Release Date: - ABB



Release Date: 19 April 2007 Serial No: ABB039

Flexible manufacturing technology can help fight generic erosion for branded drug producers

Paradoxically, both pharmaceuticals giants and the smallest of contract manufacturers, while facing very different market challenges, can share a common solution to gaining competitive advantages. Bengt Stom, Global Segment Manager Pharmaceuticals with ABB Robotic’s Consumer Industries Division, explains how flexible automation is a key to beating off price, quality and delivery pressures.

The threat that generic drug producers pose to manufacturers of branded treatments has been well documented. A report from the US publisher URCH entitled “Generic Competition 2007-2011 – The Impact of Patent Expiries on Sales of Major Drugs” suggests big pharma companies stand to lose up to $100 billion over the next five years to generic rivals. An earlier report from the same source recorded that “The period 2005 to 2009 will see the expiration of patent protection for 39 major drugs in the United States, an average of 8 a year…There is clear evidence that the loss of revenue from patent protected drugs will impact upon the growth of the industry when so few new drugs are reaching the market”.

Yet, the world relies largely on the biggest pharmaceutical companies for molecular development that will battle both perennial and increasingly threatening diseases. On 18 April the “Patent Reform Act 2007” came into force in the USA. This act, some argue, effectively opens the doors for challenges from generic producers throughout the lifetime of valid patents. The Biotechnology Industry Organization (BIO) President Jim Greenwood stated on the day of the reform’s passing into law: "Unfortunately, the 'Patent Reform Act of 2007,' as introduced today, contains provisions that will weaken the enforceability of validly issued patents, and fails to include necessary reforms to make the patent system more objective and efficient. The bill threatens the ability of biotechnology companies and researchers to find and develop innovative treatments for some of the world's most deadly diseases, such as cancer, heart disease, Alzheimer's, Parkinson's and HIV/AIDS, as well as new solutions to address critical agricultural and environmental challenges facing the global community”.

The reality within the pharmaceutical industry is that while the value of sales is high, most drug companies face escalating costs and tight financial controls if they are to continue to uncover new treatments. The cost of developing new drugs is astronomical. Findings published at the end of 2001 by the respected Tufts Center for the Study of Drug Development in Boston, USA, suggested that the average cost to develop a new prescription drug is $802 million. Moreover, it still takes between 10 and 15 years to develop a new treatment from patenting the molecule to reaching the market.

Patents are essential to protect investors in new pharmaceutical products, but the manufacturers are unlikely to find support from governments in this regard. It comes down to a case of the physicians having to heal themselves. Yet, the industry clearly needs new drug developments to achieve growth against generic competition – a classic chicken and egg situation. In short, if molecular development is to continue at the pace required, the manufacturers and research companies need either protection, investment (by governments of the WHO) or to progress new manufacturing methods. The latter is the most viable option.

Patent losses hit molecular development

Also in 2001, Jim McKiernan, Partner at PricewaterhouseCoopers in Basel, Switzerland, highlighted in a published article that the complexities (and costs) of the value chain had to be addressed by the pharmaceutical manufacturers. At that time he estimated that, “most advanced pharmaceutical companies have rationalised down to between ten and twenty plants globally, compared with sixty and upwards at others”. At the same time he argued that the ideal vision of two primary and between five and ten secondary plants was a long way away for most companies.

Considering that many drug treatments can literally spell the difference between life and death, the failure to supply products is not an option. However, this very factor can lead to a very high cost of service for the drug manufacturer, since continuity of supply is often met by holding excessively large inventories of product. To improve the move towards a more “just in time” production requires dramatically better integration of the value chain – information flow must be fast and unambiguous and lead times have to be reduced.

The build up of inventory is a constant problem in the industry, particularly in the big pharma companies. Inventory turns of just one or two per annum are not uncommon – a situation that would be intolerable in most manufacturing operations where turnover of product is usually measured in high tens or even hundreds. Similarly, because of a combination of the validation process and poor planning, many new products have production lead times of up to two years. While this is understandable, the often cited three to six month lead times for packaging, labelling and distribution will soon be intolerable to the market.

