The pharmaceutical market continues to expand despite the current economic turbulence, and there are a number of reasons why this is the case. The rapidly aging population in the Western industrialized nations and in emerging markets such as China is driving demand for medication. Certain types of illnesses including diabetes, Alzheimer’s disease and some forms of cancer are becoming more prevalent as life expectancy increases. In the wake of recent advances in molecular biology and cytology, medication is being tailored to an increasing extent to the needs of the individual patient, creating new incentives for alternative therapy strategies. ACHEMA 2009, which will take place on 11-15 May in Frankfurt am Main, Germany, will showcase the latest advances at every step in the pharmaceutical supply chain, starting with R&D and continuing right through to packaging. More than 4,000 exhibitors and 180,000 visitors from all over the world will meet at this leading event for process industry.
According to figures published in the IMS World Review 2008, worldwide turnover of pharmaceuticals rose to 713 billion US-$ in 2007, which was around a 10 % increase year-on-year. 82 % of total turnover in the worldwide pharmaceutical market is generated in North America, Europe and Japan. Sales in North America were up 4.5 % to 305 billion US-$ in 2007, accounting for nearly half (43 %) of worldwide pharmaceutical turnover. The pharmaceutical market in Europe rose by nearly 16 % to 213 billion US-$. The increase was due in part to the stronger euro. Sales in Latin America were up by more than 17 %, reaching nearly 43 billion US-$ in 2007.
The outlook remains good despite the fact that generics continue to put considerable pressure on pharmaceutical prices. To meet the challenge, the pharmaceutical industry has taken a number of steps including outsourcing, relocation or consolidation of production sites, efficiency improvement and workforce reduction. These efforts have produced results. IMS Health forecasts indicate that average growth in EU member states will be about 5.5 % over a five year period compared to nearly 11 % in countries that are outside the EU.
A study published by PricewaterhouseCoopers (PwC) predicts that five years after that turnover will double, reaching 1.3 trillion US-$ by 2020. According to PwC, demographic change and strong economic performance in the E7 countries (China, India, Brazil, Russia, Indonesia, Mexico and Turkey) are the primary factors that will drive growth.
Increased investment in research
Nevertheless, the pipelines in the pharmaceutical industry are not as full as they were just a few years ago. R&D for a new pharmaceutical active ingredient still costs an average 800 million US-$. More than half of the money is spent on clinical development, and in particular on the logistically complicated multi-national Phase III trials. The complexity of the diseases which are being treated, for example Morbus Parkinson, is also increasing. According to figures published by VFA (German Association of Research-Based Pharmaceutical Companies), R&D expenditure by pharmaceutical producers in Europe, Japan and the US rose to about 60.2 billion euros in 2006, a 52 % increase compared to 2000 (excluding exchange rate fluctuations). Calculated in local currency, R&D spending in the US (61 %) and Japan (57 %) increased at a higher rate than in Europe (39 %). Nearly half of R&D investment worldwide still takes place in the US.
Biopharmaceuticals are the market of the future
There is particular interest in biotechnology-based pharmaceuticals. According to information supplied by VCI (the German chemical industry association), 177 biopharmaceuticals had been approved at the end of 2007. These products have now captured a 15 % share of the total German pharmaceutical market across all indications. Insulins are the largest category of biopharmaceuticals in the world market (about a third) followed by immunomodulators, erythropoetins, vaccines and other hormones.
The development of synthetic medication is already an elaborate process, but the design requirements for equipment which is used to produce biopharmaceutical drugs are highly complex. Companies may easily have to spend more than a billion euros on development of a new product, and that is the reason why few products make it to the approval stage. However, the ones that do make it that far are very lucrative and can generate annual turnover in excess of one billion euros.
These products are very difficult to produce. The contamination risks have to be carefully managed, and isolation and purification of these substances is very complex. Formulation requires special expertise. To mention just a few of the differences to conventional products, the molecules are generally very large and unstable, they degrade very quickly even when they are stored properly and scale-up is more difficult compared to conventional pharmaceuticals.
The production base is expanding rapidly in India
Production system and equipment suppliers are coming under increasing pressure, and this applies equally to the conventional and biopharmaceutical markets. The days when production costs in the pharmaceutical industry did not appear to be an issue are long gone. Virtually every high-profile company has launched programmes to streamline operations.
Corporate production sites compete with each other. Unprofitable sites face the threat of closure or sale. VFA predicts that additional major production sites will be set up in India and China by 2020. India could become a leading producer of gene technology products. Experts agree that only the ability to maintain technological superiority compared to producers in countries which have low labor costs can guarantee sustained market success for European equipment manufacturers.
High-speed filling systems
In response to these demands, a highly specialized pharmaceutical machinery industry has developed around the world, which according to VDMA (German Engineering Federation) estimates generates worldwide turnover of about 4 billion euros. This industry went through a period of rapid expansion during the past ten years. Fill and seal machines for liquid medication are a good example. New drug delivery systems are dictating the pace of development.
Pre-filled syringes and freeze-dried products are currently very popular. The filling operation has to be fast, safe and gentle. Growth in the disposable syringe segment has remained in double-digits for the past five years. Performance is the overriding engineering challenge in this segment. For many years, production rates on filling machines for disposable syringes were around 5,000 units per hour. High-performance machines now fill and seal up to 60,000 units per hour.
Every aspect of aseptic production must be considered during system design and implementation. Every subassembly must be packed into a very tight space, but it still must be possible to access and clean the machine. Other demands include fully-automated CIP/SIP (cleaning-in-place/sterilising-in-place) systems, in-process control (IPC) and isolator technology.
