Increased demand for CDMO microbial outsourcing services
Earlier this week the Swiss company announced it was enhancing services at its Visp site to address the growth in the microbial-derived pipeline.
To get a deeper dive on trends in the microbial development space, we spoke to Shiva Khalafpour, vice president, head of microbial business unit, at Lonza.
We first asked her to identify where the greatest demand is for microbial systems in terms of molecule work:
“Generally speaking, the worldwide demand for microbial fermentation production capacities has been steadily increasing over the past few years. This can be viewed as an indicator of the quality of this biosynthetic approach and recognition for its potential.
“We see significant interest in smaller, complex next-generation molecules, such as antibody fragments, antibody mimetics, and bioconjugated biotherapeutics, such as pegylated proteins and polysaccharide-conjugated vaccines, enzymes, fusion proteins and other therapeutic recombinant proteins.”
Additional capacity at the Visp, Switzerland facility was required to align with increasing demand in manufacturing, said the microbial expert.
“This additional demand is coming from current customer requirements and our industry projections for growth in contract development manufacturing organization (CDMO) microbial outsourcing needs.
“Microbial-derived molecules represent the second largest segment in the biologics market and the microbial CDMO market had an estimated size of US$2.2bn in 2020. The market is expected to grow, at a CAGR of 7.8%, to reach US$3.2bn in 2025.”
Speed and yield
One of the main contributing factors for the increased demand is the expression system and its productivity and yield, said the Lonza executive.
“The host strains we use, Escherichia coli and Pichia Pastoris have much faster doubling times than CHO cells usually used for mammalian expression, which significantly shortens fermentation times.
“In addition, effective 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, and this leads to longer and more complex downstream processing for microbial processing – meaning that overall production time may be only slightly shorter than mammalian processes.
In terms of limitations of microbial expression systems, she said certain posttranslational modifications are not possible during microbial expression, including human glycosylation.
“Additionally, microbial expression systems may lead to intracellular aggregation, accumulation of proteins as inclusion bodies, or misfolding of heterogeneous proteins.
“Microbial systems may not support very large molecules such as monoclonal antibodies well.”
Lonza’s expanded services at Visp will include new throughput equipment and automation processes. Khalafpour explained how they are set to help drive efficiency and enhance project delivery:
“Our development activities rely more and more on generating a lot of data in a short timeframe as early as possible to make data-driven decisions while keeping our development timelines as short as possible.
“The new concept of automation in the microbial development service that will be implemented in our new lab combines the capability of high throughput screening in upstream - parallel micro fermentations - and downstream - solubility, refolding and chromatography screenings - with analytical tools using dedicated robotic workstations.
“This approach will debottleneck the generation of analytical data as no manual interventions are required and will greatly improve the dataset quality and quantity used to define the manufacturing process, thus improving its robustness.
“In addition, this comprehensive data set supports the notion that regulatory authorities expect a sounder process understanding as early in product/process development as possible – including those on a path to IND.”