(505g) SEMI-Continuous Manufacturing Process for Generic Drug Products

Claims are made regarding the semi-continuous manufacture for a drug that has extremely limited demand and can only be economically produced using batch process. Generics has an opportunity to capitalize on economies of scale to create better and more robust continuous or batch processes. Since generic companies know the molecule while the drug is under patent, they have ample time to create a process that is efficient, superior and can be commercialized after patent expiration. Continuous manufacturing does not fit every hand. It has to be custom fitted. It is not a fashion that is economical and suits everyone’s needs. Principles of chemistry and chemical engineering can be applied for the manufacture of chemicals and their blends. A distinctive operations management and regulatory strategy is needed to stay competitive amidst the radical changes occurring in the small molecule drug product manufacturing industry.

Organizations must retain a large product portfolio to remain visible. They will also need to deliver products from their portfolio with a high supply chain velocity to meet customer expectations. This trend has become more prominent with the consolidation of wholesalers and pharmacy benefit managers in the U.S. market. Consequently, supply chain flexibility is a key element to success in the generic business. Manufacturing operations are expected to increase throughput while simultaneously minimizing operational disruptions resulting from deviations or failures. Scaling products with variable batch sizes is an option; however, this incurs substantial R&D costs and increased CAPEX spending due to additional infrastructure and time requirements. Capacity optimization across global operations is typically conducted by larger establishments. The best solution would be manufacturing operations that provide ample supply chain flexibility.

This paper/presentation discusses the fit for purpose semi-continuous manufacturing operations for generics. The proposal of converting existing batch processes to semi-continuous processes for solid dose manufacturing sites also involves application of integrated PAT, statistical process control (SPC), and predictive modeling software technologies. Implementing fully continuous manufacturing lines would result in engaging multiple fixed assets until the end of the manufacturing process, and hence may not be a desired option for manufacturers just yet. The semi-continuous strategy will improve production planning flexibility, enabling just-in-time manufacturing and injection of orders based on market demands, while avoiding backorder scenarios. Manufacturing of drug products only as required would allow for minimal overstock and prevent short expiry situations that would have otherwise resulted in further erosion of margins. The semi-continuous model enables manufacturers to maintain larger product portfolios with flexible supply chain prospects. The batch size flexibility, minimal footprint, and prospective decrease in development costs provides a distinct advantage. The improved ability for capacity optimization and enhanced production controls will ensure supply chain reliability, resulting in customer satisfaction.