1. Area II – Products and Structures
Stefan Leitgeb
15.06.2010
K1 Competence Center – Initiated by the Federal Ministry of Transport, Innovation &
Technology (MMVIT) and the Federal Ministry of Economics & Labour (BMWA).
Funded by FFG, Land Steiermark and Steirische Wirtschaftsförderung (SFG).

2. RCPE
The Research Center Pharmaceutical Engineering GmbH (RCPE GmbH)
is an interdisciplinary research institute in the area of pharmaceutical
process- and product-development in Graz.
The RCPE focuses on the development and production of
pharmaceuticals using rational, science-based methods derived from a
mechanistic understanding of relevant phenomena at all scales.
Our goals are:
• the development of modern pharmaceuticals and therapeutics,
• new drug-delivery methods and diagnostic tools,
• implementation of new quality-based production processes based on
state-of-the-art scientific knowledge.
RCPE - Area 2
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3. Vision and Mission
Vision
„RCPE“ – We make tomorrow’s drugs possible
Mission and Approach:
Combination of multi-disciplinary knowledge from process
engineering, pharmacy, chemistry, biotechnology, materials science and
nanotechnology to develop a coherent scientific basis for process- and
product-development.
Close collaboration with Austrian and international partners from the
pharmaceutical, biopharmaceutical and diagnostics industry, to develop
methods for design, optimization, scale-up and control of their new
manufacturing processes.
Development of innovative processes and process simplification.
Establishment of technology platform for science and industry with
focus on knowledge transfer.
Integration of targeted education and gender mainstreaming
activities.
RCPE - Area 2
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4. Location Graz
Graz is not only the second largest city in
Austria it´s also a leader in the field for life-
sciences. The city hosts the Graz University of
Technology, University of Graz, Medical
University of Graz and the Joanneum
Research. These institutions work closely
together in teaching and research and host
excellent researchers and high-end equipment.
Additionally Graz is hosting the Austrian
Center for Industrial Biocatalysis (ACIB) and
the cluster human.technology.styria. In recent
years a couple of small companies working in
the fast-growing field of life-science were
founded and settled in Graz. Therefore the city
of Graz can offer a great infrastructure and
facilities for the investigation of life-science
products like pharmaceuticals.
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5. Area 2 – Products and Structures
Area II nucleates research efforts focusing on experimental and computational studies to obtain
an understanding of product quality and behavior, as well as on structuring methods (e.g., nano-
particle formation, hierarchical particle technology, micro-particle formation, scalable production
processes, etc.). Area 2 can be divided in two divisions:
→ large molecule drugs → small molecule drugs
Goals: Goals:
→ Protein engineering and analysis for improved → Nano-particle formation processes
formulation properties → Development of stable formulations
→ Development of stable formulations → Development of drug delivery systems
→ Investigation of inactivation pathways → particle structuring methods
→ Understanding aggregation propensities
→ Characterization of API – polymer interactions
RCPE - Area 2
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6. Pharmaceutical biotechnological
products
One of our key research focuses within Area II is located in the field of
recombinant pharmaceutical proteins. The market of pharmaceutical
biotechnological products is an emerging, fast-growing field. These
products can be divided into several classes:
→ Vaccines
→ Therapeutics from blood or animal organs
→ Antibiotics
→ Recombinant proteins
→ Cell and gene therapeutics
Pharmaceutical biotechnological products bear a huge potential in
medical treatments, however, they are often difficult to handle and
show limited lifetimes. We focus our research on the field of
recombinant proteins – which is by far the largest group of
biotechnological pharmaceutical products – and especially on the
improvement of their quality in terms of stability. Examples for
pharmaceutical recombinant proteins are monoclonal antibodies or
insulin.
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7. Production of pharmaceutical
proteins
Main field of expertise:
pharmaceutical
development
Cloning into
expression
Trans- vector Fermen-
formation in Storage
tation and
host cell protein
expression
Integrated quality by design approach:
Packaging
Intelligent product design
Isolation of
gene of
Protein
interest
purification
Formulation
of protein
Identification product
of target Manufacturing
protein
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8. Formulation of pharmaceutical
proteins
Process
engineering level
(Freeze)- Freeze- Stirring+
storage transport
drying thaw mixing
Crystal-
Filtration Refolding filling
lisation
Product at
API Formulation
customer
Shear Hydration Environ-
Excipients
stress effect ment
Phase Surface Formulation Packaging
transition interactions conditions material
Molecular level
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9. One-stop shop
Pharmaceutical
proteins
Influence of Stability
Modifications of
process-relevant investigation and
Formulation proteins for
parameters of optimisation of
Development improved
critical operations biopharma-
performance
on proteins ceutical products
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10. Formulation development
We offer the knowledge and competence for the development and improvement of liquid
protein or peptide formulations. We can provide you a one-stop-shop with profound
knowledge in several fields of research. Our strength is the combination of a set of
different tools which is outstanding in this field. We benefit from the infrastructure in Graz
where the Graz University of Technology, University of Graz and Joanneum Research build
a large cluster of expertise.