Production methods must be addressed

Given that it is typical for large manufacturers of branded drugs to have production accounting for just a low single figure percentage of the overall turnover, a simplistic view can be taken that the overwhelming value of such a business relies on a relatively small cost. One example known to ABB Robotics is a big pharma company whose production represents 3% of turnover – suggesting that any kind of production failure would have potentially devastating consequences for profits. Such a scenario would also presumably impact directly on available research funding.

What pharmaceutical companies might do is examine closely how their manufacturing methods can meet changing market needs and reduce the stockpiling that is so evident. While the pharmaceutical industry has been notoriously conservative in its approach to production, it is this very fact that invites makers of cheap generics to exploit volume demand, just-in-time delivery and flexibility in the packaging and supply of products.

Meanwhile, at the other end of the pharmaceuticals supply spectrum sit the contract manufacturers and co-packers. Generally speaking, smaller and ostensibly less well resourced companies, this group of businesses exist only to produce goods. Unsurprisingly therefore, contract companies are usually more attuned to production needs. They are more akin to other commercial processor or manufacturers.

However, at this end of the pharmaceutical industry many of the value pressures felt by big pharma companies are passed on. Most notably are the needs to produce goods on time, on demand, to prescribed quality and at lowest possible price.

Similarly, while large pharmaceutical manufacturers have a very low percentage of turnover devoted to production, for contract manufacturers and co-packers the value of production proportionate to turnover is high.

For contract manufacturers and co-packers to meet the pricing and delivery needs of their customers, they must invest in flexible, productive and reliable production technology. Flexible automation to enable both fast and cost effective response to market demand is at the forefront of available solutions to meet these requirements.

Most chemical processes cannot be altered radically – both for fundamental physical reasons and also because compromising such processes leads to costly and lengthy revalidation and even new stability trials. The key production areas to address are the product handling and packaging.

Manufacturing solutions

Coupled with the above factors, most pharmaceutical companies also face the challenge of increasing costs through to ongoing globalisation and the growing importance of product differentiation for primary and secondary packaging. This necessitates new levels of efficiency, cost effectiveness and flexibility within the packaging process. In addition, the packaging methods must be integrated within the entire supply chain. There has to be an interface with the preceding drug manufacturing steps, as well as the warehouse and distribution steps that follow.

Furthermore, the packaging must guarantee product stability within a specified timeframe, and has to ensure safe and secure storage and transport until final use. Packaging also has to satisfy its function as a marketing and communication device. Finally, child resistance, tamper evidence, protection against counterfeiting and increased patient convenience, are increasingly important.

Clearly, new packaging styles and formats bring about fresh challenges for the integration, system validation and security measures – including not just tamper evidence, but also patient information leaflets and track and trace data such as bar codes, or, in future, RFID tags.

The net result of these pressures has been that pharmaceutical companies must now carefully examine their production methods, costs and flexibility. Manufacturing processes are largely governed by the laws of chemistry and hence, present few opportunities for savings achieved from efficiency or efficacy improvements. At the end of the line, however, there remains scope for investment that can yield dividends; not just in economies and cost reductions, but also to introduce commercial differentiators such as pack sizes, types and styles.

Many analysts in the industry suggest there will never again be blockbuster drugs. Even if this sweeping statement is not entirely founded, it does highlight the unequivocal shift towards greater competition and variety in pharmaceutical products. Moreover, this is a trend that shows no sign of abating. To satisfy the changing market needs for variety and flexibility, the pharmaceutical industry might perhaps look at its high volume, high variety counterparts in the food sector.

Customer-specific and innovative packaging designs are gaining importance, while the variety of products is increasing and batch sizes are shrinking. Hence there is an increasing demand for intelligent and versatile packaging systems, which can handle a multiplicity of different products safely, quickly and cost-efficiently at the end of the production line.

Integration is a panacea

Modern packaging machinery can accommodate all sorts of programmable flexibility in blister packing, wrapping, cartooning and secondary packing. But, it remains in the handling and in-line quality control that challenges remain. Use of robots can save not only space and costs, but also ensures the required precision and reliability of packaging operations. Easy programmability of robots is the key to enabling minimum resetting times when the plant is set to new products or packages. Moreover the integration of advanced software, diagnostics and modern machine vision systems can integrate entire process through packaging lines.

