Analysis Of Engineering Manufacturing Risk Utilizing A Modularized And Standardized Single-Use Manifold Design Approach

By Robert Hendrix, Staff Engineer, Systems Design; Levi M. Larsen, Market Intelligence Analyst III, BioProduction; Kayla J. Spivey, Content Specialist III, BioProduction, Thermo Fisher Scientific

Process design for the production of recombinant proteins becomes an increasingly important focus for the commercialization and delivery of a variety of rapidly expanding pharmaceutical modalities including monoclonal antibodies, cell therapies, and gene therapies. Process design is also important for the successful manufacturing of critical subcomponents to support processes for mRNA vaccines. Manufacturing processes are customized for the manner of terminal sterilization of the product; therefore, a thorough understanding of proper aseptic design and low bioburden design practices is required to safely mitigate risks for the targeted patient or mitigate manufacturing risks for subcomponent contamination in downstream processes. Specifically, the risk of potential ingress of adventitious agents or nonviable particulates that can copurify with the product  must be mitigated in the design of the process.

In this white paper, we present a manufacturing risk analysis for a novel standardized and modularized single-use manufacturing strategy for 2,000 L scale single-use recombinant protein production using the mAb Process Playbook Modular Library developed by Thermo Fisher Scientific. We evaluate manufacturing risk of this approach by calculating engineering risk profiles for 10 unique end-to-end 2,000 L processes and evaluating these risk profiles against a 98% manufacturing success rate standard.