pack azine PHARMA · Issue 01/2009 Axellia | Filling first, packaging after Sanofi-Aventis | Ultimate quality control Bayer | Turnkey system solution for Aspirin® Effect
packazinePHARMA · Issue 01/2009
Axellia | Filling first, packaging afterSanofi-Aventis | Ultimate quality controlBayer | Turnkey system solution for Aspirin® Effect
2 | packazine Table of contents | Editorial
www.boschpackaging.com [email protected]
News
Facts & Trends
04 Interdisciplinary knowledge exchange for pharmaceutical packaging and processing
06 Meeting the challenges of an ageing population
Customers & Markets
Pharma & Cosmetic
08 Axellia | Filling first, packaging after
12 Pharmatec | New fermenter for multipurpose use in pilot plant stations
14 Sanofi-Aventis | Ultimate quality control through 100% control
16 Bayer | The classic Aspirin® gets a makeover
Events
18 Events Pharma 2009
Cover
Aspirin® Effect – packed in a
convenient stick pack
06 08
Tableof contents
packazine | 3
Dear Readers,
A look back on last year shows that we were extremely successful. In 2008, our as-
sociates generated sales of around 700 m Euros, which represented a sales increase
of around eight percent. This powerful development makes us proud
and underlines our technological leadership position. Above all,
however, it is firm proof of our customers’ trust.
Long-term customer trust is important to us. In particular, in difficult
economic times, Bosch is a reliable partner. As a one-stop shopping
supplier, we offer solutions along the whole value added chain and
provide the highest safety, flexibility and optimal total cost of owner-
ship.
We are happy to personally convince you of our know-how and look forward to seeing
you at Achema 2009, in Frankfurt. In hall 3.1, we will show you tried and tested and
forward-looking solutions from five areas of competence: processing technology,
primary and secondary packaging, qualification and services. It is not just our stand
at the exhibition that will be impressive. Our lectures at the Achema conference are
not to be missed either and will include informative presentations such as “Medical
Confectionery – medicine packed into sweets” and an analysis of “Bio-decontamina-
tions and their influence on production processes”.
In preparation for Achema, we present some interesting customer projects in this
edition of “packazine”. You will also find important information relating to trends and
their influence on the packaging industry.
We look forward to continuing our successful partnerships with you.
I hope you enjoy the reading,
Friedbert Klefenz
12 16
Friedbert Klefenz
President
Bosch Packaging
Technology
Editorial
4 | packazine News Facts & Trends
Under the Bosch umbrella, the pharma-
ceutical businesses comprise of product
brands such as Moeller & Devicon,
Pharmatec, SBM Schoeller-Bleckmann
Medizintechnik, Sigpack Systems and Va-
licare. United, we serve customers in the
pharmaceutical and biopharmaceutical
industry.
The individual strengths of the group,
with sites across the globe, account
for Bosch’s position as a global leader
with one of the most comprehensive
technology and service portfolios in the
industry. The interdisciplinary approach
of Bosch directs an international
network of engineers to optimize project
execution and integration processes for
customers.
The company’s strengths can be divided
into five key areas of competence:
process technology, primary packaging,
secondary packaging, qualification and
services.
Pharmaceutical manufacturers around the world consistently turn
to Bosch Packaging Technology for innovations in packaging and
processing technology. They benefit from decades of expertise and
knowledge in optimizing production processes and safety, enhancing
efficiency and reducing total lifetime costs.
Interdisciplinary knowledge exchange for pharmaceutical packaging and processing
Bosch Packaging Technology
Moeller & Devicon | Pharmatec |
SBM Schoeller-Bleckmann Medizin-
technik | Sigpack Systems | Valicare
Visit us in Hall 3.1, Stand F2 – J11.
