A bit of -on line- science in Pharma manufacturing

A bit of -on line- science in Pharma
manufacturing
2012, June 28th
JP Bovée A Labiche
IS Innovation Awards 2011: Communication Kit
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A bit of -on line- science in Pharma manufacturing
WYSIWIG 2.0
Breaking walls between Lab and Production Plant
WYSIWIG 2.0: What You Simulate Is What You Get
Short introduction
Business / technical issue: more and more process understanding in order to implement QBD (Quality by Design
concept) and to cut production costs are at stake. This requires to quickly experiment new ideas born in the Lab at
industrial level. However technical roadblocks are on the way from LAB to Industrial scale: actually there are 2
worlds with different IS equipment and languages, substantially slowing down the process transfer or even
collapsing it.
Usually simulations done at Lab scale must be transposed to industrial equipment requiring to translate programs
into very specific languages and sometimes heavy re-validation tasks. This takes time, money and sometimes
makes smart projects never reaching industrial scale or even pilot scale.
The solution: a PC profiled to process control area + a skilled simulation tool (SCILAB / INRIA) with real time
connection capabilities to industrial equipment above hurdles can be fully overcome.
It applies to a wide variety of projects, from process production improvement to energy management optimization.
(*) SAWv7 (LPC LAB Process Control), based on Windows 7 and office 2010
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Granulation
1.  Raw materials preparation and
Binder 1
Weighing
Disintegrant
Paracetamol
(powder)
2. 
3. 
4. 
5. 
6. 
7. 
8. 
loading
Granulation
Drying
Discharge
Sieving
Mixing
Compression
Packaging
Packaging
Exhaust Air
Buffer
Doliprane
(tablets)
Granulation
Drying
Compression
Compressed Air
Lubricant
Water + Binder 2
Glidant
Process Air
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Sieving
Mixing
No reliable nor affordable on- line moisture
measurement
Doliprane
(granules)
Process modeling: Mass balance
● 
● 
Principle: water mass conserva2on Assump2ons: ●  Pulverized water  used to wet solid ●  Vaporized water  100% to outlet air ●  No water losses
Partial mass flow rates of water in air :
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4 Process modeling: Heat balance
● 
● 
Principle: energy conserva2on Assump2ons: ●  Heat parameters constant during a batch ●  Heat capacity of air such that Cpair = Cpdry,air
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5 Results
● 
Es2ma2on of solid moisture: 3 models for the Fluid Bed Granulator/Dryer ●  Mass balance: water mass conserva2on ●  Heat balance: energy conserva2on ●  Mollier chart: thermodynamics and equipment efficiency + 1 model for the buffer tank ● 
Es2ma2on of fluid bed clogging: Increasing of pressure drop over a campaign of produc2on JP Bovée A Labiche
Results: quality of on line estimation better than
0.5% (target)
Accuracy better
than 0.5%
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Why is this delivered so late?
●  On the one hand
●  LABs: Powerful computers able to run big models
●  On the other hand
●  PLANT: at industrial equipment level: very poor calculation capacities
(PLCs, SCADA)
No direct connection with industrial systems (PLC + SCADA)
●  Proofs of concepts remain at lab level
JP Bovée A Labiche
A bit of -on line- science in Pharma manufacturing
WYSIWIG 2.0
Industrial scale can progress only if R&D and Industrial scale can communicate easily
Nevertheless big differences stand in progress’ way
LAB SCALE
Concept, model, equations,
control strategy
As per design and
technological specificities:
NO TRANFER
(Reptiles can not read
equations)
Good ideas
remain future for ever
•  Big Brain
•  Armless
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INDUSTRIAL SCALE
Real time oriented
Specific systems
(SCADA, PLCs)
•  Big hands
•  Tiny / reptilian brain
A bit of -on line- science in Pharma manufacturing
WYSIWIG 2.0
The challenge: a big roadblock over the way from Lab to Industrial scale
2 worlds, 2 systems and languages needing permanent translation
INDUSTRIAL SCALE
LAB SCALE
Concept &
simulation tool
Tuning
different Systems
and, languages 
substantial:
Back
•  adpatation
•  translation
(i.e. Excel, Matlab,
Scilab)
•  Validation costs
 Quite long time
to market
And forth
The TRANSLATION WALL
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Industrial / pilot
equipment
SCADA specific
system
IS Global Innovation Awards 2011
WYSIWIG 2.0 What You Simulate Is What You Get
THE SOLUTION : how to remove barriers
INDUSTRIAL
SCALE
LAB SCALE
Concept &
And
forth
Back
simulation tool
(Scilab)
Industrial / pilot
equipmentSCA
DA specific
system
Tuning
Direct connection between the 2 worlds
SAWv7
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Bi directionnal
transparent pass
through PC PLC
A bit of -on line- science in Pharma manufacturing
WYSIWIG 2.0
Application to online estimation of Relative Humidity in Fluid bed Dryers
From Lab to Industrial scale on the same machine
just a PC as a bridge!
