Biologic medicines are increasingly transforming the lives of people throughout the world, but the increasing complexity of the molecules means that it isn’t easy to develop the right manufacturing process.
Over fifteen years have been spent working in the industry on viral vaccines and therapeutic process, focusing on upstream process development, scale-up as well as cGMP manufacturing. The result has been the development of processes for over a dozen different molecules.
It is always important to think about what makes an “optimised” or “good” process as well as where the pitfalls lie. A protein purification company can optimise the process which can be defined as one that results in highly purified materials in the least number of batched to meet clinical timelines and prepare for commercial launch, all while managing quality, cost and supply.
An optimised process should also streamline operations, enhance consistency and robustness, as well as reduce the opportunity for failures. It is equally important to consider engineering controls for preventing contamination events or even the addition of adventitious agents. All that should result in manufacturing success in the long run.
All this is easier said than done. With so many essential areas in the bioprocessing workflow, determining where best to focus your attention can be challenging. Success typically lies in taking a cautious approach, by balancing the trade-offs that are associated with speed-to-clinic as well as process optimisation that’s customised to the specific needs of the molecule.
You can focus on several different areas when it comes to optimising your upstream process, but balance is still critical. It isn’t always about getting the highest titter. For instance, developing a process capable of achieving a titter of 5g/L can be more sensible than identifying the ideal set of conditions needed to achieve 7g/L. If the process must run perfectly, even a tiny deviation may lead to much lower titters than the initial 5g/L and possibly failure.
Overall, there are 3 key questions that you need to ask throughout the process of optimisation:
1. Is It Possible to Simplify the Process?
A process that’s easy to run at small-scale in the laboratory can result in unnecessary risk and variability in a large-scale GMP environment. You can replace a complicated feeding strategy with a simplified approach thus reducing the risk of failure. You can also reduce the risk of contamination by replacing open manipulations with closed systems. You can even reduce your variability through the streamlining of cell expansion or media preparation.
2. How Can You Ensure Consistent Performance?
The closer that you are to a commercial manufacturing process, the higher the number of batches you will be required to run, and robustness and consistency become critical considerations, particularly if you are aiming for commercial manufacturing of several batches every month, or perhaps dozens every year.
3. How Does the Upstream Affect the Downstream?
It is also important to consider the implications of the upstream process on the downstream – making sure that the material that is made can be purified consistently downstream.
Management of Quality and Supply
The assurance of supply is another key consideration that the need for quality raw materials ties into. Suppliers or even biopharmaceutical companies or even anyone for that matter ever wants to deal with stock-outs.
It is always important to consider the reliability of the raw material supply chain while developing a biological process. Supply continuity is critical; companies should have strategies for mitigating disruptions in supply.
Transparency in raw material supply requirements and the necessity for safety stocks, redundant sit qualification, or any other means to prevent interruptions in supply is key in all approaches.