EPM June/July 2013 by EPM Magazine

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IN THIS ISSUE: Pumps & Valves Tablet Tooling Labware Excipients

European Pharmaceutical Manufacturer June/July 2013

Volume 13 | Issue 04

Front cover image: Natoli uses advanced cryogenic technology to achieve superior quality, dramatically improving performance and increasing the durability and life of your tooling.

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Achieving Fast and Economical Production of High Quality Tablets

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Excipients

Volume 13 Issue 4 © July 2013. While every attempt has been made to ensure that the information contained within European Pharmaceutical Manufacturer is accurate, the publisher accepts no liability for information published in error, or for views expressed. All rights for European Pharmaceutical Manufacturer are reserved and reproduction in part or whole without written permission is strictly prohibited.

ARTICLE: Increased Bioavailability Using New Formulation Technology By Professor Anant Paradkar, the Centre for Pharmaceutical Engineering Science, University of Bradford.

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In previous years, this issue has tended to be somewhat quieter on the news front, most likely owing to the better weather and the long summer hols, but not so this time around it seems. There are a couple of highly informative features and a particularly newsworthy customer story that I would like to draw your attention to. First off is the Expert Insights feature on page 16, in which I have

questioned senior staff from tabletting equipment specialists Elizabeth, I Holland, IMA and Natoli as to what the priority considerations should be for ‘Achieving Fast and Economical Production of High Quality Tablets’. The participants advise on the avoidance of the most prevalent issues in tablet production, ‘sticking’ and ‘picking’, as well as share what they believe to be the most effective developments for increasing speed and their views on how Quality by Design (QbD) and continuous manufacturing will impact tabletting in the future. Also worthy of mention is the ‘Increased Bioavailability Using New Formulation Technology’ Article on page 31, provided by Professor Anant Paradkar at 17 the Centre for Pharmaceutical Engineering Science (CPES), University of Bradford. In his article, Professor 23 Paradkar explains how hot melt extrusion (HME) is being utilised in pharmaceutical development to improve drug delivery. He cites that “nearly 40% of the new chemical entities (NCEs) being discovered have poor water solubility … and as a consequence many new potential drugs fail in the formulation stages.” Recent research undertaken by the CPES into the formation of pharmaceutical co-crystals using HME has shown to significantly increase water solubility and bioavailability, and the Centre is looking to explore the potential of this process further through industry partnerships. I have been inundated with case studies these last few weeks, one of which can be found on page 7. Provided by Watson Marlow Pumps, this story concerns a tabletop filling and stoppering machine’s replacement of a previously labour-intensive and time-consuming manual process at the Cancer Research UK Biotherapeutics Development Unit (BDU). The machine fills and stoppers biological therapeutic products, handling up to 25 vials per minute, and in the words of BDU’s Senior Scientific Officer Tim Hillyer is “quicker than [the] old manual process by a ratio of 29 several factors”. Contained in an isolator, it also significantly reduces the risk of cross contamination between batches. This issue’s Regulatory Affairs instalment on page 34 is titled ‘Regulatory Affairs Vs Regulatory Sciences’ and on this occasion has been submitted by Dr. Paolo Biffignandi’s colleague Dr. Parvinder Punia, a Senior Regulatory Affairs Manager at ELC Group. As the heading implies, Dr. Punia discusses the role of the regulatory affairs professional, summing up the skillset as a “mix of scientific knowledge, negotiation skills and business intelligence.” She also considers “how much of it is really science, and how much of it is affairs” in relation to which stage or aspect of the development pipeline the role is focussed. Lastly, we at EPM are always keen to hear your feedback and suggestions, so if you have found a feature especially helpful or there is a regulatory affairs topic you feel should be covered, please get in touch.

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eab members

from the editor

Henrik Broholm, Senior Specialist, H. Lundbeck A/S Henrik has been working in the pharmaceutical industry for the last 15 years, mainly in connection with finished goods packaging (blisters, ampoules and containers). At H. Lundbeck, he has gained valuable experience of working at both vendor and customer sites, further extending his pharmaceutical packaging expertise. Henrik is for the most part involved with user requirement specifications, machinery and process qualification and validation, the introduction of new products on packaging lines and incorporating new features as required by authorities, e.g., 2D matrix coding with track and trace and child resistant blisters and packs. James Cartwright, Global Granulation Leader, Particle Generation, Control & Engineering, GlaxoSmithKline James began working within the pharmaceutical industry in 1996. During this time, he has been instrumental in developing and launching three products for various clinical indications spanning acute Otitis Media, Lymphatic Filiarisis and Type II Diabetes Mellitus. James studied Chemistry and Chemical Engineering and is a Fellow of the Royal Society of Chemistry. Dr. Dimitris Dogramatzis, RPh, PhD Dimitris is a registered pharmacist and pharmacologist, whose industry career encompasses medical affairs, marketing, country and regional management positions. Dimitris has served as Regional VP — Northern Europe for SERONO and authored two textbooks entitled ‘Pharmaceutical Marketing: A Practical Guide’ (2001) and ‘Healthcare Biotechnology — A Practical Guide’ (2010). Dr. Dave Doughty, Director of Pharmaceutics, GlaxoSmithKline In his 30 plus years in the pharmaceutical industry, Dave has a superb track record in leading teams to develop and commercialise products. This is underpinned by his expert knowledge of the science and mechanistic principles of dosage form design and processing, including PAT, manufacturing operations and GMP. Dave has co-authored product and process patents. Product innovations include oral and transdermal dosage forms. Process innovations include compression and coating of tablets and continuous manufacturing methods and associated PAT. Continuous processes include feeding, mixing, granulation, drying, coating and a novel method of manufacturing low-dose, high-potency drugs. John Gamble, Senior Research Scientist, Bristol-Myers Squibb After graduating from the University of Salford in 1998 with a degree in Chemistry with Industrial Experience, John began his career in quality control analysis of parental vaccines, later moving on to physical analysis of inhaled drugs, before arriving at his current position as Senior Research Scientist within the Powder Properties Optimisation group at Bristol-Myers Squibb. John has a keen interest in understanding the interrelationships between the physical properties of drugs and excipients and their subsequent behaviour during formulation and manufacturing. Aidan Mc Nabola, Engineering Director, UCB Group, SCHWARZ PHARMA Ltd Aidan is Engineering Director at Schwarz Pharma Ltd, based in Shannon Co. Clare, Ireland, and is responsible for site infrastructure, engineering systems — including capital projects — utilities, IT and automation on site. Aidan holds a B. Eng Degree in Mechanical Engineering and has more than 23 years experience in primary and secondary manufacturing in the pharmachem and medical device industries. Grégory Poujol, Manufacturing Maintenance Manager, Sanofi Grégory is an ‘Arts et Métiers’ engineer. He started working in one of Sanofi’s injectable plants in 2003, before moving to a solid form plant as a Project Manager in 2004 to install new process equipment. In 2009, Grégory moved to one of the group’s solid form plants in Spain to lead new equipment installation projects as well as take charge of process maintenance and improvements. He returned to France in 2013 and continues with projects at one of Sanofi’s API production plants. Grégory has experience of the most well-known providers of solid form equipment. Kostas Saranteas, Senior Director, Process Chemistry and Engineering, Sunovion Pharmaceuticals Inc. Kostas is Senior Director of the Process Chemistry and Engineering Dept. at Sunovion’s R&D Division. He holds BS/MS/PhD degrees in Chemical Engineering and an MS degree in Environmental Engineering. For 15 years, Kostas worked at Polaroid Corp., specialising in batch process equipment modelling, process optimisation and scale-up. For 11 years, Kostas has been employed at Sunovion. He leads cross-functional teams, championing accelerated process development for drug substance and drug product synthesis from laboratory-scale to full-scale manufacturing.

MANUFACTURING PRODUCTS & EQUIPMENT Tablet Tooling Manufacturer Introduces Maintenance Audit Service Tablet compression tools are generally viewed as consumable items that can easily be replaced, but I Holland is turning this idea on its head with the 7 Step PharmaCare Process, which offers simple steps for maintaining punches and dies to help improve profitability by limiting tablet press downtime. Andy Dumelow, PharmaCare Equipment Manager, explained: “Rather than maintaining tools, many companies decide to just replace them as they think it is the easier option, however we want them to re-think this approach and adopt the 7 Step PharmaCare Process. It will help to extend the life of the tablet tooling and more importantly improve profitability and return on investment by considerably reducing downtime. “The process is a programme of professionally planned maintenance that outlines an appropriate method for the maintenance of tablet compression tooling. The seven steps include clean, assess, repair, measure, polish, lubricate and store. I Holland will visit the site and audit and review a customer’s tool maintenance procedure, methods and equipment. An introduction to the 7 Step PharmaCare Process will then be made, resulting in a presentation of recommendations and full audit report. “The process takes just three days but in the long run will save many hours of reduced production through unplanned tooling maintenance and replacement. Our experienced and professional team will uncover the root cause of a

customer’s problem, for example, wear or corrosion, and advise on an informed and working solution or optimisation of current maintenance techniques.” Correct maintenance is critical in obtaining maximum life from punches and dies, with a high proportion of problems being traced to poor handling and maintenance procedures. The audit is a way to directly detect this and rectify it with a simple process of steps. Step 1: Clean — An essential start to the process to ensure tooling is free from contamination. Step 2: Assess — Following cleaning, punches and dies must be inspected to determine general condition. Step 3: Repair — Rectify any damage to the tooling, including any light corrosion and damage, through polishing and repairing. Step 4: Measure — This is essential after polishing and repair to ensure critical tooling dimensions have stayed within tolerance. Step 5: Polish — Automated polishing is recommended to ensure an even polish and consistent finish. Step 6: Lubricate — This step is

important to protect, preserve and aid the smooth operation of tooling in the tablet press. Step 7: Store — The final step is important to protect and minimise damage of tooling. Correct storage facilitates good tooling management. It is recommended that specially designed storage cabinets are used. I Holland Ltd +44 115 972 6153 info@iholland.co.uk www.iholland.co.uk

Bright Future Pharmaceutical Invests in Three Carton Packing Lines Hong Kong pharmaceuticals manufacturer Bright Future Pharmaceutical Ltd has commissioned OYSTAR A+F for three new ModuLine carton packing lines that will package cough syrup sachets. The lines will be connected to four sachet filling systems with an output of 180 packet strips per minute each. The sachet strips are tested for leakage and weight within the cleanroom. For this purpose, a three-lane weighing system with reject gate has been incorporated into each of the lines. Upon successful testing, the sachet strips leave the cleanroom on a slide, are stacked into product carriers and then transported to the A+F ModuLine carton packing machine in a fully automated process. Within the carton packing system, the sachets are removed from the product carriers and packed into cartons in sets of five, ten or fifty strips. The cartons themselves are erected from flat blanks,

packed, glued and sealed. Every A+F ModuLine is also equipped with a laser printer for coding of the completed cartons before these are transferred to other machines for final packaging. The entire system is subject to IQ/OQ documentation and validation. Bright Future Pharmaceutical is already using various tube filling machines and carton packing machines manufactured by OYSTAR IWK. This order marks the first achievement reported by the new management team at OYSTAR A+F, headed by Managing Director Achim Wapniewski since the end of 2012.

