There is growing interest in the development of integrated continuous bioprocesses for the production of important biotherapeutics due to the potential for enhanced productivity, greater flexibility, and improved product quality.  The transition from batch to continuous bioprocessing requires a major re-thinking of the downstream purification process, creating exciting new opportunities for membrane technology. This talk will focus on the use of continuous countercurrent staged membrane systems for initial product capture and for final formulation. Continuous Countercurrent Tangential Chromatography (CCTC) provides truly continuous steady-state product capture and purification using a column-free system in which the chromatographic operations are conducted on a flowing slurry using hollow fiber membranes to control the resin flow. Results using a Protein A affinity resin show high levels of host cell protein removal from a monoclonal antibody product, with the countercurrent staged providing significantly greater throughput with improved product yield and purification. A similar approach can be used for continuous selective precipitation of monoclonal antibodies, completely eliminating the high cost of the affinity resin. Countercurrent staged diafiltration has been developed as a new strategy for providing high levels of buffer exchange in a single-pass continuous format.  These examples highlight how one can adapt membrane systems to continuous bioprocessing, providing exciting opportunities for improved manufacturing of high-value biopharmaceuticals.

Learning Objectives:

1. Explain the benefits of implementing continuous bioprocessing.

2. Identify the opportunities for using countercurrent staging to enhance the performance of downstream processes.
 

The vast structural diversity of proteins is responsible for their functional versatility, but also makes their expression and purification a demanding task. Tagging proteins with affinity tags can overcome the complexity of conventional purification by enabling affinity chromatography. An overview will be given for the purification of tagged proteins and then a purification system using a circular permutated caspase will be described in detail. It has been developed for process fusion protein processing to generate an authentic N-terminus for all 20 amino acids. The system employs widely available affinity chromatography resins, and a simple process can be used regardless of the specific nature of the protein of interest.

Learning Objectives:

1. Explain the processing of fusion proteins and non-mAb proteins.

2. Discuss the generation of an authentic N-terminus.

3. Discuss the effect of enzyme kinetics on process of fusion proteins.

The application of modeling tools to better understand and control bioprocess development and manufacturing has become a hot topic within the last few years. However, what do we actually need? Is it just about data and powerful modeling algorithms, or is there more to consider to accurately describe a process and transfer the knowledge and model structure from early-stage development until manufacturing?

Learning Objectives:

1. Discuss the overall goal of process modeling.

2. List experimental design concepts.

3. Discuss different modeling approaches for different requirements.

The design, optimization and troubleshooting of industrial bioprocesses are still largely based on empirical knowledge. Thus, the goal and motivation is to base these processes on a comprehensive view of the physical and chemical processes within the reactor. By applying the latest numerical algorithms and graphical processing units (graphics cards), the inner workings of the bioreactor can be studied in detail for the first time. This lays the foundation for new apparatus designs as well as for optimization of operating parameters and process characterization on the computer. Using the example of aerated stirred bioreactors, I will show how this new simulation tool integrates and accelerates your workflow from lab to market. 

Learning Objectives:

1. Explain the benefit of having a scale-up method based on first physical principles.

2. Define the usage of new CFD tools for accelerating the path from the lab to the market.

3. Identify areas where simulation can help.

Viral Vector gene therapy has been the focus of intense research driven by the safety profile and several clinical breakthroughs. As of March 2022, there are two viral vector gene therapies approved and many are in active clinical trials. The expected increase in demand for specific viral vectors still poses many challenges. The current talk tries to summarize the key aspects related to Research and development needs and Chemistry, Manufacturing and Control (CMC) efforts to help this growing demand. We will primarily discuss applying the different orthogonal bioanalytics to identify, monitor and control Critical Quality Attributes (CQAs) during the process development activity.

Learning Objectives:

1. Discuss different next generation bioanalytics applications.

2. Discuss unique challenges in implementing the new generation bioanalytics application.

3. Discuss and determining different Critical Quality Attributes (CQAs) for process development.

Currently over 95 % of pharmaceutical products and transport fuels are derived from petroleum. Sustainable alternatives are critical to achieving net-zero emissions without detriment to quality of life. The blockbuster chemotherapeutic Taxol is naturally scarce, difficult to extract, and their chemical complexity often hinders total synthesis. Industrial scale production is therefore a monumental challenge. Microbial biosynthesis is an alternative, sustainable production route, which has been widely reported at laboratory scale. However, the translation of these breakthroughs to industrial bioprocesses remains a critical bottleneck, specially towards the recent shift into continuous flow operation. This work will exemplify an accelerated bioprocessing strategy to optimise, scale up and move towards continuous flow production of these valuable natural products using an integrated downstream/upstream continuous flow bioprocess based on solid/liquid extraction of the natural high value compounds.

Learning Objectives:

1. Discuss the advantages of using of microscale tools mimicking large scale conditions to optimize a microbial cell factory.

2. Discuss the advantages of using an integrated bioprocess approach using solid/liquid extraction to enhance the production of natural products.

3. Applying in situ solid/liquid extraction methods to recover high value compounds in microbial cell factories.

Biopharmaceuticals produced with mammalian cells are the key drivers for the medication of former untreatable diseases. The development of their production processes is still challenging because of regulatory requirements and complex and sophisticated process strategies. Development and scale-up of cell culture processes are still mainly based on expert knowledge, one-factor-at-a-time or experimantal Design of Experiments approaches. This significantly increases the time and costs and simultaneously limits the obtained knowledge.

New design and process control strategies mainly based on mathematical process models are en route from academia to industry. The key component is a model, which aims to describe the real phenomena as simple as possible and as accurate as necessary. Model-assisted methods can therefore increase the process understanding, process control and monitoring and shorten the development times for cell culture processes. 

Learning Objectives:

1. Discuss the potential of a model-assisted process design for a pharmaceutical production processes.

2. Explain coupling of statistical design of experiment (DoE) methods and mathematical models.

3. List examples for model-assisted DoE for the reduction of experimental effort as well as the model-assisted interpretation and evaluation of process management strategies.

In the last decades, the upstream processing in biopharma industry has been revolutionized regarding the production of bioactive materials such as monoclonal antibodies, proteins and biotherapeutics. More and more cell lines are produced with an aim to increase the productivity and quality of biologics produced. For instance, the mammalian cell lines have gained extreme importance in production of recombinant proteins for different applications. This is in general because of the fact that mammalian cell lines allow proper protein folding and post-translational modification. Although, the process itself starts with introduction of a “gene of interest” in to the cell line, there are a number of factors which needs to be taken in to account before claiming the cell line for biologics production. 

The key factors which drive this process are selection of a suitable cell type, stable cell line development, cell culture media optimization and bioreactor control strategies. 

This talk will focus on the current strategies in stable cell lines development, selection of suitable media for biologics production from cell lines and the current advances in the field of upstream bioprocessing using cell lines. 

Learning objectives:

1. Explain how cell lines are produced and selected for biologics production.

2. Discuss what critical role the media for cell cultivation play in upstream processing.

3. Discuss what the new technologies are that can better the quality of bioprocessing as well as shorten the time for cell lines development.