Angela Myers, Head of Gene Editing and Novel Modalities at Merck, outlines the challenges arising with the increasing demand for safe and efficacious treatments and new technology development to improve and standardise the manufacturing process
Although conventional medicines must be taken for weeks, months or even a lifetime, cell and gene therapies (CGTs) offer the potential for one-time treatments. As such, the cell and gene therapy market is growing at a steady rate. And, with an increasing demand for safe and efficacious treatments to treat a wide range of diseases and ailments, this trend is expected to continue.
The number of gene-modified cell therapy clinical trials rose 39% from 2018 to 2019. According to Arizton, the cell and gene therapy market is expected to reach revenues of more than US$6.6 billion by 2024.1 Similarly, the US FDA predicts that it will receive more than 200 investigational new drug applications for cell and gene therapy products in next few years and approve 10–20 new cell and gene therapy products each year by 2025.2
With opportunity comes challenges. These are critical therapeutics that are often fast-tracked … but driving clinical development and market approval in a short period of time requires managing many topics in parallel, including clinical operations, manufacturing processes, regulatory filings and market access strategy, to name a few.
Often, manufacturing challenges and time required to overcome them are under-estimated in the commercialisation process. It’s doubly challenging for gene modified cell therapies, for which manufacturing challenges exist in both viral vectors as well as cell processing.
With any emerging therapies, the production process takes time to mature. In the viral vector field, many processes are academic and not ready for commercial-scale production. Time is needed to understand the critical quality attributes of the process, establish ways to maintain control and process consistency, and ensure that cGMP documentation and regulatory requirements are strictly adhered to.
If there is no investment upfront to ensure process is robust and commercial ready, it will postpone market entry when process changes are needed late in the game. Compromises that may be considered for rare diseases are impossible to manage for more mainstream therapeutic areas.
There is immense opportunity to optimise process technology, which has mostly been adapted from monoclonal antibodies processing. Today, we are producing empty virus particles and yield is low. Losses are high in the downstream steps. Considering the fact that productivity of monoclonal antibodies processes increased 40-fold in the span of 2–3 decades, there is definitely a long way to go for viral vectors.
To address these challenges and meet patient needs for cell and gene therapies, we have a responsibility to drive technology development to improve and standardise the process. As a pioneer in the CMO space for more than 25 years, we are developing process technology that drives higher yields and efficiencies.
Our innovative technology enables us to develop a standardised template that is informed by decades of viral vector manufacturing experience. These templates, together with a closer partnership with therapeutic companies, will shorten the time spent on process development/validation and avoid unnecessary rework and delays. Only then, as an industry, will we be able to realise the potential of cell and gene therapies.