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OYSTAR A+F GmbH +49 7244 747 0 info-finalpackaging@oystargroup.com www.oystar-group.com

MANUFACTURING PRODUCTS & EQUIPMENT ROUNDUP White Paper Outlines Key Considerations for Enhancing Product Integrity The increasing number of counterfeit pharmaceutical products throughout the global supply chain has created regulatory variations across differing regions and countries. Mettler Toledo’s White Paper ‘Serialisation - The Key to Success for Pharmaceutical Manufacturers’ discusses the challenges faced by manufacturers in addressing this issue. The process of serialisation allocates each manufactured product a unique code that is then backed up by a central database. This allows each item to be tracked from manufacturing source to end user, ensuring its integrity. The paper also outlines the serialisation

information required to maintain an effective and compliant production process. Also detailed are the data requirements of the first countries and regions to adopt the new regulations. By learning more about the challenges and issues raised in the paper, manufacturers can discover a range of solutions offering protection for both their product and brand. Request the free white paper by visiting: www.mt.com/uk-serialisation-whitepaper. Mettler Toledo Ltd +44 116 234 5069 jonny.leeson@mt.com www.mt.com

Vision System Delivers Vital FMD Quality Checks

Travtec has launched the Lixis PVS, a high-end OCR/OCV imaging system that offers reliability, accuracy and speed for a wide variety of inspection requirements throughout the packaging process. In particular, it provides effective monitoring to ensure that coding operations are meeting the requirements of the forthcoming EC Falsified Medicines Directive (FMD). The Lixis PVS can carry out a variety of quality checks. Its character recognition software reads both preprinted and in-line printing, and it automatically detects shift or rotation variations. Colour verification can also be specified. All types of barcodes can be monitored, including standard formats (EAN, Code 128), pharmaceutical industry variants such as Pharmacode and Datamatrix and 1D and 2D codes. In addition, the system can be programmed to check the accuracy of logos and artwork and for the presence and position of labels, caps and other items. An easy-to-use colour touchscreen interface, including on-screen help and interactive tutorial, ensures fast setup and simple day-to-day operation. An unlimited number of pre-set patterns and character details can be stored in the memory for fast changeovers, and detailed production reports and defective images can be outputted for process analysis. The Lixis PVS is easy to integrate into existing production equipment, including cartoners, leaflet folders, labelling machines, blistering machines, carton codifiers and tube fillers. Up to 800 images per minute can be verified, depending on the application. The new vision system joins Travtec’s proven range of pharmaceutical coding equipment, including the Wolke m600 thermal inkjet printer and the Pharmacarton Elite online and TR-760TT offline carton feeders, meaning the company can provide a bespoke coding and monitoring system tailored to the needs of individual customers. “This is an important addition to our range,” commented Travtec Group Managing Director Harry Thomason. “Pack and coding accuracy have always been essential for any pharmaceutical packing operation, but the new requirements of the FMD will make it all the more important that companies not only comply with the regulations but ensure that their equipment continues to operate effectively. Our new Lixis PVS will provide the necessary level of quality control and reassurance.” Travtec Ltd +44 1942 677664 info@travtec.co.uk www.travtec.co.uk EPM 6

MANUFACTURING PRODUCTS & EQUIPMENT ROUNDUP CASE STUDY A Flexicon FP50 tabletop filling and stoppering machine from WatsonMarlow Pumps Group has automated a previously manual process at a Cancer Research UK facility in Hertfordshire. The FP50 is delivering increased speed and reliability into this critical operation as well as enhanced vial filling accuracy. The Cancer Research UK Biotherapeutics Development Unit (BDU) was constructed in 2010, at South Mimms, near Potters Bar. It is a modern, MHRA licensed, fully cGMPcompliant, 2000 m2 facility that is engaged in the process development and GMP production of novel investigational medicinal products (IMPs) for phase I clinical trials sponsored by Cancer Research UK. Recent challenges at the BDU included the introduction of an automated filling and stoppering procedure, which was previously performed manually using a dosing pump. This was very hands-on and labour intensive, which resulted in a slow process throughput. The manual procedure was unsatisfactory for such a leading edge facility, and a reliable automated vial filling process was required for the delivery of future BDU projects. “We wanted a vial filling and stoppering process more in step with our modern facility,” explained Tim Hillyer, Senior Scientific Officer at the BDU. “To help deliver this, we set out to source a machine capable of rapid, repeatable filling but without any compromise to process quality and control.” The answer arrived in the shape of a Flexicon FP50 tabletop filling and stoppering machine from Flexicon Liquid Filling, part of the Watson-Marlow Pumps Group. Capable of filling up to 25 vials a minute (up to 100 ml capacity), the system also

FILLING AND STOPPERING MACHINE AIDS BIOTHERAPEUTICS DEVELOPMENT AT CANCER RESEARCH UK

offers quick and easy changeover between batches. “As a multi-product facility producing small batch size, highvalue IMPs, the flexibility offered by the FP50 was ideal for our purposes,” said Hillyer. “Our most recent batches involved not more than a few litres in quantity so having a reliable method for product filling and stoppering enables us to bring new drugs into the clinic in a controlled and reproducible manner.” Today, the Flexicon FP50 is used as and when required to fill and stopper biological therapeutic products (solution-form drugs) produced at the BDU. “Not only is the FP50 quicker than our old manual process by a ratio of several factors, it is easy to adapt for different vial and stopper sizes,” said Hillyer. “An adjustable walking beam transports vials from the feeding turntable to the different working positions (filling needle and stopper plug). Only two parts require changing to cater for the entire range of vials and stopper sizes used. Furthermore, the pump is very accurate, allowing us to closely control the dose volume going into each vial. “Finally, the FP50 unit is fully contained within a six-glove isolator, allowing us to gas the equipment prior to each product fill using hydrogen peroxide vapour. This containment, twinned with the speed and efficiency of the FP50, greatly reduces the chances of batch contamination.” The Flexicon FP50 is a universal and aseptic tabletop filling system with integrated full or partial stoppering of rubber stoppers for use in pharmaceutical R&D departments and biopharma facilities. All materials and surfaces are designed to meet cGMP standards for aseptic filling, therefore providing a ready-to-use validated filling system to

carry out clinical trials and small batch production. The filling accuracy of the peristaltic filling system is better than ±1%. The operator interface is an easy-to-clean touchscreen and keypad. The panel is mounted on a separate control box, remote from the filling unit. This allows the control panel to be placed outside the horizontal laminar airflow (LAF) bench or isolator. It is possible to store up to 20 sets of filling parameters as complete working programs. Ultimately, these features and capabilities make the Flexicon FP50 well-suited to the needs of the Cancer Research BDU, where such manufacturing equipment enables the development of processes that are scalable and transferable if a product is licensed to manufacturing partners later in the project. Watson-Marlow Pumps Group +44 1326 370370 heatherbeale@watson-marlow.co.uk www.wmpg.co.uk

Variable Gap Dry Granulator Meets Continuous Processing Requirements

Accurate Compressed Air Diagnosis Brings Healthy Savings For Pharma Manufacturer

The pharmaceutical industry’s demand for continuous processes is increasing because they offer clear advantages such as cost savings, process robustness and no scale-up hurdles. Continuous dry granulation is now often the process of choice for large-volume or moisture-sensitive products. L.B. Bohle meets this growing demand by offering the new Bohle BRC 100, a variable gap dry granulator. The BRC 100 offers high-production capacity with minimal loss of material. This is achieved by fast and precise control of the compaction force with a new electromechanical spindle drive for the two rollers. In combination with a sensitive control of the variable gap via the screw feeding system, constant ribbon properties are assured over a wide production range from <1 to 200 kg per hour. Sophisticated equipment design facilitates easy handling and shortens mounting procedures during working shifts. A hygienic design and properly integrated cleaning nozzles allow for an effective WIP process. The BRC 100 achieves ribbon granulation with the Bohle Turbo Sieve (BTS 200). The conical sieve design allows gentle particle size reduction at

Major European contract pharmaceuticals developer and manufacturer Recipharm recently called in Thorite engineers to carry out a data logging survey of compressed air production at the company’s UK facility in Ashton-under-Lyne. The plant's two existing compressors, which power the total processing requirement, were found to be far from energy efficient. This led to Thorite recommending a single advanced HPC CSD125SFC variable speed compressor to take their place. The new compressor is now fully commissioned and already providing impressive benefits. Compared with figures prior to the new compressor’s installation, Recipharm’s annual energy profile will see carbon output reduced by nearly 64 tonnes, whilst electricity consumption will fall by well over 100,000 kWh and energy bills will drop by nearly £9,500 each year. Speaking of this much improved situation, Les Williams, Recipharm's Project Engineer, said: “Thorite’s data logging exercise enabled inefficiency problems to be precisely identified, and their expertise has produced a fast and economic solution. The new system will pay for itself from cost savings alone in

low sieve speeds, which is also applicable at high material throughputs. A variety of different sieve types makes it flexible for different product and ribbon properties. The BRC 100 meets QbD requirements with its functional GMP design as well as its ability to implement different PAT tools. L.B. Bohle Maschinen + Verfahren GmbH +49 2524 9323 150 t.borgers@lbbohle.de www.lbbohle.de

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considerably less than three years, leading to an increase in overall profitability, but the environmental advantages are just as important and already happening.” Thorite’s data logging, leak reduction programmes and complete compressed air audits and surveys are just some of the services available to any company that utilises compressed air and needs to ensure improved energy efficiency whilst complying with all current legislation. Thorite +44 1274 663471 ross.gowler@thorite.co.uk www.thorite.co.uk

MANUFACTURING PRODUCTS & EQUIPMENT ROUNDUP Granulation and Drying Process Eliminates Operator Contact The ROTO CUBE is a high shear granulator and single pot processor for the complete wet granulation and drying process of any type of product, from the loading of raw materials to the discharge of dry granules. The process is carried out in a single, contained bowl, thus reducing risk of contamination and increasing protection for the operators. Therefore, the Roto Cube is highly recommended for manufacturing high potency drugs. The ROTO CUBE design allows for the optimisation of room layout. The product bowl is located in the processing area, hinged to a column, and installed through the wall. Utilities can be located in a technical area, minimising the process area. ROTO CUBE can be equipped with a lifting system to adjust the height according to the task. During the process, as well as maintenance and inspection, the machine can be lowered to facilitate access to the bowl. In addition, the bowl can be positioned higher for a good product flow into a collecting intermediate bulk container (IBC) during discharge. The product bowl can tilt during the vacuum drying phase to provide gentle treatment of granules, preserving them from breakage. Moreover, the gas stripping system (GA.ST.), by injecting an inert gas through the product mass, enhances evaporation rate. Microwave assisted drying is also available. The machine guarantees reliable monitoring and control of all process

Focus on Process Control Ensures High Tablet Coating Uniformity

parameters, including accurate detection of the process end-point. The ROTO CUBE CIP system, with selfcleaning metallic filters, is very quick and easy to validate. A complete range of machines for laboratory and production purposes, up to 3,000 l (bowl capacity), are available. IMA S.p.A. IMA Active division +39 051 6514111 mktg.soliddose@ima.it www.ima-pharma.com

Gebr. Lödige Maschinenbau has developed the new LC coater series especially for the coating of tablets. According to the company, during the designing stage, optimum process control was priority and applied to all three sub-processes — spray coating, mixing and drying of tablets. The LC coater series is characterised by a new nozzle arm concept to spray on the coating, which allows the nozzle position to be perfectly adapted to the tablet bed. This makes it possible to easily adjust the correct spraying distance and angle at any time in order to achieve an outstanding result. The arrangement and number of nozzles accelerate the process. The applied high-performance air system also ensures short processing times. A fully perforated drum, with a free area of more than 40%, allows for a very high air flow. Therefore, an excess of energy is available for the coating process, guaranteeing a smooth and reliable process. Efficient mixing elements also contribute to excellent product quality. They allow uniform and gentle mixing of tablets, even with variable degrees of filling from 30 to 100% — an absolute prerequisite in order to achieve the extremely high coating uniformity required by the pharmaceutical industry. The drying process has also been

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improved. The drying energy applied is used effectively by guiding the drying air flow directly beneath the spraying zone onto the tablet bed. In this manner, the airflow ensures fast drying of wet surfaces. The air supply is extracted through the tablet bed. Owing to their sophisticated processing technology, the coaters of the LC series operate up to 40% faster than conventional devices, while saving roughly 20% on costs. The coaters also collect plus points in terms of their ease of operation. When designing the new Lödige LC coater series, emphasis was placed on comfortable loading, unloading and maintenance. Gebr.Lödige Maschinenbau GmbH +49 5251 309 208 spittka@loedige.de www.loedige.de

MANUFACTURING PRODUCTS & EQUIPMENT ROUNDUP Hand Contact-Free Mopping System Reduces Risk of Cross Contamination Available exclusively in the UK from Cleanroomshop.com, the new PurQuip ERGO precision cleanroom mopping range is designed to lessen user cross contamination with its hand contact-free system. PurQuip ERGO provides consistent results, ergonomic usability and efficiency at outstanding value. When faced with so many options to clean and disinfect cleanroom floors, walls and ceilings, it is hard for organisations to find the right solution for them. In most cases, using a wet mopping system offers better ongoing value than using a wipe mopping system. However, some organisations have found the initial investment in a quality mopping system prohibitive. ERGO’s resistant and autoclavable

plastic buckets form part of an excellent value wet mopping system, suitable for use in ISO Class 5–8 cleanrooms and GMP Grade A, B, C and D areas. They provide a lightweight alternative to higher value stainless steel bucket options, which are typically only required for ISO Class 3–4 pharmaceutical environments. Housed in an electro-polished stainless steel frame fitted with ESD castors, the double or triple bucket systems are durable and easily manoeuvrable. The time-saving, hand contact-free mop-wetting system reduces cross contamination risks. The PurQuip ERGO double bucket system is ultra-compact for use where space is at a premium, whereas the ERGO triple bucket systems offer the perfect results in just three

steps: hand contact-free pick-up of a new mop, activation of the mop wetting device and discarding of the used mop following wiping. The ERGO range is available exclusively in the UK from Cleanroomshop.com. A wide range of compatible mop frames, mop sticks and mop heads to suit every grade of cleanroom and application, as well as disinfectant solutions, are also available. Connect 2 Cleanrooms & Cleanroomshop.com +44 1524 813022 info@cleanroomshop.com www.cleanroomshop.com

Brochures Describe Complete PAT Implementation Suite Optimal Industrial Automation has produced a new set of brochures describing the features, benefits and range of applications for all the modules in synTQ V4.0, its newly released software suite for process analytical technology (PAT) implementation in the life sciences, food and petrochemical sectors. synTQ V4.0 is designed to provide companies with a single, robust and proven software platform to develop, deploy and manage PAT from their research laboratories to global production networks. The modular structure of the synTQ platform allows users to select the functionality best suited to their specific needs, allowing a quick and cost effective implementation, with the confidence that it will always be possible to upgrade or add additional capabilities

without the need to revise or rebuild existing data structures. Currently, synTQ V4.0 comprises the following modules, each of which is described in detail in the new brochure pack: • synTQ Lite is a cost-effective, entrylevel PAT implementation manager that can be deployed on any single instrument system, whether in the development laboratory or on the shop floor. • synTQ Flexible Manufacturing is a fully capable, flexible PAT implementation solution that can be deployed on any number of instruments and processes. • synTQ Reporting Services is an application that allows the creation of printed- and web-based PAT reports from data stored within the synTQ database, independent of plant level, real-time synTQ systems. The system allows plant

management, operators and R&D engineers full visibility into current and historical process performance, without disrupting the real-time control of production. • synTQ Enterprise Master is a comprehensive, web-enabled server that allows companies to connect and coordinate multiple, separate, real-time synTQ applications with centralised storage and data management. synTQ Enterprise Master is designed for modern global manufacturing supply chains, where process owners may wish to manage manufacturing at multiple owned or supplier sites. In addition, an overview brochure provides a detailed introduction to the capabilities of the complete synTQ V4.0 suite for users unfamiliar with the system or those new to the concept of PAT implementation management.

