Customer magazine of Bosch Packaging Technology · Pharma ...

packazin

e | Issue 2016

Customer magazine of Bosch Packaging Technology · Pharma · Issue 2016

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acka

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Issu

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016

2 | packazine Table of contents | Editorial

News

Facts & Trends

04 Container Closure Integrity | Heading towards 100 percent CCI Testing

Customers & Markets

Pharma

07 LGLS | A perfect match: gentle, high-speed vial filling

10 Klosterfrau | The healing power of nature modern packaged

13 Hikma | State-of-the-art serialization solution

16 Oncotec | Cytostatic drugs in a closed system

19 Novo Nordisk | Joint effort for less downtime

22 Pfizer | Capsule filling machines – perfectly integrated!

25 SBM | Terminal sterilization: on the safe side

Events

28 Events 2016/2017

Table of contents

7

10

13 22 25

Customer magazine of the Packaging Technology Division,Robert Bosch GmbH

EditorialCentral Marketing & CommunicationsAnnette Soyke (Leitung)Phone +49 711 [email protected]

DesignCentral Marketing & Communications Karin Schmückle

PhotosB.J.Y.L.D (picture editing); Bosch Packaging Technology; Ralf Grömminger Fotografie GmbH; Stock-Asso (Shutterstock)

PublishingBoard of Management Stuttgarter Straße 130 71332 Waiblingen

© Copyright · Packaging Technology Division, Robert Bosch GmbH

The contents of this publication may not be reprinted except by permission. Subject to alterations.

Imprint packazine

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Editorial

Friedbert KlefenzPresident, Bosch Packaging Technology

Dear readers,

Welcome to the new packazine edition! As usual, we will provide you with a broad overview of stories about our versatile solutions. As of late, Osgood Industries and Kliklok-Woodman from the U.S. and UK, as well as our joint venture with Klenzaids in India, contribute to the expansion of our portfolio on an international level.

This internationality is also reflected in numerous articles. Pozuelo from Costa Rica, for instance, uses Bosch technology to bring its cookies safely from the oven into the packaging. The pan-European food producer Rapunzel Naturkost relies on the comprehensive system competence from Bosch in both primary and secondary packaging.

Complete solutions are also a major decision criterion within the pharmaceutical industry, for instance for our new customer LG Life Sciences from South Korea. We also proved our line competence with a syringe filling system for cytostatics manu-facturer Oncotec.

The CPI software that Hikma is using in Jordan and Saudi-Arabia along with 25 CPS modules for serialization shows that we always see the bigger picture. How and where can we further use our cross-divisional competencies for your projects and complete solutions? Read about it in our new brochures, which I am happy to present you together with this packazine. You might be in for a surprise!

Enjoy reading the new packazine.

Friedbert Klefenz

4 | packazine News Facts & Trends

The U.S. Food and Drug Administration (FDA) defines con-tainer closure systems as “the sum of packaging compo-nents that together contain and protect the dosage form1”. The integrity of these systems is key to ensure product and patient safety. Container closure integrity (CCI) defects can be highly hazardous to patients, as they might lead to a change in the active pharmaceutical ingredient (API) with unexpected side effects.

Heading towards 100 percent CCI TestingNon-destructive inspection methods ensure product and patient safety

Regulations to be extendedThe United States Pharmacopeia (USP) has recently re-vised General Chapter 12072, with the aim of listing the various CCI testing methods, and identifying the most appropriate ones. Deterministic technologies are quantita-tive and less subject to (human) error than probabilistic methods. A further distinction is made between destruc-tive and non-destructive tests, with a clear focus on

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non-destructive methods that preserve the often costly product inside the container.New packaging formats and pharmaceutical formulations necessitate regulations to be extended beyond the current scope. For instance, EU GMP Annex 1 states that contain-ers closed by fusion, such as glass or plastic ampoules, should be subject to 100 percent integrity testing3. How-ever, not only ampoules are prone to leakage or sterility breaches. Vials, syringes or cartridges are even more demanding in terms of CCI, as they consist of several dif-ferent parts involving more potential risks. A vial, for in-stance, consists of a glass container, a stopper and a cap. Here, all parts of the container closure system need to be thoroughly inspected at all levels.

Example lyophilizationA large number of new parenteral products, such as anti-infectives, biotechnology-derived products and in-vitro diagnostics are freeze-dried. The lyophilization process consists of three separate, interdependent steps: freezing, primary drying, and secondary drying4. Each of these steps

bears its own risks and calls for in-depth testing of both product and container closure system. Freeze-dried vials, for instance, can have identical CCI rejection rates as ampoules. The significant difference, to date, is that 100 percent CCI is only mandatory for ampoules but not for other containers. However, many experts expect that regu-lations will be changed accordingly in the near future.The USP does not issue a recommendation for a certain technology. Every product and manufacturing process still requires a careful selection from the available methods. Pharmaceutical manufacturers are encouraged to adopt technologies that significantly increase the level of quality assurance and detection rates. The choice for the appro-priate technology depends on the specific characteristics of product and container, such as conductivity, headspace parameters, alcohol content or API.

