Patricia Hurter is the senior vice president of Global Pharmaceutical Development at Vertex Pharmaceuticals Inc. She has a Ph.D. in chemical engineering from the Massachusetts Institute of Technology and worked in the paper industry and at Merck prior to joining Vertex in 2004.
Most pharmaceutical manufacturing is conducted using batch manufacturing processes, in which all materials are charged before the start of the process and discharged at the end. Most other industries transitioned to continuous manufacturing (CM) around the time of the Industrial Revolution. CM, in which material is simultaneously charged and discharged from the process, is generally considered to be more efficient in consistently delivering a higher quality product and is the norm for most other industries. The first continuous paper machine was patented in 1799, and the oldest known continuous process is the blast furnace for producing pig iron, which was first operated in approximately the first century AD in China. And the Haber process, which converts nitrogen and hydrogen to ammonia at high temperature and high pressure, was run as a continuous process producing 20 tons per day by 1914.
There are many perceived obstacles to introducing a new manufacturing paradigm in the pharmaceutical industry. The two considered most challenging are presumed regulatory hurdles and existing batch process infrastructure. However, since the Food and Drug Administration’s Pharmaceutical cGMPs for the 21st Century initiative in 2002, regulatory authorities have encouraged the pharmaceutical industry to adopt new technology. The International Conference on Harmonisation (ICH) guidelines Q8/9/10 introduced the concepts of quality by design (QbD) and using science and risk-based approaches to assure product quality.
The second perceived hurdle is the cost associated with shifting from existing batch infrastructure to continuous equipment. In reality, the capital costs for new CM equipment can be offset by active pharmaceutical ingredient (API) savings during development, because smaller quantities of API are required for process development on continuous equipment. However, to realize the potential API savings, new products need to be developed using continuous processes at the outset. Once commercialized, the CM processes have the potential to realize quality, operational, environmental, and financial benefits. CM’s streamlined development will allow more rapid development and scale-up of new medicines, which can be particularly important for breakthrough therapies, ultimately benefiting patients.
An additional benefit of CM is the potential to bring manufacturing back to the United States. In recent years, there has been a tendency to send manufacturing offshore, which makes economic sense in the case of low-tech manufacturing which requires a low-skill, labor-intensive workforce. However, CM requires a smaller, highly trained, and highly skilled workforce, making it ideal for implementation in the United States. CM is environmentally friendly, so it is well suited to the United States and other regions where there is more emphasis on “green” manufacturing. In addition, having manufacturing located in close proximity to the innovation hub of the company can stimulate further innovation and ensure a more seamless transition from development to commercial manufacturing.
The article “Implementing Continuous Manufacturing to Streamline and Accelerate Drug Development,” featured in the August issue of the AAPS Newsmagazine and developed by the Manufacturing Science and Engineering section, explores how CM is ideally suited to QbD development and breakthrough therapies. Read the article and then participate in the discussion question below.
Discussion Point: What do you perceive as the largest barrier to implementing CM? How do we transition to a more flexible and responsive manufacturing paradigm that CM is certain to provide?