The increased popularity of freeze-dried products is another hot topic in the industry. This method can extend the shelf-life of many pharmaceuticals, and the technique is particularly useful for drugs that contain proteins. For filling machinery, this means that the systems have to guarantee very gentle material transport.
Validation effort has risen dramatically
Besides PAT(Process Analytical Technology)-enabled design, fast-track projects and highly automated production systems, the emphasis in the pharma equipment supply industry is clearly on a reduction in GMP (Good Manufacturing Practice) space requirements, shorter changeover times, process reliability optimisation and maximum flexibility. Developers are also trying to improve yields, lower the consumption of auxiliary materials and increase system availability. The overriding goal is to maintain maximum patient safety standards and ensure the reproducibility of a production process after initial validation.
A huge effort is involved in validation and documentation of a production process, and the amount of work needed for these activities has risen dramatically in recent years. Few changes are made to a process once it has been approved. This is understandable from the safety point of view, but it impedes engineering innovation. New technologies remain in the drawer until new products are introduced.
The effort involved in validation is one of the reasons why PAT is such an attractive option for the pharma industry. PAT solutions move end-of-line quality control back into the production process, creating an opportunity to reduce the cost of quality control and release batches faster.
The key concept here is real time release, where batches do not have to be held back until analysis results are available. Monitoring the quality parameters contributes to a better understanding of the process. The data that is collected can help identify factors which have an influence on the quality of the drugs, and it provides an empirical basis for determining cause and effect relationships. Overall process control becomes more discriminating, making it possible to ensure that product quality stays within tighter limits. However, the breakthrough of this new approach, which includes parametric product release, is probably about 10-15 years over the horizon.
Many equipment manufacturers will be drawing attention to PAT at ACHEMA 2009. Exhibitors will point out which quality-relevant data can already be captured on current pharma machinery and what new analytical techniques could reasonably be embedded into the machines.
Increased emphasis on highly active ingredients
The trend towards highly active ingredients continues unabated. A lot of effort is being invested into galenic formulation. The goal is to develop active ingredients that act faster and more directly on the patient. The dosage unit of today’s pharmaceuticals is significantly smaller compared to earlier formulations, yet they are more effective. Patients are not the only ones who notice the difference. Cleanroom designers have to come up with solutions for handling these ingredients.
Pharmaceutical companies which produce highly potent APIs (Active Pharmaceutical Ingredients) or use them in production have to balance occupational safety and product safety needs. The situation is often very complex, and designers face some formidable challenges. To comply with work regulations, employees can only be expected to wear a limited amount of protective clothing and then only for a reasonable amount of time, so there is a need to find other alternatives.
Closed process systems reduce occupational exposure. The same precautions must be taken as with protective clothing to prevent cross-contamination and microbiological degradation. The list includes closed processes, aerodynamic and physical barriers, design for ease of cleaning and high-grade materials. A broad spectrum of contamination-free systems for handling APIs along with other new containment and isolation solutions will be on display at ACHEMA 2009.
Pharma packaging ensures safety
Packaging also has a role to play in treating diseases. The British-based firm MSI (Marketing Research for Industry) estimates that in Germany alone the market for medication packaging increased by 14 % from 27.5 billion units in 2001 to 31.4 billion units in 2005. MSI expects the figure to reach 37.2 billion units by 2010.
The expectations of patients, doctors and pharmaceutical producers are rising along with the quantities. Functional aspects of prescription medication are the major consideration. There is an unmistakable trend to make pharmaceutical packaging more user-friendly and safer to handle. The packaging should be resealable, come with a pocket for the patient information leaflet, have additional information on the flaps or have aids to remind the patient when to take the medication, because it is estimated that half of medication is not taken as prescribed.
According to estimates released by the International Association for Pharmaceutical Technology (APV), 80 % (by quantity) of medication produced today is supplied in tablet or capsule form. The rest comes in semi-solid form (e.g. ointments, lotions, suppositories), liquid form (e.g. oral solutions, injections, infusions and aerosols) or as therapeutic systems (e.g. transdermal systems). In contrast to the US market where tablets are sold mostly in plastic containers, these products in Germany are predominantly supplied in blister packaging which projects a professional image in the eyes of consumers.
Solid medication is less expense than non-solid products. The 80 % market share (by quantity) only generates 50 % of turnover. Parenterals and alternatives such as aerosols and therapeutic systems are becoming increasingly popular. Regardless of the drug formulation, the cost-performance ratio and protection of the product are more important than ever.
Brand loyalty is another major factor. Even a standard folding carton must now stand out from the rest. There are a number of design options which help to achieve this goal including shape, opening aids and print technology. The latter is also used to frustrate professional counterfeiters.
Besides the need to strike the right balance between high performance and flexibility, counterfeit protection is another major issue for packaging designers in the pharmaceutical industry. Pharma producers now use a number of techniques to combat counterfeiting, ranging from very simple methods to highly complex systems. The list includes security features such as guilloché and moiré patterns, holograms and special colors. Besides combining several of these special features, the safest way to prevent counterfeiting is to keep an eye on the entire distribution channel. More and more companies are turning to track & trace technology. Identification systems are being integrated into the production process, providing a mechanism for tracking the product throughout the entire supply chain. ACHEMA 2009 is at the forefront of this technology as well, and visitors in Frankfurt will have access to a wealth of useful information which will provide stimulus to the pharmaceutical industry.