Leane, Michael, Pitt, Kendal, Reynolds, Gavin, Andersen, Sune, Bartsch, Jens, Carlin, Brian, Crean, Abina, Gamble, John, Gururajan, Bindhu, Khimyak, Yaroslav, Kleinebudde, Peter, Koynov, Sara, Kuentz, Martin, Misic, Zdravka, Moreton, Chris, Peter, Stefanie, Sheehan, Stephen, Stone, Elaine, Suzuki, Hirofumi, Tantuccio, Anthony and Van Snick, Bernd (2024) Ten Years of the Manufacturing Classification System: A review of literature applications and an extension of the framework to continuous manufacture. Pharmaceutical Development and Technology. pp. 1-45. ISSN 1083-74501097-9867

Abstract

The MCS initiative was first introduced in 2013. Since then, two MCS papers have been published: the first proposing a structured approach to consider the impact of drug substance physical properties on manufacturability and the second outlining real world examples of MCS principles. By 2023, both publications had been extensively cited by over 240 publications. This article firstly reviews this citing work and consider how the MCS concepts have been received and are being applied. Secondly, we will extend the MCS framework to continuous manufacture.The review structure follows the flow of drug product development focussing first on optimisation of API properties. The exploitation of links between API particle properties and manufacturability using large datasets seems particularly promising. Subsequently, applications of the MCS for formulation design include a detailed look at the impact of percolation threshold, the role of excipients and how other classification systems can be of assistance. The final review section focusses on manufacturing process development, covering the impact of strain rate sensitivity and modelling applications.The second part of the paper focuses on continuous processing proposing a parallel MCS framework alongside the existing batch manufacturing guidance. Specifically, we propose that continuous direct compression can accommodate a wider range of API properties compared to its batch equivalent.

Item Type:	Article
Date Deposited:	30 Apr 2024 00:46
Last Modified:	30 Apr 2024 00:46
URI:	https://oak.novartis.com/id/eprint/52466