Continuous downstream processing for biomanufacturing: an industry review

Abstract

BioPhorum’s First Edition Technology Roadmap outlines a ten-year vision for therapeutic protein production in the biopharmaceutical industry. This paper builds on the first edition by using a model monoclonal antibody (mAb) process to look at technology and regulatory gaps in the area of continuous downstream drug substance processing of therapeutic proteins. Increasingly, continuous processing (CP) for the manufacture of biologics is being discussed as a feasible approach, with commercially available, production scale equipment for the key unit operations now available. The pharmaceutical industry recognises that CP offers advantages over batch-based processing by:

• producing products with a more consistent quality attribute profile
• allowing greater flexibility to react to changes in market demands
• reducing up-front capital investment in facilities,
  due to process intensification
• optimizing cost of goods (COG) through process intensification.

In the small-molecule manufacturing arena, continuous manufacturing has been used to make five FDA-approved products2, but CP has not yet been adopted more widely for clinical or commercial production of therapeutic proteins. This is a timely opportunity to discuss the gaps, limitations and regulatory landscape across continuous downstream unit operations.

This paper performs an end-to-end gap analysis of a typical continuous mAb downstream process from primary capture to bulk drug substance (BDS), identifying current technology and regulatory gaps that are preventing the implementation of continuous biomanufacturing. The intention is to provide a focus to enable the industry and its suppliers to target effort and resources most effectively to generate solutions. This approach results in a catalog of challenges facing continuous biomanufacturing (see Table 1). The authors, members of both the biomanufacturing and supplier communities, believe this list can be used to address the root causes that limit adoption of CP to date.