit acceptance criteria appear to be:

High agreement with expected identification (ground truth).
Absence of wrong identifications (false positives).
Maintenance of performance across different conditions (e.g., positional effects, culture age, different MALDI-TOF MS systems and target types, different operators, different Colibrí systems).
Comparable performance to manual preparation.
No cross-contamination.

Here's a table summarizing the reported device performance, which serves as the evidence that these implicit criteria were met. The percentages below represent the agreement with the expected ID (ground truth) for high-confidence results where available, or overall agreement as calculated by the study.

Study Type	Implicit Acceptance Criteria	Reported Device Performance and Notes (Colibrí System)
Colony Picking for Microbial Identification	High accuracy (close to 100%) in picking designated colonies and correct identification with high confidence, with no wrong identifications. Comparable performance across different MALDI-TOF MS systems.	VITEK MS: 100% correct colony picking (no wrong colony picked).Overall 98.4% agreement with expected strain identity (1368/1390 spots with high confidence or low discrimination).0 wrong IDs.Bruker MALDI Biotyper CA: 100% correct colony picking.Overall 90.8% agreement with expected strain identity (1534/1690 spots with high confidence or low discrimination).0 wrong IDs.Noted lower proportion of concordant results for Gram-positive species, but no incorrect identifications. Recommended manual repeat testing for low/no ID results.
Positional Effect Study	No positional effect observed; consistent identification accuracy across all target slide positions. No wrong identifications.	VITEK MS: 100% agreement for E. coli (432/432), 99.8% for S. aureus (431/432).0 wrong IDs.No positional effect detected.Bruker MALDI Biotyper CA (US IVD 48 Spot): 99.8% agreement for E. coli (431/432), 96.8% for S. aureus (418/432).0 wrong IDs.No positional effect detected.Bruker MALDI Biotyper CA (MBT Biotarget 96 US IVD): 99.9% agreement for E. coli (845/846), 95.7% for S. aureus (810/846).0 wrong IDs.No positional effect detected.
Inclusivity Study	High agreement with expected identification for "on-panel" species, with no false identifications. Performance should be comparable to manual preparation.	VITEK MS: Overall 97.2% agreement (334/392 high confidence; 47/392 low discrimination included in agreement, total 381/392) with expected ID.0 wrong IDs.Manual preparation agreement: 91.6% (combined for high confidence and low discrimination). Colibrí system performed comparably or better.Bruker MALDI Biotyper CA (US IVD 48 Spot): Overall 93.2% agreement (436/468 high confidence) with expected ID.0 wrong IDs.Manual preparation agreement: 97.2% (combined for high confidence and low discrimination). Performance lower for Gram-positive species.Bruker MALDI Biotyper CA (MBT Biotarget 96 US IVD): Overall 85.7% agreement (401/468 high confidence) with expected ID.0 wrong IDs.Manual preparation agreement: 88.0% (combined for high confidence and low discrimination). Performance lower for Gram-positive species.For both Bruker systems, device labeling will recommend manual repeat testing for low/no ID results, consistent with predicate IFU.
Specificity Study	"Off-panel" species should yield no identification, or results consistent with their "off-panel" status, with no false positives for "on-panel" species.	VITEK MS: 100% agreement (20/20) that "off-panel" organisms yielded no identification or uninterpretable results.0 false positives for "on-panel" species.Bruker MALDI Biotyper CA: 100% agreement (20/20) that "off-panel" organisms yielded no identification or uninterpretable results.0 false positives for "on-panel" species.
Reproducibility Study	Highly repeatable results across multiple Colibrí systems, operators, and replications, with high agreement to expected ID and no wrong IDs.	VITEK MS: 99.9% agreement (1799/1800) with expected ID (including low discrimination results that are considered acceptable by the VITEK MS system).0 wrong IDs.Bruker MALDI Biotyper CA: 88.1% agreement (1585/1800) with high confidence ID.0 wrong IDs.Lower agreement for Gram-positive species (76.7% high confidence) compared to Gram-negative (99.4% high confidence), consistent with other studies. Device labeling to recommend manual repeat testing for low/no ID Gram-positive results.
Cross-Contamination Studies	No false-positive results due to contamination of adjacent spots.	VITEK MS: "On-panel" species: 99.3% correct identification (284/286) with high confidence."Off-panel" species: 100% yielded no identification (286/286).No false positives observed.Bruker MALDI Biotyper CA (US IVD 48 Spot): "On-panel" species: 95.0% correct identification (190/200 high confidence, 10/200 low confidence included in performance evaluation)"Off-panel" species: 100% yielded no identification (200/200).No false positives observed.Bruker MALDI Biotyper CA (MBT Biotarget 96 US IVD): "On-panel" species: 85.3% correct identification (122/143 high confidence, 11/143 low confidence included in performance evaluation)"Off-panel" species: 100% yielded no identification (143/143).Lack of ID not due to cross-contamination, but lower performance for Gram-positives for this system.
Colony Stability Study	Maintain expected identification performance across various culture ages and media types.	VITEK MS: 99.8% agreement overall (575/576) at various time points (18h, 24h, 48h, 72h depending on media type).No false identifications.Bruker MALDI Biotyper CA (MBT Biotarget 96 US IVD): Generally good agreement for Gram-negative species regardless of culture medium or incubation duration. Lower agreement for Gram-positive species.No incorrect identification results reported.Specific note for B. pertussis on Bordet Gengou Agar showing decreased high confidence scores after prolonged ambient temperature holding.
Spot Stability Prior To and After Matrix Deposition	Stable identification performance when testing is delayed (before and after matrix application).	VITEK MS: Colonies stable up to 60 mins without matrix.Targets stable for 48h at room temp on Colibrí deck, and 72h in original box.Identification performance not different from standard conditions.Bruker MALDI Biotyper CA: Colonies stable up to 60 mins without matrix on both target types.Targets stable for 24h at room temp when held on Colibrí deck and lab bench.Lower agreement for Gram-positive species with 96-spot disposable format noted.

2. Sample Sizes Used for the Test Set and Data Provenance

Test Set (Analytical Studies):
- Colony Picking: 1390 spots (VITEK MS) and 1690 spots (Bruker MALDI Biotyper CA).
- Positional Effect: 864 spots (VITEK MS), 864 spots (Bruker MALDI Biotyper CA US IVD 48 Spot), 1692 spots (Bruker MALDI Biotyper CA MBT Biotarget 96 US IVD).
- Inclusivity: 392 spots/strains (VITEK MS) and 468 spots/strains for each Bruker MALDI Biotyper CA system (US IVD 48 Spot and MBT Biotarget 96 US IVD).
- Specificity: 20 spots (VITEK MS) and 20 spots (Bruker MALDI Biotyper CA).
- Reproducibility: 1800 spots (VITEK MS) and 1800 spots (Bruker MALDI Biotyper CA).
- Cross-Contamination: 572 spots (VITEK MS) and 686 spots (Bruker MALDI Biotyper CA total for both systems).
- Colony Stability: 576 spots (VITEK MS) and 1440 spots (Bruker MALDI Biotyper CA).
Data Provenance: The document generally indicates "on-panel" and "off-panel" strains, often referring to common clinical isolates in the US. No explicit country of origin for the clinical samples/strains themselves is stated beyond generic "human specimens" or "commonly isolated Gram-positive and Gram-negative species in the US". The studies were conducted by a single operator (Inclusivity, Specificity, Cross-Contamination, Colony Stability) or two operators (Reproducibility) on multiple Colibrí systems (Reproducibility, Colony Picking, Inclusivity, Cross-Contamination) in laboratory settings. The studies are prospective as they are designed experiments to evaluate the device performance.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document implies that the ground truth for identification was established by the expected strain identity of the stock cultures used in the analytical studies. This means the identities of the bacterial strains were known beforehand (e.g., ATCC strains or well-characterized lab strains).
For the performance results themselves, identification was based on the output of the VITEK MS or Bruker MALDI Biotyper CA systems, which generate confidence values or log scores. The interpretation of these scores (e.g., what constitutes a "correct single choice") is intrinsic to the performance specifications of these established MALDI-TOF MS systems.
No human experts (e.g., radiologists) were used to establish the ground truth for these microbial identification studies. The "ground truth" is the presumed identity of the bacterial strain used in the experiment.

4. Adjudication Method for the Test Set

Not applicable in the conventional sense. Since the ground truth for the test set was the expected strain identity of known bacterial cultures, there was no need for human expert adjudication to resolve discrepancies in interpretation. The output of the MALDI-TOF MS system for each sample was compared directly to the known identity of the inoculated strain. Discrepancies (low confidence, no ID, wrong ID) were noted and analyzed against the overall performance.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No. An MRMC study is typically performed for image-based diagnostic aids where multiple human readers interpret cases with and without AI assistance. This study involves microorganism identification, a laboratory process, not direct human interpretation of images for diagnosis.
The study compares the performance of the automated Colibrí System to manual preparation (the standard of care, as listed in the predicate device comparison tables), which is a different type of comparison than human readers with/without AI assistance.
Effect size of human reader improvement: Not applicable, as no human reader study was conducted. The comparison is between an automated sample preparation method (Colibrí) and a manual sample preparation method for laboratory identification.

