transition from batch to continuous processing

Automation in pharmaceutical industry, Leiden Oct 8th 2009.

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Raf Reintjens

Competence manager process intensificationDSM Pharmaceutical ProductsGeleen, The [email protected]

Transition frombatch to continuous processing


1Content

• Introduction

• Why switch to continuous?

• Barriers to transition

• About process intensification

• How can PI help to make the transition?

• The pharma plant of the future

• Conclusions


2Introduction

Life Science Products

Coal

Fertilizers

Petrochemicals

Performance Materials

Bioterials / Biologics

Chemical engineering

Polymer technology

Fine chemical synthesis

Material science

Mechanical engineering

Modern Biotechnology

Technological competences1902 1930 19701950 1990 2000 2010

DSM’s evolution


A Century of successful transitions


3Why switch to continuous?

Pharma industry is experiencing economic, social and environmental pressures

• Decreasing growth rate• Increasing cost for healthcare• New API molecules become more complex• Low manufacturing efficiency (waste, energy)

• Long development time• Increasing competition from generics



Batch

• Segmented individual steps • Processing a specific quantity• Multi purpose equipment• Quality managed by repetition

and testing

Continuous

• Integrated synchronized operations• Continuous flow of product

• Equipment dedicated for purpose• Quality managed by design and

process control of steady state

Benefits

- Lower cost level (operational, invest)

- Increased productivity (small plant, low hold-up)

- Shorter through put time (less inventory)

- Consistent quality (less off-spec, less byproducts)



Historical change of course

1900 1950 2000 2050

batch

continuous

automotive

petrochemical

electronics

pharma

• Efficiency and cost pressure (competition) have driven the transition in other processing industries

• Pharma is experiencing pressures and starts exploring continuous processing

• Managing quality in continuous processing made significant progress (6sigma)

Sep 2007


6Barriers to transition

Regulatory - Barriers are perceived, FDA stays tough on criteria but opens up to new solutions

Culture - Conservative attitude towards continuous processing mode

Education - Skill-base of personnel is batch oriented

Technology - Existing continuous processing technologies are oriented on dedicated bulk production

Equipment - Existing batch multi purpose plants will be standing idle- Industrial equipment for new technologies is not available or too expensive

Process Intensification helps removing barriers


7About process intensification

Process intensification is…..

The effective use of a set of innovative technologies aiming at:Driving a chemical process from the equipment limits to the limits of chemistry and physics


8About Process Intensification

PI competence development at DSM

FeasibilityNeeds

Stimulate external developments

academic, PPP, suppliers

Monitor and select

Develop promising technologies

Partner with suppliers

Information feedback

Learning curve

Business projects


9How can PI facilitate the transition

How to switch to continuous operation?

Integral Process & Plant Design• Identify the required functionalities

• Understand what drives them

• Understand how they interact

• Take a science based holistic view

PI technologies (modular)• Highly productive (small, safe, fast)

• Flexible (function, capacity)

• Reconfigurable (high OSF)

• Broad toolbox (reactive, DSP)

Process control• Secure steady state (design space)

• Use predictive models

• Incorporate PAT (real time release)

• Reliability, redundancy, accuracy

Chemistry• Choice of route

• Intrinsic kinetics

• Catalysis

• New domains (operating window)



Transition through hybrid state

Partly continuous

- For discrete section

- Start-up / shutdown



Example continuous nitration

extraction decomposition

Business needs- Intrinsic safety- High productivity- High selectivity- GMP production



centrifugalextractors

distillationcolumns

Micro reactor


13The pharma plant of the future

Con

vers

ion

For

mul

atio

n

Sha

ping

Pac

kagi

ng

Process control

PI equipment

PI technologies

MIT-Novartis

Continuous operation� All process steps integrated (short throughput time)

� Quality by design (hardware, control)

� Low operational cost (manpower, utilities)

APPI


14Conclusions

• Continuous processing provides significant benefits that can help the pharma industry to face the current challenges.

Thanks for your attention

• Process intensification facilitates the transition from batch tocontinuous processing. Small modular PI equipment can satisfy the need for versatility and flexibility

• Process control and PAT technologies will play an important role in quality management.

transition from batch to continuous processing

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