Master-Studiengang Medical and Pharmaceutical Biotechnology

• the ethics of end-of-life decision making
• Embryo screening
• Predictive medicine
• Transplantation medicine
• Legal issues
• Stem cells
• Assisted dying
• Moderated discussions on relevant topics

Students learn about the processes involved in preparing and managing fermentation with microbiological organisms and mammalian cells. The lectures will cover:

• Different useful Host Organisms, their advantages and disadvantages
• Fermentation kinetics (e.g. product formation rate, glucose fermentation rate, oxygen requirements and energy input)
• Calculations describing fermentations (Mass Balancing, Feed Calculations, Heat Generation and Dissipation)
• Fermentation process development and scaling based on different parameters

Students perform calculations of parameters for reaction kinetics, feeding and heat dissipation based on typical sets of information given in the industrial environment.

• Overview of the most frequently used protein production organisms for research and industrial applications
• General principles of protein production
• Impact of biochemical properties of proteins, their amino acids and chemical modifications on protein production and protein purification
• Comparison and discussion of standard protein purification strategies

• Demonstration of the principles of gene expression/protein production in the Pichia pastoris production organism demonstrated using a cytokine
• Purification of a cytokine
• Using this protein to learn about typical methods of biochemical analysis for the characterisation of proteins
• Specific content includes transformation of yeast cells, expression of cytokine genes from an inducible promoter, breaking open cells and obtaining cell extract, purification of the desired protein using affinity chromatography, defining the protein concentration, visualisation of the protein using western blotting, tests to characterise the bioactivity of the protein.

• Specifications (facilities, product, instrumentation), analytical systems (e.g. sensors)
• Costing and design of utility systems (gas and air supply, water for injection, cooling and heating mediums)
• IQ, OQ, PQ, URS, process qualification
• Inspection, acceptance and commissioning of production facilities (cleaning, water runs, sterility and conformity testing)
• Process standards
• Media design (complex, defined) including media preparation and sterilisation techniques (in situ, ex situ)
• Inoculum preparation and fermentation management; microbial organisms vs. mammalian cells
• Fermentation kinetics (e.g. product formation rate, glucose uptake rate, oxygen requirements and energy input)

• Overview of the development of company specification standards based on national and international standards
• Specifications
• Standards (open, proprietary, basic, product, planning and service)
• Distinction between specifications, standards, regulation and company standards
• The standardisation process
• National standards (ÖNORM, DIN)
• International standards (ISO, CEN)
• Structural design of standards
• Dealing with national and international standards in the course of routine work in the biotechnology industry
• Legal aspects of standardisation
• Distinction between standardisation and accreditation
• The accreditation process Students complete an exercise on the specification of part of a facility using the relevant national and international standards.

• The haematopoietic and lymphoid system
• Genetic variability in the immune system
• Antigen recognition by B-cell and T-cell receptors
• Antigen presenting cells (DCs, macrophages, B-cells), cytokines and chemokines
• Innate immune response (complement, macrophages, NK cells)
• Development and classification of lymphocytes
• Cell-mediated and humoral immune responses
• Primary immune response and memory cells
• Resistance, autoimmune disorders and transplants
• Allergies and hereditary immune deficiencies
• Viral and bacterial infections
• Treating protozoan and fungal diseases
• Immunology research methods

• The ageing process in cells
• The ageing process in living organisms
• Theories and molecular mechanisms of ageing
• Genetic programming for ageing
• Environmental factors and genetic predisposition
• Premature ageing: selected examples and molecular causes of the condition
• Lifestyle, stress and hormonal status
• Age-related diseases and their cause

• The history of cancer research
• Molecular causes of cancer
• Genetic changes and their causes
• Fundamental molecular features of cancer development
• Multi-stage process of cell transformation
• Tumour-stromal interactions
• Metastasis
• Tumour immunology
• Tumour metabolism
• Targeted therapies and personalised medicine

• Fundamentals and mechanisms of embryogenesis
• Early embryogenesis and topological patterning of the axes (fertilisation, initial cell division, morula, gastrulation and neurulation)
• Late embryogenesis (organ development from ectoderm, mesoderm and endoderm)
• Embryonic models for drug development
• Somatic cell reprogramming and regenerative medicine

• Precision and reliability of confidence limits
• Significance tests (T-tests, chi squared test, F-test and non-parametric alternatives)
• Variance analysis (parametric and non-parametric)
• Trend analysis
• Analysis of contingency tables

• Biomolecules: basic biochemical and biophysical principles
• Structural alignment of biomolecules
• Experiment-based structural determination of biomolecules
• Predicting biomolecular structural features
• Modelling the 3D structure of biomolecules
  • Force fields
  • Conformational analysis methods
• Principles and common methods of drug design

