WHAT S NEXT? Containment Guard: new standard. FEC40: double output. EU19 FS : maximum service life

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1 WHAT S NEXT? FETTE COMPACTING MAGAZINE 1/2017 Containment Containment Guard: new standard Capsules FEC40: double output Punches EU19 FS : maximum service life

2 4 4 Containment Guard 8 Rethinking capsule filling 10 Suspended capsules 12 From the doser into the blister percent control 16 Stability to the 4th power 18 Less is more 20 An entire shift gained 22 News Dear readers, The pharmaceutical industry is increasingly shifting its focus from machinery to the process line and the entire production process. This is confirmed by all sectors activities around the Continuous Manufacturing: the continuous production merges partial processes and taps new potentials for efficiency. The machine fits into a mechanically and digitally fully integrated process. The importance of in-process control elements (PAT) is increasing. Those who know how to command in-process control and use it intelligently in standardized concepts, will develop the enormous efficiency potential of continuous systems as customer benefits in the future. Especially high process requirements can already be found in containment: manufacturers are increasingly processing highlyactive substances. Operator protection demands comprehensive containment which is tailored exactly to operator requirements. This is exactly what the new Containment Guard offered by Fette Compacting does. It is the first international quality certificate for tablet production under containment conditions, whereby this no longer involves individual machines or general guidelines such as the standardized SMEPAC measurement. Instead, the Containment Guard includes all practical process aspects. The ensuing results in reproducible outcome are simple and correct. In short, we make containment efficient! Efficiency in the process also means that all system elements, i.e. machinery, process equipment, tools and operators, interact productively. In fact, many different levers are involved, as demonstrated by our practical examples: for the FEC40, the most efficient capsule filling machine available on the market, we collaborated with our partner to design the upstream and downstream processes more efficiently. In the area of tableting tools, we can present a new punch format which applies FS technology to standardized punches for the first time. And new consulting approaches also show the economic potentials offered by spare parts management and everyday routines. I hope you enjoy reading. Sincerely, Olaf J. Müller CEO LMT Group Division President Fette Compacting TECHNOLOGY stands for everything we offer in production technology from tablet presses and capsule filling machines through process equipment to tableting tools and format parts. SERVICE covers all the services related to machines, process equipment and installations such as spare parts supply, plant modernization and technical field service department. COMPETENCE is the overarching idea behind all our process-related services. This includes training, product trials, application and Performance Consulting as well as engineering. 2 3

3 CONTAINMENT GUARD Less effort involved for safe and exact containment solutions for tableting SMEPAC Commissioning Maintenance Training C-Guard3 Training C-Guard5 Tablet press Safety Equipment Process Equipment An increasing application of highly-active and toxic substances goes hand in hand with increased demands on user, product and environmental protection in the pharmaceutical industry. But despite unambiguous guidelines issued by the regulatory authorities concerning risk assessment and detailed processes on determining toxicity, no standard has been available to date that classifies the containment performance displayed by plants. Fette Compacting is now taking the first step in the form of its Containment Guard. This quality certificate is based on a standardized process with which Fette Compacting determines and documents the retention efficiency displayed by containment tableting systems. Advantages for the user: faster and easier commissioning as the efforts associated with measurements during the subsequent risk assessment are reduced, and maximum process reliability across the entire life cycle of the plant. The growing significance of highly-active substances (High Potency Active Pharmaceutical Ingredients, HPAPI) for the pharmaceutical industry is not only apparent in economic prognoses but also in the work carried out by the regulatory authorities and industrial initiatives. Accordingly, market researchers are anticipating almost double-digit annual growth rates for HPAPIs in the next five years. And the European Medicines Agency (EMA) is actively involved in developing the regulatory guidelines; triggering intensive discussions among experts in the process. On the industry side however, the International Society for Pharmaceutical Engineering (ISPE), for example, plays a key role when it comes to establishing methods for risk assessment and general determination of the retention efficiency of technical systems, bringing together the knowledge of its members in a research group and publishing a containment manual in An English edition will be published in summer 2017 while the ISPE subjects the recommendations to continuous development. Limit values as a basis for plant design The significance of these activities becomes obvious in view of practical pharmaceutical production. And the requirements on user protection not only increase in the case of highly-active medication. More stringent specifications now also apply for many drugs previously manufactured without any special precautions, whereby user protection is increasingly shifting from personal protective equipment to plant containment which is integrated in the process. The starting point is always represented by a toxicological evaluation