Achieving continuous manufacturing for final dosage formation: challenges and how to meet them. May 20-21, 2014 Continuous Manufacturing Symposium.

We describe the key issues and possibilities for continuous final dosage formation, otherwise known as downstream processing or drug product manufacturing. A distinction is made between heterogeneous processing and homogeneous processing, the latter of which is expected to add more value to continuous manufacturing. We also give the key motivations for moving to continuous manufacturing, some of the exciting new technologies, and the barriers to implementation of continuous manufacturing. Continuous processing of heterogeneous blends is the natural first step in converting existing batch processes to continuous. In heterogeneous processing, there are discrete particles that can segregate, versus in homogeneous processing, components are blended and homogenized such that they do not segregate. Heterogeneous processing can incorporate technologies that are closer to existing technologies, where homogeneous processing necessitates the development and incorporation of new technologies. Homogeneous processing has the greatest potential for reaping the full rewards of continuous manufacturing, but it takes long-term vision and a more significant change in process development than heterogeneous processing. Heterogeneous processing has the detriment that, as the technologies are adopted rather than developed, there is a strong tendency to incorporate correction steps, what we call below "The Rube Goldberg Problem." Thus, although heterogeneous processing will likely play a major role in the near-term transformation of heterogeneous to continuous processing, it is expected that homogeneous processing is the next step that will follow. Specific action items for industry leaders are: Form precompetitive partnerships, including industry (pharmaceutical companies and equipment manufacturers), government, and universities. These precompetitive partnerships would develop case studies of continuous manufacturing and ideally perform joint-technology development, including development of small-scale equipment and processes. Develop ways to invest internally in continuous manufacturing. How best to do this will depend on the specifics of a given organization, in particular the current development projects. Upper managers will need to energize their process developers to incorporate continuous manufacturing in at least part of their processes to gain experience and demonstrate directly the benefits. Training of continuous manufacturing technologies, organizational approaches, and regulatory approaches is a key area that industrial leaders should pursue together.