Biopharmaceutical manufacturing and flexible design: what does the future hold?

The biopharmaceutical manufacturer of the future is nimble by design to rapidly adapt to new products and improved processes. The facility is primed with technical proficiency to anticipate consequences of process improvements, characterization of their current capabilities, flexibility to rapidly introduce new technology and expertise to mitigate risk. Recombinant protein manufacturing to date has primarily been orientated for timely delivery of exclusive large-volume products, ‘blockbusters’ to patients with access to the highest standard of care. Process development for the most part has focused on the regulatory requirements for quality, safety and efficacy. Thus, manufacturing science has evolved around issues such as elimination of animal-derived products, extractable leachables, and process qualification for viral and prion safety. Process development has achieved culture titers and recovery yields needed for a commercially viable process [1]. Thus, in the interest of speed to market, single-product facilities were built and more complex manufacturing efficiency issues were given secondary consideration. The future of recombinant protein products will include biosimilars, regional manufacturing and smaller volume, specialized products in multiproduct facilities, as biopharmaceutical manufactures strive to deliver drugs to a more diverse patient population at cheaper cost. As with most maturing industries, manufacturing efficiency will become more important. The biotechnology facility of the future will probably not be a ‘green field’ new installation. It could be an existing facility owned by a biopharmaceutical manufacturer, a facility acquired through merger or acquisition, or one rented from a contract manufacturing organization. It will probably be a hybrid with a layout suitable for single-use equipment, and piping and utilities for installed stainless steel equipment with reduced clean-inplace (CIP) and steam-in-place (SIP) systems [2]. Selection of the facility will depend on modifications required, portfolio of products manufactured and the new process fit. Facility modification will continue with adjacent areas such as warehouses and lobbies being added to the clean area of the facility and closed systems being installed in uncontrolled space. In addition, the demand for each product and facility staffing will often determine the best value along with the process flow diagram and regulatory requirements. Equipment selection to optimize return on investment will require analysis of each unit operation. For example, selecting a new bioreactor would need consideration of at least three options: single-use plastic, automated stainless steel or hybrid stainless steel surrounded by single-use auxiliary equipment to simplify CIP and SIP. For a multiproduct facility, each option will need analysis of the capital, component, raw material and utility costs for four operating modes: production, turnaround between batches, product changeovers and idle. The best decision could be different in a facility that operates one shift 5 days a week with a high value to minimizing the time to turnaround equipment than in a 24 × 7 operation where CIP and SIP can be accomplished Biopharmaceutical manufacturing and flexible design: what does the future hold?