Pulling Out All the Stops in mAb Manufacturing

Published on: 
BioPharm International, BioPharm International, June 2023, Volume 36, Issue 06
Pages: 16

Compliance with GMP standards remains an integral focus in bulk mAb manufacturing.

While the biopharma industry is pushing the barriers with antibody development, it must also contend with contemporary challenges in bulk monoclonal antibody (mAb) manufacturing. The need for good manufacturing practice compliance for mAbs going forward is increasingly crucial.

To highlight some of the bottlenecks and solutions in bulk mAb manufacturing, BioPharm International® spoke with Lee Seung-sun, lead scientist for the Manufacturing Science and Technology team at Samsung Biologics.

BioPharm: What specific aspects in bulk mAb manufacturing are the most challenging?

Lee (Samsung Biologics): As intensified process and continuous process are on the rise, many products these days have high cell number and titer. As a result, perfusion has been introduced to N-1 or N stage of cell culture process, and process development has involved using more feeds in high concentration.

Especially with mass production, companies, including Samsung Biologics, have operated with more trains for cell culture than for purification as the cell culture process used be the bottleneck. However, with a significant increase in titer these days, the purification process is becoming the bottleneck. Such changes accelerate transition to continuous processing and an automation platform.

As market demands for various types of modalities such as antibody drug conjugates (ADCs) are increasing, the traditional workflow process of cell culture to purification to fill/finish cannot thoroughly respond to the rapidly changing market. Continuous investment and rapid adoption of new technologies are required.

Since the COVID-19 pandemic has disrupted global supply chain, it has been hard to procure as much raw materials as required at the right time, and everyone is suffering from the prolonged situation. Especially for manufacturing of mAb drug substance, it is challenging to find the alternative to the raw materials that have been used, and, even if [alternatives are] found, it will take a considerable amount of time and effort to identify all risks related [to these alternatives] and introduce [them] to the actual manufacturing process.

BioPharm: How much improvement in the overall mAb manufacturing process has resulted from the implementation of process analytical technology (PAT)?

Lee (Samsung Biologics): The use of various in-line sensors, including Raman, allows for more immediate responses to various issues during manufacturing, and better fine-tuning of the process itself compared to the past. People are getting more process knowledge as more data [are] acquired. However, to take full advantage of PAT, a system that can enable on-line and real-time use of information sensed by the in-line sensor needs to be established together, implying that an automated manufacturing facility that can be operated based on electronic batch records is required. This would be accompanied by large investment.


With the implementation of PAT, we are now in the process of transitioning from traditional process control to predictive process control, and the importance of data science has emerged in the biopharma industry accordingly. Establishment of a continuous process in an automated facility using PAT will enable manufacturing of high-quality mAb drug substance with much less time and cost, compared to the traditional manufacturing process. Samsung Biologics is in the process of digital transformation to keep up with these changes.

BioPharm: What strategies have thus far been successful in improving process control over bulk mAb manufacturing?

Lee (Samsung Biologics): Time required for tech transfer and potential risks during engineering run and process performance qualification can be reduced by utilizing platform processes. Use of well-defined scale-down models and establishment of scale-down models with pilot scale can be alternatives to reducing risks for large-scale production. For commercialized products with a sufficient amount of historical data, data-driven improvement of process control can be done based on the historical data accumulated.

BioPharm: What unmet needs still exist in bioprocessing (e.g., a technology, a piece of equipment, or an analytical requirement) that limit the ability to effectively control the mAb manufacturing process?

Lee (Samsung Biologics): Compared to other advanced manufacturing industries, the mAb manufacturing process is less automated and more labor intensive. Not only is it hard to predict and manage various issues that could potentially occur during the process, but it also takes significant amount of money, manpower, and time to find root causes of the issues and fix them.

BioPharm: What other methods, or technology, or approaches can be used to further streamline the mAb manufacturing process (especially removing bottlenecking)?

Lee (Samsung Biologics): The mAb manufacturing process is in the process of eliminating bottlenecks through transformation into automated and continuous processes. The introduction of digital twins is expected to reduce time, manpower, and material spent on manufacturing in the near future.

About the author

Feliza Mirasol is science editor for BioPharm International.

Article Details

BioPharm International
Volume 36, No. 6
June 2023
Page: 16


When referring to this article, please cite it as Mirasol, F. Pulling Out All the Stops in mAb Manufacturing. BioPharm International 2023, 36 (6), 16.