Developments in the world of biologic medicine are transforming the lives of increasing numbers of individuals across the globe. However, as the complexity of molecules increases, designing scalable manufacturing processes is a challenge. An optimised process results in highly purified material from the smallest number of batches to meet clinical timelines as well as get ready for a commercial launch, at the same time as managing quality, supply and cost. Furthermore, an optimised process should streamline operations, minimise the risk of failure, and improve consistency and robustness. In addition, you need to use engineering control to stop contamination events or adventitious agent introductions. Accounting for all those factors should result in manufacturing success over the long term.
There are essentially three key questions you need to refer back to during the optimisation process:
1. Can the Process Be Simplified?
In many cases, a process that is easy to carry out small-scale in the testing lab can result in unnecessary variability and risk in a large-scale commercial manufacturing environment. It’s possible that the risk of failure can be reduced by replacing a complex feeding strategy with a more simplified method. You might also be able to decrease the contamination risk by using closed systems in place of open manipulations. And it might be possible to lower the variability using media preparations or with streamlining cell expansion.
2. What Can I Do to Guarantee Consistent Performance?
The closer you approach a viable commercial manufacturing process such as co affinity purification, the greater the number of batches you need to run, and robustness and consistency become key – particularly if your goal is to commercially manufacture multiple batches every month.
3. How Is Upstream Affecting Downstream?
It’s vital to look at the downstream consequences of the upstream process – making sure that material produced can be purified downstream consistently.
When it comes to quality, there are two key factors to pay attention to: product quality and raw material quality. A large number of studies demonstrate that raw material quality – the absence or presence of impurities – not only affects process performance but also significantly affects drug substance quality. As a result, it’s critical to analyse the quality of all raw materials used during process development and consider how they compare to the quality of raw materials available for commercial or clinical manufacturing.
Managing raw material supplies is often a daunting task, but collaboration can boost success. Rather than focusing on the singular function aspects of the downstream or upstream process, a holistic approach can lead to a more successful outcome. The MHRA is demanding increasing efforts from drug companies in regards to supply chain transparency – a further reason to collaborate with raw material suppliers to ensure all parties have sufficient understanding of the origins of the raw materials, how they’re processed and how the entire manufacturing chain is managed.
The importance of a close relationship with suppliers should not be underestimated, as it impacts everything from product quality to perform and supply assurance. You should be able to trust the suppliers you work with to deliver exactly what you expect so that troubleshooting any process deviations is effective. In a lot of cases, it’s hard to identify the root cause of an issue, but maintaining a trusted relationship with your suppliers can help you evaluate whether the raw materials are a potential cause.