Impact of Quality by Design (QbD)-Induced Changes in Manufacturing Control Methods on Prolonged Supply Interruptions of Non-conforming Pharmaceutical Products in Japan

Abstract

 Since 2020, non-compliance of good manufacturing practices (GMPs) and quality-related problems have induced Japan’s prolonged large-scale supply disruption of generic pharmaceuticals. This manuscript outlines the changes in the manufacturing control method and GMP regulation based on quality by design (QbD) concept in the last two decades. It also discusses the rapid increase in the use of generic products during the government-supported campaign, resulting in violations such as non-conformity in manufacturing methods and/or non-compliance with the quality standards recommended for monitoring the stability of specific products. Insufficient verification of commercial-level production in the product development process by some marketing authorization holders was cited as a significant cause of the intensive occurrence and prolongation of the problem. It is essential to design processes emphasizing the product life cycle and to build systems allowing for rational changes to ensure a stable and ethical supply of pharmaceuticals.