Power CFD based simulation a) In Pharma mixing process optimisation b) In compressing the time to market c) In delivering affordable and profitable drug

1. © 2011 ANSYS, Inc. April 27, 20171
Overview of ANSYS simulation
software for pharmaceutical
mixing applications

2. © 2011 ANSYS, Inc. April 27, 20172
LEAP Australia Overview
• ANSYS Partner in Australia since 1996
• 45+ permanent staff and growing
• Sales and Support for Best in Class Engineering Software
• Engineering Consultancy Services
• Training & Mentoring

3. © 2011 ANSYS, Inc. April 27, 20173 *Busines
ANSYS is the Worldwide Simulation Leader
FOCUSED
This is all we do.
Leading product technologies in all physics areas
Largest development team focused on simulation
CAPABLE
2,700+
75
40
employees
locations
countries
TRUSTED
FORTUNE 500 Industrials
96 of the top 100
ISO 9001 and NQA-1 certified
PROVEN
Recognized as one of the world’s MOST
INNOVATIVE AND FASTEST-GROWING
COMPANIES*
INDEPENDENT
Long-term financial stability
CAD agnostic
LARGEST
3x The size of our
nearest competitor

4. © 2011 ANSYS, Inc. April 27, 20174
Top Healthcare and Pharmaceutical Companies
Rely on ANSYS software
Medtronic
Boston
Scientific
St Jude
CR Bard
Thoratec
Quest Medical
Edwards
Cortronik
Nikkiso
Berlin Heart
Philips
Healthcare
Synthes
Joghnson &
Johnson
(Depuy)
Medtronic
Zimmer
Stryker
Biomet
Mayo Clinic
Orthofix
BIEN-AIR
Dental
United
GE Healthcare
Siemens
Healthcare
Philips
Healthcare
Hitachi
Medical
Toshiba
Medical
Samsung
Olympus
IBA
FluidDA
Baxter
Becton
Dickinson
Beckman
Coulter
Carl Zeiss
Covidien
Drager Medical
Fresenius
Resmed
Starkey Labs.
Thermo Fisher
GN Resound
Roche
Pfizer
Merck
Novartis
AstraZeneca
GSK
Ely Lilly
Takeda
Pharmaceutical
Abbot
Alcon Labs
Johnson &
Johnson
Sanofi Aventis
Boehringer
Ingelheim

5. © 2011 ANSYS, Inc. April 27, 20175
ANSYS Partners with Thought Leaders,
Influencers and Decision Makers
Regulatory Authority
Interaction
Industry Consortia
Participation
Academic Thought
Leader
Collaboration

6. © 2011 ANSYS, Inc. April 27, 20176
Pharmaceutical industry leaders have adopted engineering
simulation to meet their key performance indicators
The mass transfer uniformity of a 15,000 liter
mammalian cell culture bioreactor with modified
pitched blade impellers was demonstrated by a
computational fluid dynamics (CFD) model
using ANSYS Fluent1.
We have successfully demonstrated that scale-up of
solid dissolution can be achieved using a systematic
process of lab-scale experiments followed by simple
CFD modeling [ANSYS Fluent] to predict commercial-
scale experimental conditions.
In particular this method is sought to identify major
dissolution issues at lab scale before the large expenses
of processing and raw materials (particularly API) are
committed. […]
This approach paves a way to utilize modeling in
scaling up liquid mixing processes towards
the direction of quality by design2.
An accurate prediction of Oxygen Transfer (OT)
requires the use of multiphase models. The Mixture
multiphase model in FLUENT is ideally positioned to
enable prediction of OT. The Mixture multiphase
model can be used to predict hydrodynamic conditions
of both gas and liquid phases. It can also track Oxygen
transfer from a gas phase to a liquid phase. With
suitable kinetic models for OT, it is possible to model
the local Oxygen transfer from the gas phase to the
mammalian cells3.
"Boehringer Ingelheim is taking
advantage of CFD analysis to gain more
process understanding during
development of new drugs."
Testimonials
1: Mixing Uniformity Characterization of 15K Mammalian Cell Culture Bioreactor., Schmidt, B., ASTRA ZENECA Hodson, D., Astra Zeneca Boyds, A.,
Astra Zeneca Reynolds, G., Astra Zeneca, 2010 AIChE Annual Meeting
2: “Application of Modeling to Scale-up Dissolution in Pharmaceutical Manufacturing” Venkat Koganti,1,4 Fred Carroll,1 Richard Ferraina,1 Rick Falk,2
Yogesh Waghmare,2 Mark Berry,1 Yang Liu,1
Kenneth Norris,1 Robert Leasure,3 and Jeffrey Gaudio3, October 2010
3: “Predicting Dissolved Oxygen Concentrations in Bioreactors”, Gary Finka, GSK, Mammalian Process Research

7. © 2011 ANSYS, Inc. April 27, 20177
Effective
Medical
Innovation
Ensuring
Extreme
Product
Reliability
Personalized
(P4)*
Medicine
Affordable
and
Profitable
Medicine
Compress
Time to
Market
To Meet these Global Trends We See Investment in
a Number of Key Business Initiatives (KBIs)
* Personalized, Participatory, Predictive, Preventiv

