Axellia | Filling First, Packaging After Sanofi-Aventis | Ultimate Quality

packazine PHARMA · Issue 01/2009

Table of contents 06 08

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

www.boschpackaging.com [email protected] packazine | 3

Editorial 12 16

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 Friedbert Klefenz economic times, Bosch is a reliable partner. As a one-stop shopping President Bosch Packaging supplier, we offer solutions along the whole value added chain and Technology provide the highest safety, flexibility and optimal total cost of ownership.

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 4 | packazine News Facts & Trends

Interdisciplinary knowledge exchange for pharmaceutical packaging and processing

Pharmaceutical manufacturers around the world consistently turn Under the Bosch umbrella, the pharma- to Bosch Packaging Technology for innovations in packaging and ceutical businesses comprise of product brands such as Moeller & Devicon, processing technology. They benefit from decades of expertise and Pharmatec, SBM Schoeller-Bleckmann knowledge in optimizing production processes and safety, enhancing Medizintechnik, Sigpack Systems and Va- efficiency and reducing total lifetime costs. 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 Come and experience Bosch at the ACHEMA convention. Bosch Packaging Technology Visit our lectures. Moellerof Bosch & Devicon directs | Pharmatec an | international SBMnetwork Schoeller-Bleckmann of engineers Medizin- to optimize project technik | Sigpack Systems | Valicare 12th May 2009, 3.30 pm, Konstant Forum: execution and integration processes for Influence of Humidity, Concentration and Condensation on Efficacy and Penetration in customers. 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 The company’s strengths can be divided into five key areas of competence: 12th May 2009, 5 pm, Agenda Forum: Medicated Confectionery – Technological Challenges and Solutions process technology, primary packaging, secondary packaging, qualification and 14th May 2009, 10.30 am, Illusion 3, CMF: Image Processing as Useful Technology in the High-Throughput Analysis of Formulations services. and Coatings

Visit us in Hall 3.1, Stand F2 – J11. For more information please visit www.boschpackaging.com packazine | 5

} Process Technology } Secondary Packaging maximize the availability of production Bosch’s process technology expertise For secondary packaging, Bosch offers equipment. Bosch Packaging Services combines aseptic and sterile processing, cartoning and toploading systems, is determined to meet future market which includes equipment, container and flow wrapping machines with hermetic requirements to reduce total cost of product sterilization, isolator systems sealing, and end-of-line packaging equip- ownership and protect capital equipment and restricted access barrier systems ment. This product range enables custo- investments. (RABS). Equipment for clean facilities mers to work with Bosch from primary that produce, store and distribute packaging to end-of-line applications. Our Promise sterile and aseptic products complete Bosch Packaging Technology’s promise the portfolio to serve customers from } Qualification is to continue its leadership role in the biopharmaceutical to medical device Part of Bosch’s full service offering also pharmaceutical industry with innovative, industries. Furthermore Bosch offers includes qualification and validation reliable and economical solutions. production and forming lines for medi- services for laboratory equipment as Bosch’s overall objective and driving cated confectionery and other formable well as manufacturing processes for force is enabling customers to get one- masses. pharmaceutical, biopharmaceutical stop-solutions and create sustainable and life science applications. To meet business growth through state-of-the-art } Primary Packaging international qualification requirements, services, processing and packaging Primary packaging is an essential area of Bosch ensures that its customers meet technology. Bosch’s competence and is a key pillar Good Manufacturing Practice standards, of its portfolio. Check weighing, sterile ensuring smooth and safe production For more information please contact: filling and finishing equipment, blister processes. Inga Strobel packaging, capsule filling and sealing Phone +49 7951 402 648 are at the core of its expertise. The } Services [email protected] application portfolio contains filling and Bosch is a committed partner throughout sealing for ampoules, bottles, cartridges, the entire product lifecycle, offering injection and infusion bottles as well as reliable after-sales, audit, and mainte- injection vials and pre-filled syringes. nance services. The superior training standard of our engineers ensures the latest in quality service products, such as the Embedded Engineers program to 6 | packazine News Facts & Trends