The benefits of a truly effective integrated approach to automation are the overall reliability and profitability of the resultant system. Moreover, integrated systems can share common control platforms. This enables electronic signaturing, foreshortened and cheaper validation because of common hardware and software platforms, simplified and cheaper maintenance and even shared risk on the output and uptime of the lines.

Robots have been used in the packaging industry since the late 1970s, originally being used to handle heavy goods in the palletising process. The pharmaceutical industry has been somewhat slower to react simply because the palletising of bulky packages is rare. However, the use of robots in all types of packaging has become established and they form the basis of over 25,000 units around the world. A wide range of different robots make up this figure, as they are now used in many areas of packaging, from the handling of unpackaged goods through the secondary packaging stage right up to palletising and transportation. In pharmaceuticals they are largely restricted to feed placing, secondary handling, cartooning and occasionally palletising.

Robots are predominantly used to pack large numbers of small products into multi or mixed packs within a very short time, such as blister cards into cartons or onto conveyors for wrapping. Increasingly, fields such as medical devices, for example inhalers, prefilled syringes and so forth are packed using robots.

One potential for compromise from pharmaceutical businesses has been the fact that most high speed packaging lines have been developed for very high volume output in the food industry. Many systems now in use are capable of packaging several thousand products per minute. However, rarely are these speeds required by the pharmaceuticals industry and almost never are linear high speed systems needed for end of the line packing, cartooning and palletising. Of far greater importance are flexibility, availability and reliable uptime efficiency.

For end of line packing a preferred choice is to adopt robot cell arrangements. In such a configuration, multiple axis – usually six-axis - machines perform a variety of flexible functions. These can even include case or carton forming, as well as picking and placement of the products into the completed cases. Integration of ancillaries, such as check weighers and packaging printing such as bar coding, can not only be incorporated, but also located within the cell to consume minimal floor space. Indeed, the cell approach consumes significantly less floor area than a comparable linear packing line. Indeed, access to the ancillaries, also makes maintenance or replacement of units very quick and easy – an important consideration where availability of the system is key.

Getting to grips with robots

Some handling processes use SCARA or hexapod delta robots. Thanks to the compact dimensions of the delta kinematics, and the associated high speeds and acceleration properties, it is now possible to handle high numbers of products, in small spaces, in a very short time and with relatively low energy requirements. Some of these robots have acceleration up to 10G with picking capabilities of well over 300 parts a minute!

The fast handling speeds are due, in part, to the fact that in today’s generation of robots, the control concept makes use of the very latest advances in computer processing speed. PC-based solutions, with their open architecture, have really made their mark. For instance, ABB Robotics uses an industrial PC platform with drag and drop graphical user interface for ease of programming.

Some applications use machine vision systems and image processing and, for more reliable operation, this can be directly integrated into the motion controller of the robot. This comprehensive integration of all components into one platform facilitates efficient communication and guarantees reliable robot operation. Peripheral devices, which are used in large numbers in packaging systems, are also easily integrated into a system via standard interfaces or field bus.

Users are now able to control robots via user-friendly programming interfaces. These have been simplified so that engineers familiar with programmable logic controls are also able to program robots. The user interface for every robot is a simple screen. The user can easily implement parameter changes during operation, which significantly increases the quality and efficiency of the system. Simple machine programming can also be used for new product shapes and sizes as well as the possibility of viewing production statistics.

This open technology is being used more and more by smaller operators. For this reason, there is currently a boom in the use of this technology in stark contrast to the comparatively inflexible proprietary systems. There are also advantages when it comes to service and maintenance.

In many packaging lines, primary packaged products are usually discharged from the packaging process in a single track, before being passed on to the secondary packaging process. This is often achieved manually or by using more conventional methods such as “side loading” or a “wrap around” solution. Conventional methods offer little flexibility and take up a great deal of space, whereas manual workers can expensive. As a result, for both ergonomic and economic reasons, robotic systems are very much in demand in this area. The story is similar in secondary packaging, where the trend of replacing manual work with flexible robot systems continues unabated. Again, the use of six-axis machines brings enormous benefits in terms of flexibility and capability to handle varying products – especially when configured in cells rather than lines.

