If cell and gene therapy products are to successfully reach patients and deliver transformative cures, then the industry will need more facilities capable of manufacturing them.
A huge number of advanced therapy medicinal products (ATMPs) are being developed, with many already in clinical trials. The growth predicted for these therapies over the next decade is significant because of their potential to deliver real cures rather than just managing a disease. Many ATMPs are personalized, which means that the manufacturing process must also be personalized (one batch per patient). These autologous therapies require very small-scale production as compared to the industry’s traditional mass production facilities. It’s clear that autologous ATMPs are quite different to what the biopharma industry is used to.
There is currently an ever-increasing demand and lack of capacity when it comes to facilities capable of manufacturing ATMPs – and specifically autologous cell therapies. At the end of 2018, there were over 1000 ATMPs in clinical trials (spanning phase I to phase III). Not all of these will make it through trials, of course, but for those that do, where will they be manufactured? Autologous ATMPs are not traditional biopharmaceuticals; they require different processes and manufacturing facilities. Because of this, many biopharma companies are looking to build dedicated facilities for ATMPs. Contract manufacturers are also looking to add capacity for ATMPs so that they will be able to capitalize on the market and attract new customers looking to manufacture ATMPs.
Given the growth prospects of the field, it’s not surprising that a lot of companies want a slice of the ATMP pie. Many new partner companies are emerging, but over the next few years there will likely be a lot of changes and consolidation. Not everybody has the experience capable of navigating the challenges of the ATMP field. The keys to finding the right partners to enhance the delivery of these manufacturing facilities is to focus on those with experience, particularly with the regulatory expertise around facility design and construction. To the untrained eye, these facilities might look like glorified labs, but they are GMP facilities with very specific regulations around design, operations and supply chain management.
From paper to physical facility
At first glance, the job of a facility design and construction specialist is simple: design the facility, build the facility. There is a clear starting point on paper and a clear endpoint in terms of delivering the physical construction. But in my view, the job should go beyond this and encompass end-to-end project execution. ATMPs could transform health for many patients – and all of us involved in the field, including those of us specializing in facility delivery, have a role to play in helping this new era of medicine to reach its potential. The end goal is not to simply finish the construction of a facility, but to get the product to the patient. To do this, you need to design and build a facility that is capable of delivering the product safely, in the right quantities, and able to adapt to future demands.
Time and money can be saved by getting the facility design right at the onset. A holistic view is essential. You must understand the science, logistics, operations, manufacturing processes, regulatory requirements, and expected demand of your final product. This knowledge serves as the foundations of the facility and will influence the final building design. As with physical construction, if you don’t build a solid foundation it will cause instability and inefficiencies later on, preventing future phases of the project from moving smoothly. During the design process, you also need to set out your target budget and schedule, and optimize based on that. Designing a good facility is not just about ensuring it has the right capabilities, but making sure it accommodates business needs and drivers. Over the years, I’ve seen far too many projects where the design progresses according to certain requirements, but then has to backtrack when the cost estimate is received. This wastes a lot of time and money because work has to be redone.
One of the biggest challenges with manufacturing ATMPs (and specifically autologous cell therapies) is that the process is manual and labour intensive. Few automated technologies or platform technologies exist, and large numbers of staff are required, as well as large facilities to accommodate the need to scale out. This may all change in the future as the industry comes to grips with manufacturing ATMPs, but companies can’t simply sit and wait for the process to be optimized or technologies to be developed. Facilities need to be built now – but the good news is that they can be designed for flexibility so that they can adapt to future trends and technologies. Operations improvement and simulation modelling can help manufacturers to understand what is happening in their facility, what improvements can be made, and how this might affect the facility down the road.
Autologous cell therapy manufacturing is currently a very small scale and open process requiring high levels of classification and manual manipulations. In the future, however, manufacturing processes will likely become more automated, which means additional equipment and the ability to operate with less people, but higher throughput. Can you imagine that situation with the same floorspace, potentially doubling throughput? You need to think about future scenarios when designing your current facility. Predicting the future is difficult, but I think it is possible to make some fairly reasonable predictions about how facilities will look in the next five years.
Closed processing is one technology that is likely to change autologous cell therapy manufacturing as we see it today. We may also see innovations in isolator design and robotics. Given that human interaction is prominent in autologous cell therapy manufacturing, I expect we will see innovations focused on robotics that can replicate this interaction, while reducing the potential for human error. Removing the human element from the environment significantly reduces risk to product safety and, ultimately, to the patient. The main themes for innovation in the field will be how ATMPs can be manufactured and delivered safer, faster, more efficiently and cost effectively.
The fast lane
The ATMP field is changing fast and I would encourage companies to continuously review new technologies and trends. What we do not want to happen is that a facility based on what is currently available becomes the model for multiple facilities down the road. Five years from now, if we are still designing and building the same facilities that are being built today then I think we would be doing the whole industry (and patients) a disservice. This industry is highly regulated and there is a common saying that everyone wants to be the second to try out a new technology – no one ever wants to be the first because of the perceived risks! We need to be careful and not fall into the copy/paste facility cycle that was experienced in early biologics production.
But it’s amazing to see the industry coming together to tackle the challenges of the field. Manufacturing companies, regulatory authorities, engineering, construction companies and others are all coming together to examine how we can get these therapies to market faster. The regulatory authorities have done a lot of work to develop new approval pathways designed to expedite access to patients, and the agencies have also been offering support and encouragement for manufacturers to use new technologies that can improve the production processes.
Article originally appeared in The Medicine Maker | March 22, 2019