Overview of ANSYS simulation

software for pharmaceutical

mixing applications
1 © 2011 ANSYS, Inc. April 27, 2017
 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

2 © 2011 ANSYS, Inc. April 27, 2017

 ANSYS is the Worldwide Simulation Leader

FOCUSED TRUSTED
This is all we do.
Leading product technologies in all physics areas
Largest development team focused on simulation 96 of the top 100
FORTUNE 500 Industrials
ISO 9001 and NQA-1 certified

CAPABLE PROVEN
2,700+ Recognized as one of the world’s MOST
employees INNOVATIVE AND FASTEST-GROWING
COMPANIES*
75
locations INDEPENDENT
Long-term financial stability
CAD agnostic
40
countries

LARGEST
3x The size of our
nearest competitor

3 © 2011 ANSYS, Inc. April 27, 2017 *Busines

 Top Healthcare and Pharmaceutical Companies
Rely on ANSYS software

Synthes Baxter Roche

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

4 © 2011 ANSYS, Inc. April 27, 2017

 ANSYS Partners with Thought Leaders,
Influencers and Decision Makers

Regulatory Authority Industry Consortia Academic Thought

Interaction Participation Leader
Collaboration

5 © 2011 ANSYS, Inc. April 27, 2017

 Testimonials
Pharmaceutical industry leaders have adopted engineering
simulation to meet their key performance indicators

"Boehringer Ingelheim is taking The mass transfer uniformity of a 15,000 liter

advantage of CFD analysis to gain more mammalian cell culture bioreactor with modified
process understanding during pitched blade impellers was demonstrated by a
development of new drugs." computational fluid dynamics (CFD) model
using ANSYS Fluent1.

We have successfully demonstrated that scale-up of

solid dissolution can be achieved using a systematic An accurate prediction of Oxygen Transfer (OT)
process of lab-scale experiments followed by simple requires the use of multiphase models. The Mixture
CFD modeling [ANSYS Fluent] to predict commercial- multiphase model in FLUENT is ideally positioned to
scale experimental conditions. enable prediction of OT. The Mixture multiphase
In particular this method is sought to identify major model can be used to predict hydrodynamic conditions
dissolution issues at lab scale before the large expenses of both gas and liquid phases. It can also track Oxygen
of processing and raw materials (particularly API) are transfer from a gas phase to a liquid phase. With
committed. […] suitable kinetic models for OT, it is possible to model
This approach paves a way to utilize modeling in the local Oxygen transfer from the gas phase to the
scaling up liquid mixing processes towards mammalian cells3.
the direction of quality by design2.

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
6 © 2011 ANSYS, Inc. April 27, 2017 Kenneth Norris,1 Robert Leasure,3 and Jeffrey Gaudio3, October 2010
3: “Predicting Dissolved Oxygen Concentrations in Bioreactors”, Gary Finka, GSK, Mammalian Process Research
 To Meet these Global Trends We See Investment in
a Number of Key Business Initiatives (KBIs)

Effective
Medical
Innovation

Ensuring
Compress
Extreme
Time to
Product
Market
Reliability

Affordable
Personalized
and
(P4)*
Profitable
Medicine
Medicine

7 © 2011 ANSYS, Inc. April 27, 2017

* Personalized, Participatory, Predictive, Preventiv
 Solution for Pharmaceutical Process

Chromatography Column
Packaging

Mixing scale up:

20 liter 20000 liter

Drug Delivery

Bioreactor – Cell Growth

Powder coating

Patch
Crystallization
Spray Drying Tablet
8 © 2011 ANSYS, Inc. April 27, 2017 compaction
 Drug Manufacture

Mixing
Scale up
Gas sparging
Mass transfer
Macro mixing structures, colored by vorticity
Reacting flows contours, in a mixing tank with a 6-bladed
Rushton impeller
Crystallization
Distribution of product Short circuiting
Mechanical stability molecular weight in an LDPE
reactor
at baffles

Solid suspension
Shaft vibration

Picture

Velocity vectors (left) and gas

9 © 2011 ANSYS, Inc. April 27, 2017 distribution (right) calculated in a tall
 Core benefits of using Virtual Prototypes
• 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

10 © 2014 ANSYS, Inc. April 27, 2017 ANSYS Confidential

 What is CFD?
Geometry and Meshing
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

11 © 2014 ANSYS, Inc. April 27, 2017 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

12 © 2014 ANSYS, Inc. April 27, 2017 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.

Characterizing meso-mixing.

21 of the top 35 biotechnology and pharmaceutical companies use ANSYS tools

13 © 2014 ANSYS, Inc. April 27, 2017 ANSYS Confidential
 Simulation results – flow and blend time
20-Liter 200-Liter
20-
Types of simulations done Lite
 Flow r
 Blend Time
 Exposure Analysis (TDR, Shear Rate) 2000-Liter 20000-Liter

 Zonal Residence Time Distribution

(RTD)

Power Numbers:
20L 200L 2000L 20000L
Time taken for the study ~ 1.5 days
RPM 63 37.7 22.6 13.6
CFD Upper Po 0.85 0.84 0.83 0.82
Observations:
CFD Lower Po 0.5 0.49 0.48 0.48 • Vendor specified “single impeller”
Power Number for both impellers power number is 0.75
Blend Time – Upper impeller close to that
20L 200L 2000L 20000L – Lower impeller draws lower power
Blend Time 25.8s 41.9 61.2s 111.8s
• Blend time increases with scale
Blend time for different sizes

14 © 2014 ANSYS, Inc. April 27, 2017 ANSYS Confidential

 Simulation results –
exposure analysis and zonal RTD
Zone1
Zonal Residence Time Distribution: Zone 1
Exposure Analysis: Dissipation Rate

Zone3

Zone2

Zone1

Dissipation Rate Exposure Analysis – Almost

Zonal Residence Time Distribution – Similar distribution at Identical environment
different scales
Observations:
Exposure Analysis: Shear Rate
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
15 © 2014Low intensity
ANSYS, Inc. at highApril
reactor
27, volumes
2017 Time taken for the CFD study ~ 1.5 days
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

16 © 2014 ANSYS, Inc. April 27, 2017 ANSYS Confidential