Several good manufacturing practice (GMP) compliance issues and their associated quality problems that have been revealed since 2020 have led to large-scale recalls and supply suspensions of drug products in Japan. This paper provides an overview of the causes and countermeasures for supply disruptions of low-molecular-weight chemical pharmaceutical agents, focusing on quality-related issues. A recent increase in the use of generic drugs emphasized the importance of strengthening active pharmaceutical ingredient (API) supply chains and ensuring GMP compliance among drug manufacturers. In addition, increasing recalls in the drug products of certain marketing authorization holders due to storage stability problems strongly suggests the need to improve their development process considerably. Other measures to stabilize the supply of pharmaceuticals, including increasing stockpiles of APIs, were also discussed.
Keywords: active pharmaceutical substance; drug shortage; formulation development; good manufacturing practice (GMP) compliance; process control; quality.