Optimal Industrial Automation Ltd +44 1454 333 222 mgadsby@optimal-ltd.co.uk www.optimal-ltd.co.uk

Downflow Booth Meets Customer Demand for Low Noise Operation

Software Product Ensures Transparent Management of Starting Materials at Grünenthal

Hosokawa Micron has launched the new design, low noise Whisper-Booth. This compact downflow booth achieves noise levels of approximately 60 dba, which is less than a normal conversation, making it one of the quietest downflow booths on the market today. Capable of delivering OELs of <1 µg/m3, this new downflow booth is ideal for applications where it needs to be positioned within quiet zones or within multiprocessing areas where acoustic interference would be a problem and when silent running is more preferable. Always at the forefront of containment technology design, Hosokawa Micron engineers have worked closely with customers in the development of the Hosokawa WhisperBooth to ensure it meets both containment and low noise level requirements. “In using a combination of high efficiency, low vibration and quieter running motors, low noise fans and high

The research-based international pharmaceutical company Grünenthal will deploy the PAS-X Process Development package. The group is a leader in the field of pain therapies and invests more than a quarter of its revenues in R&D. Operating Werum’s PAS-X Process Development, pharmaceutical and biotech companies can simplify and accelerate the modelling of manufacturing processes for preclinical and clinical studies. Grünenthal will initially install the package for substance tracking of clinical batches at its plant in Aachen, Germany. “With PAS-X Process Development, we are capable of tracking the use and consumption of all raw materials in pharmaceutical development,” said Dr. Martin Lueck, Vice President Head of Pharmaceutical Development & Drug Delivery at Grünenthal. “This enables us to further increase the efficiency of our development activities.” In addition to PAS-X Process Development, Grünenthal will deploy the PAS-X business functions Master Batch Records, Warehouse Management and Weighing & Dispensing.

density sound attenuating insulation, we have been able to create a unique downflow booth that operates at whisper sound levels,” explained Carl Emsley, Hosokawa Micron. Hosokawa Micron Ltd +44 1928 755100 info@hmluk.hosokawa.com www.hosokawa.co.uk

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Grünenthal bundles all research and development activities at its campus in Aachen, Germany. Werum Software & Systems AG +49 4131 8900-689 dirk.ebbecke@werum.com www.werum.com

MANUFACTURING PRODUCTS & EQUIPMENT ROUNDUP Bag Dumping System Ensures Contained Dust-Free Material Transfer A new Flexicon bag dumping system, with glove box, bag compactor and flexible screw conveyor, isolates bulk material from the operator and plant environment throughout the opening, dumping and compaction of bags and conveying of material downstream. Bags are staged on a stainless steel tabletop and then transferred through a plastic strip curtain into a dumping enclosure comprised of a glove box, empty-bag chute and dust collector on top of a receiving hopper. The dust collector maintains negative pressure within the enclosure, preventing the escape of dust through the curtain, while containing dust generated during bag opening and dumping activities. A bag infeed chute through the sidewall of the enclosure allows the operator to pass empty bags directly into the bag compactor, causing dust generated from compaction as well as dumping activities to be drawn onto the system’s two filter cartridges. An automatic reverse-pulse filter cleaning system releases short blasts of compressed air inside the

Dust generated from bag opening, dumping and compaction is isolated from the operator and plant environment by means of a glove box, dust collector and integral bag compactor with sealed infeed chute. An enclosed Flexicon flexible screw conveyor transfers material downstream at any angle, dust free. filters at timed intervals, causing dust build-up on the outer surfaces to fall into the hopper, conserving useable product. Filters are readily accessed by removing the interior baffle and replaced rapidly using quick-disconnect fittings. The compactor employs a large pneumatic air cylinder to compress bags into a removable bin that accommodates 50 to 80 bags. The main waste access door and a flapper door within the bag infeed chute are equipped with safety interlocks that prevent operation of the compactor unless both doors are closed. The hopper discharges into an enclosed Flexicon flexible screw conveyor for dust-free transfer of a broad variety of products, including free- and non-free-flowing materials from large pellets to sub-micron powders, including products that pack, cake, seize, smear,

fluidise, break apart or separate, with no separation of blended products. Flexicon Europe Ltd +44 1227 374710 sales@flexicon.co.uk www.flexicon.co.uk

Automated Sampler for Dissolution Testing Minimises Cross Contamination The new Dissofract from Copley Scientific is a compact standalone unit for the automated sampling of tablet dissolution testing apparatus. It delivers minimal cross contamination and short sampling times, enabling accurate assessment of the dissolution profile of even fast release tablets. With a design based around the use of highly accurate bidirectional pumps, Dissofract offers the additional advantages of low dead volume and first in/first out (FIFO) operation, enabling data matching with manual results. The widespread use of tablets makes drug release or dissolution testing one of the most routinely applied analyses in the pharmaceutical industry. Manual dissolution testing is time-consuming and manually intensive as well as potentially subject to significant error, creating a demand for automation accessories. The Dissofract automatically removes samples from six to eight dissolution vessels at predetermined intervals and deposits them in test tubes or vials for subsequent analysis. It uses a series of bidirectional, small-volume diaphragm pumps (one line per vessel) to eliminate the problems associated with alternative designs centred on peristaltic or syringe pumps. The bidirectional pumps that drive the flush-samplepurge functions within Dissofract are extremely accurate, with a volumetric precision of <0.25 ml, typically around 0.1 ml. They deliver samples from the vessels on the FIFO principle employed in manual testing and provide a low dead volume system that keeps flush, sample and purge times to an absolute

minimum. Flush media recycling eliminates any requirement for media replacement and simplifies dissolution calculations. Cross contamination is typically <1%, even at the short, two-minute sample intervals required for quick release formulations, bringing new testing capability to the market. Copley Scientific Ltd +44 115 961 6229 m.copley@copleyscientific.co.uk www.copleyscientific.com

Ultrasonic Cleaning System Significantly Prolongs Life of Tablet Tooling An effective cleaning programme maximises the longevity of tablet compression tooling. Ultrasonic cleaning units complete this crucial maintenance step more quickly, thoroughly and cost-effectively than manual cleaning. Natoli Engineering’s ultrasonic cleaning system has features that reportedly improve the cleaning process even further, including: • convenient side-by-side design that makes transfers from washing to rinsing to drying quick and easy and reduces the risk of tool damage during handling • wash unit that offers 1,000 watts of ultrasonic power and includes filtration • drying unit with an additional air wand to ensure drying of the punch heads and a blower to dry the punch cups, ensuring that there is no water left in the cups, barrels or keys. EPM 10

According to Natoli Engineering, its ultrasonic cleaning solution is the safest, fastest and most comprehensive available to the tablet compression industry. Natoli Engineering Company, Inc. +1 636 926 8900 info@natoli.com www.natoli.com

MANUFACTURING PRODUCTS & EQUIPMENT ROUNDUP Airborne Particle Counter Reduces Cleanroom Certification and Monitoring Costs Merck Millipore, the Life Science division of Merck, has announced availability of the APC SmartTouch airborne particle counter for cleanroom monitoring, which is fully compliant with the ISO 14644-1 update expected to be released in 2013. The units are factory calibrated in compliance with ISO 21501-4. The APC SmartTouch is an easy-to-use airborne particle counter, designed to reduce cleanroom certification and monitor costs while minimising the likelihood of human sampling errors. “Environmental monitoring is essential in today’s industries,” noted Anne Connors, Regional Marketing Manager, Merck Millipore. “It not only minimises

risks to consumers and producers, it saves time and reduces costs by preventing the release of potentially contaminated products. Our complete portfolio for environmental monitoring solutions includes the APC system for particle counting, active and passive air monitoring as well as surface and personnel monitoring, all of which improve quality, increase safety and reduce production risks and expenses.” The system offers dual flow rates for cleanroom filter testing and monitoring, therefore eliminating the need to invest in multiple instruments and reducing costs associated with routine calibration events. Equipped with two high-capacity

batteries, the instrument is designed for continuous sampling and reportedly offers the largest memory capacity on the market. The visual representation of sampling locations, including designated sampling points, minimises risk of human errors. The instrument’s large colour touchscreen with commonly used icons facilitates easy and intuitive operability. All required actions start from the main screen, with no need to access sub-menus, increasing operating efficiency and saving time. The instrument is easy to clean and disinfect and comes with many accessories, including a compressed gas adaptor for high pressures.

Merck Millipore +1 978 715 1567 karen.hall@emdmillipore.com www.emdmillipore.com

Multifunctional Milling System Granulates Heat-Sensitive Products

A core component of Frewitt’s new mill, the OscilloWitt, is its oscillating rotor, which was borrowed from the previous model (MF line) in order to provide customers with the advantages of the company’s tried and proven oscillation process — less heat build-up and a milled product with more uniform grain size and minimal fine particles. It is possible to work in the oscillating as well as rotary mode when working with both the OscilloWitt-3 and the OscilloWitt-6, offering more flexibility while lowering investment costs. Due to the new step-by-step readjustment of the oscillation amplitude, the unit requires less frequent maintenance, which in turn lowers maintenance costs. The simple acceleration of the oscillatory motion by a variable angle and the simplified setting of the rotor/sieve distance also ensures greater ease of use. The OscilloWitt was specifically made for milling and dosing dry, moist and heat-sensitive, hard-to-process products. The minimum necessary impact energy and the continuously variable rotor speed ensure that just the right amount of shearing and friction forces are exerted on the product in order to convey it gently through the sieve. This special process, complemented by the tight seals and the automatic cleanability of the system, results in an exceptionally uniform and consistent product quality, which is equally important for processing ingredients in the pharmaceutical industry as it is for preparing flavourings, vitamins and proteins in the food industry, not to mention the diverse processes in the fine chemical industry that are based on gentle methods. Frewitt SA +41 26 460 74 00 info@frewitt.com www.frewitt.com EPM 12

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I Holland Ltd, UK +44 115 972 6153 info@iholland.co.uk www.iholland.co.uk

Punch and Die Oils, Lubricants and Cleaning Agents

10 11 12 13

11 12 13

10 11 12 13

EPM 15

Tooling Storage Systems

Tooling — Rotating Head

Tooling — Prototype

IMA S.p.A., Italy +39 051 651 4111 mktg.soliddose@ima.it www.ima-pharma.com Natoli Engineering Company, Inc., US +1 636 926 8900 info@natoli.com www.natoli.com

Fette Compacting GmbH, Germany +49 4151 12 0 tablet@fette-compacting.com www.fette-compacting.com

Tooling Validation and Storage Systems

10 11 12 13

Tooling — Multi-Tipped

Tooling — Interchangeable

Selection of Steels

Punch Polishers

Elizabeth Europe, France +33 2 54 90 21 20 gautier@epmo.com www.elizeurope.com

Punch Design Analysis

Casburt TMS, UK +44 1782 332511 info@casburt.com www.casburt.com

Punch Bellows and Drip Cups

Bosch Packaging Technology Ltd - Manesty, UK +44 151 547 8000 sales.packaging-kny@bosch.com www.manesty.com

Punch and Die Measuring Software

Adamus HT, Poland +48 91 4599 101 marketing@adamus.com.pl www.adamus.com.pl

Punch and Die Coatings and Treatments

tablet tooling

Punch and Die Cleaners

buyers’ guide

Additional

Service/technical support.

