With the age of the blockbuster drug passing, the business model for the biopharmaceutical industry is changing. The personalization of medicine, the emergence of biosimilars and biobetters, and the need to provide vaccines globally are just some of the factors forcing biomanufacturers to rethink how future manufacturing capability is implemented. One thing is clear—the traditional manufacturing strategy of building large-scale, purpose built, capital-intensive facilities is not going to meet the industry's emerging production and economic requirements.
Single-use technologies have the potential for helping companies execute their developing strategies for flexible manufacturing. The adoption of disposables continues to increase year over year and is already established in many process steps within the industry. The benefits of single-use technologies, such as reduced cleaning and validation, reduced downtime, and reduced equipment footprint, are well recognized and continue to drive the development of new and innovative products. Over the past decade, manufacturers have witnessed the progression from disposable encapsulated filters and tubing sets for small-scale production to today's 2000-L bioreactors and 2500-L single-use mixing systems in licensed biomanufacturing processes.
A fundamental change in the way biopharmaceutical facilities are designed and constructed is required. The pressure to reduce facility-investment costs and the cost of goods manufactured is a primary driver in the paradigm shift occurring in industry's approach to facility design (1). Innovation is required to design facilities that are more flexible, more rapid to construct, less capital-intensive, and can be repurposed as product requirements change. The new facilities must be of high quality and rapidly reach compliance after construction. New facility concepts and products from suppliers are beginning to emerge that anticipate the unmet needs of the biopharmaceutical industry, as are the expertise and innovative thinking to meet the challenge.This article discusses how a single-use manufacturing process for a monoclonal antibody (mAb) can be integrated into self-contained modular cleanroom systems, such that a total "out-of-the-box" solution for manufacturing capability can be realized. Overviews of both the process and facility elements considered as well as the related advancements and enabling technologies now available are provided.
A conceptual integrated design is presented that can be used as a blueprint for the next generation of biomanufacturing facilities. The benefits of this approach with respect to flexibility, cost, and schedule are discussed. The concept presented here can be applied to other biopharmaceutical manufacturing processes and facilities, including, but not limited to, vaccine manufacturing, multiproduct/multiprocess capability, and clinical manufacturing.
The development of technology platforms is an approach that is becoming more prevalent within industry today. The ability to use platforms to standardize upstream and downstream biopharmaceutical manufacturing processes as well as analytical methods has the potential to significantly reduce the time and costs associated with bringing a product from development to commercialization. Platform cell lines and expression systems have been successfully implemented in upstream processes by a number of biomanufacturers. Companies such as Bristol Myers Squibb are developing antibodies and other molecules by applying platform-based approaches (2).
The standardization of processes logically drives the standardization of process equipment and technologies. An equipment technology platform can, therefore, be engineered for a process and used as a basis of design for similar molecule types, such as mAbs. This template provides a starting point that can save significant time and effort during the engineering and operational design phases in the product lifecycle. Implementation of single-use technologies within a platform can further reduce the project timeline for establishing manufacturing capability.