One of the challenges that impacts The phenomenon itself is strongly con- general product design from dosage to our business is the ageing population. nected to a higher life expectancy, which usage. The social phenomenon recognized as is, going one step back in this process, the “graying” of Europe, according to related to better medication and phar- The steadily increasing demand for self the research of William H. Frey of the maceuticals. Better formulas, ingredients and home medication will challenge Brookings Institution think tank, stems and substances in pharmaceuticals have both brand owners and their suppliers. from the finding that the median age in led to people having healthier and longer New designs for the more convenient Europe will increase from 37.7 years old lives. There are also changes in the ways use of pharmaceuticals are needed. But in 2003 to 52.3 years old by 2050. These that an ageing population purchases, how will this develop in combination figures are especially significant in terms consumes and chooses its lifestyle. with child resistance, dosage form or of the future percentage increase of Besides product pricing, product quality production efficiency? Is it possible to Europe‘s elderly population relative to its or method of recycling, the consumption design convenient packaging for elderly workforce. of a consumer good will become more people, which is, at the same time, child heavily reliant on new ways of presenting resistant? convenience of use. The average elderly consumer will be the main target for Products such as Burgopak are typical of the consumer products industry and, highly convenient packaging styles. They especially the Western World, will have support patient compliance and are child enough money to afford a convenience resistant at the same time. Other new lifestyle. The drive for more “conven- applications, such as those that combine ience for the grey” in combination with confectionery products (Conf-Med) with further essential features will define 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 weekly blister could be a solution for working today on solutions for the next will challenge producers to find new and mass market applications. decades. Together with our customers, effective processing and packaging. we develop technologies and partner- More than ever, experience and innova- ships to give the “graying” of Europe a Maybe the blister package will undergo tion are the tipping points. For research colorful future. a renaissance. In particular, for ap- and production, the pharmaceutical plications that require daily intake for a industry relies on its suppliers and For more information please contact: period of weeks, such as birth control or partners to provide consumers with the Ulrike Probst antibiotics, the well-proven blister still “all-in-one package”. Such relationships Phone +41 52 674 8053 represents state-of-the-art packaging. For are essential for success and survival. [email protected] long-term medication with a standard The scientists and engineers at Bosch assortment of tablets and capsules, the Packaging Technology are already

Development of the European median age 52.3 years

37.7 years

2000 2010 2020 2030 2040 2050 8 | packazine Customers & Markets Pharma and Cosmetic

1 The filling machine is integrated into the separation wall between clean room and washing room Delivery and loading of 2 The FLC vial filling machine is equipped with an the empty vials to the automatic non destructive checkweighing system compact line in the wash- 3 Clear separation of machine operation and ing room checkweighing analysis with 2 panels packazine | 9

Filling first, packaging after

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.

Fully automated filling injectable vials, to ensure a reasonable In order to meet its customers’ diversi- shelf life of the finished product. fied requirements, Axellia recently began producing dosage forms of APIs in Axellia ordered a complete filling line injectables. This enables the company to from Bosch in the summer of 2007, offer both raw APIs as well as finished consisting of a washing machine, sterili- products in an injectable format. zation tunnel, filling and sealing machine, and an overseal capping machine. To Axellia’s existing filling line for injecta- meet the unique requirements of this bles was exclusively devoted to powder project, Bosch delivered the FLC 3080 filling, which was limited to only a few filling and sealing machine, which API products. To expand capacity for fin- offers time-pressure filling, automatic ished injectables and extend its portfolio cleaning-in-place (CIP) and sterilizing-in- to different API products, Axellia sought place (SIP) systems, and an automatic a liquid filling solution with sterile checkweighing system. processing and lyophilization capabilities. Due to the unstable nature of certain API The time-pressure filling system was products, they must be freeze-dried into selected instead of the traditional pump a dry powder form, after being filled into filling station because it is easier to

1 2 3 10 | packazine Customers & Markets Pharma and Cosmetic

1 2

validate the CIP and SIP process. There Automated checkweighing costs and minimizing the total cost of are less mechanical parts in the time- The fully automated, non-destructive ownership. pressure filling system compared to the checkweighing in-process control system pump filling system, which minimizes ensures the best product quality control. Uniquely for Axellia, the checkweighing maintenance and offers an easier clean- The filling machine runs on an eight-hour in-process control offers a tracking ing and sterilization process. shift at a speed of 300 vials per minute. system, designed by Bosch engineers The check weighing system controls eight in cooperation with the supplier of The automatic CIP/SIP system offers random samples every three minutes the freeze driers. This tracking system major benefits to Axellia. Firstly, it covers and incorrect dosage amounts are provides direct communication between the in-line integrated sterilizing filter so automatically rejected without process the filling machine, the freeze driers and there is no need to dismantle the system. interruptions. At the same time, the the capping machine, which ensures that The system also complies with GMP checkweighing system gives real-time, incorrect vials are automatically rejected, regulations, minimizing production times in-process feedback to the time-pressure even after the freeze-drying process. and eliminating the danger of product filling to ensure accurate dosing. This The whole automatic process and com- contamination. fully automated system reduces the munication gives Axellia further quality necessity of having quality insurance assurance. engineers on site, thus reducing labor packazine | 11

