PHARMACEUTICALS during the upstream processing of antibody therapeutics . A significant challenge with tangential flow filtration ( TFF ) is membrane fouling , which can lead to reduced permeate flow and increased product retention . 6 The adoption of continuous diskstack centrifugation has enabled developers and manufacturers to avoid fouling effects while facilitating continuous operation at high throughputs . 7
Filtration systems have also evolved to meet the demands of intensified unit operations . Improved designs of depth filters , virus removal filters and microfilters have enabled higher volumetric throughput and flux rates , contributing to increased bioreactor productivity . These advances have facilitated the production of more material in fewer batches , with typical mAb productivity rising from around 0.1 g / L to 10-20 at the bioreactor volume .
The adoption of platform processes has played a crucial role in streamlining mAb production . With standardised methods and technologies that can be applied across multiple mAb products , platform processes can reduce development time and costs . This approach has been particularly beneficial in accelerating the transition from clinical development to commercial manufacturing .
Single-use technologies ( SUTs ) have become increasingly popular in mAb production due to their costeffectiveness , flexibility and ability to streamline processes . By reducing reliance on traditional stainlesssteel equipment , which requires cleaning , validation and downtime between batches , SUTs enable manufacturers to quickly adapt to changing production needs . This eliminates the need for cleaning , sterilisation and validation steps between batches , enabling quicker turnaround times while reducing the risk of cross-contamination .
SUTs also facilitate easier technology transfer and allow for rapid scale-up of production to meet the growing demand for mAb therapies . Additionally , the use of presterilised components minimises the risk of cross-contamination , offering increased microbial control . The flexibility and scalability offered by SUTs are particularly advantageous in this rapidly evolving field .
Continuous manufacturing processes are being increasingly adopted to enhance flexibility , cost-efficiency and quality in mAb production . Continuous bioprocessing , such as perfusion , allows for the continuous replacement of spent media with fresh media , leading to higher productivity and reduced facility footprint needs .
This approach also enables the rapid development of parallel manufacturing lines , increasing capacity for multiple batches . By maintaining a steady state of production , continuous processes can achieve higher yields and more consistent product quality compared to traditional batch processes . This also reduces the need for largescale bioreactors , leading to lower capital investment .
Navigating regulatory requirements
Meeting the rising global demand for mAbs not only requires innovative approaches to production but also to ensure the processes used can guarantee both high quality and strict regulatory compliance . A commitment to quality and compliance is essential to meeting the growing need for these life-saving therapies .
As mAbs are typically administered parenterally , developers and manufacturers must follow stringent guidance for sterile manufacturing outlined by regulatory authorities such as the US FDA and global health boards such as the WHO . Annex 1 of the EU GMP guides the sterile manufacture of medicinal products in the EU , outlining strict aseptic processing standards . 8
Developers and manufacturers must prioritise compliance with relevant requirements throughout the entire development and manufacturing process while remaining adaptable to potential future changes in regulatory guidelines .
Recent updates to Annex 1 have further emphasised the need for state-of-the-art facilities , robust quality systems and a deep understanding of evolving regulations . These revisions highlight stricter contamination control measures through robust facility design , environmental controls and aseptic processing . Key updates include :
• The requirement for a formal contamination control strategy
• Increased emphasis on quality risk management and stricter environmental monitoring
MAR / APR 2025