For more information please visit www.boschpackaging.com
12th May 2009, 3.30 pm, Konstant Forum:
Influence of Humidity, Concentration and Condensation on Efficacy and Penetration in
Bio-Decontamination Processes Applying H2O2 Vapor
12th May 2009, 4.30 pm, Konstant Forum:
Electron Beam Sterilization of Tubs with Nested Syringes – Challenges and Innovation
12th May 2009, 5 pm, Agenda Forum:
Medicated Confectionery – Technological Challenges and Solutions
14th May 2009, 10.30 am, Illusion 3, CMF:
Image Processing as Useful Technology in the High-Throughput Analysis of Formulations
and Coatings
Come and experience Bosch at the ACHEMA convention. Visit our lectures.
packazine | 5
} Process Technology
Bosch’s process technology expertise
combines aseptic and sterile processing,
which includes equipment, container and
product sterilization, isolator systems
and restricted access barrier systems
(RABS). Equipment for clean facilities
that produce, store and distribute
sterile and aseptic products complete
the portfolio to serve customers from
biopharmaceutical to medical device
industries. Furthermore Bosch offers
production and forming lines for medi-
cated confectionery and other formable
masses.
} Primary Packaging
Primary packaging is an essential area of
Bosch’s competence and is a key pillar
of its portfolio. Check weighing, sterile
filling and finishing equipment, blister
packaging, capsule filling and sealing
are at the core of its expertise. The
application portfolio contains filling and
sealing for ampoules, bottles, cartridges,
injection and infusion bottles as well as
injection vials and pre-filled syringes.
} Secondary Packaging
For secondary packaging, Bosch offers
cartoning and toploading systems,
flow wrapping machines with hermetic
sealing, and end-of-line packaging equip-
ment. This product range enables custo-
mers to work with Bosch from primary
packaging to end-of-line applications.
} Qualification
Part of Bosch’s full service offering also
includes qualification and validation
services for laboratory equipment as
well as manufacturing processes for
pharmaceutical, biopharmaceutical
and life science applications. To meet
international qualification requirements,
Bosch ensures that its customers meet
Good Manufacturing Practice standards,
ensuring smooth and safe production
processes.
} Services
Bosch is a committed partner throughout
the entire product lifecycle, offering
reliable after-sales, audit, and mainte-
nance services. The superior training
standard of our engineers ensures the
latest in quality service products, such
as the Embedded Engineers program to
maximize the availability of production
equipment. Bosch Packaging Services
is determined to meet future market
requirements to reduce total cost of
ownership and protect capital equipment
investments.
Our Promise
Bosch Packaging Technology’s promise
is to continue its leadership role in the
pharmaceutical industry with innovative,
reliable and economical solutions.
Bosch’s overall objective and driving
force is enabling customers to get one-
stop-solutions and create sustainable
business growth through state-of-the-art
services, processing and packaging
technology.
For more information please contact:
Inga Strobel
Phone +49 7951 402 648
6 | packazine News Facts & Trends
One of the challenges that impacts
our business is the ageing population.
The social phenomenon recognized as
the “graying” of Europe, according to
the research of William H. Frey of the
Brookings Institution think tank, stems
from the finding that the median age in
Europe will increase from 37.7 years old
in 2003 to 52.3 years old by 2050. These
figures are especially significant in terms
of the future percentage increase of
Europe‘s elderly population relative to its
workforce.
The phenomenon itself is strongly con-
nected to a higher life expectancy, which
is, going one step back in this process,
related to better medication and phar-
maceuticals. Better formulas, ingredients
and substances in pharmaceuticals have
led to people having healthier and longer
lives. There are also changes in the ways
that an ageing population purchases,
consumes and chooses its lifestyle.
Besides product pricing, product quality
or method of recycling, the consumption
of a consumer good will become more
heavily reliant on new ways of presenting
convenience of use. The average elderly
consumer will be the main target for
the consumer products industry and,
especially the Western World, will have
enough money to afford a convenience
lifestyle. The drive for more “conven-
ience for the grey” in combination with
further essential features will define
general product design from dosage to
usage.
The steadily increasing demand for self
and home medication will challenge
both brand owners and their suppliers.
New designs for the more convenient
use of pharmaceuticals are needed. But
how will this develop in combination
with child resistance, dosage form or
production efficiency? Is it possible to
design convenient packaging for elderly
people, which is, at the same time, child
resistant?
