packazine - bosch packaging | 5 pharmaceutical ingredients, foreign mat-ter or filling material...

packazinePharma · Issue 2013

C.A.F.-D.C.F. | Highly purified water for the Red Cross Vetoquinol | Containment solution for veterinary medicineSchwabe | Reduced delivery times for spare parts

2 | packazine Table of contents | Editorial

www.boschpackaging.com [email protected]

News

Facts & Trends04 Highest product quality | Protection of patients from contaminated medicine

07 Pre-filled syringes | Facilitated handling of pharmaceuticals and increased dosing accuracy

Customers & Markets

Pharma10 Nuova Ompi | Successful modification project and quick line delivery

12 Eisai Co. | Capsule filling at its best

15 C.A.F.-D.C.F. | Highly purified water for the Red Cross

18 Vétoquinol | Higher safety for veterinary medicine

20 Penn Pharma | True containment capsule filling

22 Schwabe | New stocking solution for new site

Events

25 Events 2013

CoverThe semi-manual inspection unit

ETAC Easy View examines vials, ampoules, syringes and cartridges for particle

contamination and cosmetic container defects.

04 14

Table of contents

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Dear readers,

No matter which industry we work in – packaging is part of our daily life. It protects food and pharmaceuticals, from coffee to insulin. In this regard, you as our customers

and we, as a provider of process and packaging solutions, are not only manufacturers but consumers. It is we who make greater and greater demands for improved product quality, safety and shelf life. These requirements are reflected in the introduction of increasingly stringent regulations for product protection, both in the pharmaceutical as well as food and confectionery industries. More and more, packaging is also perceived as a means of extend-ing shelf life to save resources and improve food provision for millions of people. Packaging is Invented for Life. Product protec-tion and quality, therefore, is the focus of this edition of packazine.

Goods, both pharmaceutical and food, should reach the customers with the quality they expect. We are dedicated to helping manufacturers meet this goal with the innovative process and packaging technology we offer. This is why we constantly seek to advance existing technologies and to develop new methods to optimize product quality, from production to the consumer: “Produced and packaged as promised” – as consumers and we ourselves would expect. Our acquisitions in 2012 mirror this philosophy. With Eisai Machinery we extended our competencies in the field of inspection technology for the pharmaceutical industry, helping to make our customers´ products safer by inspecting for filling levels or for contamination from foreign particles. Fully-automatic inspection will be one of the key technology topics in the coming years. Our entry into product inspection via Eisai Machinery is a cornerstone for further technological developments. With the acquisition of Ampack, we extended our equipment portfolio with cup and bottle filling machines for the filling and packaging of highly sensitive food, such as dairy products and baby food. Once again, our technology reflects the same motto: Invented for Life.Many of the products you encounter in your daily life will be represented in the exciting success stories in this edition of packazine. Learn more about how our process and packaging technology helps our customers ensure their products reach consumers safely.

Enjoy the new packazine!Yours,

Friedbert Klefenz

18 22

Friedbert KlefenzPresident,

Bosch Packaging Technology

Editorial

4 | packazine News Facts & Trends

Complying with strictest quality and safety regulations is especially important for parenteral products filled in vials, ampoules, syringes and cartridges. Other liquid pharmaceuticals, as well as solid dosage forms such as tablets and

capsules, must also undergo thorough inspection. Sophisticated inspection technologies are used, for instance, in the development of biotech products and anti-cancer treatment. They are able to evaluate processes in real time, to

detect and quantify process- or compo-nent-related defects and to take correc-tive actions.Product contamination occurs when particles or foreign matter are found within a pharmaceutical. Contaminated

Growing production capacities, complex manufacturing processes

and high production speeds are changing the pharmaceutical

landscape all over the world. At the same time, the production

of pharmaceuticals underlies increasingly strict safety regulations.

They determine highest product quality to protect patients from

contaminated medicine. Manufacturers are able to meet

this challenge by using future-oriented inspection technologies.

Highest product quality for pharmaceuticals

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pharmaceutical ingredients, foreign mat-ter or filling material might get into the product during manufacturing or filling operations. Cosmetic container defects, such as cracks in syringe flanges or defects in the sealing integrity of am-poules might either already be present or occur during handling. The choice of suitable inspection technologies de-pends largely on product consistency, form and size of the containers. Manual, semi-automated and fully-automated systems are used either for the detection of product-related contamination, cosmetic container defects, or both.

