Continuous oral solid dosage manufacturing 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, continuous manufacturing is not a one-size-fits all offering.
As noted in blogs I have written and numerous other articles and presentations on this topic, the continuous oral solid dosage 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.
Here are three primary system types and configurations that I have seen employed in today’s modern oral solid dose form manufacturing facilities and 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
Continuous oral solid dosage manufacturing 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.