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

Yes, indirectly. The Colibrí System is a semi-automated pre-analytical processor. While an operator designates the colony, the picking, spotting, and matrix application are automated.
The performance metrics provided (e.g., % agreement, no wrong ID) are for the Colibrí System's ability to prepare samples for subsequent MALDI-TOF MS analysis, which then generates the identification result. The Colibrí software records location and transmits information to the MALDI-TOF MS analyzer.
The study evaluated the effectiveness of the automated sample preparation step compared to manual preparation, which directly impacts the downstream MALDI-TOF MS identification. However, the identification itself is performed by the MALDI-TOF MS analyzer, not the Colibrí system's "algorithm" in isolation, except for tracking sample positions. The Colibrí's key "algorithm" is in its vision system and robotic picking/spotting, which impacts the quality of the sample for the MALDI-TOF MS.

7. The Type of Ground Truth Used

Expected Strain Identity: The ground truth for the analytical studies was the known, expected identity of the bacterial strains used. These were presumably well-characterized laboratory strains (e.g., ATCC cultures) with a confirmed identity. This is a highly controlled form of ground truth.

8. The Sample Size for the Training Set

Not explicitly stated in terms of a "training set" for an AI/machine learning model used within Colibrí's core functions. The Colibrí System is described as a "semi-automated pre-analytical processor" that uses "a pipetting system" and "Colibrí software records the identity of each sample and its position". It's unclear if the "Colibrí Vision System" employs complex machine learning that would require a dedicated training set beyond basic image processing for colony detection and localization.
The document implies that the system is automating a manual process, meaning its "training" pertains more to engineering and calibration rather than a machine learning model for diagnosis. The performance studies focus on the system's accuracy in physical manipulation and compatibility with existing MALDI-TOF MS systems.

9. How the Ground Truth for the Training Set Was Established

Not applicable as a distinct ML training set is not described. If the "Colibrí Vision System" used internal algorithms that were "trained" to recognize colony morphology for picking, the ground truth would likely have been established by manually annotating colonies on images or physical plates as "pickable" or "not pickable" based on expert microbiological judgment, but this is not mentioned in the provided text. The current text suggests the operator "chooses the plates exhibiting adequate growth and selects the isolated colonies to be processed assigning the automatic ID tasks" on a "digital plate", implying human-in-the-loop for key decisions.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the words "U.S. FOOD & DRUG" on one line and "ADMINISTRATION" on the line below. The FDA logo is in blue.

December 27, 2021

COPAN WASP S.r.l.

% Enrico Bisson Consultant Studio D'ingegneria Enrico Bisson Via Marzia 9 Abano Terme, 35031 Italy

Re: K193138

Trade/Device Name: Colibri System Regulation Number: 21 CFR 866.3378 Regulation Name: Clinical mass spectrometry microorganism identification and differentiation system Regulatory Class: Class II Product Code: QQV, QBN Dated: June 16, 2020 Received: June 19, 2020

Dear Enrico Bisson:

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

{1}------------------------------------------------

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 mediation-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,

Ribhi Shawar. Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K193138

Device Name Colibrí System

Indications for Use (Describe)

The Colibrí System has not been validated for use in identification of yeast species.

Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CER 801 Subnart D)	Over-The-Counter I Ise (21 CER 801 Subnart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

I. SUBMITTER

Applicant Name:	Copan WASP Srl
	Via A. Grandi 32
	25125 Brescia, Italy
	+39 030 2687211
	copan.regulatory@copangroup.com

Contact Person	Enrico Bisson
	ISOPLAN CONSULTING
	Studio di Ingegneria Enrico Bisson
	Via Marzia, 9
	35031 Abano Terme (PD), Italy
	+39 030 2687211 +39 3286439091
	copan.regulatory@copangroup.com
Establishment Registration Number:	3009288740
Date Prepared:	December 23, 2021

II. DEVICE NAME

Proprietary Name	Colibrí System
Common/Usual Name	Colibrí System
Classification Name	Clinical mass spectrometry microorganism identification and differentiation system (21 CFR 866.3378)
Device Class	II
Product Code	QQV, QBN
Panel	Microbiology

{4}------------------------------------------------

III. LEGALLY MARKETED PREDICATE DEVICE

Device Name	VITEK MS
510(K) Number	K181412

No reference Devices were used in this submission.

IV. DEVICE DESCRIPTION

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.

{5}------------------------------------------------

performed during the normal usage to automatically check the proper functioning of the Colibrí Vision System and the Colibri Preparation Station.

V. INTENDED USE/INDICATIONS FOR USE

The Colibrí System is an in vitro diagnostic device comprised of the Colibrí Vision System and Colibri Preparation Station for use with the bioMérieux VITEK MS or Bruker MALDI Biotyper CA mass spectrometry systems for qualitative identification of isolated colonies of Gram-negative and Gram-positive bacterial species grown on solid culture media. The Colibrí System is a semiautomated 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. 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.

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 identification of yeast species.

VI. COMPARISON TO PREDICATE DEVICE

The Colibrí System is designed to automatize the standard manual workflow for the preparation of targets for MALDI-TOF MS identification via Direct Colony Transfer decreasing the risk of crosscontamination among colonies grown on the culture plate and scratching from the media plate surface. Specifically, the Vision System aids the operator in selecting a single, well-isolated colony. The Preparation Station allows the automatic picking of the preselected colony, its spotting in the available position and the addition of the manufacturer recommended matrix.

With reference to the sample preparation flow, comparison with the predicate is provided in the following tables:

Similarities
Item	New Device	Primary Predicate Device	Other
Device Name(K number)	Colibrí System(K193138)	VITEK MS(K181412)	MALDI Biotyper CA System(DEN170081)
DeviceClassification	Class II (special controls)	Class II (special controls)	Class II (special controls)
RegulationNumber	21 CFR 866.3378 Clinical MassSpectrometry MicroorganismIdentification and DifferentiationSystem	21 CFR 866.3378 Clinical MassSpectrometry MicroorganismIdentification and DifferentiationSystem	21 CFR 866.3378 Clinical MassSpectrometry MicroorganismIdentification and DifferentiationSystem
Product Code	QQV: Automated System forSample Preparation And	QBN: Mass Spectrometry, MaldiTof, Microorganism Identification,	QBN: Mass Spectrometry, MaldiTof, Microorganism Identification.
	Identification Of Microorganisms From Cultured Isolates By Mass Spectrometry	Cultured Isolates	Cultured Isolates
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 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. The Colibrí software records the identity of each sample and its position on the target slide and communicates this information electronically to the MALDI-TOFMS analyzer. 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 identification of yeast species.	VITEK MS is a mass spectrometry system using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) for the identification of microorganisms cultured from human specimens. The VITEK MS system is a qualitative in vitro diagnostic device indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial, yeast and mould infections. (list of claimed organisms omitted for brevity; refer to K181412)	The MALDI Biotyper CA System is a mass spectrometer system using matrix-assisted laser desorption/ionization - time of flight (MALDI-TOF) for the identification and differentiation of microorganisms cultured from human specimens. The MALDI Biotyper CA System is a qualitative in vitro diagnostic device indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infections. (list of validated organisms omitted for brevity; refer to DEN1 70081)
Sample/Media Type	Isolated bacterial colonies from any patient source on plated culture media.Acceptable media when Colibrí System is used in connection with VITEK MS:• Columbia blood agar with 5% sheep blood• Trypticase soy agar with 5% sheep blood• Chocolate agar• MacConkey AgarAcceptable media when Colibrí System is used in connection with MALDI Biotyper CA:	Isolated bacterial colonies from any patient source on plated culture media.Acceptable media:• Columbia blood agar with 5% sheep blood• Trypticase soy agar with 5% sheep blood• Chocolate polyvitex agar• MacConkey agar	Isolated bacterial colonies from any patient source on plated culture media.Acceptable media:• Columbia blood agar with 5% sheep blood (Gram-negative bacteria)• Trypticase soy agar with 5% sheep blood (Gram-negative bacteria)• Chocolate agar (Gram-negative bacteria, Gram-positive bacteria)• MacConkey Agar (Gram-negative bacteria)• Columbia CNA agar with 5% sheep blood (Gram-positive bacteria)
	• sheep blood• Trypticase soy agar with 5%sheep Blood• Chocolate agar• MacConkey Agar• Columbia CNA agar with 5%sheep blood• Bordet Gengou Agar with 15%sheep bloodNote: media are selected amongthose recommended fortheLegally marketed PredicateDevices and suitable for Gram-negative and Gram-positivebacteria.Strains used to evaluate ColibríSystem performancecharacteristics have been selected		• Bordet Gengou Agar with 15%sheep blood ( Bordetella species
	among those claimed from theLegally marketed Predicatedevices.
Method ofSamplePreparation	Direct spotting to target/slide ofGram-negative and Gram-positivebacteria.	Direct spotting to slide of Gram-negative and Gram-positivebacteria.	Bacteria: Direct spotting to targetof Gram-negative and Gram-positive bacteria.
	A portion of microbial colonyfrom an agar plate is automaticallyspotted on a VITEK MS-DS targetslide or MALDI Biotyper target byusing the pipetting system.	A portion of microbial colony froman agar plate is manually applied toa spot of VITEK MS-DS targetslide using a 1uL loop.	An isolated colony of bacteria issmeared as a thin film using asterile colony transfer device,directly onto a sample position on acleaned US IVD 48 Spot Target oran unused sample position of aMBT Biotarget 96 US IVD plate.
Target Slide	When connected with VITEK MS,VITEK MS-DS Target Slides, 48positions disposable plastic targetsWhen connected with BrukerMALDI Biotyper CA, followingtargets may be processed:Bruker US IVD 48 Spot targetBruker MBT Biotarget 96 US IVDplate.	following target may be processed positions disposable plastic targets	IVD 48 Spot TargetMBT Biotarget 96 US IVD plate.
Matrix	1 µL VITEK MS-CHCA matrix isautomatically applied to the spotusing the pipetting system.The dried target slide is thenmanually loaded into the VITEKMS instrument.1 µL US IVD HCCA portioned isautomatically applied to the spotusing the pipetting system.The dried target slide is thenmanually loaded into the MALDIBiotyper CA instrument.	1 µL VITEK MS-CHCA is appliedto the spot using a pipette.The dried target slide is thenmanually loaded into the VITEKMS instrument.	1 µL US IVD HCCA portioned isapplied to the spot using a pipette.The dried target slide is thenmanually loaded into the MALDIBiotyper CA instrument
Calibration/	For VITEK MS: Escherichia coli	Escherichia coli ATCC 8739	US IVD Bacterial Test Standard
QualityControls	ATCC 8739 (calibrator strain) and Klebsiella aerogenes ATCC 13048 (positive control strain) are manually spotted in predetermined positions.For MALDI Biotyper CA: USIVD Bacterial Test Standard(BTS) is manually spotted before loading in the instrument.	(calibrator strain) and Klebsiella aerogenes ATCC 13048 (positivecontrol strain) are manually spotted in predetermined positions	(BTS) is manually spotted beforeloading in the instrument.
CultureStability	For Bacteria:When connected with VITEK MS,incubation of culture should be 18- 72hrs (18-48hrs for ChocolateAgar).When connected with MALDIBiotyper CA, incubation of cultureshould be 18-48hrs (+12hrsstorage at RT).	For Bacteria:Incubation of culture should be 18-72hrs	For Bacteria:Incubation of culture should bebetween 18-48hrs (+12hrsstorage at RT).
Spot Stability	When connected with VITEK MS, after matrix addition, targets arestable for 48h at room temperaturewhen held on the Colibrí deck andfor 72h when held in the originalbox.When connected with MALDIBiotyper CA, after matrix additiontargets are stable for 24h at roomtemperature.	After matrix addition, targets arestable for 72h when held in theoriginal box.	After matrix addition, targets arestable for 24h at room temperature
MALDI-TOFMS Analyzer	bioMérieux VITEK MSBruker MALDI Biotyper CA	bioMérieux VITEK MS	Bruker MALDI Biotyper CA
Method ofTesting	When connected with VITEK MS,direct testing from isolatedcolonies.When connected with BrukerMALDI Biotyper CA, directtesting from isolated colonies. Ifafter initial analysis the log(score)is reported at <2.00, organismsmay be processed by manualpreparation using the Extraction(Ext) procedure or extended DirectTransfer.	For bacteria:Direct testing from isolated colonies	For bacteria:Direct testing from isolatedcolonies; If after initial analysis thelog(score) is reported at <2.00,organisms may be processed usingthe Extraction (Ext) procedure orextended Direct Transfer (eDT,70% aqueous formic acid)procedure.If eDT procedure still yields log(score)<2.00, organisms may beprocessed via Ext procedure.