of the substances, on the basis of which the manufacturers derive maximum permissible limit values and define the technical requirements on plants. For this, they use models such as the occupational exposure limit (OEL), permitted daily exposure (PDE), acceptable daily exposure (ADE) or maximum workplace concentration (MAC). The limit values thus specified form the basis for plant design and are also a reference for the conclusive risk assessment during commissioning. SMEPAC and more: new test procedure for tableting systems As precise as the specifications may seem, there is still a significant need for action in practice. One reason: the manufacturers are in charge of specifying the parameters for determining toxicity. Accordingly, the machine manufacturers are always required to tailor their containment solutions to the individual requirements of pharmaceutical manufacturers. With SMEPAC (Standardized Measurement for Equipment Particulate Airborne Concentrations) there has been established a standardized method for measuring the concentration of particles emitted by a plant, its universal applicability for a variety of plant types means that SMEPAC cannot however cover all of the requirements for assessing a containment tableting system. For example, positioning of the measuring probes is still required and guidelines must be defined concerning the operators location during the measurement process. The number of tablet samples drawn during the measurement and what operating conditions are possible, including any potential error situations, also play a role during tableting. The SMEPAC Directive must therefore be supplemented by additional practical aspects in order to achieve a reproducible analysis specifically for containment tableting systems. This will also significantly reduce the effort involved for pharmaceutical manufacturers concerning installation, test setup and possible improvements prior to commissioning. 4 5

4 Simple, safe, efficient Fette Compacting has developed the Containment Guard in order to make the entire project planning and design process easier and safer for the pharmaceutical manufacturer. The Containment Guard is the world s first quality certificate for marking the retention efficiency of containment tableting equipment prior to the subsequent risk assessment. Certification is based on a standardized test method establishing the retention efficiency of the entire plant, including its process equipment, based on SMEPAC. Fette Compacting carries out the test in a specially designed room in its Customer Center in Schwarzenbek. Successful testing is followed by the plants receiving the Containment Guard certificate. The certificate levels are oriented toward the limit values of the occupational exposure band (OEB) of the containment pyramid and the permitted daily exposure (PDE) values. Fette Compacting supplies the measurement protocols when handing the plant over to the customer. They form the basis for risk assessments by the operator and significantly reduce the ongoing effort associated with measurements after commissioning. Comprehensive solutions for containment tableting systems The standard platforms offered by Fette Compacting for low-dust production are represented by the FE55 and FE75 tablet presses which can be fitted with an optional containment package from Containment Guard 3. The solutions for higher containment requirements use machines in the containment/wip i-series which feature isolator technology. Automatic cleaning of the tablet presses significantly reduces the strain on machine operators and shortens downtimes. When processing highly-toxic substances, users can rely on containment/wip tablet presses with integrated process equipment in the isolator. All solutions comply with the safety philosophy pursued by Fette Compacting in which containment is integrated in the process cycle. These include the following standards: no dust released during production and preparation for cleaning no contact with toxic products waterproof and dustproof press room manual and/or automated pre-cleaning maximum safety in the workplace protection of operators throughout the entire production process Implementation is also simplified for the user by the fact that Fette Compacting pursues a risk-based approach when developing containment systems which is aligned toward the criteria of the Containment Guard. This process comprises seven steps: 1. Definition of the system components and limits 2. Safety concept 3. Plant design 4. Prototyping 5. SMEPAC test 6. Final risk assessment 7. Declaration of Conformity This process makes it possible to regard all system components as a whole. This applies in particular to process and safety equipment offered by suppliers as well as the patented Air Management System offered by Fette Compacting. Users thereby receive a solution which is tailored to their requirements both technically and economically. They invest in an optimal cost-benefit ratio for a sustainable and innovative solution. Apart from technical development, Fette Compacting also offers comprehensive international services, training and consulting as part of the Containment Guard which are specifically coordinated to the requirements of production under containment conditions. These include, in particular, supporting users during ongoing production as well as training operating personnel. Users benefit from safe, simple and swiftly available solutions along the entire life cycle of the plant. This way we make containment efficient. Further Information: 6 7

