Mark Brower, Ph.D.
Principal Scientist at Merck

Mark Brower is currently a member of the BioProcess Development group at Merck Research Labs.  There, he is responsible for leading a team of scientists investigating novel upstream and downstream initiatives towards a low cost protein production platform including perfusion cell culture,  continuous biomanufacturing and single-use systems.  Prior to this, Mark has developed purification processes for both natural product secondary metabolites and small molecule enzymatic biotransformations.  Mark earned his BS in Chemical Engineering from The Pennsylvania State University, and a PhD in the same field from Cambridge University.

“Current State of Integrated Continuous Manufacturing for the Production of Therapeutic Proteins”
The growth of therapeutic proteins and vaccines continues to gain momentum in the marketplace with biologically derived molecules owning a predominant position among the top 10 selling drugs.  Despite this growing success, the biopharmaceutical industry faces strict competitive challenges from multiple pressures including economic, regulatory and political.  In response to these demands, bioprocesses have been intensified to yield higher titers in cell culture, reduce capital investments by moving into smaller single-use bioreactors and boosting productivities of downstream unit operations.  Some have proposed that the next step in this evolution will be fully integrated continuous bioprocessing where further efficiencies may be achieved with sophisticated automation strategies and adaptive process control to ensure protein quality and patient access to the product.

Advances in technology for traditional unit operations such as cell-retention devices in perfusion cell culture, continuous multi-column chromatography and single-pass tangential flow filtration have led to pilot-scale demonstrations of both semi-continuous and fully-continuous protein production processes operating at periodic steady states.  In this paradigm, integration of process analytical technologies and real-time multivariate data analysis for quality monitoring in near real-time may ultimately lead to real-time disposition of drug substance and forward processing/filling of the drug product in the same facility.  Obstacles for implementation of this final state vision for continuous bioprocessing exist however, including the lack of characterization tools for unit operations that are truly dynamically linked to one another.  This presentation will include an overview discussion on continuous bioprocessing, continuous unit operations (continuous Protein A chromatography, in-line diafiltration, continuous process monitoring), aseptic sampling of perfusion bioreactors, and a case study for material tracking throughout an integrated continuous biomanufacturing processing line.