Tight deadlines, extreme quality standards and massive cost pressure—these are the demands which currently dictate pharmaceutical plant engineering. The new but familiar market of the future is biotechnology, although chemical syntheses are also back in demand.
The demands the pharmaceutical industry makes on the construction of its plants do not at first glance appear to differ from those of other industries. “They include complying with specific quality standards and deadlines while keeping costs competitive throughout all stages of a project: from engineering and production through installation, the absolute maximum in quality standards applies throughout,” is Managing Director of MCE Industrietechnik Salzburg Ludwig Paradeiser’s summary of the general requirements. And as if this wasn’t enough, the pharmaceuticals industry sets even higher standards.
As well as the technological requirements, they also need for example to get a grip on the organizational aspects, which in the experience of Rolf Mönig, Head of Plant Construction and Engineering at the Chemgineering Group, is anything but easy: “The stress on deadlines stems from the fact that high investment costs require that ROI (return on investment) commences as soon as possible. At the same time, the initial phase, i.e. project development, tends to drag on to some extent and is not always particularly well focused.” All of which results in a very intense period where planning and construction overlap. Another aspect which is a major influence on cost is the highly technical complexity of systems. “In many cases, this is pushed to the limits of research in terms of material requirements and the degree of automation,” says Mönig.
As well as the need for PAT-enabled plant design, short project spans and highly automated production lines, Ralf Roepenack, the new Managing Director of NNE Pharmaplan, sees a further massive challenge in the need for conversions or GMP upgrades to be undertaken during production operations. These have to be carried out with minimal disruption to production, while protecting the safety of both product and staff during construction. His view is that it will be interesting to see what happens when technologies are transferred to the pharmaceutical industry from other related industries, such as the drinks industry, with the aim of increasing productivity and plant performance.
How to become more cost effective
Nor is the pharmaceutical industry spared the pressure on cost, according to Stephan Backhaus, Biotechnology Plant Sales Project Manager at Linde-KCA-Dresden. “Pharmaceutical lines will be more cost-effective; even though the desire for individual solutions remains as strong as ever, this is why there is an inexorable trend toward standardization”—in spite of the fact that new classes of active ingredients require the development of new technologies.
Backhaus sees this as a contradiction: “On the one hand, individual plant engineering solutions secure competitive advantage, but on the other hand the relentless rise in regulatory requirements and the ever-increasing corporate risk involved in the time-to-market for medicines create a climate which is increasingly hostile to innovation.” He is left to conclude that: “Where there are validated production processes, there is little chance for technical innovation. Therefore, new technologies are always in effect aimed at new products.” These types of commissions can only be undertaken on an economic basis by means of a close partnership based on trust with investors and planning partners.
Current trend is biopharmacy
“We are currently seeing greater investment in the areas of vaccine production, biotech plant in general and multi-purpose lines,” Roepenack lists as the current fields of work. Others also see biopharmaceutical products as a distinct focus of development: “We sense a willingness on the part of our customers to invest—particularly in top quality and complex biotechnology systems for the pharmaceutical industry,” is Paradeiser’s evaluation of the industry as well. This area will be the key mainstay for MCE Industrietechnik Salzburg in future and is a position which is supported by the two large orders the company has recently won.
For example, a Swiss pharmaceutical group is to extend its pilot operation, whereby it develops manufacturing processes for the production of biotechnology test specimens. Here, MCE is supplying four processing units for fermentation. And Merck Serono is to invest around € 300 million in future in the development of the Merck Serono Biotech Centers in Vevey by Lake Geneva. The order includes the construction of new biotechnology production plant for active ingredients which are used in cancer therapy. The active ingredients should be available as early as 2012 from the new production site. Here, MCE is supplying ten process units for product purification.
“The future market in the pharmaceuticals industry is biotechnology,” is how Backhaus casts his vote as well, and he is convinced that investment in this technology will be disproportionate over the coming decades . “In the search for new medicines, the pharmaceuticals industry today profits particularly well from the dynamic increase in knowledge in genetics and cell biology. Innovative medicines are manufactured for example with the help of genetically modified cells and permit completely new approaches to treatment.”
Industrial scale complex
Backhaus does not conceal the fact that growing such cells and extracting their products on an industrial scale places complex demands on the design of biotechnological plant. What is more, the degree of difficulty of corporate decisions for pharmaceutical companies involved in biotechnology has increased greatly in recent years. “The cost of developing a product through to production standard is exceptionally high and amounts in some cases to more than a billion euros. Thus, only a few products can be developed through to licensing. These may then however gain a relatively high sales share of more than one billion euros per year,” is Backhaus’s reading of the scale of the issue.
Then again, biotechnological production presents the plant engineering sector with quite different requirements, as Backhaus emphasizes: “At a time when we are seeing dynamic development in biotechnology, trends need to be recognized early and our response based on flexible planning and implementation structures. With our use of front end engineering, Linde-KCA-Dresden is a leader and extremely well placed in the biotechnological plant engineering market.”
While there is a need to develop capacity for the biotechnological production of complex molecules such as monoclonal antibodies, at Chemgineering there is a noticeable renewal of interest in chemical syntheses. “This is definitely due to the fact that to some extent young companies, such as Actelion, are specializing in the development of new active ingredients in this segment. This results in an increased need for state-of-the-art synthesis plant, suitable for the safe production of highly active substances, for example,“ says Dr. Herbert Matthys, CEO of Chemgineering Group. “This movement follows extremely intense development in the production of new and more sophisticated forms of administrating drugs, such as prefilled syringes and inhalers.”
Responsibilities must be defined
The challenges have been defined; now they just need to be tackled. “The greater the intention, the more important it is for all factors involved in its realization to be efficiently interlocked in order to achieve the customer’s requirements,” is the Managing Director of NNE Pharmaplan’s conviction. “We have in-house planning expertise in all technologies and systems: from the actual process, automation, building services and architecture through the planning of piping systems. Thus, we can supply everything from a single source. Added to this is a high degree of processing expertise provided by specialists in all key process technologies in the pharmaceutical and biotech sector. Many of our experts have experience in production and a high level of professional knowledge in state-of-the-art technologies, such as the use of disposables in the biotech sector,” continues Roepenack.
Another key factor for Mönig at the first phase of a project is to establish a distinct project structure with clear responsibilities and interfaces. “The process planner needs to be commissioned as early as possible in order to get together with the customer to establish the basics of the project (i.e. process, quality, cost and deadlines) in a “programming workshop”. This is the only way to ensure that pharmaceutical companies will be able to cope well with the shortening of investment periods whilst maintaining a high level of flexibility and the necessary planning reliability.
His colleague, Dr. Armin Mayer, Head of Account Management and Southern Europe Business Development at Chemengineering, also lists flexibility and professionalism in engineering and project and construction management as necessary for life sciences which are highly regulated and therefore very documentation-intensive.
In the realization of pharmacy and biotechnology plant, deadlines need to be kept and the cost of solutions optimized even under difficult conditions, such as in narrow confines or whilst production operations continue. Without all-round expertise in project management and engineering, it is simply not possible to develop complex process chains in a cost and time-effective manner. Linde-KCA-Dresden therefore utilizes various tools to optimize the planning process, such as typical functions for effective flow chart development, typical layouts for effective layout development, as well as a GMP planning manual for achieving and maintaining GMP compliance.
However, with all the professional project management and intelligent planning tools available, there is yet another component to consider—employees’ experience. As Paradeiser ultimately concludes, this needs to be cultivated and maintained: “Employees form the basis of the success of the company. That’s why the challenge for the future lies in the development and support of skilled personnel in all areas.”
Who makes what?
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