Up- and downstream:
Process development for up- and downstream processing with different host organism (bacteria, yeast, mammalian cell culture,…)
Fermentation scale up from µ- to lab- and pilot scale
On-line monitoring platform and development of monitoring strategies for critical control parameters in real-time in up- and downstream
Manufacturing and processing of products at pilot scale (non-GMP, but under “GMP-like” conditions)
Available in-house model systems
- e.g.: rhSOD, GFP, scFv (IB or soluble)
Available model organisms
- E. coli, P. pastoris, CHO, Sf9
Open for model systems and organisms provided by partners
Method development for cell harvest, IB harvest, refolding, precipitation; small scale development and transfer to pilot scale
Filter testing for Depth- and Sterile filtration including upscale
- method development and upscale; membrane testing
- method development and scale up; benchmarking of different resins with in-house model systems (different feed)
Test of equipment provided by supplier
The requirements for gaining a level of process understanding are not new, it is recognised that the use of multivariate analysis, in combination with modern process analytics and knowledge management tools can enhance the identification of critical parameters that affect the individual processes. One of the goals is to ensure that all sources of variability affecting a process are identified, explained and managed. This is in accordance with the fundamental principle that quality cannot be tested, but is instead built into the product by design (QbD).
In this respect, we have established certain analytical methods for analyzing media compounds, secreted metabolites, manufactured products in terms of quality and quantity as well as liposomal formulations. The existing techniques and newly developed methods can be used in different research projects, teaching and services. The reliability of the applied methods is ensured by our installed Good Laboratory Practice (GLP) procedures.
Liposomology: Preparation and Formulation
The formation of stable lipid bilayers can be performed by several techniques. At the working group “Liposomology” a portfolio of different methods to prepare liposomes with almost all kind of lipid compounds in small- and large scale were established.
Small-scale methods using organic solvents, or detergents respectively alcohols are convenient to produce lab-scale volumes. Depending on the methodology multi- uni- or oligo-lamellar vesicles can be prepared. To offer homogeneously distributed liposomes of different mean sizes, down sizing of preparation is required. For this purpose we routinely apply extrusion, using varying cut-off-membranes. Separation of non-entrapped molecules and unwanted residues is performed by centrifugation or ultra-dia-filtration devices.
Large-scale methods for different approaches such as stability studies, in-vitro and in-vivo models, toxicology studies and preclinical studies are still limited. Although in the past big efforts were made only few, industrialized methods are still available. One of these techniques was established in our working group. The so-called Cross Flow Injection Technique is based on the ethanol injection method, investigated by Batzri and Korn. The principle of this method is that lipid compounds solubilized in water miscible solvents, such as ethanol, are injected into a defined buffer system of choice. During this process unilamellar liposomes are formed continuously. In the past, this simple method was less recognized due to the lack of industrial realization. By our investigation we succeeded to overcome the bottlenecks of this method, making this technique attractive for research and production.