Wide range of methods in the marketHigh-voltage leak detection (HVLD) is used to inspect con-tainer closure systems including parenteral vials, pre-filled syringes and cartridges, as well as plastic containers, bags

1 http://www.fda.gov/downloads/Drugs/.../Guidances/ucm070551.pdf2 United States Pharmacopeia, General Chapter <1207> Sterile Product Packaging –

Integrity Evaluation (USP38-NF33 2S). USP Pharmacopeial Forum 40, no. 5, September 2014.3 http://www.gmp-compliance.org/guidemgr/files/ANNEX%2001%5B2008%5D.PDF4 http://www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074909.htm

6 | packazine News Facts & Trends

and pouches filled with pharmaceutical liquids, suspen-sions and oily products. The principle is based on quanti-tative electrical conductance measurements. It measures the electrical resistance of containers with conductive solutions at up to 25 kilovolts. In case of a leak, the resis-tance diminishes significantly.The non-destructive vacuum/pressure decay method is suited for liquid dosage forms, lyophilized products and dry powders. It facilitates the identification of package leaks by capturing the quantitative measure of pressure rise or decay resulting from headspace leakage or liquid product evaporation.Last but not least, headspace analysis (HSA) is applicable to lyophilized products and medicines filled under vacuum or purged with gas. It measures the quantity of light pass-ing through the headspace via laser spectroscopy, and monitors changes in headspace gas composition or total headspace pressure. Leak defects will allow gas to flow from outside a container into the headspace. If a container is initially processed with a modified atmosphere in the headspace, then a total pressure rise or a partial increase in oxygen pressure can be correlated to a leak rate.

Selecting the suitable technologyTo select the appropriate testing method for each product and container, a thorough understanding of the product is paramount: is it sensitive to oxygen or moisture? Is a spe-cific vacuum level required? What is the structure of the molecule? What is the critical defect size that must be detected to keep the product sterile and stable across its entire shelf life? Here, equipment suppliers who know the market and regulatory requirements are of invaluable as-sistance, and are able to deliver more than just a machine.While industry is heading towards 100 percent CCI, lead-ing equipment manufacturers such as Bosch Packaging Technology have already established an extensive range of both visual inspection and CCI testing technologies. This way, every pharmaceutical producer receives a solution tailored to the exact requirements of API, dosage form, container type and size.

For more information please contact:

Mahmoud Hamada

Phone: +49 7951 402-1620

E-mail: [email protected]

The electrical conductivity leak test – or high-voltage leak detection (HVLD) – detects leaks in the wall of a container.

packazine | 7

A perfect match: gentle, high-speed vial fillingLG Life Sciences increases output thanks to FLC vial line from Bosch

Filling vials with liquid pharmaceuticals at high speeds while ensuring a safe and gentle transportation is a chal-lenging task. Especially if conveyor belts need to be used for longer distances, the stability of these fragile glass containers is at risk. Furthermore, lyophilized products re-quire more complex process steps, leading to even longer transportation routes. This was the starting situation of the first joint project between LG Life Sciences (LGLS)

and Bosch Packaging Technology. The South Korean phar-maceutical manufacturer was planning to expand its pro-duction capacities for biopharmaceuticals and vaccines. With a complete vial line based on the FLC filling machine from Bosch, the company found the ideal solution. “Bosch is one of the top pharmaceutical equipment manufactur-ers. We believed that they would be able to supply a high-capacity and stable filling line that would meet our expec-

8 | packazine Customers & Markets Pharma

tations. And this is exactly what they did,” says Sung-Kyu Lee, project manager at LG Life Sciences.

Hepatitis B immunization for the worldWhat started out as a spin-off from LG Chemical Invest-ment in 2002, is now one of the largest pharmaceutical manufacturers in South Korea. The subsidiary of the LG Group develops, produces and distributes antibiotics and vaccines, and is a major supplier of hepatitis B immuniza-tion drugs to the World Health Organization (WHO) and the United Nation’s agencies. Its human growth hormones and drugs for diabetes treatment are exported to more than 104 countries worldwide.At its manufacturing facility in Osong, LGLS processes and fills vaccines and biopharmaceuticals into liquid and freeze-dried vials. The latter comprise vaccines and other injectables, which are freeze-dried to increase the prod-ucts’ shelf life. By removing the water from the product and sealing it in a vial, the drugs are easy to store and ship. They can also be easily reconstituted back to their original form for injection purposes. Due to the rising mar-

ket demand for these products, LGLS decided to add a second multi-purpose vial line to its production facility. “The offer from Bosch complied with all our requirements. Furthermore, the excellent service and very good coopera-tion tipped the scales for Bosch,” says Sung-Kyu Lee. LGLS ordered a complete line solution consisting of a washing machine, a sterilization and depyrogenation tunnel, fol-lowed by a filling and a capping machine. A freeze-dryer from a third party supplier was also integrated into the line.

Ensuring safe and stable transportation“One of the main challenges for us was to ensure safe and gentle transportation of the vials at very high speeds of up to 600 containers per hour,” says Manuela Freisinger, proj-ect manager at Bosch Packaging Technology in Crailsheim. “In LGLS’ line layout, the vials are not transferred via scrolls. Instead, they need to pass longer distances on conveyor belts including several intersections such as rotary tables and buffers. To prevent the vials from tum-bling, we needed to carefully combine all steps of the line and make transportation as stable as possible.”

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present in this market for more than 30 years. “Thanks to our long-term agent Hakoplan, we can offer our customers across South Korea constantly high equipment and service quality, as well as one dedicated point of contact,” Rainer Wahl, regional sales manager at Bosch Packaging Technol-ogy explains. The first cooperation with LG Life Sciences underlines this approach: Bosch was able to deliver on all promises. “Bosch has fully justified the trust we put into them right from the beginning by proving that gentle trans-portation and high-speed vial filling can indeed be the per-fect match,” Weon-Kyo Oh, production team leader at LG Life Sciences concludes.


