The rising popularity of a future-focused approach to tableting
Over the past several years major pharmaceutical producers have started adopting continuous manufacturing methods for oral solid dosage forms, both for development as well as commercial production. With the approval of a number of drugs produced continuously as well as the ICH Q13 and “Quality Considerations for Continuous Manufacturing Guidance for Industry” of the FDA being close to release, the industry is gaining further confidence in implementing the technology. However, continuous manufacturing has not seen the breakthrough as the paradigm shift predicted by many yet. Batch manufacturing is still a default platform for many new drug products, but a change of mindset has started to turn this around.
Most early equipment (built in the past 15 years) used for continuous manufacturing of oral solid dosage forms was designed for medium product volumes (e.g. matching a tableting capacity of 25-50kg/h) and low potency drugs. This fact made it difficult for many pharmaceutical companies to justify a business case around switching from batch to continuous. The benefits of going for continuous manufacturing simply didn’t outweigh the higher investment costs in more complex equipment, higher API consumption during early development and the formation of new production teams familiar with highly complex equipment. And put simply, the relatively high production volumes did not fit with the pipeline of most new drug products.
Gericke has been one of the leading companies in developing and commercialising continuous feeding and blending equipment to produce oral solid dosage forms. It presented the first formulation skid at Achema 2012 and has since successfully supplied the continuous manufacturing. The company has also additionally realised the demand for equipment specifically for the other ends of the spectrum: low-volume, high potent and high-volume drug products.
For low volume, high potent drugs, a semi continuous feeding and blending unit (the Gericke Formulation Skid Batch GFS-B) was developed. The main benefits are around reduced API consumption during development, no startup and shutdown losses, less complex control strategy as well as suitability for very low dosages (below 1% drug load) and high containment (OEB4/5). This enables the use of continuous manufacturing for batch sizes below 1kg.
For high-volume products a new variant of the Gericke Formulation Skid Conti GFS-C can be used. This is a traditional continuous feeding and blending approach suitable for high throughputs up to 500 kg/h and even the supply of multiple tableting or capsule filling lines with a single blending unit. This allows business cases to be built around operational costs as an additional benefit of continuous manufacturing. This solution is very attractive for generics manufacturers or over-the-counter products.
Gravimetric Feeding And Blending Solutions
With around 50 continuous blenders installed for pharmaceutical applications, Gericke is a key player in providing flexible and modular feeding and blending solutions for the continuous production of oral solid dosage forms. Systems role in 2021 ranged from gravimetric feeders and blender integrated into isolators, semi continuous blending for direct compression, modular units with eight gravimetric feeders as well as high volume lines supplying multiple double sided rotary tablet presses. With installations all over the world, it goes to show that continuous manufacturing is not only a trend and will soon become the paradigm shift everyone is hoping for.