Biopharmaceutical Production and Development Unit (BP&DU)
The Biopharmaceutical Production and Development Unit (BP&DU) supports research-associated topics:
Viral vectors and oncolytic viruses
- Large Scale production and purification of parvovirus (vector) stocks for pre-clinical applications or basic research
- Development and optimization of new production, purification and analytic methods with the aim to establish working protocols for GMP-production of virus (vector) stocks necessary for clinical applications and possible market release.
- Accompanying research in two ParvOryx clinical trials with patient tumor and shedding assessment (see: Research - Treat (dkfz.de))
- In the establishment of GMP-produced parvovirus, the unit plays a pivotal role in the interaction and support of various organizations involved in the approval and application of procedures for virus (vector) production under GMP and GLP-conditions. Cooperation with GMP company (IDT Biologika GmbH) and GLP companies (Biogenes GmbH, Eurofins GmbH, Labor Enders & Kollegen)
Bovine Milk and Meat factors
- Production and purification of different BMMF´s in prokaryotic and eukaryotic cells.
- Characterization of BMMF´s regarding quantity, purity, aggregation, stability and activity, isoelectric point (pI), formulation
- Optimization of the process (upscaling, purity)
- Optimization of diagnostic assays in different matrices
- Stability and Stress tests of BMMFs in different formulations
Parasites
- Large scale (up to 5 Liter) production and purification of parasites including optimization strategies
DNA
- Large scale (up to 5 Liter) production and purification of pre- GMP- DNA
Assay-Development, Optimization and Qualification
- Divers immunological, biological and molecular-biological assays (e.g. ELISA, potency, qPCR, endotoxin, stability, deactivation) with standardized SOPs
- Stability and stress tests for possible drug candidates or antigens for diagnostic
- Consulting and technical support for production-related inquiries
Focus of the group lies in:
- Upstream process: establishment, optimization and upscaling of production process
- Downstream process: optimization of purification process according to impurity profile, quality and quantity
- Qualified and validated analysis (quantity and quality)
- Establishment of good process and quality controls
- Safety assessment (i.e. establishment of optimal deactivation protocols)
- Consideration of ecological and economical aspects
- Statistical experiment planning using Design of Experiment approach
Methods-Portfolio
Upstream process:
- Micro- and macrocarrier up to 2.5 Liters for adherent cells
- Suspension (shaked or stirred) Bacteria and Parasites cultures up to 5 L
- Production in 10-layer Cell factories (6360 cm², Corning) or fixed bed bioreactor (4 m²) iCellis nano (Pall) For detailed description see Leuchs et al 2016 and Wohlfarth et al 2021
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Downstream process:
- Clarification (centrifugation, filtration with diverse filters up to 0.2µm)
- Chromatographic purification with ÄKTApure (Cytiva). For H-1PV purification see Leuchs et al 2017
- Sterile filtration and final formulation
Specific qualitative and quantitative Analysis:
- Metabolite analysis (Glucose, Lactate, Ammonia, LDH, etc.) with CEDEX Bio analyzer (Roche)
- Cell and cell cycle characterization with Nucleocounter (Chemometec)
- Photometric, fluorometric and luminometric analytical methods with FLUOstar Omega (BMG Labtech) for e.g. ELISA, immunoassays, protein-, DNA analysis
- Characterization of the product using size exclusion chromatography, 2D electrophoresis, protein profile (WB), endotoxin assessment
- Stability testing as well as establishment of optimal deactivation protocol of H-1PV in regard to regulatory requirements (Frehtman et al; 2023)