Cell and gene therapies (CGTs) are no longer an emerging modality. With – as of late 2025 – 38 gene therapies, 36 RNA therapies and 71 non-genetically modified cell therapies approved globally for clinical use and hundreds more in development (1), the field has entered a more mature phase. Increasingly, manufacturing capability is shaping which programs succeed.
Advances in adeno-associated viral (AAV), lentiviral (LV) and retroviral (RV) vectors are helping unlock new therapeutic possibilities across oncology, neurology and rare diseases. However, the ability to manufacture high-quality viral vectors at scale has become a defining constraint.
For many developers, the challenge is no longer whether a therapy works, but whether it can be produced reliably, consistently and in a way that supports regulatory expectations over time. In this context, viral vector manufacturing is shifting from a technical hurdle to a strategic discipline.
Rising expectations in a growing field
The expansion of CGTs across both clinical and development phases has brought increased regulatory scrutiny, including a deeper process understanding, solid analytical control and a clear demonstration of consistency across development phases. These expectations are particularly pronounced for viral vectors, where variability and sensitivity to processing conditions remain persistent challenges.
Demand for AAV, LV and RV vectors also continues to rise in line with CGT development. The CGT manufacturing ecosystem has responded with expanded capacity and more standardized approaches, but viral vector development and manufacturing experience remains uneven, particularly at later stages of development. This highlights the importance of considering vector manufacturing strategy early to support clinical timelines, costs and long-term viability.
Treating scalability as an early design choice
Early decisions on process architecture, materials and intended scale can significantly affect how easily a vector can transition from research to good manufacturing practice (GMP) production. Programs designed with a narrow focus on early clinical needs may progress quickly at first, only to stall later when processes must be rebuilt to support larger volumes or tighter regulatory requirements.
Understanding the target patient population is a critical first step in vector manufacturing. A therapy for a rare disease indication may only require modest production volumes, while broader indications can drive demand into the hundreds or thousands of liters. Processes that can adapt across this range offer greater flexibility and reduce the need for reinvention.
Different vector types introduce different scaling considerations. While these platforms share common manufacturing principles, each has its own distinct risks as manufacturing scale increases. Managing these differences while maintaining quality and speed has become one of the central challenges of CGT development. For example, AAV processes often struggle with yield consistency as volumes increase, while LV and RV vectors are particularly vulnerable to shear stress and prolonged processing. Addressing these risks early through thoughtful process design rather than reactive fixes can significantly reduce development friction later on.
Many of the most consequential manufacturing decisions are made long before GMP production begins. Early-stage choices directly shape not only technical performance but also supply chain stability, regulatory readiness and long-term scalability. In practice, development success is often determined by how deliberately these early decisions are made.
Key considerations include:
● Plasmid strategy: GMP-grade plasmids involve extended lead times and delays in procurement can disrupt manufacturing schedules and clinical milestones. Proactive planning helps protect timelines and reduces the risk of missed production slots.
● Cell substrates and raw materials: Early alignment on well-characterized cell banks and scalable, GMP-compatible and multi-compendial raw materials simplifies technology transfer, supports smoother scale transitions and eases comparability assessments as programs advance.
● Manufacturability vs. speed trade-offs: Approaches that prioritize rapid early progress without considering scalability often introduce hidden downstream costs. Processes built on non-scalable materials or insufficiently characterized inputs may suffice for first-in-human studies but frequently require significant redevelopment for late-phase or commercial production.
● Long-term process continuity: Designing development processes with future GMP expectations in mind reduces the need for major process redesign, conserving time, capital and organizational focus.
Analytics are a driver of confidence and control
Robust analytics are central to successful viral vector scale-up. Regulators expect validated, phase-appropriate assays capable of measuring critical attributes such as potency, infectivity, purity and safety with confidence.
Embedding analytical development early enables teams to generate meaningful data as processes evolve. Rather than retrofitting assays after the fact, early alignment between process and analytics supports consistent monitoring of critical quality attributes across scales and phases.
Additionally, leveraging platform analytics early in the process that scale from fit-for-purpose to fully validated are value add to use data across several programs to drive specifications.
This continuity becomes particularly important as programs approach pivotal studies and commercialization. Well-established analytical frameworks facilitate comparability assessments, strengthen regulatory submissions and reduce uncertainty during scale transitions. In the fast-moving CGT regulatory landscape, analytics are a critical tool for both compliance and informed decision-making.
Managing the balance between speed and sustainability
Speed remains a defining pressure in CGT development. For many biotech companies, rapid progression to the clinic is essential for securing investment and validating the platform. However, speed achieved through short-term compromises often proves unsustainable. Inefficient processes, delayed material sourcing or underdeveloped analytics can quickly negate early gains. This means that as timelines slip and costs rise, programs may struggle to recover momentum.
A more sustainable approach is one that focuses on strategic acceleration rather than time-saving shortcuts. Even in early phases, these strategies can compress timelines without undermining robustness. Examples include:
● Running development activities in parallel
● Aligning process scale with clinical intent
● Applying quality systems consistently
As cost and speed are tightly linked, well-designed processes reduce rework, improve yields and support smoother transitions between phases, ultimately helping lower the cost per dose of the final product and preserving optionality as programs evolve.
Making manufacturing a strategic advantage with collaboration
The complexity of viral vector manufacturing has made collaboration a defining feature of successful CGT programs. Whether enabled through tightly integrated internal teams or external partnerships with contract development and manufacturing organizations (CDMOs), access to manufacturing experience expertise allows early development decisions to be informed by late-stage and commercial realities.
This alignment is particularly critical for smaller organizations, where a single CGT program may represent the majority of enterprise value. In these cases, manufacturing strategy is inseparable from business strategy. Clear communication and the ability to adapt as programs evolve are essential safeguards against avoidable risk.
As development progresses, priorities inevitably shift. Technical challenges emerge and clinical data reshape program direction. CDMO partners can help navigate this uncertainty by adopting a set of manufacturing principles:
● Early alignment on long-term goals, ensuring development choices support both clinical and commercial needs
● Transparent decision-making frameworks, enabling rapid response when timelines, scope or data change
● Stage-gated development models, balancing speed with technical and regulatory readiness
● Continuity across development phases, minimizing disruption as programs scale or transition between environments
When these elements are in place, viral vector manufacturing begins to shift from a perceived constraint to a strategic capability. Designing platforms with scalability, quality and analytics embedded from the outset reduces late-stage friction and strengthens long-term viability.
The right CDMO partnership can play a pivotal role in translating early process design into scalable execution. Experienced partners bring perspective across multiple programs, allowing common scale-up risks to be anticipated rather than discovered reactively. Established platform knowledge, regulatory familiarity and integrated analytical capabilities can help ensure that early development decisions remain aligned with later-phase and commercial requirements.
As the CGT sector continues to mature, manufacturing excellence is increasingly separating durable programs from those that stall. Scientific innovation remains essential, but it is no longer sufficient on its own. Programs that pair compelling biology with scalable, well-characterized manufacturing strategies are better positioned to navigate regulatory scrutiny, control cost of goods and respond to growing patient demand. In a field defined by innovation, the ability to execute at scale is becoming one of the most powerful enablers of progress.