From manual to fully automatedThe United States Pharmacopeial Con-vention (USPi) requires that particulate and other foreign matter visible to the human eye shall not be present. A human inspector can detect approximately 50 percent of all particles sized 50 mi-

cron. He therefore physically agitates each container to set the liquid and any possible contaminants into motion, and to subsequently inspect each individual container carefully. Semi-automated inspection systems minimize the need for manual handling. The automatic feeding, sorting and discharging functions facili-tate the inspector’s work and enable him to focus entirely on the quality control of containers. Some automated inspection systems are able to detect particles below the human capabilities. The “static division” (SD) technology, for instance, projects light through the liquid onto an optical SDx sensor, leading to the differentiation of static from moving objects. Automated camera-based systems, in turn, are used for both particle and cosmetic inspec-tion. While the containers are agitated and rotated by more than 360 degrees, cameras take a series of high-resolution

images. By comparing these images, the system can also identify particles stuck to the sidewall, as well as crimp or seal-ing defects. Integrated product qualityThe Process Analytical Technology (PATii) guidance, issued by the American Food and Drug Administration (FDA) in 2004 triggered the development of entirely new inspection technologies, especially in the area of solid dosage forms. PAT is “a system for designing, analyzing, and controlling manufacturing through timely measurement (i.e., during processing) of critical quality and performance attri-butes of raw and in-process materials and processes, with the goal of ensuring final product quality.”The main focus of PAT is “building quality into products”, instead of inspecting quality after the product has already been manufactured. Machines with x-ray

6 | packazine News Facts & Trends

technology, for example, are suited for this purpose. They enable comprehensive quality and weight control, for instance of capsules. New software developments and imaging capabilities contribute to a rapid advance of these technologies. Most recently developed inspection units are able to simultaneously check all quali-ty features like weight, foreign particles, deformation of capsule top and bottom, as well as length in real-time and at high throughput rates.

Combinations on the riseParenteral products are typically injected and go directly into the bloodstream, where they might cause adverse reaction to contamination and particles. The EU Guideline to Good Manufacturing Prac-tice (GMP), Annex 1iii states that “filled containers of parenteral products should be inspected individually for extraneous contamination or other defects.” It fur-ther emphasizes the need for validation where other than visual inspection meth-ods are used.

Within the validation process of fully- automated inspection machines, samples are crucial to ensure that inspection machines also maintain their validated state under dynamic conditions. Manual and semi-automated inspection tools are especially suited to inspect these sam-ples. They are mainly used for small batch sizes, laboratory analyses, re-work of ejects, and benchmarking of fully- automated machines.

The key to pharmaceutical quality Due to the growing number of parenter-als and especially generic products, manufacturers require ever faster ma-chines for larger production quantities. Here, manual inspection is quickly stretched to its limits. Even the best-trained human inspector cannot keep up with the high speeds of all production types. Depending on size and type of the pharmaceutical product and container, a combination of automated and manual inspection is sure to be the most reliable approach.

To ensure that inspection machines oper-ate at their best, manufacturers must pay attention to validation requirements and perform regular maintenance activities. They must also carefully monitor their processes and regularly check new regu-lations and guidelines, as well as the availability of new technologies. The pos-sibilities of inspection technology are immense. Therefore the decision for robust and reliable technologies from high-quality suppliers is of utmost impor-tance for high product quality and best possible patient safety.

For more information please contact:

Joachim Baczewski

Phone: +81 3 5466 2550

E-mail: [email protected]

Bosch Inspection TechnologyWith sites in Japan, China, USA and Europe, Bosch Inspection Technology offers a wide range of manual, semi-automated, and fully-automated inspection systems. They are used in the area of liquid pharmaceuticals, such as ampoules, pre-filled syringes, cartridges or vials, as well as in the production of solid pharmaceuticals such as tablets. Since April 2012, the product brand Eisai Machinery is part of the Bosch group. The SD technol-ogy, developed by Eisai Machinery in 1975, currently inspects the majority of parenteral products in clear solutions in over 50 coun-tries worldwide.

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Pre-filled syringes have developed from a niche product to a primary container of choice. The advantages over tradi-tional packaging not only include ease of use. Modern pre-filled syringes reduce the need for vial over-filling. With the advent of biotech drugs with high devel-opment costs, this is advantageous as it means less waste and helps eliminating

the dangerous risk of dosing errors. Bosch began serving the syringe market over 30 years ago and today is one of the world’s leaders in the manufacturing of machines for sterile filling of ampoules, vials, cartridges and syringes. We observe several trends with mid- and long-term influence on processing pre-filled syringes.

Influences on pre-filled syringe processingA major trend is the ongoing boom for biotechnology. In this market segment, highly individual products of high quality and value are produced in small batches. In general, biotechnological and chemical drugs are best supplied in liquid form filled in syringes. As a result,

Processing pre-filled syringes in the future

Pre-filled syringes have introduced convenience and accuracy. They are easy to handle

and always ready to be used. The emergence of biotechnology is another main driver

for the development of the pre-filled syringes market with double-digit growth rates.

For equipment manufacturers this development has implications for the future

of processing syringes, in particular for the filling and closure process.

8 | packazine News Fakten & Trends

syringes themselves are a booming market. And although it is often required, freeze drying to improve shelf life is being perceived as the second-best solu-tion due to its more elaborate process.The extent of automation in production will continue to increase, as this has the potential to minimize manual interven-tions, which are the main cause for particles and germ cell entry. Automatic solutions are intensely sought after. For example the fully automatic opening of sterile syringe packaging has long been a standard requirement for new filling lines. In-process control plays an impor-tant role for further improving the quality of pre-filled syringes. Modern fill-

ing equipment therefore should at least open up the possibility to improve qual-ity by providing in-process control which applies not only to filling weight but also to variables such as closure elements and siliconisation. Regulatory require-ments for the use of Process Analytical Technology (PAT) are expected to be expanded.

