Ready to unlock your cells’ potential?
No other teamis as dedicated to advancing cell culture media as Multus. Talk to our mediaspecialists today!
No other teamis as dedicated to advancing cell culture media as Multus. Talk to our mediaspecialists today!
.jpg)
Cell culture media can influence almost every aspect of a biomanufacturing process, from cell growth and viability to product quality, scalability and manufacturing costs. However, media formulations are often only revisited when they stop performing adequately. In many cases, an off-the-shelf formulation is selected early in development, and kept the same while other aspects of the process are gradually adjusted. Regularly reassessing media compositions can help to determine how well a formulation is working today, as well as if it is likely to continue meeting the needs of the process as development progresses. This becomes particularly important as biomanufacturers approach chemistry, manufacturing and controls (CMC) development, after which changing an established formulation becomes considerably more complex.
Early bioprocess development typically involves refining cell lines, expression systems and bioreactor conditions to meet specific performance and manufacturing objectives. In contrast, culture media often receive less attention, with off-the-shelf formulations selected for convenience and rarely revisited as other elements of the bioprocess evolve. However, a formulation that provides sufficient cell growth at the bench may become increasingly mismatched with the wider process as it develops. This can result in significant effort going into optimising a process around a medium that was never designed specifically for it, in an attempt to overcome scalability challenges related to titres, product quality, raw material costs and ingredient availability.
These early media decisions can shape the entire downstream manufacturing workflow, so it is important to consider the suitability of the selected media for the end goal of the process. Choosing a medium that meets the immediate needs of early development may result in it becoming a limiting factor as requirements change, or as the process moves towards commercial manufacturing. Identifying these potential constraints before the manufacturing process is established gives greater flexibility to address them, and treating media as a key process variable from an early stage provides an opportunity to optimise it alongside other parameters. This can help to ensure that the formulation supports both cell growth and the broader technical and scale-up requirements of the process. The question is therefore when in the development process media optimisation is most valuable.
There is no single stage that is right for media optimisation in every process, but there are several points when it can be useful to reassess the media formulation. Considering the media requirements from the outset – particularly when an existing formulation does not closely match the needs of the application – is obviously the ideal starting point, especially when introducing a new cell line, product or manufacturing process.
Another opportunity arises as process objectives become clearer. Manufacturers may initially focus on establishing sufficient growth and viability, but later need to balance titre and product quality with cost, ingredient availability, supply security and scalability. Media can also be reviewed when these requirements change – for example, if an ingredient becomes expensive or difficult to source – or as regulatory requirements evolve.
One of the most important, but potentially overlooked, opportunities to reassess culture media is before moving into CMC development. This is a crucial time to determine whether the existing medium is suitable in the long term, as the window for optimisation begins to narrow once the process becomes more established and data is generated to support regulatory submissions. Any further changes to the media formulation beyond this point may require additional development, comparability work or documentation,1 so manufacturers relying on off-the-shelf formulations should pay special attention to the limitations of their media. Even if a formulation is not seen to be ‘failing’, any issues that limit productivity, increase costs, create supply risks or mean that the medium is unlikely to meet future manufacturing requirements should be addressed at this stage to avoid carrying unnecessary constraints into later development.
Timing is only one part of the decision when it comes to media optimisation; manufacturers also need to establish what they want their media formulation to achieve based on the specific needs of the process. This is where media development can become particularly challenging, as an effective formulation needs to balance numerous, often competing, factors such as cell growth and health, titre, product quality, yield, cost, ingredient availability and scalability.
Crucially, the best formulation may not maximise every metric. Instead, biomanufacturers need to distinguish between objectives – areas where improved performance adds value – and constraints that simply need to stay within an acceptable range. For example, cell growth may only need to reach a defined threshold, while increasing titre is the main objective.
There are also trade-offs between competing factors. For instance, while media costs might need to remain below a certain level, the price of the medium alone does not determine its impact on process economics. A more expensive formulation that delivers higher cell growth or titre may still reduce overall costs if less media is required to achieve the same output. Assessing these factors together helps manufacturers to find the right balance for their process, rather than optimising each metric in isolation.
This challenge grows rapidly as more variables are introduced. Media formulations can contain many interacting components, and changing the concentration of one ingredient may alter the effects of others. Testing numerous combinations and concentrations of ingredients against multiple performance criteria creates a vast optimisation space that can be difficult to explore using conventional approaches.
Once the priorities for the media have been defined, the next step is to determine how much development is needed to achieve them, which will also depend on the organisation. A media supplier, for example, may need a formulation that performs across several cell lines, while a CDMO may prioritise compatibility with a platform cell line used for different products. For a biosimilar manufacturer producing large volumes over a longer period, there may be greater value in tailoring the formulation to a specific process, where improvements in performance or cost can have a greater impact.
The most appropriate approach also depends on the starting point. If a suitable baseline formulation already exists, development may focus on refining selected components. A new cell line without an appropriate medium, on the other hand, may require a formulation to be developed from scratch.
Multus' AI-enabled media development platform, MediOP™, can accommodate these different priorities and requirements: Express uses Multus’ proprietary library of more than 8 million datapoints to identify and screen promising media candidates; Boost refines a baseline formulation; and De Novo develops a new formulation from the ground up. All MediOP™ services combine high-throughput robotic automation, artificial intelligence and biological expertise to generate large experimental datasets and systematically explore formulation spaces. This approach allows multiple objectives and constraints to be optimised simultaneously, exploring the trade-offs between different performance metrics to identify formulations that offer the right overall balance for the process. The resulting data can then guide subsequent rounds of development until the desired performance criteria are met.
This data-driven approach can shorten development timelines compared with conventional methods, while tailoring media to the objectives and constraints of each process in a way that would be almost impossible to achieve manually. It also makes it more practical to explore media as a process variable early in development, before the formulation becomes a manufacturing bottleneck.
There is no single point at which every manufacturer should optimise culture media. The right time depends on the stage of development, the requirements of the process, and the scope that remains to make changes. Ideally, this should be when there is enough information to understand what the process needs, while there is still enough flexibility to act on it.
The ability to make changes to media composition diminishes significantly as CMC development progresses. This timepoint therefore provides an important deadline for media optimisation, particularly if an off-the-shelf formulation has been carried through development without further optimisation. Ultimately, media optimisation should not wait until performance begins to fail, and taking a proactive, data-driven approach can help manufacturers to develop formulations that support both current performance needs and the transition towards scalable manufacturing.
Talk to one of our scientists about media designed for the cell types you're working with.
1. Muralidharan, N. et al. 2025. Synchronizing CMC activities with clinical development: For robust and compliant biomanufacturing from bench to BLA. BioProcess International, 23(10), 4-8.
Sign up for email updates:
