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In co-operation with:
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Advanced Development of Recombinant Protein Production
A comprehensive Introduction in Design of Experiments
Applications
The applications of advanced PAT-Process Analytical Technology
in combination with repeated fed batch
control strategies, DoE-Design of Experiments and MVDA-Multi
Variate Data Analysis offer powerful tools
for process on-line monitoring, integration, intensification and
optimization.
This course includes the theoretical background and experimental
demonstrations of especially development
devices and integrated production processes for API-Active
Pharmaceutical Ingredients as well as for RTE-
Recombinant Technical Enzymes.
The main focus is based on fast applicable tools for DoE in
upstream and downstream development.
As an example of pharmaceutical proteins whole production
processes of potential Malaria vaccines are
investigated in detail. In the field of technical enzymes
intensified processes for Lipase CALB are
demonstrated.
Fig. 1: A multi-bioreactor plant for a fast upstream
optimization with DoE
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In co-operation with:
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A fully automated multibioreactor plant, shown in fig. 1, with a
BIOSTAT Bplus cell breeding system in
connection with six BIOSTAT Qplus screening vessels (both
Sartorius Stedim Biotech) is developed for a fast
optimization of expression conditions in both, cultivation
operation parameters and media components,
with DoE.
In the field of down-stream processing an KTAavant (GE
Healthcare) system, shown in fig. 2, is used for
optimization of chromatography conditions, strategies and column
scouting in purification procedures.
Both strategies are part of a full process optimization.
Therefore two fully automated integrated production
lines are developed.
In a lower pilot scale a 5 L BIOSTAT ED5 reactor for repeated
protein production is combined with a
preparative EBA-Expanded Bed Adsorption chromatography system
for a fast in-situ cell retention and
protein pre-purification. Here methods for a sequential
production of sensitive APIs and their fast release
and recovery from the reaction space are developed and
optimized.
Fig. 2: Chromatography system KTAavant for purification
optimization
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In co-operation with:
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In order to image an industrial production plant a direct
up-scalable pilot plant with a 10 L cell breeding
reactor BIOSTAT ED10, a 30L protein production reactor BIOSTAT
C30 (both Sartorius Stedim Biotech), a
scale-down separator SC1 (GEA Westfalia Separator), two Sartocon
Slice cross flow systems for micro- and
ultrafiltration (Sartorius), and an KTApurifier 100 (GE
Healthcare) are integrated under control of SIMATIC
PCS7 (Siemens).
This plant, shown in fig. 3, is used for intensive
DoE-applications in the whole upstream- and downstream
line.
Fig. 3: Integrated recombinant protein production plant for
DoE-applications
Umetrics AB Organizers
Mr. C. Wikstrm
Phone: +46 (0)90-18 48 49
Mobile: +46 (0)73-682 48 49
Email:
[email protected]
Box 7960
SE-907 19 Umea
Sweden
URL: http://www.umetrics.com
HAW Hamburg
Prof. Dr.-Ing. R. Luttmann
Phone: +49 (0)40-42875-6357
Fax: +49 (0)40-42875-6399
Email:
[email protected]
Lohbrgger Kirchstr. 65
21033 Hamburg
Germany
mailto:[email protected]://www.umetrics.com/
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In co-operation with:
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Location
Research Center of Bioprocess Engineering and Analytical
Techniques
Hamburg University of Applied Sciences
Faculty of Life Sciences
Lohbrgger Kirchstr. 65
D-21033 Hamburg
Date
16.-18.10.2012
Contributors:
Umetrics: Dr. I.-M. Lindstrm, C. Wikstrm
GE Healthcare: Dr. M. Ahnfelt
HAW Hamburg: Prof. Dr.-Ing. R. Luttmann
Dipl.-Ings. (M.Sc.) J. Fricke, K. Pohlmann, C. Mller, K.
Lgering, S. O. Borchert, J. Paul, S. Martens
Sartorius: Dipl.-Ing. (M.Sc.) A. Ellert
Seminars:
R. Luttmann: Course overview and DoE-topics
C. Wikstrm: Introduction and statistical background of DoE
J. Fricke: Upstream optimization in a multi bioreactor plant
C. Wikstrm: Optimization theory possibilities and consequences
with different designs
M. Ahnfelt: Optimization of protein purification with
KTAavant
C. Mller: Applications of DoE and MVDA in a scale-down
production plant
C. Wikstrm: Robustness tests and more
Computer labs:
1. Set up of screening design possibilities and consequences
(Umetrics)
2. Data analysis of screening designs in MODDE and presentation
of results (Umetrics)
3. Optimization and robustness design and analysis of those
(Umetrics)
4. Implementation of Design of Experiments into cultivation
strategies (HAW, Sartorius)
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In co-operation with:
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Experimental demonstration: 1. Optimization of upstream
processes with a multi-bioreactor plant (J. Fricke, K.
