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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
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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
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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.
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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
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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 costefficiently 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.
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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.
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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.
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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
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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.
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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.
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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 (www.abb.com) 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: [email protected]
www: www.abb.com
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