With mounting pressure to bring biologics to market faster, developers face a challenge: advancing therapies quickly while managing the uncertainty of drug development timelines, regulatory requirements, and market demand. Traditional manufacturing scale-up approaches often create bottlenecks that slow commercialization and introduce significant financial risk.
The manufacturing strategy you pursue early in development has lasting downstream implications. The choice between scale-up and scale-out shapes your entire development trajectory. Scale-up involves increasing bioreactor size as production needs grow, while scale-out increases capacity by adding identical bioreactors onto the manufacturing line that operate in parallel. For many biologics developers, single-use scale-out manufacturing is emerging as a strategic solution to critical commercialization challenges.
Traditional scale-up manufacturing requires a transition from small stainless-steel bioreactors through progressively larger vessels as a product advances from early development toward commercial manufacturing. However, transitioning between different bioreactor scales alters cell culture conditions, potentially affecting both product quality and process reproducibility. Each increase in vessel size creates different environmental conditions for cells, introducing variables that must be carefully managed and validated.
The scale-out alternative leverages single-use technology to maintain consistent bioreactor scale while adding parallel units to increase capacity. Rather than investing in fixed stainless-steel infrastructure, this approach uses disposable bioreactor systems that provide flexibility to adjust production volume by running multiple bioreactors as demand evolves. Additionally, scale-out manufacturing delivers concrete advantages throughout the development lifecycle including reduced contamination and operational risk through closed single-use systems, improved process consistency and comparability by maintaining the same scale throughout development, and minimized cell culture microenvironment changes that typically occur during traditional scale-up.
Why does this decision matter more than ever? Four crucial development challenges reveal why manufacturing strategy requires early, careful consideration.
Accurately predicting market demand for biologics remains exceptionally difficult. Developers typically provide low, mid, and high demand estimates that can differ significantly from one another. These projections often struggle to account for potential label expansions or additional indications that may emerge after initial approval. The challenge intensifies when inaccurate forecasts made during pre-approval stages become locked into multi-year manufacturing contracts, leaving little room to adapt as market realities unfold.
Scale-out manufacturing provides flexibility in managing demand uncertainty. Production capacity can be increased by running additional batches in parallel, rather than requiring your manufacturing partner to build new large-scale infrastructure. This approach makes it easier to accommodate unexpected demand spikes or multiple indication approvals without the long lead times associated with traditional capacity expansion. In times when demand drops, scale-out systems can be dialed back to match customer needs, helping maintain profitability.
The financial burden of preparing for commercial-scale manufacturing can be substantial. Traditional scale-up requires significant pre-approval investment in large-scale process development and equipment. Developers face expenses for specialized equipment, media, supplements, and raw materials at commercial scale, along with costly process performance qualification (PPQ) runs and extensive process characterization. Each of these investments occur before developers know actual market demand or secure regulatory approval.
Single-use manufacturing strategies offer a more economical path forward. By launching at clinical scale with the ability to expand post-approval, developers can reduce raw material costs to better manage expenses throughout development lifecycle. Single-use systems also eliminate the need for extensive cleaning validation studies required for stainless steel equipment. Most importantly, capital investments align more closely with actual market demand, and financial commitments shift closer to the approval milestone, reducing the risk of over-investing in capacity or contracting for manufacturing slots that may not be needed.
For many development programs, manufacturing timelines pose the greatest challenge.
Large CDMOs often have significant wait times for commercial-scale capacity. Once capacity is secured, inflexible timelines for implementing new processes in stainless steel facilities can stall accelerated development programs. The timeline from initial engagement through manufacturing readiness can require up to a year with traditional scale-up strategies.
The timeline advantage of scale-out manufacturing is significant, saving 6-12 months in the transition from clinical to commercial production through minimal lead times and rapid expansion capabilities. Additionally, reduced changeover time between manufacturing campaigns means your CDMO partner can respond more quickly to your production needs, helping you reach patients faster.
Regulatory agencies offer fast-track programs, including FDA Breakthrough Therapy designation, EMA PRIME scheme, and PMDA Sakigake designation, that compress development-to-approval timelines, enabling faster delivery of innovative therapies to patients. These accelerated pathways create tremendous opportunities, yet they also intensify pressure on manufacturing readiness. Conditional approvals and adaptive pathways also require manufacturing flexibility to accommodate potential changes as real-world evidence emerges and demand fluctuates.
Adopting scale-out strategies utilizing single-use bioreactors enables regulatory agility by allowing fast product launch at clinical scale, then scaling out post-approval as production needs increase. This approach provides quicker response to post-approval manufacturing needs without requiring extensive comparability studies that would be necessary when transitioning to larger bioreactor scales.
A successful scale-out strategy depends on more than access to single-use manufacturing technology. It requires partnership with a CDMO that brings strategic manufacturing capabilities, flexibility in process design, and dedicated teams of experts whose proven experience reduces implementation risk throughout development and clinical phases.
With several decades serving the biologics industry, AGC Biologics has built its CDMO model around a core principle: configuring facilities around client processes rather than requiring processes to conform to existing infrastructure. Drawing on extensive expertise in mammalian manufacturing and cell line development, AGC helps developers navigate the complexities of drug manufacturing-from initial clinical production through commercialization-with a track record of meeting accelerated timelines.
Manufacturing decisions have cascading effects throughout the drug development process. Scale-out approaches utilizing single-use manufacturing technology can address multiple common challenges simultaneously, offering greater flexibility in managing demand uncertainty, reduced upfront costs better aligned with development milestones, faster paths to market launch, and lower comparability risk compared to traditional scale-up. Early evaluation of your manufacturing strategy is critical to avoid costly downstream constraints. This is especially true for late-stage programs, where single-use scale-out approaches often provide better alignment with commercialization goals than traditional scale-up.
The key is working with experienced partners who provide truly flexible manufacturing strategies and understand how to scale efficiently, from a single 2,000 L bioreactor to multiple parallel units, as clinical stages advance and product demand becomes clear. With the right outsourcing partner that has that experience, you can navigate development uncertainties while keeping your program on track at every stage, including commercial production.
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