5 RETHINKING CAPSULE FILLING FEC40 for double output Second only to tablets, hard gelatin capsules are an increasingly popular form of oral administration in the pharmaceutical sector. Apart from their advantages in the development of new medication, capsules also offer a high degree of variety in terms of product design. They can be flexibly dosed, efficiently manufactured and, thanks to color combinations and imprints, are easily differentiated. According to patient studies, such preparations in capsule form reduce the complexity associated with intake, thereby simplifying therapy management. The capsule production is more complex than the production of tablets, making it more cost-intensive. But capsule production relies on efficiency: when making decisions about investing in a new machine, the production costs are far more relevant than the investment costs. To date, the market has been dominated by capsule filling machines with a production output of between 100,000 and 200,000 capsules per hour. In order to achieve significant productivity advantages, machine output would need to be increased far above this level. This is the approach taken by Fette Compacting with its first capsule filling machine. The FEC40 is based on a new and patented machine construction, the Duplex Concept*, whereby Fette Compacting has applied the principle of double rotary tablet presses to capsule filling for the very first time. Accordingly, the designers succeeded in arranging a double capsule filling process in the machine, increasing output to up to 400,000 capsules and decreasing production costs by around 30 percent. 1. The FEC40 offers exchangeable filling stations as standard: tamping pin stations can be easily removed. The patented removal system thus facilitates product change and cleaning. The FEC40 is then swiftly ready for operation and without requiring any additional mechanical settings. 2. An innovative drive concept gives the operator full control of the process: each movement is generated by servo and torque motors, and controlled entirely electronically. Process cycles which have been coupled to date can now be altered and optimized independently for significant reductions in overall processing times. 3. The TRI.EASY design guarantees 360 access, even when process equipment is connected. This enables operators to see and access all stations and permits optimal cleaning of the machine interior. 4. Operation is simplified by the intuitive interface of the newlydesigned Human-Machine Interface (HMI). Intuitive graphic user guidance provides an overview of the relevant process and quality parameters at all times which are stored along with the formulas in the FEC40 database where all batches are also logged and monitored in full. * A brand of Fette Compacting 8 9

6 SUSPENDED CAPSULES Pneumatic system for safe and efficient capsule conveying The FEC40 offered by Fette Compacting achieves an output of up to 400,000 capsules per hour. This output demands that upstream and downstream process equipment is also capable of keeping pace. Process requirements also increase significantly in terms of transporting the capsules. The pneumatic conveyor system offered by our Nilfisk partner represents a safe and efficient solution. Nilfisk not only develops highly-specialized cleaning equipment, the company also designs and builds a range of machines and accessories for use in the food and pharmaceutical sector. This specialist offers standardized conveyor systems for both capsule filling and tableting. Constant pressurized air in a closed system The conveyor model 9505/2 works pneumatically: with the aid of a controlled pressurized air system, the capsules are transported smoothly by the buffer through a stainless steel pipe to the receiver hopper on the capsule filling machine without them opening during transport. The system offers various advantages in terms of product handling and for the operator: the interfaces feature tri-clamp connections and the entire system is connected via an electric signal transmission. Sensors also indicate once a minimum level of the product or empty capsules has been reached in the system. Furthermore, the sliding system can be filled ergonomically and the capsule tank can be opened during operation. Thanks to their smooth surfaces and handy design, the buffer and receiver hopper can be cleaned in no time. Automated product handling with easy conditions Fette Compacting uses the Nilfisk conveyor system for the FEC40. We have a high regard for the experience availed of by Nilfisk in handling products and we also use the equipment in our test center in Schwarzenbek, claims Johan Van Evelghem, Business Development Manager at Fette Engineering. The pneumatic sliding system replaces manual operation in the case of the FEC40. Two capsule conveyors are available for the FEC40 prototypes in the process room at Standard Process in the USA, with each one loading one side of the machine. Our system does not contain any moving parts, and is free of flaps, valves and other obstacles, explains Leonardo Bianco, Marketing Director Industrial Vacuum Solutions at Nilfisk. The receiver hopper is designed so as to gently reduce the capsule speed. Easy operation is the goal pursued by both companies. A great advantage of the conveyor system is the easy installation. All that is required is the power supply and a connection to electric signals. The FEC40 is similarly easy to operate, thanks to its ergonomic TRI.EASY design by Fette Compacting. For customers, it is also decisive that we as machine manufacturers are also available on site and worldwide for queries relating to the process equipment, adds Johan Van Evelghem, with reference to the service claim by Fette Compacting