Pohlmann)
2. Optimization of integrated processes with EBA - cell release
and protein capture (S. O. Borchert, S. Martens)
3. Optimization of protein purification with KTAavant (J.
Paul)
4. Optimization of an integrated scale-down production plant (C.
Mller, K. Lgering)
This course is targeted at biotechnologists in research and
production divisions of manufacturers of
biochemical products as well as in bioengineering research
institutes.
Audience
The objectives are also intended to give newcomers an overview
of the state of art. People from practise will
get an insight of innovative biochemical engineering
approaches.
Executives will get decision guidance for acquisition of new
devices and plants and ideas and guidance for
application of DoE in bioprocess optimization.
No prior knowledge of statistics is assumed.
Programme of seminar, experimental demonstrations and tutorials
in small groups. Detailed course guide
and documentation.
Costs and conditions
Lunch and catering while the whole course as well as a dinner at
16.10.2012 are included in the course fee
of 1.600,- + VAT. The third day is optional without additional
costs.
Early bird registration: If you book at least 2 months prior to
course date the price DISCOUNT is 150 Euro.
Also if you are more than three participants from one company
booking the same course date you will
receive an 100 Euro DISCOUNT/person.
Course fee (+VAT) includes coffee, lunch and course
documentation. An invoice will be sent and payment is
required within 30 days of the invoice date. Course application
is binding. Cancellations registered later than
two weeks before the course start will not be refunded. Provided
that Umetrics AB is notified, the
registering company may substitute its participant(s).
If the customer cancels prior to 14 days of the course, 10% of
the class fee will be applied to cover
processing costs. The balance of class fees already paid to
Umetrics may be credited towards a future
course. The registering company may substitute its
participant(s) provided that Umetrics is notified.
Umetrics holds courses based on a sufficient number of
registrants. Therefore, Umetrics reserves the right to
cancel the course 14 days prior to the course start date if the
number of registrants is too low. Full refund
will be made to these registrants. Alternately a 10% refund will
be made to any registrant(s) enrolling in the
next available course.
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In co-operation with:
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Advanced Development of Recombinant Protein Production
A comprehensive Introduction in Design of Experiments
Applications 1st day: Screening
Time Description Lecturer / moderator 08:45 09:30 Salutation and
introduction of the candidates C. Wikstrm 09:30 10:05 Course
overview and DoE-topics R. Luttmann 10:05 10:15 Coffee break 10:15
11:00 Introduction and statistical background of DoE C. Wikstrm
11:00 11:35 Upstream optimization in a multi-bioreactor plant J.
Fricke
11:35 12:35 Computer Lab 1, group A and B / Experiment 1, group
C, and Experiment 2, group D
Umetrics, HAW
12:35 13:25 Lunch and Coffee
13:25 14:25 Computer Lab 1, group C and D / Experiment 1, group
A, and Experiment 2, group B
Umetrics, HAW
14:25 14:35 Coffee break and transfer 14:35 15:20 Analysis of
screening designs C. Wikstrm
15:20 16:20 Computer Lab 2, group A and B / Experiment 2, group
C, and Experiment 1, group D
Umetrics, HAW
16:20 16:30 Coffee break and transfer
16:30 17:30 Computer Lab 2, group C and D / Experiment 2, group
A, and Experiment 1, group B
Umetrics, HAW
18:00 Course dinner in the Mensa VIP room, participants and
lecturer 2nd day: Optimization and robustness
Time Description Lecturer / moderator
08:30 09:10 Optimization design C. Wikstrm 09:10 09:50
Optimization of protein purification with KTAavant M. Ahnfelt 09:50
10:00 Coffee break and transfer
10.00 11.00 Computer Lab 3, group A and B / Experiment 3, group
C, and Experiment 4, group D Umetrics, HAW
11:00 11:10 Coffee break and transfer
11.10 12:10 Computer Lab 3, group C and D / Experiment 3, group
A, and Experiment 4, group B
Umetrics, HAW
12:10 13:00 Lunch and coffee 13:00 13:35 Applications of DoE and
MVDA in a scale-down production plant C. Mller
13:35 14:15 Robustness test and more C. Wikstrm / I. M.
Lindstrm
14:15 14:25 Coffee break and transfer
14:25 15:25 Computer Lab 4, group A and B / Experiment 4, group
C, and Experiment 3, group D HAW, Sartorius
15:25 15:35 Transfer
15:35 16:35 Computer Lab 4, group C and D / Experiment 4, group
A, and Experiment 3, group B
HAW, Sartorius
16:35 16:45 Transfer and coffee break 16:45 17:15 Course
conclusion and first fare well
3rd day: Problems and discussion
Time Description Lecturer / moderator 08:30 09:30 Course
discussion continuation Umetrics, HAW 09:30 09:40 Coffee break
09:40 12:00 Discussion of participants problems Umetrics, HAW 12:00
12:40 Lunch and coffee 12:40 13:00 Second fare well
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In co-operation with:
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Fax-Announcement (+49-40-42875-6299)
Advanced Control and Optimization of Recombinant Protein
Processes
A Comprehensive Introduction in Design of Experiments
Applications
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