Products such as Burgopak are typical of
highly convenient packaging styles. They
support patient compliance and are child
resistant at the same time. Other new
applications, such as those that combine
confectionery products (Conf-Med) with
active pharmaceutical ingredients (API),
packazine | 7
Meeting the challenges of an ageing population
As one of the leading suppliers to the pharmaceutical packaging and
processing industry, we are committed to meeting future challenges
and satisfying changing market demands for our customers to help
them prosper in an increasingly competitive environment.
may represent future dosage forms and
will challenge producers to find new and
effective processing and packaging.
Maybe the blister package will undergo
a renaissance. In particular, for ap-
plications that require daily intake for a
period of weeks, such as birth control or
antibiotics, the well-proven blister still
represents state-of-the-art packaging. For
long-term medication with a standard
assortment of tablets and capsules, the
weekly blister could be a solution for
mass market applications.
More than ever, experience and innova-
tion are the tipping points. For research
and production, the pharmaceutical
industry relies on its suppliers and
partners to provide consumers with the
“all-in-one package”. Such relationships
are essential for success and survival.
The scientists and engineers at Bosch
Packaging Technology are already
working today on solutions for the next
decades. Together with our customers,
we develop technologies and partner-
ships to give the “graying” of Europe a
colorful future.
For more information please contact:
Ulrike Probst
Phone +41 52 674 8053
2000
37.7 years
52.3 years
2010 2020 2030 2040 2050
Development of the European median age
Delivery and loading of
the empty vials to the
compact line in the wash-
ing room
1 The filling machine is integrated into the separation
wall between clean room and washing room
2 The FLC vial filling machine is equipped with an
automatic non destructive checkweighing system
3 Clear separation of machine operation and
checkweighing analysis with 2 panels
8 | packazine Customers & Markets Pharma and Cosmetic
1 2 3
packazine | 9
Axellia is the leading producer of fermented, anti-infective, active
pharmaceutical ingredients (API) and injectable finished products.
Looking to expand its manufacturing capacity for injectables, the
company turned to Bosch Packaging Technology for a compact
injectables filling line solution with integrated end-of-line secondary
packaging.
Filling first, packaging after
Fully automated filling
In order to meet its customers’ diversi-
fied requirements, Axellia recently began
producing dosage forms of APIs in
injectables. This enables the company to
offer both raw APIs as well as finished
products in an injectable format.
Axellia’s existing filling line for injecta-
bles was exclusively devoted to powder
filling, which was limited to only a few
API products. To expand capacity for fin-
ished injectables and extend its portfolio
to different API products, Axellia sought
a liquid filling solution with sterile
processing and lyophilization capabilities.
Due to the unstable nature of certain API
products, they must be freeze-dried into
a dry powder form, after being filled into
injectable vials, to ensure a reasonable
shelf life of the finished product.
Axellia ordered a complete filling line
from Bosch in the summer of 2007,
consisting of a washing machine, sterili-
zation tunnel, filling and sealing machine,
and an overseal capping machine. To
meet the unique requirements of this
project, Bosch delivered the FLC 3080
filling and sealing machine, which
offers time-pressure filling, automatic
cleaning-in-place (CIP) and sterilizing-in-
place (SIP) systems, and an automatic
checkweighing system.
The time-pressure filling system was
selected instead of the traditional pump
filling station because it is easier to
1 2
10 | packazine Customers & Markets Pharma and Cosmetic
validate the CIP and SIP process. There
are less mechanical parts in the time-
pressure filling system compared to the
pump filling system, which minimizes
maintenance and offers an easier clean-
ing and sterilization process.
The automatic CIP/SIP system offers
major benefits to Axellia. Firstly, it covers
the in-line integrated sterilizing filter so
there is no need to dismantle the system.
The system also complies with GMP
regulations, minimizing production times
and eliminating the danger of product
contamination.
Automated checkweighing
The fully automated, non-destructive
checkweighing in-process control system
ensures the best product quality control.
The filling machine runs on an eight-hour
shift at a speed of 300 vials per minute.
The check weighing system controls eight
random samples every three minutes
and incorrect dosage amounts are
automatically rejected without process
interruptions. At the same time, the
checkweighing system gives real-time,
in-process feedback to the time-pressure
filling to ensure accurate dosing. This
fully automated system reduces the
necessity of having quality insurance
engineers on site, thus reducing labor
costs and minimizing the total cost of
ownership.
