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THE YEAST EXPERTS
Industry leading expertise in developing
yeast biomanufacturing processes
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THE YEAST EXPERTS
The expression of proteins in yeast can offer a number of advantages over other systems. MSD (formerly Avecia
Biologics) has experience in developing manufacturing processes for more than 10 years in both Pichia and
Saccharomyces which has given us an enviable track record from early phase clinical through to commercial
manufacture.
Why yeast?
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Yeasts are able to secrete correctly folded protein into the culture
supernatant
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Pichia can use the methanol-inducible alcohol oxidase 1 gene (AOX1)
which can result in tight control of heterologous expression
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Yeasts have the cellular machinery to accurately fold more
complicated proteins than prokaryotic systems
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Post-translational modifications are possible eg. glycosylation
MSD’s track record spans >10 years’ experience
R&D
15L - 100L
Manufacturing
trials
100L; 1000L
MSD’s R&D capabilities
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30 modern laboratory bioreactors capable of operating high cell
density yeast processes with methanol and O2 supplementation
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Experience using FMEA methods to define Laboratory Process
Characterisation (LPC) studies ahead of validation
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LPC studies carried out using statistical experimental design,
allowing rapid and robust process characterisation
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Experience of scaling fermentation processes from 15L laboratory
to 5000L production scale
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Developed yeast processes from Phase I through
Phase II/III/Validation to NDA and commercial manufacture
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Experience of scaling expanded bed chromatography from 2.5cm
to 100cm production scale
cGMP
100L; 1000L;
5000L
Commercial
manufacture
5000L
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THE YEAST EXPERTS
MSD’s manufacturing capabilities at Billingham
Upstream
Downstream
Our manufacturing capabilities are designed to enable:
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Able to apply the full range of separation and purification options
including the use of expanded bed chromatography (EBC)
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Extensive experience of EBC capture/purification:
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The high oxygen transfer rates and cooling capacities required for
high cell density culture
G
Reproducible and robust scale up from 15L laboratory scale to 5000L
manufacturing scale
• Provides rapid and efficient scalable primary capture combined
with initial purification
G
Delivery of consistent performance at all scales
• Excellent scale-up data from a 2.5cm expanded bed up to 100cm
• Taken through commercial manufacture
Final biomass and product titres
Analytical RP-HPLC of EBC load and eluate
from 5000L run
Load
0.40
0.35
0.30
AU
0.25
0.20
0.15
0.10
15 L
non-GMP
Biomass
100 L
non-GMP
100 L
GMP
1000 L
GMP
5000 L
GMP
0.05
0.00
Product
0.00
5.00
10.00
15.00
20.00
25.00
30.00
35.00
40.00
45.00
50.00
55.00
35.00
40.00
45.00
50.00
55.00
Minutes
Eluate
EBC - yield and purity
0.40
0.35
0.30
AU
0.25
0.20
0.15
0.10
0.05
0.00
2.5cm
5cm
20cm
40cm
100cm
0.00
mg/L culture
Purity by RP HPLC
5.00
10.00
15.00
20.00
25.00
30.00
Minutes
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MSD - the yeast experts
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Strategic investment in technology advances to deliver further
improvements in performance, output and cost-of-goods
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Able to demonstrate consistent cGMP performance and ouput
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Successful track record in taking processes from early phase clinical
through to late phase and commercial manufacture
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More than 10 years’ experience in producing clinical therapeutic
proteins using yeast systems
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Yeast process (Pichia)
consistency at 1000L GMP scale
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Our capability in process development and biomanufacturing
have been shown to result in robust reproducible yeast-based
processes
Product Yield
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MSD Biologics (UK) Limited
PO Box 2
Belasis Avenue
Billingham TS23 1YN
United Kingdom
Tel: +44 (0) 1642 363511
Fax:+44 (0) 1642 364463
Email: [email protected]
www.msd-uk.com/bmn
Copyright © 2010 MSD Biologics (UK) Limited.
All rights reserved. Printed in England.
April 2010.