Capacity or Capability? The Scramble to Manufacture Viral Vectors

Behind gene therapy's medical miracles lies a monumental challenge: manufacturing the viral vectors that serve as delivery trucks for revolutionary treatments.

Gene Therapy Viral Vectors Biomanufacturing

Introduction

In a landmark case in early 2025, a team of physicians and scientists developed a personalized CRISPR treatment for an infant with a rare genetic disorder, delivering it to the patient in just six months3 . This breakthrough, alongside the first regulatory approvals of gene therapies for conditions like sickle cell disease, signals a new era in medicine. However, behind these medical miracles lies a monumental challenge: manufacturing the viral vectors that serve as the delivery trucks for these revolutionary treatments.

The field stands at a crossroads, grappling with a fundamental question: should the priority be building massive production capacity to meet booming demand, or should it be developing sophisticated new capabilities to make production more efficient, consistent, and safe? The choices made today will determine whether these life-changing therapies can move from treating a handful of patients to becoming accessible, mainstream medical solutions.

The Core Dilemma

Should the industry focus on building more manufacturing facilities (capacity) or improving the efficiency and quality of existing processes (capability)?

Current industry focus: 60% capacity, 40% capability

The Engine of the Gene Therapy Revolution

What Are Viral Vectors?

To understand the manufacturing dilemma, one must first understand the product. Viral vectors are essentially viruses that have been genetically disarmed. Scientists remove the disease-causing genes, leaving a hollowed-out shell capable of safely delivering therapeutic genetic cargo into human cells1 .

Common Viral Vector Types
Adeno-Associated Viruses (AAVs)

Primarily used for in vivo gene therapy, where the vector is injected directly into the patient1 5 .

Lentiviruses

Often used for ex vivo therapies, where a patient's cells are modified in the lab then reinfused1 .

Viral Vector Manufacturing Process
Upstream Processing

Cell culture expansion and viral vector production using HEK293 cells1 6 .

Harvest & Clarification

Separation of viral vectors from cell culture debris.

Purification

Chromatography steps to isolate and purify viral vectors5 6 .

Formulation & Fill

Preparation of final drug product for administration.

Complex Manufacturing: The manufacturing process for these vectors is notoriously complex and fragile. Unlike traditional biologics, there is no universal, standardized production line. Most processes rely on transiently transfecting human embryo kidney (HEK293) cells with multiple plasmids—a costly and inefficient method that is difficult to scale1 6 .

The Capacity Crunch: Straining to Meet Demand

The clinical pipeline for cell and gene therapies is exploding. With over 2,000 candidates in development and regulatory approvals rising, the demand for viral vectors has never been higher6 . The viral vector manufacturing market is forecast to grow by USD 4.1 billion from 2024 to 2029, expanding at a staggering compound annual growth rate (CAGR) of 19.3%2 .

This demand has created a severe capacity crunch. To meet it, the industry has seen a boom in both in-house manufacturing by large pharmaceutical companies and a reliance on Contract Development and Manufacturing Organizations (CDMOs)2 5 . By 2022, there were more than 60 GMP manufacturers globally, with the top five players holding about a third of the total production capacity.

19.3%

CAGR (2024-2029)

Viral Vector Manufacturing Market Growth2

Global Viral Vector Manufacturing Market Snapshot
Aspect Detail
Market Growth (2024-2029) +USD 4.1 billion2
Compound Annual Growth Rate (CAGR) 19.3%2
Leading Region North America (contributes 33.6% of growth)2
Most Common Production Scale 200-L bioreactors
Leading Vector Type Adeno-associated virus (AAV)
Cost Challenge: Simply building more factories may not be the right solution. Scaling up the old, inefficient processes only amplifies their shortcomings, leading to exorbitant costs. This is why many approved gene therapies carry price tags of $1-2 million per dose, straining healthcare systems and limiting patient access6 .

The Capability Gap: The Need for Smarter, Not Just Bigger

While capacity is a volume issue, capability is about quality, efficiency, and control. Focusing on capability means re-engineering the very fundamentals of how viral vectors are made. The industry's current "gold-standard" processes are often not gold-standard at all; they are legacy methods that were never designed for commercial-scale production.

Key Challenges Driving the Capability Gap
1
The Plasmid Problem

The reliance on vast quantities of costly GMP-grade plasmid DNA for every production batch is a major cost driver and source of variability6 .

2
The Empty Capsid Dilemma

In AAV production, a shockingly high percentage of capsids are produced empty, containing no therapeutic gene4 9 .

3
The Purification Bottleneck

Downstream purification is a multi-step, inefficient process, with recovery rates often being poor5 6 .

4
Analytical Challenges

Accurately measuring the potency, purity, and full-to-empty ratio of vectors requires complex, evolving analytical methods4 .

