The development of biopharmaceuticals is expanding at an unprecedented rate, as the industry now comprises around 20 percent of the global pharmaceutical market. This momentum stems primarily from an escalating demand for advanced therapeutic treatments for both previously untreatable chronic illnesses and conditions resulting from an aging population. The appeal of biopharmaceuticals also reflects a shift toward precision medicine, as the unique molecular complexities of biotherapeutics tend to offer greater targeting capabilities and fewer side effects, aligning with growing consumer demand for better healthcare outcomes.
This combination of factors means that biopharmaceuticals are opening doors to therapeutic approaches that were once out of reach with traditional small-molecule drugs. However, the impressive advances made in the sector often come with a range of critical challenges in process development. Even though each drug substance is unique, there is a common set of hurdles that each biomanufacturer faces during every process development journey. These can sometimes be related to the stability, solubility and purity of candidates, as well as bioprocessing hurdles, such as difficulty scaling up, low yields, the high cost of goods and even the need for complex characterisation methods. Taking just one of these factors as an example, scaling up production demands a high level of technical expertise and often imposes considerable constraints. These challenges can make the journey to the clinic a complex and resource-intensive process every time a new drug candidate is investigated, especially the complex ones. For instance, proteins are a highly diverse molecule class, defined by unique amino acid sequences, complex three-dimensional structures, specific post-translational modifications and, sometimes, specific cofactor requirements. This variability demands a highly customised approach to protein production, which often results in prolonged development timelines and elevated costs, and hinders the transition from discovery to larger-scale production.
Core Bioprocessing Challenges
As the biopharmaceutical sector grows, tackling the complexities of bioprocess development has become essential, and among the most pressing challenges for biomanufacturers are instability, low yields, and issues with purity and solubility.
Instability
Stability is a crucial factor in biopharmaceutical production, not least because instability of the final product frequently results in a shorter shelf life, limiting the timeframe within which biologics can be safely administered. Proteins can become biologically inactive or even provoke immune responses in patients when they lose their structural integrity, diminishing their therapeutic efficacy. They are also susceptible to aggregation, degradation, denaturation, or other structural alterations that can arise at various stages of the manufacturing process, from initial fermentation to final drug formulation. These issues can be mitigated using various approaches, including optimising cell lines, adjusting expression conditions, modifying amino acid sequences, and incorporating excipients or stabilising agents. However, this inevitably adds layers of complexity to the development process and ultimately increases manufacturing costs.
