This document summarizes the work of Area II - Products and Structures at the K1 Competence Center. Area II focuses on experimental and computational research to understand product quality, behavior, and structuring methods like nanoparticle formation. The area is divided into research on large molecule drugs and small molecule drugs. The goals for both include developing stable formulations, drug delivery systems, and understanding interactions. The document provides overviews of the areas of expertise, services offered, and fields of research, which include pharmaceutical development, protein engineering, formulation, stability testing, and computational modeling.

1. Area II – Products and Structures
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).
Area II – Products and Structures
Stefan Leitgeb
sleitgeb@tugraz.at 06.10.2010

2. 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
Goals:
→ small molecule drugs
Goals:
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→ Protein engineering and analysis for improved
formulation properties
→ Development of stable formulations
→ Investigation of inactivation pathways
→ Understanding aggregation propensities
→ Characterization of API – polymer interactions
→ Nano-particle formation processes
→ Development of stable formulations
→ Development of drug delivery systems
→ particle structuring methods

3. Production of pharmaceutical
proteins
Cloning into
expression
vectorTrans-
formation in
host cell
Fermen-
tation and
protein
expression
Storage
Main field of expertise:
pharmaceutical
development
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Identification
of target
protein
Isolation of
gene of
interest
Protein
purification
Packaging
Formulation
of protein
product
Manufacturing
Integrated quality by design approach:
Intelligent product design

4. Formulation of pharmaceutical
proteins
Process
engineering level
Stirring+
mixing
(Freeze)-
drying
Filtration Refolding
Freeze-
thaw
Crystal-
lisation
filling
storage transport
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API Formulation
Product at
customer
Molecular level
Shear
stress
Packaging
material
Surface
interactions
Hydration
effect
Phase
transition
Excipients
Formulation
conditions
Environ-
ment

5. One-stop shop
Pharmaceutical
proteins
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Formulation
Development
Influence of
process-relevant
parameters of
critical operations
on proteins
Modifications of
proteins for
improved
performance
Stability
investigation and
optimisation of
biopharma-
ceutical products

6. Fields of Expertise
Influence of critical process parameters (CPP)
on critical quality attributes (CQA)
Product optimisation
Computer simulations at various levels of theory
(QSAR, molecular dynamics, coarse grained, …)
Biophysical and biochemical characterisation of
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Biophysical and biochemical characterisation of
proteins
Stability and aggregation investigations
High-throughput formulation development and
optimisation
DoE
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7. Services
Experimental
High-throughput formulation
development of pharmaceutical proteins
and small molecules
Protein aggregate characterization
Stability testing of pharmaceutical
proteins under accelerated conditions
Computational - proteins
Rational protein design based on
molecular structure
Molecular dynamics simulations of
protein – small molecule interactions
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proteins under accelerated conditions
Biophysical and biochemical protein
characterization
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Computational – small molecules
Virtual screening
In-silico lead optimisation
Solubility calculation of small molecules
Prediction of crystal structure /
polymorphs and morphologies / habits
Design and implementation of work flows
and data streams through scripting
General
Literature studies
Design and implementation of efficient
virtual work flows and data streams
through scripting (Knime, Phyton, Perl)