7 FROM THE DOSER INTO THE BLISTER A continuous manufacturing scenario for tablet production Integrated processes, short manufacturing times, flexible production: continuous manufacturing opens new perspectives for efficient and reliable manufacture. Continuous production is therefore a subject for the future of the pharmaceutical branch. How far has this prospect now developed, and how can we conceive of fully continuous production even today? A scenario as seen by the tablet manufacturer. The way to continuous tableting presents manufacturers with serious challenges: they must say goodbye to established batch processes, and must make more use of automation techniques. Pilot projects nevertheless show that the commercial advantages clearly win out. Experience in the international pharmaceutical environment confirms that continuous production plant significantly shortens production times, reports Dr. Steffen Wehlte, Sales Director Global Accounts & EMEA at Fette Compacting. In the tableting field, scale-ups, for example, can be achieved up to ten times more quickly. Plant availability therefore rises markedly. As a result of this new way of looking at processes, the role of the tableting technology also changes: whereas the technical focus in the tablet press is usually in the production room, with continuous manufacturing it is distributed over the total process. The trend is moving toward more compact and flexible running tablet presses, which best fit the modular structure of continuous production plant, explains Wehlte. Pharmaceutical manufacturers are showing increasing interest in broadening their tablet production in the direction of this kind of integrated concept. They find the qualified advice in Fette Compacting s world-wide competence network, as well as from the partners of Excellence United. Technical experts have Dosing The example of a continuous process line* begins with a micro-doser for continuously dosing both active and auxiliary materials. measuring point Granulating After the dosing process comes preparation of the granulate in a twin-screw extruder, and then the drying process in a fluidized bed. If required, a mixing granulator can also be used, and a dry mixer can be included upstream. Tableting The granulate passes through a rotor mill to the tablet press. The FE35 single rotary press, for example, is ideally suited for continuous operation. After pressing, the tablets are vertically de-dusted, and examined by a metal detector and by an IPC Checkmaster. Checking The heart of a continuous production plant is a continuous PAT system (Process Analytical Technology). In the ideal case, this control and checking system records and logs every step of the process. Coating In the place of a batch container, the process equipment of the tablet press can also be connected to a downstream coating process. Fluidized bed equipment, coating drums and mixers can be employed for coating the tablets. Packing Users, who want to fully exploit the options offered by continuous manufacturing, can even establish a connection to packaging equipment. bundled their process expertise in the alliance, and have together realized the first continuous production projects.* *The description of the process stages from dosing up to tableting is oriented around the MODCOS modular system from Glatt, our partner in the Excellence United. MODCOS was developed in cooperation with Fette Compacting amongst others. More information: and 13

8 100 PERCENT CONTROL Near-infrared spectroscopy in tableting As a test procedure for medication, near-infrared spectroscopy (NIRS) offers some decisive advantages: it is fast, precise, gentle on the product and suitable for use on high-performance machinery. In the form of the VisioNIR LS system, visiotec, a company of Uhlmann Pac-Systeme GmbH & Co. KG, and Fette Compacting have tailored the process to the special requirements of tableting. The factors to be taken into consideration are explained in an expert interview with Dr. Sven Borchert from visiotec. Dr. Borchert, what significance does NIRS have for the pharmaceutical industry? NIRS is a key quality instrument. In particular as continuous production gains in popularity, higher process requirements are the result. One key demand in the area of tableting involves the parity of tablets in terms of content uniformity and absolute assay of sample. What innovations do you see in practice? We see a trend toward increasing the sample quantity for tablet approval. The original demand for 30 tablets per batch is often exceeded by the pharmacist. Add to this the efforts by the regulatory authorities NIRS measuring head for the tablet press to increase the number of random samples required. Quality assurance, therefore, is a driving force in pharmaceutical production. NIRS delivers reliable answers to these questions. How can manufacturers design their content controls in such a way that they optimally comply with the requirements of the authorities? There are two approaches for effective tablet control: on one hand, in-line control in the tablet press enabling fluctuations in product quality to be detected immediately during the tableting process. The other solution involves taking random samples in Dr. Sven Borchert Head of Business Development & Innovation for Pharmaceutical Industry Consulting, visiotec GmbH at-line mode, coupled with physical measurements of weight, thickness, length, width and hardness. How can controls be combined with efficient production? Both approaches permit maintenance of the tableting speed. Fast spectroscopic processes permit precise claims to be made about the active ingredients contained in tablets. For one thing, this enables swift detection of trends during the tableting process. On the other hand, users can achieve real-time releases through the combined measurement of content and physical measurements. How does NIRS work at a technical level? NIR spectroscopy involves electromagnetic radiation interacting with material in a wavelength range of 850 to 2,500 nanometers. Molecular vibrations are stimulated whose response signal permits a detailed analysis of the type and quantity of molecules. What comparable processes are available? Discussions often also involve MIRS, middle infrared spectroscopy, where the wavelengths absorbed account for 2,500 to 25,000 nanometers. But the great advantage of NIRS is that the unprepared and undiluted sample can be measured. Raman spectroscopy can also be considered as a complementary method. But very small scattering cross-sections