Biologic medicines continue to change the lives of an increasing number of people all over the world. However, as the complexity of these molecules continues to increase it means that it is not easy developing the proper manufacturing process. Highly purified material is produced by an optimised process in a minimum number of batches in order to meet clinical times and to prepare for your commercial launch, while at the same time managing supply, quality, and cost. An optimised process must also streamline operations and improve consistency and robustness, as well as minimise the chance of failures. Engineering controls, like those that Fleet BioProcessing does, must also be considered in order to prevent contamination events or adventitious agents being introduced. This should all result in your long-term manufacturing being successful.
There are three main questions you need to ask throughout your optimisation process:
Can the process be simplified? Something that is very easy to run on a small-scale inside of a laboratory might result in unnecessary variability and risk on a larger scale GMP environment. It might be possible to lower the risk of failure if a complicated feeding strategy is replaced by a simplified approach. If open manipulations are replaced with closed systems, it might be possible to reduce the risk of contamination. Variability might also be reduced by streamlining media preparation or cell expansion.
How can I ensure that performance is consistent? The closer you are to running a commercial manufacturing process, the higher the number of batches will need to be run. The key will be robustness and consistency – particularly if you aim to commercially manufacture multiple batches a month, or maybe even dozens a year.
How does the upstream impact downstream? You need to consider the implications that the downstream has on your upstream process – to ensure that the material that is produced can be purified downstream on a consistent basis.
When considering quality, two major factors need to be kept in mind product quality and raw material quality. There is an increasingly large and growing body of evidence that demonstrates that the quality level of the raw material – either the absence or presence of impurities – impacts not only performance but also has a significant impact on the drug substance’s quality. Therefore, it is essential to understand the quality level of the raw materials being used throughout process development and the way they compare to what is going to be available for suing during commercial or clinical manufacturing.
It can be overwhelming to manage raw material supplies. However, collaboration can help you succeed. Rather than focusing on just the functional aspects involved in the downstream or upstream process, if a holistic approach is taken it can provide you with a more successful result. In terms of supply chain transparency, the FDA continues to expect drug companies to put in more effort. That is another good reason for collaborating with suppliers. That way all parties involved obtain a thorough understanding of the origin of the raw materials, how they are used, and how the entire process is managed.
It simply cannot be overstated how important it is to have good relationships with your suppliers since it affects everything ranging from the assurance of supply to product quality and performance. You depend on your suppliers to deliver precisely what you expect so that you will be able to effectively troubleshoot any process deviations that arise. It is often hard to pinpoint a problem’s root cause. However, having a trusted and close relationship with a supplier can definitely help you assess whether or not the potential cause was your raw materials.