- Raw Materials Characterization Webpage
- Controlling cell culture process Variability
- Understanding and controlling raw materials variation in cell culture media
- The evolution of supply chain security-increasing our focus on raw material variability
Megan Manzano: Hello and thank you for joining this presentation titled “How costly is variability of cell culture media to your manufacturing process”. Today we are going to discuss what is your media and how costly variability of the cell culture media is to the manufacturing process. I am Megan Manzano, senior editor for BioPharm Interantional. Joining me today is Christopher Woolstenhulme, lead analytical scientist of manufacturing sciences at Cytiva. Thank you so much for being here today, Let’s begin.
Megan Manzano: What are sources of variability in cell culture media?
Christopher Woolstenhulme: That's a great question. When we discuss the sources of variability in cell culture media— it indicates that our customers are making a product and viewing fluctuations in efficacy or glycosylation pattern. It is important to make a consistent cell culture media to use and to reduce that level of variability. There is fluctuation that inherent with creating these cell culture medias. We noticed that with chemically defined medias there are between 20 to 100 different components. We use the finest raw materials we can find compendial grade, which are 99.5% pure. However, if there are several different components then there is an additive effect for impurities that are present. We also noticed that there are some components that trend and carry more materials. For example, when we view our iron carriers on slide one, we are concerned about the trace impurities which come with the iron carriers. When this study was performed, we tried to identify the kind of sources of variations. We noticed that when we compare from different vendors or the same vendors there is inherent variation in the trace impurity profiles. Once we see this variation, we go back to the source which the variation derived from which are raw materials. Additionally, it is important to review how the iron carriers are mined and how they were synthesized for the salts which were added. It helps create a good dialogue between the vendors and us in order to understand where the variations are derived from—as well as how to control them and track them over a period of time.
Megan Manzano: What impact does media variability have on my product?
Christopher Woolstenhulme: I believe if I am a customer, I would want to understand how my product is being influenced by the impurities. There have been numerous studies which have been done looking at trace metal effects on monoclonal antibodies. Some of the studies performed investigated the glycosylation patterns. For example, the small amounts of metal like zinc may influence the glycosylation pattern on a monoclonal antibody— which translates directly into the drug efficiency and effectiveness. It matters in our company to focus and control things such as trace metals as well as understand how it affects our products. However, it may become complicated because every cell line may behave different depending on the impurities present. It has been agreed upon that these trace impurities have had impacts on the final products. Our company has been working on trying to shore up and understand how these affect our product and our customer’s products.
Megan Manzano: How does Cytiva manage variability in their products?
Christopher Woolstenhulme: We have a robust raw material characterization program that we have been implementing which analyzes all our lots material. There are several different components which go into chemically defined media. We trace and track these impurities from different vendors depending on the components—some components introduce more impurities than others. We track impurities over time as well. If we are receiving amino acid from certain vendors these impurities can track changes in the process or change their supply. It helps control over our raw materials and creates an open dialogue with our suppliers. Therefore, we receive oversight into what we are putting into our product.
Megan Manzano:How do I know what I should be concerned about?
We have customers approach us with concerns and worries and due to different impurities, it can affect different cell lines. We essentially ask the customer “what are you trying to accomplish and make”—which helps create an open dialogue between us and our customers. For example, we have a formulation, and they are concerned about nickel— we look at these nickel content in these batches. For example, the nickel is coming in primarily through an amino acid component in this media. The other contributor varies between a metal salt, other amino acids, or organic compounds. If our customers are concerned about nickel, we would begin by looking at the amino acid in order to identify why it is contributing more of the nickel. If there is another vendor, we may be able to pull from under the lot of material which we may use. We can figure out what will affect the sources of impurities by opening a good dialogue between the vendors and us. We use data base which has been built in order to view raw materials to address questions and concerns.