Enhancing efficiency and reducing costs in biopharmaceutical manufacturing
In the rapidly evolving biopharmaceutical landscape, increasing process efficiency while reducing manufacturing costs is a priority. As such, innovations in upstream and downstream processing that enable higher productivity, greater flexibility, and more cost-effective solutions for monoclonal antibody (mAb) production are crucial, even as many mAb products continue to achieve commercial acceptance. Recent advancements in perfusion media, high-density cell banking, and downstream intensification are shaping the future of biologics manufacturing, paving the way for more cost-effective, efficient production.
Next-generation media in high-density cultures
Upstream intensification has advanced with the development of a chemically defined medium and feed system for CHO-based fed-batch processes. Gibco Efficient-Pro Medium is a single medium compatible with multiple CHO cell variants, which can be paired with two cell line-specific feeds: Gibco Efficient-Pro Feed 1 or 2. Designed using omics-driven insights, Gibco Efficient-Pro Medium can boost specific productivity, helping to enhance antibody yields and process efficiency.
For perfusion applications, Gibco High-Intensity Perfusion (HIP) CHO Medium supports multiple CHO lineages, enabling high cell densities and productivity at lower perfusion rates. Its flexible rehydration concentrations allow adaptation to various perfusion strategies, aimed at improving process consistency and scalability while maintaining optimal cell health.
The right bioreactor system likewise can play a crucial role in upstream intensification. Thermo Scientific DynaDrive Single-Use Bioreactors (S.U.B.) offer superior power mixing, mass transfer, and scalability, with high turndown ratios (10:1 to 20:1) that enable easy N-1 seed train steps in the same vessel. Available in sizes from 50 L to 5,000 L, the DynaDrive S.U.B. helps reduces the number of seed train steps and supports direct inoculation from high-cell-density banks, facilitating the simplification of workflows and driving process efficiency. The system’s optimized design also helps to enhance gas transfer and mixing, promoting robust cell growth and productivity across scales.
Ultra-high density cell banking for intensified seeding processes
Ultra-high cell density (UHCD) cell banking is revolutionizing bioprocessing by eliminating traditional inoculum expansion steps and allowing direct inoculation into bioreactors. Conventional multistep workflows rely on shake flasks, wave-mixed bioreactors, or stirred bioreactors to gradually expand cultures before transferring them to production-scale systems. By contrast, cryopreserved high-density cell banks enable direct inoculum to 50 L or 500 L DynaDrive S.U.B., aiming to significantly reduce workflow steps, time, and resource requirements.
In a case study by ZHAW Zurich University of Applied Sciences, researchers bypassed traditional seed train steps by inoculating a 50 L DynaDrive S.U.B. directly from a cryovial containing Gibco ExpiCHO-S cells in UHCD suspension. A single 4.5 mL cryovial was thawed and transferred into the bioreactor with an initial volume of 5 L, which was gradually increased to 38 L over six days using Efficient Pro Medium, followed with daily feeding with Efficient Feed 2. Comparative analysis showed that the DynaDrive S.U.B. achieved similar cell growth kinetics and IgG titers to conventional shake flask processes with consistent product quality attributes such as charge variant distribution and glycosylation patterns.
By eliminating traditional inoculum expansion, the seed train timeline was reduced from ten days to just four, helping to accelerate overall production. Furthermore, direct bioreactor inoculation supports continuous perfusion setups, offering additional process flexibility.
The impact of high-density cell banking on upstream operational efficiency
The adoption of high-density cell banking facilitates mAb seedtrain intensification by helping to reduce multiple scale-up steps. This approach can reduce seed train duration from 21 days to just 6 days, contributing to improve operational efficiency as well as labor and resource savings. Traditional seed trains require extensive manual handling, with operators investing 66 hours of hands-on time over 21 days. High-density cell banking can reduce this to 37 hours over 6 days, helping to decrease the required workforce from 14 personnel to eight. Moreover, this can reduce consumable costs and help optimize the use of facility space for other critical operations by eliminating intermediate steps.
The high turndown ratio of DynaDrive bioreactors allows direct inoculation of the N-1 bioreactor, while the perfusion process facilitates rapid culture expansion before transfer to production-scale systems. This can reduce turnaround times, allowing for more frequent batch production and increased equipment utilization. In some cases, intensified workflows enable an additional batch per year.
Downstream intensification: Improving efficiency and reducing costs
While upstream intensification drives productivity, downstream processes must keep pace to avoid bottlenecks. MabCaptureC Affinity Matrix features a high-binding-capacity protein A resin that enables multiple cycles, helping to revolutionize capture chromatography. This allows manufacturers to achieve the same purification efficiency with less resin, which can significantly lower costs of goods. In addition to enhanced protein A capture, flow-through chromatography strategies can optimize purification efficiency. Using POROS hydrophobic interaction chromatography (HIC) in flow-through mode allows for high aggregate removal while reducing buffer consumption by 60% when compared to a cation exchange resin. This not only helps to simplify operations but also contributes to sustainability goals by minimizing waste.
A new era in bioprocessing
By integrating these advancements—Gibco Efficient-Pro media and feeds, HIP-CHO perfusion media, DynaDrive bioreactor systems, high-density cell banking, and advanced resins—biomanufacturers can aim to achieve unprecedented levels of manufacturing productivity. The combination of optimized upstream processes with innovative purification strategies paves the way for cost-effective, high-yield biologics production. As these innovations continue to evolve, the industry moves closer to fully intensified bioprocessing, ultimately aiming to deliver therapeutics to patients faster and more affordably.
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