Uniquely for Axellia, the checkweighing
in-process control offers a tracking
system, designed by Bosch engineers
in cooperation with the supplier of
the freeze driers. This tracking system
provides direct communication between
the filling machine, the freeze driers and
the capping machine, which ensures that
incorrect vials are automatically rejected,
even after the freeze-drying process.
The whole automatic process and com-
munication gives Axellia further quality
assurance.
3 4
1 Axellia vial packaging line
2 Bosch horizontal cartoner
type CUC 2001
3 Carton erection system with
counter vacuum
4 Online carton printing and
verification
packazine | 11
Whole-line integration
When Bosch delivered the complete
filling line in the summer of 2008, the
project manager at Axellia, Mr. Knud-E
Andersen, was impressed with the
on-time delivery and the overall quality
of the system. At the same time, he was
also looking for an end-of-line secondary
packaging solution to package the vials
into cartons. As a result, Axellia again
turned to Bosch for a solution.
For the end-of-line packaging, Axellia
needed a labeling machine, a turntable,
a cartoning machine, checkweigher,
stretch bander and a case packer.
However, Axellia didn’t want to source
these individual modules from different
suppliers. Bosch was able to offer a
customized, one-stop-shopping solution
by sourcing the labeling machine, stretch
bander and case packer from outside
vendors and integrating them with its
own cartoning machine and checkweigh-
ing unit. Thus, Bosch provided Axellia
with a complete end-of-line packaging
solution together with on-site installation
and support.
The CUC cartoning machine from Bosch
offers excellent accessibility. The
servo technology, industrial PC control
systems and the ergonomic touch screen
operating panel provide secure, reliable
and trouble-free production runs. The
product insertion, from the back of the
machine, significantly reduces mainte-
nance time and allows easier cleaning
and trouble-shooting. The encapsulation
of the drive components and the slanted
guards considerably reduce the time
required for line clearance.
The modular KWE 4000 checkweighing
system meets pharmaceutical safety
and cGMP requirements, as well as
offering simple operation and easy
line integration. The control cabinet
at the rear of the checkweigher and
the operator terminal allows excellent
accessibility. Production statistics, trend
curves and current weight are displayed
on the standard screen, which can be
configured to show further information
if required. The weight display can be
changed to large numbers for at-distance
reading by one single touch on the
screen.
From fully automatic filling lines to
customized cartoning lines, Bosch has
provided Axellia with highly reliable
machine quality, easier validation proc-
esses and excellent customer service.
The exceptional level of Bosch’s service
and support has also given Axellia the
convenience of interacting with only
one supplier and makes the whole line
integration and validation process easier.
As a result, Mr. Knud-E Andersen has
been generous in his praise for Bosch
and said: “I have had a good experience
with Bosch. We believe in Bosch, that’s
why we buy it from Bosch.”
For more information please contact:
Klaus Schreiber
Phone +49 7951 402 367
Ralph Pfister
Phone +49 711 811 57 293
12 | packazine Customers & Markets Pharma and Cosmetic
With its many years of experience in the
production of pharmaceutical process
systems, Pharmatec, a Bosch Packaging
Technology company, offers tailor-
made solutions for the fermentation of
microorganisms. Pharmatec is known
throughout the pharmaceuticals industry
for its high-purity media production
systems, plus process and CIP systems.
The development of bioreactors and
their relevant upstream and downstream
processes will be increasingly pushed
forward by Pharmatec in the future.
To create the optimum environment for
live cells and bacteria, the challenge
lies in designing systems which firstly
offer conditions under which the desired
organisms can grow optimally and
secondly meet the high cGMP regulation
standards prevalent in the pharmaceuti-
cals industry.
In the pharmaceutical industry,
the production of complex-
structured active substances,
or biocatalysts, using biotech-
nological methods has been
increasing in significance for a
number of years.
packazine | 13
The success of such a project is
dependent on a number of technical and
biological process details. Diverse pro-
cess parameters, such as the pH value,
oxygen content, foam formation and tem-
perature control plus their time lapses,
have to be constantly monitored and
corrected throughout the entire fermen-
tation process in case deviations arise.
Perfectly coordinated measurement and
control technology is therefore essential
for successful cultivation. More extensive
deviations from the specifications may
significantly impair the process and,
under certain circumstances, render an
entire batch useless.
