Transforming healthcare equity: How modular factory systems can spur the gene therapy revolution

Gene therapy interventions stand front and centre in healthcare innovation.

As the most rapidly growing therapeutic modality, over 50 new in vivo and ex vivo gene therapy launches are planned for the next few years. At present, pretty much all viral vectors for gene therapy are one of three types: adeno-associated virus (AAV) vectors, adenovirus vectors, or lentivirus vectors. AAV and adenovirus vectors are generally used in in vivo interventions, while lentivirus vectors find applications in ex vivo therapies, in which cells are harvested from the body, modified in the lab, and retransplanted into the body. Particularly, AAVs and induced pluripotent stem cells are expected to have the most profound implications on disease treatments.

As of late 2020, there were only about four in vivo gene therapy interventions on the market. As of 2022, 8 were approved by the US Food and Drug Administration (US FDA). Plus, there were at least 25 viral vector therapeutics in late-stage development and 120 in phase 2 trials by biotech companies and academic labs. Big pharma has also recognised the potential of viral vector manufacturing, if biotech acquisitions are anything to go by. And global sales of viral vector-based gene therapies are predicted to grow at an astounding rate of over 50% year-on-year for the next couple of years.

The rapid pace at which the field of gene therapy vectors is developing is exciting for many reasons.

For starters, cell and gene therapy vectors may not only improve existing treatments but also result in groundbreaking solutions for currently incurable diseases. They offer patients the prospect of a one-time cure for certain conditions and symptom-free living post-intervention. Second, gene therapy vectors were initially developed to address rare and ultra-rare indications through in vivo tissue administration or ex vivo cell modification. Now, viral vector manufacturing is expanding to treat non-rare diseases and for immunization, with Covid viral vector vaccines being the most obvious example. This means that gene therapy will be a boon for a much wider section of the global population.

The need for equitable development in viral vector manufacturing

As the gene therapy field and its relatively nascent technology make huge strides in the coming decade, it is important that scientific and manufacturing advances have an equitable impact globally.

Cell and gene therapies are already used in cancer treatment, immunisation, and in treating other rare conditions which require personalised treatments. In future, the use of gene therapy vectors could mean that patients don’t need immunosuppression after a transplant. It could mean that some patients could avoid transplants altogether. It could mean a cure for debilitating lifelong conditions like Parkinson’s disease.

Why should patients in only a few geographies benefit from the vast potential of gene therapy interventions? Why should viral vector manufacturing be out of reach of manufacturers in low- and middle-income countries (LMICs) in Africa, Latin America, Asia, and beyond?

As the world of cell and gene therapy gets wider, with the potential to positively impact hundreds of thousands more lives, the field faces many challenges. In addressing these challenges, governments, entrepreneurs, and pharma companies must focus on agility, flexibility, and scalability. As they build up the necessary infrastructure for viral vector manufacturing, it is important that they do so worldwide to ensure that when gene therapies become ubiquitous in healthcare, no one is left behind.

Modular factory systems can spur the gene therapy revolution, in developed and developing countries.

Challenges in manufacturing viral vectors for gene therapy; prefab factory systems as the solution

Prefabricated modular factory systems can streamline the development and production of gene therapy vectors. With plug-and-play systems like PodTech™️’s podules™, even countries without substantial preexisting infrastructure can take advantage of the upcoming revolution in viral vector manufacturing.

As such, the gene therapy revolution is fertile ground for transforming health systems, developing biopharma capabilities, and bridging healthcare inequities.

Challenge 1: Capacity expansion to meet increasing demand.

As viral vectors for gene therapy go from addressing rare indications to non-rare ones – and as more programmes go from clinical stages to commercialisation – viral vector manufacturing needs rapid expansion to meet increasing demand. For instance, some rare disease treatments needed about 1,000 doses across development, access programmes, and two years of commercialisation. On the other hand, AstraZeneca’s viral vector vaccine was produced in billions.

