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Pharmaceutical Technology APIs, EXCIPIENTS, AND MANUFACTURING eBOOK 2021 41 process parameters, such as time and temperature, are also important to consider. Above all, it is important to design development processes with the commercial stage in mind. Scale-up often entails moving to multiple items of equipment and the involvement of multiple people, which means a process that was originally designed at small scale using single items of equip- ment and a restricted group of people has to be replicated multiple times. Developing robust processes, including robust analytical test methods, with minimized varia- tion of critical parameters, is key from the very beginning of the project to streamline scale-up. The ability to automate or at least semi-automate pro- cesses needs to be considered during the product development process. In addition, it is critical to ensure a robust manufacturing strategy is in place prior to in- dustrialization. An understanding of the factors that inf luence the finished product batch size and manufacturing throughput is fundamental in de- termining both capacity and unit price. Where commercial-scale equipment already ex- ists, which is more often the case for pMDIs, prod- uct development should consider the process that is already installed and, where possible, design the new product accordingly. This forethought will save considerable development time and capital outlay associated with modifying existing equip- ment or procuring new. Munro (Vectura): One important consideration is working in development with equipment and ma- terials that are felt to be representative of what will be used at the clinical or commercial scale. A good example in the DPI space might be to use the same filling principle to fill the powder into the capsule or blister as is going to be used in the clinic and the commercial product. The methodology used to fill powder products can have a huge inf luence on how well the powder aerosolizes when the device is used, so there can be a clear connection between the filling technology used and the performance of the product; every effort should be made to keep the performance of products consistent throughout the development process. Often, what makes the most sense is getting to a commercially relevant manufacturing scale as soon as possible or picking processes that are more readily scalable. The early adoption of lean manufacturing tech- niques ensures optimal utilization of resource and equipment. Bottlenecks and constraints are iden- tified early, enabling efficient capacity planning. Repurposing existing equipment and challenging existing set-up, clean-down, and turn-around pro- cesses aid in efficient utilization. It is important that new equipment should be sourced that is di- rectly scalable from that used during early-phase development to prevent unnecessary duplication in setting critical quality attributes and critical process parameters. Involving late-phase manu- facturing teams early in the development phases to 'debug' any potential challenges early in the product lifecycle really helps streamline scale-up. "Developing robust processes, including robust analytical test methods, is key from the very beginning of the project to streamline scale-up." —Robin Heath and Peter Hirst, Recipharm