Tooling audits, training and troubleshooting.

Ceramic and carbide-lined dies, teflon tip punches and training and troubleshooting.

EXPERT INSIGHTS Achieving Fast & Economical Production of High Quality Tablets

The tablet remains the most popular dosage form and tabletting equipment has evolved significantly over the last decade to accommodate the ongoing demand for its advancement. Big pharma and their generic opponents increasingly seek to gain the competitive edge, producing tablets that boast improved ‘drug delivery’ capabilities, attained through the application of taste-masking, enhanced solubility and timed/delayed release technologies. EPM Editor Elizabeth Valero consulted key representatives at tabletting equipment providers Elizabeth Carbide, I Holland, IMA and Natoli Engineering on current trends and key factors for achieving the fast and economical production of high-quality tablets.

Ryan Keefer General Manager at Elizabeth-Hata International, a division of Elizabeth Companies. Steve Deakin Business Development Director at I Holland Ltd. Stefania Barzanti Marketing Manager at IMA S.p.A.IMA Active. Charles Kettler Director at Natoli Scientific, a division of Natoli Engineering Company, Inc. ‘Sticking’ and ‘picking’ (where product adheres to the punch faces or within the embossing of the tooling), are cited as the most common and costly issues during tablet production, resulting in substantial losses of product and lengthy periods of downtime, how can their occurrence be minimised or eliminated? Keefer: Elizabeth’s tablet design staff work with customers to maximise the overall tablet design and eliminate areas in the tablet configuration that could cause sticking and picking. Certain tablet design characteristics can be utilised on the punch face to reduce and eliminate these issues. Another alternative method is the use of specific tool steel coatings that can be used to reduce sticking and picking on the punches. Depending on the product application and type of tool steel being used to manufacture the punches, there are several good coatings that can be used to help resolve these issues. Deakin: Good tablet design can often reduce the possibility of both sticking and picking. Whilst picking can normally be eliminated completely by design changes, the root cause of sticking can be attributed to many different factors associated directly with the type of formulation; Van der Waal Forces and capillary action for example. The use of anti-stick tool coatings is now accepted across the industry as these new and innovative coatings or treatments can eliminate sticking. It has always been difficult to persuade people to try different coatings owing to the additional costs involved, but now there are good case studies available showing the increased production value of such coatings. Specialised coatings can significantly increase the price of tooling but when successful, the savings clearly outweigh

the additional costs as the increase in product yield and manufacturing efficiency is easily quantifiable. When selecting the correct coating, it is essential to share the full details of the problems being experienced so the correct recommendation can be made. Barzanti: Reasons for sticking and picking can be related to the product to be compressed, like quality and characteristics of the raw materials — for example, particle size and moisture content — plus inconsistent wetting and drying during granulation, lack of lubricant or inefficient blending. A careful drying process is essential to achieve a more consistent blend. Lubricants must be properly screened to remove over-sized particles and must be evenly blended into the formulation. When sticking is related to a melting and/or hygroscopic powder, achieving compression at a low temperature and low humidity can help a lot in solving the problem. Also, the tablet press can be adjusted to minimise these problems, reducing punch penetration and increasing dwell

time; while with a gravity press to extend dwell time it is necessary to reduce the speed, with our Comprima tablet press dwell time can be easily extended by playing with the compaction and precompression axis. In some cases, changing the tool surface finish is enough to stop sticking and picking; chrome plating, for instance, produces a smooth and nonadherent face on punches and this can be a solution. Kettler: Many of the sticking and picking problems that we see are due to required changes in process variables as the product moves from clinical supply production to larger scale product launch manufacturing, often after the formulation has been submitted and accepted by the regulatory agency. The desire to have a direct compression formulation, driven by the perceived capital and labour cost reduction, often prompts a speed to market mentality that limits the R&D required to design a formulation that runs with minimal problems at both production scales.

Adhering to a well-thought out drug product design process and flowchart can minimise future problems by identifying the potential risks and addressing them through thoughtful studies. Having qualified and experienced drug formulators who can utilise their experience of past successes and failures is key to knowing what studies are required and what the consequences are when data are not generated to address the risks identified during the drug product failure mode and effects analysis (FMEA). To what extent is quality and consistency of tablets contributable to choice of excipient and granulation specs and flow? Keefer: These are major factors. Pharmaceutical R&D groups are involved in many different product development processes, trying to determine the best excipient choice for a particular product. Formulation characteristics, tablet specifications and granulation flow are all important factors in order to achieve consistent quality during tablet production.

A scientist performing tablet compression research on the NP-RD10A in the Natoli Scientific laboratory (Natoli Engineering Company, Inc.). EPM 16

MANUFACTURING PRODUCTS & EQUIPMENT EXPERTINSIGHTS Deakin: With regard to sticking, spatial heterogeneity of the ingredients within the tablet is critical. This is because of the possibility of one ingredient causing sticking; so if this ingredient is concentrated in one area of the compressed tablet, then the Van der Waal Forces in bulk behavior could initiate sticking. To ensure improved tablet quality and consistency, and to avoid the possibility of sticking and picking, one should check the moisture content of the granule and increase lubrication in the granule if necessary. Also, check humidity within the compression room. Granule characteristics will always play a major part in the behaviour of the product during compression. Quality product, formulation and process controls will always assist in the compression of a successful tablet.

which reduces with increased speed. This may cause issues such as air entrapment, leading to capping and scrapped tablets, sticking and tablet weight variation caused by poor flow. There are available solutions for reduced dwell time, an example being the EU441 extended dwell tooling, although these types of innovation mean considerable outlay as the turret and associated parts of the tablet press have to be changed to accommodate the tooling design. There is an option to modify the head flat of a standard B or D type punch, which has to be done in a controlled way but can increase dwell time without the need for major modifications to the tablet press. This is a relatively small enlargement of the head flat and it can help reduce the negative effect of increased press speed.

Barzanti: To obtain a tablet, the powder to be compressed must possess very precise physical and mechanical properties. A good flowability is required for consistent filling of the product in the die, while at the same time the granulate must feature enough compressible and cohesivene properties to form a tablet. As a general note, a high content of fines should be avoided as it is one of the major causes of problems during tabletting and this is why a granulation process is normally required. The choice of excipient and granulation specs are of major importance to obtain a tablet of good quality and consistency and of course these are different from product to product. Performing tests of the complete process — granulation, blending and tabletting — can be of great help in understanding how the processing parameters can be adjusted to achieve the best result. With this aim, IMA makes available to customers a team of process specialists and a process and development laboratory where all the appropriate instrumentation is available to carry out different technological tests.

Barzanti: Speed depends on two main factors — accurate feeding of powder into the die and dwell time, i.e. the time during which compression is applied, ejecting the air contained in the powder and locking the particles in place. In 1994, IMA introduced the COMPRIMA tablet press, which we believe still represents the real innovation in tablet compression at high speed. The powder is fed from an upper loading hopper into the central rotor area and moves towards the dies through the specially shaped radial channels, pushed by the centrifugal force generated by turret rotation. This system ensures accurate and consistent feeding of the dies, even at high production speeds and with difficult-tohandle products, while at the same time minimising the quantity of air incorporated into the powder and to be ejected during the compression process. It is a unique system owing to the fact that if offers an extended dwell time, made possible by the combination of compression wheels and bearings applied on punch heads, which results in a longer compression time, even at high speeds.

Speed is critical in today’s tabletting production environment, what have been the most effective speedincreasing developments in recent years and what is the outlook for bettering the production rates currently being achieved? Keefer: Production speed is definitely a key factor, however making consistent quality tablets to certain specifications with limited machine downtime seems to be even more important. High production speeds without maintaining quality is a recipe for disaster. The tablet presses and automation features continue to improve as far as mechanical capabilities, but sometimes the product granulation can be a major limiting factor due to poor flow characteristics that ultimately affect the machine production speeds. Deakin: Whilst increased tablet output is a main driver for most tablet manufacturers, increased tablet press speed is not always the answer. Productivity can be increased by the use of multi-tip tooling without the need to increase tablet press speed. Increased tablet press speeds can have a negative impact on tablet quality because of a reduction in dwell time,

Kettler: Multi-tip tooling has presented an opportunity to quickly increase tablet production. The cost difference is not significant relative to the increase in production as well as the value of the drug product delivered. If a formulation performs well with single station tooling, then the probability of encountering problems when shifting to multi-tip

Hata CVX triple layer and core tabletting press (Elizabeth Companies).

Comprima high efficiency tablet press (IMA S.p.A.-IMA Active). tooling is low. It is low as long as the tablet press operators realise that there will be a measurable increase in the need to be diligent in press setup as well as the need to run trial lots of material to ensure tablet weight uniformity and hardness meet the specifications for tablet disintegration and content uniformity. As with any formulation design, the potential for sticking and picking is reduced during the development process. For a presentation that will be manufactured using multi-tip tooling, consideration for that reality should be addressed during drug product development.

popular as part of the lifecycle management strategies to extend intellectual property and minimise generic exposure of mature pharmaceutical products. For sure, technical solutions have to be developed in the tabletting process to really exploit the potential of this market trend.

Also, multi-layer is significantly slower and has a far greater scrap rate than single-layer tabletting, do you foresee the speeds and scrap rates for multilayer improving in the near future?

Keefer: Yes, we do think that this trend will continue for multi-layer products. Multi-layer tabletting is a unique way to extend the life of a product’s patent or combine two different drugs for an extended release or slow release product. Many companies are involved in multi-layer and some newer coretabletting developments for tablet-withina-tablet technology. These are all unique methods for specific product applications that should continue in the future.

Keefer: Yes, Elizabeth has developed a very good mechanical design on the Hata tabletting press for multi-layer production. The Hata press has single-, bi- and tri-layer production capabilities. More recently, tablet press speeds have been able to increase along with tablet quality because of better tablet rejection methods and enhanced tablet layer sampling. Scrap rates should also continue to decrease owing to these mechanical improvements. Barzanti: Definitively, speed and scrap rates are well-known problems when dealing with layered tablets; first layer compression, sampling, final compression and both hardness of layers and their separation are all issues. Some technical solutions trying to improve these are available, although so far there is no real solution. This is why, as a global supplier, we see an increasing trend of capsule filling machines for dosing product combinations, as this process can be accurately controlled and performed without affecting machine speed. However, fixed dose combination drugs are becoming increasingly

EPM 17

Interest in multi-layer tabletting has increased considerably in recent years — mainly because of its ability to accommodate multiple and often incompatible products — do you envisage this continuing and are there any recent or pipeline developments worthy of mention?

Barzanti: If we think of fixed dose combination drugs as a way to treat two closely related diseases or to improve compliance and thus efficacy of prescribed medicines, we believe that this trend will continue. However, multilayer tablets could be a less frequent option if in the future the drugs to be combined are designed for being mixed in a unique powder to be processed in a standard tablet press. In fact, today most of the combined actives are existing drugs, while in the future a higher number of combinations will be achieved with new formulations specifically designed to be combined from the development stage. In this case, the properties of the different compounds are optimised to be combined, minimising possible interactions so that it is not necessary to keep the different drugs separated in layers. Continued on page 18

MANUFACTURING PRODUCTS & EQUIPMENT EXPERTINSIGHTS Quality by Design (QbD) and continuous manufacturing are steadily gaining traction in the pharmaceutical industry, how do you predict these strategies will affect or change tabletting in the future? Keefer: Continuous manufacturing seems to be a key buzz phrase right now. We believe a stronger focus on reducing machine downtime and performing equipment cleaning processes off-line is paramount, as these will continue to be key to bettering overall tablet production efficiency. This falls in line with the methodology behind continuous manufacturing. Tablet press machinery providers must continue to focus on reducing machine downtime and improving cleaning methods as these will be important factors in tablet press selection. Deakin: The ethos of QbD will most certainly have an impact across the tablet manufacturing marketplace and we are beginning to see this initiative take shape already. We expect this to result in more stringent demands on suppliers of tablet tooling and the associated services we offer such as tablet design. QbD by definition is that quality can be planned and that most quality crises or problems relate to the way it was planned in the first place. This is exactly the philosophy that we have applied day in, day out to our tablet and tooling design process for many years, trying to design out any potential production problems through adopting best practice

techniques before the tooling hits the compression room. Barzanti: The concept of QbD is strictly related to critical quality attributes (CQAs) of the product and to the critical process parameters (CPPs) that are controlled in order to ensure that the product attributes are within the desired limits. Most tablet presses are now fitted with indirect weight control through compression force, allowing 100% in-line control of the most important CQAs of a tablet, such as the weight, as well as self-adjustment of machine working parameters to keep the process within the proper design space. Tablet hardness and thickness can be statistically controlled with an IPC auxiliary unit. In the future, an increasing number of process parameters will be controlled on-line, with the aim of ensuring the quality of other critical tablet attributes and possibly to achieve a real-time release. Concerning continuous manufacturing, this is not an issue for the tabletting process as this is already running continuously. Probably one of the most important changes will be an increasing integration with upstream and

Tool coatings are accepted industrywide as a solution for sticking (I Holland Ltd). downstream processes (granulation and coating) as soon as they have been developed to operate in a continuous mode. Again, a very important presupposition for such an integration is a good control of the process and a quick feedback on the machine parameters, therefore avoiding any disturbance in the upstream parameters to propagate downstream. Kettler: QbD will be adopted, in one form or another, by all drug providers who recognise the need to present their drug development process in a format

EPM 18

that is expected by the regulatory agencies. Continuous manufacturing offers opportunities for companies to better leverage return on their capital assets as well as produce drug products on a reduced timeline. QbD will play an integral part in continuous manufacturing. The formulation generated by a continuous process must perform on the tablet press without problems so that the tablet manufacturing process is indeed continuous. Powder flow and compression must be designed to meet the needs of all of the unit operations, not just the tablet press.