Rainer Wahl

Phone: +49 7951 402-843


The new vial filling line starts with an RRU 3125 washing machine. After the empty containers have been washed and treated with different cleaning media, they are loaded into the HQL 3480 tunnel, where they are sterilized and depyrogenized. The centerpiece of the line is the FLC 3120 filling machine with its twelve-head filling station. Since the FLC runs in continuous motion, it provides ideal condi-tions for a gentle and nearly flawless handling. At the FLC’s stoppering station, the stopper is placed on top of the vial but not sealed immediately to leave room for the liquid to escape during lyophilization.Once the vials have been filled and stoppered, conveyor belts transport them several meters to the freeze-dryer. During the lyophilization process, water is removed from the product after it is frozen and placed under vacuum, allowing the ice to change directly from solid to vapor without passing through a liquid phase. The process con-sists of three separate, interdependent processes: freez-ing, primary drying, and secondary drying. The lyophilized vials are loaded and unloaded automatically. During the last step, the stoppers are fully pressed into the vial open-ing before the vials are unloaded from the freeze-dryer. The vials are then transferred to the VRK 6160 B capping machine and crimped.

A high-quality marketThe interfaces during transportation are amongst the big-gest challenges for half-stoppered lyophilized vials, which require a great amount of technical ex-pertise. “Together with the experts from Bosch and their state-of-the-art technology, we managed to achieve highly stable transportation routes. This approach resulted in very high product quality along the entire line, while enabling us to improve production efficiency through high-speed pro-cesses,” says Sung-Kyu Lee. “During the project, Bosch was always very open to our suggestions, and we solved all minor issues together,” he adds. “The cooperation with LGLS was very harmoni-ous,” Manuela Freisinger confirms. “It was a plea-sure working with the entire team.”South Korea, in general, is known as a high-quality market for pharmaceuticals with high demands. Bosch has been


The name Klosterfrau is associated with tradition. Founded almost 200 years ago in Cologne, Germany, the Klosterfrau Healthcare Group is today one of Germany’s major pharmaceutical producers with over 1000 employ-ees. Known for its popular natural medicine ‘Klosterfrau Melissengeist', the company markets more than 220 prod-ucts across Europe from its headquarters in Cologne.

With its medicines, Klosterfrau is striving to improve the health of its customers, increase their well-being and offer them the best and most sound natural medicines available. At Klosterfrau, entering new markets also means con-stantly expanding the entire range with new, innovative products and finding the latest technical solutions to opti-mize the production process. In all of these efforts, the

The healing power of nature modern packaged

Klosterfrau benefits from Bosch’s flexible line

for bottling its medicines

packazine | 11

company demands the highest quality from both its prod-ucts and its services. As Klosterfrau will consolidate most of its production at its plant in Berlin, it was looking for a flexible filling and capping line to bottle various liquid and viscous medicines in glass bottles ready for oral consump-tion.

Flexible bottlingThe volumetric filling system from Bosch handles a wide range of products from liquid to high-viscous with differ-ent product characteristics, achieving maximum filling accuracy and output. “Given the diversity of the products, the two key require-ments of a filling technology are flexibility and a reliable

cleaning system. The taste and smell of the various prod-ucts processed on the same machine can vary tremen-dously. The problem here is that the differing smells and tastes might mix with one another, altering the intended end product and ultimately taking away from the end con-sumer experience. In this respect, the innovative cleaning system from Bosch provided the perfect solution,” sums up Lutz Müller, head of the department ‘Liquida’ at the production site in Berlin.

Validated cleaningThe integrated Cleaning-In-Place (CIP) Plus system of the filling machines ensures residue-free and reliable cleaning, thereby preventing any potential cross-contamination when processing different products at the same machine. With the CIP Plus system, Klosterfrau can set an individual cleaning program for each product. This allows the clean-ing process to be repeated and validated, despite the diverse range of filled products. Particularly with products containing no preservatives, it is important that CIP Plus is integrated to guarantee the shelf life and the quality of the product. Since cleaning occurs within a closed process, there is no need to disassemble the machine, which in turn reduces downtime.

Variable cappingKlosterfrau also demanded high flexibility in terms of the different caps available. After the filling machine, the con-tainers pass through capping machines, which hold several capping stations. Based on the end consumer use of the particular product, individual pouring spouts are attached to the bottles at the first machine. The caps are then fitted


at the second machine. Thanks to servo technology, it is possible at this stage to attach a wide variety of caps, with the torque and position being adjusted to suit the respec-tive cap format. Klosterfrau also has the option of placing a measuring cup on top of the cap. The modular configura-tion of the lines enables the processing of different pack-aging materials. This ensures a high level of flexibility for future applications.

Efficient productionThe entire line, from filling to capping, is protected by a laminar flow hood. This stops any foreign particles from getting in. Having benefited from this protection, the bot-tles, in pharmaceutical-grade packaging, reach the feeding table at the start of the production process, ensuring a clean and continuous production process. Due to the large size of the feeding table, the production line can run unin-terrupted for 20 to 30 minutes.The continuous operating principle of the rotating filling machine allows high output levels. All production steps are performed in the same flow rate without any breakpoints. This enables Klosterfrau to fill up to 160 bottles per min-ute, depending on the product. The number of filling points in the modular rotary system has been adapted ac-cordingly to reflect Klosterfrau's preferred capacity level. Tobias Pabst, project manager at Klosterfrau, is delighted: “Compared to an intermittent linear filling system, we can

process our products much quicker on a continuous rotary system. Thanks to the higher capacity of the new system, we are now able to more than double our production speeds.”