Last year, a well known pharmaceu-
tical company based near Frankfurt
commissioned Pharmatec to supply a
fermentation system to investigate long-
term cultivation involving streptomyces,
filamentous fungi, bacteria or yeasts for
the production of natural substances or
recombinant proteins. Different proce-
dures, such as the batch or fed batch
process and scale-up trials, were to be
tested. Various demands were also made
concerning CIP cleaning, continuous
sterilization capability and the tempera-
ture control of the unit. The specialist‘s
innovations and wealth of ideas were
required to achieve this. Together with
the customer, the Pharmatec team deve-
loped a concept which was successively
implemented within seven months in
Dresden. After commissioning and a
successful Factory Acceptance Test by
the customer, the system was installed
precisely in its target location, started
up and transferred to the customer
following IQ and OQ.
The first trial for the new system was a
long-term sterility test called media-run.
Following full sterilization of the system,
complete fermentation is undertaken
with all of the media. Inoculation with
a cultivated strain additionally took
place. The sterile tests were verified with
outstanding results. The requirements
made on the fermenter were optimally
met and the Site Acceptance Test was
also successfully completed. Commissi-
oning of the Pharmatec bioreactor was
therefore judged to be an unqualified
success. Further operation of the system
under production conditions proceeded
to our customer‘s satisfaction.
For more information please contact:
Sonnhild Fleischer
Phone +49 351 28 27 819
New fermenter for multipur-pose use in pilot plant stations
Fermentation system – various perspectives
1 GKF 1400 ASB 100% 2 Operator setting up
the machine
3 Empty capsule control
with ejection
4 Online documentation of
product quality 1 2
14 | packazine Customers & Markets Pharma and Cosmetic
Sanofi-Aventis, a leading global
pharmaceutical company, provides a
broad range of medicines, vaccines and
integrated healthcare solutions.
To produce oral forms of quality clinical
trial samples, the company was looking
for a flexible capsule filling solution for
a variety of product formats. Having
worked closely with Bosch Packaging
Technology for many years, it decided
to invest in a new GKF compact
machine that offered 100 % check
weighing.
Solution for small batch clinical trials
During the clinical trial phase of the drug
development process, it is important for
Sanofi-Aventis R & D to provide different
dosage forms to its patients. Additionally,
a diverse range of dosage formats gives
Sanofi-Aventis R & D the flexibility and
reactivity to supply on time with the
required quality medicines for clinical
trials. In order to produce small batches
of clinical trial samples, Sanofi-Aventis
required a flexible machine for a large
variety of capsule formats, including
liquid capsules, powder in capsules,
pellet capsules, and even tablets in
capsules. Having worked with Bosch for
the last 20 years, the product manager,
Mr. Luc-Andre Claustres, decided to try
the GKF 1400 ASB 100% (automatic
trouble shooting) machine, for its precise
and innovative filling of powders, pellets
and micro-tablets and liquids.
Improved quality control
The major benefit that Sanofi-Aventis
receives from the new GKF 1400 ASB 100% machine is the high degree of
quality control. This is key for clinical
trial samples, with the correct weight
and dosage of each unit ensuring accu-
rate results. Also, since the trial product
is very expensive and there is often no
spare product for a second batch run,
the machine needs 100 % quality control
prior to the filling process for both empty
capsules and product amounts.
Ultimate quality control through 100 % control
3 4
packazine | 15
The GKF 1400 ASB 100% machine
ensures 100 % weight control. Each
capsule is weighed individually and with
high precision on the integrated control
unit. The filling station readjusts the
integrated weight regulation system for
pellets and powder applications. This
ensures that the dosing weight is within
the required tolerance limits throughout
the production process. Software
generates a mean value and constantly
compares the actual value with the
target value. All dosing changes are
documented in the production report to
ensure regulatory compliance and any
capsules outside of the tolerance range
are dependably ejected.
Increased productivity
Fast changeovers and short cleaning
times have improved the production
speed. With the GKF 1400 ASB 100%
filling 80,000 capsules per hour, com-
pared to the 40,000 capsules per hour
machines used previously, Sanofi-Aventis
R&D is now able to manufacture a full
batch in only a few days. “It saves time
while maintaining a high degree of qual-
ity control,” says Luc-Andre Claustres.
