Cell and gene therapies (CGT) are changing the treatment landscape for many diseases and, with each new headline, patients are putting their hope in the promises that these novel therapies may bring. However, these new approaches come with many challenges that the industry needs to address – from delivery paradigms, to regulatory and supply chain issues. BioPhorum Cell and Gene Therapy has worked hard for two years and is beginning to deliver on its promise to address the key challenges in this area.

Lili Belcastro, Scientist at Janssen, explained the importance of the Phorum. “CGT is a rapidly growing field and we have a lot of work to do. We need to understand processes and regulations where guidance is being regularly updated.”

The Raw Material Sourcing and Supply Workstream is assessing the problems the industry may face in raw material variability. According to Aaron Mack, Senior Engineer at Biogen, “The cellular processes involved in gene therapy are more complicated than antibodies due to the increased complexity of using cellular machinery to assemble multiple proteins into a capsid and stuff it with DNA. As a result, we expect to see more of an impact from raw material variability. However, there are lots of unknowns that may not appear until we have an issue on a commercial scale, wherein a higher volume of raw materials will be used to meet patient needs.”

The team is assessing and proactively identifying raw material risks that could interrupt the production of CGT products, and prioritize resources for risk mitigation and resolution. Belcastro explained, “The team is building a risk assessment paper for CGT raw materials that considers another BioPhorum paper on biopharmaceutical products and other sources. Instead of reinventing the wheel, we are leveraging the similarities and defining the differences. The risks in CGT are different from biopharmaceuticals; we needed to determine how to address these and mitigate them based on safety.”

“CGT is where biologics were 20-years ago regarding understanding the impact of material variability.”

AARON MACK, SENIOR ENGINEER AT BIOGEN

Guidance for commercial-scale manufacturing EHS and biosafety The Environmental Health and Safety (EHS) and BioSafety

Workstream has written a paper called Environmental Health and BioSafety Risk Assessment Guidance for Commercial Scale Cell and Gene Therapy Manufacturing, which detailed the EHS areas to be considered when establishing a new CGT manufacturing facility.

Kim DiGiandomenico, Senior Manager – Biological, Radiation & Laboratory Safety at AstraZeneca, shared a draft of it at the Association for Biosafety and Biosecurity Annual Conference in November 2019, and the paper has been accepted for publication by the Journal of Applied BioSafety. According to DiGiandomenico, “Guidance for commercial-scale manufacturing EHS and biosafety is mainly limited to the Guidelines for Recombinant and Synthetic Nucleic Acids from the NIH, which is a US-centric government entity,” said DiGiandomenico. “Through the collaborative efforts of BioPhorum, we hope to establish an industry standard for assessing the risks in this advancing field without being prescriptive, as each organization and pipeline project will be unique.”

Working collaboratively has been a rewarding experience for members and they are excited about the potential of the workstream to make meaningful change. According to Mack, the fact that the Phorum includes both suppliers and manufacturers is beneficial. “In the past, making some of these decisions without suppliers led to issues, in which we assumed that the Phorum had incorrectly assumed suppliers’ capabilities. Including suppliers lets us know what is reasonably achievable in terms of controlling variability when considering commercial development or capital investment,” said Mack.

Belcastro added, “Working with the CGT Phorum has been a great process. We can learn from other companies and their processes and take these lessons back to our own companies to make improvements.”

“Being connected to this group, I have become aware of obstacles others have encountered, which has prompted me to rethink how we function at our own facilities and if there are ways we can do our science safer.”

KIM DIGIANDOMENICO, SENIOR MANAGER – BIOLOGICAL, RADIATION & LABORATORY SAFETY AT ASTRAZENECA