December 9, 2020 PAP-Q4-20-CL-010
There are several important trends in the pharmaceutical industry that are impacting the ways manufacturing facilities are designed and constructed. As companies bring outsourced projects in-house, they need to maintain the versatility afforded through contract manufacturers. They also require flexibility in scale-up from the lab/benchtop to pilot production through to commercial manufacturing.
Overlying these needs is the emergence of new modalities and next-generation products that require specialized manufacturing facilities in equipment, from cell and gene therapies to highly potent small molecule active pharmaceutical ingredients (APIs). Achieving the appropriate containment levels is essential for minimizing cross-contamination while also ensuring operator safety and protection from exposure to these highly potent compounds.
With the advent of COVID-19 vaccine approvals, there is also likely to be a shortage of aseptic filling capacity in North America, and biologics manufacturers — both biopharma companies and outsourcing partners — need to be versatile and adaptable enough to expand their capabilities to meet this growing demand.
In the end, working flexibility into business models is essential to remaining competitive. Drug developers must be able to move rapidly from development into production and scale-up in order to be the first to market. Indeed, timeframes are being drastically compressed for both pharmaceutical and biotech products with new facilities built faster.
There is also likely to be a shortage of aseptic filling capacity in North America, and biologics manufacturers — both biopharma companies and outsourcing partners — need to be versatile and adaptable enough to expand their capabilities to meet this growing demand.
Construction of facilities for the production of new modalities and more highly potent compounds can carry significant uncertainties with respect to the specific design and equipment that will support still-evolving production practices. In many cases, decisions on the exact nature of the product and processes are delayed as long as possible, leaving less time to get to market.
To overcome these challenges, Environmental Systems Corporation (ESC) uses a process we call “enhanced conceptual design,” which allows us to reduce the number of detailed reviews that are needed. We build a comprehensive team, bringing contractors and trade partners onboard early on so they can participate in initial discussions with the client. These teams bring a lot of great ideas on how to do things more efficiently and effectively from a construction and installation standpoint.
Taking this approach, it is possible even without having exactly defined the entire process to begin construction activities. With an understanding of a basic level of information and estimates for electrical power demand and cooling/heating loads, for instance, these components can be sketched in and confirmed once the process is further refined.
The enhanced conceptual design approach provides clients with a better, more granular number when executing capital planning, forecasting, and seeking budget approvals. They can avoid the typically iterative and costly process of getting to the conceptual design stage, putting it out for bid tender, and then developing a detailed design, which leads to many changes and a need for further design revisions, and so on.
Of course, some clients already have a more sophisticated, complex project team in place to match the size of the project. We work within that type of environment as well. But we’ll often try to implement the enhanced conceptual design–build approach.
When the enhanced conceptual design approach is combined with the use of modular construction and parallel process and facility engineering, it is possible to dramatically reduce the time required for facility construction. Modular construction is ideal for upfront pieces that can be decided on fairly quickly, allowing modules to be built in advance. These modules can then be bridged with a larger process room. While some clients elect to implement a fully modular solution, a hybrid approach often provides the best solution to meet their needs in minimal time.
Any systems that can be standardized and do not require detailed components specific to any one client’s process can be modularized. Good examples include gowning rooms, anterooms, material handling spaces, airlocks, corridors, and laboratory, analytical, and QC spaces. If the traffic flow and number of people going into and out of a cleanroom are known, the gown room can be sized appropriately, for instance, predesigned standard modules can be put together like pieces in a puzzle.
What is very important at this stage is to understand how much space will be needed for the actual process operations so that appropriate room can be allotted during these initial stages when the modular systems are installed. Once the details for the processing and pilot suites are finalized by the client, they can be customized and installed.
With a completely modular solution, everything can be constructed in a controlled environment within a factory setting. Multiple spaces can be leveraged, with fabrication in one facility and the internal fit-out and infrastructure in another, to enable parallel processing and rapid sequencing of the modules. At the site, the only needs are the concrete padding/fittings/foundation depending on the size of the facility, and there is no waiting for a full building envelope to be enclosed.
Using a hybrid approach, the modules can be constructed in advance, and then the infrastructure is built into them. ESC typically adopts a two-storied approach for our modules, with personnel and processing areas in the ground floor modules and the infrastructure in the second-floor modules, including HVAC equipment, ductwork, and process piping, to maximize accessibility.
Using this approach, it is possible to fast-track construction and generate savings on project timing of anywhere from 15% to 30%, depending on the project. It also allows clients to identify which information has to be decided upfront to get construction underway and which decisions can be pushed out a little longer once greater process understanding is gained, and processes can be better defined.
In the face of the COVID-19 pandemic, modular construction also provides the advantage of dispersing work on a facility to multiple locations, rather than having everything done at the site. The fabrication unit works in its own “bubble,” then the modules move to a different site where the electrical and mechanical components are roughed in a different “bubble.” As a result, the risk of exposure and potential labor stoppages/shortages is limited because, if someone does get sick and people need to quarantine, only the immediate bubble is involved, and not everyone involved in the construction of the facility.
