Microcarrier Process Development –Expertise from Concept to Clinic
Challenge
Gene therapies, viral vaccines and viral immunotherapies have become leading therapeutic options for the treatment and prevention of different diseases. But as these candidates enter human trials, an advanced level of CMC expertise is needed to develop and execute a manufacturing strategy at clinically relevant timelines.
Adherent cell lines are often most biologically suitable to express these candidates but often prove difficult to adapt to suspension cultures - meaning they remain the workhorse for producing many advanced therapeutics. Roller bottles and cell trays play a key role in very early development, but as clinical demands increase, bioreactor-based processes are necessary to deliver the titer, robustness and scalability needed to deliver meaningful and timely quantities of material to expanding clinical trials.
Here, high powered CMC and process development expertise, capable of rapidly developing a GMP-ready bioreactor-based process for adherent cell lines offers a unique time-to-patient advantages. The challenge for many biotech companies is that this advanced process development expertise is difficult to build internally and sorely missing at large manufacturing-focused CMOs.
The result is often a transformative therapeutic stuck in a cell factory instead of being dosed to a patient.
Solution
High powered process development for adherent cell lines using microcarriers in single use bioreactors.
The APC Approach
At APC, we’re pioneering bioreactor-based process development for adherent cell lines using microcarriers; with proven success up to 500L scales. The high surface area to volume ratio afforded by microcarriers enables us to develop processes with high virus productivity and best-in-class titers, coupled with the scalability and ease-of-use of single use bioreactors.
Growing adherent cells is no easy task and requires a distinct level of expertise. By combining our unique process development knowhow with novel microcarrier selection strategies we can move from proof of concept to large scale bioreactor production in months. In doing so we remove the unnecessary complexity and risks associated with roller bottles and cell factories and instead provide a CMC path to increased patient enrollment, additional trial sites and a sustainable expanding clinical strategy.
APC’s track record developing these processes has been demonstrated together with Bavarian Nordic on a novel, broad spectrum RSV vaccine candidate.
The Power of Expertise
APC’s experience with microcarrier process development and process optimization is unique and extensive. Our science-first approach to problem solving and client-first approach to program management in this highly specialized area includes:
Proof of concept studies for the transfer of cell-stack production, spinner flask or roller bottle processes to a microcarrier-based process.
Evaluations of viral infectivity using fixed conditions for differing cell line-micro carrier combinations.
Screening studies of alternative cell lines to evaluate growth potential using different microcarriers.
Optimization of infection parameters including the MOI, TOI and TOH.
Exploration of optimal harvest strategies (batch vs. perfusion) to maximize titer.
Upstream process development to support viral titer improvement that will support anticipated clinical and/or commercial requirements.
Advanced Process Modeling and Engineering Characterization to model microcarrier environment in the bioreactor and increase process understanding.
Computational Fluid Dynamic (CFD) simulations to compare differing mixing environments to ensure mixing environment is consistent across scales.
Utilizing Ambr® 250 high throughput automated bioreactor system to enable efficient, cost effective and scalable process development on microcarriers.
Leveraging Process Analytical Technology (PAT) to build processes knowledge and rapidly define improved control strategies.