“It’s a pleasure to work with Bosch, and
I am very satisfied with the quality of
the machine. From documentation, to
risk analysis, functional analysis, and
isolation qualification, it provides an
unprecedented level of quality which
makes the qualification and validation
process on our behalf much easier.”
For more information please contact:
Thomas Ripke
Phone +49 711 811 57527
Aspirin® Effect is a convenient
solution as it can be taken without
water. It dissolves quickly in the
mouth and has a pleasant taste
16 | packazine Customers & Markets Pharma and Cosmetic
RAD-10 stick pack machine
packazine | 17
New form and packaging style
Still a registered trademark in over 80
countries, Aspirin® has been around for
over a century and is universally known
in its tablet form. The introduction of
Aspirin® Effect has seen the classic
tablet become available in a granulated
form that is taken without the need to
dissolve in water and comes packaged in
stick packs. The stick pack itself has an
incision, which makes it easy and safe to
tear open. To guarantee optimal access
to the product, the longitudinal seam is
positioned at the edge, which results in
an enlarged opening cross-section. This
ensures not just easy opening but also
quick and safe emptying of the package.
Aspirin® Effect is sold in award-winning
folding cartons, used exclusively by Bayer
and containing 10 or 20 stick packs.
The project
Ever since its launch in 2004, Aspirin®
Effect has enjoyed increasing sales.
Following large increases in demand, a
new packaging line was introduced in
2008.
Apart from a compact design and high
output levels, Bayer‘s priorities were
adherence to project schedules and,
above all, technological safety. Also
having to be taken into consideration
was the fact that Aspirin® Effect is a
highly moisture-sensitive product and
demands high impermeability levels for
its primary packaging.
To ensure optimum performance of the
entire line, it is vital to provide highly
efficient interfaces between primary
packaging, transportation/grouping and
secondary packaging. A “one-stop shop-
ping” system is the ideal solution and, in
this respect, Bosch has full responsibility
for project handling and guarantees the
efficiency of the system.
The classic Aspirin® gets a makeoverAt its plant in Bitterfeld, Germany, Bayer HealthCare AG produces Aspirin® for a number of applications
and in various dosages. In order to extend production capacity for its Aspirin® Effect product, the installa-
tion of a highly efficient packaging system from Bosch Packaging Technology is scheduled for 2009. This
system solution provided by Sigpack Systems in Beringen (Switzerland) and Bosch Packaging Technology
in Waiblingen (Germany) will achieve output levels of 1000 Stick Packs and 100 cartons per minute.
Working principle
stick pack system
RAD10 / CUT120
18 | packazine Customers & Markets Pharma and Cosmetic
The equipment
The packaging system consists of the
10-track Stick-Pack-RAD-10, which is a
transportation and grouping unit, and
a horizontal cartoning machine, the
CUT-120.
The RA Stick Pack machine is fitted with
a tipping filler, which achieves output
levels of 1000 stick packs per minute.
This dosage technology, used primarily
for free-flowing products, offers highly
accurate dosing, careful product han-
dling and excellent accessibility.
Stick pack transportation, grouping
and stacking are areas in which Bosch‘s
experience with handling fast-moving
consumer goods and stick packs comes
to the fore. All interfaces are designed
with efficiency and safety in mind. For
handling the special Aspirin® gable
carton, a variation of the well-proven
intermittent CUT-120 cartoning machine
is used. Achieving 100 cycles per minute,
stacks of five stick packs and an informa-
tion leaflet are inserted into the carton,
which is then sealed with hot glue.
This tailor-made CUT for gable cartons
exemplifies Bosch‘s customer-specific
approach to engineering.
Following the validation process, produc-
tion of the RAD-10 / CUT-120 Stick Pack
system will start, for eventual delivery
to the various sales regions. Thanks to
the close cooperation and partnership of
Bayer and Bosch PA project teams, and
following a tight production schedule,
another packaging system by Bosch
Packaging Technology will be ready to be
put into operation.
For more information please contact:
Holger Botsch
Phone + 41 52 674 89 28
Cartoning machine CUT120