Raw Material Variability Control: Where Do We Go From Here?

Managing raw material variation and process risks is critical to ensuring a high level of quality and consistency in drug development and manufacturing. Supply chain partners across the industry must work together to understand the issue of raw material variation and the impact it can have on the safety and efficacy of therapeutic products. A conjoined effort of all stakeholders is needed to identify best practices and apply them in their daily roles to mitigate potential risks.

In May 2018, Cytiva hosted the second annual Raw Materials Variation and Control Symposium as one way to bring experts from across the industry together to discuss how they are addressing raw material variability issues in their companies and what they are doing to overcome them. Life Science Connect recently sat down with Cory Card, Principal Scientist at Cytiva, to talk about not just what ideas were shared at the symposium, but, most importantly, where we need to go from here.

Life Science Connect: It is evident from this year’s conference that progress has been made to improve the quality of raw materials as well as gain more control over variation. In your opinion, where are you seeing the most progress?

Cory Card: I believe the greatest progress has been a better understanding by the industry of the current quality of raw materials used in cell culture, specifically with regard to impurities that are significant sources of variation in the production of biotherapeutics. A number of cell culture media manufacturers and drug substance manufacturers are characterizing these impurities and their impact on cell culture processes and products. As a result, there are healthy conversations taking place across the supply chain that are developing a greater awareness about the challenges we all face and, even more importantly, how we can collaborate to mitigate risks. For example, the BioPhorum Operations Group (BPOG) has published several resources, including a white paper titled “Patient-Centric Requirements for the Supply of Raw Materials into Biopharmaceutical Manufacturing” and a standardized raw material technical questionnaire for suppliers. BPOG is also working to understand variability in test results among various laboratories and across companies within the industry. In addition, an ASTM International standard has been developed to enable electronic data exchange. These are all excellent steps in developing the alignment needed to influence positive changes in the quality of raw materials.

LSC: What else do you think needs to be done across the supply chain to influence even more change?

Card: Well, we have a lot of work to do. Many of the changes we need are going to take a united effort in order to really have a positive impact on this issue. The cell culture market is relatively small compared to other markets competing for the same raw materials, which potentially have lower sensitivity to impurities or other aspects of quality. Even if the suppliers of these raw materials are striving to meet the quality standards required for cell culture, they may have little choice in where or how the materials originate or are harvested. There are added costs if additional processing is the only answer to improve the quality of the materials. In general, we need to collaborate throughout the supply chain to identify and implement best practices of sourcing, collecting, deriving, processing, and testing these materials.

LSC: The ASTM E3077 standard offers a way to standardize digital electronic information sharing across the industry, which is critical when it comes to controlling raw material variation. Where are we with its use across the industry? What, if any, are the current challenges of, or roadblocks to, implementing it?

Card: There have been some great cases of implementation of the ASTM E3077 standard among some drug substance manufacturers, cell culture media suppliers, and raw material suppliers. However, I feel broader adoption is needed. In my experience, the main reason for a lack of adoption by some companies is that they do not understand it yet or do not have simple tools to implement it. Instructions and converters are available, though, to define and simplify the creation of these files. It is important to keep in mind that this standard allows digital transfer of data in a very flexible way. Data that is traditionally printed and included on hard copy Certificates of Analysis, for instance, can be shared electronically. Therefore, it is much more easily implemented into a database or material/information management system.

LSC: What concerns are you aware of when it comes to establishing a standardized system for data sharing, and what value do you see in that collaboration?

Card: When we speak of data sharing, it is often met immediately with hesitation and concern. This reaction typically stems from a lack of clarity around what kind of data is expected to be shared. Concerns over loss of intellectual property or other data typically held private are common. Yet, the data to be shared electronically could be limited to data that is already shared in a nondigital format, (e.g., a Certificate of Analysis). When such data can be shared in a digital format, it reduces manual transcription of the data, preventing typographical and other errors. Sharing data digitally also facilitates integration into a database or data management system, such as a laboratory information management system (LIMS). This can help simplify quality control and other efforts, as well as make electronic lot genealogical information more accessible.

LSC: In general, how can the industry work together better, specifically with suppliers, to proactively identify raw material issues? Are there any specific resources that would help achieve this goal?

Card: I have been involved in many discussions with raw material suppliers in an attempt to clearly convey the current challenges with quality and what impact it has on our products and processes, and especially on the quality of drug substances. Initially, these discussions can be difficult, as we often do not get to talk to the appropriate audience. It is also a challenge if those we are speaking to do not understand the technical aspects of raw materials, their use, as well as the capabilities of the suppliers to monitor and control variation. I think forums, such as the Raw Materials Variation and Control Symposium, are a great way to increase awareness and understanding, align resources, and drive the creation of standards that will be important in addressing raw material challenges. However, many supply chain stakeholders are not yet participating in these discussions, and are thus unaware of these challenges. It is important to reach out through supply chain networks to spread more awareness about raw material variation and control and to foster greater collaboration and communication throughout the industry.

Cory Card – Principal Scientist, Cytiva

Cory serves as principal scientist for the cell culture business. His experience includes more than 24 years’ experience in cell culture and biotechnology. His roles during the past 18 years include leading research and development efforts as a scientist, team leader, and director of research, product, and process development. He received his MS in Virology from Utah State University with a primary focus on factors influencing pathogenicity of the influenza virus.