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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”
26M. Glogovsky - February 2012 26
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
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