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Jennifer Markarian is manufacturing editor of BioPharm International.
BioPharm International spoke with INTERPHEX 2013 conference-session presenters to gain insight on trends in facility and process design.
The conference schedule at INTERPHEX 2013 covered a wide range of topics, including facility and process design. BioPharm International interviewed Craig Sandstrom, director of process engineering at Fluor; Par Almhem, president of ModWave and Modular Partners; and Jeff Odum, director of operations at IPS–Integrated Project Services, to gain their perspectives on trends in facility and process design.
Modularization has been used by other industries for decades and, over the past few years, has been more accepted by the bio/pharmaceutical industry. Modularization is fast becoming an essential component of bio/pharmaceutical facility design. Use of modularization is growing because it meets the industry needs for reduced cost, accelerated construction schedules, and quality construction.
BioPharm: What are some of the considerations for using modularization?
Sandstrom (Fluor): Typically people have certain cost, schedule, and quality goals for their projects. Early on in a project, an effort is undertaken to look at the site and region where the facility will be constructed and also the facility design itself to determine what opportunities exist to address these cost, schedule, and quality issues.
Some of the local or regional issues include labor availability, labor rates, and associated logistics, such as what the site has in terms of being able to get people and materials to the site. Limitations in this area may drive a desire to try to move some of those activities offsite.
In addition, there is a desire to accelerate schedules. People want to make decisions and capital commitments as late as possible to save money and also to meet product demand, which causes project schedules to be increasingly compressed. One of the ways to address compressed schedules is via modularization. Modularization allows you to parallel path many of your activities, such as process-piping and equipment construction, and in parallel with some of the activities that take place to erect the building shell.
Finally, there are quality issues. Some places that you may want to build may not have quality labor resources available, or the weather or site conditions may be prohibitive. Moving the construction offsite allows you to do your construction in a better-controlled environment with higher-skilled labor.
BioPharm: What is involved in standardization of modular unit operations?
Almhem (Modular Partners): A module, in itself, is intended to be standardized. A module has a defined function with defined inputs and outputs. Once you identify a part of the process as a clear function with a clear input and output, you can design and build that as one unit. You can combine these units in different ways to create a variety of systems from a limited number of building blocks, which are the module units or unit operations. One example is a mixing skid, with the mixing system and controls all in one module.
BioPharm: What types of modules are used in pharmaceutical production?
Sandstrom (Fluor): One common type is the building module, in which all the architectural features, equipment, and piping are preinstalled. Another commonly used concept is the tank-array module, which may include several different process-unit operations in one module. There are many other varieties of modules. In piping-specific modules, for example, you modularize just the equipment, such as a pipe rack or a large cluster of instrumentation.
BioPharm: What do you see as the future of modular manufacturing?
Sandstrom (Fluor): I see modularization as an essential component of almost all facility designs. We see it now, and we see the trend continuing in the future.
One driver is that as facilities increasingly move to more remote locations, such as in Asia or South America where local trades aren't as mature as they are in the US and Europe, there's a desire to modularize to get the hygienic components of the facility designed and fabricated in a controlled-quality location.
Almhem (Modular Partners): Modularization doesn't actually change the manufacturing itself; it's more about how you manufacture. Modules will be used as the building blocks for more and more processes simply because it's a more efficient way of building a process function, or indeed building almost anything. Nobody would consider building a software system any other way than using modules (or objects as they are called in software), for example. We will see more and more modular systems and modular pieces in pharmaceutical and biotechnology facilities and processes.
BioPharm: What are some of the advantages of implementing single-use systems?
Odum (IPS): Advantages include reduction of cleaning costs via the decrease in the size or elimination of costly clean-in-place (CIP) systems because you are now getting away from fixed stainless-steel equipment. Along that same line, there can be a reduction in floor space because equipment is smaller and easier to move in equipment modules. Work is being done to consider how the implementation of single-use systems can reduce the amount of classified space that you must maintain during your manufacturing operations, via validation of system closure. Perhaps the biggest advantage of single-use systems is flexibility, especially if you are looking at the issues related to process changes in early-stage development.
