This webcast features: Kathleen McLaughlin, Senior Scientist, BioProcess R&D, Merck & Hironobu Shirataki, PhD, Senior Consultant, Scientific Affairs, Global Marketing, Bioprocess Division, Asahi Kasei Medical.
There are two presentations during this webcast.
Evaluation of the Planova™ BioEX Virus Removal Filter in Continuous Bioprocessing of a Monoclonal Antibody by Kathleen McLaughlin
Standard batch monoclonal antibody biologics manufacturing processes are costly and time-consuming. A switch to intensified continuous processing enables much higher productivity, notably > 1.5 g/L/day over 25+ days of bioreactor and 17+ days of downstream operation.
Our innovative platform has been tested across multiple scales and locations. It automatically operates end-to-end between staggered startup and shutdown operations. After the upstream process starts and specific thresholds are reached, the downstream process is automatically initiated. When stable mass throughput is achieved, the next unit operation begins.
Key challenges during continuous manufacturing include managing process pauses, particularly critical for viral clearance and handling frequent filter switches from an operational perspective.
This presentation will provide an overview of Merck’s continuous manufacturing strategy with a focus on the process development of the viral filtration step. This includes an evaluation of the load amount, pH, and conductivity across two nanofilters, with load pH being the most significant factor. This resulted in the selection of Planova BioEX as the virus removal filter and its use (one of the first to our knowledge) in a continuous manufacturing run over 21 days.
Constant Flow Rate Viral Clearance Study of Planova™ BioEX and S20N Virus Removal Filter and Implementation into an End-to-End continuous Process for MAb Purification by Hironobu Shirataki, PhD
Virus filtration is located at the end of downstream processing and is a critical step in removing viruses from biopharmaceutical products. However, research and technological developments for integrating virus filtration into continuous processes are still ongoing. One suggested solution is integrating filters after column chromatography processes, but there are challenges such as balancing throughput capacity and flow rate across the system, process pauses affecting virus filter robustness, and pressure stability in long duration filtrations.
We investigated the filtration behavior and virus removal capability for a monoclonal antibody (MAb) process in an integrated column chromatography and virus filtration setup under constant flow rate. Mixed-mode AEX and modified CEX columns were run in-series in a pool-less integrated setup with a 0.0003 m2 Planova BioEX virus filter connected.
In order to investigate filter robustness, viral clearance tests for the filter were conducted using the inline spike test method. To address the concern of virus breakthrough, a 60 minute process pause between MAb solution load and recovery flush was conducted during the virus filtration step. A MAb solution with quantified host cell protein content that was processed in the integrated setup achieved high HCP reduction and high MAb recovery. Inline virus spike test at 40 LMH constant flux had robust MMV virus reduction.
The two column in-series process also showed high virus reduction, with tests for MMV yielding a virus LRV greater than five even at a flow rate less than five LMH for Planova BioEX filters. Thus, confirmed integrated setup connecting two columns and virus filter directly was implemented into the end-to-end continuous process.
In the process, batch virus inactivation was executed with auto pH control to clarify the production batch concept. The stable MAb continuous process from perfusion cell culture to virus filtration with high purification and recovery was demonstrated by this process.
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