make its response signal less conclusive than NIRS. What is so special about the VisioNIR LS system? In collaboration with Fette Compacting, we have developed a GMP-conformant inspection system for tableting. This system determines the active ingredient content either directly in the tablet press (in-line) or via a UTS Extended Checkmaster (at-line). One particular feature is represented by the fact that we use a diode array system without moving parts, enabling us to record spectrums very swiftly and evaluate them using our software. This permits 100 percent monitoring of even high-speed tableting processes. What are measurements in the tablet press dependent on? Measurements are in real time during the process with the result that fluctuations are detected immediately. This process is correspondingly time-critical and occurs at processing speed. For this to be realized reliably, we joined Fette Compacting in integrating the test system in the FE35 single rotary press and offering userfriendly visualization directly on the tablet press Human-Machine-Interface (HMI). How does this differ from measurements using the Checkmaster? At-line mode usually involves random measurements for which tablets are transferred to the Checkmaster. As speed no longer plays a primary role here, the tablets can be inspected in detail. One particular feature of the UTS Extended Checkmaster is the fact that it can both scan (reflexion) and fully penetrate (transmission) the tablets depending on the measurement requirements. It also features a Rapid Area Scan (RAS) for measuring local distribution of the active ingredient on the tablet and recording its overall content. UTS Extended Checkmaster for analyzing active ingredients in at-line mode How compatible is VisioNIR LS with continuous production? Thanks to its small measuring head, the sensor can be easily integrated in a tablet press. Optical transmission systems mean that the evaluation unit can be up to 100 meters away from the press, dispensing with footprint in the production area. The Checkmaster is also very space-saving and efficient. Both variants are eminently suitable for a continuous plant

9 STABILITY TO THE 4TH POWER EU19 FS for high life and smooth running EU19 and EU19 FS compared FEM (Finite Element Method) simulations for an example of an active force of 50 kn: the EU19 FS (right) exhibits significantly lower stresses in the transition reason between the plane mirror surface and the centre of the punch head. high stress medium stress low stress EU19 EU19 FS Tableting tools in the EU and TSM formats EU and FS: two worlds merge Innovative mirror surface geometry Valued advantages easy conversion are available for standardized processes. As Punch standards with consistent process The approved service life of the EU19 FS is a result of a special This means that users can change over immediately to the an alternative, the FS punches from Fette parameters have become established in order punch head geometry, which differs from the EU19 through advantages of the FS punch technology, without the need Compacting offer longer tool lives and even to simplify the design of the tools. The European two innovative features: the transition between the run-in area to convert processes. All the valued technical options are smoother running. There is now a link between standard is known as EU, while the related and the plane mirror surface follows a fourth-order polynomial available: every punch material and every coating, single these two, formerly separate, format worlds : American standard is known as the TSM function an important further development of the FS technology. and multiple tools in combination with dies or with segment for the first time, the new EU19 FS brings (Tablet Specification Manual); the particular This leads to lower stresses on entering the plane mirror technology. the advantages of the FS technology to the standards most often applied are known as surface (see illustrations). Fette Compacting has introduced an standard punch and with its innovative mirror B (EU19/TSM19) and D (EU1"/ TSM1"). additional depression in the central head area. The mirror surface Experts from the Business Unit Tableting Tools at Fette Compacting surface goes even one step further. Fette Compacting offers punches for differing of the EU19 FS therefore forms a ring-like area around the are available to help find the best possible options for any standards. For years, manufacturers have, as an centre of the punch head, and is therefore significantly smaller. particular application. The business unit makes punches, dies There is one, central, quality-critical moment alternative, used the patented FS format from During compression, the lower-lying centre does not make and segments in a customized interaction between shape, in tablet production: when the upper and lower Fette Compacting, which brings longer tool lives, contact with the pressure roller, even at maximum pressing material and coating. The services it provides include, for example, punches move together and the tablet forms pressure dwell times and smoother running. force. The transition region from the annular region to the calculations of maximum pressing force, materials and FDA certificates, between them. The punches must here transfer Until now, the EU and FS formats were not, punch centre has constant curvature, which has a particularly general pressing trials for optimum parameters and for the enormous compression forces reliably to the however, mechanically interchangeable. Users beneficial effect on load-bearing capacity. This special transition, right selection of tool and coating. powder or granulate. The punches used also have had to decide in favor of one format or the other. only dropping away gently to the centre, is the crucial prean effect on other machine parts with which they condition for a depression in the centre of the punch being at come into contact. An optimum