Streamline your system
PAT implementation projects don’t have to
be complicated. Leveraging supplier expertise
and documentation can significantly reduce engineering
efforts, help shorten project timelines
and reduce commercial risk. The cost benefits
can be significant, explains Alon Vaisman,
Applications Development Manager Pharmaceuticals
of Malvern Instruments.
Prompted by the FDA's Process Analytical
Technology (PAT)
initiative and subsequently by the advent of Quality
by
Design (QbD), pharmaceuticals companies have invested
substantially in projects to improve process control.
Today there are
few that do not have a PAT, QbD or other group,
and many have
partnered with academic institutions conducting
research in related
areas. However, when the question of cost savings
resulting from
PAT and QbD is raised, there is rarely a clear
answer.
Determining ROI
Return on investment (ROI), the usual business
driver for
improvement projects, can sometimes seem elusive
in the
pharmaceuticals industry. However, quality is
the key. The cost of a
single out-of-spec batch may dwarf the investment
in the PAT
system that would have saved it. When PAT is deployed
at a critical
point in the process and can influence the quality
of the product . at
a step where specifications are tight and risk
of failure is high
(narrow design space), for example . ROI can be
substantial.
| |
 |
| |
On-line
particle size analysers automatically control
API milling. |
Influencing the process while it is running is
relatively new in pharmaceuticals manufacturing,
requiring real-time, or near realtime, data and
a decision-making (open- or closed-loop control)
system that acts on the process. Such systems
maintain product specifications through minor
feed variability and generate an alarm when something
goes wrong so the process can be stopped.
These control systems are widespread in industries
where manufacturing is continuous. The pharmaceuticals
industry is moving towards continuous manufacturing,
but the transition may span decades and batch
manufacture remains the norm. Compared with continuous
processes, batch processes spend more time in
transient states, where product losses and variability
can be higher.
A PAT system offers dual benefits: tight control
of the steady state
portion of the process and swifter transition
times that reduce
product losses. An example is the installation
of an Insitec online
particle size analyser by Malvern Instruments
to monitor and control
active pharmaceutical ingredients (API) milling.
This closed-loop
system automatically controls the milling process
and eliminates
offline testing, which alone could save tens of
thousands of dollars
per milling campaign.
A similar online particle size analyser in a
consumer health
products plant is monitoring the final product
after jet-milling and
sieving steps, activating an alarm if particle
size is out of spec. Outof-
spec material is then diverted until the process
is back on track.
Before online particle size analysis, around US
$200,000 worth of
product was scrapped each year, but since its
installation, no
batches have been rejected on the basis of size.
Building advantage
In the examples cited, ROI is achieved because
the PAT system:
- is deployed in commercial manufacturing
- is monitoring a critical control parameter
- provides information in real time, allowing
timely action
- uses measurement principles the same as/easily
comparable
with the existing QC method.
Unlike many PAT tools that require complex statistical
modelling to apply the data, particle size analysis
by laser diffraction is well understood. Bringing
this technology to the factory floor therefore
carries a lower risk and gives direct payback
through labour reduction and real-time product
release.
Once a target application is identified, implementation
starts with
an engineering study to test the system in the
process, and
determine all application and integration requirements.
Here the
applications expertise of the supplier as well
as the ability of the
analytical unit to exchange information with other
system
components are important. Standard data exchange
protocols (such
as OPC) and flexible instrument control software
(such as Malvern
Link) allow Insitec analysers to operate as embedded
and
standalone units, with local operation or remote
control.
Taking the consultative approach described here
with its upfront
engineering streamlines later commissioning, process
qualification
and validation. This approach also supports project
justification and
minimises unknowns. As more companies follow this
route, it is
increasingly clear that the right technology used
in the right place
will pay for itself . and more!
|