A convincing long-term solutionBosch's long lasting experience, in terms of designing and building top-class filling and capping lines, was the decid-ing factor for Klosterfrau: “Bosch has put together the op-timal solution for our individual needs. The machines are both reliable and user-friendly. The reproducibility in terms of both operating and cleaning modes – as well as format changes – creates a much easier and smoother operation. We are also really flexible when it comes to our products,” explains Pabst. “While conventional machines can only work with a limited range of products, the Bosch line in Berlin is currently handling ten different formats.” Pabst is also deeply impressed by the service provided: “Help is available immediately – either by phone or on site – for any issues relating to the new technology, which creates a very pleasant working relationship. I am sure that other proj-ects will run just as smoothly.” A very promising future!


Pasquale Giunta

Phone: +49 2162 248-389


Left: Lutz Müller, head of departement ‘Liquida’; middle: Angelika Scholtz, assistant of Lutz Müller; right: Tobias Pabst, project manager

Watch our video: http://bit.ly/1VUX8Sd

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State-of-the-art serialization solution

Bosch updates packaging lines for

Hikma Pharmaceuticals


Safety comes first in drug manufacturing. This is not only true for the production process but also for pharmaceuti-cal packaging. Nearly all over the world, serialization standards are becoming stricter. Subsequently, phar-maceutical manufacturers must adapt their production lines with Track & Trace solutions according to the different countries’ requirements. In the MENA region, for example, Saudi-Arabia has already introduced obligatory data matrix codes with batch numbers on packages in 2015.As of 2019, products sold in the EU not only need serial-ization but also tamper-evident features (application of security labels) to prove that the packaging has not been previously opened. The U.S. Food and Drug Administra-tion (FDA) aspires to apply a standardized code identifier (standard numerical identification, SNI) to the packaging of all prescription drugs, which will be implemented step by step until the end of 2017. Hikma Pharmaceuticals is committed to applying high standards of quality in its production lines. In its manufacturing facilities across the globe, Hikma seeks production lines that flexibly fulfill all those different demands.

Meeting all future serialization requirementsHikma Pharmaceuticals is a fast-growing multinational group focused on developing, manufacturing and market-

ing a broad range of both branded and non-branded generic and in-licensed products. Hikma’s operations are based principally in MENA, where the company is a mar-ket leader, as well as the U.S. and Europe. The company is committed to the highest quality manufacturing and takes on a pioneering role in applying serialization stan-dards and fighting pharmaceutical counterfeiting. “In order to fulfill all guidelines of the Saudi Food and Drug Authority in advance, we decided to upgrade our packag-ing lines at several sites,” says Ayman Abusalem, MENA Technical Purchasing Manager at Hikma Pharmaceuticals. Since the company already utilizes Bosch machines, Bosch was also the partner of choice for this project. “Bosch is able to provide versatile machines with fast changeover, low running costs and an efficient design. Moreover, they provide good after-sales services,” says Abusalem. In September 2014, Hikma ordered 25 CPS modules with the corresponding CPI software from Bosch to upgrade its existing packaging lines in Jordan and Saudi-Arabia.

Connecting machines and softwareBosch’s CPS 0800 base module prints and verifies up to 400 cartons per minute and can be equipped with a wide variety of marking systems such as inkjet or laser. It is able to print serial numbers, 1D or 2D codes, as well

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as batch data and expiry dates on the folding cartons. The CPS 1400 is additionally equipped with a weighing system, while the CPS 1900 not only has a checkweigher but also a tamper-evident function. By combining the new serialization equipment with the existing machines and the corresponding software, Bosch managed to supply Hikma with an efficient and reliable serialization solution.The new CPI software from Bosch ensures a reliable con-nection of software and machines within the serialization process. The different lines can now all be monitored from a central office at the company’s headquarters in Amman. The CPI not only takes care of generating serial-ization numbers, it also simplifies the order management of the numbers, as it could be easily integrated in the company’s ERP system. “The management view function allows Hikma to check and compare the status of each line immediately,” explains Daniel Sanwald, Bosch expert for Track & Trace. Moreover, the machines of each site are able to access the recorded data and the specific serial numbers, which are required to start production. With the new solution, Hikma can also export the data to an external database, for instance of regulatory authorities.

Ready for the next level“The short time frame from the order in September 2014 until the commissioning in early 2015 was quite

a challenge, not least because of the volume,” says Sanwald. “Thanks to good project management and team work we managed to get the 25 lines running their first batches right on time in February.” Thanks to the newly implemented serialization features, Hikma is able to enter the next level in pharmaceutical manufacturing and pack-aging. “We are very satisfied with the Bosch solution. The machines not only have a compatible design but also run with minimum downtime and highest efficiency. Bosch provided us with exactly the solution we needed for all serialization requirements,” summarizes Abusalem.