SHOWCASE PUMPS & VALVES Hygienic AODD Pumps with Full Stroke Diaphragms Deliver Outstanding Containment Wilden’s Saniflo HS (Hygienic Series) metal air-operated double-diaphragm (AODD) pumps have been specifically designed with a variety of features to help pharmaceutical manufacturers maximise their process efficiency, including a number of elastomer options such as its new full stroke PTFE integral piston diaphragms. These diaphragms offer exceptional product containment and are an excellent choice when pumping highly aggressive fluids within the pharmaceutical processing industry. Wilden Saniflo HS metal pumps are FDA and EHEDG certified. Saniflo HS pumps are available in four sizes from 13 to 76 mm. They are available with flow rates up to 918 l per minute and are offered in 316 stainless

steel. A variety of connection options are available, such as DIN clamp, SMS clamp and Tri-clamp styles, to meet specific requirements. Saniflo HS pumps are also available with specialised air distribution systems such as the Pro-Flo X air-distribution system (ADS), which offers operational flexibility through its state-of-the-art efficiency management system (EMS). The EMS allows each pump to be finely tuned by adjusting the air volume at the pump inlet with a variable control dial. By turning the EMS dial, users can either maximise flow to get the job done fast or maximise efficiency to reduce processing costs. In addition, Wilden offers an online Pro-Flo X simulator that can help pharmaceutical processors fine tune

their pump performance and lower operational costs. The simulator is located on the ‘See More Green’ website at: www.wildenpump.com/seemoregreen.

Wilden Pump & Engineering +1 909 422 1730 wilden@wildenpump.com www.wildenpump.com

Advanced Slide Valve Technology Guarantees Dust-Free Operation Process Components, manufacturer of the successful MUCON iris diaphragm valve, recently launched a range of pneumatic and manually actuated, double flanged, in-line slide

valves. This advanced series of MUCON slide valves has a patent pending with no less than fifty-three claims. Quick to gain recognition, the MUCON SD-P slide valve was put forward as a contender for this year’s POWTECH/TechnoPharm New Innovations award. The salient features and benefits of the MUCON SD-P slide valve are: • robust total shut-off solution, ideal for use with powders, granules and pellets

• durable self-compensating polymer seal that ensures the blade on the slide valve is fully dust tight and therefore prevents material escaping into the atmosphere • total unobstructed full bore opening • smooth, non-jamming operation • ability to cut through a static column • self-cleaning, owing to low friction resilient polymer sealing surfaces • seal loading system that ensures the slide valve requires exceptionally low

levels of maintenance, resulting in reduced manufacturing downtime, increased productivity and cost savings • ATEX Cat. 1D/2D approved as standard. Process Components Ltd +44 1625 412000 sales@mucon.com www.mucon.com

Heavy Duty AODD Pump Handles 9 MM Solids at Up to 17 M3/Hr Flow Rates

Two-in-One High Containment Valve Guarantees Safe Transfer of Active Products

Almatec has expanded its line of BIOCOR Series aseptic air-operated double-diaphragm (AODD) pumps with the addition of the B40 model. Like all BIOCOR pumps, the B40 is ideal for use in sanitary product-handling applications found in the pharmaceutical and biotech industries. The B40 is the third member of Almatec’s BIOCOR family, joining the B20 and B32 models. It is the largest and heaviest BIOCOR pump at 67 kg. and dimensions of 462 x 270 x 681 mm. This added weight and size gives it the capability to handle solids as large as 9 mm and deliver flow rates up to 17 m3 per hour (75 gpm), all at operating pressures of 7 bar (100 psig) and maximum operating temperatures as high as 80˚C. The BIOCOR B40 model features no drives, no rotating parts, no shaft seals within the fluid and a stepless flow control that operates via air pressure and volume without the need for complex mechanical control units, which prevents overpressure while ensuring outstanding output and efficiency. The material for the wetted housing parts is electro-polished 316L stainless steel with

The TWINVALVE is a simple and reliable solution for the high containment handling of powders, granules, tablets and capsules. It can be used as a standard butterfly valve on bins, and it can be easily retrofitted on existing powder handling plants, allowing containment during powder transfer and high flexibility. The TWINVALVE system has a simple design based on the combination of two independent sanitary butterflys; one positioned on the loading/discharge port of the container/bin and the other on the loading/receiving station. The valve on the container is a standard sanitary butterfly valve, while the other one is a sanitary butterfly valve fully integrated in a cylindrical mini hopper. TWINVALVE is equipped with a patented cleaning spray head assembled inside the active part of the valve. This head is telescopic and is extracted only during the cleaning phase, while during the standard product transfer operations it remains on its site. The intermediate chamber between the

a centre block of PE conductive, while the diaphragms, ball valves and O-rings are made of PTFE or EPDM. Almatec B40 pumps are compatible with the certifications for hygienic design and cleanability from the EHEDG, FDA and Class VI regulating organisations as well as the ATEX 94/9/EG directive for pump use in potentially explosive atmospheres. Almatec Maschinenbau GmbH +49 2842 961 0 frericks@almatec.de www.almatec.de

EPM 19

two valves can be cleaned by compressed air, water or solvent and/or steam, allowing the processing of a wide range of active products. During the cleaning phase, this chamber is kept on negative pressure conditions, avoiding any possible contamination of the environment and/or product. OEB 5 (≤1 µg/m3) can be achieved by cleaning with compressed air. IMA S.p.A IMA Active Division +39 051 6514111 mktg.soliddose@ima.it www.ima-pharma.com

Industry News

Major Re-Brand for Tablet Testing and Bulk Handling Equipment Supplier

The launch of a new Accessories division and e-commerce website mark the latest stage of development for JB Pharmatron Group (JBPG), a leading supplier to the pharmaceutical and life sciences sector. The new online shop offers over 1,000 consumables and dissolution products at competitive prices from a range of manufacturers. Three other key business units cover consulting, equipment and servicing. This new Accessories division is an integral element of a major re-branding

initiative following an extensive review to support the evolution of the business as a specialist consultant and supplier of tablet testing and bulk-handling equipment. JBPG is a preferred supplier to many of the world’s leading research and manufacturing pharmaceutical companies. With offices in the UK and Republic of Ireland, the company is now better positioned to maximise its increasing recognition as an industry leader and provider of these specialist services. Unveiling a new logo, tagline and interactive website, Managing Director Jamie Barnes said the new brand identity reflected the Group’s commitment to providing the very best service to meet clients’ needs. The dynamic new website strengthens the Group’s online

presence by enhancing its digital marketing capabilities. Among the special features is a real-time ‘Q&A’ forum. The tagline ‘Proven When Tested’ underpins the Group’s dedication to providing the exceptional standards of testing and after-sales service expected by those working in such a demanding environment. Advertising and marketing agency Passion for Creative was selected after a stringent pitch process to lead the re-brand project, working closely with staff across the business to devise an identity that would reflect JBPG’s core values and forward-looking strategy. Barnes said: “While retaining our established values, it’s vital that we continue to evolve and promote a contemporary image to encompass our new services and everything that

we can offer as a one-stop provider. This change is a logical step in our succession plan and creates a platform from which we can continue to expand our products and services during our next phase of growth. “Our new brand identity communicates both to our existing and potential customers that we provide products and services that consistently outpace our competitors with a flexibility that many others cannot match. It demonstrates that we are an innovative and forward-thinking organisation working in partnership with our clients to ensure their success.” JB Pharmatron Group +44 1604 878420 theresa.percival@jbpharmatron.com www.jbpharmatron.com

Acquisition of Pharma and Healthcare Packaging Specialist Completes Filtrona plc has confirmed the completion of the acquisition of Contego Healthcare Ltd, which will now operate as part of its Coated and Security Products (C&SP) division, which includes Payne, Payne Security and Duraco. The Contego business will be led by Managing Director Gerard Harford, who will report into Alison Evans, Managing Director, C&SP. The acquisition enhances the range and opportunities offered to existing Contego and Filtrona customers and also provides access for both companies to potential new customers through leveraging their combined skills. “Through our Payne business, we are already focused on the development of packaging solutions that deliver added value in terms of convenience, safety and brand image through the incorporation of features that meet the critical demands of effective opening, closing, informing and protecting,” explained Evans. “We believe the

addition of Contego’s capabilities to the Filtrona C&SP Division will provide pharmaceutical and healthcare manufacturers with an extensive range of tailored packaging solutions that meet a wide variety of product and end-user requirements.” Evans said a number of C&SP technologies are highly complementary to Contego’s proven expertise in the production of cartons, leaflets, foils and labels: “The combined business can offer an impressive depth of resource and enhanced global reach and will continue to innovate in the development of new products and solutions to meet the fast-changing demands of this dynamic sector.” Harford explained that the new expanded business is well-positioned to deliver a fast-response service to many different types and sizes of companies: “Our in-depth knowledge of the market and strong existing relationships with many blue-chip companies means we

have a solid understanding of the many demands and challenges of the sector. Now, as part of a stable and growth-oriented plc, we have an excellent opportunity to work together in the development of packaging solutions that will make a real difference.” Following the completion of the acquisition, it has been announced that Tom Reid and Leon Taviansky will step down from their respective positions as Chief Executive Officer and Chief Financial Officer of Contego. “Tom and Leon’s contribution to the success and growth of Contego has been immense,” said Evans. “Working

with the experienced management team they have established, we are confident we will take their vision to the next level of success and growth.” Filtrona plc +44 1908 359100 www.filtrona.com

Pharma Testing Solutions Provider Extends Global Reach with Major Acquisition The SOTAX Group, a global leader in the development and manufacturing of dissolution testing, automated sample preparation and physical testing equipment for the pharmaceutical industry, has acquired Dr. Schleuniger Pharmatron. Dr. Schleuniger Pharmatron, with headquarters in Thun, Switzerland, and a US subsidiary in Manchester, New Hampshire, is a company engaged in the engineering and manufacturing of equipment for the physical testing of pharmaceutical dosage forms, such as tablets, capsules, ampules and other solid dosage forms. With this acquisition, the SOTAX Group strengthens its global leadership

position as a solution provider for the pharmaceutical industry and reportedly becomes the world’s largest manufacturer of equipment for testing the physical properties of pharmaceutical dosage forms. “The acquisition and integration of Dr. Schleuniger Pharmatron is a further step towards ensuring sustainable growth by strengthening our innovation leadership,” explained Thomas Pfammatter, Chief Executive Officer of the SOTAX Group. “The Dr. Schleuniger Pharmatron brand stands for a long history of high quality and innovative technology. This will complement our existing product lines in an ideal way.” “Being part of a leading global

company with the worldwide sales and service capabilities of the SOTAX Group will open up new opportunities for us,” said Martin Strehl, Chairman of the Board and Chief Executive Officer of Dr. Schleuniger Pharmatron. “It puts us in a position to serve our customers and partners even better.” Dr. Schleuniger Pharmatron’s Manchester, New Hampshire based operations will be integrated into the Westborough, Massachusetts based Americas organisation of SOTAX Group. The Thun, Switzerland, site of Dr. Schleuniger Pharmatron will remain as a separate entity and become the hub of

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the physical testing business of the SOTAX Group. Leveraged by the extensive worldwide sales and service network of SOTAX, product and application specialists from Dr. Schleuniger Pharmatron and SOTAX will continue to deliver exceptional service and support to customers. SOTAX AG +41 61 487 54 54 info@sotax.com www.sotax.com

LABORATORY PRODUCTS & EQUIPMENT

Lab Information System Speeds Up Sample Storage Process For biobanks and laboratories looking to securely organise and track their stored samples, the new version 4.903 Track-IT information management system from Micronic enables users to scan tube codes directly into the software. With Micronic Traxcer code reader software now fully integrated with TrackIT, users can directly trigger tube or rack barcode scanning from the Track-IT program. The new version of the automation-friendly information management solution is capable of scanning in only five seconds and transferring the codes directly into the Track-IT database program. Track-IT is a LIMS/LIS solution designed to enable scientists to organise and securely track their storage tubes and samples in mere seconds. Fully compatible with most commercial barcode readers, rack scanners and tubesorter systems, Track-IT catalogues samples quickly and efficiently. The central information database produced by Track-IT is customisable to match a laboratory’s workflow as well as to match the unique aspects of different sample types. Track-IT has been designed to empower laboratory scientists to simply manage sample data and information and make it available to other colleagues in their organisation.

