Continuous OSD manufacturing—A 2019 technology update

/// By David DiProspero

The system types being employed in today’s modern oral solid dose form manufacturing facilities

Introduction:
As noted in blogs I have written and numerous other articles and presentations on this topic, the continuous oral solid dose manufacturing ball is clearly rolling, and our industry is well-positioned for even further continuous manufacturing (CM) advancement, as many more new drug approvals are stamped in the years ahead. CM for oral solid dose form products is a transformational processing platform that is here today and is here to stay. Although the industry is working on harmonization and some level of standardization of the platforms, CM is not a one-size-fits all offering.

In this blog, I focus on the three primary system types and configurations that I have seen employed in today’s modern oral solid dose form manufacturing facilities and note a few of the key elements associated with these systems.

Fully integrated CM systems
A fully integrated CM system begins at bulk powder handling and ends at tablet coating. There is full integration and process control from “powders in” to final dose form coated “tablets out.” The system provides the following capabilities:

  • Upstream bulk powder material handling and feed of excipients and active pharmaceutical ingredients
  • Processing platforms that include direct compression, wet granulation or dry granulation
  • Conventional tablet compression with fully automated tablet testing
  • Post tablet compression/pre-coating tablet relaxation
  • Continuous coating
  • Final dose form collection and handling
Partially integrated and hybrid continuous CM systems
A partially integrated and hybrid CM system typically begins at powder feed and ends at tablet compression. There is a separation of the bulk powder handling and tablet coating operation, making use of more traditional batch operations for these unit operations. The system provides the following capabilities:

  • Feed of excipients and active pharmaceutical ingredients
  • Processing platforms that include direct compression, wet granulation or dry granulation
  • Conventional tablet compression with fully automated tablet testing
Advanced end-to-end (active pharmaceutical ingredient to final dose form) continuous CM systems
An even more exciting and innovative area evolving is advanced end-to-end CM systems that combine drug substance manufacturing with drug product manufacturing for a truly continuous operation. In this configuration, there is full integration and process control from chemical synthesis to final dose form coated tablets. The system provides the following capabilities:

  • Upstream bulk raw material storage and feed of chemical entities
  • Continuous integrated drug substance processing platforms that include dissolution, crystallization/filtration, drying and sizing
  • Continuous integrated drug product processing platforms that include direct compression, wet granulation or dry granulation
  • Conventional tablet compression with fully automated tablet testing
  • Post tablet compression/pre-coating tablet relaxation
  • Continuous coating
  • Final dose form collection and handling
In summary, oral solid dose CM is not a one-size-fits-all approach, and there are many options and configurations for the user to enter the arena. Fully integrated CM systems are among the most complex to implement; however, they also represent a growing number of installations around the world, allowing for the widest range of capabilities. Partially integrated and hybrid continuous CM systems offer a great launch pad and entry for the user to enter this arena. Direct compression systems are among the most popular and easiest to implement. Advanced end-to-end continuous CM systems are truly transformational and offer exciting potential but have the greatest complexity of all. 

About the author:
Dave DiProspero has 25+ years of pharmaceutical engineering experience in internationally regulated oral solid dose form manufacturing operations. He has worked as an owner's representative and as a direct employee for well-known equipment/technology suppliers and engineering firms. As an associate and director of pharmaceutical process technology for CRB, DiProspero is involved in front-end/back-end project consultation and planning, strategizing, design and engineering implementation/execution and is an experienced team communicator. He has a strong facility/process, design/engineering, containment, equipment, material handling and facility systems integration background. He is the current co-chair of the International Society for Pharmaceutical Engineering’s OSD Continuous Manufacturing Subcommittee, a frequent writer and speaker on various oral solid dose topics and an industry advocate for CM.

LinkedIn: https://www.linkedin.com/in/davediprospero/

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About the Author

David DiProspero, Director of Pharmaceutical Process Technology

David DiProspero, Director of Pharmaceutical Process Technology

David DiProspero is the director of pharmaceutical process technology at CRB in our Philadelphia, Pennsylvania office.
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