design, balancing These two worlds have now become one: all possible in the first place. As a result, both the contact the machine against the tool, is therefore the with the patent pending format of the EU19 FS, conditions between the pressure roller and the mirror surface precondition for efficient tablet production. developers at Fette Compacting have success- and the stability of the punch structure are both improved. fully transferred the FS structure to the standard tool structure. An EU19 bunch can now be The inlet region and the depression also have a positive effect replaced one-to-one by the EU19 FS punch. on machine and consumable parts that come into contact All existing cams can continue to be used, and with the punch, as is shown, for example, in the case of the the process parameters remain the same. The pressure roller: the depression lowers stress on the centre of the change, nevertheless, has significant effects: the running surface of the pressure roller, while the edge regions life of the punch rises, the punch head is stressed more are subjected to additional stress. The overall effect is that the evenly, and its maximum loading capacity increases. pressure roller runs more smoothly, and its service life increases. On top of this, the life of the pressure rollers and In addition, the length of the contact line between the pressure of all the other parts that come into contact with the roller and the plane mirror surface is shortened by the diameter punches is also improved. Altogether, the EU19 FS of the depression. This improves smooth running, and reduces leads to smoother running, which has a positive effect noise creation. 16 on the tableting process. 17

10 LESS IS MORE Spare parts management with FMECA in tableting Die screws do not have to be stored. A more economical delivery is overnight. The better the spare parts store is stocked, the higher the machine availability this is a common assumption in pharmaceutical production. On the whole, this is true as high stocks can reduce unscheduled downtimes. But there s a catch to this strategy: stockpiles of spare parts often tie up considerable capital which could be used better elsewhere. Thankfully, there is an efficient alternative to this bought Spare Parts Management represents a key lever for capital flows, whereby the aim is to find the optimal balance between the demands of high availability through high stocks and high liquidity through lower stocks. A risk analysis is best used to establish how to achieve this balance in individual cases. Unlike pure stock optimization, it is not only oriented toward historical consumption data, but also includes numerous other factors. Fette Compacting has tailored such an analysis to the demands associated with tableting. The FMECA (Failure Mode and Effects and Criticality Analysis) plays a central role as an efficient method for optimizing spare parts as it identifies critical spare parts, i.e. those parts which are most risky to fail. The FMECA, therefore, makes it possible to see and evaluate the main reasons for machine downtimes. Four steps for an optimal spare parts management Fette Compacting offers spare parts optimization including the FMECA as a component of its Performance Consulting service. Just how effective this lever can be is illustrated in the following practical example of 4-step optimization: die screws no longer need to be stocked as overnight delivery is more feasible. Step 1: Type-appropriate packages A pharmaceutical manufacturer stored numerous spare parts for six different tablet press models with a stock value of 176,000 euros. In an initial step, Fette Compacting reduced the store to one recommended spare parts package per machine type. The value of these spare parts stocked amounted to 132,000 Euro. Step 2: No multiple storage Then the Consulting Team identified all of the spare parts installed in more than one machine type, e.g. oil wiper rings. Users no longer need multiple stocks of such identical parts. Usually it suffices to order them as a package and save them in others. In this example, the value of parts stored amounted to 68,200 Euro. Step 3: Overnight delivery Not all components need to be permanently in stock. One alternative is offered by overnight delivery as offered by Fette Compacting for around 60 percent of all spare parts. In the case in question, die screws were removed from stocks as they can always be supplied within 24 hours. This enabled overall stocks to be reduced by a further 27,280 Euro. Step 4: Planning with maintenance Fette Compacting can include other selected spare parts in its standard maintenance plans. This does not require producers to stock the parts as they simply receive them in time for maintenance deadlines. The stock value in this example was reduced to an optimal level of 25,916 Euro. In this example, the pharmaceutical manufacturer reduced his spare parts stock by about 85 percent, thereby releasing more than 150,000 Euro in capital. This case illustrates the great potential offered by Spare Parts Management. THREE QUESTIONS FOR LARS PLÜSCHAU Mr. Plüschau, why do you use the FMECA and how does it benefit customers? Our tablet presses comprise around 5,000 individual components. The FMECA analysis method enables us to identify wear-intensive parts and evaluate them from an economic aspect. By specifically aligning our supplies of spare parts with this method, we can achieve a lot for our customers with minimum effort, i.e. high plant availability despite very low storage costs. Lars Plüschau Director Global Customer Support, Fette Compacting What results have been achieved by the FMECA so far? We have been able to identify a critical base of around 30 parts which each manufacturer should have in stock. These involve components subject to wear which therefore require replacement. Furthermore, we have identified another 50 parts with a low downtime probability but which are renewed as standard during maintenance procedures, for example. 40 more parts are low-risk but should also be available in certain cases, e.g. when downtime by a single machine is capable of incurring high costs. The three spare parts packages are referred to as Basic, Comfort and Premium. How do customers decide which one is most suitable for them? There are recommended spare parts packages depending on the type of machine involved. What is decisive however is the possible savings in individual cases. To this aim, our Performance Consulting service analyzes stocks on site and develops a report containing individual proposals for optimizing spare parts. This measure soon pays off in the form of capital released. security

