2021 FDA Science Forum
Product Quality Assessment in a Continuous Bioprocessing Approach Using a Perfusion WAVE Bioreactor and an Acoustic Wave Separator
- Authors:
- Center:
-
Contributing OfficeCenter for Drug Evaluation and Research
Abstract
Continuous bioprocessing is an important approach in current biopharmaceutical manufacturing to enhance manufacturing speed, operation flexibility and reduce production costs. Importantly, continuous drug substance harvest clarification is a critical interface needed for a successful integration of upstream (cell culture) and downstream (purification) bioprocesses. This integration needs to occur without decreasing process performance and product quality but is a critical challenge due to flow considerations at high cell densities that can restrict working flow rates and eventually build up pressure when using filtration. In this study, we implemented a novel continuous upstream bioprocessing approach and explored potential regulatory concerns regarding potential risks to product quality. We integrated a perfusion GE WAVE 25 bioreactor which allows prolong cell culture to a PALL Cadence acoustic wave separator (AWS) which provides continuous cell clarification of harvested material. Using the perfusion WAVE bioreactor, we were able to achieve representative operating conditions and batch growth kinetics. The AWS allowed effective cell clarification/filtration and product recovery. Product quality was evaluated to determine any potential impacts on the monoclonal antibody from the process. Lastly, the impact of acoustic wave on cellular damage and its potential effect to any cell debris were tested. Overall, we believe our assessment provides useful information for the implementation of a continuous cell clarification tool and further understand its impact on product quality.