Key Challenges in Viral Vector Manufacturing
Challenge Impact on Production
Transient Transfection High raw material cost, low scalability, batch-to-batch variability6 .
Empty Capsids Reduces therapeutic potency, increases risk of immune reactions, complicates dosing9 .
Fragile Vectors Lentiviruses are especially delicate, easily damaged during purification, leading to low yields6 .
Complex Analytics Difficulty in characterizing the product accurately slows down development and quality control4 .
Empty Capsid Challenge

Percentage of empty capsids in AAV production can reach up to 90%, significantly impacting therapeutic efficacy9 .

In-Depth Look: Modeling Future Capacity Needs

How does the industry plan for such an uncertain future? Strategic consultancies like Latham BioPharm Group have developed sophisticated models to forecast supply and demand. In a 2025 presentation, analyst Andrew Harmon detailed this approach.

Methodology: A Step-by-Step Modeling Process

1
Data Collection

Primary and secondary research to map global CDMO capacity, including yields, batch sizes, and expansion plans.

2
Capacity Assumptions

Standardizing data with assumptions like one batch per month for ten months a year.

3
Demand Forecasting

Using clinical trial data to determine dosing requirements and timeline needs.

4
Analysis and Insights

Generating forecasts and identifying trends from cleaned data.

Modeling Insights

The model projected that while demand would surge from about 2,000 batches to 8,000 by 2031, the more likely scenario is a leveling off at around 3,000 batches.

Key Finding

The model highlighted that commercial demand is projected to grow at a much faster rate (31% CAGR) than clinical demand (4% CAGR). This shifts the priority from simply making "enough" vector for clinical trials to making "high-quality, affordable" vector for the commercial market.

The analysis concludes that long-term success "depends on establishing economically viable production processes," placing the focus squarely on enhancing capabilities.

Next-Generation Capabilities Reshaping Manufacturing

The good news is that the industry is not standing still. A wave of innovation is targeting the very heart of production inefficiencies. These are not merely incremental improvements but fundamental shifts in capability.

Innovative Solutions Enhancing Manufacturing Capability
Innovation Description Impact
Stable Producer Cell Lines Engineered cells that stably contain all viral genes, eliminating the need for plasmid transfection1 6 . Reduces cost, improves consistency, simplifies scale-up.
Synthetic DNA Enzymatically produced DNA that replaces bacterial plasmids6 . Eliminates bacterial impurities, shortens production timelines, reduces cost.
Advanced Purification New affinity ligands (e.g., AVB) and chromatography methods that better separate full and empty capsids5 . Increases yield and purity, improves product safety and efficacy.
Suspension Bioreactors Moving from adherent cell cultures in stacks to large-scale suspension cultures in stirred tanks5 . Enables larger batch sizes, automation, and closed-system processing.
The Scientist's Toolkit

Driving these innovations forward requires a specialized toolkit. Here are some of the essential materials and reagents used in modern viral vector development and production:

HEK293 Cell Lines

The predominant mammalian cell factory used to produce AAV and lentiviral vectors1 5 .

1
Sf9 Insect Cells & Baculovirus

An alternative production system using insect cells1 9 .

2
Affinity Chromatography Resins

Critical downstream tool for efficient capture and purification5 .

3
Polyethylenimine (PEI)

Common chemical transfection reagent used to introduce plasmids into HEK293 cells1 .

4
ddPCR (Droplet Digital PCR)

Advanced analytical technique for quantifying viral genome titers4 .

5
Technology Adoption Timeline

Current and projected adoption rates of next-generation manufacturing technologies in the viral vector industry.

Conclusion: The Path Forward is Integration

The question of "capacity or capability?" presents a false dichotomy. The future of viral vector manufacturing does not lie in choosing one over the other, but in their strategic integration. The industry must build capacity with new, smarter capabilities already baked in.

The modeling data shows that unchecked capacity expansion is not the answer. Instead, the focus must be on developing platform processes that are scalable, consistent, and cost-effective from the start. Success will be defined by transitioning from fragile, artisanal production methods to robust, industrialized platforms.

This will require deep collaboration between biotech companies, CDMOs, and equipment suppliers to overcome technical barriers. It will also demand a regulatory environment that encourages innovation in process design. By prioritizing the right capabilities, the industry can build the right capacity—ensuring that the gene therapies of tomorrow are not just miraculous, but also accessible to all the patients who need them.

Key Takeaways
  • Capacity and capability must be developed in tandem
  • Platform processes are essential for scalability
  • Cost reduction is critical for accessibility
  • Innovation in production methods is accelerating
  • Collaboration across the industry is necessary
  • Commercial demand will drive capability improvements

The Future is Integration

Building capacity with advanced capabilities already integrated will determine the success of gene therapy accessibility.

Industry Outlook

Projected balance between capacity expansion and capability development in the viral vector industry.

References