packazineIssue 01/2007
Adamed | Take a deep breath Hikma | Powder manufacturing under optimized aseptic conditionsBLS | Bosch Lab Systems – Throughput counts
packazine-01-07_Pharma_ENG.indd 16 04.04.2007 16:55:38 Uhr
2 | packazine Table of contents | Editorial
www.bosch.com/pa [email protected]
04 06 10
News
Facts & Trends
04 Increasing popularity of prefilled syringes
Customers & Markets
Pharma & Cosmetic
06 Adamed | Take a deep breath – Inhaler systems on the march
08 Service | Old becomes new
10 Hikma | Powder manufacturing under optimized aseptic conditions
13 Bosch Lab Systems | Throughput counts
Events
15 Pharma 2007
Cover
Your competent partner for
pharmaceutical solutions
Friedbert Klefenz
President Bosch
Packaging Technology
Table of contents
packazine-01-07_Pharma_ENG.indd 1 04.04.2007 16:53:49 Uhr
packazine | 3
13
Dear Readers,
After we had the opportunity to celebrate three centennials in the past year, the
20th of October 2006 gave us a renewed cause for celebration.
We officially opened our new location in Hangzhou (China) with
a magnificent celebration. Customers, suppliers, employees and
other guests fêted the completion of the premises and toasted to
a successful future. As has been shown, this was for a very good
reason: Emerging markets such as China and India have registered
strong growth. In these countries we achieved an extremely gratifying
growth rate of over 50 per cent in turnover. In addition, the incoming
orders of the entire group have also developed very positively in the
past financial year and at 17 per cent lie over the average market
growth rate (11 per cent). The World Packaging Organization‘s award of the “World
Stars” for the new “Pull Pack” flexible bag package gave us an additional reason to
celebrate. This award is only presented for packaging with the highest level of quality,
innovation and technology. In the recent past, combinatorial chemistry and high-
throughput research has significantly changed the way the pharmaceutical industry
develops new drugs.
Currently a similar paradigm change is happening in the chemical industry. Automat-
ed high-throughput synthesis and screening methods for the development of more ef-
ficient catalysts as well as better materials and formulations open new, efficient and
faster methods of materials research. Together with BASF, Bosch Lab Systems has
designed a robotics unit that for the first time permits a comprehensive investigation
of complex coating formulae. This innovative concept is scalable for the most diverse
applications.
The application areas for inhalers are being constantly extended. The filling lines,
cartoning machines and flexible bag makers from our product portfolio allow us to
profit from this welcomed market development.
Surely you noticed the new organization of the Packazine into Pharma and Food/Non
Food sections. I wish you even more reading enjoyment with this new reader-friendly
design!
Friedbert Klefenz
Friedbert Klefenz
President Bosch
Packaging Technology
Editorial
packazine-01-07_Pharma_ENG.indd 2 04.04.2007 16:53:59 Uhr
20062006200620062006200620062006 20072007200720072007200720072007 20082008200820082008200820082008
Worldwide Prefill Growth12,8 % CAGR
Quantityin Billions
years
2,500
2,000
1,500
1,000
500
20092009200920092009200920092009 20102010201020102010201020102010 200620062006200620062006200620062006 200720072007200720072007200720072007 200820082008200820082008200820082008
Sales inMillions
years00
50
100
150
200
250
300
350
400
450
2002002002002002002002002009 29 29 29 29 2010010010010010010010010010
15 % CAGRMarket Growth for Self-Injection Devices
4 | packazine News Facts & Trends
Increasing popularity of prefilled syringes
Advantages and driving factors
of prefilled syringes
Self-filling a syringe can be a cumber-
some process, which is not only slow
but can also result in incorrect dosages
and spillages. The availability of prefilled
syringes introduced both convenience
and accuracy to self-administered
drugs. The increased use of prefilled
syringes is not only following the general
consumer trend of a growing demand
for convenient and easy-to-use products
– it is also driven by the pharmaceutical
producers as a consequence of improved
safety and the reduction in drug overfill.