{6}------------------------------------------------

{7}------------------------------------------------

Copan WASP S.r.1., Traditional 510(k)-Colibrí System

{8}------------------------------------------------

Differences
Item	New Device	Primary Predicate Device	Other
Device Name(K number)	Colibrí System(K193138)	VITEK MS(K181412)	MALDI Biotyper CA System(DEN170081)
TargetOrganism	Colibrí System has been validatedfor direct spotting to target/slide ofGram-negative and Gram-positivebacteria only.	VITEK MS also includesmycobacteria, nocardia, yeast andmould indications for use, aninactivation and extraction processis required for sample prep, prior tospotting the sample to the slide.	MALDI Biotyper CA also includesyeast indications for use. If afterinitial analysis the log(score) isreported at <2.00, organisms maybe processed using the Extraction(Ext) procedure or extended DirectTransfer (eDT, 70% aqueous
	Differences
Item	New Device	Primary Predicate Device	Other
Device Name(K number)	Colibrí System(K193138)	VITEK MS(K181412)	MALDI Biotyper CA System(DEN170081)
			formic acid) procedure. If eDTprocedure still yields log(score)<2.00, organisms may be processedvia Ext procedure.
ColonySelection	The colony to be picked is selectedby an operator on a digital plateusing the Graphical User Interfaceof a Colibrí Vision System.	The colony to be picked is selectedby an operator on a real platethrough the visual inspection.	The colony to be picked is selectedby an operator on a real platethrough the visual inspection
SampleTraceability	A unique identifier (Sample ID) isautomatically linked to each spotposition and transferred to theMALDI-TOFMS analyzersthrough ethernet protocolcommunication.	Sample ID is manually entered byusing the VITEK MS Prep Station.	Sample ID is manually entered byusing the User Graphical Interface.
Method ofSamplePreparation	The colony is picked and spotted onthe target by automated preparationusing the Colibrí PreparationStation	The colony is picked and spotted onthe target by manual preparation bythe operator.	The colony is picked and spotted onthe target by manual preparation bythe operator.
CultureMedia	Colibrí System includesindications for use for bacterialisolates only (no yeast) fromvalidated solid culture mediaeither in whole or bi-plateformat.Acceptable media:When connected with VITEKMS:• Trypticase Soy Agar + 5%sheep blood/ MacConkeyWhen connected with MALDIBiotyper CA:• Trypticase Soy Agar + 5%sheep blood/ MacConkey• Columbia CNA Agar /MacConkey	Other acceptable media forbacteria and yeast:• BacT/ALERT MP• Brucella agar base• Buffered charcoal yeast extract• Campylosel agar• chromIDCPS• Coletsos• Lowenstein-Jensen*• MGIT• Middlebrook 7H10 agar• Middlebrook 7H11 agar• Modified Sabouraud dextroseagar (glucose: 20 g/l - pH: 6.1)• Potato dextrose agar• Sabouraud dextrose agar(glucose: 40 g/l pH: 5.6)• Sabouraud dextrose agar withGentamicin &Chloramphenicol• Trypticase soy agar• Trypticase soy agar withneutralizersVITEK MS includesmycobacteria indications for usefrom both solid & liquid culturemedia, and nocardia and mouldindications for use from solidculture media only.	Other acceptable media forbacteria and yeast:• Brucella Agar with 5% horseblood (Gram-negativeanaerobic bacteria, Gram-positive anaerobic bacteria)• CDC anaerobe Agar with 5%sheep blood (Gram-negativeanaerobic bacteria, Gram-positive anaerobic bacteria)• CDC anaerobe 5% sheep bloodAgar with phenylethyl alcohol(Gram-negative anaerobicbacteria, Gram- positiveanaerobicbacteria)• CDC anaerobe laked sheepblood Agar with kanamycinand vancomycin (Gram-negative anaerobic bacilli)• Bacteroides bile esculin Agarwith amikacin (Bacteroidesspecies)• Clostridium difficile Agar with7% sheep blood (Clostridiumdifficile)• Sabouraud-Dextrose Agar(yeasts)• Brain Heart Infusion Agar( yeasts )• Campylobacter Agar with 5Antimicrobics and 10% SheepBlood (Campylobacter species)• Buffered Charcoal YeastExtract Agar• Buffered Charcoal Yeast
Differences
Item	New Device	Primary Predicate Device	Other
Device Name(K number)	Colibrí System(K193138)	VITEK MS(K181412)	MALDI Biotyper CA System(DEN170081)
			Extract Selective Agar withpolymyxin, anisomycin andvancomycin• Modified Thayer-Martin AgarMALDI Biotyper CA Systemincludes indications for use forbacteria and yeast isolates fromsolid culture media.
Age ofCulture	Bordet Gengou Agar with 15%sheep blood: incubation shouldbe prolonged to 5 (+12hrsstorage at RT) - 7 days.	For yeast: Incubation of cultureshould be 18-72hrsIncubation of Brucella sppshould be 48-96 hrs (2-4days)	For yeast: Incubation of cultureshould be between 18-36hrs
Method ofTesting	Colibrí System has beenvalidated for direct spotting totarget/slide of Gram-negativeand Gram-positive bacteria only.	(For yeast)Direct testing from isolatedcolonies(For mycobacteria, Nocardia,moulds) Inactivation andextraction prior to samplespotting on the target slide(For Brucella spp)Inactivation required prior tosample spotting on the targetslide	(For yeast)Direct testing from isolatedcolonies; If after initial analysisthe log(score) is reported at<2.00, organisms may beprocessed using the Extraction(Ext) procedure or extendedDirect Transfer (eDT, 70%aqueous formic acid) procedure.If eDT procedure still yields log(score)<2.00, organisms may beprocessed via Ext procedure.

Copan WASP S.r.l., Traditiona1 510(k)-Colibrí System

CONFIDENTIAL Page 5-6

{9}------------------------------------------------

{10}------------------------------------------------

These differences do not affect substantial equivalence of Colibrí System and the Predicate Devices. Both Systems are intended for the identification 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 performed analytical studies verified and validated the use of the Colibri System in conjunction with the bio Mérieux VITEK MS or Bruker MALDI Biotyper CA mass spectrometry systems. The analytical studies carried out to evaluate the performance of the Colibrí System demonstrated that the device can automatically prepare the proprietary branded target slide for both MALDI-TOF MS analyzers by spotting colonies and the necessary matrix, starting from Gram-negative and Grampositive bacterial colonies grown on solid culture media. The used methodology (direct colony spotting) and claimed prerequisites for sample preparation are in line with the IVD analyzer

{11}------------------------------------------------

manufacturer IFU and with the relevant guidance.

