Expert view: GMP proteins for therapeutic manufacturing: combining consistency, safety, and supply

Proteins are made in biological systems, and thus they can be susceptible to variability. Suppliers should have at the very least an ISO 9001:2008/2015-certified facility. At its core is a quality management system with extensive documentation that includes records of employee training, manufacturing records and SOPs, equipment calibration and maintenance records, and traceability of materials. Physical characteristics of all lots, including purity and activity, should be consistent and fall within the reported range. A formal stability testing program should also be in place. Suppliers should be open to examination of historical records during audits of facilities.

Patient safety is of the utmost importance. As a result, it is often preferred that GMP cytokines and growth factors be produced in an animal‑free process. This helps mitigate risks from adventitious agents such as viruses, TSE/BSE, or other potential unknown pathogens. Animal-free is typically defined by protein expression in non‑eukaryotic systems, such as E. coli, and dedicated manufacturing spaces, equipment, and labware. If animal components are used, careful traceability should include certificates of origin that detail applicable safety testing results. Viral testing of cell banks and viral reduction studies should be considered. In all cases, quality control testing should include sterility testing and host cell component assessment.

A stable supply chain is necessary to avoid changes that might require costly revalidation. This becomes increasingly significant the closer to commercialisation drug development becomes. Quality and supply agreements will help ensure that needs will be met. Secondary suppliers should also be considered. The same growth factor or cytokine sourced from different suppliers may look identical on a certificate of analysis but could behave differently in your cell culture system.