Wishing to maximise the solid dosage production of a highly potent hormonal product, a leading drug manufacturer tasked GEA with significantly increasing output, providing a safer and more efficient factory environment, and introducing new systems that would replace the existing isolator-based process.
Manufacturing tablets using isolators is a laborious process, requiring production staff to wear protective air suits and gloves and operate through thick windows. The challenge for the GEA technicians was to use their product flow and containment expertise to remove as much isolator-based processing as possible, and to increase the batch size — making the production flow more efficient, whilst maintaining the high levels of containment and operator safety required.
Another key factor was maintaining blend homogeneity: with very low levels of API in the final yield, product consistency was essential. The effectiveness of the mixing process would be vitally important.
Blending and Tableting Trials
Blending and tablet press trials done with actual product proved to be crucial. GEA first demonstrated a patented high containment system, the MODUL™ S rotary tablet press with a wash-off-line (WOL) Exchangeable Compression Module (ECM). Because all the product-contact components are contained in the sealed ECM that can be removed, exchanged and washed offline, production can be resumed within 30 minutes of changeover.
The MODUL™ S was combined with a Pharma Flex deduster (Pharma Technology Inc.), a metal detector and a tablet weight, hardness and thickness tester (Kraemer Elektronik). The powder in-feed system used Human Machine Interface (HMI)-controlled BUCK® split butterfly valves. GEA also demonstrated the use of multi-tip tooling: using two tips per punch (station) doubled the tablet press output. The MODUL™ offers unique features for this type of tooling and incorporates an air compensator that, unlike other tool protection systems, eliminates the risk of punch damage.
The dwell time during pre-compression testing was extended to 200% compared with a conventional press to allow optimal product deaeration prior to compression. A specially designed feeder and dedicated software ensure optimal output. GEA then demonstrated their ability to successfully blend the low levels of API with poor-flowing excipients — a crucial requirement for a direct compression product. This was achieved using the Buck Systems™ blending Prism™ technology, a very effective aid to the bin-blending process.
Scope of Supply
GEA engineers worked closely with the customers’ project team to design the most effective system and agree on the total scope of supply. The project included laboratory blending containers, blenders, various size IBCs, and proven GEA technology such as the Vibroflow™ discharge technology, that combine to help poorly flowing materials blend together, and to discharge without segregation — an important feature when the API:excipient ratio is low. Dust-free product transfers are achieved using high containment MC BUCK® valves. The finished powder is transferred to an IBC and into the MODUL™ S rotary tablet press for direct compression. Only the initial weighing of the API prior to transfer into the blending process remains isolator-based.
The new system was fast tracked; the preliminary details were agreed within 4 months and the equipment was delivered less one year after contract signing. Removing much of the isolator-based processing, and expanding into the new factory space will enable a significant increase in both batch size and yield. At the same time, the overall working environment will improve immeasurably.