The Biologics Bottleneck: How Conventional Manufacturing Technologies Limit Access
Over the past two decades, biotherapeutics, particularly monoclonal antibodies (mAbs), have transformed the therapeutic landscape for a range of prevalent health conditions, from autoimmune diseases to cancers. It’s also been estimated that some 7,000 rare disease indications could be addressed with biotherapeutics (1). However, while biologics have shown remarkable efficacy in clinical settings, access to these therapies remains a significant challenge globally.
Most biologics developers rely on fed-batch systems for bioproduction. However, this approach brings several key challenges that create risks and inefficiencies in the production pipeline, including:
- High manufacturing costs
- Difficulty in adapting to demand
- Expensive and risk-prone commercial development process
In this blog, we’ll explore these major factors influencing the supply and access of commercial biologics, before highlighting how adopting a continuous manufacturing approach can address these challenges.
Challenges in biotherapeutics supply and access
High manufacturing costs
Fed-batch manufacturing involves discrete unit operations where production occurs in separate, sequential steps. Each step must be completed before the next one begins. This means large volumes of intermediates must be stored, which requires a substantial facility footprint.
Running these large-scale facilities is expensive and contributes to the high costs of manufacturing. Additionally, fed-batch processes often require significant manual input, needing large teams of operators for their execution, increasing costs further. As a result, fed-batch facilities run at a higher operational cost compared with continuous bioprocessing units.
Difficulty in adapting to demand
It’s challenging for biologics developers to accurately predict the take-up and global demand for a biologic, especially during early production phases. If demand is too low, it can lead to sponsors paying out for idle manufacturing capacity. Should demand be higher than forecasted, sponsors run the risk of underproduction, causing shortages and patients going without medicines.
Further adding to this problem, fed-batch processes rely on large-scale stainless-steel units for commercial supply that are expensive and time-consuming to build. This creates inflexibility, bringing difficulties in adapting fed-batch units to fluctuating demands. This scenario was experienced by the developers of rheumatoid arthritis therapy Enbrel®. During times of increased demand, such as when new indications were approved or patient populations grew, inability to rapidly scale up production of their fed-batch process caused serious supply constraints (2).
Expensive and risk-prone commercial development process
Fed-batch biomanufacturing processes face significant risk when it comes to scaling up production, especially for sponsors moving from clinical trials to commercialization. This can limit the ability of manufacturers to meet global demand.
Fed-batch processes must be scaled up by a factor of 5 to 20-fold in order to meet commercial demand, because of the inefficiency of the process.
Scaling up in this way creates the following risks:
- The large-scale process might not replicate the smaller-scale process performance
- Product quality attributes (PQAs) might change at increased scale
- A limited number of large-scale facilities exist worldwide, causing major supply issues during increased production demands
A better approach to biologics manufacturing
Biologics provide life-saving treatments, but access and supply have been limited due to their high cost structure, inflexible production processes, and unpredictable demand. Continuous manufacturing addresses these challenges by offering a more agile, cost-effective, and stable production process.
This approach involves raw materials being continuously fed into the bioprocessing system, while products are continuously yielded. By automating workflows and maintaining a steady state of operation, companies can improve scalability, adaptability, productivity, and consistency. Companies that have started their clinical journey with a fed-batch process should consider converting to a continuous manufacturing platform before commercialization to take advantage of these benefits.
Learn how continuous manufacturing can slash biologics production costs by 75 %
To maximize manufacturing outcomes, opt for an industry-leading partner like Just – Evotec Biologics. Partners can benefit from cutting-edge continuous manufacturing technologies, well-established process development systems, and state of the art J.POD facilities.
References
1. Chediak L. I have a rare disease. This is my hope for the future of medicine. World Economic Forum.
2. Gellene D. Immunex says Enbrel shortage worse than anticipated. Los Angeles Times.