Possible future developments in processingAll syringes should be able to be pro-cessed on all machines. Hence, the most important parameters should be equal independent of the manufacturer. These parameters include materials, dimen-

sions, and features such as the connec-tion of tub and stretch sheet.From a PAT point of view, examination of silicon distribution should take place before filling – even more so as highly automated filling machines with flexible handling units are already able to pick predefined syringes from a nest. Thus, single syringes could be fed into a line integrated control station easily. Today there are methods to examine the thick-ness and distribution of the silicon layer inside the syringe, as stoppering should fulfill its sliding function in autoinjection devices with minimal silicon entry. In the long run, new coatings could become serious alternatives with the use of

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plasma technology being one example.Fully-automatic bag and tub opening are trending in industrialized countries, and beyond. Due to intensive competition the speed of development for new solutions is very high. Semi-automatic processes are partly being accepted for bag opening. This does not apply to the transfer of tubs into the sterile room, in particular for zone crossing from clean room C to A. A main driver for the discussion is the electron beam steriliza-tion tunnel for the surface decontamina-tion of tubs. The solution is almost a standard on high performance produc-tion lines with isolators.

Filling process: rising request for single useSingle-use filling systems are widely discussed for filling syringes because cleaning and validating parts in contact with the product is very expensive when processing biotechnological products. In this context, peristaltic pumps are becoming interesting again since they do not have contact with the product that is to be filled. Filling volumes typically vary between 50 microliters and three milliliters.How can the syringe be tested before it is filled with an expensive drug? Possi-ble check parameters could be the completeness of the nest, the existence of tip closures and the identification of bent needles. In order to check syringes prior to filling, camera systems could be used. Although control systems on filling equipment have long been called for, companies disclaim their use for techni-cal and business reasons. Yet compared to other trends discussed, these systems are most likely to be implemented.

Different closure methodsAfter filling is complete, the traditional stoppering technique is vented place-ment. A stopper is placed inside a tube that is then inserted into the syringe. A rod pushes the stopper out of the tube and the stopper is sealing the syringe. Driven by the biotech boom, more stop-pers that incorporate coating will be used. They are often too sensitive for vented placement. An alternative stop-pering technique is vacuum placement. A vacuum is pulled in each syringe, and the vacuum draws the stopper into the syringe. Vacuum placement does not compress stoppers as much as vented placement does. However, vacuum placement contains more variables and places stoppers less precisely.

Bulk or nested syringesThe market has already decided: Few new projects are being launched for bulk. Pre-sterilized syringes are prevail-ing. Yet some production lines have a very high output, whereas pre-sterilized syringes are designed for much smaller batches and disposal issues have a low ranking. Maybe in this particular field the development will change but there is no evidence yet.

An irreversible trendOverall, the trend towards pre-filled syringes is irreversible. Biotechnology will determine the development of this packaging in the future. For equipment manufacturers this implies the develop-ment of individual solutions for individ-ual product features. It also requires a better process understanding on the basis of PAT which means better quality and higher yield. Given the success of pre-sterilized syringes, the industry might also start thinking about pre-ster-ilized vials and cartridges. A possible niche product today – but keep in mind that nested syringes have also once started as an “exotic product”.


Klaus Ullherr

Phone: +49 7951 402 517


Courtesy of Nuova Ompi

10 | packazine Customers & Markets Pharma

Good as new

Nuova Ompi’s expertise in handling glass goes back more than 60 years. The company belongs to the Glass Division of the global Stevanato Group, a leading manufacturer of glass tubing containers for pharmaceutical applications. Nuova Ompi is based in the North of Italy and specializes in glass primary packaging for injectables. Its standard portfolio includes different types of syringes, vials and cartridges for insulin, anesthetics, and a wide range of biotech products. Thanks to the company’s extensive experience and in-depth knowledge, Nuova Ompi is well equipped to serve the needs of global pharmaceutical manufacturers.

In-line with the trendOver the past few years there has been growing demand for ready-to-use glass containers in the pharmaceutical indus-try. This development is driven by the space challenges many manufacturers face, increasing the need for technology with a small footprint. By using sterile ready-to-use glass containers, pharma-ceutical manufacturers can move directly to product filling as no washing machine and tunnel for cleaning and sterilization are required in the production line. This further allows them to save additional staff and training. Following this trend, Nuova Ompi prepared to launch its EZ-fill™ product line of sterile and ready-to-fill containers such as vials and cartridges. Witnessing

Bosch speeds up line delivery for Nuova Ompi with successful modification project

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the strong demand in the market, it decided to ramp up production and sought to acquire appropriate line technology. Since the company needed to increase production sooner rather than later, it required a partner like Bosch Packaging Services who could deliver the line quickly with the flexibility to handle both vials and cartridges.