11 AN ENTIRE SHIFT GAINED Increased performance taking a pharmaceutical manufacturer as an example 259 days of freed-up personnel capacity Friede: The customer was positively surprised by the results in the report, especially by the potential, where annual savings possibilities came to a total of 2,072 hours or 259 working days. In other words, it would be possible to free up an entire shift by optimizing the workflows. Together with the free machine capacities, this would make it possible to include another product in the manufacturing range without necessitating any major investments. The greatest effect was displayed by the cleaning and conversion process: as a general rule, three people were involved in primary cleaning of a tablet press. The task took three to four hours for each person to perform and was carried out manually, in some cases involving minimum structured teamwork. As an alternative, Fette Compacting recommended an automatic washing system which cleans most of the tablet press. Parallel to this, an operator can clean the process equipment and certain machine components manually. This reduced each primary cleaning process by six hours, accounting for annual savings of 269,280 USD. The once-off investment in the washing system amounts to the same sum and the investment has been armored in about a year. Interplay by technology and know-how Furthermore, the Performance Consulting team also discovered additional process steps where a technical upgrade frees up machine and personnel capacities permanently. For example, Fette Compacting recommended changing from conventional die tables to segment technology in order to shorten conversion times. The use of FS19 stamps also proved advantageous for some products in an aim to achieve higher output at optimized dwell times, while Higher performance with minimum effort: the TRI.EASY case system (patent pending) offered by Fette Compacting covers all of the steps of tool handling during the tableting process. a newly-developed case system offered by Fette Compacting for safely storing, transporting and even cleaning tableting tools also seemed practical. Apart from these technology-based solutions, we also advised our customers to consistently improve their operators expertise through training, claims Friede. We will soon be kicking off a comprehensive training program with the company. In fact it will be rolled out at several locations worldwide. After all, performance is ultimately dependent on the best possible interplay by technology and operators and not just technology on its own. Annual personnel time savings Annual machine time savings Annual machine cost savings Once-off investment The plants are working at full speed, the operators are a well-coordinated team all in all, things are running smoothly. But routines and technology often harbor some considerable efficiency reserves. A producer of solid formations, for example, was hugely satisfied after Performance Consulting which enabled him to release capacities to the tune of an entire shift, thereby expanding his production. The Consulting Team at Fette Compacting had the task of examining tablet production in a US plant for possible levers to improve performance. The aim was to release capacities for a new product without necessitating investments in additional production machinery. On-site analysis identifies savings potentials The analysis took around 20 days, of which 8 were spent on site. During this time in the plant, we were able to adapt initial production parameters, reports Florian Friede, Consultant at Fette Compacting. This enabled us to design production processes in a more flowing manner during the analysis phase while also reducing the number of bad tablets. The full savings potentials were highlighted by reports which even exceeded the expectations of the pharmaceutical manufacturer. This process saw Fette Compacting developing numerous options for releasing capacities: from cleaning and converting the tablet presses to handling the tableting tools. The chart on the right provides an overview of the analysis results. Polishing tools Cleaning tools Storing tools Converting tablet presses Production Type A Production Type B Total 55 hours 160 hours 53 hours 1,584 hours 108 hours 112 hours 2,072 hours 55 hours By combining changed work routines and once-off investments, the pharmaceutical manufacturer was able to free up significant capacities. 1,584 hours 108 hours 112 hours 1,859 hours 9,350 USD 41,280 USD 6,396 USD 269,280 USD 18,364 USD 19,097 USD 363,767 USD 40,000 USD 2,500 USD 270,000 USD 30,000 USD 20,000 USD 362,500 USD 20 21