Tobias Schiek

Phone: +49 711 811-57309


Connected Industry solutions from Bosch

The Bosch CPI software takes care of batch management as well as serialization – from the allocation of serial numbers right through to the last aggregation step. It is an ideal solution to reliably connect software and machine modules within the production process to receive a true Connected Industry solution. Customers benefit from a visualization of all their packaging lines with real-time overview of all activities on a single dashboard. The software is suited for both the import of external serial numbers and the management of self-generated ones. The CPI also exports serialization and aggregation data for convenient and reliable product verification.


Cytostatic drugs in a closed systemFDA grants approval for Bosch syringe filling line

at Oncotec

Cytostatic agents are used to treat cancer and autoim-mune diseases and are among the most complex and deli-cate drugs. The active ingredients consist of cell poison; highly potent substances which interfere with the growth of cancer cells and inhibit cell division. Regarding pro-duction and handling, the highest quality requirements apply.

“Protecting the pharmaceuticals against contamination and ensuring operator safety have equally high priority when filling cytostatic drugs,” explains Saskia Killer, responsible for the syringe filling line at Oncotec Pharma Produktion in Dessau-Rosslau, Germany. “The filling technology must be able to minimize the risk of contamination through highly automated processes. Therefore, all components of the line must be exactly aligned to one another.”

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Cytostatic drugs in a closed system

FDA inspection ensures access to U.S. marketAs far back as 2008, Bosch Packaging Technology was able to convince the company with a user-friendly overall concept. It consists of a compact FXS 3100 filling and closing machine with 100 percent in-process control and an additional sample check. Further elements include an auto-matic bag opener ABO, an automatic tub opener ATO, and a tailor-made isolator for all modules. Oncotec placed special importance on obtaining the entire line, as well as the isola-tor from a single source. “During the five years following the installation, the technology from Bosch has stood the test. We have complete confidence in the line,” Killer says.Oncotec reached another milestone in summer 2014, when the line scored top marks during FDA inspection. The certification indicates the reliability of both drug production and filling to customers all over the world. “The line passed the FDA inspection without findings. Only a few months later, we could produce the first cytostatic drugs for the U.S. market,” Saskia Killer says. Oncotec now not only has access to the largest pharmaceutical market worldwide with a growing demand for cytostatic drugs. The company also fulfils the requirements to expand into further markets.

Cytostatic agents are mainly used in chemotherapy, which is a common treatment for almost all cancerous diseases. Since cancer rates are growing fast globally, the market for cytostatic drugs is expanding, too. Oncotec’s products encompass a broad range of different cancer therapies. Apart from oncology, cytostatic drugs such as Methotrexat (MXT) are employed for the treatment of autoimmune diseases. State-of-the-art technologies with isolator protection are essential for market success.

Aseptic tub transfer into isolator“The isolator is a closed system that completely separates the operator and the process area and thus protects all staff in the best possible way. Isolator systems ensure higher product quality and facilitate machine operation,” Killer explains. The specially developed, fully automatic tub loading process enables an aseptic transfer of the pre-sterilized syringes into the isolator without additional treatment steps. “The automatic loading and unloading of the tubs was decisive for us, because a contamination-free transfer is an important prerequisite for the syringes’ sterility.”


Automated transportation is particularly characteristic for the FXS filling and closing machine. It fills the pre-steril-ized syringe nests with an output of up to 12 000 syringes per hour. After only one nest row, the filled syringe is closed, thus reducing the opened product’s dwelling time in the isolator to only a few seconds – a key indicator of the FXS platform. Together with the bag and tub openers ABO and ATO, the line has set new standards for Oncotec in the aseptic filling of pre-sterilized syringes.

More than 100 million syringesThe focus of the installation five years ago was on a fast implementation. The line was installed in an old building, posing specific demands on the machinery and ventilation experts from the Bosch Packaging Technology site in Crailsheim, Germany. The machine needed to be tailored to both building opening and beam at an early stage – a basic prerequisite for the fast and smooth implementation from delivery to production start. Since all line compo-nents were provided from a single source, an especially low coordination need between the interfaces contributed

towards the result. Moreover, Bosch also supported Oncotec in qualifying and validating the line.Since start of production, Oncotec has already filled more than one hundred million syringes on the line. It is cur-rently running at least 45 weeks per year in three-shift op-eration around the clock from Sunday to Friday. “Our goal is to have production running with as few interruptions as possible. Therefore, we greatly welcome the immediate technical support from Bosch. If required, the technicians can access our machines via a remote service connection and make sure we can quickly resume production,” Killer comments.The growing market for cytostatic drugs will probably lead Oncotec to expand its filling lines. “Bosch will of course be shortlisted as supplier again,” Killer says.


Klaus Ullherr

Phone: +49 7951 402-517


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Unexpected machine downtime can quickly lead to substantial financial losses for manufacturing companies. Although there is no complete remedy for abrupt and unforeseeable production shutdowns, the risk can be significantly reduced by implementing a pro-active main-tenance strategy. This makes production more reliable, as the equipment is systematically maintained at regular intervals. An individually tailored replacement schedule for all machine components, which is closely aligned to

the susceptibility of each part to wear and tear, is key to success. Thanks to its customized Preventive Maintenance Kits (PM Kits), Novo Nordisk Pharmaceutical Industries, Inc. is already saving time and costs at the U.S. site in Clayton, NC.Founded 1923 in Denmark, Novo Nordisk has become a global market leader in the field of diabetes care medica-tions and devices. The production process of Novo Nordisk in Clayton, includes product formulation, aseptic filling

Joint effort for less downtimeBosch Packaging Services develops

Preventive Maintenance Kits for Novo Nordisk


of vials and cartridges, inspection and packaging. Novo Nordisk also assembles and packages pre-filled insulin de-vices for the U.S. market. The site in Clayton is equipped with three complete filling lines for liquid pharmaceuticals from Bosch Packaging Technology. Injectable solutions are packaged and sealed on two cartridge and one vial line.