The key advantages and driving factors of
prefilled syringes are:
Ñ Time, cost and resource savings
Ñ Convenience
Ñ Easier home use and use in
emergency situations
Ñ Prefilled dosage reduces medication
errors
Ñ Increased assurance of sterility
Ñ Easy storage and disposal
Ñ Fewer material costs
Ñ Elimination of vial overfill
Ñ Reduced risk of needlestick injury
Ñ Eliminates cross-infection from
needle re-use
Ñ Differentiation of product
Ñ Demand for technologies that
improve production
Ñ New solutions in the pen / auto-injec-
tors markets due to new formulations
suitable for self-injection
Ñ Needle safety regulations
Current market and requirements
These advantages of prefilled syringes,
together with the emergence of bio-
technology drugs in the early 1990s,
led to an enormous, worldwide surge
in demand and this product class still
offers the highest future growth. The
The last two decades saw an increase in the administration of
parenteral drugs by prefilled syringes. The worldwide market for
prefilled syringes alone is estimated at 1,500 billion units and
worth US $ 1.5 bil. (see graph 1).
Market Growth for Prefillable Syringes Market Growth for Self-Injection Devices1 2
packazine-01-07_Pharma_ENG.indd 3 04.04.2007 16:54:06 Uhr
packazine | 5
predicted annual growth rate of 10 %
can be explained by the increase in
home-care, with very different end-user
needs in self-injection (see graph 2).
Besides geographic expansion and the
shift to unit-dose packaging, the market
for biological parenteral applications has
also increased demand. Over the entire
last five years, the US market has been
growing by 20 %*. The US pharmaceuti-
cal packaging market is set to grow at a
compound annual rate of 3.3 % between
2004 and 2011. 16.8 % of this revenue
is set to come from the fastest growing
prefilled syringes sector. Frost and Sul-
livan stated that the European market in
2005 was worth US $300 million and is
growing at 8–10 % per annum.
Continuous innovation for safer
injections
Needles and syringes can expose the
user to an injury risk and the World
Health Organization estimates that, an-
nually, there are three million accidental
needle-stick injuries worldwide. In
November 2000, the US implemented
the Needlestick Safety and Prevention
Law. This was followed in Germany by
legislation to prevent needlestick injuries
and, more recently, the UK issued guid-
ance in 2005. As a result, the market for
pen injectors continues to benefit from
significant growth, while the whole mar-
ket for self-injection systems is changing,
with the increased use of prefilled
syringes and auto-injection devices in
new therapeutic areas.The pen injector
is a cartridge-based device designed for
frequent, usually daily, manual injection
of mainly diabetes or other hormone
replacement therapies.
Auto-injectors automatically insert the
needle and perform the injection and are
usually designed for use with fillable or
prefilled syringes.
Small details are of high importance
Medical personnel increasingly prefer
“ready-to-use” syringes for delivering a
precise dosage of a medication safely
and efficiently. To supply this market,
presterilized syringes are delivered in
sealed plastic containers, or tubs, direct-
ly to the filling and packaging operation,
eliminating the need for cleaning and
heat sterilization. Increasing numbers
of suppliers of presterilized, ready-to-fill
syringes have given this segment a
stronger market share compared to bulk
syringes, which need to be processed
prior to filling. Bosch began serving the
syringe market over 20 years ago and is a
world leader in sterile filling of ampoules,
vials, cartridges and syringes. Bosch is
now the first company to offer all the
production steps, from filling to inspec-
tion to final packaging, which allows our
customers to deliver a safer, and easier
to use, product to end users.
For more information please contact:
Denise Beele
Phone +41 52 674 80 53
* “Pre-filled Syringes Report”, 2005ONdrugDELIVERY
packazine-01-07_Pharma_ENG.indd 4 04.04.2007 16:54:14 Uhr
Maciej Adamkiewicz, owner
and CEO of Adamed
6 | packazine Customers & Markets Pharma und Cosmetic
Take a deep breath Inhaler systems on the march
Whether for the treatment of asthma, chronic bronchitis or diabetes II,
the application areas for inhaler systems are constantly increasing.
The Freedonia Group predicts an annual average growth rate of 11 % to
the year 2010.
Basically, inhaler systems can be
characterized as nebulizers, dry powder
inhalers or metered dose inhalers. For
nebulizers, glass or blow-fill-seal am-
poules are used as the primary package.
On Bosch compact lines, glass ampoules
are cleaned, depyrogenized, filled and
closed, followed by marking, checking
and labelling. Today, environmentally
friendly, mono-material boxes are fre-
quently used for the follow-on secondary
packaging. Bosch has also developed line
solutions for blow-fill-seal ampoules, in
which the ampoules are cut out, individu-
alized and then packaged as flowpacks
and finally into folding cartons.
Metered dose inhalers are assembled
prior to packaging and, with relatively
complex geometry, can present a major
handling challenge. With dry powder
inhalers, there is the additional require-
ment of reliable protection for the
powder dosages. Here, blister-packaged,
hard gelatin capsules, as well as dental
cartridges, are used. These can be
packaged, either individually, or together
with blister trays, on Sigpack Systems’
horizontal bag makers, in hermetically
sealed aluminum laminate bags.