• The concept of systems biology
• Areas of overlap with other disciplines and network theories
• Forthcoming high-throughput technologies
• Interactions between components of cellular systems
• Applications of systems biology strategies for the development of therapies and identification of drug targets

• Pharmaceuticals legislation in Europe and the US
• Definition of pharmaceuticals and important distinctions
• Development and lifecycles of pharmaceuticals
• Quality aspects of pharmaceuticals, safety and efficacy
• Structure and content of specialist and patient information
• Pharmaceuticals approval process in Europe and the US
• Maintaining approval
• Generic drugs, internet and product liability
• Pharmacovigilance
• Pharmaceuticals marketing and sales
• Medical Products Act: requirements for medical products (harmonised standards, CE marking, carrying out conformity assessments)
• Classification of medical products

• Quality management systems, standards and guidelines, comparison of ISO, ICH and GMP
• Statistical methods and elements of QM
• Principles of QM and its elements
• Auditing quality management systems; principles and methods

• Statutory quality assurance regulations in the pharmaceutical industry
• OECD Principles of Good Laboratory Practice (GLP); applicability of the study plan and study report
• EU Guide to GMP and CFR 210/211; applicability of the GMP regulation
• Setting up a product facility
• Regulations relating to personnel, production, documentation, quality control and QM
• QM during the biotechnological development process
• Testing of active substances and additives
• Formulation development, developing production processes; form of administration and container closure systems
• Microbial controls; compatibility
• QM in the pharmaceutical industry: ICH Q8,Q9 and Q10

• Risk management in accordance with ICH Q9 and other guidelines
• Methods of risk assessment: preliminary risk analysis:
  • Preliminary hazard analysis (PHA), event tree analysis (ETA), failure mode and effect analysis (FMEA), fault tree analysis (FTA), HAZOP (hazard and operability studies)
  • Corrective measures: HAZOP
  • Critical control point hazard analysis and critical point methodology (HACCP)
  • Risk management and reliability planning, risk assessment for development projects, environmental risk assessment

• Key aspects of project management in the pharmaceutical industry
• Portfolio management
• Corporate strategy
• Project structure planning, work packages, project network diagrams, critical path analysis
• Managing integration
• Developing biotechnological pharmaceuticals

• Clinical trials: phases and management
• Setting up and monitoring clinical trials
• Quality standards for clinical trials
• Interface management during trials, academic versus industry-funded research
• Risk-benefit analysis
• Investigational product management
• Project management in clinical trials

• Gain and loss of function experiments (knockdown, overexpression)
• Cell fractionation
• Flow cytometry
• Finding evidence of post-translational modifications
• Immunoprecipitation/co-immunoprecipitation
• Mass spectrometry
• Chromatin immunoprecipitation
• Electrophoretic mobility shift assay

• DNA and RNA isolation and analysis
• cDNA synthesisv
• Real-time quantitative PCR (qPCR) with SYBR® Green and TaqMan™ probes (comparison)
• Gene expression analysis
• Allele-specific qPCR
• SNP analysis
• High-resolution melting curve analysis
• PCR RFLP
• Pyrosequencing

• Methods of DNA/RNA isolation and analysis of nucleic acids
• Methods of real-time qPCR (including primer design in the PC lab) and their applications (gene expression analysis, allele-specific qPCR)
• Methods of identifying genetic variations (e.g. sequencing, pyrosequencing and massive parallel sequencing) – personalised medicine
• Analysis of epigenetic modifications
• protein interactions (ChIP, EMSA, DNase footprint)
• Flow cytometry
• Cell fractionation
• Analysis of post-translational modifications (phosphorylation, glycosylation, ubiquitination)
• Loss and gain of function experiments (incl. CRISPR/CAS, knockdowns, knock in/out, LoxP/Cre system and overexpression)

• Updating CVs and covering letters
• Career and internship opportunities in industry and research
• Coaching support with research semester applications

• General pharmacology
• Quantifying the effects of pharmaceuticals
• Concentration-effect relationships for in vitro and in vivo models
• Characterisation of agonists and antagonists
• Molecular mechanisms of action and target proteins in pharmaceuticals
• Types of receptor, receptor subtypes, pharmacodynamic and pharmacokinetic causes of resistance
• Pharmacological studies in preclinical pharmaceutical development
• Use of animal models
• Pharmacological studies in clinical development
• ADME: fundamental principles of resorption, distribution, metabolism, and excretion of pharmaceuticals
• Determining ADME parameters in practice
• Phases of clinical trials
• Preparation of investigator's brochures

