At first glance, the needs of an advanced therapy medicinal product (ATMP) facility may seem to be no different from those of a traditional bioprocessing facility – and indeed the clean rooms, testing and admin facilities will be very similar. Once you move into the commercial manufacture of ATMPs, however, more specific requirements will become apparent, particularly the “scale-out” rather than “scale-up” concept, gowning and segregation requirements, as well as community perception of the facility.
Building a facility that is fit for purpose begins with site selection. Your first choice is whether to build on a greenfield site – an undeveloped site with no pre-existing buildings – or fitout an existing shell building. It is common for companies to have surplus pharmaceutical manufacturing sites or warehouses that they wish to make use of, but in our experience, it can be difficult to optimize existing buildings for ATMP manufacture. With ATMPs, you need to consider expandability when creating the facility – how are you going to expand to accommodate future capacity as the business grows? This is particularly relevant for many autologous ATMP processes, since these can be manual and labor intensive, requiring additional space for expansion of capacity. These same limitations can apply to utility systems. If your space is constrained from the start by an existing building, then it can be tricky to truly optimize the facility.
One cell therapy client we worked with selected what seemed to be an appropriate site in an urban city block in New York, but the project came undone once they considered their liquid nitrogen distribution strategy. There was no space for bulk tank storage (space is always at a premium in big cities), so they had to consider the use of portable cylinders, but that meant there would be an enormous quantity of cylinders to move throughout the building. When moving liquid nitrogen in enclosed spaces, such as an elevator, you cannot have an operator in the same space because of asphyxiation hazards. You need to set up a shipping and receiving dock for the cylinders, and you need a way of getting them into the elevator and transporting them without a person. Additionally, you need to ensure everything is logged. Ultimately, it would have commandeered one or two elevators during shifts. And logistically that wasn’t going to work, so the site choice was abandoned. The client moved to another site where there was a shell of an existing warehouse that could be better designed to suit their needs. If you are opting for an interior fitout option, then try to ensure that the space selected allows for flexibility.
Making the location work
Local incentives from governments and municipalities will almost certainly play a large role in the choice of location. Many areas offer local funding or workforce training to attract business investment, which will ultimately affect the overall cost of developing a new facility. The help available can also impact the time it takes to get the facility up and running – perhaps by accelerating the granting of necessary permits, for example. For ATMPs, however, the most important aspect regarding location often involves transportation logistics. Autologous ATMP therapies involve getting cells from and to patients or treatment centers – often very quickly. Some companies consider a chain of regional distribution centers, but being located close to a major airport or transport hub is usually desirable. If your site is to be located in a remote region, you can still set up your own transport links using private couriers – although few companies choose this option. It can also be necessary to rule out certain areas because of their weather patterns. If roads or airports are frequently closed because of storms, then it could seriously affect the therapy reaching the patient – and ATMPs really can be a patient’s last chance at life so delayed treatment could be fatal.
You also need to consider access to a skilled workforce. Given the fact that there are few automated solutions for manufacturing ATMPs, processes are manual and require attentive and highly trained workers who can perform the process in line with cGMP. An obvious solution is to locate your factory in a populated area with other ATMP companies, as well as prestigious universities. This makes the hiring process easier – and you can also partner with universities and local schools to raise awareness among younger talent – but it can also result in high staff turnover because of the competition. If you are planning to locate your facility in a competitive area, it pays to think about what you can do to retain staff. Companies like Google have gone to extreme lengths to make their facilities attractive to staff! Few pharma companies are willing to go that far but considering lounge space and amenities, such as a creche or a fitness center, can be hugely beneficial in attracting and retaining staff. If this isn’t an option – many ATMP companies are small so may not have the capital available for optional extras for staff – consider alternative options that will make the company attractive, such as partnerships with local facilities and cafes. You can also partner with nearby companies to share meeting spaces.
It is also worth considering the fact that in populated areas, space can be at a premium, which brings us back to the need for potential expansion during the lifetime of the ATMP therapy. In a less populated area, while it may be initially harder to staff employees, there is the opportunity to train a stable, dedicated workforce. Sites may be larger and less expensive too, but this may be offset against the transportation logistics and other factors including access to vendors, and disposal of medical waste, which can be more expensive.
In many cases, we find that companies lean towards populated areas. But the final decision may also be influenced by upper management – who may simply want to choose a location that is nice to live in or that is close to the company’s roots.
Flexibility for the future
From the very start of a project, you need to go through your process every step of the way. Where is your incoming material coming from? How frequently will it come? What space does it require? Where will it be stored? How do the materials move about the facility? What space do you need for cleanrooms? And then how is the therapy transported back out to the patient? You need a good picture of the physical space involved in all aspects of the manufacturing process. We recommend using modeling to understand what will happen in each of the key spaces and to determine the requirements. In our experience, the hardest part for clients is making key, pivotal decisions early in the project and keeping to those decisions throughout the project lifecycle. If you cannot decide what your needs are then it will be difficult to choose the right site and to optimize the facility design. As one consideration, if you don’t know how many employees you’ll have, then it will be difficult to plan for parking, employee facilities, gowning, and how many people you’ll actually have in a cleanroom and how this affects the facility layout. Cleanrooms and quality laboratories are often the main considerations and it’s very easy to overlook everything else that is required for a facility.
We’ve outlined only a brief selection of factors that may influence site selection – there is far more to consider. But for ATMPs, the biggest advice we can offer is to choose a site that is flexible – this could be a greenfield site or a flexible shell building for interior fitout. The era of ATMPs is only just beginning; technology is changing fast and a lot of lessons are being learned as more therapies reach the market. Your facility needs to be flexible to adapt to new trends and to be future-proofed for next generation therapies.
Article originally appeared in The Medicine Maker.