The perfect matchTo meet the high demand for its new brand, Nuova Ompi acquired parts of a Bosch line consisting of a RRN 3063 washing machine and HQL 3680 tunnel designed with advanced smooth hand ling technology. The line had originally been sold to another customer who decided not to pursue production of the products for which the line was designed prior to market launch. As the machinery’s ad-vanced technology offered the flexibility for rapid changeover between various containers, it was the perfect basis for the modifications needed to meet Nuova Ompi‘s requirements. The project timeline was rather tight. Within six months, the line had to be able to handle both vials and cartridges. The original line was designed for cartridges only. After having agreed on the general conditions of this modification project, Nuova Ompi and Bosch Packaging

Services set up their project teams closely working together. According to Nuova Ompi the expertise and experi-ence of the Bosch team made the entire project a success from the beginning.

Modification step by stepTo ensure the EZ-fillTM product line meets pharmaceutical standards, the renowned company emphasized the significance of perfectly siliconized containers. There-fore, extensive siliconization tests were performed prior to starting the project. In the first stage the entire line was brought into the Bosch factory. Bosch experts fully disassembled the washing machine and retrofitted the gripper turn-ing unit to additionally allow the cleaning of vials. Furthermore, Bosch modified the complete infeed area to ensure gentle handling, designing a sleeve to safely transport the primary glass packaging into and through the washing machine. Nuova Ompi supplies its ready-to-fill glass containers to a number of com-panies with a number of requirements. Therefore, not only quick changeover between vials and cartridges but also the ability to handle different sizes was a core requirement. For their vials in sizes of up to 10R as well as 3 milliliter and 20 milliliter cartridges, Nuova Ompi ordered several sets of size parts for

the washing machine and tunnel from Bosch to enable the required flexibility in handling. To ensure its proper functioning with all sizes, Bosch Packaging Services per-formed a thorough mechanical check of the tunnel. As the actual filling process is realized by Nuova Ompi’s customers, the vials do not have to be closed but are transported directly from the tunnel into the company’s tub nesting machine. For the cartridges, the Italian company included a new MRD 1010 filling and sealing machine from Bosch – but with-out the filling station. The cartridges are closed on one side with either a stopper or cap in the MRD filling and sealing machine before they are transferred to the tub nesting machine. Bosch custom-ized the machine to meet the unique requirements of its customer.

Excellent team work for quick resultsDuring the Factory Acceptance Test at the Bosch plant, Nuova Ompi praised the entire Bosch team for the quick and successful implementation of this customized project, describing Bosch as “easy to work with”. In particular, in terms of the validation and qualification process Nuova Ompi and Bosch had the same high standards. Thanks to the professional cooperation of the two teams involved throughout the develop-ment process, the project was a great success. The modified machine with format flexibility was delivered within a short period of time so Nuova Ompi could kick off mass production of its new EZ-fillTM line.

www.nuovaompi.com, www.ez-fill.com


Roland Bringmann

Phone: +49 7951 402 18 77



Pharmaceutical manufacturer Eisai, situated in Tokyo, Japan, is a globalplayer producing research driven medi-cine, over-the-counter (OTC) drugs, as well as generic products in solid and liquid aseptic dosage. Guided byits corporate philosophy of “giving first thoughts to patients and theirfamilies”, and to increase the benefits health care provides, Eisai strives to fulfill its “human healthcare” (hhc)mission. Continuous investments in new machinery enable state-of-the-artproduction conditions. For many years, Bosch Packaging Technology has been

a trusted partner for Eisai. Among thesuccessful joint ventures is the deliveryof no less than five GKF capsule filling machines from Bosch to different Eisai facilities since 2007.

Lights-out-operations for KawashimaAt its Kawashima site, Eisai producessolid pharmaceuticals, such as tablets,capsules and granulates. 800 millioncapsules of Selbex, a remedy for gastri-tis and gastric ulcer, are manufactured here every year. In 2007, Eisai startedto successively replace its capsulefilling machines, aiming to reduce

space requirements and to increase Overall Equipment Effectiveness (OEE). What’s more, Eisai wanted to operate with lights-out-management (LOM). “Our target was simple,” says Hideo Murakami, capsule production manager at Kawashima, “Make a machine run as long as possible without operator in the evening”.Eisai carried out a test trial with the original product on a GKF 1400 at Bosch’s factory in Funabashi back in 2006. “The purpose of the test trial wasto check the frequency of machine shortstops as well as its filling accuracy for a

Capsule filling at its bestBosch Packaging Technology and Eisai Co., Ltd. have a great deal

in common: Both are internationally known for their experience

in the pharmaceutical industry, and both have successfully completed

numerous joint ventures. GKF capsule filling machines manufactured

in Waiblingen, Germany, are installed at different Eisai facilities

around the globe.

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continuous eight hour shift,” Murakami explains. After investigating other sup-pliers, Eisai placed an order in thefollowing year and Bosch sent its firsthigh-speed capsule filling machines, two identical GKF 2500 ASB IPK, toKawashima.