Colony Picking for Microbial Identification Study

To assess the accuracy of Colibrí System in picking designated colonies of various microbial species from different culture media (whole and bi-plated colonies from mixed cultures prepared with "on-panel" Gram-positive and Gram-negative strains have been used to prepare the bioMérieux VITEK MS-DS and Bruker MALDI Biotyper CA System target slides. The preparation has been repeated on 3 different Colibrí Systems and compared to the manual preparation.

Colonies designated by the operator were picked correctly at 100% without any event in which a wrong colony was picked and no wrong identifications were obtained. For the VITEK MS, a total of 1390 spots were prepared: as overall, 98.4% of designated colonies has been identified correctly with high confidence in comparison to the expected strain identity.

Colony Picking Study identification results of the Colibrí System obtained with the bioMérieux VITEK MS stratified per species.

Test strain	Total no. of picked colonies	Correct Single Choice (≥60% Confidence value)	Low discrimination (<60% Confidence value)	No ID	Wrong ID	% agreement* between Colibrí and expected ID
Gram-positive
Enterococcus faecalis	168	152	1	15	0	90.5%
Streptococcus agalactiae	162	156	0	6	0	96.3%
Staphylococcus aureus	292	292	0	0	0	100.0%
Total Gram-positive	622	600	1	21	0	96.5%
Gram-negative
Klebsiella pneumoniae	310	310	0	0	0	100.0%
Proteus mirabilis	158	158	0	0	0	100.0%
Escherichia coli	300	300	0	0	0	100.0%
Total Gram-negative	768	768	0	0	0	100.0%
Total	1390	1368	1	21	0	98.4%

*Calculated as Agreement (%) = =============================================================================================================================================== Total number of picked colonies

For the Bruker MALDI Biotyper CA System, a total of 1690 spots were prepared: the identification performance varied among the species with a lower proportion of concordant results for Grampositive species: nevertheless, the overall performance (calculated only on results providing High Confidence Log (Score)) is considered acceptable because no incorrect identification occurred. Colonies designated by the operator were picked correctly at 100% without any event in which a wrong colony was picked and no wrong identifications were obtained. In addition, consistent with the Instructions for Use of the Bruker MALDI Biotyper CA System, if a low-confidence identification or a no identification result is obtained, the Copan Colibrí System Package Insert will recommend repeat testing of the isolate manually using the extended Direct Transfer (eDT) or Extraction (Ext) Sample Preparation Procedure.

{12}------------------------------------------------

Test strain	Total no. of picked colonies	High confidence ID Log (Score) ≥ 2	Low confidence ID 1.7≤ Log (Score) <2	Combined performance	No ID	Wrong ID	% agreement* between Colibrí and expected ID
Gram-positive
Enterococcus faecalis	150	122	22	144	6	0	81.3%
Streptococcus agalactiae	150	105	26	131	19	0	70.0%
Staphylococcus aureus	364	316	48	364	0	0	86.8%
Staphylococcus epidermidis	148	118	30	148	0	0	79.7%
Total Gram-positive	812	661	126	787	25	0	81.4%
Gram-negative
Proteus mirabilis	168	168	0	168	0	0	100.0%
Klebsiella pneumoniae	330	330	0	330	0	0	100.0%
Escherichia coli	380	375	5	380	0	0	98.7%
Total Gram-negative	878	873	5	878	0	0	99.4%
Total	1690	1534	131	1665	25	0	90.8%

Colony Picking Study identification results of the Colibrí System obtained with the Bruker MALDI Biotyper CA System stratified per species.

No. of correct results with High Confidence Log (Score)≥2 x100 *Calculated as Total number of picked colonies

Positional Effect Study

The Positional Effect Study was performed to demonstrate that the Copan Colibrí System can prepare target spots for MALDI-TOF MS analysis at each location on the target slide. For this test, media plates showing growth of bacteria included in the knowledge databases of the bioMérieux VITEK MS and Bruker MALDI Biotyper CA System ("on-panel" strains) were used to challenge the accuracy of the Copan Colibrí System in spotting the picked colonies in all the target slide positions. The study conducted in conjunction with Bruker MALDI Biotyper CA System was performed using both the US IVD 48 Spot target (48-position reusable target) and the MBT Biotarget 96 US IVD (96-position disposable target) that have different geometry and spot diameters. No positional effect was detected, and no wrong identification results were obtained with either mass spectrometry analyzer.

Positional Effect Study identification results of the Colibrí System obtained with the bioMérieux VITEK MS

Test Strain	No. of spots	Correct Single Choice Confidence value ≥ 60%	Low Discrimination Confidence value < 60%	No ID	Wrong ID	% agreement* between Colibrí and expected ID *
Escherichia coli	432	432	0	0	0	100%
Staphylococcus aureus	432	431	0	1	0	99.8%

No. of correct results with Good Confidence value (≥60%) x100 *Calculated as Total number of picked colonies

{13}------------------------------------------------

Positional Effect Study identification results of the Colibrí System obtained with the Bruker MALDI Biotyper CA System with US IVD 48 Spot target

TestStrain	No. ofspots	CorrectIdentificationwith highconfidence(Log scorevalue 2.00-3.00)	LowConfidenceIdentification(Log scorevalue 1.70-1.99)	Combinedperformance	No ID	WrongID	% agreementbetweenColibrí andexpected ID *
Escherichiacoli	432	431	1	432	0	0	99.8%
Staphylococcusaureus	432	418	14	432	0	0	96.8%

*Calculated as Total number of picked colonies

Positional Effect Study identification results of the Colibrí System obtained with MALDI Biotyper CA System with MBT Biotarget 96 US IVD

TestStrain	No. ofspots	CorrectIdentificationwith highconfidence(Log scorevalue 2.00-3.00)	LowConfidenceIdentification(Log scorevalue 1.70-1.99)	Combinedperformance	No ID	WrongID	% agreementbetweenColibrí andexpected ID *
Escherichiacoli	846	845	1	846	0	0	99.9%
Staphylococcusaureus	846	810	34	844	2	0	95.7%

No. of correct results with High Confidence Log (Score)22 x100 *Calculated as Total number of picked colonies

Inclusivity Study

The Inclusivity Study was performed to demonstrate that Colibrí System is able to prepare targets with "on-panel" species that provide the same microbial identification as the manual preparation when analyzed with the bioMérieux VITEK MS and Bruker MALDI Biotyper CA Systems without false identifications. A variety of bacteria included in the knowledge databases of the bioMérieux VITEK MS or Bruker MALDI Biotyper CA System ("on-panel" strains) were included in this study. Strain selection criteria included representative isolates of different genera and organisms exhibiting a broad range of colony characteristics (size, morphology and viscoelastic proprieties). The study was designed as to include multiple strains of the most commonly isolated Gram-positive and Gram-negative species in the US, as well as examples of less common/rare pathogens. The identification results obtained by bioMérieux VITEK MS and Bruker MALDI Biotyper CA System

{14}------------------------------------------------

using the Copan Colibrí System as sample preparator were compared to the expected strain identity and to those obtained by manual preparation.

For the bioMérieux VITEK MS, the study was conducted by one operator on one Colibri System and a total of 123 bacterial strains belonging to 29 different species were analyzed. An overall agreement of 97.2% in the identification results between organisms spotted automatically and the expected strain identity was found, and no wrong identification results were obtained with the automatic preparation. More specifically, 85.2% of picked colonies (334/392) provided an identification corresponding to the expected strain identity with a Confidence Value ≥ 60%. In addition, the calculation of agreement includes 47/48 colonies of Enterobacter cloacae and Proteus vulgaris reported with Low Discrimination as Enterobacter cloacae/Enterobacter asburiae and Proteus penneri/Proteus vulgaris, in accordance with the labeling for the VITEK MS analyzer.

For the Bruker MALDI Biotyper CA System, the study was conducted by one operator on two Colibrí Systems, one configured for the processing of the US IVD 48 Spot target (48-position reusable steel target) and the other for the MBT Biotarget 96 US IVD (96-position disposable target). A total of 124 bacterial strains belonging to 30 different species were analyzed: when Copan Colibri System was used in conjunction with Bruker MALDI Biotyper CA System on the US IVD 48 Spot Target, 93.2% of picked colonies (436/468) provided an identification corresponding to the expected strain identity with a High confidence ID Log (Score) ≥ 2.

When Copan Colibrí System was used in conjunction with Bruker MALDI Biotyper CA System with the MBT Biotarget 96 US IVD, 85.7% of picked colonies provided an identification corresponding to the expected strain identity with a High confidence ID Log (Score) > 2.

Performance of the Copan Colibrí System for preparation of Gram-positive target organisms for the Bruker MALDI Biotyper CA is lower when compared to manual preparation; however, none of the colonies in the study provided a wrong identification. Instructions will be included in the Colibrí System Package Insert for the operator to repeat testing of the isolate manually using the extended Direct Transfer (eDT) or Extraction (Ext) Sample Preparation Procedure if a lowconfidence identification or no identification result is obtained. This is consistent with the Instructions for Use of the Bruker MALDI Biotyper CA System.

