Cutting Down Process Time and Costs

Because the biopharmaceutical industry operates as an industry rather than a nonprofit, the bottom line is an important consideration in every aspect of product design. From laboratory automation methods that speed discovery to streamlined manufacturing processes that incorporate the themes of operational excellence, Lean manufacturing, and quality by design, the industry is undeniably focused on minimizing cost and maximizing revenue.

At the BioProcess International European Conference and Exhibition, the Scale-Up and Manufacturing track will focus on economic strategy and technology transfer for outsourcing and contract manufacturers, process development and management strategies for operational efficiencies, protein aggregation, scale-up of cell culture and fermentation for production quantities, and strategies for optimizing recovery and purification.

Christopher Dale, head of microbial technology at Lonza, USA, will discuss the impact of technology in microbial fermentation on volumetric capacity and the cost of goods. His talk will look at factors that play into economic analysis for the production of bulk drug substance.

“If you do cost analysis, the proportion of manufacturing costs to total cost of finished goods is somewhere between 10 and 20 percent,” said Dale in an interview with BioProcess International. Therefore, creating more efficient manufacturing processes would reduce the cost of finished products. This is the current economic battle that product manufacturing groups are involved in: slicing away the excess, and leaving a lean manufacturing process. Microbial fermentation has unique challenges and, according to Dale, holds unique promise in this area.

Microbial systems have a long history of expressing protein products at high volumetric productivities in the multiple grams-per-liter range. However, Dale explained that with the development and refinement of bacterial and yeast systems, these productivities are expected to improve greatly in the next five to 10 years through use of appropriate expression systems and mechanisms for extraction and recovery of soluble material within cells.

Mammalian expression systems have benefited in recent years from the adoption of platform approaches. These involve setting up processes that can be applied to various products, reducing process development timelines and ultimately speeding time-to-market.

“The approach to process development has not changed in microbial expression and purification because of the diversity of systems,” said Dale. “However, once platform approaches are adopted for microbial expression and purification, then we can see the development timelines could be greatly accelerated because a toolbox of appropriate systems will be in place in an integrated package.”

Dale’s talk will focus on answering the question of what is an appropriate volumetric capacity for a microbial production facility and how this relates to product category, expression technology, processing platform, and facility cost. Understanding these aspects of manufacturing will help people make better business decisions.

Manfred Brunen, director of production at Novartis Vaccines and Diagnostics, will also focus on the bottom line in his case study presentation on technology transfer, industrialization, registration, and validation of a novel cell-culture–based vaccine production process. The vaccine that Brunen will talk about produced in a production-optimized licensed MDCK (Madin-Darby canine kidney) cell culture system. Novartis has used this licensed cell line for over 15 years, having chosen it for this vaccine product because of familiarity and comfort with its high productivity and proven safety.

“Improving the productivity of the cell line is part of the development process, and the know-how of the development people that worked with this cell lines is what makes it superior to other cell lines in the end,” explained Brunen in an interview with BioProcess International. “To start with a new cell line is a higher risk and requires more effort and may take longer than using an established cell line.”

Brunen also discussed the role that analytical and risk-based tools play in manufacturing efficiencies and process development. “What I see is that the idea of using statistical approaches for design of experiments is something that will contribute to the biotech industry’s ability to accelerate product development and improve revenue. In production, I clearly see that there is more use of risk analysis in processes design in the recent years.” Brunen noted that the role of failure modes and effect analysis (FMEA) in quickly and systematically analyzing process deviations will also be important.