Achieving Fully Continuous End-to-End Processing

The current “continuous” downstream is a complex sequence of batch operations, almost a slight-of-hand continuous process that cannot take advantage of most of the value of truly continuous processes. While the current chromatography-based processes are sufficient to bring the cost of goods manufactured down by 40-60%, there is significant benefit from a truly continuous process.

We have demonstrated the use of recombinant affinity nanoparticles and complexes in a dialysis and tangential-flow filtration-based capture step. The development of the nanoparticles is challenging and we have tested over 100 nanoparticles evaluating expression, their ability to bind antibody, and their stability under acidic elution conditions. We believe many are economical enough to allow commercial use, though we have found many to have suboptimal stability at low pHs and that most of the high-pH constructs have significantly reduced capacity. Finally, we have found that the wide pore-size distribution on UF membranes have allowed 10% or more of the nanoparticle to pass through along with the antibody.

We will discuss general methods we’ve used to quickly evaluate nanoparticles including small scale, ~1000kDa MWCO dialysis, and centrifugal dead-end ultrafiltration.  We will also discuss associated analytical techniques including mass photometry, SEC, and native blue electrophoresis.

The data we have generated allows us to be confident that these methods are worth continued effort. Truly continuous processing allows the reuse of solutions from a cleaner downstream to a dirtier upstream. This reuse of solution, and the continuous nature of the process, should decrease cost of goods beyond the current ICB processes while increasing the level of sustainability.

Presented by Jon Coffman, Executive Director of Bioprocess Technology and Engineering at AstraZeneca

Jon leads the Bioprocess Technologies and Engineering (BTE) function in Biopharmaceutical Development at AstraZeneca. He is responsible for development of transformative new process technologies and engineering solutions in support of AZ biologics portfolio. BTE is a specialized function created to ensure leadership within bioprocess engineering and bio-manufacturing technologies within AZ. He was recently inducted as an ACS Fellow.

Jon is a thought leader within Biologics Process Sciences with 30 years of experience in major biopharmaceutical companies, including 15 years at Pfizer (formerly Wyeth Biopharma and Genetics Institute) and 6 years at Boehringer Ingelheim (BI), and 5 at AstraZeneca. Jon is a strong technical leader who has pioneered the development of novel purification technologies while at Wyeth/Pfizer and continuous manufacturing technologies at BI and AstraZeneca. Much of his work has been recognized via strong peer reviewed publications record and patents.  Jon received his B.S. in Chemical Engineering from University of Maine and his Ph.D. in Chemical Engineering from University of Wisconsin, Madison.Dr.. Jon and his team are instrumental in driving the implementation of AstraZeneca’s bioprocessing innovation vision.