With commercial demand for cell and gene therapies now higher than ever, the pressure is on for companies to scale up manufacturing while minimizing cost of goods. Process automation offers many benefits, but not without challenges in areas such as cost and implementation.
Yet, with so many options for tech solutions out there, where to start? What steps can organizations take to decide what is best, not only for their business, but also for patients? We asked three industry experts for their advice:
Stefano Baila
You have to know your process and start to challenge it: moving away from exclusive operator’s skill-based steps and evolving them introducing closed and automated solution.
The ultimate goal of automation is to allow treating your target patient population in an affordable way (sustainability of your manufacturing paradigm), automation should as well guarantee identity, safety, purity and potency.
Automation should be considered in all steps of the vein-to-vein journey of your product including production, analytics and logistics.
Colby Colasanto
Automation should be considered as a progressive operation, and explored with stage by stage approach. Identify the most critical sets of operations to automate, optimize each one, then integrate them together to establish a new automation standard. It is important to remember that information management is also part of automation.
Katleen Verleysen
Ideally, you have an all integrated solution, whereby the target cells are purified, reengineered and cultured, as well as all the necessary steps to quality control the process. The number of manual handling steps and interventions are to be avoided at all cost, certainly because purity is of utmost importance and a minor contamination could have a severe adverse effect. The future of cell manufacturing is an all-in-one disposable chip/cartridge per patient, whereby the vein-to-vein time and overall cost is significantly reduced. Due to the complexity of the process, we firmly believe the solution will contain a few silicon-based sensor chips, because of its versatility towards high throughput and multiparameter sensing, system integration and read out, commingling the different processes of the manufacturing process.
For CGT there are multiple automation implementation limitations facing manufacturers, e.g. controls of cell seeding, monitoring of cells in situ, monitoring of potency of cells, monitoring of key nutrients, feeding them progressively, harvesting efficiently, cell preservation, etc.
In the early phases of development, the cost of automation might not be balanced by the advantages that come with it. On the other end in a more mature phase, time might become the limiting factor as you may not have the necessary time to adapt your process to an automated one.
Automation is not always an easy step as it rarely comes custom made for a specific process; therefore, a proper process development is necessary and the industry is still lacking of experienced process developer to lead this change.
Last, I think it is important to mentioned that different devices don’t necessarily “talk” well to each other, meaning it is not straight forward how to transfer material and related information from one tool to another (e.g. between a bioreactor and a washing device, tubing and software might not be compatible).
Automation through miniaturization is advisable, but has the challenge of processing a rather large amount of patient sample (ie. 300-500mL), so key will be to find ways of processing these large volumes in a timeline manner without the loss of cell viability. Automation will be crucial otherwise these therapies will be hard to scale up.
A lot of funding goes towards the reengineering of the target cells, but only limited funding is made available towards optimizations of the manufacturing process. The government, through grants or other, could provide financial support towards these efforts.
Automation in the C> (Cell & Gene Therapy) industry pair up with the concept of closed systems. Together the two strategies have the potential to create new manufacturing paradigms: for example, to lead to manufacturing outside cleanrooms. It is important for the Authorities to remain updated on new technologies and their potential impact on processes and products so that they can easily understand and properly evaluate new ideas and proposals coming from the industry.
Governments like Singapore are actively supporting cell manufacturing, i.e. Singapore set aside S$80M to support the development of cell manufacturing for autologous, allogeneic cell therapies. This support is to improve regulatory pathways, address crucial quality attributes and release assays that will shorten the time to patient delivery and significantly reduce costs.
We are seeing increased activities of mid-sized cell therapy companies getting engaged with the allogeneic stem cell manufacturing programme (ASTEM) and early discussions with multinationals about building contract manufacturing of cell therapies in Singapore. This leadership by the government has been a catalyst to increased high quality enquiries from multiple companies looking to bring cell manufacturing from a cottage industry to one that is comparable to the biologics and vaccine industries.
When looking at the simple manufacturing aspects, automation may not result immediately favorable in terms of economics involved. What needs to be properly considered is the overall positive impact of implementing automation, as for example: the opportunity to reduce the risk of contamination, etc. or more simply the fact that only automation can make a process sustainable (and manufacturable) at commercial level.
It is a rather difficult case to illustrate a solid return on investment based on process improvements of cell therapies alone. These processes are customized to one’s needs and it might be challenging to find a ‘one-fits-all’ solution, therefore the smaller innovative start-up companies working on process improvements might be forced to tailor their solution towards specific end users (ie pharmaceutical companies and their cell manufacturing partners), with a potential impact on return on investment. Advice for the VC community is that investing into cell therapy companies might be even more successful if the cell manufacturing process is becoming part of the innovation and the necessary means are made available to give these companies an even more competitive edge. A treatment that is not scalable due to a flawed manufacturing process is not a sustainable business in the long term.
