Around the world, a lot of people’s lives have been changed by biologic medicines. However, the manufacturing process is quite complex because of the increasing complexity of the molecules used in the production process. A lot of experts are still wondering what makes the best and most optimised process, especially those that have years in the industry focusing on upstream process development, cGMP, bioconjugation services and scale-up manufacturing.
In their line of work, they have handled numerous molecules but the debate is still raging about an optimised process. However, in the simplest terms, an optimised process will guarantee production of purified material in the fewest batches possible to meet the clinical timelines. It also prepares everything for a commercial launch while handling quality, cost and supply. The most optimised process will improve robustness, streamline operations and ensure consistency while minimising failures.
Engineering controls should also be in place to prevent any contamination or addition of adventitious agents. All these factors contribute to long-term success in the manufacturing process. It might seem obvious but there is a lot of work to do. The bioprocessing workflow involves a lot of critical areas so it’s tough to identify the right place to focus your efforts.
However, ultimate success relies on taking a very measured approach in the process, balancing the trade-offs in speed-to-clinic and the optimisation process specific to the molecule needs. There are different areas of focus to optimise the upstream process performance but don’t forget to consider proper balance. In most cases, it’s not prudent to focus on getting the highest titer.
You should create a process that achieves a titer of 5 g/L for instance. It’s more sensible compared to identifying the perfect set of conditions required to achieve 7 g/L. If the process is going to be successful, a small deviation will result in lower titers than the previous 5g/L. Obviously, this is a huge failure in the manufacturing process. Throughout the manufacturing process, you should ask the following questions.
1. Can the Process Be Simplified?
Something that can run effortlessly in a small-scale in your lab results in unnecessary risk and variability in a large-scale GMP environment. It’s easy to reduce the risk of failure if there is a complicated feeding strategy using a simplified approach.
You can reduce the risk of contamination by replacing open manipulations with closed systems. It’s also easy to reduce the variability through streamlining media preparation or cell expansion.
2. How Do I Ensure Consistent Performance?
As you get closer to the commercial manufacturing process, you will need to run more batches. As such, robustness and consistency are very important. If you are hoping to achieve commercial manufacturing of multiple batches every month or dozens annually, this is important.
3. How is Upstream Affecting Downstream?
You need to consider how the upstream affects the downstream process. Start by ensuring that the material is purified consistently as it goes downstream to prevent further consequences.
Managing Quality and Supply
The need for raw materials of the highest quality also factors into the assurance of supply. Suppliers or biopharmaceutical companies don’t want to deal with stock outs. In the development process of a biological process, you need to consider if the raw material supply chain is reliable.
It’s prudent to ensure continuity of supply. Companies should have strategies to mitigate any disruptions in supply. The most important factors in all these strategies include transparency in the supply requirements of the raw materials, redundant site qualification, the necessity for safety stocks and any other means of preventing the interruption of supply.