Understanding Variability in Biopharmaceutical Manufacturing
September 3, 2019
It is critical to account for variability when developing a process for your therapeutic. Acknowledging and understanding the potential causes of variability in process and platform development allows teams to engage in productive discussions. It is then possible to prospectively plan for potential challenges that may be encountered throughout all stages of process development (PD). This interaction will simplify the process of addressing short-term risks, especially when trying to scale-up the process. It also avoids being caught off-guard when entering clinical manufacturing.
Process variability studies tend to be deprioritized during PD. This is not recommended and can result in significant expenses at later stages in the drug development process, caused by the need to troubleshoot and establish these parameters.
So, what can you do?
1. Start by asking if your outsourcing partner will perform qualification studies of your process.
Don’t assume this activity will be performed. It is a significant and costly undertaking and many PD providers don’t offer it or have the capability. If some type of qualification is provided, make sure you understand if the partner will establish a range that is deemed acceptable for manufacturing. Regardless of whether your current PD partner offers qualification or not, you will need a plan for testing relevant critical quality attributes of your product that will be used as release criteria during clinical manufacturing.
2. Ensure that robust and predictive assays are in place before you initiate process development.
Without these tools, you won’t be able to accurately assess the consequences of process changes as you scale to larger volumes.
3. Define your acceptance range for product yield potency and purity before entering clinical manufacturing.
Not having established these conditions and ranges can cause release delays and impacts to your bottom line.
4. Inform your partner on the number of molecules in your portfolio.
Ask if they can test (not validate) if their process can be adapted to those molecules. It is sensible to ask yourself how many rounds of testing would give you confidence at production scale before transfer to manufacturing. You need to strike a balance between demonstrating robustness and qualification which will encompass many runs.
Learn more about what to expect when outsourcing process development in the blog post by Dr Ruta Waghmare.
Dr Mark Szczypka – Global Director, Process Development Services
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