400 million capsules per year and machineThe GKF 2500 ASB IPK is particularly suited for difficult and sensitive prod-ucts like Eisai’s Selbex. “On the one hand, Selbex is difficult to handlebecause of its sticky characteristics. On the other hand, we must avoid empty capsules in the filling process,” says Murakami. In-process control (IPK) enables weight control via statisticalevaluation, while the automatic troubleshooting system (ASB) automaticallydetects and ejects deformed capsules. In addition, the cGMP-compliant produc-tion cabin ensures easy accessibility,user-friendly operation and cleaning. These features provide for smooth production processes and optimizedproductivity with minimal downtime.Before the replacement, Eisai filledSelbex capsules on four capsule filling machines. “Now only two GKF machinesare running, each of them producesaround 400 million capsules per year,”explains Murakami. Thanks to thespace-saving equipment, two emptyproduction compartments can be usedfor other projects. “This is essential forus, since our production site cannot be expanded,” Murakami confirms. Each batch has a size of 7.2 million capsules

and takes three to four days. “With the four old machines, we had interruption rates of 60 times per batch. Thanks to the two new GKF 2500, we reduced them to only three times per batch. You can imagine how much we improved our OEE and how happy we are.”

An extremely tight timelineAfter completion of this very satisfying project, others were soon to follow. The Eisai EMEA Knowledge Centre (EKC), based in Hatfield, UK, undertakes a variety of manufacturing and packaging operations of solid pharmaceuticals.

The new GKF 1400 ASB 100% capsule filling machine is the first of its kind for the UK plant, adding a new solid dose operation to the portfolio. It is used to fill various strengths of Zonegran, an antiepileptic medicine for the treatment of partial seizures.“As with most projects, the main chal-lenges were the tight timelines in getting the machine built, commissioned and installed,” James Woodhall, process engineer at Eisai explains. “The machine was ordered to be built on a very short lead time. Fortunately, Bosch was able to deliver the equipment on time.” The GKF 1400 project formally began with the order of equipment in March 2011. Factory Acceptance Testing (FAT) took place at Bosch’s site in Waiblingen, Germany, in July 2011, and Site Accep-tance Testing (SAT) was performed at Eisai during the month of August 2011.

To be continuedLike all capsule filling machines from the GKF series, Eisai’s GKF 1400 ASB 100 % works with intermittent motion and doses powder via the proven tamping pin principle. Changeover and cleaning time are minimized for maximized productivity. “So far, our GKF has per-formed impressively, displaying unique filling accuracy and resulting in very low reject rates”, James Woodhall sum-marizes. “The 100 percent checkweigher gives us an exceptional level of quality assurance.” It individually weighs every capsule; incorrectly filled capsules are removed and separated into the bad capsule container. Moreover, Eisai has very strict validation documentation requirements for new items of equip-ment. Bosch was able to adapt to these requirements.

“We enjoyed an excellent working relationship with Bosch throughout the project, with thorough flexibility and un-derstanding of our timelines,” Woodhall emphasizes. “Bosch technicians were amongst the best I have ever worked with.” Hideo Murakami from Eisai’s Kawashima plant even takes it one step further, “When it comes to capsule filling projects, I contact Bosch.” Another GKF 1400 is used for pellet dosing activities at Eisai’s Misato plant, and a GKF 702 for research and development purposes was delivered to Kawashima at the end of 2012. And these five GKF capsule filling machines will surely not be the last joint ventures of the two global players.


Andreas Mergenthaler

Phone: +49 711 811 57247



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C.A.F-D.C.F. is an independent unit of the Belgian Red Cross in Brussels. In addition to supplying Belgium with plasma products, C.A.F.-D.C.F. with its two hundred employees acts as a contract supplier for coagulation factors, immunoglobulins, and albumin solutions. Highly purified water (HPW), which is

more economical to produce, is used instead of water for injection (WFI) in several steps in the production process, especially in cleaning procedures. Both water qualities fulfill the same purity requirements. However, substituting WFI with HPW is only allowed in a few situations.

The “Central Fractionation Unit of the Belgian Red Cross” (C.A.F.-D.C.F.) headquartered in Brussels

supplies the domestic market with plasma proteins and acts as a contract manufacturer. The company

produces highly purified water for cleaning and production purposes. This pharmaceutical quality

product is suitable for use as water for injection. Manufacturing and installing a highly purified water

plant that would fulfill the various customer requirements for water processing was a process

engineering challenge for Pharmatec.

To increase its HPW production capacity, C.A.F.-D.C.F. required a highly purified water plant to supply washing machines and CiP (Cleaning in Place) plants. C.A.F.-D.C.F. was well aware of Pharmatec’s expertise in process engineering. Therefore the company was awarded the contract for this project.

Highly purified water for the Red Cross

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The Pharmatec GmbH, a subsidiary of Bosch Packaging Technology, delivered everything from plant engineering and construction to installation of the pipes and the complete distributor system in this turn-key project.

