Roadmap Design For Implementing QbD In Generic Drug Engineering

Large pharmaceutical companies are running out of patent protection, and the presence generic market is boosting. The generics business is quite lucrative and many Chinese Pharmaceutial enterprises now intent to produce high-quality generics qualified international standards. Quality by design (QbD) is an approach of product development where a comprehensive understanding of the effect of various inputs (e.g. process parameters, materials) on the final product (active pharmaceutical ingredient or drug product); it leads to a process or product design that ensures reliable manufacture of a high-quality product. The aim of this research is to develop and characterize an implementing roadmap for establishing a generic drug manufacturing process under QbD principles.The research contents are divided into two parts. process development and road map design. The dissertation starts with critical quality attribute identification, followed by process parameter and input raw material risk assessment, design of experiment, and process parameter classification, and concludes with a design space. Finally, a rational QbD implementing roadmap is established and documented. In the presented case study, QbD approach was applied in order to optimize a routinely used method. A compliant QbD methodology based on a Design of Experiments (DoE) approach was evaluated within the framework of implementing roadmap. This approach allows the investigation of Critical Process Parameters (CPPs), which have an impact on Critical Quality Attributes(CQAs).Finally, a case study of generic drug applied QbD in Yangguang Company was carried out, highlighting the benefit of QbD strategy in developing generic drug. On this basis, the challenges and advantages of systematical using QbD methodology were discussed.