Compared to more complex unit operations, the medium solution preparation step is often overlooked in process design and optimization, scale-up and technology transfer.
This has been borne out by a BioPhorum collaboration, which also showed that supplier partners and biopharmaceutical companies take significantly different approaches to ensuring effective medium solution preparation.
However, variation in cell culture media solution can significantly impact product quality (e.g. glycosylation, charge variants and bioactivity) and process performance (e.g. growth rates and yields). Also, a lack of adequate controls to limit and detect process variabilities can result in costly out-of-specification investigations, disruptions in manufacturing schedules, logistics and inventory, and increased environmental waste.
This is why BioPhorum has published its Best practice guide for preparation of cell culture media solution.
The paper supports a proactive approach to the evaluation and self-audit of internal processes and outlines recommendations on:
- Design and controls of the media manufacturing process
- Design, development and scale-up of medium solution preparation process
- Viral mitigations and controls
- Analytical testing and controls.
It also includes two case studies. The first is on technology transfer of medium solution preparation to a contract manufacturing organization, and the second on the application of spectroscopic online monitoring.
A bottom-up approach
Media solution preparation was not originally on the Raw Material Variability Workstream’s plans, but the highly collaborative and safe environment of a BioPhorum workshop meant it was informally discussed as a ‘blind spot’. It is an excellent example of a bottom-up approach as the team identified enough connectivity and opportunity on the subject to enable BioPhorum to nurture the discussion and start gathering a team to develop the paper.
Bruce Vickroy, MSAT Platform Leader at GSK, said, “This document allows readers to quickly share the team’s knowledge, give people an overview and let their teams – whether in technology transfer or a trouble-shooting root cause analysis – know that these are typical industry challenges that we can improve. It helps emphasize that we need to work on this area but also gives people hope that we can solve the problems.”
The paper focuses on key considerations and recommendations related to medium formulation; components, process and equipment design; scale-up and technology transfer; medium preparation process controls; and measurements.
Understanding sources of variability in production will help avoid issues that can lead to a range of adverse consequences – from minor effects on yield to the potential loss of a whole batch. Using the recommendations, biopharmaceutical organizations can minimize potential variation and maximize productivity, performance and product quality while improving operational efficiency and costs.
The guide is designed to encourage companies to take a proactive approach to evaluating and self-auditing their internal processes, which will benefit themselves, supplier partners, and patients.
“I hope that as more people see this paper and realize many others have similar challenges, that industry invests more in medium solution preparation,” said John Cunningham, Director, Material Sciences at Janssen Pharmaceutical. “We need more of a coherent strategy that is baked-in to our process design, scale-up and technology transfer processes.”
This best practice guidance shines a spotlight on the challenges associated with variability in media solution. In the future, it will support a consistent industry-wide approach and help justify investment in this critical yet often overlooked area.
Mixing raw materials might seem a mundane topic but how you mix a powder from your media supplier is a critical part of the process.