Approaches to Scaling Up Chromatography Processes

Scale-up is a challenging process that must take various factors into account, including the desired and existing manufacturing capacity as well as intended use functions. BioPharm International spoke with Henrik Ihre, global director of strategic technologies at Cytiva, to get a perspective on scaling up chromatography resins, specifically frequent challenges unique to this process and recent and upcoming advances in the field.

Challenges in scale-up

BioPharm: What are the most frequent challenges that occur when scaling up chromatography resins? Are there any that you feel are of particular importance?

Ihre: From a resins manufacturer perspective, model systems and analytical methods need to be designed and developed to reflect the customer’s needs. This can be challenging since resins are used for a variety of processes but also for different target molecules. Hence, there are defined and limited sets of analyses and methods that need to capture what could influence the performance of the resin when scaling up to ensure consistent performance in each customer’s process.

From a user perspective, it is important to consider that each resin comes with its own specification range, which means the full range needs to be evaluated during process design and scale-up to ensure that a robust process is developed that can handle all process variations from both a raw materials and process related perspective.

Advances in chromatography resins

BioPharm: Are there any recent advances that have improved the technology surrounding chromatography resins and/or the scale-up thereof?

Ihre: There have been several new chemistries invented for resin design and the processes on how to use the resin that has positively impacted scale-up and cost. Process intensification— meaning, the ability to produce more products in less time and at a lower cost—has been a key improvement over the last decade. This is often a combination of improving the actual throughput by increased base matrix rigidity, combined with fine-tuning the pore structures and the ligand features. Also, new methods on how to clean resins between cycles have been developed, allowing for increased resin lifetime.

The scale-up process

BioPharm: What is your company’s process for scale-up? What are some considerations that are often overlooked by those not directly involved in the process?

Ihre: The key consideration during scale-up is always to ensure high and consistent product quality of the up-scaled manufacturing process. While scaling up or transferring a process, it may be tempting to also implement changes and improvements, which could be the right thing to do. However, such changes and improvements must be validated in a way that does not negatively impact the customer experience. In most cases, the same performance is required for a resin that comes from a new and scaled-up manufacturing process. An improvement from the supplier may not be seen as an improvement by the end-user.

Innovations on the horizon

BioPharm: Focusing on monoclonal antibodies (mAbs), specifically, can
you talk about some upcoming innovations that may be on the horizon? What do you envision as the next step of the technology?

Ihre: Recently, we have seen several new modalities such as messenger RNA, adeno-associated vectors, and oligonucleotides filling up the
biologic pipelines. However, mAbs and antibody fragments will continue to be a solid foundation of the
industry for years to come, and this is why innovations in this area continue to be important.

In short, I believe we will see some further fine-tuning and improvements of the protein A resins in terms of process intensification. Perhaps the biggest steps will be taken within specific affinity resins and processes focused on antibody fragments where the traditional protein A resins may not be the best alternative.

Situational focus

BioPharm: Is there anything else of interest you would like to discuss?

Ihre: To scale up and down will always be important for suppliers and manufacturers of APIs to meet variations in market demand. However, the focus may be different depending on the situation. For instance, when scaling up an existing resin for an already existing API process, the key focus is to ensure the very same performance for the scale-up resin.

However, when designing a new API process, the focus should also be on designing the entire API process in such a way that all possible variations have been considered in advance, ensuring a process that could be scaled up or down independently of variations in raw materials and normal process variations. Working according to the basic principles of quality by design will ensure successful and predictable scaling of processes both for resin suppliers and manufacturers of APIs.

About the author

Grant Playter is the Assistant Editor of BioPharm International.

Article details

BioPharm International
Vol. 35, No. 9
September 2022
Pages: 26-27

Citation

When referring to this article, please cite it as G. Playter, “Approaches to Scaling Up Chromatography Processes,” BioPharm International 35 (9) 2022.