ISPE-DACH Conference Tomorrow's Drug Manufacturing: How the Pharmaceutical Industry Fights Cost Pressures
What formula is the pharmaceutical industry developing in the face of constantly increasing costs? How are companies coping with the growing regulatory pressure? What will production be like in tomorrow's world? There were serious topics on the agenda at the 20th anniversary of ISPE-DACH in Hamburg/Germany.
The world of the pharmaceutical industry has revolved faster in the last 20 years than the original protagonists were probably expecting when they became the founding members of ISPE-Dach (Germany, Austria, Switzerland Affiliate) in 1993. It is indeed so long ago that a few pharmaceutical engineers joined forces and set up a regional German-speaking branch of the ISPE. The aim then, as it is today, was to facilitate the sharing of experience and expertise among professionals working in the production of pharmaceuticals.
The little group has since grown to an organization with over 1000 members and has just celebrated its 20th anniversary in Hamburg—with speeches and a fitting program to mark the work of two decades.
It is not only the number of members that has increased, though: the demands on pharmaceutical production have also risen. The overarching theme, "Regulatory pressures and cost pressures in the pharmaceutical industry: Winds of change in production processes", was chosen for a reason and reflects a changing world with a bitter pill to swallow for the pharmaceutical sector which is more used to the sweet taste of success.
The substantial changes in the demands on the sector were underlined by Marcel Staudt of Novartis, the new chairman of ISPE-DACH, in his welcome address and backed up by way of three examples.
- Example 1—The patent gap: Patents which currently account for sales worth around 250 billion US dollars are due to expire between 2010 and 2015. For the companies concerned, said Staud, this will mean an abrupt drop in total sales of 75% and in sales of the original medicinal products of 90%.
- Example 2—Warning letters: The FDA has also tightened up procedures, and the number of warning letters has rocketed since 2009. The inspectors have become more critical in their assessments and are not shying away from taking drastic measures. Factories are also being closed if there are difficulties with the supply situation.
- Example 3—Patents and emerging markets: The pharmaceutical industry is seeing above-average growth in the emerging markets and patent protection is being undermined to some extent, as was the case recently in India. There is also increasing pressure from generic drugs and counterfeit products. An observation added by Ulf Schrader of McKinsey & Company was that 30% of all medicinal products in circulation in Africa are fake.
- Eight different trends were identified, with the speakers exploring the changes ahead for production in the next few years and the position to adopt in future.
Recognising these changes, all participants agreed that the pharmaceutical industry has to adopt to raise productivity and cost efficiency 0 But how? Discover some ideas of market insiders on the ext page!
Identifying Trends: What Will be Normal in Future?
McKinsey partner and management consultant Ulf Schrader had his own view of the controversial issues, which were bound to be hotly debated. Indeed, some of the listeners questioned whether a sector which makes products for health and is therefore subject to strict regulatory oversight should be faced with the same productivity standards as, for example, the automotive industry. Schrader was keen to introduce his audience to the "new normality" in his keynote speech. He particularly bemoaned the low productivity in comparison with other branches of industry, saying that the pharmaceutical sector was producing at a three-sigma level while production in the automotive industry was twice as high, and that the stability of the processes was well below the maximum.
Information from more than 30 pharmaceutical companies is fed into the Pobos database and the resulting anonymous productivity comparison is fascinating, showing a broad spread. There is a group of companies which are well out in front in terms of productivity, he continued, but none which attain the role-model proportions of Toyota in the automotive industry.
Pharma–Companies Aiming for Operational Excellence
Operational excellence is undoubtedly an important trend in the production of pharmaceuticals. This may not be a new topic but there is obviously still a need for action in this area, as highlighted by Jörg Wassenhoven, Director of Operational Excellence at Takeda, in his address. The managers of the Japanese pharmaceutical company have been working on a five-phase roll-out of a business assessment process since 2012 with the aim of reducing operator costs. Central to the initiative is the value stream mapping process which Takeda is using in the first instance to analyze the top products and to standardize the definition of opex.
Employees are attending three-month workshops designed to raise their awareness and ownership of the process but, as with every opex initiative, the skill lies in breaking the abstract term down into bite-sized pieces of practical relevance. For example, the operators are now recording reasons for downtimes involving machine breakdowns of more than three minutes based on a predefined guide. And—as was to be expected—interface management has been identified as a major influence...
No Patent Remedies for Escaping the Cost Pressure
None of the speakers had any patent remedies as to how to escape the cost pressure, but there were plenty of suggestions and examples of best practice, such as the one from Prof. Fernando Muzzio of Rutgers University. Muzzio is the Director of C-SOPS (Engineering Research Center for Structured Organic Particulate Systems) and has been developing continuous processes for particulate matter since 2006 in various applications including pharmaceutical production.
Since 2012 C-SOPS has been operating a production line with Janssen, combining dosing unit, grinder, mixer and tablet press in one continual process. Janssen now wants to build a production line based on the tested design with a view to putting it into operation in 2014. The FDA has also signaled its interest in the demonstration project. Nevertheless, there are still some skeptics because the specter of continuous production has been haunting the sector for some years now with the usual ups and downs associated with new manufacturing techniques. Typical responses therefore include the remarks of one delegate claiming to have been in the industry for 22 years and to have seen all sorts of initiatives come and go.
The efforts to introduce continuous production are centered on particulate production. The greatest leverage also lies in the fact that 80% of all medicinal products are still administered in solid form and therefore began their life cycle as powder at some stage. The potential significance of continuous production has therefore occupied the mind of Dr Ralf Weinekötter of Gericke, who wants to counter the cost pressure with reduced production times. The mixing technology specialist has been interested in the subject of continuous mixing since 1993 and is also at Rutgers University with Muzzio.
Continuous Production Makes its Way into Pharmaceutical Industry
Gericke and Gerteis have developed a continuous line for direct compression which mixes, granulates and compresses, and takes just five minutes to go from compound to tablet. The clever part is to replace the tablet press feed container by a miniature continuous metering/mixing line.
The continuous line has several advantages. There is no need for scale-up because the same line is used regardless of whether six kilograms or 600 kilograms are being made—only the mixing times are lengthened, and the continuous process reduces the risk of segregation as there is no interim storage.
Project efficiency could become the 'make it or break it' factor for pharma companies - read more what the ISPE conference thought about this issue on the next page!
PAT in Tableting – What to Expect
The real-time release is an important step, if not the most important step, in continuous production, explained Lorenz Liesum, Head of PAT at Novartis, and the subject of specifications set out by the EMA in its guidelines ICH Q8, Q9 and Q10. One of his main conclusions: A PAT project is not completed right after validation, then it actually starts with automation, maintenance and using it at a daily basis
Project Efficiency as Answer for the Cost Challenge
The leap from continuous production over opex and onto project efficiency may seem large, but optimized planning of investment projects is also a building block on the way to making cost savings. Quality, time and costs are the points of the magic triangle which have occupied the mind of Dr Michael Atzor of Bayer. In the majority of cases it is not possible to satisfy all the demands, he said, as quality is the primary, and therefore non-negotiable, factor insisted upon by the companies. There are a few sticking points in the planning process. One is the time at which investment decisions are made. This normally happens in clinical phase 1 and therefore at a time when the development work is far from complete, as neither the formulation nor the production process has been finalized. Overlapping planning phases are virtually unavoidable in a pharmaceutical project, with process development and engineering work inevitably running in parallel. It is just as important, however, to define the rules of the game clearly, according to Atzor, who gave the delegates five dos and don'ts to take away with them and follow in order to at least pave the way for success.