• Analysis of the business environment (analysis of the market, environment, location as well as legal, political and technical considerations)
• Choice of legal form
• Drawing up a business plan

• Designing a cost accounting and cost-type system
• Cost-centre accounting
• Cost unit accounting (calculation), analysis of operating profit

• Budgeting
• Budgets and financial plans
• Objectives, tasks and functions of management control
• Management indicators
• Analysing annual financial statements
• Management case studies

• Purification steps for biopharmaceutical products and methods for shifting from laboratory-scale to pilot-plant or production scale processes
• The four main operations in downstream production: removal of insolubles, product isolation, product purification and product polishing
• Filtration, lysis and flocculation, sedimentation, extraction, chromatography and adsorption, precipitation, crystallisation, spray drying and centrifugation
• Dimensionless indicators and an introduction to dimensional analysis
• Calculation exercises: characterisation of individual purification steps and scaling up elements of facilities
• Application of scale-down models for process modelling to resolve problems with current production processes

• Fermentation of single cell organisms
• Operating process control systems
• Working with bioreactors under sterile conditions
• Offline measurement methods
• Online measurement methods
• Calculating fermentation control parameters
• Preparing defined and complex media
• Sterile addition methods
• Troubleshooting
• Analysis of fermentation parameters
• Evaluating parameters to arrive at a process management approach
• Setting up, dismantling and maintaining bioreactors
• Analytical methods of evaluation (e.g. electrophoresis, FPLC and ELISA)
• Cell disruption methods

• Fermentation of extremophile organisms
• Co-cultivation of organisms
• Mammalian cell fermentation
• Use of alternative carbon (C) sources with specialised organisms
• New types of host systems (content selected by the available visiting experts)

• Theoretical principles and technical options in process control
• Theoretical principles of the measurement, control, regulation, properties and operation of probes
• Selecting and monitoring critical measurement parameters
• Automated process definition
• Process mapping
• Input-process-output diagrams
• Process flow diagrams
• Value stream mapping
• Top-down charts
• Swimlane diagrams
• Process performance
• Process capability and stability
• Cp and Cpk
• Sigma quality levels
• Simulation calculations and practical exercises

• Fundamentals of equipment, test and process validation based on legal guidelines and using practical examples
• Design qualification
• User requirements specification
• Functional specifications
• Installation qualification (IQ), drawing up IQ plans
• Operational qualification (OQ)
• Drawing up OQ plans
• Performance qualification
• Retrospective qualification
• Requalification
• Maintaining qualification status
• Process validation
• Defining the scope of a validation, risk analysis
• Validation master plan and validation matrix
• Cleaning validation
• Optimising cleaning procedures and drafting cleaning policies
• Cleaning validation master plan
• Defining the scope of validation
• Acceptance criteria, computer validation
• Prospective and retrospective validation, validation master plan
• Operating computerised systems

• Pathology of selected example illnesses
• State-of-the-art therapy strategies
• Developing new therapy concepts
• Standard strategies and future approaches to vaccination
• Development and application of the latest mouse models

• Drug discovery equipment (imaging, detection in microplate format, detection of fluorescence, time-resolved fluorescence spectroscopy, luminescence, absorption, pathway analysis, assay quality parameters)
• 3D cell culture techniques for drug discovery
• Development of small molecular weight compounds
• High-content screening and cell cycle checkpoint drug targets
• Marine organisms as sources of new therapeutic agents

• Stem cells for therapeutic applications
• Principles of cell and tissue therapy
• Principles of gene therapy and its applications
• Tissue engineering techniques
• Examples of cell and tissue therapy applications

• Key properties of immune cells for immune therapy
• Immune therapy techniques
• Examples of immune therapy application

• Production of a state-of-the-art bioactive, therapeutic biomolecule
• Quality control of this product
• Characterisation of the product’s functionality

• Literature research on the latest trends in the relevant fields
• Reviewing the relevant literature
• Presentation of results
• Discussion of the contents of the literature selected

• present and discuss their research question, research design and results in a manner that is appropriate to the target audience
• make links to scientific findings from their specialist subject and adopt them as part of innovative approaches in practice and research
• interpret the relevant data collected
• apply theories and principles to address specific topics and discuss and evaluate them critically
• effectively communicate problems, ideas and solutions and defend the findings of their thesis
• present their chosen topic in a multidisciplinary (research) context
• identify links with relevant topics/subjects from the degree programme and their profession or fields of research
• apply specialist knowledge to various related fields or connected areas
• apply theories and concepts to solve problems and find new approaches
• defend solutions and approaches and effectively present their ideas and arguments