December 6, 2023 PAO-10-23-CL-01
Strong growth in the underlying biologics market, including traditional recombinant proteins and antibodies, next-generation antibodies, and new modalities, such as cell and gene therapies, is driving strong growth in the cell culture media market.
Effects of the COVID-19 pandemic on both shifts in demand and the underlying supply chain continue to reverberate in the cell culture media market for both upstream and downstream sectors. Before the pandemic, interest in cell-culture media products was distributed across a wide array of biologics manufacturing applications. However, during the pandemic, many areas of research and development considered non-essential during the crisis were put on pause to allow a shift in focus to the development of COVID-19 therapeutics and vaccines. While sectors like mRNA vaccines continue to command elevated attention and investment, there is an ongoing resurgence of activity in the wider biologics market and broader innovation across modalities, as reflected in demand for cell culture media.
To meet this growing demand, suppliers of cell culture media and its key ingredients have been expanding capacity. Simultaneously, a wave of new entrants is seeking to make a play in the media market. Some of these companies are moving laterally or upstream from their existing offerings, expanding their portfolios to include cell culture media products.
The COVID-19 pandemic also highlighted the importance of openness and transparency at every link in the biopharma supply chain. Many companies can make the decision to begin to offer supply of cell culture media and/or media components, but not all firms can be true supply partners. Open and transparent relationships are essential to driving innovation, and biopharma innovators and manufacturers are expecting more agility and dependability from suppliers. With true partnerships rather than transactional relationships, biomanufacturers see fewer supply chain disruptions as local supply partners understand and prioritize their current and future needs.
True supply partners develop products in collaboration with their customers and help them to solve the specific problems that they face. That collaboration necessitates back-and-forth conversation around key aspects of the supplied product, including optimizing an ensuring consistency in a growing number of attributes that might impact the customer’s processes and ultimately final drug production. The most successful suppliers invest the time to determine the impacts of their products — not only as they are used by the customer but all the way through to the ultimate end users, patients. Members of the industry group BioPhorum, for instance, are tackling the issue of transparency in the supply chain, more specifically a lack of sufficient transparency — particularly with respect to suppliers outside of the pharmaceutical industry that are not aware of how their products and processes can impact the production of cell culture media, which in turn impacts aspects of drug product manufacturing ranging from cost-efficiency to patient safety.
Going forward, partnerships between media suppliers and their customers are likely to continue to grow in importance, and ever-greater levels of integration between partners spanning the supply chain are anticipated. In part, this trend can be attributed to the need for rapid access to data needed for decision-making throughout the production process.
Concerns about animal-derived components, including raw materials used in manufacturing processes and materials used to produce equipment components, continue to increase. The result has been a shift away from animal-origin materials to chemically defined and animal-free alternatives where possible, a trend that continues to accelerate. In addition to eliminating concerns about contaminants that can be introduced with animal-based materials and the long-term sustainability of scaling the animal-derived supply chain, chemically defined materials are thought to be more consistent. Chemically defined materials may provide greater reliability in identity and composition but often sacrifice higher titers when they are not supplemented in a culture media. Supplementation with sustainable plant-based or yeast-based material is easier to remove later downstream and provides the upside of higher titers without introducing animal-origin concerns. Tighter control of the inputs into upstream processes can have a significant impact on reducing the demands and complexity of downstream purification processes. Furthermore, for suppliers that understand the exact impacts of their products — and their attributes and ratios — on customer processes, it is possible to adjust production of critical media components to generate products that better meet the specific needs of different customers.
For cell culture media, the most significant undertaking has been the transition to alternatives from the widely used fetal bovine serum (FBS). While chemically defined media exhibit significantly less variability than FBS-derived media, it is again worth noting that they are not entirely free of variability. In addition, many manufacturers ultimately add FBS (albeit in reduced amounts) to their chemically defined media to obtain the desired properties. Importantly, it is not easy and often not practical to revise processes for products that have already received approval — there is far less incentive to switch from legacy FBS-based processes to chemically defined media or animal-free hydrolysates in processes for post-approval products. Making such a change requires extensive comparability studies and thus significant time and cost, which likely offsets the benefits from making the switch. Generally, these processes are only updated in times of crisis or once a product loses patent protection and faces competition from biosimilars and biobetters.
