Poor quality or inconsistent starting materials can introduce variability into the performance of cell culture media, leading to unpredictable cell growth, reduced protein expression, or even complete batch failure. To avoid this, robust raw material qualification, supplier auditing, and risk-based assessments are essential.
With its extensive experience in cell culture formulation and manufacturing, Merck, is a trusted partner for biopharma companies looking for high quality cell culture media solutions. We speak with Scott Wilson, Director of Upstream and Process Materials R&D, and Damon Talley, Head of Quality for Cell Culture Media, to learn more about the importance of cell culture media and quality management.
Why is it so important to control raw materials for cell culture?
Scott Wilson: When raw materials fail, failure carries downstream. Batch failure can lead to financial losses and serious delays or disruptions in the supply of life-altering therapeutics. Undetected impurities or changes in cell culture composition can trigger regulatory compliance issues.
The raw material attributes for cell culture media are directly tied to the critical quality attributes of the final product. We use smart control strategies, quality management, and innovative solutions to develop cell culture media solutions, including dry powder and liquid cell culture media, that offer consistency. When you control raw materials, you can better control the final product, including potential impurities.
Damon Talley: To build quality into the process, you must start with consistent, high-quality building blocks. Raw materials are foundational – without quality at that level, you can’t expect to deliver a quality product. All aspects of raw materials need to be as consistent as possible, from lot to lot. We insist on resilient, reliable behavior from our suppliers. We need to know our partners are dependable and prepared to support us and our customers now and into the future with well-qualified supply chains and minimized risk.
What are the common challenges when managing raw materials?
DT: Biopharma manufacturers need consistency, so a big part of our roles is protecting customers from variability and change. The reality is that change will always occur in raw material manufacturing, so our ability to anticipate and respond to this is key. Any change, whether in the raw materials themselves or at the supplier level, must be managed correctly to avoid supply disruptions. This is why we have rigorous controls in place for any supplier changes, especially around change notifications.
We have also built-in flexibility into our supply chains so that we can pivot quickly if needed. With five – soon to be six – manufacturing sites, we’ve been actively localizing supply chains, which gives us more options. That said, having alternative supply chains isn’t always possible or the right solution. We also build resilience in other ways, such as maintaining higher inventory levels or negotiating supply chain agreements that provide added security. It’s all about creating multiple layers of flexibility.
SW: When using a particular cell culture media formulation, a customer needs to be confident that every batch performs just like the last. We identify where variability may exist within a product and then use our capabilities to either minimize or eliminate that variability. There is now a strong understanding of how trace elements, including manganese, copper, or zinc, can directly affect cell culture performance. If those levels vary too much from batch to batch, it can cause significant problems.
We have focused our innovation on removing inconsistencies. By reducing impurities and controlling trace element levels with precision, we help customers achieve more stable, predictable outcomes. Without that, they’d have to pour resources into troubleshooting variability – which is something we can help them avoid entirely.
How does Merck ensure quality?
DT: My primary role is to make sure our cell culture media manufacturing sites are consistent and aligned. We work to fully understand our supply chains and what’s happening before the raw material arrives. All our sites share a single approved supplier list, we have quality agreements in place, and we assess how well our suppliers are monitoring their suppliers. We have a very comprehensive raw material and supplier assessment process built around a risk-based approach. This allows us to focus time and resources where they’re needed most: on high-risk materials or suppliers.
We’ve also made significant progress in reducing the supplier qualification timeline. Traditionally, a lot of the qualification activities happened end-to-end, but by running many of them in parallel, we have dramatically shortened timelines. In addition, we’ve started allowing our sites to bring in bulk material earlier in the process, such as before full qualification is complete. The benefit is that we can begin release testing during the qualification phase. When the qualification is finalized, the material is already in place and ready to go.
SW: It’s all about building transparency and trust into our quality management systems. Our programs and processes have all been developed and driven by people with deep technical knowledge. Our raw material risk assessments were created by R&D teams and raw materials support teams who really understand the nuances of raw materials in cell culture media. That technical foundation makes all the difference. It’s not just about following a process, but building those processes with a true understanding of what they are meant to achieve.
How does the company support customers’ regulatory requirements?
DT: Over the last 18 months, we moved forward with EXCiPACT Pharmaceutcial Auxiliary Materials certification for pharmaceutical auxiliary materials. EXCiPACT is a key GMP standard for cell culture media – and we’re proud to say we were the first organization to have all of our manufacturing sites certified under this program. EXCiPACT framework is specifically designed for cell culture media and I believe it is absolutely the right model for our industry.
In addition, we offer customers access to our Emprove Program, which provides comprehensive documentation, including regulatory, technical, and supply chain aspects, for hundreds of raw materials. It’s a powerful resource that helps support customer risk assessments and regulatory filings.
How is the company innovating in terms of new cell culture products?
SW: As a chemical producing company ourselves, we have a solid understanding of which raw materials pose higher risks and have developed innovative solutions to tackle specific challenges. For example, we have developed starting materials with low-impurity iron salts. These are manufactured to contain extremely low – or even no – trace element impurities. The goal is to give far greater control over how trace elements influence cell performance. In the past, some iron salts were sourced through mining, which naturally can introduce variability and unwanted impurities. With cleaner, low-impurity alternatives, we can build in precision. We can even add specific trace elements back in controlled amounts to hit precise targets for customers, rather than dealing with uncontrolled fluctuations.
Another area of innovation is modified amino acids. Some amino acids can be extremely beneficial to cell growth and protein production, but are hard to solubilize at high concentrations. We have developed new amino acid forms that dissolve more easily and can be added at much higher levels – giving customers the ability to fine-tune their cell culture media for better performance.
These are just two examples. We also offer many other solutions, including low-foaming poloxamers and cell culture media fingerprinting.
What are your top dos and don’ts when it comes to raw materials for cell culture?
SW: From my perspective, a big “do” is to collaborate on a technical level with your suppliers. If you’re facing a challenge, working closely with your supplier can help you find a path forward – and also gives you insight into their confidence and technical depth around the raw materials they provide.
As for the “don’t” – don’t stop asking questions. Don’t stop innovating. Don’t assume something can’t be done. Be curious. Push boundaries. In R&D, especially when it comes to raw materials in cell culture media, there’s still so much opportunity to innovate.
One of the guiding principles for our R&D team is innovation with the goal of enhancing quality. We are working to solve some of the industry’s biggest challenges and we always aim to innovate in ways that directly improve product quality.
DT: The dos are – definitely audit us! And your other suppliers too. Make sure you fully understand their processes and dig deep into how they handle qualifications. Do they have a solid, structured program in place that gives you confidence?
The don’ts. Never overlook the importance of a risk-based approach. A risk-based framework is an incredibly valuable way to ensure you’re managing resources efficiently and effectively.
Everything we’re doing, whether it’s the innovation Scott’s team is driving or the systems we’ve built around supplier qualification, is ultimately about delivering the best quality possible for our customers. We genuinely care that what they receive works well in their hands – and more importantly, that the patients downstream receive high-quality medicines that improve their lives.
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