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October 20-21 2016

Hotel Gran marquise Fortaleza

Philippe Gadal

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Contribute to the improvement of public

health worldwide through in vitro diagnostics

OUR MISSION

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Marcel Mérieux

1897 - Creation of Institut Mérieux

Dr Charles Mérieux

1937 - Dr Charles Mérieux

took up the reins

Dr Alain Mérieux

1963 - Creation of bioMérieux

Alexandre Mérieux

A pasteurian tradition: Marcel Mérieux worked with Louis Pasteur in 1894.

An historic family commitment to medicine

and public health worldwide

Marcel Mérieux,

student of Louis Pasteur in 1894.

A commitment that transcends generations:Ever since the creation of Institut Mérieux, a generation

has worked one after another to expand its legacy.

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A Long Term Commitment in Emerging Countries

BRAZIL

44years

INDIA

18years

CHINA

25years

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An original innovation model based on international research

partnerships and joint research units to bring multidisciplinarity

to develop tomorrow’s diagnostic solutions.

50 years of M&A and partnerships

1986API Systems, France

1988VITEK (McDonnel Douglas), USA

2012RAS, India

2011AES, France

ARGENE,France

2001Organon Teknika Diagnostic, Netherlands

2008Joint venture with Sysmex, Japan

Joint venture with SKB, China

AB BIODISK, Sweden

AviaraDx: bioTheranostics, USA

PML Microbiologicals Inc., USA

2010Meikang Biotech, China

Shanghai Zenka Biotechnology, China

2006Bacterial Barcodes, USA

2007Biomedics,Spain

BTF, Australia

2004Entering on the stock exchange

2013BioFire, USA

API®

DiversiLAB®

Etest®BacTALERT®CHEMUNEX®

AES Blueline™

Adaviet

FilmArray®

2014Ceeram,Advencis,France

VIDAS®

VITEK®

M&A

Partnerships

2016Applied Maths, Belgium

Hyglos, Germany

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PRODUCT CONTROL

QUALITY

CONTROL

ENVIRONMENTAL CONTROL

METHOD

VALIDATION

PROCESS CONTROL

Count-Tact®

Tubes & bottles

Quantiswab™

DETECTION

DETECTION

Media Fill 3P™

(Final Release, Water, Raw Materials, Etc.)

(Air, & Surfaces)

EndoLISA® EndoZyme®

Power Ionising Vacuum NegativePower Ionising Vacuum NegativePower Ionising Vacuum Negative

(Identification & Strain Typing)

EndoLISA® EndoZyme®

World leader in Pharmaceutical Microbiology

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RAPID MICROBIAL METHODS

BacT/ALERT®

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ScanRDI Overview

Solid Phase Cytometry

Used in industry for over 20 years

Qualitative and Quantitative

Detect a single live microorganism

in samples of 1-1000 mL

No need for enrichment or growth

Stressed organisms or viable but non-culturable (VBNC) are detected

400 strains in the DMF, over 2000 strains detected by the ScanRDI

Using the Scan RDI, traditional Pharma customers have validated sterility testing, bioburden or in cleaning validation.

Major Drug Compounders are equipped and use as routine for all compounding products.

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Workflow

Filter1

Label2

Scan & Confirm3

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Workflow - Filter

Performed under laminar flow ISO 5

or Grade A using filtration ramp

Filter1

Filter Apparatus Options Fluorassure Integral Filtration Unit (FIFU)

Cyclo Black 04 Porosity (CB04)

Track-Etched Membrane (TEM) Polyester (non-fibrous)

0.4µ pores created by charged-particle bombardment and

chemical etching

Organism(s) remain on surface for labeling

Black color reduces fluorescence interference

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Workflow - Label

Counterstain (background fluorescence, block particles and dead cells)

Pre-labeling step (activates dormant and spore cells)

Viability substrate added and enters the cells passively

Living cells enzymatically cleave the non-fluorescent viability substrate

Free fluorochrome is released within the cell

The cell's membrane holds the fluorescent

molecules within the cell

Label2

Criteria of Viability Enzymatic activity

Membrane activity

Labeling is not

destructive

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Workflow – Scan & Confirm

Membrane is transferred to the solid-phase cytometer

Complete surface of the membrane is scanned (0.5 miles) with an Argon neon laser at a wavelength of 488nm within four (4) minutes

Any labeled cells on the membrane surface fluoresce and emitted light is collected by 3 photomultipliers (500-530nm, 540-570nm & 570-585 nm)

The total # of living cells on the membrane are displayed

The scan map and microscope attachment allow for visual confirmation

Scan & Confirm3

Incident Light

488 nm

(Blue)

Fluorescent Signal

515 nm

(Green)

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Applications and Time to Result

Environmental testing

Water testing: < 2 hours

Air monitoring (with Coriolis®): < 3 hours

Surface monitoring using ChemSwab: < 3 hours

In Process testing

Bioburden for bulks: < 2 hours

Bioburden for raw materials: < 2 hours

Sterility testing

Sterility test for filterable products: < 4 hours

Cleaning validation protocol: < 2 hours

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VALIDATION AND IMPLEMENTATION OF SCANRDI IN CLASSICAL PHARMA

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Classical Implementation of the ScanRDI

Installation and Commissioning

Instrument is installed and calibrated in accordance with requirements

Installation Qualification (IQ)

Instrument conforms to the manufacturer’s description and installation requirements

Operational Qualification (OQ)

Instrument meets the operational expectations and specifications. Includes security tests, conformance tests, challenge tests or stress tests

Training of Operators

On-site training by bioMérieux Field Application Specialist

Performance Qualification (PQ)

Verify the analytical performances of the system in concordance with Pharmacopeia and the equivalence of the results obtained with the current reference method for a given product

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Classical Implementation of the ScanRDI

Scan RDI Installation, Commissioning, IQ and OQ

Executed by a certified bioMérieux Field Service Engineer (FSE)

Commissioning, IQ and OQ documents are referenced and available from bioMérieux

Workload for execution = 1 week

After successful completion, the documents are signed by the executor (bioMérieux FSE) and the reviewer (customer)

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Classical Implementation - Training

Performed at customer site by a certified bioMérieux Application Specialist to 1 – 4 operator(s)

Duration of the training = 3 days – Includes “hands-on” by the operator(s) and observation / corrections by the trainer

Training certificates are provided to the operator(s) after successful completion of the training.

Close communication between the bioMérieux Application specialist and the operator(s) during the implementation / qualification phase after the training, including follow-up visits at the customer site

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Classical Implementation - PQ

Divided in 2 steps :

PQ1 – validation parameters tested to verify that the ScanRDI method gives the expected results on pure cultures

PQ2 – method suitability to verify that the final product(s) are compatible with the ScanRDI method

bioMérieux provides model protocol that follow USP <1223> and PDA Technical Report 33 recommendations, and data for the Robustness / Ruggedness tests

Validation parameters for the PQ1 phase are selected depending on the final application(s): qualitative or quantitative application(s)

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PQ1 & Equivalency to USP<71>

Parameters support a qualitative approach for a sterility test

Limit of detection

- Detection rate of the ScanRDI system method is as good or better as the USP <71> sterility test method on the 6 USP microorganisms

Specificity

- Ability of the ScanRDI method to detect the strains associated with Compounded Sterile Preparations (CSP) contaminants causing illness or death (2001-2012)

Robustness

- Small variations within ScanRDI method will not impact results

Ruggedness

- Different instruments, operators, reagents lots changes will not impact results

Data collected by bioMérieux is available for 503B Drug Compounders

Type V DMF # 14621 is amended by the PQ1

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STERILITY TESTING APPROVAL WORLDWIDE

Oldest Customer in the USA with 82,000 data points claims they have

tested over 1,400 family products successfully!

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References in the Pharma industry

BacT/ALERT® - TECHNOLOGY

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bacT/ALERT Overview

Patented Colorimetric Technology ( LES)

Fully automated, non destructive ,dual Tᵒ

Qualitative method (P/A)

up to 10 ml sample per bottle

Walk away system with reading every 10 mn

No need for interpretation.

Positive bottle can be immediately gram stained or streaked to a plate

Many varieties of media for use for Aerobic, anaerobic, neutralizing

etc…

4 drawers per incubator module (60 bottles per drawer, 240 for each

module, up to 6 incubator module per control module 1,440 bottles!)

