Session 1: Expression System Design

Expression system design involves the optimization of expression vectors at the molecular level to bring about desirable downstream effects at the cellular level. The technologies presented here are targeted to the engineering of mammalian or insect cell expression vectors. The molecular basis of stable expression will be discussed as one of the key aspects of ensuring high quality protein production and reproducibility. Translational control is also important for further improvement in the enhancement of productivity. Furthermore, the choice of promoter has a significant effect on protein expression. The question concerns not only the strength of promoter activity as for many expression systems cell type specific and time-dependent (early and late) promoters exist. Closely related to promoters is the issue of generating inducible expression systems. The advantage of this approach is that expression can be turned on and off in a controlled manner to maximize protein production. Additionally, the session will deal with site-specific integration and insulators. In the context of engineering stable cell lines it has become evident that the chromosomal integration site plays an important role for construct stability and expression levels. Introduction of insulator sequences or matrix attachment regions have a strong influence on stability and protein production.

Session 2: Gene Delivery

The development of vectors and methods that are capable of efficient gene delivery is crucial to the success of recombinant protein production, studies of cellular mechanisms, assay development and gene therapy. This session will include presentations that highlight advances in the development and application of adeno-associated virus (AAV), baculovirus and adenovirus vector gene delivery systems as well as improvements in non-viral gene delivery systems.

Session 3: Cell Engineering Session

Cell engineering is considered as any manipulation that results in some change to the cell of interest. The subjects and topics within the area of cell engineering are wide, covering a diverse range of topics including, but not limited to, stem cell research, metabolic engineering, the up-regulation/knockdown(out) of target genes and proteins, the development of new cell lines and media, and many other topics besides. As such, cell engineering could be considered a seamless subject that transcends into many other areas, lying directly at the research interface between engineers, biological scientists, mathematicians and product manufacturing specialists. Perhaps a more encompassing description of cell engineering would therefore be the investigation, manipulation, and enhancement of the biological processes that underpin cellular performance. This session intends to promote discussion of current leading edge research in this diverse area.

Session 4: Post-translational modifications/product integrity

Many proteins depend on complex post-translational modifications (PTM) relating structure to appropriate functionality. PTM has influence on biological activity, half-life of the protein, its immunogenicity and stability. The choice of host cells for expression of recombinant therapeutic proteins is of utmost importance. Nowadays a lot of research is carried out trying to humanize other expression systems than mammalian cells, still considered the biological system of choice. Glycosylation is often very accurate and precise, causing serious impact on product consistency. As many natural proteins present
molecular heterogeneity and glycan isoforms, it can be a problem to understand the acceptable biological range. Other frequent PTM include amination, phosphorylation, carboxylation, hydroxylation, sulfation, folding, and pegylation. The regulatory authorities are raising the standards for demonstrating product consistency thus making process development and in-process control of great impact at industrial level. Endeavors for the development of sophisticated analytical tools have demonstrated the feasibility of ensuring consistent quality of products, synthesized as expected and not degraded by impurities or additives. To understand naturally occurring PTM, build biological systems capable of accomplishing PTM at acceptable levels, design and operate large-scale processes, and develop analytical tools to control PTM and protein integrity depend on multidisciplinary efforts with many interfaces. This session will present and discuss examples of PTM and product integrity both at development and industrial levels.

Session 5: Integrated process development

This session will highlight advances and challenges in accelerating cell culture process development and scale-up for clinical and commercial manufacturing of proteins as biopharmaceuticals. Topics for the session include enabling tools and technologies, including Process Analytical Technology (PAT), that stimulate real-time monitoring, process control and early product characterization, novel approaches and practices for rapid and efficient process development or characterization, such as scale-down, optimization, scale-up and improved integration with downstream processing. Industrial best practice examples to improve culture productivity, while ensuring product quality, are particularly welcome.

Session 6: Viral vaccines

Cell culture derived viral vaccines play an increasingly important role in current clinical approaches and recently a number of good new targets have been successfully evaluated. Also, there is a growing interest in the use of advanced technologies for efficient manufacturing. The session will include presentations on topics related to the development and production of viral vaccines, such as attenuated or inactivated influenza virus, sub-unit cancer vaccines and development strategies for emergent or emergency vaccines. This will include cell line and vector development based on new animal-cell based expression systems, improvement of viral vector design or safety. New analytical technologies related to the determination of viral titers, infectivity, safety and process robustness will be discussed as well as strategies for improved productivity and downstream processing.