Continuous Processing in Secondary Production

Continuous Flow Synthesis. A Pharma Perspective

“…In the pharmaceutical industry multipurpose plants are common because they limit capital investment costs, whereas in the bulk chemical industry dedicated continuous plants are generally the solution of choice . The continuous processing strategy allows a just in time (JIT) production approach and has a reduced footprint. , A JIT approach produces less waste and reduces costs because, among others, the product accumulation and storage requirements are significantly less. A dedicated continuous plant, commonly used in other industries, is only feasible when large amounts of API are required (∼100 T/year), because of the logistics to put it in place.…”

Advances in Instrumental Technology, Industry Guidance and Data Management Systems Enabling the Widespread Use of near Infrared Spectroscopy in the Pharmaceutical/Biopharmaceutical Sector

“…37 CM is a culmination of all of the unit operations, working in tandem, converting raw-material input into final product in one continuous operation. 9 A number of academic research groups, including the GEA-NUS Pharmaceutical Research Laboratory, Singapore, headed by Professor Paul Heng, the CSOPS group at Rutgers University, headed by Professor Fernando Muzzio, and the Novartis MIT Center for Continuous Manufacturing, to name a few, are all leading the way in the application of PAT tools for monitoring and controlling CM processes. Figure 5 provides a schematic view of a typical CM operation for solid dose manufacturing.…”

“…Since all unit operations are connected to each other in CM, the reliance on PAT tools to predict product quality is essential. NIR spectroscopy in particular finds use in the following: 9 n Raw material dispensing: Continuous monitoring of the raw-material components can provide information to downstream unit operations on how to process the materials based on their characteristics. It also provides a continuous verification mechanism (i.e.…”

“…As opposed to batch production, CM processes combine all unit operations in an end-to-end configuration from raw-material dispensing through to coating and packaging. 9 As such, in order to pass process intermediates from one unit operation to another, a high level of process monitoring and control must be put in place to ensure that the quality of the product is maintained throughout the entire process. The role of NIR spectroscopy in CM operations will be discussed in the section "Role of NIR spectroscopy in CM".…”

The Current State of near Infrared Spectroscopy Application in the Pharmaceutical Industry

“…While NIR spectroscopy may find niche applications in clinical trial studies, its focus is more on developing process monitoring and control strategies that allow the process to adapt to any changes to the materials induced by the process or the natural variability of the raw materials. This has culminated in approaches such as continuous manufacturing, 10 which has a great reliance on PAT tools such as NIR spectroscopy to make quality decisions in real time in order to pass material seamlessly from one unit operation to the next. A continuous manufacturing process is by definition a QbD process, in which PAT tools such as NIR spectroscopy play prominent roles.…”