The GPCG 2 Isolator
Research and development with highly active substances

by Klaus Gröschel

The application of highly active substances in the pharmaceutical industry is gaining in importance. Thus, technical specifications must fulfil high demands.
Throughout the world, strict legal requirements stipulate that employers must safeguard the health of employees but it is practically impossible to guarantee absolute safety when active pharmaceutical ingredients are used. A certain extend of exposure is inevitable and must be knowingly accepted.
Limit values at the workplace are either regulated by national authorities or, if not existing, by the company itself under awareness of the product’s toxicity, such defining a maximum daily exposure level.
Common limit value regulations are the OEL (Occupational Exposure Limit) and the DEL (Design Exposure Limit). The OEL defines an average during a period of 8 hours. The DEL narrows the average down to shorter individual steps.
In pharmaceutical process engineering these limit values have a serious effect on the techniques. This primarily affects the product handling, i.e. the charging and discharging of a machine.
As a matter of principle, fluid bed machines have the advantage of working at negative pressures such actively avoiding that any dust is emitted during operation. During charging and discharging, however, the machine and consequently the product are handled openly. In case of working with highly active substances inherent protection must be considered – including all restrictions which are necessary.
Over the years, unique seal and valve systems have been developed for production scale machines which enable a low contamination operation. The designs of all critical components are always product-specific. This is a small problem for production scale equipment because the machines are normally only used for one or a few known products.
Unlike the production scale, the machine technology must provide flexibility with maximum safety in the field of research and development where new and unknown materials are developed.

The GPCG 2 Isolator is based on the familiar laboratory scale device GPCG 2 Labsystem. It is therefore ensured that all basic factors and process parameters are comparable and scalable with standard processes.
To ensure maximum flexibility for active substances Glatt has decided to offer an isolator concept, thereby allowing an OEL level of up to 1 µg/m3.
Essential for the quality of an isolator is the continuity of the safety concept, in particular the actual isolator technology as well as the fluid bed machinery. The product can be charged via RTP-ports (Rapid Transfer Port) or – if required – air locks. As an alternative, a tubing system can also be used. When using RTP-ports or tubing systems for product discharge, cleaning of the locks is not required.
Handling is of great importance to the operator. All components must be well accessible and visually perusable. For these purposes a Mock-Up was built by Glatt to locate the optimal positions of all operation and display systems.
The simple charging and discharging of the product bowl is practically identical to the GPCG 2 LabSystem. The product bowl can be moved sideways and tilted by 180° to discharge material from the bowl.
The fluid bed process itself does not differ from the standard. Whether in developer’s mode or fully automatic sequence of operation; the modern touch-screen control provides optimal ergonomic comfort for the operator as well as quickest possible access to all adjustable parameters – essential for developers. The controls for the isolator and the fluid bed unit are integrated into one operation terminal.
A good isolator concept must prove its value when changing the product. All contaminated parts must either be easy to clean or able to be sealed for contamination-free discharge. The machine tower is cleaned automatically from the HEPA inlet air filter to HEPA exhaust air filter by a built-in WIP System. Cleaning nozzles are situated inside the isolator box. The exterior of the machine tower as well as the complete isolator can therefore be cleaned comfortably.
It is needless to say that essential details such as smoothed and easy-to clean corners, polished and slightly sloped surfaces were emphasized. Even the peristaltic pump heads were modified according to the definition of the project: the drive unit is sealed off outside of the isolator and the pump head can be removed for cleaning by means of a bayonet coupling.
A particular highlight is the push/push-filter technology which is used in the inlet and exhaust air of the isolator as well as in the exhaust air side of the machine tower. When changing a filter, a ”clean” filter is inserted, thus pushing the contaminated filter into the interior of the isolator. From there the filter can safely be bagged, sealed and discharged via a tubing system (endless tube). The unique filter change principle and the gasket of the filter itself guarantee that there is no danger of contamination to environment while changing filters.
Of course, the machine can also be used for non-toxic substances with opened isolator hatches. There are no differences in comparison to conventional laboratory systems when operating in this mode.
Glatt offers the GPCG 2 Isolator in dust- or solvent-explosion-proof design. All laboratory scale process inserts of the conventional GPCG 2 LabSystem for drying, granulation and particle coating are available. Even the Plug&Play-concept was implemented consistently. All parts have been integrated into the shapely design of the housing.

		Klaus Gröschel passed his engineering exams in 1980 and is working for the company Glatt since, originally on various engineering tasks and for a few years as manager of the Binzen sales office.