A dry powder inhaler packaging solution
for Novartis, in England, was introduced
in the 2/2006 issue of Packazine. In
this issue we take a look at Adamed of
Poland.
Adamed – a growing company
Founded in 1986, by a family in the
medical profession, Adamed conducts
its own research, as well as developing,
producing and marketing generic and
licensed pharmaceutical drugs. Adamed
is one of the largest pharmaceutical
companies in Poland, with 500 highly
qualified employees and an 88 million
USD turnover.
Besides two factories in its Polish
homeland, Adamed has a site in both
the USA and the Ukraine. The company’s
growth is continuing, with a plant in
Spain already being planned.
One of the core principles at Adamed
is the uncompromising adherence to
packazine-01-07_Pharma_ENG.indd 5 04.04.2007 16:54:20 Uhr
Inhaler and blister in
the packaging machine
– reliably guided for an
efficient and troublefree
production run.
packazine | 7
quality standards. All production is
carried out in accordance with the
requirements of the European Union and
GMP (Good Manufacturing Practice). In
addition, research and development into
new products is an integral part of the
company philosophy. In the last three
years alone, 20 new patents for active
substances and new formulations have
been registered.
Adamed is a partner in many national
health education programs. One of these
is the “Deep Breath” program, which
is concerned with “chronic obstructive
pulmonary disease” (COPD). This pro-
gram provides public education on the
symptoms, causes and consequences of
the disease, as well as offering informa-
tion on the diagnostic and treatment
possibilities.
Inhaler packaging at Adamed
For packaging dry powder inhalers
and blister strips into a folding carton,
Adamed uses a horizontal cartoning
machine from the Bosch CUT series. Cur-
rently, the inhalers are manually placed
on the blister stacks. However, equipped
with seven servo drives, the CUT can be
easily adapted to fit new requirements
and is already set up to accept the
retrofitting of an automatic infeed.
For more information please contact:
Frank Scholl
Phone +49 711 811 57581
packazine-01-07_Pharma_ENG.indd 6 04.04.2007 16:54:38 Uhr
1 Washing machine RRU
2 RABS with glove ports
3 Filling and stopperting station FLP
8 | packazine Customers & Markets Pharma und Cosmetic
Old becomes New
With the updating of two lines, GlaxoSmithKline Biologicals relied on
Bosch Packaging‘s experience of many years. The main focus was to
upgrade and increase the capacity of the new lines.
In 2005, GlaxoSmithKline (GSK)
Biologicals acquired the research and
production facilities of a well-known
pharmaceutical company in the United
States. Among the production equip-
ment, there were two lines for cleaning,
filling and closing of vials which Bosch
Crailsheim (Germany) had delivered
to the United States in 1999. These
lines, however, had never been put into
operation. In order to process its own
products on these lines, GSK Biologicals
needed a competent partner able to
bringing the machines to a technological
state complying with current require-
ments. It was thus self-evident to count
on the experience, which Bosch Packag-
ing Technology in Crailsheim had gained
in many years.
Professional adaptation to new product
range
The upgrading of the first line started
March 2006. Since October 2006 it
has been at a GSK site in Europe. After
having been adapted to the European
voltage system, it was equipped with
new size parts for processing 3 milliliter
vials. The sterilizing tunnel HQL 3480 was upgraded by retrofitting a belt
speed display. Furthermore, a new
turntable infeed was mounted, and the
Distributing an average of 3 million
doses a day, GlaxoSmithKline
Biologicals is one of the world‘s
leading vaccine manufacturers,
employing approximately 6,200
people worldwide. Almost a quar-
ter of its staff work on developing
new safe and effective vaccines.
GlaxoSmithKline Biologicals
packazine-01-07_Pharma_ENG.indd 7 04.04.2007 16:54:43 Uhr
packazine | 9
time-pressure filling system of the filling
and closing machine FLP 4080 was
upgraded. The second line, designed
for its original site in the United States,
is now able to process 3, 10 and 15
milliliter vials for freeze-dried and liquid
products. In addition, a new sterilization
and depyrogenization tunnel HQL 5221S was integrated.
Higher output by upgrade
The RRU 3063 washing machines of
both lines were upgraded to RRU 3084 washing machines. The gripper turret of
the washing machine was extended from
three to four grippers per cycle. As a re-
sult, eight instead of six vials are cleaned
at once. The output was thus increased
from 300 to 400 vials. In addition, the
washing machines were equipped with a
siliconizing station.
