The main driver influencing all aspects of the pharmaceutical industry is the growing downward pressure on costs. Shifting markets, the end of the blockbuster era, government healthcare mandates, and the linkage of insurance reimbursement with medical outcomes are all affecting drug pricing around the world. In response, pharmaceutical companies are taking many different actions to reduce their costs and increase efficiency and productivity.
The recent rise in mergers/acquisitions in the pharma industry is one mechanism by which companies hope to reduce costs through synergies and access to new therapeutic classes and/or regional markets. Outsourcing of pharmaceutical manufacturing is on the rise, as is the use of third-party service providers for business activities traditionally considered core to sponsor companies, such as logistics. Interest in continuous processes is also intensifying, and emphasis is now placed on the deployment of equipment and technologies that enable higher production yields, the reduced need for purification and more rapid scale-up and commercialization.
As a result, equipment needs across the value chain are changing, from initial discovery efforts to the packaging of final products. Suppliers of research and development and production equipment, analytical instrumentation and packaging systems are responding with innovative technologies that meet these needs. At the same time, the surplus equipment market has experienced strong growth due to the increased availability of high-quality equipment and the need of contract and generic manufacturers, and even branded drug companies, for low-cost equipment solutions.
SINGLE-USE TECHNOLOGY: COMMERCIAL-SCALE
Single-use, or disposable, technology is widely used in biopharmaceutical drug development, and more recently has begun to gain acceptance in biologics production at increasingly larger scales. This interest is driven by the advantages that disposable technologies provides in terms of decreased capital expenditures and operating costs due to the reduction of cleaning and sterilization steps and the need for validation. In addition, processes based on single-use equipment are more flexible, require shorter set-up times and have significantly reduced cross-contamination risk, all of which translates to a faster time to market and more robust and reliable production.
Numerous types of single-use bioreactors are employed for the production of the major types of biopharmaceutical products, including recombinant proteins and monoclonal antibodies. Different designs are also available for batch, fed-batch and perfusion reactions. While the initial focus was on the development of disposable technology for upstream processes, single-use formats are now available on the market for many downstream bioprocess steps, including filtration and chromatography. For instance, modular, disposable tangential flow filtration (TFF) systems can be readily integrated for the concentration of downstream biopharmaceutical process streams.
CONTINUOUS BIOPHARMA MANUFACTURING
In fact, many newer single-use systems are designed for use in continuous bioprocesses, and disposable technology is an enabler for the implementation of fully integrated continuous biopharmaceutical production. Continuous manufacturing is attractive because it leads to more consistent products and processes, which equates to the consumption of fewer resources (raw materials, energy, water) and less waste generation, for lower operating costs.
For upstream biopharmaceutical manufacturing, perfusion has become a well-established process that affords high quality biologic drug substances with high productivity. Other types of upstream equipment under development include continuous centrifuges, acoustic resonance devices and cell settlers. For continuous downstream bioprocessing, simulated moving bed chromatography and as mentioned above, TFF systems, are also available and being adopted by the industry. New flow-through absorbers are also being developed for integration with chromatography and virus filtrations steps. Advances in process analytical technology (PAT) systems are also crucial to the successful implementation of integrated continuous bioprocesses.
The benefits of continuous processing are not limited to biopharmaceutical production. In fact, the industry has recognized the value of flow-through chemistry for the production of active pharmaceutical ingredients (APIs) and continuous tableting for many years.