Raw Materials Production and Manufacturing Process Control Strategies

Abstract

Strategies for the quality control of complex mixture drugs are illustrated using plant-derived complex drug products and are comprised of unique challenges in the management of raw materials supply chains as well as the control of processing into drug product. This chapter is focused on quality control approaches from collection of medicinal plants to formulation of a botanical drug and includes cultivation, harvest, drying, processing, storage, extraction of biomass, and formulation of a botanical drug product. Naturally derived complex mixtures carry inherent biological source variabilities, but these can be exaggerated by seasonal or climatological or geographic changes as well as varying agricultural and collection practices. When the large-scale production to that satisfy national and global markets is considered, control strategies for raw material production must consider even such basic criteria as ensuring authentication of batches of plant materials as well as prime sources of variability within the range of sources. A raw materials control program must thus be tailored for each supply chain to ensure quality and consistency across the whole production platform. Many “downstream” issues can be eliminated or mitigated by rigorous control and consistency of raw material inputs, and their comprehensive documentation. The processing and manufacturing controls employed will generally be more focused—e.g., fewer processing/manufacturing sites as compared to sourcing inputs. However, process control strategies will be increasingly refined and technically complex, to include parameters of finished product and formulation consistency, safety and stability. These usually require orthogonal approaches that utilize a number of independent technologies.