{15}------------------------------------------------

Inclusivity Study identification results of the Colibri System obtained with the bioMerieux VITEK MS and stratified per species

Test strain	Total no.of pickedcolonies	Correct Single Choice(≥60% Confidence value)	Low discrimination(<60% Confidence value)		No ID		Wrong ID		%agreement*betweenColibrí andexpected ID	%agreement**betweenmanual andexpected ID
		Colibrí	Manual	Colibrí	Manual	Colibrí	Manual	Colibrí	Manual
Gram Positive
Enterococcus faecalis	12	11	12	0	0	1	0	0	0	91.7%	100.0%
Enterococcus faecium	12	11	11	0	0	1	1	0	0	91.7%	91.7%
Listeria monocytogenes	4	4	3	0	0	0	1	0	0	100.0%	75.0%
Staphylococcus aureus	12	12	12	0	0	0	0	0	0	100.0%	100.0%
Staphylococcus epidermidis	12	12	12	0	0	0	0	0	0	100.0%	100.0%
Staphylococcussaprophyticus	8	6	6	0	0	2	2	0	0	75.0%	75.0%
Streptococcus agalactiae	16	13	15	0	0	3	1	0	0	81.3%	93.8%
Streptococcus pyogenes	8	7	7	0	0	1	1	0	0	87.5%	87.5%
Total Gram-positive	84	76	78	0	0	8	6	0	0	90.5%	92.9%
Gram Negative
Acinobacter baumannii	24	24	20	0	0	0	4	0	0	100.0%	83.3%
Bacteroides fragilis	2	2	2	0	0	0	0	0	0	100.0%	100.0%
Citrobacter koseri	24	24	21	0	0	0	3	0	0	100.0%	87.5%
Eikenella corrodens	2	2	2	0	0	0	0	0	0	100.0%	100.0%
Enterobacteraerogenes/Klebsiellaaerogenes	24	23	22	0	0	1	2	0	0	95.8%	91.7%
Enterobacter cloacae	24	0	0	23a	20a	1	4	0	0	95.8%a	83.3%a
Escherichia coli	24	24	23	0	0	0	1	0	0	100.0%	95.8%
Haemophilus influenzae	4	4	3	0	0	0	1	0	0	100.0%	75.0%
Klebsiella oxytoca	24	24	20	0	0	0	4	0	0	100.0%	83.3%
Klebsiella pneumoniae	24	23	21	0	0	1	3	0	0	95.8%	87.5%
Moraxella catarrhalis	4	4	4	0	0	0	0	0	0	100.0%	100.0%
Morganella morganii	16	16	15	0	0	0	1	0	0	100.0%	93.8%
Neisseria gonorrhoeae	4	4	4	0	0	0	0	0	0	100.0%	100.0%
Neisseria meningitidis	2	2	1	0	0	0	1	0	0	100.0%	50.0%
Test strain	Total no. of picked colonies	Correct Single Choice (≥60% Confidence value)		Low discrimination (<60% Confidence value)		No ID		Wrong ID		% agreement* between Colibrí and expected ID	% agreement** between manual and expected ID
		Colibrí	Manual	Colibrí	Manual	Colibrí	Manual	Colibrí	Manual
Proteus mirabilis	24	24	23	0	0	0	1	0	0	100.0%	95.8%
Proteus vulgaris	24	0	0	24b	23b	0	1	0	0	100.0%b	95.8%b
Pseudomonas aeruginosa	24	24	24	0	0	0	0	0	0	100.0%	100.0%
Salmonella typhimurium	8	8	8	0	0	0	0	0	0	100.0%	100.0%
Serratia marcescens	16	16	16	0	0	0	0	0	0	100.0%	100.0%
Stenotrophomonas maltophilia	8	8	7	0	0	0	1	0	0	100.0%	87.5%
Vibrio parahaemolyticus	2	2	2	0	0	0	0	0	0	100.0%	100.0%
Total Gram-negative	308	258	238	47	43	3	27	0	0	99.0%a, b	91.2%a, b
Total	392	334	316	47a, b	43a, b	11	33	0	0	97.2%a, b	91.6%a, b

Copan WASP S.r.l., Traditiona1 510(k)-Colibrí System

CONFIDENTIAL Page 5-1

{16}------------------------------------------------

"Aconding to VITEK MS instrument considered as a suashine esult, intervoacer concae Entervoacer assurial (50%) 0%). Therefore, the Lov disemination results for this strain are included in the Agreement calculation

b Aconding to VTEK MS instrument, Protes vegeris identifications are considered as a stashine result, Protex w/goris (5/%/5/%). The for, the Low disciniminoresults for this strain are included in the Agreement calculation.

x100

No. of correct results with Good Confidence value (≥60%) *Calculated as: Colibrí performance identification(%) = x100

Total number of picked colonies **Calculated as: Manual performance identification(%) =

No. ofcorrect results with Good Confidence value (≥60%) Total number of picked colonies

{17}------------------------------------------------

Inclusivity Study identification results of the Collori System obtained with the Bruker MALDI Biotyper CA System on US VVD 48 Spot target and stratified per species

Test strain	Total no. ofpickedcolonies	High confidence IDLog (Score) ≥2	Low confidenceID1.7≤ Log (Score)<2	Combinedperformance	No ID	Wrong ID	% agreement*betweenColibrí andexpected ID	% agreement**betweenmanual andexpected ID
		Colibrí	Manual	Colibrí	Manual	Colibrí	Manual	Colibrí	Manual	Colibrí	Manual
Enterococcusfaecalis	24	19	24	4	0	23	24	1	0	0	0	79.2%	100.0%
Enterococcusfaecium	24	21	24	3	0	24	24	0	0	0	0	87.5%	100.0%
Listeriamonocytogenes	4	4	4	0	0	4	4	0	0	0	0	100.0%	100.0%
Staphylococcusaureus	24	21	24	3	0	24	24	0	0	0	0	87.5%	100.0%
Staphylococcusepidermidis	24	18	20	6	4	24	24	0	0	0	0	75.0%	83.3%
Staphylococcussaprophyticus	16	12	15	2	1	14	16	2	0	0	0	75.0%	93.8%
Streptococcusagalactiae	24	19	21	2	3	21	24	3	0	0	0	79.2%	87.5%
Streptococcuspyogenes	16	14	16	2	0	16	16	0	0	0	0	87.5%	100.0%
Total Gram-positive	156	128	148	22	8	150	156	6	0	0	0	82.1%	94.9%
						Gram Negative
Acinobacterbaumannii	24	23	22	1	2	24	24	0	0	0	0	95.8%	91.7%
Bacteroides fragilis	2	2	2	0	0	2	2	0	0	0	0	100.0%	100.0%
Bordetella pertussis	2	2	2	0	0	2	2	0	0	0	0	100.0%	100.0%
Citrobacter koseri	24	24	24	0	0	24	24	0	0	0	0	100.0%	100.0%
Eikenella corrodens	4	4	4	0	0	4	4	0	0	0	0	100.0%	100.0%
Enterobacteraerogenes	24	24	24	0	0	24	24	0	0	0	0	100.0%	100.0%
Enterobactercloacae	24	24	24	0	0	24	24	0	0	0	0	100.0%	100.0%
Test strain	Total no. ofpickedcolonies	High confidence IDLog (Score) ≥2		Low confidenceID1.7≤ Log (Score)<2		Combinedperformance		No ID		Wrong ID	% agreement*betweenColibrí andexpected ID	% agreement**betweenmanual andexpected ID
		Colibrí	Manual	Colibrí	Manual	Colibrí	Manual	Colibrí	Manual	Colibrí	Manual
Escherichia coli	24	22	23	2	1	24	24	0	0	0	0	91.7%	95.8%
Haemophilusinfluenzae	4	4	4	0	0	4	4	0	0	0	0	100.0%	100.0%
Klebsiella oxytoca	24	24	24	0	0	24	24	0	0	0	0	100.0%	100.0%
Klebsiellapneumoniae	24	24	24	0	0	24	24	0	0	0	0	100.0%	100.0%
Moraxellacatarrhalis	4	4	4	0	0	4	4	0	0	0	0	100.0%	100.0%
Morganellamorganii	16	16	15	0	0	16	15	0	1	0	0	100.0%	93.8%
Neisseriagonorrhoeae	4	4	4	0	0	4	4	0	0	0	0	100.0%	100.0%
Neisseriameningitidis	2	2	2	0	0	2	2	0	0	0	0	100.0%	100.0%
Proteus mirabilis	24	24	24	0	0	24	24	0	0	0	0	100.0%	100.0%
Proteus vulgaris	24	23	23	1	1	24	24	0	0	0	0	95.8%	95.8%
Pseudomonasaeruginosa	24	24	24	0	0	24	24	0	0	0	0	100.0%	100.0%
Salmonellatyphimurium andspp	8	8	8	0	0	8	8	0	0	0	0	100.0%	100.0%
Serratia marcescens	16	16	16	0	0	16	16	0	0	0	0	100.0%	100.0%
Stenotrophomonasmaltophilia	8	8	8	0	0	8	8	0	0	0	0	100.0%	100.0%
Vibrioparahaemolyticus	2	2	2	0	0	2	2	0	0	0	0	100.0%	100.0%
Total Gram-negative	312	308	307	4	4	312	311	0	1	0	0	98.7%	98.4%
Total	468	436	455	26	12	462	467	6	1	0	0	93.2%	97.2%
Test strain	Total no. ofpicked colonies	High confidence IDLog(Score)≥2		Low confidenceID1.7≤Log(Score)<2		Combinedperformance		No ID		Wrong ID		% agreement*betweenColibrí andexpected ID	% agreement**betweenmanual andexpected ID
		Colibrí	Manual	Colibrí	Manual	Colibrí	Manual	Colibrí	Manual	Colibrí	Manual
Enterococcusfaecalis	24	21	24	0	0	21	24	3	0	0	0	87.5%	100.0%
Enterococcusfaecium	24	20	24	2	0	22	24	2	0	0	0	83.3%	100.0%
Listeriamonocytogenes	4	4	4	0	0	4	4	0	0	0	0	100.0%	100.0%
Staphylococcusaureus	24	22	23	1	1	23	24	1	0	0	0	91.7%	95.8%
Staphylococcusepidermidis	24	9	10	11	11	20	21	4	3	0	0	37.5%	41.7%
Staphylococcussaprophyticus	16	9	13	2	2	11	15	5	1	0	0	56.3%	81.3%
Streptococcusagalactiae	24	7	9	10	9	17	18	7	6	0	0	29.2%	37.5%
Streptococcuspyogenes	16	13	16	3	0	16	16	0	0	0	0	81.3%	100.0%
Total Gram-positive	156	105	123	29	23	134	146	22	10	0	0	67.3%	78.8%
Gram-negative
Acinobacterbaumannii	24	24	20	0	3	24	23	0	1	0	0	100.0%	83.3%
Bacteroides fragilis	2	2	2	0	0	2	2	0	0	0	0	100.0%	100.0%
Bordetella pertussis	2	2	2	0	0	2	2	0	0	0	0	100.0%	100.0%
Citrobacter koseri	24	23	24	1	0	24	24	0	0	0	0	95.8%	100.0%
Eikenella corrodens	4	4	4	0	0	4	4	0	0	0	0	100.0%	100.0%
Enterobacteraerogenes/Klebsiella aerogenes	24	24	24	0	0	24	24	0	0	0	0	100.0%	100.0%
Enterobacter	24	21	22	2	2	23	24	1	0	0	0	87.5%	91.7%
Test strain	Total no. ofpicked colonies	High confidence IDLog(Score)≥2		Low confidenceID1.7≤Log(Score)<2		Combinedperformance		No ID		Wrong ID		% agreement*betweenColibrí andexpected ID	% agreement**betweenmanual andexpected ID
		Colibrí	Manual	Colibrí	Manual	Colibrí	Manual	Colibrí	Manual	Colibrí	Manual
cloacae
Escherichia coli	24	20	18	4	5	24	23	0	1	0	0	83.3%	75.0%
Haemophilusinfluenzae	4	4	4	0	0	4	4	0	0	0	0	100.0%	100.0%
Klebsiella oxytoca	24	19	21	2	0	21	21	3	3	0	0	79.2%	87.5%
Klebsiellapneumoniae	24	22	20	1	1	23	21	1	3	0	0	91.7%	83.3%
Moraxellacatarrhalis	4	4	4	0	0	4	4	0	0	0	0	100.0%	100.0%
Morganellamorganii	16	16	16	0	0	16	16	0	0	0	0	100.0%	100.0%
Neisseriagonorrhoeae	4	4	4	0	0	4	4	0	0	0	0	100.0%	100.0%
Neisseriameningitidis	2	2	2	0	0	2	2	0	0	0	0	100.0%	100.0%
Proteus mirabilis	24	23	24	0	0	23	24	1	0	0	0	95.8%	100.0%
Proteus vulgaris	24	24	24	0	0	24	24	0	0	0	0	100.0%	100.0%
Pseudomonasaeruginosa	24	24	22	0	0	24	22	0	2	0	0	100.0%	91.7%
Salmonellatyphimurium andspp	8	8	7	0	0	8	7	0	1	0	0	100.0%	87.5%
Serratia marcescens	16	16	15	0	1	16	16	0	0	0	0	100.0%	93.8%
Stenotrophomonasmaltophilia	8	8	8	0	0	8	8	0	0	0	0	100.0%	100.0%
Vibrioparahaemolyticus	2	2	2	0	0	2	2	0	0	0	0	100.0%	100.0%
Total Gram-negative	312	296	289	10	12	306	301	6	11	0	0	94.9%	92.6%
Total	468	401	412	39	35	440	447	28	21	0	0	85.7%	88.0%

