The acceleration of development and innovation in cell and gene therapy (CGT) – together with greater fast-tracking of regulatory approvals – has resulted in the CGT ecosystem being unable to keep pace with production, creating a global supply bottleneck. Whilst various alleviative solutions have been suggested, addressing viral vectors seems the most viable approach given the fundamental role they play in CGT’s potential – in particular CAR-T therapy – to change lives. Indeed their true potential can only be unlocked if production and manufacturing costs are reduced, as this translates directly to lower patient costs and increased accessibility. Novel approaches must therefore be considered to ensure that patient-centricity remains the heart of the biotechnology (biotech) industry.
One such approach is to expand partnership focuses beyond incumbent contract development and manufacturing organisations (CDMOs) to explore collaborations with new market entrants This might mean broadening horizons to less traditional production regions, such as the Asia-Pacific region. Usually smaller and nimbler, these CDMOs are more adept at innovation and reducing costs via faster, more effective processes. Strategic global positioning can also offer competitive savings and distributive advantages, making treatments more accessible not just to directly proximate regions, but worldwide. This approach would diversify geographical production areas, potentially reducing bottlenecks, and enable better fulfilment of the industry’s ethos to reach, treat and heal the greatest number of people in the most efficient manner possible.
Reducing costs from production to bedsides whilst maintaining quality
Given the complexities of vector manufacturing, there are always concerns around compromising quality when reducing costs. However, there are a few ways biotechs can alleviate these. Firstly, they can identify CDMOs which have obtained government conformity assessment certifications in environments with robust regulatory frameworks. This provides a basic guarantee of quality assurance and compliance.
Secondly, they can evaluate whether the CDMOs have a demonstrable commitment to addressing existing CGT barriers through technological innovation. For instance, some believe that “early intervention” initiatives at the production and manufacturing stages are key to cost reduction through embracing a “process is the product approach. In doing so, they avoid the need for costly regulatory approvals for any process modifications which are also time-consuming when done downstream. Incorporating compliance into the process can therefore result in significant savings. Additionally, because cost-cutting is a priority at every stage, these CDMOs make attempts to holistically streamline their operational developments such as using Benzonase® endonuclease as an alternative to expensive enzymes traditionally used in novel suspension processes.
CDMOs which manufacture in-house (as some niche organisations do) are also able to achieve high process consistency through optimizing helper and packaging construct expression to upstream and downstream processes, all whilst maintaining high titre and high purity. With these advanced in-house capabilities, they can also support small biotechs and research institutes (who often lack these systems) to transition into the vector delivery system by designing their vectors to yield high titre products. This further enables production scaling and overcoming genetic instabilities, which can then lead to meaningful opportunities such as the ability to address commonly occurring cancers.
Some up-and-coming CDMOs have the additional ability to customize and tailor treatments to order, which ensures that product quality is maintained and even enhanced. Whilst autologous products are often associated with higher costs, these CDMOs use techniques such as first-expired-first-out (FEFO) to manage inventory and manufacture only what is needed, thus avoiding the stockpiling of pre-ordered raw materials or excess stock and reducing inventory loss by up to 40 percent. They also consistently invest in business improvements to enhance efficiency – like digitalizing the management of supply chains – and make procurement decisions using their subject-matter expertise, such as timing orders based on the projected shelf life of materials. This maximizes their capacity for on-time delivery, further translating into lower costs and improved treatment accessibility for patients.
A final and pertinent consideration of working with nimbler, more niche CDMOs who actively innovate at every stage of production is the speed at which they enable treatments to reach patient bedsides. Through technological innovation, they can reduce production times to two weeks instead of the industry’s standard of one month or more. This is a huge advantage due to the significance of shortened time frames of treatment accessibility in saving lives especially where chronic and serious diseases are concerned. Faster production times also translate to a reduction of manpower and consumable costs, making it both a competitive and humanitarian advantage for biotechs to work with CDMOs that possess this agility and flexibility.
Leveraging geographical advantages for the greater good
Chronic diseases have been on an upward trajectory worldwide. That, along with greater healthcare awareness (especially after the pandemic), has resulted in more investments in this space globally – including in CDMOs. With an expected market growth of 8.4 percent between 2021 to 2026, CDMOs are therefore well-positioned in the upcoming years to deliver patient-centric solutions and leverage geographical advantages in tandem with savvy biotechnology partners.
For example, over 4.5 billion people (59.5 percent of the global population) reside in Asia. Unsurprisingly, the region also has some of the highest numbers of chronic disease patients and deaths; in 2020, 58.3 percent of global cancer deaths are estimated to have occurred in Asia. These sombre statistics display, catalyze and heighten the urgent need for expedient and targeted treatments, along with equitable access for those that might be unable to afford it.
With larger incumbents typically based in the West, CDMOs based in the Asia-Pacific region have the competitive advantage of being able to cater to a large, underserved population on their doorstep and further enhance distributive efforts in the world’s most populous region. Besides lower transport and distribution costs, biotechnology companies can also benefit from other inherent cost-saving advantages such as these CDMOs having access to a large, skilled workforce and reduced costs in research and development This can translate to a lower cost of production and empower distribution further impacting accessibility favourably – not just in underserved regions, but worldwide.
Life-saving goals for the maximum volume of patients
Given the projected market growth is 22.3 percent for 2021 to 2026, the promising future of CGT will play an increasingly important role in addressing some of humanity’s most problematic diseases. As populations and healthcare awareness grow, it is important to democratize access for all who need it – not just those who can afford it.
Biotechnology companies have a major role to play in realizing this ideal scenario. It is thus imperative for them to look beyond traditional solutions and explore partnership opportunities with smaller, more agile CDMOs, which will pave the way for them to achieve new breakthroughs in alleviating the supply bottleneck issue and enhancing patient accessibility in diverse geographical regions.
Whilst these partnerships might require a leap of faith for some biotechnology companies in venturing beyond traditional comfort zones, embracing collaborations with smaller CDMOs encourages healthy competition and accelerates industry growth. Most importantly, it moves the industry closer towards achieving its overarching mission to deliver effective treatment to patients in the most expedient and humanitarian manner possible.