Because the cell and gene therapy (CGT) industry is still so relatively young, it is an emergent sector in which companies are constantly innovating to find new solutions to new implementation problems. As a result, those on the outside looking in can often find their understanding of the sector to be rapidly outdated, with perceptions based on the challenges that confronted CGT studies in earlier years but from which new approaches have already started to evolve. In this blog post, I thought it would be a good idea to briefly outline 4 areas in which the CGT industry has confronted its challenges and converted operationalization threats into opportunities.
CHALLENGE #1: Scale
CGT studies are typically far smaller than traditional randomized controlled trials (RCT), with fewer participants and a shorter operational window.
- Current cell and gene therapies often target rare diseases. As a result, they are commonly considered to be hamstrung by smaller market opportunities and a restricted ability to scale output or pivot research outcomes to other conditions.
- It’s true that some CGTs are highly personalized treatments that are tailored to an individual’s specific tumor environment (e.g. cancer vaccines) and that this can severely limit the scope for mass treatment.
However, a smaller pool of severely ill patients can lead to lower thresholds for success in terms of efficacy. Even superficially minor improvements can still have significant positive impacts on quality of life. This means even partially successful treatments can have a relatively easier regulatory approval process. This leads to faster commercialization and thus lower development costs.
In addition, not all CGT products and studies even result in personalized treatments: the industry has already used the lessons learned in autologous studies to invest in AAV gene-therapies and allogeneic therapies. These therapies are successfully used to develop generalized treatments for a range of complex diseases.
CHALLENGE #2: Resourcing
The relatively small size of the CGT industry today places a lot of strain on the limited pool of available trained specialists who can work with these novel methodologies.
- Such capacity issues can be further compounded by the scale of individual studies (as outlined above). This means that many small LSOs engaged in CGT research and development (R&D) may not have the scope to employ the full range of experts and technicians required to manufacture their product.
- This suggests to some that the future of CGT belongs to the large pharma/biologics companies with the existing resources to deliver products in-house.
In reality, there is a split in approaches to CGT production: build vs buy. Increasingly, companies look to either establish their own manufacturing facility (build) or enlist the support of Contract Development and Manufacturing Organizations (CDMOs) (buy). The scope of CDMOs is growing annually and, while some companies partner with several organizations due to capacity limitations at the CDMOs themselves, the contract sector is rapidly developing more biologics resources.
Organizations like Lonza, Resilience, Charles River, and many others are heavily investing in establishing or acquiring new facilities to manage growing demand. However, a severe lack of trained personnel remains, further slowing the process of contracting CDMOs on a larger scale.
Thankfully, both CDMOs and established in-house developers (as well as medical research institutions) are also investing significantly in training a new generation of specialists in an attempt to lockstep resource growth with the growth in demand for cell and gene therapies, helping to secure the future of the field.
CHALLENGE #3: Product management
Because some CGT products rely on live cells as the primary source material, product variability and shelf life can represent serious issues. These are often cited as significant logistical barriers when studies must collect, transport, modify, harvest, and administer the product within a short timeframe.
- For instance, “fresh” source materials might have an ex-vivo lifespan of only 24-48 hours, after which they are no longer usable.
- Even within that window, product consistency can be affected.
While it continues to be a complication for many studies, companies have unsurprisingly identified this bottleneck as a serious challenge and are investing in solutions. The industry is researching and refining processes so that source material can be safely frozen immediately after collection, therefore significantly extending the shelf life. This allows for greater flexibility in managing capacity at the manufacturing facility and fewer constraints on supply chain logistics.
In contrast to the earlier, ground-breaking CGT studies, the standard practice today is to cryopreserve the final product. This not only dramatically extends the shelf life of the CGT product, it also significantly facilitates treatment scheduling and allows product to be stored while the patient is undergoing conditioning to receive the treatment.
CHALLENGE #4: Service model
Cell and gene therapies have a significantly higher price tag compared to most traditional treatments. Therefore, Healthcare Providers (HCPs) and patients expect a world-class service consistent with that cost.
- Each hospital and healthcare institution investing in these therapies will become a direct client of the relevant development company.
- However, providing efficient and direct customer service is an unfamiliar paradigm for even the big players in the pharmaceutical sector.
CGT developers aspiring to commercialize therapies with or without large pharmaceutical partnership will need to adopt a new business and service model. Delivering a great customer experience includes providing timely information to the HCPs, supply chain partners, and, most importantly, to the patients. Scheduling patient enrolment, starting material collection (apheresis, biopsy, BM, etc.), infusion, and follow-ups must all be seamless. Any changes to the overall treatment timeline should be effectively communicated to manage patient and caregiver expectations.
Companies aiming for a 100% service level, where every patient experiences a perfect service, are continuing to invest in achieving flexible buffer capacity, establishing a robust manufacturing strategy (buy vs build), and new process technologies to minimize manufacturing risk. The increasing adoption of automation, in particular, is already helping companies meet some of the challenges. Partnering with specialist vendors to implement off-the-shelf technological innovations also facilitates service improvement without requiring extensive in-house R&D.
We at Binocs support CGT companies to adapt to new service models by optimizing the use of resources and assisting them in delivering a great customer experience.