GEA Pharma Systems (GPS) formerly known as Niro Pharma
Systems, part of the GEA Group, has helped develop a complete process line for
one of Europe’s most successful pharmaceutical companies for the manufacture of
generic medicines.
The pellet processing project includes the supply and integration of;
granulation technology with a Collette UltimaGral™ and Aeromatic-Fielder NICA™
Pelletizing System, coating technology with GPS’s unique PRECISION COATER™ and
fluid bed drying.
Synthon BV, based at Nijmegen in the Netherlands manufactures a range of
products for worldwide distribution through its marketing partners in Europe,
the USA, Canada, Australia, New Zealand, Chile, Argentina and South Africa. The
development of the generic version of a drug will usually begin several years
before the expiration of the patent with the aim of introducing it to the
market within a few hours of the protected period ending. Synthon focuses on
the more complex pharmaceuticals as fewer of its competitors have the human and
technical resources to replicate them.
Initially small batches of the
drug are produced in the laboratory before up-scaling production to meet the
demands of the market. Up-scaling production from a laboratory batch size of
200g to a typical production batch size of 500kg while maintaining the exacting
standards of the formulation represents a major challenge to drug
manufacturers. The choice of equipment and the expertise available from its
manufacturers plays a key role in getting the product to market quickly and
maintaining the required standards in production.
After evaluating the
systems offered by the GPS group, Synthon approached the company in 2002
when new equipment was required for a partner manufacturing plant in Greece to
up-scale production of one of its products. The first requirement was for the
NICA™ extrusion/spheronization equipment to manufacture tiny pellets containing
the active ingredient followed by the PRECISION COATER™ with its unique airflow
characteristics, giving a very exact and even coating of product both
technologies supplied by Aeromatic-Fielder. Coating of the tiny pellets, which
can be less than 1 mm diameter, is necessary for several reasons, for example
to mask unpleasant tastes, improve appearance or, as in this case, to provide
controlled release of the drug in the body. The aim is to evenly coat the
pellets with just enough material to achieve the desired result and no more.
Additional NICA™ pelletizing equipment was subsequently supplied and
integrated with the system to manufacture the pellets themselves. Synthon chose
the NICA™ equipment, partly because of its exceptional performance and
flexibility, but the co-operation of GPS as a business partner played an
important role. “We looked carefully at what equipment was available
commercially to do the development work,” said Synthon’s director of technology
Derk Sanders. “After looking at all the possibilities we decided on
the GPS Nica system for our development and up-scaling activities. GPS
allowed us to rent the necessary equipment to produce batches under GMP
requirements. The whole exercise went very well and we subsequently upgraded
the systems to the largest available from GPS. We now have three NICA™
integrated extruders/Spheronizers producing a total of 2700kg a day”
Derk Sanders sited the simplicity of the GPS equipment as being a key
factor in the successful development of the process. “Production has now been
underway for just over a year with around 300 batches of the drug produced,” he
said. “So far not a single batch has been rejected due to failure of the
equipment.”
The GPS technology centre in Bubendorf Switzerland, which
opened in 2003, has been used extensively by Synthon to develop its production
processes. The technology centre provides pharmaceutical companies with a
one-stop GMP environment to enable them to develop new solid dose products
using the latest equipment. The centre is equipped with the full range of NPS
equipment from powder mixing, through granulation and drying to tablet pressing
and coating.
“The technology centre is a very important resource for
Synthon. One of the main benefits is that it enables us to test our processes
using small quantities of API (Active Pharmaceutical Ingredient),” continued
Derk Sanders. “We need to know that the equipment we select for production will
produce the formulation in large batch sizes and the facilities at the centre
allow us to do that. To d
o the same test here in the factory would require API test batches of 500kg
which would be a huge risk and prohibitively expensive. Our R&D department
is using the centre more and more to help develop processes for future
products.”
“We have a very good relationship with the technology centre
and they’ve been very flexible in accommodating us, often at short notice. We’
re a dynamic company and we have to move quickly to stay ahead, they have
always given us excellent service: it is a partnership.”
Mark Driessen,
GPS’s regional sales manager added, “Having the technology centre means that we
can work closely with customers to conduct tests and make sure the equipment is
suitable for an application before they place an order. This safeguards the
customer’s interests and allows us to prove the system we are recommending. It’
s a perfect tool for us.”
The vast practical experience of the machine
operators is a further advantage of using the test centre. During testing,
conditions are often taken to levels far beyond those experienced in normal
production. The data collected often shows that conventional processing
techniques can be modified with beneficial results.
Development
engineers from Aeromatic-Fielder’s factory in the UK make frequent visits the
test centre to see at first hand the machines working in a production
environment. This provides Synthon’s R&D engineers with the opportunity to
share information and give feedback to the equipment manufacturers. This
regular close contact provides Synthon with valuable information for use in
future projects.
GPS’s relationship with Synthon has grown during the
last 4 years and looks set to become even stronger in the future. “Our
experience of working with GPS has been very favourable,” said Derk Sanders.
“Business is always a two-way thing and both companies have worked together to
achieve excellent results. I am very comfortable with GPS and I look forward to
working with them in the future.”
One of the main obstacles for
pharmaceutical companies in the development of drugs is the cost of trials. The
use of the test centre in Bubendorf significantly reduces these risks giving
manufacturers confidence that critical manufacturing processes are viable
without major capital expenditure.