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 3 4

Whole-line integration The CUC cartoning machine from Bosch From fully automatic filling lines to When Bosch delivered the complete offers excellent accessibility. The customized cartoning lines, Bosch has filling line in the summer of 2008, the servo technology, industrial PC control provided Axellia with highly reliable project manager at Axellia, Mr. Knud-E systems and the ergonomic touch screen machine quality, easier validation proc- Andersen, was impressed with the operating panel provide secure, reliable esses and excellent customer service. on-time delivery and the overall quality and trouble-free production runs. The The exceptional level of Bosch’s service of the system. At the same time, he was product insertion, from the back of the and support has also given Axellia the also looking for an end-of-line secondary machine, significantly reduces mainte- convenience of interacting with only packaging solution to package the vials nance time and allows easier cleaning one supplier and makes the whole line into cartons. As a result, Axellia again and trouble-shooting. The encapsulation integration and validation process easier. turned to Bosch for a solution. of the drive components and the slanted As a result, Mr. Knud-E Andersen has guards considerably reduce the time been generous in his praise for Bosch For the end-of-line packaging, Axellia required for line clearance. and said: “I have had a good experience needed a labeling machine, a turntable, with Bosch. We believe in Bosch, that’s a cartoning machine, checkweigher, The modular KWE 4000 checkweighing why we buy it from Bosch.” stretch bander and a case packer. system meets pharmaceutical safety However, Axellia didn’t want to source and cGMP requirements, as well as For more information please contact: these individual modules from different offering simple operation and easy suppliers. Bosch was able to offer a line integration. The control cabinet Klaus Schreiber customized, one-stop-shopping solution at the rear of the checkweigher and Phone +49 7951 402 367 by sourcing the labeling machine, stretch the operator terminal allows excellent [email protected] bander and case packer from outside accessibility. Production statistics, trend vendors and integrating them with its curves and current weight are displayed Ralph Pfister own cartoning machine and checkweigh- on the standard screen, which can be Phone +49 711 811 57 293 ing unit. Thus, Bosch provided Axellia configured to show further information [email protected] with a complete end-of-line packaging if required. The weight display can be solution together with on-site installation changed to large numbers for at-distance and support. reading by one single touch on the screen. 12 | packazine Customers & Markets Pharma and Cosmetic

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.

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 pharmaceuticals industry. packazine | 13

New fermenter for multipurpose use in pilot plant stations

Fermentation system – various perspectives

The success of such a project is dures, such as the batch or fed batch outstanding results. The requirements dependent on a number of technical and process and scale-up trials, were to be made on the fermenter were optimally biological process details. Diverse pro- tested. Various demands were also made met and the Site Acceptance Test was cess parameters, such as the pH value, concerning CIP cleaning, continuous also successfully completed. Commissi- oxygen content, foam formation and tem- sterilization capability and the tempera- oning of the Pharmatec bioreactor was perature control plus their time lapses, ture control of the unit. The specialist‘s therefore judged to be an unqualified have to be constantly monitored and innovations and wealth of ideas were success. Further operation of the system corrected throughout the entire fermen- required to achieve this. Together with under production conditions proceeded tation process in case deviations arise. the customer, the Pharmatec team deve- to our customer‘s satisfaction. Perfectly coordinated measurement and loped a concept which was successively control technology is therefore essential implemented within seven months in For more information please contact: for successful cultivation. More extensive Dresden. After commissioning and a Sonnhild Fleischer deviations from the specifications may successful Factory Acceptance Test by Phone +49 351 28 27 819 significantly impair the process and, the customer, the system was installed [email protected] under certain circumstances, render an precisely in its target location, started entire batch useless. up and transferred to the customer following IQ and OQ. Last year, a well known pharmaceutical company based near Frankfurt The first trial for the new system was a commissioned Pharmatec to supply a long-term sterility test called media-run. fermentation system to investigate long- Following full sterilization of the system, term cultivation involving streptomyces, complete fermentation is undertaken filamentous fungi, bacteria or yeasts for with all of the media. Inoculation with the production of natural substances or a cultivated strain additionally took recombinant proteins. Different proce- place. The sterile tests were verified with 14 | packazine Customers & Markets Pharma and Cosmetic

