Developments and Efficiency Gains in Clone Selection and Upstream Process Development

Although biopharmaceutical manufacturing involves multiple interdependent processes, improvements to cell lines and culture techniques continue to be the primary drivers of bioprocess innovation. Reliable, genetically stable, and high-producing mammalian and bacterial cell lines have improved upstream production significantly, along with high-quality serum-free culture media and new options for flexible fed-batch, perfusion, and hybrid single-use bioreactor systems.

^{This article is posted on our Science Snippets Blog}

Upstream gains have led to innovations in downstream purification, including the development of capture and polishing chromatography formats. These increase capacity and selectivity and have introduced rapid membrane-based solutions into connected and continuous manufacturing settings.

Advances have driven the development and implementation of process analytical technology, including novel sensors for in-line, on-line, and at-line monitoring of critical quality attributes and product critical process parameters. Adoption of flexible, high-performing detection methods for multi-attribute monitoring —e.g., mass spectrometry (MS) — are expediting analytical turnaround times and enabling real-time release of drug products.
 

To continue to accelerate development, the biopharmaceutical industry needs to improve clone selection and process development (PD). By partnering together, Sartorius and Waters are enabling process engineers to maximize yield, manufacturing efficiency, and drug-product quality — all while reducing development timelines.  

Clone selection typically takes up to 10 weeks. Sartorius and Waters are reducing that timeline by developing a solution based on Sartorius Ambr^® multi-parallel bioreactors and Waters’ small-footprint BioAccord System, that can analyze critical parameters for recombinant-protein production within 48 hours.  

Currently, scientists in PD partner with core analytical groups using techniques like MS to support their process understanding. However, separating process and analytical functions can cause inefficiencies because PD laboratories must rely on one central facility’s limited capacity to generate data.  

Data packages can be comprehensive, comprising many hundreds of measurements for multiple attributes, timepoints, and samples. Engineers acquire the data using complex, specialized equipment that requires both expertise and time. It can take two to six weeks or more to generate the requisite data from each culture run. Analytical bottlenecks can lead biomanufacturers to measure fewer timepoints, assess fewer conditions, or accept long turnaround times.
 

By combining an Ambr^® platform and BioAccord system in the same laboratory, engineers can acquire comprehensive and near real-time information about product quality attributes and the complex changes in cell culture media over the course of a culture run.

Enabling PD teams to generate key analytical data themselves reduces the dependency on the limited capacity and long turnaround times associated with core analytical facilities. Removing this restriction on analytical bandwidth allows engineers to capture product and media data throughout a culture. By being able to compile a broad panel of product quality attribute data alongside media analysis and bioreactor information within 24-48 hours of a culture ending, engineers can proceed with data review meetings. This can result in more efficient decision-making processes for clone selection and process optimization studies, and potentially reduce the number of culture runs required.