Continuous manufacturing of drug substance and small molecules: process and equipment view
The continuous manufacturing of pharmaceutical compounds and fine chemicals is in high interest for the industry due to significant technical, quality, and economical advantages. This manufacturing method has its own challenges. Beside the more efficient, safer, and greener synthesis rout, a new process design paradigm and equipment selection and design is required. Defining system dynamic to correlate critical quality attribute of final product to critical process parameters is crucial for ensuring consistence product quality and process robustness. This work will provide a high-level overall view on the advantages and challenges of continuous manufacturing and review the process and equipment design considerations.
The continuous manufacturing (CM) of pharmaceutical compounds and fine chemicals is well practiced in the industry. However, the maturity of the technology and implementation of the technology is not uniform across the board. Some developed techniques and industrial applications go back to early 1900s, extensively in petrochemical and fertilizer industry. The Pharmaceutical industry has started adopting the technology in the recent decades, at different scales and applications. The overall concept of “Continuous Pharmaceutical Manufacturing” has been treated unfairly by industry and regulators, since the investors, regulators, and managers have used a single measure for the entire pharma industry. The bio/pharma manufacturing processes can be categorized into four sections, Small Molecule Drug Substance (DS) or active pharmaceutical ingredients (APIs), Small Molecule Drug Product (DP), Upstream Bioprocessing, and Downstream Bioprocessing. Hence, each section has its own nature, work-flow, challenges, sensitivity (technical, quality, regulatory, and financial), and potentiality for CM. Most of the regulatory scrutiny is on the DP for safety, conten ...