Ultimate quality control through 100 % control

Sanofi-Aventis, a leading global Solution for small batch clinical trials the GKF 1400 ASB 100% (automatic pharmaceutical company, provides a During the clinical trial phase of the drug trouble shooting) machine, for its precise broad range of medicines, vaccines and development process, it is important for and innovative filling of powders, pellets integrated healthcare solutions. Sanofi-Aventis R & D to provide different and micro-tablets and liquids. To produce oral forms of quality clinical dosage forms to its patients. Additionally, trial samples, the company was looking a diverse range of dosage formats gives Improved quality control for a flexible capsule filling solution for Sanofi-Aventis R & D the flexibility and The major benefit that Sanofi-Aventis a variety of product formats. Having reactivity to supply on time with the receives from the new GKF 1400 ASB worked closely with Bosch Packaging required quality medicines for clinical 100% machine is the high degree of Technology for many years, it decided trials. In order to produce small batches quality control. This is key for clinical to invest in a new GKF compact of clinical trial samples, Sanofi-Aventis trial samples, with the correct weight machine that offered 100 % check required a flexible machine for a large and dosage of each unit ensuring accu- weighing. variety of capsule formats, including rate results. Also, since the trial product liquid capsules, powder in capsules, is very expensive and there is often no pellet capsules, and even tablets in spare product for a second batch run, capsules. Having worked with Bosch for the machine needs 100 % quality control the last 20 years, the product manager, prior to the filling process for both empty Mr. Luc-Andre Claustres, decided to try capsules and product amounts.

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 packazine | 15

The GKF 1400 ASB 100% machine Increased productivity For more information please contact: ensures 100 % weight control. Each Fast changeovers and short cleaning Thomas Ripke capsule is weighed individually and with times have improved the production Phone +49 711 811 57527 high precision on the integrated control speed. With the GKF 1400 ASB 100% [email protected] unit. The filling station readjusts the filling 80,000 capsules per hour, com- integrated weight regulation system for pared to the 40,000 capsules per hour pellets and powder applications. This machines used previously, Sanofi-Aventis ensures that the dosing weight is within R&D is now able to manufacture a full the required tolerance limits throughout batch in only a few days. “It saves time the production process. Software while maintaining a high degree of qual- generates a mean value and constantly ity control,” says Luc-Andre Claustres. compares the actual value with the “It’s a pleasure to work with Bosch, and target value. All dosing changes are I am very satisfied with the quality of documented in the production report to the machine. From documentation, to ensure regulatory compliance and any risk analysis, functional analysis, and capsules outside of the tolerance range isolation qualification, it provides an are dependably ejected. unprecedented level of quality which makes the qualification and validation process on our behalf much easier.”

3 4 16 | packazine Customers & Markets Pharma and Cosmetic

Aspirin® Effect is a convenient solution as it can be taken without water. It dissolves quickly in the mouth and has a pleasant taste packazine | 17

RAD-10 stick pack machine

The classic Aspirin® gets a makeover

At 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 installation 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.

New form and packaging style quick and safe emptying of the package. having to be taken into consideration Still a registered trademark in over 80 Aspirin® Effect is sold in award-winning was the fact that Aspirin® Effect is a countries, Aspirin® has been around for folding cartons, used exclusively by Bayer highly moisture-sensitive product and over a century and is universally known and containing 10 or 20 stick packs. demands high impermeability levels for in its tablet form. The introduction of its primary packaging. Aspirin® Effect has seen the classic The project tablet become available in a granulated Ever since its launch in 2004, Aspirin® To ensure optimum performance of the form that is taken without the need to Effect has enjoyed increasing sales. entire line, it is vital to provide highly dissolve in water and comes packaged in Following large increases in demand, a efficient interfaces between primary stick packs. The stick pack itself has an new packaging line was introduced in packaging, transportation/grouping and incision, which makes it easy and safe to 2008. secondary packaging. A “one-stop shop- tear open. To guarantee optimal access ping” system is the ideal solution and, in to the product, the longitudinal seam is Apart from a compact design and high this respect, Bosch has full responsibility positioned at the edge, which results in output levels, Bayer‘s priorities were for project handling and guarantees the an enlarged opening cross-section. This adherence to project schedules and, efficiency of the system. ensures not just easy opening but also above all, technological safety. Also 18 | packazine Customers & Markets Pharma and Cosmetic

Working principle stick pack system RAD10 / CUT120

The equipment is used. Achieving 100 cycles per minute, Bayer and Bosch PA project teams, and The packaging system consists of the stacks of five stick packs and an informa- following a tight production schedule, 10-track Stick-Pack-RAD-10, which is a tion leaflet are inserted into the carton, another packaging system by Bosch transportation and grouping unit, and which is then sealed with hot glue. Packaging Technology will be ready to be a horizontal cartoning machine, the This tailor-made CUT for gable cartons put into operation. CUT-120. exemplifies Bosch‘s customer-specific approach to engineering. For more information please contact: The RA Stick Pack machine is fitted with Holger Botsch a tipping filler, which achieves output Following the validation process, produc- Phone + 41 52 674 89 28 levels of 1000 stick packs per minute. tion of the RAD-10 / CUT-120 Stick Pack [email protected] This dosage technology, used primarily system will start, for eventual delivery for free-flowing products, offers highly to the various sales regions. Thanks to accurate dosing, careful product han- the close cooperation and partnership of 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 Cartoning machine CUT120 intermittent CUT-120 cartoning machine