The way to pure waterGenerating highly purified water from drinking water requires three treatment steps: pretreatment, processing, and final cleaning. Pretreatment begins with coarse filtration of the water, after which it flows through a water softening plant. The treatment step that follows involves initial reverse osmosis and final electro-deionization. Reverse osmosis withdraws the salt from the water. The medium now has only a residual salt content of one to five percent, which is further reduced by electrodeionization. The purified water (PW) generated in this manner, is now transformed into highly purified water by means of ultrafiltration.The HPW obtained is temporarily stored in a 25 000 liter tank before being conveyed via the distributor system (the loop) to the loads throughout the facility. The distributor system must be regularly sanitized to maintain the high microbiological quality of the water.

To this step, C.A.F.-D.C.F.’s customers demand different methods of sanitiza-tion in the loop. As a rule, the company prefers ozonization because of its high efficacy. At the same time, C.A.F.-D.C.F. must remain flexible not only in the pro-duction of its plasma products but also with respect to the respective required sanitization methods. This means being able to switch back and forth between ozonization, hot water sanitization, and pressurized water sterilization.

Very unusual combinationIn ozonization, the gas is dissolved in cold water inside the tank and from there is conveyed throughout the entire loop. The thermal disinfection methods differ in the temperatures used; hot water sanitization involves a temperature of 85 degrees Celsius and pressurized water sterilization of 121 degrees Celsius. In the latter method, the tank is also closed to the atmosphere to pressurize the system. Because the tank contents are drained to a defined level prior to sanitization, the free surface within the tank increases. Both gasless methods require the use of spray nozzles to sanitize the surface. The stainless spray nozzles are installed in the return

line of the loop and regularly spray the tank. Yet if the water in the return line contains ozone, the spray heads will cause the ozone to escape due to a loss of pressure. This means it is no longer dissolved in the water. Therefore, the combination of hot water and ozone is highly unusual.The situation at the site required the use of a horizontal tank for the C.A.F.-D.C.F. project. The reduced height of the water column within the tank results in the risk of too little gas being dissolved in the water during ozonization. This challenge was solved by extending the pipe that feeds ozonized water into the tank to make it as long as the entire tank.

Double valve solution for cleaning branch linesSanitization of the loop also includes the branch lines to the consumers. Here, Pharmatec opted for a double valve solu-tion. A compressed-air valve is placed at the beginning of every branch line and a normal valve at the end. This solution makes it possible to drain residual water from the branch line and dry the line after the load has been disconnected, which avoids microbial contamination of the line.

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Even the nozzles in the plant are unique. Their design minimizes dead space and requires fewer pipe, which reduces the risk of bacterial contamination. A unique solution was also developed for removal of hot and cold water. The basic circulating temperature of HPW is 20 degrees Celsius. However, certain loads such as washing machines require a higher temperature. An additional sub-loop was constructed for these cases, which conducts the water through a heat exchanger.

Project objectives successfully achievedAll of these specific challenges were effectively addressed with customer-specific solutions. The result is a complete highly purified water plant tailored to C.A.F.-D.C.F.’s specific needs. The team consisting of seven employees implemented the project on schedule and the plant was able to go into opera-tion in just over a year. „We are perfectly satisfied with how the plant runs,“ says Kris Raspoet, assistant manager engi-

neering at C.A.F.-D.C.F. „Pharmatec’s experienced team focused squarely on quality and planning in order to achieve the project objectives,“ adds project manager Eric Hoogenes. This successful cooperative venture paved the way for a subsequent project for Pharmatec.


Astrid Braun

Phone: +41 61 465 10 96


Due to the close collaboration of C.A.F.-D.C.F. and Bosch during the whole project, it became a full success.

In only three steps highly purified water is generated from drinking water. Highly purified water is used with some process steps during the production of blood plasm, coagulation factors, immunoglobulins, and albumin solutions.


The production of veterinary medicines involves highly active ingredients. This is why the international company Vétoquinol required a tailor-made con-tainment system for the expansion of it production capacities at its French site in Lure. Hüttlin GmbH, a Bosch Packag-ing Technology company, designed a solution that exactly matches the specific requirements of Vétoquinol.

New all-in-one solutionThe Vétoquinol group has been commit-ted to the development, production and

distribution of medicines and non-drug products for the use in veterinary health-care for more than 80 years. The family-run enterprise operates six production sites worldwide and calls 700 product brands its own. The medicines are mainly used for the treatment of dogs, cats, cattle and pigs.With requirements growing at a steady pace, Vétoquinol decided to modernize its production equipment at the French site in Lure in 2010. A strong focus was placed on the required powder containment during the entire process.

To secure continuous development, the company needed a new all-in-one solu-tion for granulating and drying powders under highest containment requirements. “Bosch was open for our needs and offered us the best technical suggestions for our production conditions,” Olivier Vermot-Desroches, technical manager at Vétoquinol, explains.

