Pharmaceutical Proteins @ RCPE


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Pharmaceutical Proteins @ RCPE

  1. 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. 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 15.06.2010 - Seite 2
  3. 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 15.06.2010 - Seite 3
  4. 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 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. RCPE - Area 2 15.06.2010 - Seite 4
  5. 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 15.06.2010 - Seite 5
  6. 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. RCPE - Area 2 15.06.2010 - Seite 6
  7. 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 RCPE - Area 2 15.06.2010 - Seite 7
  8. 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 RCPE - Area 2 15.06.2010 - Seite 8
  9. 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 RCPE - Area 2 15.06.2010 - Seite 9
  10. 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. RCPE - Area 2 15.06.2010 - Seite 10
  11. 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. RCPE - Area 2 15.06.2010 - Seite 11
  12. 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 RCPE - Area 2 15.06.2010 - Seite 12
  13. 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 15.06.2010 - Seite 13
  14. 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,- - Seite
  15. 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 - Seite