Do you see solid-dosage manufacturing moving towards continuous processes?
In the academic and private sectors, work is being done to understand, from first principles, the tablet manufacturing process
and the methods needed to monitor and control the unit processes involved. Some companies have proven that real-time release
can be a reality. The companies that comprehend the need to develop continuous, controllable processes for pharmaceutical
manufacturing by using QbD and advanced control techniques will harvest the rewards that come from running capable processes
that can be operated by far fewer personnel and turned around faster than in the past. Costly deviations and lost batches
will become events of yesteryear, and the level of regulatory oversight for these companies will fall to a level that will
allow the inspectorate to spend its time overseeing the companies that continue to follow paths of greater risk.
I do think true continuous manufacturing—in which starting materials with predefined specifications are fed continuously and
product is continually produced and removed from the process—is possible and can be achieved. Issues to be resolved include
traceability in the event of a recall, contamination or adulteration of starting components, procedures for start-up and shut-down,
and ways to deal with the inherent variability of the starting components. An interesting point is that many of the excipients
used in the manufacture of pharmaceutical tablets and capsules are manufactured by true continuous manufacturing where the
equipment is operated continuously 24 hours per day and seven days a week. These issues have been resolved for these materials,
so why shouldn't they be resolvable for pharmaceutical tablets and capsules?
Large-volume products can benefit significantly from the efficiency and throughput improvements delivered by continuous processes.
However, at the current time, we are seeing a trend towards smaller volume products due, in part, to our focus on personalized
medicines. One key to effective manufacture of small-volume products is the development of flexible modular manufacturing
units that can be quickly assembled anywhere. These units will have some of the aspects of continuous processing (especially
where it improves robustness), but will be more flexible for multiple small volume products.
What may be the most significant advances of the next 5–10 years?
As the QbD mantra rises in volume, the use of PAT will increase in order to acquire more molecular and process information
earlier in the development process. PAT generates large volumes of data and can be implemented on most drug-product unit operations.
The institutions and individuals capable of managing this mountain of information and turning it into knowledge will gain
a competitive advantage by learning to bring molecules to the clinic faster and being prepared to manufacture the final drug
product at a lower cost. In five years, this will be a common practice for perhaps 10% of the pharmaceutical industry. In
10 years, there will be new measurement techniques that will come to bear on every one of the solid-dosage unit operations.
These measurements will provide new insight into powder formulation, powder handling, and powder compaction processes. This
new knowledge will offer the committed manufacturer the opportunity to design more processes based on first principles and
the confidence that they can reach the end in mind with a minimum of experimental work to validate their design.
In the next five years, current research in API particle engineering will result in better control of API properties, enabling
the use of simpler direct-compression processes for downstream drug-product processing. Within the next 10 years, the focus
will be on technologies that improve efficiency in R&D and production. The development of flexible, modular manufacturing
platforms for solid-dosage manufacturing will reduce the experimentation needed for technology transfer, getting drugs to
The trend towards local manufacturing on a market-by-market basis is likely to drive demand for highly standardized, modular
manufacturing units at medium-size scale and the flexibility to ensure manufacture of high quality product at any site with
only limited operator input. Advanced process control will also play a bigger role. We will no longer just measure online
intermediate and product attributes but will use feedback loops to optimize process parameters and product quality online.
Ten years from now, the proportion of solid dosage forms will have decreased, and parenteral dosage forms of biotech products
will play a bigger role.