Embracing sustainable pharmaceutical manufacturing using greener technology and processes that maximise production efficiency is one of the most critical ways the industry can innovate. New processes that reduce or eliminate hazardous products but increase profit margins are what manufacturers are looking for. In some cases this is being achieved through new catalytic or enzymatic reactions, or a move from batch to continuous production, more flexible plants, single-use equipment, and through greater automation.
Greener chemical processes are a starting point: developing new routes of chemical synthesis that eliminate waste, reduce process steps and cost. Companies such as Evocatal, for example, look for and develop novel enzymes that can work at higher temperatures, with higher activity and with greater resistance to organic solvents. Evocatal’s current focus is on chemical intermediates but others, such as Codexis, are focusing on the active ingredients.
Other companies focus on the mechanics of the production process through projects such as SYNFLOW.1 This large-scale EU research project, launched in 2010 at RWTH Aachen University, Germany, aims to enable the paradigm shift from batch-wise large volume processes comprising many separate unit operations to a more integrated but flexible catalytic continuous-flow process. The four-year EU-funded project, which involves 19 partners embracing industry (AstraZeneca, Bayer, Britest, CNRS, DECHEMA, Evonik Oxeno and Johnson Matthey) and 12 universities from the EU, combines molecular understanding of synthesis and catalysis with engineering science in process design and plant concepts.
One of the partners, Britest, has also worked with Foster Wheeler on the design and build of what is described as the world’s first multiproduct process intensified plant. According to Foster Wheeler’s Nigel Fletcher, the work started with a one-batch process with multiple syntheses, then added several more multiple-step batch processes, working through all of these with the client’s research chemists and development engineers to convert them all to continuous processes.
Process intensification is here to stay and it will develop in the future
Companies who have invested in this new technology have seen a radical change, with batch reactors disappearing and being replaced by small continuous reactors. ‘Process intensification is here to stay and it will develop in the future,’ says Fletcher. ‘Even clients who want to retain batch manufacturing can benefit by the selective addition of continuous processing and create hybrid processing by mixing batch with continuous processing,’ he says.
The main benefits of continuous processing include:
- Improved products, i.e. higher quality with significant reductions in impurity levels
- The ability to generate product or intermediates quickly, allowing the next stage of processing to proceed more quickly and leading to reduced work-in-progress
- Improved environmental performance, since continuous processing means fewer vessels are filled and emptied, so emissions are reduced
- Reduced utility demand, as continuous plant designs have small, compact utility generation systems providing steady low-level utility supplies
Overall, Foster Wheeler believes continuous processing can deliver a 10-fold reduction in utility demand, with lower carbon emissions and a more sustainable energy position.
Continuous processing can deliver a 10-fold reduction in utility demand, with lower carbon emissions and a more sustainable energy position
Not surprisingly, the continuous flow reactor market is seeing good growth. According to a new report, this market is expected to reach US$1.22bn by 2018, a CAGR of 9.4%.2 The micro-reactor systems market is the fastest growing with an estimated CAGR of 22.8% up to 2018. The continuous stirred tank reactors and plug flow reactor markets are growing, but at a slower pace due to ‘lower efficiency and manufacturing issues’.
The concept of continuous manufacture is being applied to all areas of the production process, and granulation technology is no exception. Manufacturers frequently use wet granulation as a precursor to tableting, and with the current trend moving from traditional batch manufacturing towards integrated continuous processing, Freeman Technology and GEA Pharma Systems are collaborating to advance the application of continuous wet granulation and drying technology.
Using data from Freeman’s FT4 Powder Rheometer and GEA Pharma Systems’ ConsiGma 1 continuous granulation unit, they are looking to quantify the influence of the operating conditions of the ConsiGma 1 on the bulk characteristics of the granules being manufactured. These data are then correlated to attributes of the tablets, providing the link between granule and tablet properties. The ConsiGma 1 is a lab-scale version of GEA Pharma Systems’ ConsiGma concept, which incorporates a patented continuous high shear granulator and small batch dryer, and has been developed specifically to meet continuous wet granulation needs.
More flexible production
Biopharmaceuticals manufacture has also seen rapid process innovation with the introduction of single-use products and more flexible manufacturing facilities. Equipment for this sector has had to develop to meet the rapid rise in product demand. Developments such as GE’s FlexFactory biomanufacturing platform and single-use technologies, for example, can help to reduce commissioning time and allow rapid reconfiguration of production facilities when required.
Jacobs Engineering Group, meanwhile, is collaborating with Pfizer on a modular process system to address the rapidly changing requirements of localised pharmaceutical manufacturing in emerging markets. The collaboration brings together Pfizer’s aseptic drug product process expertise and Jacobs’ capabilities in modular engineering, fabrication and testing to create a Rapid Deployment Module that integrates modular equipment, fully-automated control systems and single-use technology for bags, mixers, sterile connectors, manifolds and filters. The portable system is said to be scalable for different batch sizes, adaptable for various products and offers significant cost and schedule advantages compared with traditional manufacturing facilities.
The production systems are currently in their final stages of validation at a number of local pharmaceutical manufacturing sites around the world.
Process automation potential
There is still much to be achieved in terms of automation of pharmaceutical processes, and particularly packaging. However, the International Federation of Robotics3 claims a noticeable increase in their use. The main type of robots used in these sectors are said to be articulated arm robots (mostly 6-axes) for picking, packaging, handling and palletising. A large number of SCARA robots are used for picking and packaging.
A six-axis FANUC LR Mate 200iB handling syringes
Robot developer FANUC says that although not currently well used in the sector, there is a growing trend towards the use of delta robots, which offer a very high-speed picking solution for small parts. Merck, for example, has successfully employed a FANUC M-1iA delta robot on a bottling line, to place dispenser caps onto bottled allergy medications. The M-1iA is capable of operating at 120 cycles/sec and 10 variants of the bottle can be run on the system by selecting the appropriate programme.
Whereas in the past pharmaceutical processing has been slow to modernise due to regulatory concerns, today lower profit margins, new niche products and very different pharma business agendas are all driving through more rapid change.
References
1. http://www.synflow.eu
2. http://www.marketsandmarkets.com/Market-Reports/flow-chemistry-market-1316.html
3. IFR – International Federation of Robotics – World Robotics Industrial Robots 2011 Report
Featured companies
- Companies:
- Johnson Matthey
- Evonik
- Jacobs Engineering
- Codexis
- Pfizer
- AstraZeneca
- Foster Wheeler AG
- DECHEMA
- Bayer
- FANUC Robotics Europe
- evocatal GmbH
- Britest
- MarketsandMarkets
- Freeman Technology