Many developments in the biopharmaceutical industry have added to the challenges of designing, building, and operating the traditional manufacturing facilities that we've used over the past three decades. As our insights into product requirements and product characterization increase, the crucial path for the development of many new products is now shifting to the process development stage, and manufacturing timelines are being condensed. Speed and flexibility are thus becoming crucial to many of our clients.
Future manufacturing systems must be agile enough to deliver on this flexibility with regards to a wider variety of product types and in a shorter timeframe. Single-use systems can provide a means to allow for this increased flexibility and a focus on speed to market, even if you are dealing with a stainless steel-based facility.
BioPharm: Who should consider implementing at least some single-use systems?
Odum: Implementing single-use technology must be driven by the product and process attributes, the need for flexibility, and an understanding of the critical process parameters. Any number of manufacturing organizations could benefit from the implementation of single-use technology.
One group that I think is going to see a significant benefit is contract manufacturers. Because their business model is driven by both speed and flexibility, single-use technology could provide some distinct advantages in terms of their ability to adapt to new processes based on not only new clients but existing clients. Single-use technology gives them the flexibility to change their platform technology rather rapidly and probably with a lower cost. Lower need for classified space would also decrease capital expenditures.
Other business models would also benefit from this type of technology. Organizations that are focused on process development, such as research-driven organizations that do high-level development work, would benefit. Manufacturers focused on pandemic response would benefit from the ability to adapt very rapidly. Flexibility and adaptability, again, are key.
Another group that could benefit from single-use technology, in a way that perhaps they haven't started to look at in depth, is the academic institutions, which are being squeezed by their ability to fund capital expenditures for facility infrastructure. Any manufacturing organization should really explore the potential advantages of this type of technology.
BioPharm: What are some of the unique challenges of implementing single-use systems, particularly when you have an existing stainless-steel facility?
Odum: We work with a number of clients who have a stainless steel-based platform and are creating what we refer to as hybrid facilities. Three challenges stand out. First is a real understanding of the process definition and description. Although this may seem obvious, we have found that companies sometimes have a knowledge gap, especially from a developmental standpoint, on exactly how a specific process-unit operation may or may not be impacted by going to this technology.
The second challenge is looking at flows. Single-use systems are very flexible and modular in their approach from an equipment standpoint, and the ability to move components in and out of a particular space creates some logistical issues. As a part of that, there also needs to be a close investigation of accessibility. When your scenario includes a fixed stainless-steel asset that resides in a particular manufacturing suite—maybe due to size or maybe due to a future need—the ability for operators to access equipment and perform their day-to-day operations is extremely important.
The third challenge is process support. When you are dealing with single-use systems, you are now going to also deal with many single-use components that are absolutely necessary in order for each process unit operation to be executed and work the way it's supposed to. Tube sets, for example, are needed to connect components and allow the process to occur. Instruments, such as those to measure flow or temperature, must be integrated into the system. The design and development of these support items becomes a complex effort because there are a lot of parts and pieces that are going to have to be put together. Some companies get outside vendors to do this for them. Others have chosen to do some of it internally, but it's very different from designing a fixed piece of stainless-steel pipe in a building to run from point A to point B. Because of the fact that you're dealing with tubing, you have issues with regard to accessibility and logistics. Where do these hang? How do you support them? How do you make sure that they do not get damaged, or stepped on, or run over during the movement of equipment?
Wrapping around all these issues is the idea of closure. One of the things that we pay very close attention to is the idea of looking at system-closure analysis to make sure that, as all these components are designed, we are doing everything that is necessary to, first and foremost, protect the product from any potential contamination source and, in doing so, making sure that the system components are designed properly so that this closure can be validated.
Single-use technology is not without its challenges, but these are challenges that are being addressed to create systems that are efficient and bring a much higher utilization to a facility.