The Covid pandemic has shown that capacity for certain gene therapies, like the adenovirus-based vaccine, can be expanded rapidly. However, other gene therapy modalities still experience capacity constraints, high cost of goods, large upfront investments, and long lead times. GMP-grade AAV and lentiviral capacity, particularly, is in short supply, causing bottlenecks in clinical trial manufacturing.

This is where prefab systems have a crucial role to play. With 50% shorter lead times compared to traditional factory construction, prefabricated factories can be rapidly deployed to meet surges in demand. PodTech™️’s podules™ can be deployed to manufacture cell and gene therapies, including viral vector vaccines. Standard podules™ for gene therapy and small-scale cell therapy can further accelerate the timeline to production.

Challenge 2: Uncertainty in demand forecasting and platform standardisation.

As a biopharma manufacturer, you would make investment decisions about manufacturing facilities based on demand forecasts. However, at this stage in the evolution of gene therapy as a therapeutic field, accurate prediction is hardly easy. As the landscape evolved and processes improved, a global pharma company sold its production facility to a CDMO just 14 months after opening it. As the field continues to advance and optimise processes, manufacturers must accept some level of uncertainty. While data-based digital tools, like digital twins, can help manufacturers model future demand to some extent, they must also make investment decisions that favour flexibility in capacity development.

Additionally, there is currently no standardised platform for commercial viral vector downstream processes. Industry experts predict that, over the years, different methods will converge to form industry standards. But what that will look like in another decade, we don’t yet know. So it is important that biopharma manufacturers make intelligent decisions today, investing in capacity which can be adapted to the future of viral vector manufacturing.

Plug-and-play systems—with their built-in flexibility, scalability, and speed of deployment—are ideal solutions to the gene therapy demand and capacity problem, which currently has too many variables. By adopting biopharma manufacturing systems like PodTech™️’s podules™, gene therapy manufacturers can strike the perfect balance between expanding capacity and retaining the flexibility to integrate innovative technologies that will likely emerge in coming years.

Challenge 3: A trade-off between flexibility, scalability, and quality.

Rapidly developing and commercialising safe and efficacious gene therapies calls for flexibility, scalability, and quality. But at present, no single platform meets all three requirements. For instance, the highly popular transient-transfection systems permit the highest levels of flexibility but don’t offer much in terms of scalability.

Once you, as a cell and gene therapy manufacturer, select a production system, it becomes difficult to make changes later on without significant costs and delays. But as we’ve just discussed, the nascent stage of gene therapy tech means that changes in the future are inevitable. As you explore production platforms, industry analysts like McKinsey highlight what modular production suites can offer. For instance, PodTech™️’s prefabricated factory system, made of self-contained podule™ clusters, offers flexibility to adapt certain processes and expand capacity when key milestones are met. Such podule™ clusters can sometimes even be set up in platform-agnostic ways, giving you the freedom to adapt to evolving technologies and the market and regulatory landscape.

Challenge 4: The need for speed.

In gene therapy development, timelines are often compressed due to the speed with which pipelines evolve, the granting of accelerated regulatory pathways for rare disease treatments, and tech advancements in the manufacturing and CDMO market. Agile decision-making is indispensable in production decisions; accordingly, production capacity also needs to keep up. Scalable

Companies should leverage the speed of agile decision-making in production decisions, as timelines for viral-vector products are compressed compared with other modalities due to the rapid pipeline evolution, accelerated regulatory pathways (for example, rare diseases), and the rapidly changing capacity and offerings across the CDMO market. Scalable podule™ clusters can shoulder a large part of this need for speed.

Essentially, cell and gene therapies have the potential to bridge healthcare gaps in the coming decade. Prefabricated factory systems for gene therapy manufacturing will be an indispensable part of this revolution. With shortened timelines, easy scalability, flexibility, and essential utility inclusions, they will be at the forefront of healthcare equity globally.

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