Continuous manufacturing versus batch manufacturing: benefits, opportunities and challenges for manufacturers and regulators

Abstract

Continuous manufacturing (CM) is the integration of a series of unit operations, processing materials continually to produce the final pharmaceutical product. In recent years, CM of pharmaceuticals has transformed from buzzword to reality, with at least eight currently approved drugs produced by CM. Propelled by various driving forces, manufacturers and regulators have recognized the benefits of CM and are awaiting the completion of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q13, a harmonized guideline on CM that would be implemented by ICH members. Although significant progress is evident, the uptake of CM is still sluggish in the pharmaceutical industry due to many existing challenges that have hindered manufacturers from adopting this technology. The top two barriers that manufacturers currently face are regulatory uncertainties and high initial cost. These issues are crucial in unleashing the untapped potential of CM, which has significant implications on patients’ access to life-saving medicines, while mutually benefitting manufacturers and regulators. Despite numerous studies, there have been few existing publications that review current regulatory guidelines, highlight the latest challenges extensively and propose recommendations that are applicable for all pharmaceuticals and biopharmaceuticals. Therefore, this critical review aims to present the recent progress and existing challenges to provide greater clarity for manufacturers on CM. This review also proposes vital recommendations and future perspectives. These include regulatory harmonization, managing financial risks, hybrid processes, capacity building, a culture of quality and Pharma 4.0. While regulators and the industry work towards creating a harmonized guideline on CM, manufacturers should focus on overcoming existing cost, technical and cultural challenges to facilitate the implementation of CM.