Here is what we can offer:
Complete formulation development for your needs
Statistical optimisation
Extensive biophysical characterisation of pharmaceutical proteins
Stability and aggregation investigations
Accompanying computer simulations
taking these parameters together we not only can give a formulation recipe at the end
of the project but also a deep insight into the structure-activity-stability relationship of
your pharmaceutical protein.
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11. Influence of process-relevant
parameters of critical operations on
proteins
Pharmaceutical proteins have to face several steps after purification of the bulk product until
they are used by humans. Those steps are a source for stress that is applied to the proteins and
which can have negative effects on the product.
Critical standard operations can be:
Freezing and thawing
Stirring
Freeze-drying
Filtration
Storage and transport
We offer a detailed characterisation of the influence of critical parameters on pharmaceutical
products. The combination of statistical methods, simulation tools and biophysical
characterisation is used for the efficient investigation of the protein and its properties. The use
of diverse techniques and approaches offers a high potential for detailed understanding of the
effect of stress parameters on proteins leading to detailed solutions and improvement of the
final product.
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12. Stability investigation and optimisation
of biopharmaceutical products
A main drawback for the use of pharmaceutical proteins in therapy is their often limited
stability. The cause for the loss of function is often poorly understood and can be assigned
to diverse reasons. However, even if the reason is identified the mechanism for
inactivation or reduced stability remains mostly elusive. There are several factors that can
influence pharmaceutical proteins on a molecular level:
Liquid environment (buffer type and pH)
Surface interactions (liquid – gas, liquid – solid)
Environmental influence (temperature, light)
Interaction with storage / packaging material
Physical stress (shear stress)
…
We offer a detailed mechanistic investigation on a molecular level of the inactivation /
loss of stability of pharmaceutical proteins. We will not only identify critical influences on
the target proteins performance but will also work on revealing the underlying mechanism
to get a better understanding for the process. Based on these results we will provide
possible solutions for improved performance of the pharmaceutical proteins
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13. Modifications of proteins for
improved performance
Proteins are getting a lot of attraction in the pharmaceutical industry due to their high
potency. The main problems when working with proteins are usually their stability and
solubility which limit the use of proteins as therapeutics. Improving these properties is
usually very time-costly and needs a lot of ressources. Processes that lead to
destabilisation or aggregation of proteins are usually poorly understood and therefore the
improvement of proteins is based on trial and error.
To overcome these problems we can offer you the following:
Detailled characterisation of the problem using a set of biophysical techniques and
computer simulations.
Modification of proteins for improved performance.
Optimisation of proteins for/by pegylation
We can offer you a complete package that includes the capturing of the state of the art,
detailled characterisation of an inactivation mechanism and target-oriented protein
modification leading to improved performance and lifetime.
RCPE - Area 2
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14. IPRS AND FUNDING MODEL
Full IPR to industry partners
Defined IPRs Gratuitous, non-exclusive, timely unlimited non-transferable
(Intellectual right of use to RCPE
Properties Rights) Exploitation and utilization rights to RCPE after 12-24 months
Details must be singularly clarified in cooperation contract
Project Financing (Example)
Project Volume € 500.000,-
5% scientific min. 26% cash
Funding 49% € 245.000,-
max. 20% Inkind University 5% € 25.000,-
in-kind
Cash Industry 26% min. € 130.000,-
Inkind Industry 20% max. € 100.000,-
49% fundings
2 Industry Partners: 3 Industry Partners:
Cash per each industry partner € 65.000,- Cash per each industry partner € 43.333,-
Inkind per each partner € 50.000,- Inkind per each partner € 33.333,-
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15. RCPE - KEY BENEFITS
RCPE provides independent R&D in the field of pharmaceutical
engineering, bridging the gap between science and industrial applications
Defined IPRs provide maximum benefit for industrial partners
Long-term cooperation with the RCPE possible
(funding period of 7+ years)
Diversity in research activities: small preparatory studies
(literature review, initial measurements, proof of concept)
up to extensive multi-year research programs are possible
Only 26% cash contribution required in joint research projects
No time-consuming project application procedures; project work plan
can be defined bilaterally and the project can be started immediately
RCPE can provide additional scientific partners if expertise is required
RCPE can provide additional industrial partners if industrial cooperation
is desired and/or for project cost-sharing
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