Driving Progress in Biomanufacturing
As demand for increasingly complex biologics grows, technological advances and innovative approaches are enabling companies to progress their biomanufacturing efforts.
Biomanufacturing is experiencing significant growth, with recent research estimating the market value to reach USD 967.7 billion by the year 2033 (1). This market expansion will be bolstered by investment in manufacturing infrastructure and production capacity and driven by various trends.
For Hanns-Christian Mahler, CEO, ten23 health, points out that there have been several trends that have propelled progress in the field of biomanufacturing. “Generally, in relation to sterile fill/finish for biologics, there are various important areas of progress I see: a trend towards smaller batches (given more focused patient stratifications), the necessity for Quality and Annex 1 compliance and related updates (still to happen with many companies), a trend towards (subcutaneous) self-administration in combination with delivery devices, and finally, more focus on sustainability,” he emphasizes.
“Biomanufacturing has progressed from the recombinant production of naturally occurring proteins to specifically targeting antibodies to highly engineered non-natural proteins such as bispecific T cell engagers to hybrid molecules, which include biologic and synthetic combinations,” asserts Alison Moore, Chief Technical Officer, Codexis.
Demand for Increasingly Complex Biologics
“One of the primary drivers of progress in biomanufacturing is the growing demand for increasingly complex biologics, including bispecific antibodies, fusion proteins, and antibody-drug conjugates (ADCs),” states Magdalena Leszczyniecka, CEO of STC Biologics. “These next-generation therapies require innovative approaches to both design and production due to their structural complexity and difficulty with expression, purification, and analysis.”
Focusing on the nascent field of gene therapies, Scott Broughton, CCO, Ascend, highlights two key areas of biomanufacturing that have advanced. “One is higher quality and [the other is] greater yield, two aspects that increase safety and lower the cost of production for our clients,” he says.
As a CDMO with roots in the chemistry, manufacturing, and controls (CMC) labs of drug developers, technology has significantly evolved over the past 20 years to deal with increasingly potent compounds, Broughton explains. “Higher potency translates directly to improved patient safety through lower required doses, while simultaneously reducing cost of goods,” he adds. “Most importantly, these advances are making gene therapies accessible to broader patient populations who desperately need these treatments.”
Computational tools are allowing biomanufacturers to overcome certain challenges associated with more complex therapies, notes Leszczyniecka. “These technologies allow scientists to predict protein folding and assess potential sequence liabilities early in the construct engineering phase. This helps optimize domain architecture, inter-chain pairing increasing expression levels and reducing downstream developability issues,” she says.
Technological Advances and Innovative Approaches
“Biomanufacturing is a fast growing and evolving field,” specifies Steve Lavezoli, VP, Curia Biologics at Curia Global. “Technologies like AI [artificial intelligence] and continuous manufacturing are becoming more feasible in the industry, with advances constantly on the horizon.”
For Minni Aswath, VP of Process Development, Bionova, significant strides have been made in biomanufacturing over recent years, with advanced analytics and AI proving to be key for industry. “Machine learning models are being used to predict yields, streamline process and formulation development, optimize manufacturing, and detect deviations,” she says.
Aswath also highlights continuous bioprocessing as a key advancement for the sector. “[Continuous bioprocessing] enables real-time monitoring and control, offering greater efficiency and consistency,” she notes.
“Over recent years, the field of biomanufacturing has seen remarkable progress, driven by several technological advancements and innovative approaches,” remarks Vinay Saluja, Global Head Development Services, Novartis Contract Manufacturing. Process intensification, through intensified fed-batch and the N-1 production processes, has been a significant development for biomanufacturing he notes.
Intensified fed-batch and N-1 production processes have allowed companies to optimize the efficiency and productivity of biomanufacturing, continues Saluja. “Additionally, the supply chain, logistics, and distribution process of the innovative CAR-T [chimeric antigen receptor T cell] based products have seen huge improvements ensuring the timely delivery of these critical therapies to patients in a very short time,” he says.
“In the mammalian field, the change from random integration to targeted integration (via transposases or landing platforms) has been a step change in driving higher titers,” comments Kenneth Holbourn, Senior Director of Technical Project Lead Group (PD), FUJIFILM Biotechnologies. “This update coupled with high intensity culture and accelerators like N-1 perfusion has driven the bottleneck from USP [upstream processing] capacity to DSP [downstream processing].”
USP productivity has been pushed to new heights through intensification, while also reducing footprint and cost, concurs Leszczyniecka. “Furthermore, DSP technologies have evolved to match this complexity. New chromatography resins offer better selectivity and capacity for difficult-to-purify molecules, while ADC manufacturing has benefited from innovations in site-specific conjugation and novel linker chemistries that improve stability, homogeneity, and payload control,” she says.
For small interfering RNA (siRNA) therapeutics, which are an important modality in the genomics medicines space, challenges associated with their manufacture and scale up are being overcome through the application of biocatalysis, Moore reveals. By applying biomanufacturing through an evolved enzymatic platform that synthesizes siRNA through biocatalysis, it is possible to scale more effectively than with chemical alternatives, she explains.
Other advancements such as cell line development, cleaner microbial cell lines, the expansion of single-use technologies, and modular facilities are also affording biomanufacturers more robust, safe, and rapid operations, Aswath adds.
However, CDMOs need to be selective in their technological investments, warns Lavezoli. It is important to make sure the right investments are made, considering how such technologies can best serve the biotech companies, he specifies.
Challenges Remain Despite Technical Progress
Altogether, the technological advancements that have been discussed are “enabling faster, more efficient development and manufacturing of complex biologics, making it possible to deliver these complex therapeutics at scale and in a more cost-effective manner,” Leszczyniecka specifies.
“Progress is science, but also people coming together to solve problems,” Broughton summarizes. “We've made significant technical progress: improving quality, increasing yields, and developing innovative capacity solutions. However, our greatest challenge isn't technical; it's economic sustainability.”
Reference
IMARC. Biopharmaceutical Manufacturing Market Report by Cell Culture (Mammalian Cell Culture, Microbial Cell Culture), Class (Monoclonal Antibodies, Recombinant Proteins, Interferon, Granulocyte Colony-Stimulating Factor (G-CSF), Erythropoietin, Recombinant Human Insulin, Vaccines, Human Growth Hormones (HGH)), and Region 2025–2033. Market Research Report, December 2024.