Built around independent modules that can interact with each other, version 4.903 Track-IT software is able to manage a wide variety of useful day-today laboratory information. The main concept behind Track-IT is that each scientist in the laboratory can quickly manage data and information and make it available to the rest of the laboratory community. Using Intranet support, data can be accessed from any connected computer in the laboratory, which accelerates information retrieval. Consequently, laboratory staff spend less time on recurrent and time-

consuming operations and dedicate more precious time to research activity. Track-IT allows users to simply import data from existing files into a common presentation, undertake cross database searches, quickly retrieve information and produce reports. Combining reliability, efficiency and ease of use with affordability, a single Track-IT licence covers all users within an organisation. Micronic Europe BV +31 320 277070 sales@micronic.com www.micronic.com

SIMS System Family Accommodates Broad Range of Budgets Secondary ion mass spectrometry (SIMS) is a versatile, highly sensitive technique for surface analysis and surface depth profiling of diverse materials. Hiden Analytical expands its primary system options to offer the choice of three initial equipment levels to suit a broad spread of budget capacities. All systems offer full ultrahigh vacuum (UHV) operation and expandability to the top-level specification. The dual-mode MAXIM mass spectrometer features operation both in the secondary ion mode and in the secondary neutral (SNMS) quantification mode. The Foundation SIMS system includes the IG20 fine-focus (50 µm) oxygen/argon ion gun, multiple sample holder and primary ion beam monitor. An uplifted version — the SIMS

Workstation — is configured for higher throughput rates with the addition of a sample load lock and sample manipulator, together with chargeneutralising electron flood gun and system backout facility. The SIMS Workstation Plus has the most comprehensive specification with the addition of the IG5C Caesium ion gun for electronegative species, having a spot size of just 20 µm. The MASsoft Professional SIMS PC data system provides automated measurement of positive and negative ions and of neutral species. It enables full control of the mass spectrometer and ion gun operating parameters and ion beam raster, with acquired data presented in real time. The ESM LabVIEW SIMS imaging program acquires, stores and displays the data

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for presentation in the form of elemental surface maps with both 2D and 3D view capabilities. Hiden Analytical Ltd +44 1925 445 225 info@hiden.co.uk www.hiden.co.uk

LABORATORY PRODUCTS & EQUIPMENT ROUNDUP Extensive Range of GPC/SEC Systems and Detectors Showcased on Website

Fully Automated System Allows for Drying or Concentration of Very Large Volumes

New pages on the Malvern Instruments website provide information that enables scientists to make informed choices about detector configurations for their specific gel permeation chromatography/size exclusion chromatography (GPC/SEC) applications. Showcasing the company’s comprehensive range of Viscotek systems and detectors for GPC/SEC, these pages help analysts to identify high productivity configurations for polymer, macromolecule and protein applications. Malvern’s product range includes high sensitivity refractive index (RI), ultraviolet (UV), dynamic and static light scattering detectors and a viscometer, all of which are available as part of a complete Viscotek GPC/SEC system or as individual modules to offer exceptional flexibility to those with existing chromatography systems. GPC/SEC is a central analytical technique for the analysis of proteins, polymers and macromolecules because of its ability to measure defining characteristics such as molecular weight, molecular weight distribution and molecular size. Modern GPC/SEC systems typically incorporate multiple detectors that work together to deliver information about the physical and structural features of the sample,

Genevac has announced the launch of the ROCKET 4D for the automatic drying or concentration of volumes from a few to 100 l in one operation with no user interaction. Simply load the sample, select a method, press start and walk away — the system will do the rest. Compact in size, the ROCKET 4D allows for the drying or concentrating of samples with complete confidence as it uses proprietary vacuum technology to suppress solvent bumping and foaming; problems associated with sample loss when using large-scale rotary evaporators. Rocket 4D comes as standard with a single, 5 l 316 stainless steel vessel for drying or concentrating products. This has detachable handles and is easily lifted into and out of the evaporator. Access to the dried or concentrated product in the vessel is very easy. Dried products can be scooped out or, where enhanced user protection is needed, re-dissolved while the vessel is still in the system. Liquid products can be easily drained via a drain port in the side of the rotor, using a dedicated pouring stand. Users wishing to dry volumes larger than 5 l require the ‘Autofeed’ option, which enables the Rocket 4D to draw in product from the user’s own external supply. The Rocket 4D controls product feed, drying and the discharge of condensed waste solvent without any external intervention. The autofeed system has an integrated rinse circuit that enables dried products to be automatically re-dissolved in a small volume of solvent at the end of the

enabling detailed investigation of, for example, polymer branching or the aggregation behaviour of proteins. The Viscotek range of detectors includes RI and UV technology for concentration measurement. A viscometer enables universal calibration, eliminating the need for relevant calibration standards, or, when used with a light scattering detector, supplies structural insight. Malvern offers both a low angle light scattering (LALS) detector and a dynamic light scattering detector (Zetasizer µV), either of which can be used to directly measure molecular weight and/or molecular size. By offering detectors individually and making each compatible with every make of GPC/SEC system, Malvern Instruments provides the analyst with the flexibility to tailor a detector array to maximise information flow and experimental productivity for their specific application. Visit the new pages at www.malvern.com/viscotek and discover more about the benefits of optimised GPC/SEC. Malvern Instruments Ltd +44 1684 892456 salesinfo@malvern.com www.malvern.com

process. Alternatively, the same circuit can be used under manual control for solvent exchange by selecting a different solvent for re-dissolve. Cleaning the Rocket 4D between cycles is also very straightforward. The PTFE feed tubing is easily detached for cleaning or replacement and the vessel can be readily cleaned, wiped, inspected and even put in a dishwasher. The ROCKET 4D also includes powerful cold traps that maximise solvent recovery, protecting the environment and improving drying of samples. Genevac Ltd +44 1473 240000 salesinfo@genevac.co.uk www.genevac.com/rocket4d

Reaction Monitor Provides Fast and Flexible Device for Labs and Pilot Plants ABB has launched a dedicated in-situ monitor for research laboratories and pilot plants in the chemical, petrochemical, pharmaceutical and biopharmaceutical industries. The MB-Rx reaction monitor features a rugged Hastelloy ATR probe and an intuitive software interface, offering a fast and flexible solution for setting up a wide variety of experiment templates. The MB-Rx provides a powerful tool for operators looking to obtain a realtime insight into chemical reaction dynamics. The MB-Rx enables key

parameters such as kinetics over different phases, reagent consumption and the synthesis of products and byproducts to be assessed in real time. Compact and easy to install, the MB-Rx can be fitted inside crowded fume hoods, providing convenient access to reactors. A major benefit of the MB-Rx is its virtually maintenancefree design. Permanently aligned optics and a light source with an average lifespan of 10 years mean that the MBRx requires little servicing throughout its operational life, providing extended

uptime and reducing the cost of ownership. Further savings can also be achieved through the elimination of any consumables. The MB-Rx uses no hygroscopic optics or a cryogenic detector, ruling out the need for optical purging, desiccant cartridges, liquid nitrogen or Stirling coolers. ABB +44 1925 741 111 moreinstrumentation@gb.abb.com www.abb.com

University of Nottingham Further Invests in Green Chemistry Lab The School of Chemistry at the University of Nottingham, UK, has placed a sizeable order with Asynt to upgrade its undergraduate teaching facilities with DrySyn Scholar Plus heating block systems. The School of Chemistry is one of the leading chemistry departments in the UK and is recognised internationally for its outstanding research portfolio, excellence in teaching and extensive engagement with industry. Its expertise spans the spectrum of modern chemical technology, including synthesis, analysis and characterisation, ranging from the core chemistry disciplines to areas at the interface with biological sciences and engineering (sustainable chemical

processing). In 2012, GlaxoSmithKline (GSK) and the University of Nottingham formalised a collaboration to establish a new laboratory to accommodate a Centre of Excellence for sustainable chemistry and to construct an innovative carbon neutral sustainable chemistry facility. David Chambers-Asman, Director of Operations & Administration at the School of Chemistry, commented: “In line with Nottingham’s commitment to develop ‘green and sustainable’ chemistry methodologies, we wanted to find a safe, more environmentallyfriendly alternative to heated oil baths for our undergraduates to learn about organic synthesis. Using heated oil

baths presented a risk to our students (through accidental spillage) and involved periodic requirement to dispose of large quantities of oil, a risk and environmental burden eliminated by using the DrySyn Scholar Plus.” Specifically designed for safety conscious teaching laboratories, the DrySyn Scholar Plus kit enables single 50, 100 or 250 ml round bottom flask reactions to be performed safely without the mess or inherent hazards of a hot oil bath or heating mantle. Prominent, permanently fixed lifting handles ensure moving even hot reaction blocks is easy, fast and safe. Compatible with almost any magnetic hotplate stirrer, the low thermal mass design of the DrySyn

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Scholar minimises both power consumption and reaction heat-up time. Asynt Ltd +44 1638 781709 sales@asynt.com www.asynt.com

LABORATORY PRODUCTS & EQUIPMENT ROUNDUP Mass Directed Flash Purification System Confirms Compounds in Fewer Steps Biotage has launched the Isolera Dalton, a fully automated, miniaturised mass directed flash purification system. According to the company, the new system raises the bar for flash purification by integrating a miniaturised mass detector and an advanced flash chromatography system into one commercially available platform. The mass detector and Isolera Spektra flash purification system are seamlessly integrated via the Isolera Dalton Nanolink unit, an intelligent sampling device that handles all fluids and synching calculations between the two units. Isolera Dalton easily fits inside a standard fume hood, requires no external pumps and is capable of both

normal and reverse-phase separations, so it is completely compatible with the diverse purification needs of the modern research laboratory. Dr. Sunil Rana, Global Product Manager, Biotage, said: “Compounds are identified in real time during purification and this informs the flash fractionation process, enabling the correct product to be collected by the system. The system automatically accommodates different column sizes and flow rates, overcoming major issues with simple splitter-based systems. “Isolera Dalton significantly reduces the number of steps required to purify and confirm a target compound, thus improving workflow and increasing

confidence that chemists have synthesised what was intended. Quite frankly, there is nothing else like it on the market today, or that even comes close.” The instrument uses a wizard-based approach to method development; simple on-screen prompts guide chemists through the system, even those whose expertise or priorities lie in compound synthesis rather than analysis.

Biotage AB, Sweden +46 18 56 57 10 info@biotage.com www.biotage.com

Thermoregulation Machines Provide Ecological and Economical Temperature Control The Huber Petite Fleur, Ministat and Minichiller are environmentally friendly and cost-effective thermoregulation machines charged with natural refrigerants, perfectly suited for laboratories, being eco-friendly, with small dimensions and boasting low investment costs. Preserving natural resources and protecting the environment is an important obligation. Small and simple changes in design can result in effective and positive contributions to preserving the environment. A simple but effective change has been made by Huber — technical modifications that allow the use of alternative, environmentally friendly refrigerants. The Huber Petite Fleur, Ministat and Minichiller are environmentally friendly thermoregulation solutions with low running costs. They are offered with the natural hydrocarbone refrigerant propane R290 as standard. R290 has no

significant global warming potential (GWP) and no ozone depilation potential (ODP). The refrigerant has an unlimited availability worldwide so is easy to source. Also, most notably, it provides the same performance as synthetic, conventional refrigerants. According to the company, Ministat is the smallest cooling circulator in the world. It allows temperature control of objects directly in the bath or to thermoregulate external applications. It has enough power to thermoregulate photometers, refractometers, viscosimeters, distillation apparatus, reactor vessels and mini plants. Three models are available with working temperatures from -45 to +200˚C. The compact Minichiller is a space saving, environmentally friendly and economic cooling solution for laboratory applications. It is suitable for cooling of reactor blocks, vapour traps, vacuum pumps, rotary evaporators and heat

exchangers. It ensures constant temperatures and highly efficient condensation of flow through vapours. The Minichiller is designed for continuous operation in ambient temperatures up to +40 °C. The Petite Fleur, with a working temperature of -40 to +200˚C, is the smallest, hydraulically sealed dynamic temperature control system in the Unistat series and ideally suited to controlling small research reactors. It has exceptional thermodynamic properties and is reportedly unrivalled when it comes to responsive temperature control. All three machines can be placed on the benchtop, in cabinets or integrated into automated systems. They are fitted with the new touchscreen controller Pilot ONE and operation is via a coloured 5.7” TFT display with intuitive menu icons, prompts and full text menu guidance in 11 languages.