Barrier system – restricted sterile room
After the upgrade, both filling lines are
surrounded by a RABS unit (Restricted
Access Barrier System) enabling a pro-
cess, which is mechanically isolated from
the surrounding room. Interventions
into the process are only possible via
integrated gloves.
Reach a common goal
The close cooperation between the
teams of the two companies was a deci-
sive factor for the successful implemen-
tation of the project. All activities were
coordinated by the project managers of
GSK Biologicals and Bosch.
For more information please contact:
Walter Albrecht
Phone +49 7951 402 215
Ñ Competent contacts
Ñ Disassembly of machine at its
present site
Ñ Handling of customs clearance
Ñ Customized upgrade of the line
by experts in Crailsheim
Ñ Qualification and function tests
Ñ Shipment and reassembly
Ñ Validation and commissioning
Ñ Production start-up at customer
Ñ Update of documentation
Ñ Training of operating staff
Advantages of an upgrade by Bosch
1 Washing machine RRU 30842 Siliconizing station3 Sterilizing tunnel HQL 34804 Filling and closing machine with TPFS5 Gross-tare weighing6 BAD discharge7 Time-pressure filling system (TPFS)8 RABS with glove ports
1
23
45
56
7
8
packazine-01-07_Pharma_ENG.indd 8 04.04.2007 16:54:58 Uhr
AFG - stoppering in
continuous motion
principle
Production floor with
three powder lines in
„U-configuration“
10 | packazine Customers & Markets Pharma und Cosmetic
The Portuguese branch of the Jorda-
nian pharmacy company Hikma Phar-
maceuticals PLC choose Bosch for their
new powder filling line, not just for the
machine delivery, but also as a partner
with the same goal: an optimized and
fully functional overall system.
Hikma develops, produces and sells
generic products world wide as licensed
and patented pharmaceuticals. Because
of a production enlargement of a new
antibiotic, they are building a new, highly
modern production space for three new
production lines. The annual output of
the new production lines can go up to 60
million units when fully operational.
Transferring know-how for a perfect
overall system
“We have been giving Bosch access to
our test results, labs and raw materials
so that the production machinery can
be optimized for our needs. Bosch, on
its part, cooperated very closely with
our Engineers and Quality Department
to deliver not only machines, but a fully
functional integrated system”, explained
packazine-01-07_Pharma_ENG.indd 9 04.04.2007 16:55:05 Uhr
Hikma production facility
at Terrugem, Portugal
packazine | 11
Powder manufacturing under optimized aseptic conditions
The filling of sterile powders is a technical challenge,
not just because of the precision filling. For the
continuously sterile process area a special know how
is necessary.
Eng. Amjad Wahbeh, Engineering Direc-
tor for Hikma Portugal . This was the
recipe for success.
Of great importance to Hikma was a
simple, compact and practical solution
for the most sensitive area within the
sterile area: the filling area. Bosch was
able to meet this challenge, and convince
Hikma, with the new Bosch powder
filling machine. The slim machine design
offers the best conditions for lengthy fill-
ing campaigns with short down periods
and low maintenance efforts. Format
changes and cleaning of the machine can
be easily accomplished because of the
simple disassembly and aseptic reassem-
bling of the machine parts. In addition
to this, the AFG 3020 is constructed for
space saving wall mount installation,
exactly as Hikma desired.
Innovative closure
With the new Bosch solution, not only
can Hikma use conventional aluminum
caps but the innovative Monovial®
closure can additionally be used. This
new closure makes it easier for medical
packazine-01-07_Pharma_ENG.indd 10 04.04.2007 16:55:10 Uhr
1
Placing of the
Monovial® closures
2
AFG – module
for sterile air supply
1 2
12 | packazine Customers & Markets Pharma und Cosmetic
staff to prepare the filled powder for
infusion applications. This new closure
incorporates an attached needle, thru
which the filled powder can be mixed
with an infusion liquid (such as infusion
bag). The Monovial® closure minimizes
any non-sterile contact during the mixing
of the infusion bag, making it a very
desirable system to use.
Strict internal guidelines for the good
of the patient
Sterility is strictly required in phar-
maceutical production. In addition to
government standards, internal company
guidelines are followed to insure the
proper quality of the pharmaceutical
product.
It was important to Hikma to have an
absolute safe LF (laminar flow) system.