8. © 2011 ANSYS, Inc. April 27, 20178
Solution for Pharmaceutical Process
Mixing scale up:
20 liter 20000 liter
Drug Delivery
Packaging
Crystallization
Spray Drying Tablet
compaction
Patch
Powder coating
Chromatography Column
Bioreactor – Cell Growth

9. © 2011 ANSYS, Inc. April 27, 20179
Drug Manufacture
Mixing
Scale up
Gas sparging
Mass transfer
Reacting flows
Crystallization
Mechanical stability
Solid suspension
Shaft vibration
Picture
Velocity vectors (left) and gas
distribution (right) calculated in a tall
Short circuiting
at baffles
Distribution of product
molecular weight in an LDPE
reactor
Macro mixing structures, colored by vorticity
contours, in a mixing tank with a 6-bladed
Rushton impeller

10. © 2014 ANSYS, Inc. April 27, 201710 ANSYS Confidential
• Cost & Time: More cost effective and faster than
multiple physical prototypes & experiments
• Engineering Insight: Comprehensive prediction of
mass transfer, pressures, velocities, concentrations
allow you to quantify impact of scale-up & design
changes, as well as looking inside the product to see
what is going on
• Rapid feedback to product development/clients:
quickly answer “what if?” scenarios or perform
more detailed optimisation
Core benefits of using Virtual Prototypes

11. © 2014 ANSYS, Inc. April 27, 201711 ANSYS Confidential
What is CFD?
Physics-based fluid flow simulation, or
Computational Fluid Dynamics (CFD)
 the science of predicting fluid flow, heat
transfer, mass transfer, chemical reactions, and
related phenomena by solving mathematical
equations in 3D.
The result is detailed information about all flow
variables in the system, for example:
• Flow patterns
• Species concentrations
• Turbulence levels
• Local rates of mixing
Geometry and Meshing

12. © 2014 ANSYS, Inc. April 27, 201712 ANSYS Confidential
CFD in the Pharmaceutical and
Biopharmaceutical Industries
ANSYS provides the broadest range of CAE solutions for:
 Drug Manufacture
 Separation Processes
 Materials Handling
 Drug Delivery
 Packaging and Distribution

13. © 2014 ANSYS, Inc. April 27, 201713 ANSYS Confidential
Pharmaceutical industry - agitated vessels
ANSYS has developed dedicated models for all
aspects of pharmaceutical engineering. Recent
examples include:
 Fully-integrated simulation environment
providing the broadest set of engineering
simulation tools.
 Numerous academic and industrial partnerships
on pioneering projects.
 Participation in major research projects.
 A dedicated global team with focus on
pharmaceutical technologies.
21 of the top 35 biotechnology and pharmaceutical companies use ANSYS tools
Characterizing meso-mixing.

14. © 2014 ANSYS, Inc. April 27, 201714 ANSYS Confidential
Simulation results – flow and blend time
Types of simulations done
 Flow
 Blend Time
 Exposure Analysis (TDR, Shear Rate)
 Zonal Residence Time Distribution
(RTD)
20-
Lite
r
200-Liter
2000-Liter 20000-Liter
20-Liter
20L 200L 2000L 20000L
Blend Time 25.8s 41.9 61.2s 111.8s
20L 200L 2000L 20000L
RPM 63 37.7 22.6 13.6
CFD Upper Po 0.85 0.84 0.83 0.82
CFD Lower Po 0.5 0.49 0.48 0.48
Power Numbers:
Blend Time
Observations:
• Vendor specified “single impeller”
power number is 0.75
– Upper impeller close to that
– Lower impeller draws lower power
• Blend time increases with scale
Power Number for both impellers
Blend time for different sizes
Time taken for the study ~ 1.5 days

15. © 2014 ANSYS, Inc. April 27, 201715 ANSYS Confidential
Simulation results –
exposure analysis and zonal RTD
Zone1
Zone1
Zone2
Zone3
Low intensity at high reactor volumes
Dissipation Rate Exposure Analysis – Almost
Identical environmentZonal Residence Time Distribution – Similar distribution at
different scales
Observations:
Cells/Particles exposure to high shear rate decreases with
increase in reactor size
Dissipation rate profiles are identical
“Normalized” Zonal Residence Time behaviors similar for
all reactor sizes
At different scale particles/cells will experience similar
environment
Time taken for the CFD study ~ 1.5 days
Exposure Analysis: Shear Rate
Exposure Analysis: Dissipation Rate
Zonal Residence Time Distribution: Zone 1

16. © 2014 ANSYS, Inc. April 27, 201716 ANSYS Confidential
LEAP Australia contact details
Kuthur Sriram M.Sc., MBA.
Engineering Solutions Manager
Suite 6, 750 Blackburn Rd, Clayton Nth 3168
phone: + 61 3 8542 7880
mobile: + 61 429 155 778
fax: + 61 3 8542 7899
email: kuthur.sriram@leapaust.com.au
Website: http://www.leapaust.com.au
CFD Blog: http://www.computationalfluiddynamics.com.au