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Jennifer Markarian is manufacturing editor of Pharmaceutical Technology.
Flexibility, which involves the ability to quickly change product capacity or even product type to meet market demand, is increasingly important. In new construction or renovation, modular process skids and modular buildings create this flexibility. Experts discuss trends and challenges.
An important part of process design is optimizing manufacturing capacity, efficiency, cost, and, increasingly, flexibility, which involves the ability to quickly change product capacity or even product type to meet market demand. In new construction or renovation, modular process skids and modular buildings create this flexibility.Pharmaceutical Technology spoke with Herman Bozenhardt, principal at Bozenhardt Consulting Services; Dave Kenyon, PhD, vice-president of Process Sciences at Gallus BioPharmaceuticals; Maik W. Jornitz, president of G-Con Manufacturing; and George Wiker, vice-president, US Life Sciences and Chemicals Market Segment lead, at M+W Group, about modular bio/pharmaceutical manufacturing systems.
Trends in modular construction
PharmTech: What is driving the increasing need for flexibility in bio/pharmaceutical manufacturing?
Kenyon (Gallus): The need for ‘in country/for country’ manufacturing, pressure to reduce healthcare costs, uncertainty of molecule performance, and uncertain market demands are driving the need for flexibility.
Jornitz (G-Con): There are a multitude of drivers, including cost of goods sold (COGS) and capacity utilization. Everybody wants to use their production capacity to the fullest, which brings down COGS. Optimizing capacity utilization requires either running multiple products through a process or being able to easily scale the process without production interruptions (i.e., requalification).
Single-use technology supports flexibility in process technologies, but this flexibility can be hindered by facility inflexibility. New, flexible facility designs that enable single-use systems and enhance their flexibility are desired.
PharmTech: How would you describe the current use of modular construction and what trends do you see for the future in pharmaceutical manufacturing?
Bozenhardt (Bozenhardt Consulting): Existing facilities have three main design problems: old, large, inefficient heating/ventilation/air-conditioning (HVAC) systems that are not segregated for different production areas; architectural layouts not designed for today’s regulatory requirements for unidirectional workflow; and outdated architectural finishes that create the potential for high bioburden. Renovations, sometimes completely demolishing and then rebuilding with modular systems, are being used to eliminate these problems and, at the same time, create more flexible capacity.
Wiker (M+W): The current commercial use of modular buildings is limited. There is a broad spectrum of modularity, and newer technologies provide customers a range of options and create market competition. The spectrum includes building modules with utility systems and complete cleanrooms (i.e., pods or building modules with process systems), which are available today and expected to be more widely used in the near future. Another modular option is self-contained unit operations that are interconnected with single-use transfer systems.
Product processing systems are also becoming modular, with ‘plug-and-play’ equipment that can be rolled into a cleanroom suite, bolted-on, ands started up quickly. While one module is operating, we can install another module right next to it. Once the new module is qualified and fully functional, we can interconnect the two with just a short interruption (e.g., over a weekend) to the existing process.
Jornitz (G-Con): Today’s modular stick-built or container-built structures are becoming obsolete because most of these systems cannot be repurposed and do not have the flexibility required for the future. Modular designs will be replaced by podular designs in the near future. These structures can be used for laboratory purposes, unit operations, or whole facilities, which then could become clonable facility platforms. These structures can meet new production needs for the cell therapeutic and personalized medicine markets, for example.
Kenyon (Gallus): There are more choices on the market today, and module manufacturers are becoming more familiar with the regulatory constraints modular structures need to meet. Modular construction is an area that will continue to grow in the future as large capital investments are less available and companies work through optional strategies. Modular construction can also be a solution for CMOs and their clients to develop and manufacture products.
Benefits and challenges
PharmTech: What do you see as the key benefits of modular building in bio/pharmaceutical manufacturing?
Wiker (M+W): Key benefits of modular building include predictability (i.e., modules are pre-engineered and pre-defined) and faster execution that speeds up ‘time to manufacturing’. The construction schedule is accelerated and equipment can be brought up and running quickly.
Although the actual cost of the physical materials might be 5-10% more in a modular construction, the net present value is better because construction is faster. With this modular approach, you can add capacity when the market needs it, creating a successful outcome. Expandability (i.e., ‘bolt-on’ capacity) and repeatability (i.e., the ability to replicate plants) are also advantages.
Bozenhardt (Bozenhardt Consulting): Modular building blocks can be constructed off-site and moved to locations as needed. Off-site construction is generally more consistent with a higher level of quality.
PharmTech: What are the benefits of separating utilities from the overall process and creating self-contained cleanroom modules?
Jornitz (G-Con): Utilities include water, compressed gasses, electricity, and filtered air. Connecting these to the entire cleanroom infrastructure would be detrimental to flexibility, because it would be difficult to verify that the convolution of ductwork is truly clean and sanitized in a product changeover. Leaks, pressure losses, and temperature changes in such ductwork accumulates to high operating costs. Having unit operations as separated cleanroom structures with their own air handling systems enables the rooms to be more easily sanitized or turned down when idle, and enhances containment and process control.
G-Con created PODs, which have their own air handling system in a mechanical space in the back of the POD. This space holds the controller, fire suppression system, and a compact air-handling system; the ductwork can be sanitized with vaporized hydrogen peroxide. With its own air handling, a POD is a containment system, comparable to an isolator. With the ability to be cleaned and sanitized, the PODs are able to be used for multiple products. In addition, the system can be scaled up and down, because these autonomous air handling system do not need to be rebalanced when an additional POD is connected.
PharmTech: What are the primary challenges in implementing modular construction?
Wiker (M+W): The market still does not fully understand the value of modularity and has not grasped that modularity is closely linked with standardization and the ability to quickly and easily replicate modules. Although clients often select modular systems for process and facility systems, they often customize those systems, thus diminishing the value by increasing cost and lengthening the overall project schedule. As the bio/pharmaceutical market becomes more commoditized (similar to food and nutrition), these clients will likely have little choice but to utilize standardized modular systems to rapidly and predictably develop manufacturing infrastructure.
Jornitz (G-Con): The main hurdle we have to overcome is the typical hesitancy to adopt new, revolutionary technology. Also, some calculate only cost per square foot of cleanroom area instead of taking the total cost ownership into account. After much education and discussion, however, we are seeing rapid adoption of podular technology by some industry leaders. PT