Reducing the risk of drug development and production for Synthon BV
GEA Pharma Systems 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 GEA’s unique PRECISION COATER™ and Fluid Bed Drying.
Based at Nijmegen in the Netherlands, Synthon manufactures a range of products for worldwide distribution. 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.
Development of the generic version of a drug
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 200 g to a typical production batch size of 500 kg 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.
Investment in GEA equipment to manufacture and coat tiny pellets
After evaluating the systems offered by GEA, 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 the product. 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.
Why Synthon chose the Nica™ System
Additional NICA™ pelletizing equipment was subsequently supplied and integrated with the system to manufacture the pellets themselves. Synthon chose the NICA™ equipment because of its exceptional performance and flexibility, but also the co-operation of GEA 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 NICA™ system for our development and up-scaling activities. GEA 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 GEA. We now have three NICA™ integrated extruders/spheronizers producing a total of 2700 kg a day”
Derk Sanders sited the simplicity of the GEA 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.”
One of the main obstacles for pharmaceutical companies in the development of drugs is the cost of trials. The use of GEA’s test centre in Bubendorf significantly reduces these risks giving manufacturers confidence that critical manufacturing processes are viable without major capital expenditure.
The NICA™ Pelletizing System
The unique modular concept of the NICA™ Pelletizing System facilitates optimized solutions to meet process needs exactly. Mixer/granulator, extruder and spheronizer modules are combined to create a complete integrated pellet production plant or selected individually to suit specific requirements. Modules can be operated in either batch or continuous mode for maximum flexibility of operation and can be used stand-alone or integrated with other up- or down-stream equipment such as fluid bed processing systems. Ideal for both product development and full-scale production applications, process scale-up of the NICA™ Pelletizing System is easy – it’s simply a factor of processing time.