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SAWv
Direct monitoring
and control of…
15% of productivity increase expected (250 k€ / year), easy deployment across about 200 fluid bed dryers within IA
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Application to Air Handling Unit
 At plant level in Pharma industry: 70 to 80% of energy = Heating,
Ventilation, Air Climatisation
 Control of Temperature, Air Moisture, differential pressure between
areas
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13 Application to Air Handling Unit
 Evidence of oscillations in Air Handling Units control
Cooling
valve
Heating
valve
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14 Next potential candidates
 Lyophilisation
 Crystallization
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WYSIWIG 2.0
Paving the way for a better controlled production
Before this innovation
•  sophisticated models at lab level requiring changes to be brought to equipment, in complex languages  a lot of effort
and validation
•  no connection between the two - a "black box" at industrial equipment level where only a final output can be seen (yield,
energy consumption...)
With WISYWIG
•  Quite a simpler model is proposed on an industrial PC, making the 2 worlds communicating directly in real-time
•  This enables testing with no delay new control / production strategies based on last enhancements from labs
•  Getting actual process data speeds up, via simulation, process model improvement
•  No adaptation / translation  not delay, no additional validation effort
In the future
•  This innovation is transposable to other sites with similar or other equipment (e.g. freeze-drying, crystallization )
•  It can be used for training purposes as well
•  This paves the way to the next steps
• 
Process Analytical Technologies, as per FDA requirement
• 
Self-learning systems that will improve process understanding, then yield, OEE and industrial production costs
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A bit of -on line- science in Pharma manufacturing
WYSIWIG 2.0
•  Competitiveness & Value Creation (or Opportunities for Best PoC / Prototype Dossiers):
Because it removes quite a handsome and costly step from concept to production, this solution enables to
make quick PoC at pilot or industrial. Nice ideas that so far were not implementable become real via this
solution, paving the way for process improvement and significant cost reductions, inclusive of energy
consumption
•  Breakthrough & creativity with regard to existing technologies / processes:
Usual technologies require expertise in specific programming of PLCs and SCADA + substantial validation
effort, at least delaying innovation by half a year and sometimes never coming to an end.
Even sometimes programming languages simply do not enable to implement enhanced algorithms, brilliant
ideas then eventually crash into this roadblock on innovation path.
•  Expected savings, related to productivity as well as green savings amount to double digit figures
•  Simple & Clever: no more than a well suited PC, an open source simulation software and scientific skill
 refer to figures on next slides
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A bit of -on line- science in Pharma manufacturing
WYSIWIG 2.0
Describe how the solution answers each criteria (with examples if possible)
•  Innovation behavior:
• 
This solution is new within sanofi and very likely beyond our company
• 
From budget perspective: accessible to the most penniless sites
• 
Collaboration with different entities / breaking silos
•  Involvement and support of / from Operations, IS, R&D, external companies,
University
•  Sustainability / Green value
• 
Another immediate application is the control of thousands of Air Handling Units across our
Production sites (120 plus), resulting in energy cuts of double digit figures
• 
This tool creates independency from odd and scarce languages: this PC platform (SAWv7
+ SCILAB), by concept ensures solution portability, as a result this solution appears as
sustainable over 2 decades from now on.
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A bit of -on line- science in Pharma manufacturing
WYSIWIG 2.0
WYSIWIG 2.0: What You Simulate Is What You Get
monitor
control
•  Benefit = 250 k€ / year / equipment
•  About 200 similar equipment across IA 
•  potential 25 Mi € for this sole category of equipment
•  30 Mi € when applied to HVAC control
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Crea%ve Mindset, Innova%ve Solu%ons Thank you!
JP Bovée A Labiche
IS Innovation Awards 2011: Communication Kit
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