more complex and increasingly expensive to produce.
PAT is a key component to continuous processing. By using
different analytical methodologies, such as raman spectroscopy,
infrared and lazer diffraction, key process parameters can be
measured non-invasively in real-time. Post compression hardness and tablet dimensions can be measured using auto sampling. This greatly enhances the amount of relevant data that
can be analyzed and with modern computational techniques,
allows for precise analysis of the robustness of the process validation. Theoretically with PAT demonstrating that a process in
running within the validated variable space, the final batch quality control testing can minimized to microbiological checks. This
must be acceptable to regulators before implementation.
The regulatory agencies, including the FDA and EMA, have
long been supportive of QbD and have outlined frameworks for
PAT implementation. The novelty of end-to-end continuous tablet manufacture has clearly been a concern to pharmaceutical
company regulatory departments. This is primarily because
it overlays an extra layer of uncertainty to any new product
application. The regulatory agencies have always been open
to discussion on new technologies, particularly when they embrace QbD and PAT. To this end, Aesica in collaboration with its
partners, has hosted pre-operation visits for FDA, MHRA and
EMA to discuss continuous processing.
Another key advantage of continuous processing lies in re-
duced floor space requirements as the same equipment can
be used for the development and commercial manufacturing
stages. To add to this the combined unit has an overall smaller
footprint. Aesica has been able to demonstrate that an existing
GMP area can be refurbished, a continuous line installed and
the first registration batches produced for clinical trial supply
in as little as 6 months.
Clearly there is significant investment required to install continuous tablet processing equipment. Once in place it has the
versatility to be used for a variety of products whilst lending
itself to 24/7 continuous production to lower production costs.
By its very nature it is highly flexible. If more product is required, the process is simply run for a longer period of time.
LOOKING TO THE FUTURE
Continuing processing is set to play a central role in modern pharmaceutical manufacturing. It is already established
in other industries and in single units of operation in pharmaceutical manufacture such as compression and coating. With
CDMOs like Aesica having equipment available for third party
use, and regulators becoming more familiar with the technology and positively encouraging it’s take-up, the perceived barriers to using the technology are disappearing.
To conclude, continuous processing has enormous scope
to improve the efficiency of pharmaceutical development and
manufacture. It reduces development times, goes hand-in-hand
with Quality By Design and PAT, uses up much less API in development and provides cost effective and robust production
and rapid process validation. ■