The bioprocessing sector is rapidly growing to encompass more complex biotherapeutics and bioprocesses, each of which come with their own unique challenges. Compared with the more established world of protein therapeutic development, the path from advanced therapy medicinal product (ATMP) discovery to biomanufacturing is far less traveled. ATMP development is a new but rapidly growing field that aims to develop medicines for human use, based on genes, tissues, and cells. As ATMPs and the processes required for their manufacture are relatively new, their unique challenges are still being identified.
In addition to the many unknowns associated with cell and gene therapies, manufacturers must navigate the standard bioprocessing challenges; speed to market, bioprocess optimization, scaling, logistics, and safety are among the many issues to be considered. As the road to biotherapeutic and vaccine development is long, challenging, and expensive, it pays to take a step back and identify key opportunities for creating a more streamlined and effective approach to production.
Identifying key challenges in bioprocessing
Improving and optimizing cell culture media formulations represents one of the key challenges in the field. Manufacturers are working to produce the required dose at maximum speed, while minimizing the use of expensive materials. When producing a therapeutic product of desired yield and quality, cell culture media formulations play a critical role in allowing high cell densities to be reached.
The key to high-performing cell cultures is effective nutrient utilization through a balanced cell culture medium formulation. Improving that process input represents a major opportunity for manufacturers to become more efficient and is therefore a key area of development. For autologous therapies, where the therapy is based on the cells of one patient, one piece of equipment might be required to make one treatment for one individual. Supporting technologies, along with the optimization of cell culture processes, are therefore going to be essential to this field.
Harnessing technology to advance bioprocessing
While it has somewhat lagged behind other industries, the biomanufacturing sector is increasingly adopting new technologies that support a more efficient future. This is partly driven by the complexity of new biotherapeutics. When developing a bioprocess for ATMPs, a phenomenal number of variables must be monitored and optimized. Subsequently, process analytical technology (PAT) is being implemented to help define processes and improve reproducibility. Artificial intelligence (AI) and machine learning (ML) are expected to play a significant role in PAT data analysis and will become a critical tool for optimizing production and enhancing product quality.
Organizations such as AIDPATH, the Academia and Industry Collaboration for Digital Pathology, are pursuing AI to support new therapies. As different biomarkers and cellular phenotypes influence how a media composition should be optimized, the European consortium is developing a system capable of integrating patient-related data and biomarkers into the therapy manufacturing process. Specifically, AIDPATH is focused on the use of AI to manufacture chimeric antigen receptor T-cell therapies, alongside other advances in digital pathology. Those in the industry look forward to seeing this become an AI-driven reality.
Shortening process development allows a faster entry to market and reduces development costs—which ultimately, makes therapies more accessible for patients.
The power of a strong partnership
Within the biopharmaceutical sector, standardized processes smooth the transition from discovery to production. For monoclonal antibodies, the handover from the discovery phase of cell line engineering to process development is well established. In contrast, the transition from ATMP discovery to manufacturing is far less defined; guidelines are yet to be established for many bioprocessing stages, including formulation, packing, and protocol and process optimization. Furthermore, ATMPs also require a higher level of media optimization, and the regulatory requirements are yet to be clarified. Overall, ATMPs are highly complex, and the field is still in its very early days. The successful transition from ATMP discovery to manufacturing, therefore, requires a high level of expertise and close collaboration between the two groups. By taking a collaborative approach and committing to a high level of knowledge exchange, developers, manufacturers, and suppliers can move the ATMP field forward together—as is being done with protein therapeutics.
Throughout the recent pandemic caused by the novel coronavirus SARS-CoV-2, speed to market has been shown to have a significant bearing on public health. When working on process intensification and continuous processing, partnering with the right supplier is therefore critical. As markets change, manufacturers sense a need for their vaccine or biotherapeutic, and must respond rapidly to the changing demands. Achieving this, however, requires robust supply chains. New production targets may require new equipment, raw material, and instruments—all of which must be qualified to ensure quality. In response to the pandemic, critical suppliers have worked closely with customers to ensure new raw materials could be qualified quickly to meet the surge in demand. In some cases, suppliers of major components, such as cell culture media, have expanded global capacity to ensure continued support of high quality, large-scale production.
Working with the right partner can drive innovation in the field, as even the simplest improvement can improve efficiency. For instance, vendors have realized cost savings for customers by eliminating steps in the media preparation process, changing packing configurations, and altering the way media is hydrated. Evidently, having a fresh set of expert eyes can be critical to removing development bottlenecks. It is important, therefore, to select a partner that is willing to work as an advisor at every phase. Ideally, your partner will be there to tour facilities to identify where processes can be optimized—from goods receiving to incoming quality control, to media and buffer preparation through to bioprocessing.
Moving forward together
In recent times, vaccines and therapeutics have been brought to the market at an unprecedented speed, highlighting the importance of collaboration and robust supply chains. Increasingly, a greater need has been seen for optimized processes, strong partnerships, and suppliers who work with customers to identify and eliminate bottlenecks in development and manufacturing. Working with a flexible, responsive partner willing to provide timely advice can be a critical catalyst for driving innovation and finding solutions to complex challenges.