Taking maintenance strategy one step furtherNovo Nordisk’s vial filling line is equipped with a Bosch RRN 3084 vial washing machine, a HQL 3480 sterilization tunnel, a FSM 2700 filling machine and a VRK 4010 capping machine. “In order to increase the life-span of our machines and to improve their cost effectiveness, we execute regular maintenance shutdowns twice a year,” Jim Buckley, reliability engineer at Novo Nordisk, explains. During one of these shutdowns, the company started developing its own PM Kits for three key machines – wash-

ing, filling and capping – to take the company’s preventive maintenance strategy one step further.When the Novo Nordisk engineers first contacted Bosch Packaging Services for support, the timing was ideal. The Bosch engineers had recently defined new PM Kits exactly for these machines. By combining the respective PM Kits and new maintenance intervals, the two partners were able to develop a highly efficient solution. “We regularly consulted the Bosch service experts during earlier shut-downs,” Buckley says. “They were always a great help in adjusting and improving our strategy. So it was only logical to count on the same expertise when defining the right sets of spare parts that need replacing on a regular basis.”

A highly customized solutionThe RRN, FSM and VRK are complex machines with a great number of moving parts. This makes continuous servicing

Kits Type

Specification

Assortment Preventive Maintenance

Overhaul Modernization

Machine Life Cycle

Basic and Extended Exchange Interval (h+1) Obsolescence Upgrade

Wear Parts or Reserve-, Electro Parts Wear Parts Reserve-, or

Electro PartsAll

Machine Level

Machine System Assembly Group All

Application

Initial Equipment

Ass

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Ove

rhau

l

Mod

erni

zati

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Pre

vent

ive

Mai

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Regular Maintenance State-of-the-Art Parts State-of-the-Art Technology

FAT

FAT

Commissioning

Regular Preventive Maintenance Activities

Mac

hine

Per

form

ance

SAT

SAT

TimeRamp-up ModernizationTransition

Reactive Maintenance & Opportunistic Parts ManagementFactory Acceptance TestSite Acceptance Test

Functional Module

Bosch’s “House of Kits” offers spare parts kits for the entire machinery lifecycle.

packazine | 21

crucial. In addition, the RRN and the VRK were relatively new additions to the vial line, and the operators had little experience in maintaining the equipment. The Bosch engineers not only focused on the visible parts of each machine but also suggested to regularly replace additional key components in the respective assemblies. “We effectively combined our engineers’ application-oriented point of view with the long-term technical expertise from Bosch to come up with a highly customized solution,” says Carrie Walker, product transfer engineer Novo Nordisk. The Bosch service team and the line engineers from Novo Nordisk met on-site several times to discuss different strategies and to refine the time intervals until they matched Novo Nordisk’s specific needs.

Defining new maintenance intervalsThe PM Kits from Bosch usually consist of minor and major kits. Minor PM Kits comprise wear parts which need replacing after a production interval of approximately 2000 hours. Major PM Kits are designed for replacements after 4000 hours. In comparison, Novo Nordisk’s maintenance concept originally envisioned three intervals of six, twelve and 24 months. The new jointly-developed concept com-bines Bosch’s hour-based model with Novo’s idea of three exchange intervals.The hourly-based schedule allows for parts to only be ex-changed when they have performed the expected amount of hours, rather than parts being replaced at a fixed date regardless of how long and often a machine has been in operation. The newly arranged PM Kits now include parts that are replaced either after 2000 (category A), 3000 (category B) or 4000 hours (category C). Category A comprises components that are highly susceptible to wear, for instance washer bearings which are constantly exposed to water. Category B is designed for parts with an intermediate susceptibility to wear such as belts, while parts from category C have a relatively long life-span and wear slowly like guides.

Savings in time and costsThe development of the new PM Kits was completed within a couple of weeks. For Novo Nordisk the advantages are already making themselves felt. “Having all required parts right at hand allows us to execute our shutdowns much more smoothly than before. We also need less manpower since we are better prepared and organized,” Walker says. “However we not only save time. Thanks to the PM Kits we are also able to reduce costs since we have

a much better overview of what is needed at any moment and avoid unnecessary stocking.” Describing the collabora-tion with Bosch as a “truly joint effort”, the Novo Nordisk engineers in Clayton are considering developing further PM Kits with Bosch for several machines of their cartridge lines.


Mike Diethart

Phone: +1 763 424 4700


Regular maintenance is especially important for highly complex equipment such as the VRK 4010 closing machine.

Bosch supports companies in developing tailor-made maintenance plans so that all equipment operates smoothly.

22 | packazine

Pfizer in Freiburg, Germany, operates with

GKF machines from Bosch for over 30 years

Capsule filling machines – perfectly integrated!

Sustainable, efficient and fully automated is the best way to describe the production of Pfizer Manufacturing GmbH in Freiburg, Germany. The site, currently employing 950 staff, has built up a reputation for environmental protec-tion and sustainability. It is also known beyond the Pfizer group for its high competence in lean manufacturing. Every year, six billion tablets and capsules, as well as more than

200 million drug packages in more than 3000 layouts for the global market are produced.