510K approved for blood bank

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Reflectance Detection

Each sample has its own baseline reading and is individually monitored.

Readings taken every 10 minutes (144 times per day)

Red LED illuminates Sensor

As more CO2 is produced, the concentration of hydrogen ions increases and the pH falls causing the sensor to become lighter in color.

The result is an increase of red light reflected back to the photodiode

Signal Transmitted to Computer

Reflectance Units plotted over time (hours or days)M. Glogovsky - February 2012

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Technology “in a Bottle”

Enhanced media to obtain faster and optimal growth conditions.

Bottles optimized for specific uses.

Patented LES (Liquid Emulsion Sensor)

Bottle sensor (LES) only reacts to CO2

produced by organism growth.

iAST Bottle media is standard Tryptic Soy Broth.

Every lot produced is 100% inspected

Each bottle is individually barcoded

Possible to perform gram Stain & subculture directly from positive bottle (non-destructive technology) 25

M. Glogovsky - February 2012

Peel-off Barcode

Colorimetric “LES”

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Bottles are continuously agitated at controlled temperature(s)

Bottles are scanned every 10 minutes

Sophisticated algorithms analyze measurements of every individual bottle

Each cell is “flagged”, knowing which exact location a bottle is loaded into

Bottle Handling

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Simple Workflow

Obtain sample and inoculate

into BacT/Alert®

bottle (as little as 0.5mL)

Use the screen on the

controller module to

begin sample entry

Scan unique barcode on individual

bottle

Load sample bottles into the

incubator modules

BacT/ALERT® will perform analysis and

provide detailed results.

27M. Glogovsky - February 2012

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VALIDATION AND IMPLEMENTATION OF BACT/ALERT IN CLASSICAL PHARMA

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BacT / ALERT Installation Qualification

Software and Hardware Component Verification

Software Verification

Computer/ Worksation Verification

Instrument/ Control Module Hardware Verification

Field Verification of Physical Location

Field Verification ( Lab physical conditions-Building/Room #, Asset ID #, Secured access.

Field Verification of Environment and Utilities

Environmental Condition & Utility Verification

Electrical Verification & UPS backup verification

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BacT / ALERT Performance Qualification PQ1

Specificity

System must identify 6 Standard USP plus up to 4 Plant Isolates

Robustness

A small variation within BacT/ ALERT method will not impact results

Ruggedness

Different Instruments, operators, reagents lots changes will not impact results.

Type V DMF # 13225 and 510 K # K954468

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BacT/ ALERT Performance Qualification PQ2

Bottle Challenge Test

Up to 3 lots of products tested by 2 analysts over 2 days

Triplicate using low-level inocula of the 6 Standard USP strains plus up to 4 Plant isolates.

Positive and negative controls are used along with purity plates to confirm inoculum levels.

Acceptance criteria: Growth is detected in inoculated bottles in 7 days or less

Equivalency testing

Use of the same organisms and inoculum levels as the bottle Challenge test

Side by side comparaison of the BacT/ALERT sterility method to the existing method

Days to recovery results from bottle challenge test compared to the detection time for existing method.

Acceptance criteria: Results for the BacT/ALERT method must be equivalent or better as compared to the compendial method.

Limit of detection testing

BacT/ALERT bottles containing product are inoculated with ≤10CFU of challenge organism.

Purity plates used to verify inoculum level and purity

Acceptance criteria: Growth must be detected within 7 days.

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Blood Bank & Platelets

Cord Blood

Stem cells

Gene and Immuno-therapy

Food and Beverage

Cell culture and Cell culture media

Pharmaceutical

Vaccine

Parenteral

Microencapsulated

Oils

Antibiotics

Applications

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References in the Pharma industry

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Do your homework and look for the instrument that will fit your major products. Is your product compatible with the instrument? If not sure require a feasibility study.

What is important to you? Time to Result? Level of detection, detection of all live microorganisms, flow in your laboratory?

If Parametric release is authorized in your country , will it require a

lot of efforts to implement from raw material to final products, if

you export your products will it pass other regulatory

requirements? is validating final products easier and more

accepted?

Look for a company that can support you, from regulatory acceptance to implementation in your lab.

Implementing a Rapid Micro method requires a lot of work, is not cheap, but the ROI is always there when it is implemented correctly.

Keys for a successful implementation