Copan WASP S.r.l., Traditiona1 510(k)-Colibrí System

CONFIDENTIAL Page 5-3

{18}------------------------------------------------

*Calculated as: Colibrí performance identification(%) =

x100 Total number of picked colonies

**Calculated as: Manual performance identification(%) =

No. ofcorrect results with Good Confidence value (≥60%) Total number of picked colonies

Copan WASP S.r.l., Traditiona1 510(k)-Colibrí System

CONFIDENTIAL Page 5-4

x100

{19}------------------------------------------------

Inclusivity Study identification results of the Colibri System obtained with the Bruker MALDI Biotarget % US IVD and stratified per species

Copan WASP S.r.l., Traditiona1 510(k)-Colibrí System

CONFIDENTIAL Page 5-5

{20}------------------------------------------------

{21}------------------------------------------------

Specificity Study

The Specificity Study was performed to demonstrate that the Colibrí System is able to prepare targets with "off-panel" species that should provide the expected organism identity when analyzed with the bioMérieux VITEK MS and Bruker MALDI Biotyper CA System without false identifications. Isolated colonies of "off-panel" Gram-positive and Gram-negative strains that are not included in the knowledge databases of the VITEK MS and MALDI Biotyper CA have been used on the Colibrí System to prepare a total of 20 spots for each IVD analyzer. For both IVD analyzers, the study was conducted by one operator on one Colibrí System; an agreement of 100% was found between the identification results of colonies spotted by Colibrí System than those spotted using the manual method. No false positive results for "on-panel" species were obtained.

Specificity Study identification results of the Colibrí System obtained with the bioMérieux VITEK MS

Test strain	Total no. of pickedcolonies	Correct SingleChoice(≥60%Confidencevalue)	Lowdiscrimination(<60%Confidencevalue)	No ID	WrongID	% agreement*between Colibríand expected ID
Gram-positive
Aneurinibacillus migulanus	2	0	0	2	0	100.0%
Exiguobacterium aurantiacum	2	0	0	2	0	100.0%
Janibacter melonis	2	0	0	2	0	100.0%
Leuconostoc carnosum	2	0	0	2	0	100.0%
Leuconostoc fallax	2	0	0	2	0	100.0%
Rothia amarae	2	0	0	2	0	100.0%
Total Gram-positive	12	0	0	12	0	100.0%
Gram-negative
Acidovorax delafieldii	2	0	0	2	0	100.0%
Burkholderia thailendensis	2	0	0	2	0	100.0%
Pectobacterium atrosepticum	2	0	0	2	0	100.0%
Pseudocitrobacter faecalis	2	0	0	2	0	100.0%
Total Gram-negative	8	0	0	8	0	100.0%
Total	20	0	0	20	0	100.0%

No. of No Identification results x100 *Calculated as: Total number of picked colonies

{22}------------------------------------------------

Test strain	Total no. of pickedcolonies	HighconfidenceIDLog (Score)≥2	LowconfidenceID1.7≤ Log(Score) <2	Combinedperformance	No ID	WrongID	% agreement*betweenColibrí andexpected ID
Gram-positive
Paenibacillushuminicus	2	0	0	0	2	0	100.0%
Bacillus licheniformis	2	0	0	0	2	0	100.0%
Bacillus flexus	2	0	0	0	2	0	100.0%
Bacillus infantis	2	0	0	0	2	0	100.0%
Geobacillusstearothermophilus	2	0	0	0	2	0	100.0%
Total Gram-positive	10	0	0	0	10	0	100.0%
Gram-negative
Cardiobacteriumhominis	2	0	0	0	2	0	100.0%
Cedecea neteri	2	0	0	0	2	0	100.0%
Brachyspira murdochii	2	0	0	0	2	0	100.0%
Gallibacterium anatis	2	0	0	0	2	0	100.0%
Novosphingobiumcapsulatum	2	0	0	0	2	0	100.0%
Total Gram-negative	10	0	0	0	10	0	100.0%
Total	20	0	0	0	20	0	100.0%

Specificity Study identification results of the Colibrí System obtained with the Bruker MALDI Biotyper CA System

No. of No Identification results x100 *Calculated as: Total number of picked colonies

Reproducibility Study

The Reproducibility Study was performed to assess the repeatability of results obtained with samples processed by the automatic preparation using the Colibrí System. For this, three Colibrí Systems have been used to prepare target slides using a blinded panel of 10 common "on-panel" clinically relevant Gram-negative and Gram-positive bacteria. The test was repeated for 5 days including 3 replications per strain, performed by two operators in rotation with different levels of experience per Colibrí System for a total of 1800 spots on both IVD Analyzers.

When Copan Colibri System was used in conjunction with the bioMérieux VITEK MS, there was 99.9% agreement (1799/1800) between the reported Good Confidence identification results and the expected identity of each colony in the Reproducibility Study. The agreement calculation includes

{23}------------------------------------------------

180 colonies of Enterobacter cloacae reported with Low Discrimination as Enterobacter cloacae/Enterobacter asburiae in accordance with the labeling for the VITEK MS analyzer.

When Copan Colibrí System was used in conjunction with the Bruker MALDI Biotyper CA, there was 88.1% agreement (1585/1800) between the reported High Confidence identification results (Log (Score) ≥ 2.00) and the expected identity of each colony in the Reproducibility Study. For Gram-positive species, 179/900 colonies (19.9%) were identified with Low Confidence (Log (Score) 1.70-1.99), compared with 1/900 colonies (0.1%) of Gram-negative species. In addition, 31/900 Gram-positive colonies (3.4%) produced no identification result compared with 4/900 Gram-negative colonies (0.4%).

The lower proportion of concordant results for Gram-positive bacteria with the Bruker MALDI Biotyper CA was noted. Consistent with the labeling for the MALDI Biotyper CA. the Copan Colibrí System Package Insert will recommend that Gram-positive species or any samples that produce a Low Confidence Identification or No Identification Result should be manually prepared using the Bruker's extended Direct Transfer Procedure (eDT), Extraction (Ext) Procedure and/or an alternative method of organism identification.

