Applied in gene therapy and vaccines used for cancer, genetic disorders, and infectious diseases, lentiviral vector demand is surging. Growth drivers include increasing research and development activities and strategic initiatives by major market players, as well as agreements and collaborations in these areas. However, bottlenecks around vector supply stand to threaten this growth, with the main challenges being lack of scalability and downstream purification.

Lentiviral vector workflow consists of: upstream, plasmid manufacturing, cell expansion, plasmid transfection and viral vector production, downstream, purification, and fill and finish.
 
According to Natalia Elizalde, PhD, Chief Business Development Officer at lentiviral vector specialist VIVEbiotech, growth will be dependent on the industry being able to optimize processes and prepare for manufacturing on a commercial scale. The implementation of automation and more controlled processes might be a source of debate, but without them the bottleneck problem may not be solved.  –KB 
 
Contract Pharma: What is the current state of the lentiviral vector market?
 
Natalia Elizalde: From an overall perspective, the Cell and Gene Therapy sector presents a significantly higher Compound Annual Growth Rate (CAGCR) than the general pharmaceutical market. Thus, while current pharmaceutical market value stands high at a CAGR of 8%, the Cell & Gene Therapy sector reaches 50%.
 
In particular, a recent report by the ARM shows that lentivirus is the most common vector across both Gene Therapies and Gene Modified Cell Therapies, being employed in the 48% of clinical trial within these categories. Moreover, based on a report by Catapult, up to 70% of ex-vivo projects are using lentiviral vectors as the gene transfer technology. Finally, just to highlight that lentiviral vectors are enhancing their position in in-vivo applications. Indeed, VIVEbiotech is already working on seven programs in which lentiviral vectors will be administered in-vivo as final product.
 
Contract Pharma: What are the main challenges associated with the lentiviral vector method in gene therapy? 
 
Natalia Elizalde: The main challenges are linked to the fact that lentiviral vectors are very sensitive to harsh environments so that every single manufacturing step must be very tightly controlled to guarantee that the vector is functional and that the reached titers make the process cost-effective and scalable.
 
VIVEbiotech, who is expert not only in manufacturing but also in virology and in bioprocessing with highly skilled personnel, has already manufactured more than 100 batches in reactors in the last 8 years in their very well controlled, plug and play, cost-effective and scalable platform. In fact, we consider that it is not just about having capacity but, more importantly, capability.
 
Contract Pharma: How can processes be optimized to prepare for manufacturing on a commercial scale?
 
Natalia Elizalde: From our point of view, it is essential to optimize the process in a way that ensures cost-effectiveness for treating a broader population, while also prioritizing scalability and regulatory compliance. 
 
To make lentiviral vector manufacturing cost-effective in commercial phases, VIVEbiotech has developed a high-capacity platform in which an adequate environment for lentiviral vectors reaching greater titers is guaranteed. Our platform allows increased recovery so that purer and more functional viruses are obtained being able to scale it up to commercial scales.
 
The fact that intermediate scales with low footprint reactors are available coupled with a straightforward tech transfer from 2 to 3D in a plug-and-play format contribute to process optimization for the preparation of manufacturing on commercial scales.
 
Contract Pharma: How will lentiviral vector manufacturers need to adapt to meet predicted growth?
 
Natalia Elizalde: In our opinion, lentiviral vector manufacturers do need to continue investing in innovation to improve the productivity of production processes both by optimizing USP and DSP manufacturing, as well as to enhance the productivity of packaging cell lines. Moreover, fine-tuning different pseudotyping strategies to infect target cells more effectively as well as automation will be key to meet the predicted growth. Finally, larger scales as well as additional facilities will be needed to target this very significant predicted increased demand.
 
In line to this, VIVEbiotech has a very well-established innovation and bioprocess optimization team working on these objectives to be sure that they are indeed ready to meet the predicted growing lentiviral vectors demands.