In today’s biopharmaceutical reality, biologics are no longer simply proteins or antibodies; they now are being combined with small molecules, prepared at the nanoscale and otherwise manipulated and modified. Biopharmaceutical facilities today rely on a wide range of equipment and processes that require a high level of flexibility to ensure they remain valuable and relevant over the lifespan of the facility.
Emerging Biopharmaceutical Reality
The emerging biopharmaceutical needs have evolved beyond the known monoclonal antibody model. Other novel drugs and therapies are being developed at a rapid pace, including antibody drug conjugates (ADCs) with highly potent or otherwise uniquely effective small molecules. Advanced physical and chemical nano-technologies, genetic manipulations, microbiome manipulation and more cell therapies challenge the flexibility and control of the biopharmaceutical facility. These modes of treatment are playing a larger role in the design of new drugs aimed at treating an increasingly large number of diseases. In addition, the varying needs of operational capacity to meet large production capacities as well as smaller orphan drug scale operations are required.
At the same time, biopharmaceutical manufacturing facilities have been evolving at an increasing rate. Production facilities are transforming from buildings that house equipment aimed at individual operations with fairly standard operations into a new type of production facility. These facilities must meet technologically challenging containment and operational needs, requiring designs with highly coordinated sets of equipment that can operate simultaneously. In addition, production platforms require thoughtful integration with the building utility and mechanical electrical and plumbing (MEP) systems. Pressure to reduce costs and accelerate the drug development and commercialization processes has greatly impacted facility designs. It is no longer economically feasible to develop custom solutions for each facility. At the same time, it is essential to be able to quickly respond to market demands. Production lines often must be scaled up or down, or even modified significantly to produce different products while remaining compliant with regulatory requirements in a global market.
The integration of facilities and the constant and rapid evolution of production technologies pose challenges for biopharmaceutical manufacturers. For instance, how can facilities be designed to operate effectively for many years into the future when the products, technologies and market demand are continually changing? To some extent it is not possible to know what might be needed during the lifetime of the plant. Many questions must be addressed beyond the process design, such as:
- How will the facility be constructed?
- Is single-use technology a viable approach?
- What types of products will be produced and with what support systems?
- How will the equipment, systems and components be sourced?
- How can the design, engineering, construction and validation efforts be optimized to ensure the most effective, highest-quality production at the lowest possible cost?
Flexibility and agility are essential in many biopharmaceutical facilities. It is imperative, therefore, that these options are incorporated into the design concept from the beginning of a project.
Pressure to reduce costs and accelerate the drug development and commercialization processes has greatly impacted facility designs.
The Changing Role of the Process Architect
Traditionally architects and, specifically, process architects have focused on facility designs that meet the needs of individual processes. Today, however, their role has changed dramatically. Rather than provide engineering solutions for a specific need, the architects together with the process engineer are helping their clients determine how flexible their production facility needs to be and the range of product it can produce. They also provide process and technology integration, adopting a holistic point of view when incorporating each process and its utility requirements into an overall facility design meeting the needs of the clients’ marketing forecasts.
This evolution of expectations for process architects has occurred in response to the challenges presented by the new biopharmaceutical landscape; traditional customer/supplier interactions are no longer sufficient. Modern process architects share the challenge of bringing new products to market. As such, they go much further in providing consultative services, not just as external advisors but as partners that are professionally invested in the outcomes of the clients’ projects.
To take on this role, process architects need to have an in-depth understanding of established pharmaceutical manufacturing methods as well as the challenges imposed when implementing emerging technologies. Process architects are now being asked to fill the role of an industrial engineer and facility architect, with knowledge of the science and equipment needed to design buildings. This serves clients in many possible ways, often for applications that customers are not yet fully aware of at conception. Because of this, the conversations that architects are having today are very different. Process architects must think differently in order to offer real value to their clients.
Designing in Best Practices
M+W Group uses a platform approach with process architects and process engineers focusing on system integration. Now, a multipurpose design can be achieved through the use of modular systems. Platform designs have the advantage of providing the limited infrastructure needed for an accelerated startup (so as not to miss market opportunities) and an efficient way of using additional investments to meet production needs as they evolve over time.
Whenever possible, modular and skidded systems and components that fit with the project needs should be used. For instance, cleanrooms with integrated recirculation systems can be purchased from a vendor who will take on the entire scope of work, including installation and validation of the system, eliminating the need to develop a custom solution. With this approach, it is possible to develop a multipurpose system in which 80%-90% of the design remains the same for each facility. Slight modifications are made as necessary, in order to fulfill the requirements of the different locations in which construction will take place.
Ultimately, standardization leads to reductions in both cost and time. Through a Quality by Design approach, many of the risks associated with design and construction of customized facilities at each location can also be avoided. The growing availability of modular, advanced processing solutions makes this approach feasible. The use of modular systems allows for a lean and integrated approach that leverages the specialized skills and capabilities of contractors, subcontractors and systems vendors.
Given the specific requirements of the biopharmaceutical manufacturer, the engineering firm can establish guidelines, which are then used by the systems vendors to design, fabricate and install process skids. This provides the added benefit of keeping much of the fieldwork offsite. Knowledge of how to integrate different vendor systems into the total facility solution is essential. Effective project management and an integrated project design remain a main component of this approach to facility design.
Creation of best practices is also imperative for the platform design method to be successful. Once a modular system has been identified for standardization, a best value analysis should be performed to ensure that it meets the specific process and overall project needs. This review loop is essential. Systems that will serve as platform standards should not only meet operating performance specifications, but also cost and delivery time requirements. Quality can also be designed into the manufacturing process, just as specifications can be built into the manufacturing equipment. These systems then become best practices and are used to construct facilities around the world.
Introducing standardized platforms in the early development phases of a manufacturing facility project helps ensure agility and predictability in production that is crucial for success in biopharmaceutical facility design. Having consistent facility and process designs affords congruent product quality across all sites. Global procurement is also possible once a system has been identified as a best practice, eliminating the need to rely on bidding. The potential to receive discounts for large quantity purchases also exists. In addition, the modular approach requires fewer engineering standards and spare parts, allowing for the standardization of operator training.
Designing for the Future
With the increasing utility and range of biopharmaceutical products entering the mainstream, there is a challenge to design new facilities capable of meeting ever-changing research and production needs. Even if all of the project requirements are unclear at the beginning of the project, the team must work collaboratively to develop a range of operating parameters and assumptions that will allow the design approach and process to continue in an efficient manner. The firm tasked with designing facilities must understand both equipment and processes well enough to identify the requirements necessary for conducting the anticipated range of research and production operations. In a biopharmaceutical facility designed through standardization, the goal is to identify the lowest cost for a given unit output and create a uniform solution that will provide consistent performance within the design space, while allowing for flexibility of expansion. For instance, rather than pay an exorbitant price to construct and install a single, large filling line, multiple smaller multi-format filling lines with ready-to-use components and a quick turnover duration can meet the needs of tomorrow’s more specialized drug products more effectively and at a lower cost. Through standardization and modularization, such a production line concept can be repeated a number of times in one building, with more added if demand increases.
M+W Group is focused on being a thoughtful leader in the creation of flexible platform designs for biopharmaceutical facilities. By taking a system-by-system rather than a project-by-project approach, we are providing a value-added service to our clients. We use modular and standardized solutions when designing buildings and production lines and carefully consider the distribution of utilities for multiple set-ups with maximum flexibility.