12 NEWS NIRS FROM CLOSE-UP: CUSTOMER SEMINARS IN ROCKAWAY Near-infrared spectroscopy (NIRS) is a reliable method of testing the materials properties of pharmaceutical products. In February 2017, customers of Fette Compacting were able to get close and realistic insight into how the method can optimally be applied CHINA:GROWTH AND NEW INVESTMENT China continues to develop from an emerging market into a top industrial nation, as pharmaceutical production shows: the most populated country on Earth is moving up to the front of the field. With total sales of about 100 billion euros, China is the second-largest pharmaceutical market after the USA. According to predictions from IMS Health, the People s Republic will even become the global number one by NANJING: FOUNDATION STONE FOR THE LMT GROUP S NEW CONSTRUCTION LAID The LMT Group will continue vigorous engagement with this growing market and will develop its manufacturing facility. The group is therefore setting up a new production factory in the eastern Chinese metropolis of Nanjing. The factory is being built on a plot of more than 50,000 square meters, and is expected to start operation at the beginning of Dr. Andreas Risch, General Manager of Fette Compacting China, had this to say on the occasion of the formal laying of the foundation stone in the spring: Fette Compacting will double its production capacity in China with this new factory. Even now, we manufacture about 70 percent of the tablet presses that we installed in China, including in Nanjing. With this new investment, we are moving forward together with our customers, who are pursuing even greater growth in China, and want to remain internationally competitive. Fette Compacting will double its production capacity with the new building planned in Nanjing. NANTONG: GREENFIELD PROJECT FROM MERCK IS RUNNING AT FULL THROTTLE Merck is a pharmaceutical company that is expanding its investments in China. In Nantong, north of Shanghai, the DAX-listed concern is setting up a production site of the highest class: no less than 250 million euros are being invested in a state-of-the-art pharmaceutical factory and in a new factory for chemical and biological products. The pharmaceutical factory has already been built, and is testing the first production runs. 10 billion tablets will later be produced here every year. In this unparalleled greenfield product Merck is also continuing cooperation with Fette Compacting as a preferred supplier, reports Dr. Steffen Wehlte, Sales Director Global Accounts & EMEA. We are installing 10 machines in Nantong for high-volume tablet production. We are also supplying tool packages with highperformance FS12 punches, and are preparing a comprehensive training program for the workers. Regular production is expected to begin in in tableting: at seminars at Fette Compacting s competence centre in Rockaway, New Jersey, USA, they were able to observe the VisioNIR LS system from close-up. The response from participants was so good that Fette Compacting will be offering further NIRS seminars as from summer You will find more information about VisioNIR on page 14. PRIZE-WINNING DESIGN: AWARD FOR THE FEC40 For more than 60 years, the if Design Award has been the seal of quality for outstanding design work. This year, the first capsule filling machine from Fette Compacting, the FEC40, was granted the coveted award in the product design category. The FEC40 won over the expert jury in all criteria: from the functional and innovative design, through to ergonomic operability. You will find more about the technology of the capsule filling machine on page 8. Good prospects in Nanjing: The bowl is considered a symbol of completion and perfection in China. From left: Erwin Geissler, Managing Director LMT Tools China, Olaf J. Müller, CEO LMT Group and Division President Fette Compacting, Shigui Li, representative of the development zone Jiangning, and Dr. Andreas Risch, Managing Director Fette Compacting China From left to right: Jan-Eric Kruse, Managing Director Fette Engineering, Steffen Ganz, Senior Designer Studio FA Porsche, and Daniel Malick, Group Manager R&D Fette Engineering Imprint Picture credits Fette Compacting GmbH, 2017; all rights reserved. The rights to all texts, images Title, p. 2 11, 14 19, 21 22: Fette Compacting GmbH and illustrations are held by Fette Compacting GmbH. p : Braun Engels Gestaltung, 2017 Responsible in terms of German press law: Volker Reinsch Editorial management: p. 20: Ernst Fesseler, 2015 Volker Reinsch, Editing and realization: Script Corporate+Public, Communication 22 GmbH, Fette Compacting Design: Braun Engels Gestaltung 23

13 A perfectly normal dream team at LMT Group At LMT Group, what belongs together, works together. We regard it as entirely normal for specialists in a wide variety of areas and with various qualifications to be involved in working toward one major goal: offering the world s best technology on the market. More information on the team approach and an enthusiasm for technology at the LMT Group is available at Dennis Peipers, Mechatronics Engineer, Ibrahim Demirci, Industrial Mechanic, Fette Compacting, Schwarzenbek, Germany Efficiency through Innovation Fette Compacting GmbH Grabauer Strasse Schwarzenbek Germany Phone Fax tablet@fette-compacting.com Fette Compacting America, Inc. 400 Forge Way Rockaway N.J USA Phone Fax sales@fetteamerica.com Fette Compacting America Latina Ltda. Av. Cambacica, 1200 módulo 10 Parque Imperador CEP Campinas / SP Brazil Phone/Fax contato@fette-compacting.com.br Fette Compacting Mexico, SA de CV Adolfo Prieto No Colonia Del Valle Sur Mexico, DF Mexico Phone tablet@fette-compacting.com 24 Fette Compacting (China) Co., Ltd. 8 Phoenix Road Jiangning Development Zone Nanjing China Phone Fax fcn@fette-compacting.com Fette Compacting Machinery (India) Private Limited 401 to 404, 4th Floor, Dynasty Business Park, B wing, Near J. B. Nagar Metro station, Andheri Kurla Road, J. B. Nagar, Andheri East, Mumbai India Phone sales@fette-compacting.in Competence Centre: Plot No S 115, Phase III B Verna Industrial Estate Verna, Goa India Phone Fette Compacting Asia Pacific Pte Ltd. 107 Eunos Avenue 3, #01-01 Singapore Singapore Phone Fax infoasiapacific@fette-compacting.com Fette Compacting Ibérica, SL Calle Saturno Tres Cantos Spain Phone Fax fcib@fette-compacting.com Fette Compacting et Uhlmann France SAS 1, Rue du Centre Noisy Le Grand France Phone Fax contact@fette-uhlmann.fr Fette Compacting Middle East FZE Jebel Ali Free Zone Jafza Lobby 14, Office 308 Dubai United Arab Emirates Phone tablet@fette-compacting.com