Selecting the right expression system is a critical step in the production of recombinant proteins. It’s a decision that impacts not only the quality and quantity of the final product but also the overall cost-effectiveness of the production process. Each expression system has its advantages and limitations. With multiple factors to consider—such as titers, cell line stability, cost-to-yield ratios, and scalability and sustainability—understanding the financial implications of the chosen expression system is key to making an informed choice.
Here, we explore some of the key economic decisions that influence expression system selection, helping manufacturers optimize resource allocation, minimize risk, and maximize the potential for commercial success.
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Titer vs cost
The production of higher protein titers has long been seen as a way to boost production efficiencies, allowing manufacturers to get more product from the same resources. However, while initial improvements in titer can dramatically reduce costs, the incremental benefits become progressively smaller as titers rise. It’s also crucial that increased protein yields don’t overwhelm downstream processing. For instance, if chromatography columns or filtration systems can’t keep up with the higher yield or biomass, the additional protein produced will not translate into cost savings. Manufacturers therefore need to carefully balance process titer with overall process yield and efficiency. While high titers are valuable, they shouldn’t come at the expense of product quality, stability, or downstream processing capacity.
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Stable pools to reduce timelines
The use of stable pools in early-stage bioprocessing has revolutionized how companies approach recombinant protein production. Stable pools enable the consistent and long-term production of recombinant proteins in large quantities, eliminating time-consuming clonal selection processes. By providing a faster route to producing testable quantities of therapeutic products, adoption of stable pools facilitates quicker decision-making and has the potential to shave months off traditional development timelines. While stable pools offer clear advantages in early-stage development, particularly in providing faster and safer routes to clinical validation for new therapeutic products, regulatory agencies typically require clonal cell lines for late-stage clinical trials and commercial production due to their increased consistency and traceability. But for companies looking to reach key milestones faster, stable pools present a cost-effective strategy to reduce the risk and financial burden of early-stage clinical development.
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Flexibility to optimize reagents
The cost of reagents, such as growth media, buffers, and purification materials, can quickly escalate in recombinant protein production, representing a significant proportion of overall production costs. The challenge is to maximize yield while keeping reagent costs under control. To address these challenges, developers are deploying multi-faceted approaches to optimize reagent use for specific cell lines and antibody products and maximize high-quality yields. However, it’s important to consider the trade-offs of this approach. Using higher-cost reagents might lead to better yields, but these benefits need to be weighed against overall finances and long-term cost-effectiveness.
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Scalability and sustainability
The shift toward sustainable therapeutic protein production represents a pivotal transformation in the biopharmaceutical industry. Companies are rethinking their production strategies to reduce their environmental impact, minimize resource consumption, and optimize energy efficiencies. The adoption of intensified and continuous manufacturing processes is one example. Unlike traditional batch processing, continuous manufacturing can significantly reduce facility footprint, cut upfront capital investment, and enhance production flexibility. Similarly, single-use technologies offer cost benefits by reducing contamination risks and enabling scale-up with lower upfront capital expenditure. However, single-use technology also generates solid waste, so companies need to consider its advantages against disposal costs and impact on the environment. Achieving truly sustainable biomanufacturing requires continued collaboration between different stakeholders. By integrating sustainability into decisions to define optimal product supply scalability, manufacturers can reduce risky upfront infrastructure investments and improve their environmental impact while saving on overheads and potentially gaining a competitive edge in an increasingly eco-conscious market.
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Making the right choice
Expression system selection is a critical decision in the production of recombinant proteins, with far-reaching financial implications. Carefully weighing up the impact of factors such as titer, cell line stability, cost-to-yield ratios, and sustainability is essential for making financially viable decisions. To learn more about these considerations, download our whitepaper: Maximizing returns in biotherapeutic investment: Financial considerations for expression systems’.