Optimum mixing qualityThe aim was to design a system that could be used for regular production requirements as well as for research

Higher safety for veterinary medicineVétoquinol choses containment solution from Bosch

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purposes and small batches. One of the most important criteria: a containment solution tailored to processing highly potent substances. The absolute separa-tion of substances and employees in the cleanroom is of utmost importance in this process. The challenge consisted in perfectly synchronizing all equipment and linking their control mechanisms to establish an optimal workflow, as well as ensuring powder transfer under consistent containment conditions.Principal components of the new system are a high shear mixer, a fluid bed system and a jointly developed closed loop cleaning system. The centerpiece of the high shear mixer HBG 600 is its Gentlewing mixing tool. Its z-shape guar-antees best mixing results, its short wall clearance minimizes discharge residue. A transfer tube sucks the granulate into the fluid bed system HDGC 200. The

tangential air outlet of the Hüttlin Diskjet leads to optimum component mixing and significantly reduced drying times. To achieve continuous cleaning of both the batching tanks and tubing, Vétoquinol uses a cleaning system with a WIP (washing in place) station.

SMEPAC test confirms performanceThe flexible system can process granulates from 60 to 240 kilograms. The production processes take place in a containment system based on double valves that reduces the volume of dust emerging from the interface between filling and emptying to a minimum, and enables the operator to work without individual protective gear. An independent environmental research institution from neighboring Switzerland performed a SMEPAC test (Standardized Measurement of Equipment Particulate

Airborne Concentration) to check the full functionality of the system. The Hüttlin system achieved very good results.The SAT (Site Acceptance Test) took place last year. This made it possible for Vétoquinol to begin working in the new building in October 2012. The ten-strong Bosch project team worked intensively with the colleagues from Vétoquinol over a two-year period. “The entire project also benefited from the linguistic skills of the Bosch personnel, who also organized operation and maintenance trainings with us in French,” Olivier Vermot-Desroches sums it up.


Bernd Wolpensinger

Phone: +49 7622 6884 412


Bosch Packaging Technology has equipped Penn Pharma’s new contained manufacturing operations in South Wales with a GKF HiProTect. The capsule filling machine processes highly potent substances and enables Penn Pharma to offer its customers safe and flexible manufacturing.

Safety meets flexibility Penn Pharma is one of the longest estab-lished pharmaceutical services compa-nies and has over 30 years of experience in providing integrated drug develop-ment, manufacturing and support ser-vices to the international healthcare in-dustry. The privately owned company op-erates at both investigational and com-mercial scale. International projects have

led to a significant experience in working with major world-wide regulatory bodies including the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK and the Food and Drug Adminis-tration (FDA) in the US. An important component for Penn Pharma’s success is the use of state-of-the-future equipment with highest safety standards. This was also one of the requirements when the


True containment capsule fillingPenn Pharma opts for GKF HiProTect

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company decided to equip its leading edge Contained Manufacturing Opera-tion with a new capsule filling machine.The facility is a purpose-built 15 000 square foot development and commer-cial manufacturing unit for solid dose tablets and capsules. In the three-floor multi-product facility, Penn Pharma is able to produce batches between one and 120 kilograms. “Because we handle highly potent drug molecules we needed to implement an engineering solution that put employee safety, regulatory compliance and reproductive batch scale up central to our design philosophy,” ex-plains Mark Dean-Netscher, COO at Penn Pharma. “Bosch’s innovative cleaning technology combined with a strong proj-ect management approach made them our preferred supplier.”

Thorough cleaning processesThe GKF HiProTect is suited for a wide range of filling operations, such as pow-der, tablets, pellets, and combination fill-ing. Its modular design concept makes it adaptable to exact customer applications by adding additional stations. The cap-sule filling machine offers different stages of checkweighing to determine

the weight of both empty and filled cap-sules. Penn Pharma’s customized GKF HiProTect is equipped with a statistical in-process weight control (IPK). The weighing station provides automatic feedback to the dosing station, enabling automatic adjustment of filling levels.An array of further automatic processes ensures that pharmaceutical researchers and manufacturers are completely iso-lated from active substances during op-eration, maintenance and cleaning. “Most importantly, Bosch’s innovative cleaning technology provides excellent confidence in cleaning the equipment from product to product and preventing cross-contamination,” Richard Yarwood, CEO at Penn Pharma, underlines. Fre-quent product or batch changes require thorough cleaning processes. The Bosch capsule filling machine has an integrated system that maintains the level of opera-tor protection during cleaning. Several spray nozzles clean the entire machine. The programmable washing system stores and recalls cleaning protocols. This ensures a reproducible wash-in-place (WIP) process which can be fully validated. Moreover, Penn Pharma was the first company to opt for Bosch’s new

GKF HiProTect with an in-line WIP deduster for capsules.

GKF HiProTect in actionFor Bosch and Penn Pharma, this coop-eration is an important step: Penn Pharma has opened a leading edge high-end facility for contained manufacturing, and both companies have worked to-gether for the first time. “We are pleased to partner with Bosch in this important project. The equipment is full of innova-tion, which makes it a world class tech-nology – safe, flexible and fully compli-ant with the demands of the global regu-latory marketplace. We believe our cus-tomers will be delighted by the new service we can offer using the Bosch equipment,” Richard Yarwood explains. And Mark Dean-Netscher adds, “Anyone looking to outsource their potent oral dose tablet and capsule development, clinical or commercial production is wel-come to visit our new UK facility and see our GKF HiProTect in action.”


