In today’s increasingly competitive pharmaceuticals market there is intense demand to both accelerate and streamline drug development. Continuous manufactur- ing technology is at the forefront of meeting this challenge by improving efficiency, speed, quality and reliability
in processing. Commercial pressures are leading the drive
towards continuous processing to shorten development
times, improve efficiency of the development process and
to reduce the amount of API used. Moreover, the drive also
comes from regulators that demand the creation of reliable
processes, supported by concepts that include Quality by
Design (QbD) and Process Analytical Technology (PAT).
Classic batch manufacture incorporating blending, granulation, drying, compression and coating has faced no major innovation during the last 50 years. Continuous tablet manufacturing brings innovation through its connectivity of precisely the
same processes as the batch process. It offers the opportunity
to catch-up with the food processing industry which has essentially been focused on continuous technology for many years.
To date outside of the traditional continuous nature of
compressing tablets, the main focus of continuous manufacturing has been in the field of coating where novel
continuous coaters are seen as a cost effective solution for
manufacturing high volume over the counter products. This
is especially the case in the United States.
In more recent times, equipment suppliers such as GEA have
been developing solutions to link all processes from the blending of excipients and API at the commencement to the output
of coated tablets at the finish. The technology is now available
to link a range of processes prior to table compression. The
feed material to the compression machine can be granulated
by dry or wet compaction processes and can be subject to additional blending or milling before or after the granulation step.
This allows for a reduction in the time from initial blending to
the creation of uncoated tablets to just 20 to 30 minutes.
While many pharmaceutical companies have been researching end-to-end processes in house, Aesica has announced the
introduction of the technology into its manufacturing facilities,
with the commercial manufacture of the first pharmaceutical
product, developed and manufactured by the technology in collaboration with a partner, expected in the next two years.
A key advantage of continuous processing is that it enables
process development and clinical scale manufacture as well
as full scale manufacture to be carried out on the same piece
of equipment using the same parameters and within the same
variable space. This means that the development process is
never lengthened by delays in supply of product and there
can be a very rapid collection of data to demonstrate the robustness and quality of the manufacturing process to support
regulatory packages. For fast tracked products, this results in
a decreased time to launch and a shorter time scale for the
product reaching full patient access on the market.
Continuous processing lends itself to developing processes
using so called QbD. This ensures that process parameters are
fully understood across what is typically a complex variable
space, reducing risk and providing a robust and reliable scientific approach to process validation. In a continuous process,
changes in a product can be set-up, run and monitored at regular and short intervals using small volumes of potentially highly
valuable materials, covering multiple variable combinations in
a relatively short period of time. By contrast, using a batch
based manufacturing system, the volumes required limit the
number of combinations that can be explored and hence the
statistical robustness of the validation.
Consequently, the amount of API required is kept to a minimum. From a development perspective, significant expenditure
is saved as less API is used. This is critical as APIs become
Schematic illustrates how a continuous tableting system can be set up in a manufacturing facility
■ By Jeremy Drummond PhD., Sales Director – Finished Dose, Aesica
An innovation that is set to transform modern day processing of
■ 20 JULY/AUGUST 2014 | PHARMACEUTICAL PROCESSING
■ PHARMPRO. COM