Peter Huber Kältemaschinenbau GmbH +49 781 96030 info@huber-online.com www.huber-online.com

Wet Sieving Unit Delivers Short Measuring Times

Muffle Furnaces Provide Rapid and Uniform Benchtop Heating

Well-known for its Alpine Air Jet Sieve for laboratory sieving and particle size measuring of fine powders, Hosokawa Micron has now introduced the Viblette VBL for fast, accurate wet sieving in the laboratory. The new unit is suitable for applications where wet sieving has to be used for analysis because of the dry material’s highly cohesive nature. Examples of such materials would be carbon black, some mineral fillers and some dielectric materials. This Viblette VBL uses enhanced vibration to deliver short measuring times up to one-third of those of conventional wet sieves. The electro-magnetic vibration mechanism breaks the liquid film formed on the sieve surface, which is reportedly a problem with other wet sieving devices. This ensures effective powder wetting and short sieving times. The incorporation of specially designed showering nozzles allow the Viblette VBL to achieve accurate sieving using up to one sixth the amount of water compared with conventional wet sieves. Liquid is sprayed through sprinkler shower nozzles onto powdery sample on the sieve. The sprinkler rotating above the sieve is driven by liquid pressure and the design ensures even wetting of the powder and independent control of both liquid rate and rotation speed is provided to ensure maximum versatility. There is very little wash liquid waste.

A new range of 1,200˚C muffle furnaces that provide rapid and uniform heating in a compact, space-saving benchtop unit has been introduced by Medline Scientific. The furnaces are available in chamber sizes ranging from 5.2 up to 20 l so there is a model that will suit the wide range of workloads typically required for most laboratory heating applications, e.g., quality control testing, ashing, heat treatment, preheating, melting, metallurgical research and sample production. The inner chamber walls are constructed using insulated fire bricks that provide optimum insulation as well as protection against mechanical abrasion, thermal ageing and deformation. A uniform temperature spread is achieved as the heating elements are located on both the sides and the top of the chamber, and they are partially recessed and embedded in quartz sleeves. This, combined with a standard thickness of the inner chamber material, ensures additional protection and enhances uniform heating of the chamber.

Repeatability of testing is ensured as sprinkler rotation, liquid rate and the amplitude of vibration can be varied and controlled to preset levels. This ensures consistent repeatability and very accurate measurement of particle size. In addition to the standard 200 mm drum size, an adaptor is provided so that 75 mm sieves can be used up to three sets for simultaneous measurement. Even 10 µm screening is possible with the new Viblette VBL. The Viblette VBL can process quantities of slurry up to 10 l per minute and uses a special optional feeding device for this application as required. Hosokawa Micron Ltd +44 1928 755100 info@hmluk.hosokawa.com www.hosokawa.co.uk

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The modular design of the inner chamber means it can be easily removed and replaced when required within 30 minutes, while its double skinned construction ensures that the outer casing remains cool to touch, even after prolonged operation. Other features include a proportionalintegral-derivative (PID) controller located on the top of the chamber to facilitate easy viewing and programming during operation and adjustable feet to enable levelling of the unit should benchtop surfaces be uneven. Medline Scientific Ltd +44 1865 892 987 mail@medlinescientific.com www.medlinescientific.com

SHOWCASE LABWARE

Entry Level Thermal Plate Sealer Provides Airtight Seal without Adhesives The MicroSeal from Porvair Sciences is a manual microplate heat sealer, designed to be compact, easy-to-use and offer great performance, all with an affordable list price. Of the various methods of sealing microplates, heating sealing has become the preferred option for many laboratories as it creates an airtight and chemically-resistant seal, without the complications of adhesives being applied to a plate. Incorporating an ergonomic pull down mechanism makes single action heat sealing of a

wide range of plates on the MicroSeal quick and simple. Using a pre-set temperature of 170˚C, ideal for most common sealing applications, and dual LED status display of power and heating, the MicroSeal is very safe and easy to use. A built-in thermostat prevents overheating of plates. With its small footprint, ease of use and ability to handle a wide range of plates, the MicroSeal is an obvious choice for laboratories looking for an affordable manual thermal plate sealer.

Porvair Sciences has specialised in the manufacture of microplates and microplate equipment since its formation in 1992. Via its global distributor network, Porvair Sciences serves life sciences, biotechnology, R&D and molecular biology with microplate solutions for all applications, from sample preparation to high throughput screening.

Porvair Sciences Ltd +44 1978 666240 int.sales@porvair-sciences.com www.porvair-sciences.com

Latest Generation of Multichannel Pipettes Offer Ease of Use and Repeatability Mettler Toledo has launched its next generation of Rainin multichannel pipettes. The manual Rainin Pipet-Lite XLS+ and electronic Rainin E4 XLS+ offer users durable, lightweight liquid ends and new mechanical designs that all but eliminate hand strain while ensuring the highest channel-tochannel consistency. This combination of improved ergonomic comfort and exceptional performance helps pipette operators work more comfortably and reduces the risk of error and potentially expensive rework. Experiment costs go down as throughput accuracy increases.

Whether a research team’s objective is to be first to publish or first to market, the Rainin XLS+ multichannel pipettes represent an intelligent advance in both performance and ergonomics. Reduced weight and lower pipetting/tip-ejection forces, combined with improved balance, reduce operator fatigue during intensive 96-well plate work. Enhanced reliability ensures data integrity. Also, operators concerned about cross contamination will appreciate XLS+’s reduced stiction (piston stickiness), which helps to eliminate splash-up. Capitalising on recent advances in moulding technology, Rainin has

reportedly achieved an optimal balance between lightness and performance — two goals that often run counter to one another. In addition to new internal designs and materials, smaller surface-area lip seals require less force and reduce drag. Taken together, these and other new design elements reduce weight and increase reliability for a more pleasurable and repeatable pipetting experience. Rainin Instrument, LLC, a subsidiary of Mettler Toledo +1 510 564 1736 terry.peckhan@rainin.com www.mt.com/rainin-mc

Reagent Reservoirs Range Expands to Accommodate 96- and 384-Well Pipettes

Pyrex Media Lab Bottles Feature Wide Mouth to Aid Filling and Pouring

INTEGRA has announced an extension of its series of reagent reservoirs for 96and 384-well multichannel pipetting systems. Adopting a standard SBS/SLAS footprint, the extended range of reagent reservoirs (100 and 300 ml) are fully compatible with all liquid handling systems, including INTEGRA’s VIAFLO 96 and VIAFLO 384 handheld multichannel electronic pipettes. Individual pyramidal indentations (96 or 384) in each reagent reservoir allow maximum liquid recovery when using the VIAFLO 96 and VIAFLO 384 electronic pipettes as well as other platforms. VIAFLO multichannel reagent reservoirs are both economically and environmentally friendly because users can reuse the reservoir base and dispose of the reservoir inserts. These reagent reservoirs are also designed to nest within one another without sticking

SciLabware’s Pyrex media lab bottles have been a trusted favourite in laboratories for over 25 years. A new range of wide mouth media-lab bottles are now available to order. Manufactured from Pyrex borosilicate glass for maximum chemical and thermal resistance, each media-lab bottle features a GLS 80 screwthread with a wide internal neck diameter to aid filling and pouring of powders and viscous liquids. Each bottle is printed with a ‘Trace Code’, making it retraceable to a specific production batch. Batch certificates are available to download from the SciLabware website. Wide neck media lab bottles are available either with or without a

and come in compact, space-saving packages. INTEGRA Biosciences AG +41 81 286 9530 info@integra-biosciences.com www.integra-biosciences.com

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polypropylene screwcap and pouring ring. Spare screwcaps and pouring rings are also available. SciLabware Ltd +44 1785 810347 www.scilabware.com

Industry News & Events

Lab Innovations 2013 to Host UKAS Pavilion Lab Innovations 2013, on 6–7 November 2013, at the NEC, Birmingham, UK, will feature the new UKAS (United Kingdom Accreditation Service) Pavilion. This is an exciting addition to the show, which as the UK’s reportedly only event dedicated to laboratory equipment, technology and services, is already supported by the Royal Society of Chemistry, Campden BRI and Gambica. UKAS is the sole national accreditation body recognised by government to assess, against internationally agreed standards, organisations that provide certification, testing, inspection and calibration services. Companies accredited by UKAS are recognised for their high standards of competence, impartiality and performance. Commenting on his organisation’s involvement, Jon Murthy, Marketing Manager at UKAS, said: “Hosting the pavilion at Lab Innovations

provides a great opportunity for us to meet delegates across a broad range of sectors in the laboratory industry. UKAS laboratory accreditation uses criteria specially to determine technical competence and this show is a chance to promote the importance of UKAS accreditation and using UKAS accredited laboratories for testing.” TMS Europe is one of the companies that has been quick to sign up to exhibit within the Lab Innovations UKAS Pavilion. The company supplies a range of UKAS calibrated laboratory ovens and furnaces used in a range of industries, including aerospace, pharmaceutical and healthcare. James Driver, Sales Coordinator, said: “There is a lot of worldbeating work going on in UK lab-based companies such as ours, but up to now there hasn’t been an event to showcase them. We were impressed by the launch show last year, so when we heard there

was a specific area this year to promote the capabilities of UKAS accredited laboratories we jumped at it.” Other UKAS accredited companies exhibiting within the pavilion include European Instruments, provider of a range of calibration services and products such as weights and software solutions, plus AMETEK, a global manufacturer of electronic instruments and electromechanical devices. Jake Morrison, Lab Innovations Event Manager, commented: “UKAS’s support is yet another indicator of how rapidly the show is developing. We were keen to provide a great showcase for the UK’s

many contract labs and service companies. The pavilion will be the perfect vehicle for doing just that.” easyFairs +44 20 8843 8822 richard.thompson@easyfairs.com www.easyfairs.com/labinnovations

Lonza Appoints UK Distributor for Cell Biology Media and Molecular Biology Reagents Scientific Laboratory Supplies (SLS) has been appointed as the sole distributor for Lonza’s BioWhittaker cell biology media and serum product lines in the UK. SLS and Lonza have entered a strategic collaboration that aims to increase and improve the visibility, availability and service associated with the supply of this Lonza portfolio, which also includes SeaKem and SeaPlaque agaroses, the FlashGel system and PAGEr precast protein gels.

“SLS is the UK’s largest independent supplier of scientific equipment, chemicals and consumables, and we are making a significant investment in our storage capabilities to accommodate the new Lonza product portfolio,” said Paul Hutchinson, Sales Manager for Life Science Products at SLS. “SLS is committed to increasing its presence in the life science sector and this alliance is the latest in a series of

Microwaves Could Make for Greener Pharma Manufacturing Microwave radiation might provide a faster, greener way to manufacture drugs, according to researchers at the University of Bradford. Published in the Royal Society of Chemistry journal CrystEngComm, the research is reportedly the first to show that microwave radiation can be effectively used for co-crystallisation, a process that creates single crystals constructed from two compounds. Drugs manufactured from these co-crystals can have improved properties such as longer shelf-life, improved solubility and easier absorption into a patient’s bloodstream. Using caffeine and maleic acid as example compounds, the researchers achieved 100% crystallisation in just one minute using very little solvent, making the process faster and more environmentally friendly than conventional methods. Professor Paradkar, Director of the University of Bradford’s Centre for Pharmaceutical Engineering Science (CPES), explained: “We chose caffeine and maleic acid as these compounds have different levels of solubility, which is a common problem in pharmaceutical

Scientific Laboratory Supplies Ltd +44 1482 649 665 http://lifescience.scientificlabs.co.uk

Analytical Instrumentation Specialist Establishes Subsidiary in Thailand

manufacturing. Conventional methods of co-crystallisation aren’t effective when you’re working with two compounds that dissolve differently, but we found that by using microwave radiation we could still get excellent results.” The team worked with five different solvents, of which water and methanol produced the best results. These two solvents were able to transmit the heat from microwave radiation more effectively than the others tested, which were acetone, ethyl acetate and toluene. The experiments have only been carried out at laboratory scale, but Professor Paradkar believes that if the process can be scaled up, it could offer significant benefits to the pharmaceutical industry. “Our research shows that microwave radiation is a very promising alternative for producing pure co-crystals quickly, with limited use of solvents,” he added. University of Bradford CPES +44 1274 233900 www.pharmaceuticalengineering.brad.ac.uk

collaborations which demonstrate how serious we are about this market.” Leigh Eastwood, European Distribution/Export Manager at Lonza, said: “Lonza selected SLS as its UK distributor because of its flexibility and willingness to provide Lonza with exactly what we were looking for in terms of logistics and market focus. With SLS’s increasing presence in the life science arena, we are excited about our new working partnership.”

