The Massachusetts Institute of Technology (MIT) recently published an article in Technology Review titled, “Why is Biomanufacturing so Hard?,” in which they discussed the challenges to biopharmaceutical manufacturing. The article outlines three manufacturing difficulties including contamination risks, maintaining high productivity, and variability in manufacturing runs.
According to the MIT article, biologics are very successful in patients and the market. In 2008 biologics represented 30% of the revenue from the top 100 drugs and that percentage is expected to rise to 50% by 2014. Biologics have advanced medicine and created treatments that simply were not possible before. While they have been hugely successful, they are also more difficult and costly to manufacture than small molecule drugs. Biologics are produced in living cells and are more sensitive to slight changes. Living cells must be grown in conditions that mimic the nutrients and conditions that cells need to thrive and this makes them more susceptible to contamination, fluctuations in productivity, and variability in manufacturing. To compound the difficulties, when biologics are approved by the Food and Drug Administration the manufacturing process is also approved. This is important to ensure safety, but also restricts improvements to the process. According to Charles Cooney, a chemical engineer at MIT, “By the time the drug is in the marketplace, you are working with old technology.” Once a drug has been approved, it is too costly and time-consuming to make process improvements, so new technological advances that could improve the most pressing problems can’t be realized.
Researchers at MIT are working on making biomanufacturing more predictable through new technologies for cell line development and selection of the most prolific cells for manufacturing. Current biomanufacturing includes a process of selecting the best cell lines for cell viability, growth, expression level, and product quality.
In addition to cell line development work, improvements to cell culture media can also address biomanufacturing challenges. In the past, most media and media supplements contained some animal components, some still do. Animal components are undesirable in manufacturing because they are undefined and yield unpredictable results due to high batch-to-batch variation. Animal products also increase the risk of contamination and evoke serious safety concerns, including the risk of viral and prion (the infectious causative agent associated with Mad Cow Disease) contamination. As a result of these challenges, many biopharmaceutical manufacturers moved away from serum and other animal products. To maintain their productivity they looked at other animal-free options such as plant-based hydrolysates, but often these hydrolysates were undefined and exhibited lot-to-lot variability making manufacturing more challenging. To solve the issues of contamination, productivity, and variability, media must have the ability to improve productivity and growth, be animal-free and be defined with lot-to-lot consistency. By improving cell line development and cell culture media many of the most pressing biopharmaceutical manufacturing challenges can be addressed.