In some chemically defined media, animal sera, such as FBS, are often replaced with plant-based protein hydrolysates in conjunction with other supplements. The hydrolysates are produced by enzymatic or acidic digestion of plant-based materials (soy, wheat, cottonseed, and others) and consist of a mixture of compounds, including peptides, amino acids, and carbohydrates.
Hydrolysates and peptones — which are also used to supplement chemically defined media — produced via enzymatic digest have been proposed as alternatives to animal-derived materials. Currently, efforts are underway to understand how hydrolysates and peptones might impact cell culture processes — not just upstream but also later in downstream production of finished goods.
The same questions must be considered when choosing among soy, wheat, pea, and other animal-free materials. Other animal-free derivates, like microbial peptones, may also play a role in the future. There are no obvious predictors yet established regarding which peptones and hydrolysates will give the best performance for a given application, so the selection of the optimal hydrolysate source for a given process is best determined empirically. It seems likely that, in the near future, artificial intelligence (AI) trained on the data produced in these experimental comparisons will be able to simulate various cell culture scenarios with different types of hydrolysates and peptones and predict the optimum composition for each process. The optimal solution might be a wheat-based material or a precise mixture of soy- and pea-derived hydrolysates, for example.
Plant- and microbial-based hydrolysates and peptones provide a natural means to transition away from FBS and other animal sera to sustainable media solutions with decreased variability. This approach requires leveraging the wealth of knowledge around existing materials for novel combinations to achieve results with greater efficiency. These animal-free alternatives also present an advantage over animal-derived materials in terms of long-term sustainability.
Sustainability considerations continue to grow in importance throughout biopharma, among many industries, particularly from a carbon footprint standpoint. Most international biopharmaceutical companies are paying close attention, not only to their own emissions and related considerations but those upstream in the supply chain. They have developed detailed plans for reducing their carbon footprints that include using sustainable materials obtained from suppliers that also have programs in place to reduce their environmental impacts. Furthermore, different options must be considered through a sustainability lens, not just from an ingredient perspective but also a long-term cost perspective.
Nu-Tek BioSciences has responded with the construction of a state-of-the-art facility leveraging modern technology that was designed with built-in flexibility to allow for true agility and responsiveness to allow the company to meet evolving customer needs in a sustainable manner — while also capturing and storing process data today to support future optimization efforts.
Nu-Tek is also expanding our pipeline beyond peptone and hydrolysate products in response to customer requirements and requests. As a producer of customized peptones and hydrolysates for use in cell culture media formulations, a further expansion into cell culture media manufacturing was a natural next step for the company that we are very excited about.
We have completed proof-of-concept to produce nearly any protein hydrolysate used in cell culture media and are working on protocols to help our customers transition away from materials of concern. We are also investing in the assets required to produce culture media and other combination products in anticipation of the application of AI in the design of media composition.
While plant hydrolysates and peptones initially suffered from variability, advances in enzyme systems and other processing technologies have led to more consistent products. Today, we are able to produce consistent precision hydrolysates at the specifications sought by customers.
Nu-Tek, with its new production facility, has already laid the foundation to support the future of precision plant hydrolysates and peptones. We are compiling large quantities of data, both internally and in collaboration with customers, and validating the output. The goal is to better understand how to achieve consistency and further minimize variability, as well as better understand the impact of changes on customer processes and products.
Nu-Tek’s focus on plant-based cell culture media ingredients reflects our commitment to support the supply chain connecting the field to pharmaceutical applications. We start with derivates of crops and produce high-quality cell culture media ingredients that enable efficient, cost-effective production of high-quality drug products. Our current efforts involve introducing in-house blending and milling capabilities to further secure our supply chain. With these additional capabilities, we will be able to support an even broader array of customer needs with regard to cell culture media and proprietary peptone blends.
The key driver for the field-to-pharma concept at Nu-Tek is a commitment to securing the full supply chain and establishing the future potential to produce not only cell culture ingredients and formulated products but someday the biologics we help support. Beginning with our foundation of a detailed, data-driven focus on key ingredients, Nu-Tek will continue to innovate to reconfigure the biopharma supply chain one link at a time to drive greater benefits in consistency, efficiency, and sustainability.
Chris Wiedel brings over 10 years of experience in the biotech industries, selling and marketing cell culture media and the ingredients that comprise them, to his role as Chief Business Officer. Chris received a Bachelor of Science degree in Biology from Towson University, and both a Master of Business Administration and a Master of Finance degree from the University of Maryland.
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