Scaling without stalling: Navigate the speed-vs-cost dilemma in viral vector manufacturing
The cell and gene therapy (CGT) landscape is maturing at an incredible pace, demonstrating real-world impact for patients with previously untreatable conditions. As of mid-2025, the global clinical pipeline has expanded to include 36 approved gene therapies and 71 non-genetically modified cell therapies [1].
At the heart of these life-changing products are viral vectors. For therapeutics relying on adeno-associated viral (AAV), lentiviral (LV) and retroviral (RV) vectors, demand is rising sharply across oncology, neurology and rare genetic disorders [1].
For small and mid-sized biotechs, as well as patients, this growth represents a significant opportunity, but it also brings a critical operational reality check: the promise of these therapies can only be realized if manufacturing can meet product demand. However, translating innovation into a viable, scalable manufacturing process is often as complex as the therapies themselves.
The hurdles of scaling: Speed, cost and complexity
When progressing a CGT to commercialization, small and mid-sized biotechs will face the challenge of managing manufacturing scalability, assay readiness and regulatory expectations, often with the additional hurdle of limited internal resources and funds.
While reaching first-in-human trials quickly is vital for securing funding, a “speed-first” strategy that ignores long-term scalability can lead to expensive re-optimization later. Balancing these priorities is essential for long-term success.
Building a scalable foundation
Smarter viral vector scale-up requires starting with the end in mind, transforming innovative science into a viable, reproducible process. Every early decision, from plasmid sourcing to analytical design, lays the groundwork for commercial readiness and long-term success.
For small and mid-sized biotechs, the transition from research-grade to Good Manufacturing Practice (GMP) production is a complex journey that demands a strategic focus on three critical pillars:
- Tailored scale-up approaches
While AAV, LV, and RV vectors share common manufacturing principles, each requires a tailored scale-up strategy to maintain performance and consistency. For example, when scaling AAV production, maintaining yield and consistency can be challenging. As a result, optimizing enhancers, sensitizers and transfection reagents early is key to maintaining efficiency at large volumes. Alternatively, when scaling LV and RV vectors, maintaining integrity is a predominant hurdle. Streamlined, shear-aware workflows and well-tuned chromatography systems can support higher recovery and product quality. - Upstream material decisions
Early material choices define vector manufacturability and determine success in downstream steps like technology transfer. For instance, producing GMP-grade plasmids can take months, making early vendor engagement critical to prevent timeline delays. Additionally, securing access to licensed master cell banks and choosing high-quality cell substrates from the start mitigates supply risks and supports comparability at later stages. - Analytical rigor and regulatory confidence
Establishing fit-for-purpose assays as part of Quality by Design (QbD) allows teams to track critical quality attributes (CQAs) throughout development, ensuring scale-up steps are grounded in meaningful data. Regulators expect validated, phase-appropriate methods that accurately measure product attributes like potency, purity and safety. Investing in these activities early enables developers to generate the necessary CMC documentation to support IND or IMPD submissions with confidence.
By addressing these core areas early, developers can ensure their processes are robust enough to meet clinical demand without requiring costly re-optimization later
Scaling smarter with a ‘perfect-fit’ CDMO
For small and mid-sized biotechs, the technical complexity of scaling viral vectors makes partnering with a contract development and manufacturing organization (CDMO) a strategic decision that directly impacts the path to commercialization.
A perfect-fit CDMO partner will provide a commercial perspective early, building phase-appropriate processes that avoid costly rework. This alignment is essential for navigating the transition from first-in-human to first-in-market without losing momentum. By acting as an extension of your team, the right partner offers the transparency and flexibility needed to manage the unique risks of emerging programs.
With direct access to technical experts and adaptive approaches, including platform, custom, or hybrid solutions, a perfect-fit CDMO ensures your scale-up is grounded in data and regulatory fluency. This model allows biotechs to move quickly and scale smartly, turning complex plans into measurable progress.
Ready to move from first-in-human to first-in-market?
Download our full eBook: A biotech’s guide to smarter viral vector scale-up to discover practical levers to protect your timeline and de-risk your path to commercial success.
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