Udo Comanns

Phone: +49 711 811 57750


The capsule filling machine GKF HiProTect allows not only the filling of capsules with powder, tablets, pellets

and combinations but also conforms to the highest safety standards.

New spare parts strategySchwabe North America manufactures and distributes botanical brands, nutri-tional supplements and vitamins under the labels Nature’s Way, Boericke & Tafel and Enzymatic Therapy all over the world. The privately-held company with

headquarters in Karlsruhe, Germany, draws on more than 140 years of experi-ence in pharmaceutical development. Over the last ten years, Schwabe doubled its sales and production volume in the US, leading to a considerable increase of production capacity and machinery.

Schwabe NA moved its manufactur-ing from the Nature’s Way facility in Springville, Utah to the newly acquired Enzymatic Therapy site in Green Bay, Wisconsin in 2010. Apart from the logistic challenges, the move also meant rethinking the spare parts procurement.


Schwabe North America banks on Stock Optimization from Bosch Packaging Services

When the pharmaceutical company Schwabe North America (NA) moved its manufacturing facility

from Utah to Wisconsin, the company had to entirely reorganize the stocking and ordering

of its production line spare parts. After a stock optimization analysis by Bosch Packaging Services,

Schwabe NA is now able to anticipate future spare parts requirements and could decrease

lead times by up to 90 percent.

New stocking solution for new site

In order to cover its spare parts requirements, Schwabe NA and Bosch developed a balanced system of using Schwabe’s own stock and ordering from Bosch.

Schwabe NA had ten Bosch GKF capsule filling machines at its Utah site and benefited from the close proximity to the Bosch spare parts warehouse in Lindon. Many parts were available the same day. However, infrequently used and specially manufactured parts had to be ordered directly from Germany which sometimes took up to four weeks because of the delivery time.

Individual stocking solution“We faced the question of how to get our spare parts without losing valuable production time. The closest Bosch facil-ity in Minneapolis was now more than 300 miles away,” says Dave Hoffman, maintenance, pepairs and operations buyer at Schwabe NA. To solve these supply problems, Schwabe NA contacted long-term partner Bosch to work on a new solution to optimize stocking and

delivery processes at the new Wisconsin site. “Usually it is necessary to have a closer look at all influencing factors after a relocation. This is exactly what we did for Schwabe NA,” Dave Bethel, after market sales manager for Bosch Packaging Services, explains.Bosch suggested a stock optimization analysis, which quickly showed potential for improvement. “To start off with, we analyzed Schwabe’s purchase history from March 2009 to July 2011,” Dave Bethel explains. Together with the stock coverage information from Bosch and the details of regularly ordered parts and order frequency, Bosch generated Schwabe’s individual spare parts profile with specially developed software. “The challenge not only consisted in defining the amount of permanent spare parts stock but also in finding a solution for less frequently ordered parts,”

Dave Bethel explains. “Based on our analysis, we then suggested which parts Schwabe will need to acquire regularly in the future.”

Ordering at any time of the day To avoid long delivery times from over-seas, Schwabe and Bosch determined parts that could be stocked at the Bosch warehouse in Minnesota and parts that should be stocked at Schwabe’s own site. “Before, we did not anticipate which parts we would require in the near future. We simply ordered parts whenever we needed them. This some-times resulted in long delivery times. Now we have a well-balanced system of our own stock and ordering from Bosch,” Dave Hoffman from Schwabe summarizes.This new proactive stocking solution is backed by the E-Portal, an online

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ordering platform from Bosch Packag-ing Services. Dave Hoffman and his colleagues at Schwabe NA were already familiar with the platform and can now use it even more efficiently in combination with the optimized stocking and ordering procedure. “The E-Portal complements our new spare parts strategy,” Dave Hoffman confirms. “We can look into costs and availability of the spare parts at any time.” For Dave Hoffman, the main asset is the portal’s 24/7 availability. The ordering process takes less time to quote and required parts can be ordered whenever needed.

Improvements on both sidesBosch used the information of the stock optimization analysis to adapt the stock of its Minnesota facility to Schwabe

NA’s needs. Bosch can now anticipate future spare parts requirements from its customer and reduce delivery times for these parts. In return, the analysis helped Schwabe NA to build up an individual and efficient stocking and ordering process at the new Wisconsin site. “We can work with a spare parts stocking system that is matched to our requirements and helps us achieve highest availability with minimal stock,” Dave Hoffman confirms. Consequently, lead times have decreased by 90 per-cent. „We are particularly satisfied with the fast turnaround times that have improved from up to four weeks to one or two days.”The process of improvement still continues at Schwabe’s Wisconsin facility. The individually tailored balance

between stocking on site and ordering via the E-Portal helped to improve planning procedures and also reduced the risk of downtime. “At the beginning, the reorga-nization required quite a learning curve. We had to define the most important spare parts and determine when we would need to place our orders. But now that we have internalized all the informa-tion, the work pays off,” summarizes Dave Hoffman. “Bosch’s stock optimiza-tion analysis helped us considerably in customizing our spare parts handling after the relocation.”


Ray Nungesser

Phone: +1 763 493 6706



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