Source: American Pharmaceutical review, April 2021, ppg 51-59
This paper will discuss a new process design paradigm and equipment selection and design for the continuous manufacturing of pharmaceutical compounds. Mechanistic modeling and simulation tools are being used for equipment sizing, equipment characterization, process design, process integration via steady state modeling, and technoeconomic analysis. Defining system dynamics to correlate critical quality attributes of final product to critical process parameters is crucial for ensuring consistent product quality and process robustness. This work will provide a high-level overall view on applications of modeling and simulation tools for the process and equipment design considerations, and a workflow for a continuous process development from R&D laboratory to manufacturing.
Source: CEP, March 2021, ppg 28-35
This paper discusses the fundamental principles of continuous process design and process intensification for pharmaceutical specific applications. The advantages and challenges of continuous manufacturing compared to batch processing are explained. The discussions cover four sections of the bio/pharma industry for continuous manufacturing of: (1) Drug substance; (2) Drug product; (3) Biologics upstream; and (4) Biologics downstream. Case studies and examples are utilized to explore fundamental technical and business considerations, workflow, technoeconomical analysis, scale-up/down issues, and regulatory considerations:
- What is continuous manufacturing, with examples and case studies
- Challenges with system integrations
- Framework for process development, and optimization
- Role of modeling and simulation
- Control strategy development
- Physical and digital connectivity and advanced process control
Source: Chemistry Today, Nov/Dec 2020, Vol 38 (6), ppg 39-44
Mechanistic modeling and process simulation, based on first principle analysis, is a well- practiced tool in the chemical industry. A mechanistic model is a knowledge-based description of a system designed to help an observer understand how the system works and predict its behavior. Mechanistic models can be used for process design, process scale-up, technology transfer, knowledge management, and risk analysis for forward decision-making. Model-based scale-up and optimization is a powerful technique for achieving the desired product quality and for reducing the cost of experimentation and the time to market. This paper aims to provide a short summary of the fundamentals, applications, benefits, and limitations of the use of mechanistic modeling for process scale- up and technology transfer for the development and manufacturing of active pharmaceutical ingredients. Two case studies of reactor and crystallization process scale-up are provided.
Source: Chemistry Today, May/June 2020, Vol 38 (3), ppg 10-13
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 route, a new process design paradigm and equipment selection and design is required. Defining system dynamic to correlate critical quality attributes of final product to critical process parameters is crucial for ensuring consistent product quality and process robustness. This paper provides a high-level overall view on the advantages and challenges of continuous manufacturing and reviews the process and equipment design considerations.