Any systems that can be standardized and do not require detailed components specific to any one client’s process can be modularized.
Biopharmaceutical facilities typically operate around the clock every day for large periods of time. For instance, plants that manufacture the flu vaccine must operate for several months without stopping in order to produce the needed quantities of product to enable delivery and administration before the onset of flu season. During that time, all of the facility systems and equipment involved in those operations must be reliable and behave in a highly predictable manner.
To ensure that facilities can remain operational 100% of the time, ESC builds in reliability and creates redundancies for key systems. We are also looking to build facilities that no longer require summer or year-end maintenance shutdowns through the use of preventive and ongoing maintenance solutions that can be implemented while systems are operational.
In addition to providing predictability, modular systems from ESC can enhance the control of process parameters, such as temperature, humidity, and pressure. Controlling temperature, humidity, and pressurization is all about removing variables, which we achieve with our two-storied approach and avoiding the need to deal with an external building envelope.
Environmental controls are located in second-story, accessible modules. Each of these modules is designed specifically to support the operations/processes taking place in their corresponding first-story modules. As a result, clients can be confident that the right environmental conditions will be established. Even in cases where a single air handler may support two or three modules on the first story, the controls are installed in advance to meet the specific needs for each of those modules.
It is important not only to control the environment in biopharmaceutical production facilities, but to consider their impact on the surrounding environment. Recyclability of modular cleanroom components is one way to reduce that impact. All of the modular cleanroom components from ESC are constructed using aluminum-based materials. Aluminum has one of the most positive recyclability profiles from both content and demand perspectives.
ESC does not use any ferrous metals to avoid concerns about corrosion or quality. All cleanroom walls are aluminum. All structural components are high-quality aluminum. All scrap materials generated during the construction process and cleanrooms at the end of their life cycles are recycled at the processing facility.
ESC is committed to helping the pharma industry achieve net-zero production facilities in the post-COVID world.
ESC is continually seeking opportunities to develop novel solutions that will enable more rapid construction of highly efficient biopharmaceutical manufacturing facilities. Two important developments are in the works today.
The first is disposable, or at least semi-disposable, cleanrooms. These inflatable structures have liners inside them and are suitable for short-term (two or three months) campaigns, perhaps involving a highly potent compound or biologic. Rather than investing time, effort, and money in the validation of a more permanent solution with required cleaning processes, these cleanrooms can be deflated and compressed into a small package that can be incinerated.
ESC is also focused on developing solutions that leverage the Internet of Things and Industry (Pharma) 4.0, including both hardware and infrastructure, to enable more effective use of sensing and data analytics technologies. We are partnering with the technology group at our local college to determine the optimum solutions for capturing and analyzing data and providing the results, including how to maximally leverage artificial intelligence and machine learning in a biopharmaceutical manufacturing facility. This work is ultimately driving toward achieving net-zero facilities.
The guiding vision and philosophy of ESC is to create environments for success, not only for the company, but also for our clients, partners, vendors, and everyone we work with, including our own team members. As a full turnkey provider of critical environments and cleanrooms, we have developed our own products including our Aluma1 ceiling and floors system. We also work closely with clients to design and build custom cleanrooms that meet their specific needs. We build and manufacture the HVAC and other systems required to supply the critical environments for pharma manufacturing in our own facility, and we offer the final piece of integration around the controls and monitoring of those environments, right up to 21 CFR PART 11–validated monitoring systems.
Once we put the COVID-19 pandemic behind us, the biopharmaceutical industry will once again have the freedom to focus on bigger-picture issues: sustainability, energy consumption, the net-zero approach. How we use resources is going to become a bigger focus as we move forward over the next 20–30 years. We have to figure out how to drive down to that net-zero application or at least get as close to it as possible. But first, we have to truly set that target.
Net-zero is not a big part of the conversation yet, but ESC is beginning to drive the conversation, because there is room for improvement with respect to the carbon footprint of construction activities. We are starting to look at carbon footprints — and the larger environmental footprints — with a net-zero approach in mind. There are some new ways of approaching this that are already under development, the question is how to bring those technologies into the biopharmaceutical industry for their facilities.
ESC is committed to helping the pharma industry achieve net-zero production facilities in the post-COVID world. We are evaluating the environmental impacts and the operational and capital costs associated with the cleanrooms that exist today. This information will be used to design and build more environmentally friendly cleanrooms with the goal of realizing net-zero facilities. ESC wants to be a tangible part of the solution. To do so, we are looking at technologies that can actually contribute to a net reduction in carbon footprint and energy consumption.
For instance, we recently partnered with an emerging technology firm developing novel membrane dehumidification systems. This startup company, which stemmed from an incubation hub at a local university, has a new approach to this method of dehumidification. We have a scale-up demonstration currently in process and are hoping to have several clients piloting the technology in real-world settings by the second quarter of 2021.
Aaron is creating environments for success and value for clients, partners, and team members and applying his diverse industry experience to develop innovative solutions for Critical Environments and Cleanrooms. He has a Bachelor of Applied Science in chemical engineering from Queen’s University and has worked in manufacturing, engineering, and operations management for 20 years holding several progressive positions.