A bit of -on line- science in Pharma manufacturing · A bit of -on line- science in Pharma manufacturing WYSIWIG 2.0. JP Bovée A Labiche 18 Describe how the solution answers each

JP Bovée A Labiche

A bit of -on line- science in Pharma manufacturing

| 1 IS Innovation Awards 2011: Communication Kit

2012, June 28th

JP Bovée A Labiche

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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

Breaking walls between Lab and Production Plant WYSIWIG 2.0: What You Simulate Is What You Get

A bit of -on line- science in Pharma manufacturing WYSIWIG 2.0

JP Bovée A Labiche

Granulation 1.  Raw materials preparation and

loading 2.  Granulation 3.  Drying 4.  Discharge 5.  Sieving 6.  Mixing 7.  Compression 8.  Packaging

Process Air

Water + Binder 2

Compressed Air

Paracetamol (powder)

Binder 1

Disintegrant

Glidant

Lubricant

Exhaust Air

Doliprane (granules)

Weighing

Granulation Drying

Buffer

Sieving Mixing

Compression Doliprane (tablets)

Packaging

No reliable nor affordable online moisture measurement

JP Bovée A Labiche

Process modeling: Mass balance

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●  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 :

JP Bovée A Labiche

Process modeling: Heat balance

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●  Principle: energy conserva2on ●  Assump2ons:

●  Heat parameters constant during a batch

●  Heat capacity of air such that Cpair = Cpdry,air

JP Bovée A Labiche

●  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

Results

JP Bovée A Labiche

Results: quality of on line estimation better than

0.5% (target)

Accuracy better than 0.5%

JP Bovée A Labiche

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

Good ideas remain future for ever


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Industrial scale can progress only if R&D and Industrial scale can communicate easily Nevertheless big differences stand in progress’ way

Concept, model, equations,

control strategy

LAB SCALE INDUSTRIAL SCALE

Real time oriented Specific systems (SCADA, PLCs)

•  Big hands •  Tiny / reptilian brain

As per design and technological specificities:

NO TRANFER

•  Big Brain

•  Armless

(Reptiles can not read equations)

JP Bovée A Labiche

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The challenge: a big roadblock over the way from Lab to Industrial scale 2 worlds, 2 systems and languages needing permanent translation


Concept &

simulation tool

(i.e. Excel, Matlab,

Scilab)

Industrial / pilot equipment

SCADA specific system

Back

And forth

Tuning different Systems and, languages substantial:

•  adpatation

•  translation

•  Validation costs

Quite long time to market

The TRANSLATION WALL


JP Bovée A Labiche

IS Global Innovation Awards 2011 WYSIWIG 2.0 What You Simulate Is What You Get

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THE SOLUTION : how to remove barriers

Concept &

simulation tool

(Scilab)

Industrial / pilot equipmentSCADA specific system


Direct connection between the 2 worlds

Bi directionnal transparent pass

through PC PLC SAWv7

And forth

Tuning

Back

JP Bovée A Labiche

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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!

15% of productivity increase expected (250 k€ / year), easy deployment across about 200 fluid bed dryers within IA

SAWv7

Direct monitoring and control of…


JP Bovée A Labiche

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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JP Bovée A Labiche

Application to Air Handling Unit

 Evidence of oscillations in Air Handling Units control

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Cooling valve

Heating valve

JP Bovée A Labiche

Next potential candidates

 Lyophilisation

 Crystallization

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JP Bovée A Labiche

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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


JP Bovée A Labiche

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•  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


JP Bovée A Labiche

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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.


JP Bovée A Labiche

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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


JP Bovée A Labiche | 20

Thank you!

IS Innovation Awards 2011: Communication Kit

Crea%ve Mindset, Innova%ve Solu%ons

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A bit of -on line- science in Pharma manufacturing · A bit of -on line- science in Pharma manufacturing WYSIWIG 2.0. JP Bovée A Labiche 18 Describe how the solution answers each