Fully automated on three levelsTo achieve these high quantities, all production and transportation processes are highly automated. Capsule filling operations are performed on three building levels.

packazine | 23

The second floor accommodates the powder containers and the empty capsules. On this level, the base material is conveyed in containers via remote-controlled automated guided vehicles (AGVs). The powder is directed through the ceiling straight into the capsule filling machine situ-ated on the first floor, where it is processed into filled capsules. On the ground floor, a container collects the weighed capsules, which are then transferred to the subsequent packaging process.“There is one operator working on the first floor,” Eric Fisch, production engineer at Pfizer in Freiburg, explains. “The two other floors are frequented by specialist person-nel for cleaning and maintenance.” The capsule filling machines also set standards in terms of energy efficiency. “Right from the beginning, we planned the factory so that the powder flow can take place without energy input,” Eric Fisch says. “And the concept has stood the test until this very day.”

Several generations beneath the same roofWhat Pfizer needs for three-shift operations is high-performing, efficient and flexible equipment. The pharma-ceutical producer has been working with Bosch Packaging Technology for more than 30 years. Several generations of GKF capsule filling machines have already carried out their

duty in Freiburg since the beginning of the 1980s. From 2001 onwards, five machines of the GKF 2000 series are in consistent operation. “All of them contribute to a good production,” Fisch underlines. After two GKF 2000 ASB 100%, two further GKF 2500 ASB 100% were added. The latest addition is a GKF 2500 S featuring the proven and patented slide-gate system in 2015.The GKF 2500 capsule filling machines with outputs of up to 150 000 capsules belong to the high-performance range. The GKF 2500 ASB 100% is additionally equipped with an integrated checkweigher that weighs each capsule individually. Only capsules with weights within the toler-ance limit are accepted. The low amount of format parts enables fast and easy format and product changeovers. In addition, the machine is easy to adapt; it requires only a few tacts to adjust the weight and start production.

Less product loss thanks to slide-gate“When investing in new machines, we always consider the product first,” says Eric Fisch. “For this reason we define the required filling technology for each drug, before we determine the parameters the machine must fulfil.” The latest capsule filling machine acquired in 2015 ideally needed to run at higher speeds and be particularly easy to maintain. Moreover, cleaning times, output and synergies with the existing machinery park played an important role in this decision – all of them criteria, which the GKF 2500 from Bosch fulfils.In particular, the slide-gate system adds further advan-tages: the slide-gate is especially gentle on the product and achieves lower powder loss in terms of dust in the suction. Eric Fisch confirms, “thanks to the slide-gate, we were able to reduce product loss to two percent, or rather halve it. Although the result was already very good before, every percent makes itself felt with our products. All in all, the Bosch machines are very efficient regarding spare parts and general maintenance.”

Continuous optimizationThe production engineer is also convinced of the underlying technology and machine operation. “New operators can be trained quickly and understand the machine without extensive instructions.” This statement is especially true for Bosch’s KKE. Thanks to its gravimetric weighing technology, the checkweigher is a lot easier to


operate than alternative measuring systems. As for the GKF capsule filling machines, Eric Fisch points out their easy trouble shooting. “You do not have to be a qualified specialist, and you do not need to dismantle the entire machine to find a small defect.”Over the years Pfizer has accumulated remarkable knowledge, which is continuously used to optimize processes and machine details. For instance, Pfizer and Bosch synchronized the GKF and KKE so that individually regulated speeds ensure consistent filling. According to the lean manufacturing strategy, the company is constantly looking for further optimization potential. This includes regular software updates, as well as the ideal adaptation of all machines to the existing room layout. For example, Pfizer was one of the first customers Bosch supplied with a separate control cabinet.

The same languageDespite space constraints, production capabilities in Freiburg are far from reaching their limits. An entirely new manufacturing plant is planned for 2017, and the

fully automated three-floor factory will also be expanded. Thus, capsule production and filling operations will be reinforced by two further machines from the GKF series in the near future. Main prerequisite for the selection of a suitable supplier is the technology. However, geographical proximity also plays an important role for Eric Fisch. “Our contacts at Bosch are on site really fast. What’s more, we speak the same language,” he says. And he not only means the local language, but also the technical expertise and the trustful cooperation between both companies.


Heike Hübner

Phone: +49 711 811-57526


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How sterilization tests provide important information

on pharmaceuticals, packaging and product safety

Terminal sterilization: on the safe side

At first glance, a syringe reveals little about how compli-cated its production is. It actually involves a very complex process, from developing the solution, choosing and filling the packaging to designing the container. Even after filling, the process is not yet completed. Depending on the active

ingredients, international regulations require terminal ster-ilization of containers to ensure the safety of both product and patient. Terminal sterilization of the packaged drugs therefore eliminates microorganisms to the maximum extent in accordance with official regulations.


Especially for new products, pharmaceutical manufactur-ers increasingly rely on customized packaging solutions made of plastic. These are often developed in close cooperation with primary packaging manufacturers to fulfill very specific design and marketing requirements. During terminal sterilization, however, plastic containers may burst, warp or lose strength, making them unusable. As a result, pharmaceutical and packaging producers must create the ideal sterilization conditions for different types of medication and containers.