An LF system that would remain running
even during cleaning for product change
(such as cleaning of the air return duct-
ing) and even during a loss of power,
because a shut down for even a few
seconds of the LF system would mean
that the whole sterile area would need to
be re-sterilized. Because of this, Bosch
developed a special air recirculation
system for Hikma with two separate
return channels to maintain sterility
during cleaning and maintenance of the
machine .
Mock-Up: A gaze says more then
thousand words
Before construction and assembly began,
Hikma was able to interact with the
system at Bosch Crailsheim. The “mock-
up”, a true to scale replica, has proved
itself as a very useful option in the layout
of many projects. Not only the filling and
closing machines, with their dust safe
panels and glove ports, but the sterile
room wall and it’s windows were rede-
signed for Hikma. The realistic simulation
helped to optimize the line early and to
clearly show process planning and insure
the success of the overall project.
“For us that was something complete
new”, said Amjad Wahbeh. “Bosch liter-
ally forced us to decide to use a mock-up,
and I have to admit that we saw the
advantage of it very quickly. Mistakes
in the planning, and even the better
solutions, we were literally able to touch.
From my point of view, the mock-up was
one of the best investments we made.”
The evolution of this project and the final
results have proved themselves; and for
the future, Hikma is very interested in
an intensive business relationship with
Bosch.
For more information please contact:
Dieter Bandtel
Phone +49 7951 402 362
packazine-01-07_Pharma_ENG.indd 11 04.04.2007 16:55:12 Uhr
Robot Handling of
BLS Syringes
packazine | 13
Throughput counts
For the first time, a fully integrated ro-
botics system allows the comprehensive
testing of complex coating formulae,
from raw material formulation right
through to the finished coating product.
BASF is ranked among the leading
chemical companies in the world. In or-
der to maintain its worldwide leadership
in the chemical coatings sector, the BASF
business unit, “Performance Chemicals”,
uses the innovative High Throughput
Screening technique for formulation and
coating applications.
Wide range of coatings
During the optimization of coating
raw materials and the investigation
of structural relationships in coating
formulations, a great variety of different
solid and liquid feedstock must be mixed,
or dispersed, and, if necessary, also
standardized in terms of solid content,
viscosity or pH value. A wide range of
coating systems need to be tested and
this would not be possible without the
syringe dosing system developed by
Bosch Lab Systems (BLS).
Reproducible production of test panels
For the investigation of product proper-
ties, newly developed coatings must
be reproducible and industrial-quality
coatings applied to test panels or other
substrates. Alongside classical doctor
blade technology, the BLS-developed
spray procedure (winner of the “2005
Color and Coating Prize”) is also used.
The subsequent hardening of the coating
film takes place directly in the unit,
either thermally or by ultraviolet radia-
tion.
Fast and objective testing
For BASF and its customers, the quick
availability of detailed and meaningful
test results is important. For this reason,
many established testing methods, such
as the measurement of color, gloss or
Bosch Lab Systems
and BASF develop
ultramodern, high
throughput screening
systems for coating
development
packazine-01-07_Pharma_ENG.indd 12 04.04.2007 16:55:16 Uhr
14 | packazine Customers & Markets Pharma und Cosmetic
layer thickness, have been integrated
into the system. New automation tech-
niques, for the determination of scratch
or chemical resistance, were jointly
developed by Bosch and BASF.
High capacity
The modular design of the system and
the simultaneous processing of several
production steps allow up to a 100 dif-
ferent coating systems to be processed
within a short period of time. For the
first time, one system integrates innova-
tive dosing, application and measuring
techniques, as well as process control,
and permits the targeted production,
application and hardening of coatings, as
well as the fully automatic determination
of the coating characteristics. Due to
the modular design and the robustness
of the modules, this flexible system can
also be used in other application areas,
such as the development of adhesive
materials, detergents, cosmetics or
pharmaceuticals. The new system is cur-
rently being installed in Ludwigshafen,
Germany, by BASF, together with Bosch
employees, and will be available during
the year to BASF‘s internal and external
customers.
Bosch Lab Systems develops and very
successfully markets high throughput
technologies and laboratory automation
for the efficient and fast development of
new materials and formulations. An em-
phasis is placed on the implementation
of customized development processes
that provide industrial-quality, highly flex-
ible and modular automation solutions.
For more information please contact:
Dr. Thomas Brinz
Phone +49 711 811 58001
Dr. Roland Emmerich
Phone +49 711 811 58008
High Througput-System for Formulations Typical BLS-Syringes
packazine-01-07_Pharma_ENG.indd 13 04.04.2007 16:55:25 Uhr