Test strain	Total no. ofpicked colonies	Correct SingleChoice(≥60%Confidencevalue)	Lowdiscrimination(<60%Confidencevalue)	No ID	Wrong ID	% agreement*between Colibríand expected ID
Gram-positive
Enterococcus faecalis	180	180	0	0	0	100.0%
Staphylococcus aureus	180	180	0	0	0	100.0%
Staphylococcusepidermidis	180	180	0	0	0	100.0%
Staphylococcussaprophyticus	180	180	0	0	0	100.0%
Streptococcus agalactiae	180	179	0	1	0	99.4%
Total Gram-positive	900	899	0	1	0	99.9%
Gram-negative
Enterobacter cloacae*	180	0	180a	0	0	100.0%
Escherichia coli	180	180	0	0	0	100.0%
Klebsiella pneumoniae	180	180	0	0	0	100.0%
Proteus mirabilis	180	180	0	0	0	100.0%
Pseudomonas aeruginosa	180	180	0	0	0	100.0%
Total Gram-negative	900	720	180 a	0	0	100.0%
Total	1800	1619	180 a	1	0	99.9% a

Reproducibility Study identification results of the Colibrí System obtained with the bioMérieux VITEK MS

"According to VITEK MS instrument, Enterobacter cloacae identifications are considered as a slashlineresult, Enterobacter cloaccel Enterobacter asburiae (50%). Therefore, the Low discrimination results for this strain are included in the Agreement calculation.

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

{24}------------------------------------------------

No. of correct results with Good Confidence value (≥60%) *Calculated as x100 Total number of picked colonies

Reproducibility Study identification results of the Colibrí System obtained with the Bruker MALDI Biotyper CA System

Test strain	Total no. of pickedcolonies	HighconfidenceIDLog(Score)≥2	LowconfidenceID1.7≤Log(Score)<2	Combinedperformance	No ID	Wrong ID	%agreement*betweenColibrí andexpected ID
Gram-positive
Enterococcus faecalis	180	139	40	179	1	0	77.2%
Staphylococcus aureus	180	159	21	180	0	0	88.3%
Staphylococcusepidermidis	180	129	42	171	9	0	71.7%
Staphylococcussaprophyticus	180	143	26	169	11	0	79.4%
Streptococcus agalactiae	180	120	50	170	10	0	66.7%
Total Gram-positive	900	690	179	869	31	0	76.7%
Gram-negative
Enterobacter cloacae	180	180	0	180	0	0	100.0%
Escherichia coli	180	178	1	179	1	0	98.9%
Klebsiella pneumoniae	180	180	0	180	0	0	100.0%
Proteus mirabilis	180	180	0	180	0	0	100.0%
Pseudomonasaeruginosa	180	177	0	177	3	0	98.3%
Total Gram-negative	900	895	1	896	4	0	99.4%
Total	1800	1585	180	1765	35	0	88.1%

*Calculated as Total number of picked colonies

Cross-Contamination Studies

Cross-Contamination Study was performed to demonstrate that the use of the Colibrí System does not cause false-positive results due to contamination of adjacent spots on the target slide. Alternating culture media showing isolated colonies of "on-panel" and "off-panel" Gram-positive and Gram-negative strains have been used to prepare the VITEK MS-DS and Bruker MALDI Biotyper CA System targets using the Copan Colibrí System as sample preparator.

For the bioMérieux VITEK MS, the study was conducted by one operator on one Colibri System for a total of 572 spots. 99.3% of colonies from "on-panel species" produced the expected result

{25}------------------------------------------------

without false identifications. None of the "off-panel" organisms yielded an identification. For the Bruker MALDI Biotyper CA System, the study was conducted by one operator on two Colibrí Systems, one configured for the processing of the US IVD 48 Spot target (48 positions reusable steel target) and the other for the MBT Biotarget 96 US IVD (96 positions disposable targets) for a total of 686 spots. For "on-panel" species spotted on US IVD 48 Spot, 95% of organisms produced the expected result. For "on-panel" species spotted on MBT Biotarget 96 US IVD, 85.3% of organisms produced the expected result: nevertheless, the result is considered acceptable because the lack of identification is not due to the cross-contamination but to the limited ability of Colibrí System to provide High Confidence results for Gram-positive organisms. None of the "off-panel" organisms yielded an identification. This is consistent with observations in other analytical studies using the Colibrí System in conjunction with the Bruker MALDI Biotyper CA to identify Grampositive organisms and is mitigated by the requirement for additional testing that is noted in the device labeling.

Cross-Contamination identification results of the Colibrí System obtained with the bioMérieux VITEK MS for "on-panel" species

Test strain	Total no.of spots	Correct SingleChoice(≥60% Confidencevalue)	Lowdiscrimination(<60%Confidence value)	No ID	WrongID	% coloniesprovidingexpectedresult*
Gram-positive
Enterococcus faecalis	46	46	0	0	0
Staphylococcus aureus	48	48	0	0	0
Streptococcus agalactiae	48	46	0	2	0
Total Gram positive	142	140	0	2	0	98.6%
Gram-negative
Escherichia coli	48	48	0	0	0
Klebsiella pneumoniae	48	48	0	0	0
Pseudomonas aeruginosa	48	48	0	0	0
Total Gram negative	144	144	0	0	0	100%
Total	286	284	0	2	0	99.3%

No.of correct results with Confidence Value ≥60 x100 *Calculated as Total number of picked colonies

{26}------------------------------------------------

Cross-Contamination identification results of the Colibrí System obtained with the bioMérieux VITEK MS for "off-panel" species

Test strain	Total no.of spots	No ID	% coloniesprovidingexpectedresult*
Aneurinibacillusmigulanus	48	48
Leuconostoc carnosum	48	48
Rothia amarae	46	46
Acidovorax delafieldii	48	48
Burkholderia thailandensis	48	48
Pseudocitrobacter faecalis	48	48
Total	286	286	100%

No. of No Identification Results x100 * Calculated as Total number of picked colonies

Cross-Contamination identification results of the Colibrí System obtained with the Bruker MALDI Biotyper CA on US IVD 48 Spot target for "on-panel" species

Test strain	Totalno. ofspots	HighconfidenceIDLog(Score)≥2	LowconfidenceID1.7≤ Log(Score)<2	Combinedperformance	No ID	WrongID	% coloniesprovidingexpectedresult*
Gram-positive
Enterococcus faecalis	24	19	5	24	0	0
Staphylococcus aureus	48	48	0	48	0	0
Streptococcus agalactiae	24	20	4	24	0	0
Total Gram-positive	96	87	9	96	0	0	90.6%
Gram-negative
Acinobacter baumannii	24	23	1	24	0	0
Escherichia coli	56	56	0	56	0	0
Klebsiella pneumoniae	24	24	0	24	0	0
Total Gram-negative	104	103	1	104	0	0	99.0%
Total	200	190	10	200	0	0	95.0%

No. of correct results with High Confidence Log(Score)≥2 x100 * * Calculated as Total number of picked colonies

{27}------------------------------------------------

Cross-Contamination identification results of the Colibrí System obtained with the Bruker MALDI Biotyper CA on US IVD 48 Spot target for "off-panel" species

Test strain	Totalno. ofspots	No ID	%coloniesprovidingexpectedresult*
Bacillus flexus	48	48
Bacillus infantis	24	24
Bacillus licheniformis	24	24
Cedecea neteri	56	56
Gallibacterium anatis	24	24
Novosphingobium capsulatum	24	24
Total	200	200	100%

No. of No Identification results
---------------------------------------------------------------------------------------------------------------------------------------------*Calculated as Total number of picked colonies

Cross-Contamination identification results of the Colibrí System obtained with the Bruker MALDI Biotyper CA on MBT Biotarget 96 US IVD for "on-panel" species

Test strain	Totalno. ofspots	HighconfidenceIDLog(Score)≥2	LowconfidenceID$1.7\u2264$ Log(Score)<2	Combinedperformance	No ID	WrongID	% coloniesprovidingexpectedresult*
	Gram-positive
Enterococcus faecalis	24	20	1	21	3	0
Staphylococcus aureus	24	22	2	24	0	0
Streptococcus agalactiae	23	10	8	18	5	0
Total Gram-positive	71	52	11	63	8	0	73.2%
	Gram-negative
Acinobacter baumannii	24	23	0	23	1	0
Escherichia coli	24	24	0	24	0	0
Klebsiella pneumoniae	24	23	0	23	1	0
Total Gram-negative	72	70	0	70	2	0	97.2%
Total	143	122	11	133	10	0	85.3%

*Calculated as Total number of picked colonies

{28}------------------------------------------------

Cross-Contamination identification results of the Colibrí System obtained with the Bruker MALDI Biotyper CA on MBT Biotarget 96 US IVD for "off-panel" species

Test strain	Totalno. ofspots	No ID	% coloniesprovidingexpectedresult*
Bacillus flexus	24	24
Bacillus infantis	24	24
Bacillus licheniformis	23	23
Cedecea neteri	24	24
Gallibacterium anatis	24	24
Novosphingobiumcapsulatum	24	24
Total	143	143	100%

No. of No Identification results x100 *Calculated as Total number of picked colonies

Colony Stability Study

Colony Stability Study was performed to demonstrate the ability of the Colibri System to prepare target slides from cultures of different ages. Isolated colonies of "on-panel" and Gram-positive and Gram-negative strains have been grown on different culture plates incubated at different incubation times including the lower and the upper incubation time specified in the labeling for the two IVD analyzers. The study conducted in conjunction with the Bruker MALDI Biotyper CA System was performed on plates incubated at the minimum and at maximum incubation time with additional of 12 hours post incubation time at room temperature. For both IVD analyzers the study was conducted by one operator on one Colibrí System.

