Increased demand for CDMO microbial outsourcing services


Earlier this week, the Swiss company announced that it improving services on its Visp siteto cope with the growth of the pipeline of microbial origin.

To dig deeper into trends in microbial development, we spoke to Shiva Khalafpour, Vice President, Head of Microbial Business Unit, at Lonza.

Shiva Khalafpour, Vice President, Head of Microbial Sector, Lonza

We first asked him to identify where the greatest demand for microbial systems is in terms of molecular work:

“Overall, the global demand for microbial fermentation production capacities has been steadily increasing in recent years. This can be considered as an indicator of the quality of this biosynthetic approach and the recognition of its potential.

“We are seeing significant interest in new generation, smaller and more complex molecules, such as antibody fragments, antibody mimetics, and bioconjugate biotherapeutics, such as pegylated proteins and polysaccharide conjugate vaccines, enzymes, fusion proteins and other therapeutic recombinant proteins. ”

Additional capacity at the Visp, Switzerland facility was needed to keep up with growing manufacturing demand, the microbial expert said.

“This additional demand stems from current customer requirements and our industry projections for the growing microbial outsourcing needs of Contract Manufacturing Organizations (CDMOs).

“Molecules of microbial origin represent the second largest segment of the organic marketand the microbial CDMO market was estimated to be US $ 2.2 billion in 2020. The market is expected to grow, at a CAGR of 7.8%, to reach US $ 3.2 billion in 2025. “

Speed ​​and efficiency

One of the main factors contributing to the increase in demand is the expression system, its productivity and efficiency, the Lonza executive said.

“The host strains we use, Escherichia coli and Pichia Pastoris, have much faster doubling times than the CHO cells typically used for mammalian expression, which dramatically shortens fermentation times.

“In addition, the efficient generation of process knowledge and data-driven decisions for process and throughput optimizations reduce cycle and batch times. “

However, she noted that due to the diverse nature of the microbial molecule pipeline, there is no single affinity capture step for purification such as protein A in mammalian production, which leads to to longer and more complex downstream processing for microbial processing – meaning the overall production time may be only slightly shorter than processes in mammals.

Limits

In terms of limitations of microbial expression systems, she stated that certain post-translational modifications are not possible during microbial expression, including human glycosylation.

“In addition, microbial expression systems can lead to intracellular aggregation, accumulation of proteins as inclusion bodies, or misfolding of heterogeneous proteins.

“Microbial systems may not cope well with very large molecules such as monoclonal antibodies.”

Automating

Lonza’s extended services to Visp will include new throughput equipment and new automation processes. Khalafpour explained how they are designed to contribute to the efficiency and improvement of project delivery:

“Our development activities increasingly rely on generating lots of data in a short timeframe as early as possible to make data-driven decisions while keeping our development times as short as possible.

“The new microbial development service automation concept that will be implemented in our new lab combines the capability of high throughput screening upstream – parallel microfermentations – and downstream – solubility, refolding and chromatography screens. – with analytical tools using dedicated robotic workstations.

“This approach will unclog the generation of analytical data as no manual intervention is required and will dramatically improve the quality and quantity of the dataset used to define the manufacturing process, thus improving its robustness.

“Additionally, this comprehensive data set supports the idea that regulators expect a better understanding of processes as early as possible in product / process development, including those on the IND path.


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