In both primary and secondary areas, replacing humans with robots can be a major cost consideration and robot suppliers should therefore be conscious of supplying machines at acceptable price levels. Recognising this need, ABB Robotics has always developed modular robot designs. The modularity keeps production costs down, but the units have the flexibility to be used across a wide range of applications in a number of different fields, such as pharmaceuticals.

In a recent study conducted at a pharmaceutical manufacturing plant in the USA, ABB Robotics calculated the labour costs for running a line with purely manual operation, using a traditional commercially available case packer, and using a robotic solution. Taking into consideration changeover times, adjustment, downtime, testing samples, cleaning and visual inspection, the results showed a labour cost per shift of $4500 for a purely manual line, $1000 using case packing machinery and just $500 deploying a robot cell solution.

Handling of all sorts of products can be achieved using robots and there are many standardised solutions that can be incorporated into system concepts that extend the packaging process. Cartoning systems are predominantly offered with differing numbers of product infeeds. The cartons can also be handled by the robots or fed in manually. With standardised carton sizes, the complexity of a system is limited and so simple operation via a menu is possible. The flexibility of the robot is also high because it is possible to work with different gripper variants.

Invaluable technology

Examples of how robot features render them invaluable in pharmaceutical businesses include the ability to create greater pack variety or to integrate packaging processes. For instance, the simple inclusion of patient care leaflets poses an additional packaging need – especially if the information is market dependent and has in itself a number of variants. There is also the ability to package multiple packs – such as one blister card, two or more in varying pack sizes within a single line.

Some advanced systems enable the robots to automatically configure themselves according to preordained recipes. This includes in some instances, the ability to change grippers as well as the motion programs. Because the automation is secure, such arrangements also simplify validation processes.

Assembled packages, such as for wrapping inhalers with associated ancillaries and leaflets, or for multi-part drug treatments such as certain cold and flu remedies that have day and night time tablets. Some linctus products include measuring spoons or cups within the carton and robots can be ideal for automatically compiling such packs.

In a recently installed end of line packing systems for a Japanese manufacturer of inhalers, an expensive plastic case design could be replaced by a cheaper cardboard version because vacuum dust extraction could be incorporated within the robot cell. The robot was also programmed to apply a clear plastic label to identify if dust or particulate contamination was evident on the outside of the inhalers. Similarly, the cell was able to apply a tamper evident seal to the carton.

Validation issues

As part of an overall system robotics technology lands itself to the stringent validation requirements of both GAMP and FDA 21 CFR Part11. Because robots once programmed are infallible, all that needs to be done to ensure compliance with validation is to have the customary software locks and electronic signatures that is becoming commonplace with pharma process software.

Also, in flexible systems where perhaps several pack styles are produced on a single line, the individual programs can be similarly secured. All that then needs to be done is to ensure the correct grippers are fitted – a function that may easily fall outside validation requirements since it is unlikely to affect the process itself if an error were to be made.

The future

In the most futuristic setting, the automatic transportation of the cartons to, for example, wire guided or laser guided vehicles that are fitted with sensors and can find their own way to the storage areas.

Robot technology means that it is now possible for a fully automated system to take a pharmaceutical product from the manufacturing process right through to the delivery point. Further development of the open control technology and existing robot mechanisms will lead to robots taking on an ever more critical role in systems of the future. Inflexible proprietary automation counterparts will be pushed further into the background and may possibly disappear altogether from potential pharmaceutical applications.

Ends – 3280 words

NOTE TO EDITORS

ABB () is a leader in power and automation technologies that enable utility and industry customers to improve their performance while lowering environmental impact. The ABB Group of companies operates in around 100 countries and employs more than 110,000 people.

ABB ROBOTICS

ABB is a leading supplier of industrial robots - also providing robot software, peripheral equipment, modular manufacturing cells and service for tasks such as welding, handling, assembly, painting and finishing, picking, packing, palletizing and machine tending. Key markets include automotive, plastics, metal fabrication, foundry, electronics, pharmaceutical and food and beverage industries. A strong solutions focus helps manufacturers improve productivity, product quality and worker safety. ABB has installed more than 150,000 robots worldwide.

FOR MORE INFORMATION PLEASE CONTACT:

Margareta Zeicu, Marketing Manager Consumer Industries

ABB AB, SE-721 68 Vasteras, Sweden

Telephone: +46 (0)21 344012

e-mail: margareta.zeicu@se.

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