For the bioMérieux VITEK MS, a total of 576 spots were prepared, and 99.8% of samples produced the expected identification at each time point for all agar media plates under evaluation. No false identification result was provided.

For the Bruker MALDI Biotyper CA System, a total of 1440 spots were prepared: a general good agreement with the expected results for Gram-negative species (i.e., the expected organism identity was reported with a High Confidence Log(Score) value) was found, irrespective of the culture medium or duration of incubation, whereas lower agreement was observed with Gram-positive species. Nevertheless, no incorrect identification results were reported for any of the isolates included in the study and therefore colony age was not shown to affect the accuracy organism identification. For Bordetella pertussis on Bordet Gengou Agar, holding cultures at ambient temperature for 12 hours after incubation for 7 days at 35 ± 2℃ resulted in a decrease in the proportion of High Confidence Log(scores) obtained. This is noted in the device labeling.

{29}------------------------------------------------

Culture Medium	Nº spot perculture medium	Culture Mediumincubation time	ID % Agreement at eachCulture Medium incubationtime*
Columbia Agar + 5%sheep blood	192	18 h	100%
		24h	100%
		48 h	100%

72 h

18 h

24 h

72 h

18 h

24 h

72 h 18 h

48 h

100%

100% 100%

100%

97.9%

100%

Colony Stability identification results of the Colibrí System obtained with the bioMérieux VITEK MS

No. of correct results with Good Confidence value (≥60%) x 100 *Calculated as

MacConkey Agar

Trypticase Soy Agar

5% sheep blood

Chocolate Agar

Total number of picked colonies

144

છેર

Colony Stability identification results of the Colibrí System obtained with the MALDI Biotyper CA on MBT Biotarget 96 US IVD for "on-panel" species

Culture Medium	N° spot perculturemedium	CultureMediumincubationtime	ID %Agreement atdifferentincubationtimes*	ID % Agreement atCulture Mediumdifferent incubationtime + 12h post-incubation at RT*
Columbia Agar + 5% sheepblood	288	18 h	93.8%	95.8%
		24 h	91.7%	93.8%
		48 h	87.5%	89.6%
MacConkey Agar	288	18 h	97.9%	100%
		24 h	100%	95.8%
		48 h	100%	100%
Trypticase Soy Agar + 5%sheep blood	288	18 h	79.2%	79.2%
		24 h	83.3%	83.3%
		48 h	87.5%	91.7%
Chocolate Agar	192	18 h	100%	100%

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

CONFIDENTIAL Page 21-9

{30}------------------------------------------------

Culture Medium	Nº spot perculturemedium	CultureMediumincubationtime	ID %Agreement atdifferentincubationtimes*	ID % Agreement atCulture Mediumdifferent incubationtime + 12h post-incubation at RT*
Columbia Agar + 5% sheepblood supplemented ofcolistin and nalidixic acid	192	48 h	100%	93.8%
Columbia Agar + 5% sheepblood supplemented ofcolistin and nalidixic acid	192	18 h	87.5%	91.7%
Columbia Agar + 5% sheepblood supplemented ofcolistin and nalidixic acid	192	48 h	87.5%	85.4%
Bordet Gengou + 15% sheepblood	192	5 days	100%	100%
Bordet Gengou + 15% sheepblood	192	7 days	97.9%	68.7%

No. of correct results with High Confidence Log(Score)≥2 x100 *Calculated as

Total number of picked colonies

Spot Stability Prior To and After Matrix Deposition

The spot stability prior to and after matrix application study was performed evaluate the stability of spots prepared by the Copan Colibrí System before matrix application and the stability of target spots before MALDI-TOF MS analysis. Spot stability was evaluated comparing the identification performance between the Standard Deposition Mode (SDM - application of matrix immediately after the colony spotting) and the Delayed Deposition Mode (DDM - matrix application after 60 minutes after the colony spotting) and when testing was delayed for 24-, 48- or 72-hours following matrix deposition. Target stability was investigated by holding the target at room temperature in ambient air or on the deck of the Colibri Preparation Station for the maximum incubation time indicated by the respective MALDI-TOF MS analyzer before analysis. For each condition, a complete target was spotted randomly alternating Gram-positive and Gram-negative colonies grown on Trypticase Soy Agar + 5% sheep blood.

For Bruker MALDI Biotyper CA System the evaluation was performed for both validated targets, MBT Biotarget 96 US IVD (96 positions disposable targets) and US IVD 48 Spot target (48 positions reusable steel target).

For the bioMérieux VITEK MS, the colonies spotted by Colibrí System are stable up to 60 minutes without matrix and, after preparation, targets can be stored for 48h at room temperature when held on the Colibrí deck and for 72 h when held in the original box, since the identification performance is not different to the performance in standard conditions.

For MALDI Biotyper CA System identification results show that colonies spotted by Colibrí System on MBT Biotarget 96 US IVD and US IVD 48 Spot targets are stable up to 60 minutes without matrix and for 24h at room temperature after matrix addition when held both on the Collorí deck and on the Lab bench. Lower agreement with the expected results was observed with Grampositive species using the 96-spot disposable target format, which is noted in the device labeling.

{31}------------------------------------------------

The Copan Colibrí device labeling recommends that prepared targets are tested within 24 hours for the Bruker MALDI Biotyper CA and within 48 hours for the bioMérieux VITEK MS.

Electrical Safety and Electromagnetic Compatibility (EMC)

Electrical safety and EMC testing were conducted on the Colibrí System, consisting of the Vision System and 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

The Colibri 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" 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 or indirectly 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, labeling 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

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

CONFIDENTIAL Page 21-11

{32}------------------------------------------------

the Copan Colibrí System meets its functional specifications and performance requirements, and complies with applicable international standards IEC 61010-2:101, IEC 61010-2:101, IEC 61010-2:081, IEC 60825-1, IEC 61326-1, IEC 61326-2:6, IEC 60601-1-2:2014, CLSI M58, IEC 62304 and IEC 62366-1.

The analytical study results demonstrated that the Colibri System when used in conjunction with its parental device 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 M58 guideline (Methods Identification of Cultured Microorganisms Using Matrix-Assisted the Laser for Desorption/Ionization Time-of-Flight Mass Spectrometry).

Regulation Number and Section

§ 866.3378 Clinical mass spectrometry microorganism identification and differentiation system.

(a)
Identification. A clinical mass spectrometry microorganism identification and differentiation system is a qualitative in vitro diagnostic device intended for the identification and differentiation of microorganisms from processed human specimens. The system acquires, processes, and analyzes spectra to generate data specific to a microorganism(s). The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infection.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use statement must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended, when applicable.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt with an indication for in vitro diagnostic use.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology and all pre-analytical methods for processing of specimens, and algorithm used to generate a final result. This must include a description of validated inactivation procedure(s) that are confirmed through a viability testing protocol, as applicable.
(ii) Performance characteristics for all claimed sample types from clinical studies with clinical specimens that include prospective samples and/or, if appropriate, characterized samples.
(iii) Performance characteristics of the device for all claimed sample types based on analytical studies, including limit of detection, inclusivity, reproducibility, interference, cross-reactivity, interfering substances, carryover/cross-contamination, sample stability, and additional studies regarding processed specimen type and intended use claims, as applicable.
(iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing.
(4) The device's labeling must include a prominent hyperlink to the manufacturer's website where the manufacturer must make available their most recent version of the device's labeling required under § 809.10(b) of this chapter, which must reflect any changes in the performance characteristics of the device. FDA must have unrestricted access to this website, or manufacturers must provide this information to FDA through an alternative method that is considered and determined by FDA to be acceptable and appropriate.
(5) Design verification and validation must include:
(i) Any clinical studies must be performed with samples representative of the intended use population and compare the device performance to results obtained from an FDA-accepted reference method and/or FDA-accepted comparator method, as appropriate. Documentation from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan, if applicable), clinical study report, and results of all statistical analyses.
(ii) Performance characteristics for analytical and clinical studies for specific identification processes for the following, as appropriate:
(A) Bacteria,
(B) Yeasts,
(C) Molds,
(D) Mycobacteria,
(E) Nocardia,
(F) Direct sample testing (
e.g., blood culture),(G) Antibiotic resistance markers, and
(H) Select agents (
e.g., pathogens of high consequence).(iii) Documentation that the manufacturer's risk mitigation strategy ensures that their device does not prevent any device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use (
e.g., safety and effectiveness of the functions of the indicated device(s) remain unaffected).(iv) A detailed device description, including the following:
(A) Overall device design, including all device components and all control elements incorporated into the testing procedure.
(B) Algorithm used to generate a final result from raw data (
e.g., how raw signals are converted into a reported result).(C) A detailed description of device software, including validation activities and outcomes.
(D) Acquisition parameters (
e.g., mass range, laser power, laser profile and number of laser shots per profile, raster scan, signal-to-noise threshold) used to generate data specific to a microorganism.(E) Implementation methodology, construction parameters, and quality assurance protocols, including the standard operating protocol for generation of reference entries for the device.
(F) For each claimed microorganism characteristic, a minimum of five reference entries for each organism (including the type strain for microorganism identification), or, if there are fewer reference entries, a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, for why five reference entries are not needed.
(G) DNA sequence analysis characterizing all type strains and at least 20 percent of the non-type strains of a species detected by the device, or, if there are fewer strain sequences, then a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, must be provided for the reduced number of strains sequenced.
(H) As part of the risk management activities, an appropriate end user device training program, which must be offered as an effort to mitigate the risk of failure from user error.