The appropriate process for each productSolid and porous equipment, pre-filled ampoules and blister-packed products are sterilized using the vacuum-steam process. The air is completely evacuated from the pressure chamber and containers, ensuring saturated steam to penetrate even into the tiny cavities of porous items. The latter are subsequently heated and sterilized by inflowing pure steam. Depending on the type of load, the process finishes either with vacuum drying or jacket cooling. Open, semi-sealed and completely closed containers such as vials and pre-filled syringes, as well as mono- and

multi-chamber bags are sterilized by the steam/air mixture process. It allows products to be removed in a dry condi-tion at the end of the cycle. The direct inflow of steam, which is circulated by fans inside the chamber, provides for heating and sterilization, while cooling is accomplished by internal heat exchangers. Supporting pressure can be adjusted as desired, thus preventing deformation, excessive stopper movement and container breakage throughout the entire cycle.The hot water shower is particularly suitable for liquids in closed containers, such as blow-fill-seal products and closed IV-bags. Fast heating and cooling cycles reduce thermal stress on temperature-sensitive products to a minimum.

Considering all process parametersLiquids and packaging are subject to highly variable thermal and mechanical stress. In case of too high pressure within the containers, walls may soften or bag seams burst. More-over, thermally instable pharmaceuticals risk to spoil when exposed to high pressures and temperatures, thus losing their effectiveness. Hence, precisely tailored sterilization parameters for liquids and containers are crucial.

packazine | 27

Pre-tests including essential process parameters like load-ing, temperature, pressure, heating and cooling speeds, as well as product storage are key. These test runs, which can take from a few hours to several days, precisely map the sterilization processes required by different products – and in case of doubt, they identify whether a new product or primary packaging material can be sterilized at all.

Negative results are just as usefulThe required sterilization procedure for approved drugs has normally already been defined. In this case, test results can deliver valuable insights regarding which

The SBM process X-pert center

Schoeller-Bleckmann Medizintechnik (SBM), based in Ternitz, Austria, is a subsidiary of Bosch Packaging Technology with more than 35 years of experience in the pharmaceutical industry. At the “process X-pert center”, SBM offers tests for the vacuum-steam and steam/air mixture process, as well as hot water shower. Two state-of-the-art sterilizers, including a combined system, provide the flexibility needed to develop precisely tailored sterilization processes for the most diverse products.Via sight glasses, products can be observed during test phases and additionally allow photo and video documentation. Test runs are further documented by experienced experts who also advise customers on optimal sterilization parameters, from temperature settings to loading. The services of SBM also include the professional storage and disposal of the products.

variables have to be adjusted in order to achieve even more efficient process and cycle times. The same applies to containers. Packaging manufacturers receive a detailed analysis of a container’s characteristics and potential weaknesses, resulting in important clues on how the packaging might be optimized.If correct procedure and parameters are still to be deter-mined, test runs can be conducted as a kind of “stress test” to answer questions regarding sterilizability and packaging quality, as well as the most suitable procedure. Manufacturers save a great deal of time and effort during qualification and validation, and can accelerate the prod-uct’s market launch. Even if the test results are negative, they will certainly not lead to the cancellation of produc-tion. Instead, packaging and pharmaceutical manufactur-ers can target their efforts more accurately and accelerate the further development of their respective products.


Isa Alkan

Phone: +43 2630 312 214



Events Food 2016/2017

Events Pharma2016/2017

DateEventLocationBranche

05.17. – 05.20.2016Expo Pack México Mexico CityFood

05.26. – 05.29.2016Afro Packaging & Food ManufacturingCairoFood

05.30. – 06.02.2016Iran Food + Bev TecTeheranFood

06.07. – 06.10.2016Fooma JapanTokyoFood

06.15. – 06.18.2016Propak AsiaBangkokFood

07.13. – 07.15.2016Propak ChinaShanghaiFood

09.14. – 09.15.2016Food & Drink Technology AfricaJohannesburgFood

09.27. – 09.29.2016FachPackNurembergGeneral

10.08. – 10.11.2016IBIE Bakery ShowLas VegasFood

11.06. – 11.09.2016Pack Expo InternationalChicagoFood

11.14. – 11.17.2016All4pack (Emballage)ParisGeneral

03.07. – 03.09.2017CFIARennesFood

05.04. – 05.10.2017InterpackDusseldorfGeneral

Date Event Location Branche

05.10. – 05.11.2016 Crailsheimer Pharmatag Crailsheim Pharma

06.29. – 07.01.2016 Interphex Japan Tokyo Pharma

09.18. – 09.21.2016 ISPE Annual Meeting Atlanta Pharma

09.27. – 09.29.2016 Fachpack Nuremberg General

09.29. – 10.01.2016 Total Processing & Packaging Birmingham Pharma

10.17. – 10.18.2016 PDA Universe of Pre-filled Syringes Huntington Beach Pharma

11.05. – 11.08.2016 CIPM China (Autumn) Wuhan Pharma

11.06. – 11.09.2016 Pharma Expo Chicago Pharma

11.08. – 11.10.2016 Maghreb Pharma Algiers Pharma

11.13. – 11.17.2016 AAPS Annual Meeting Denver Pharma

11.14. – 11.17.2016 All4pack (Emballage) Paris General

11.22. – 11.25.2016 PharmTech Moscow Pharma

05.04. – 05.10.2017 Interpack Dusseldorf General

(subject to alteration)(subject to alteration)

Customer magazine of Bosch Packaging Technology · Pharma ...

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Transcript of Customer magazine of Bosch Packaging Technology · Pharma ...