Leapfrog time?

By Rebecca Vangenechten and Ivo Backx

Pharmaceutical secondary manufacturing has long stood in stark contrast to the drug discovery end of the business, as well as to other sectors, when it comes to innovation such as continuous manufacturing. Is that about to change? Siemens' Rebecca Vangenechten and Ivo Backx argue that the coming decade could see secondary manufacturing not just catch up but leapfrog other sectors but that mindset will be a crucial factor.

Some of the reasons that explain the relatively slow pace of secondary manufacturing change also explain why the sector is likely to see a transformation. Few other industries would survive if they presided over utilisation rates around 30 or 40 percent and took as long as a month or even two months to manufacture a product that could be made in two days. Large inefficient batch manufacturing would have been consigned to the dustbin. In pharma, however, the profits that have come from the traditional blockbuster drug discovery model have masked manufacturing inefficiency and regulation has inhibited change.

Now, however, the traditional business model is breaking down with consequent pressures on all parts of the pharma value chain. Manufacturing's contribution to improving yield, reducing time, cost and waste is increasingly critical. Regulation which previously had insisted on batch testing is now moving to be much more supportive of real time product release and process analysis, heralding a future where the validation and establishment of continuous manufacturing will be easier.

A small number of companies are taking extremely innovative steps. At Siemens we are working with leading players to develop a continuous secondary manufacturing process. Such a move seeks to achieve significant business benefits. Even a one percent yield improvement translates into hundreds of millions of savings. Small, fully enclosed processes, with a high level of automation and reduced manual intervention, will enable companies to reduce variability, deliver high yields, increased profitability and lower operating, inventory and capital costs.

It is an attractive future but the barriers remain significant. However, achievability is not one of them. Continuous processing with real time release and full understanding and control of each step of the process is well established in other sectors, such as chemicals and food and beverages. What has been different in pharma is the regulatory context but, with this changing, the bigger barriers are inside companies and, in some respects, inside mindsets.

Integration of each process stage is crucial for continuous manufacturing. However, pharma companies tend to work with 'islands of automation' where every unit of operation is more or less an independent from an integration point of view. Changing to an integrated approach, which is standard in many other industries, is a big step for pharma companies. At Siemens, we have wide experience of continuous manufacturing, as well as an understanding of pharma's needs, and can partner companies to make it a reality. We find that companies are excited once they succeed with integration but find it difficult to be convinced beforehand simply because it is outside of their experience.

Another key barrier is that these changes require companies to work in a more multi-disciplinary way, crossing system worlds. For the first time, if you are in analytics you have to speak to people in process control and so on. Multi-disciplinary teams are an absolute must but not everyone is ready for that. The relatively slow uptake of process analytical technology (PAT), crucial for continuous manufacturing, following the FDA's 2004 PAT initiative, highlights the challenge facing companies.

Mindset changes and internal culture changes will be key to the successful introduction of PAT as a first step towards continuous manufacturing. The companies that are first to overcome the barriers will not just reap the reward of increased competitiveness. Because of the stage of its introduction, they have the opportunity to implement the technology to a higher level than in industries where it is already established. From being a laggard, secondary manufacturing has the potential to become a trendsetter.

Rebecca Vangenechten is a Life Sciences Industry Consultant with Siemens. She is responsible for business development life sciences US and focuses on innovative technologies, including Process Analytic Technology (PAT).

Ivo Backx is working at present as Senior Consultant for drug manufacturing at the Vertical Market Management Pharma department for Industrial Automation and Drives Technology at Siemens.