Cell culture media greatly impacts biomanufacturing in both positive and negative ways. Variability in cell culture media and associated raw materials can create variation in the upstream manufacturing process, as well as impacting final product quality. New analytical technologies have made it possible to have a better understanding of what contributes to cell culture media variability and as a result it is incumbent on cell culture media suppliers to implement control processes and a robust quality assurance program.
Key areas for consideration include:
- Employing a risk based approach to managing raw material ingredients and assessing the impact that impurities have on cell culture performance and protein quality.
- Setting high standards with raw material suppliers, which includes defining raw material quality attributes, classifying animal origin risks and establishing change notification policy.
- Purchasing the same approved raw materials for use in all manufacturing sites, thus ensuring a consistent cell culture media, regardless of which site it was manufactured at.
MilliporeSigma has defined their approach through a comprehensive quality assurance program to control cell culture media variability and ensure the quality of products worldwide. Their robust supply process incorporates the following key attributes:
Global Raw Materials and Vendor Management Program
MilliporeSigma has set high standards for suppliers and their quality systems that include communication of any change and visibility into their process when needed. Their raw material experts work with suppliers to define the right quality attributes for the raw material and once identified, procurement experts purchase the same approved cell culture media raw materials, from the same qualified suppliers, for use at all manufacturing sites. Thus ensuring media consistency regardless of manufacturing location.
A critical aspect of setting raw material critical quality attributes is to understand the source of the variability. MilliporeSigma has developed a raw material characterization program to study their raw materials and to provide the scientific rationale to create raw material specifications that comprehensively address any potential issues.
One area that is critical in the evaluation of certain raw materials is in trace elements. The role of trace elements and the impact on protein and product quality is well documented. MilliporeSigma provides the data necessary to begin understand this variability, with the option of quantitative testing by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for copper, manganese, zinc, molybdenum, nickel, vanadium, aluminum, selenium, chromium, and cobalt.
Further, they have identified raw materials that are at risk for trace element impurities and have established monitoring programs. If there is a change in the supply chain, the risk of trace element impurities is included in the evaluation of any potential variability.
Consistent Manufacturing Network
MilliporeSigma has also addressed the challenging issue of securing dual sources of cell culture media in biomanufacturing. By incorporating manufacturing redundancies with their sites in Europe and the United States, they eliminate the need for a second supplier to mitigate supply chain risks.
Global Quality Management System
In order to meet global quality requirements, MilliporeSigma cell culture facilities are governed under a Single Global Quality Manual featuring:
- All sites are certified as ISO 9001:2015 and voluntarily comply with IPEC-PQG for Good Manufacturing Practices.
- Standard quality control assays for media using harmonized current compendia methodologies
- A tiered approach for customer inquiries to provide quick and appropriate support
- A commitment to staying at the forefront of all relevant guidelines and regulations.
To learn more about MilliporeSigma’s Cell Culture Media Supply Program, please see the video below.
Or visit www.merckmillipore.com/ccmsupply
The life science business of Merck KGaA, Darmstadt, Germany operates as MilliporeSigma in the U.S. and Canada.