Analytik Jena, a leading manufacturer of analytical instrumentation technology, life science instruments and optoelectronics, has announced a new subsidiary, Analytik Jena Far East (Thailand) Ltd, giving it a presence in the Southeast Asian market. Analytik Jena is using this new company to bolster its activities in the Southeast Asian market, increase its regional service for the sales partners and customers operating there and expand its regional sales activities. In future, the company looks to strengthen its core business of Analytical Instrumentation from Bangkok with its ninth foreign subsidiary. “To be successful in growth markets, a local presence is essential. Our international network gives us access to the global markets that are important for our business. These also include Southeast Asia with Thailand,” said Klaus Berka, CEO of Analytik Jena. “The region has an economic structure with many growth sectors. We expect significant sales growth here in the next few years.”

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Analytik Jena has operated with an office in Bangkok since 2001, out of which it serves retailers and customers with an on-site team of experts. The company aims to strengthen its presence in Southeast Asia with its own infrastructure and develop a sales network for the entire Southeast Asian market via the subsidiary in Bangkok. The product portfolio, with analytical instrumentation technology in particular, is to be sold via Analytik Jena Far East (Thailand) Ltd, which is to be a regional competence centre. In individual product divisions, such as atomic absorption spectrometry (AAS), Analytik Jena already has market shares of up to 20.0% in selected Asian markets today. In the last financial year, 2011/2012, Analytik Jena achieved an increase in sales of 30.8% in Asia, its most important export market, generating sales of €39.2 million. Analytik Jena AG +49 36 41 77 70 info@analytik-jena.com www.analytik-jena.com

INGREDIENTS & CONTRACT SERVICES

Technology Platform Combines Dosage Form Solutions for Improved Formulation Development Capsugel has launched its LIPIDEX technology platform, which integrates the company’s lipid, liquid and semisolid fill technologies, extensive product development experience and commercial manufacturing infrastructure. The LIPIDEX platform will enable Capsugel’s Dosage Form Solutions (DFS) business unit to accelerate and improve the development of products for its pharmaceutical and nutraceutical customers. “Our LIPIDEX technology platform provides tailored solutions for the many challenges our customers face, whether it’s development of low solubility drugs in their pipeline, repositioning existing drugs for better therapeutic performance or rebranding them using innovative dosage forms,” said Amit Patel, President, Capsugel DFS. “Through Capsugel’s historical investments and our recent acquisition of Encap Drug Delivery, the LIPIDEX platform represents the industry’s most comprehensive and vertically integrated offering in the lipid, liquid and semi-solid arena. It spans polymer science and process engineering at the capsule level as well as API handling, dosage formulation development using expert systems, clinical trial quantity supply and commercial manufacturing.” Capsugel DFS can encapsulate formulations using several lipid, liquid and semi-solid fill dosage forms, including its established Licaps liquidfilled and SGcaps soft gelatin capsules,

which currently account for several billion capsules produced annually. Also, DFS continues to expand its dosage form options; a new solid lipid pellet dosage form is being utilised for select internal and customer projects and will be formally launched to the market later this year. These multiple dosage forms provide customers with options and flexibility to meet their target product profile. The LIPIDEX technology platform centres on Capsugel DFS’s clinical fasttrack development programme, which utilises its exclusive Lipid Expert System, developed by its formulation scientists over the past decade to streamline various aspects of the development process. The company’s formulation scientists have extensive backgrounds in simple to complex lipid systems in solution, suspension or SEDDS/SMEDDS formulations. Smallscale liquid fill manufacturing technology is also available at Capsugel DFS’ global R&D locations. “Customers are increasingly coming to us early in the R&D process to quickly solve their formulation challenges. Our Lipid Expert System can model ternary phase diagrams based on solubility in individual lipid-based excipients, so identifying the optimum formulation space for an API can happen much faster than by conventional matrix solubility screening experiments,” said Keith Hutchison, PhD, Senior Vice President of R&D, Capsugel. “The

combination of our formulation and encapsulation expertise is being leveraged for unparalleled speed and precision in product development, scaleup and manufacturing.” Rounding out the LIPIDEX platform is the company’s network of dedicated small-scale and commercial manufacturing sites in the US, Europe and Japan. This global manufacturing footprint assures business continuity planning and includes FDA and MHRA accreditation and specialty capability in high potency actives, controlled substances and hormones. Capsugel EMEA +33 3 89 20 57 25 marketing.emea@capsugel.com www.capsugel.com

UK to Australia Temperature Assured Airfreight Solution Launches for AstraZeneca As part of its ongoing relationship with AstraZeneca, Yusen Logistics has launched a major airfreight operation to transport prescription drugs from the UK to Australia. AstraZeneca was seeking to optimise flows of these temperature controlled products and Yusen Logistics was able to offer a robust and cost-effective solution. The Yusen Logistics solution involves moving the cargo by air from AstraZeneca’s UK central warehouse in Macclesfield to Sydney, maintaining a stringent temperature regime throughout the supply chain and with all movements made under high security conditions. In order to maintain the temperature regime, thermal protection is applied to each individual AstraZeneca pallet. Cargo air movements are timed to arrive in Sydney at the coolest time of day. The cargo is stored under strict temperature control during transit, ensuring product integrity at all times. AstraZeneca and Yusen Logistics have

been working in close partnership since 2007, when Yusen Logistics was appointed, initially to work with AstraZeneca purely on the creation of a lean supply chain for its European road freight. All movements are managed by means of the Yusen Logistics Control Tower, which provides an aerial view of European and global movements, across the modes of road, sea and air. All operational communications are routed via the Control Tower, giving AstraZeneca Macclesfield a single point of contact, providing a streamlined operational flow. Julian Wann, Global Category Lead: Freight & Logistics, AstraZeneca, commented: “The relationship is one that has matured since its inception, as we have identified new requirements,

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Yusen Logistics have been proactive in developing solutions that meet all our needs. The decision to give Yusen Logistics this business allows us to assess the relationship in different areas and identify further potential opportunities.” Yusen Logistics +44 1604 748500 claire.sivills@uk.yusen-logistics.com www.eur.yusen-logistics.com

INGREDIENTS & CONTRACT SERVICES ROUNDUP Partnership to Develop Amide Chemical Synthesis Technique Global CMO Aesica has announced a partnership with the University of Nottingham for the commercial development of alternative methods in amide bond synthesis. This latest partnership is already the Aesica Innovation Board’s (AIB’s) fourth with an academic institution in less than six months, established to help bridge the growing R&D gap by identifying early stage technologies for development into commercial applications. Amide bond formation is fundamental in pharmaceutical manufacturing. A recent survey conducted by the Green Chemistry Institute Roundtable identified that amide bond formation was utilised

in 84% of a set of drug candidates. The partnership’s aim is to revolutionise traditional amide formation techniques by generating alternative methods for amide bond formation that will be more eco-friendly and chemically versatile. This approach will be commercially available to Aesica customers in the next two to three months and already the company is actively seeking commercial opportunities to work with potential compounds that could benefit from this technology. Aesica envisages this new development helping pharmaceutical companies that encounter problems with amide synthesis and owing to the utilisation of more sustainable reagents,

production costs will be lowered whilst offering the potential of higher chemical yields. The University of Nottingham has a strong track record for outstanding research in green and sustainable chemistry. This collaboration builds upon recently announced plans to establish a Centre of Excellence for Sustainable Chemistry, part-funded by an investment from the Higher Education Funding Council for England (HEFCE) UK Research Partnership Investment Fund. The Centre aims to form creative partnerships with companies like Aesica to develop new chemical-based technologies that minimise

Aesica Cramlington site, in Northumberland, UK. environmental impact and are both energy and resource efficient. The University was confident about the success of this technology on a small-scale basis and was keen to test its robustness in a commercial application. Preliminary studies were undertaken using funds awarded by the Engineering and Physical Sciences Research Council (EPSRC) under the Research Development (Pathways to Impact) Funding Scheme. “Since realising the initial use of our coupling agent in 2005, one of our goals has been to see this novel technology used in larger scale industrial environments,” said Simon Woodward, Professor of Synthetic Organic Chemistry, University of Nottingham. “We look forward to collaborating with Aesica and seeing the full commercial potential of this novel technology in API manufacture.” Aesica Pharmaceuticals Ltd +44 191 218 1960 info@aesica-pharma.com www.aesica-pharma.com

CDMO Wins Two Prestigious Process Excellence Awards Catalent Pharma Solutions won two Process Excellence Awards at the PEX Network European Awards ceremony in London. The awards were presented in the categories ‘Best Business Process Improvement Programme Over 2 Years’ and ‘Best Process Improvement Project Over 90 days’. In the first of these categories, judges recognised Catalent’s corporate Continuous Improvement management initiative for setting performance standards, tracking key performance indicators and managing every aspect of operational improvement consistently across Catalent’s global network of facilities. The second award was given for its Bolton, UK, clinical storage facility, where improvement ideas generated by the team improved utilisation realised additional space and led to the introduction of further best practices. In accepting the awards for Catalent, Sridhar Krishnan, Vice President, Global Operations, commented: “Catalent competed with global companies from many industries, each having enviable reputations for process excellence. In winning these two awards the judges recognised our efforts in the continuous improvement journey and Catalent’s global commitment to reliable supply.” Catalent Pharma Solutions +44 1793 864000 chris.halling@catalent.com www.catalent.com EPM 28

INGREDIENTS & CONTRACT SERVICES ROUNDUP CASE STUDY Using a compaction simulator, Quay Pharma has helped pharmaceutical manufacturer Actavis transfer tablet production of one of its top-selling drugs to a higher throughput tabletting machine. Transfer of tablet production between machines is common as manufacturers seek to increase production or replace old equipment with newer models. However, due to the complex powder mechanics involved in tabletting, any changes in process that create increases in speed as well as the duration and/or force of compression can sometimes lead to failure of a tablet formulation to work successfully on new equipment. Even minor amendments in tooling design lead to a change in the powder compaction properties and can result in failure of the tablets due to capping or lamination. In order to help avoid these problems and ensure a smooth transfer between equipment, Quay uses an advanced MedelPharm compaction simulator, which can mimic any existing tablet press available on the market. The simulator has only one tabletting station with the punches being programmed to follow the force displacement profile of any tabletting machine. The tablets can

COMPACTION SIMULATOR PROVIDES SUCCESSFUL PRODUCTION TRANSFER FOR ACTAVIS

be compressed at both low and high speed and it enables parameters such as compression force and speed to be recorded as well as ejection force. For this study, tablets were compressed using the current machine profile and then using the new machine profile. Data was captured throughout the tabletting process to allow a thorough understanding of what impact the changes in compression profile were having on the finished tablet. From the data obtained, and using very small quantities of material, Quay was able to accurately assess the properties of the Actavis tablet and suggest how a revision in tooling would enable the tablet to be formed effectively on the new equipment, whilst maintaining the required throughput speeds. “Quay’s knowledge and experience was invaluable in helping us to successfully transfer production and avoid the disruption that can occur during this process,” commented Steve Brown of Actavis. The compaction simulator also offers a costeffective means for optimising formulations for new drugs, minimising the amount of API used and helping to simplify the process for scaling up production of a new formulation for phase II clinical trials. Quay Pharma +44 151 203 9800 enquiries@quaypharma.com www.quaypharma.com

Agreement to See CDMO’s Customers Benefit from Metal Coordination Chemistry Recipharm Pharmaceutical Development and Synthonics have announced the formation of a Joint Promotion Agreement. The contract, the first of its kind to be entered into between the two companies, will provide Recipharm customers with full access to Synthonics’s metal coordination chemistry, improving the delivery and performance of their compounds. Recipharm, a Swedish corporation, provides services that assist pharmaceutical companies throughout Europe, the US, Japan and further afield with the development and formulation of products. Synthonics, a US corporation, has developed a proprietary metal coordination chemistry that can

significantly improve a compound’s delivery and absorption. Recipharm Pharmaceutical Development’s General Manager, Maria Lundberg, commented: “We are pleased to partner with Synthonics to expand the services and solutions that we can offer our clients. The application of Synthonics’ chemistry improves important characteristics such as bioavailability and solubility and thus increases the likelihood that promising molecules will become viable products. Furthermore, our ability to offer such services through this novel partnership distinguishes us from other CDMOs.” Ken Slepicka, CEO of Synthonics, stated: “Synthonics is delighted to

partner with Recipharm to help advance promising molecules to market. We are very impressed with Recipharm’s formulation and development teams and believe that our chemistry will fit well in their existing tool kit of solutions. We expect this agreement to help us reach new clients and to expand the use of our chemistry.” Recipharm AB +46 8 602 52 00 info@recipharm.com www.recipharm.com Synthonics, Inc. +1 540 443 3645 info@synthonicsinc.com www.synthonicsinc.com

CDMO Produces First Batch of Coated Tablets in Contained Manufacturing Operation Penn Pharma has successfully completed the first batch of coated tablets in its new contained manufacturing operation. Less than a year after announcing the ambitious programme to build the new facility at Penn Pharma’s South Wales, UK, base, this marks a major achievement. The new 1,395 m2 site has been built for the clinical and commercial manufacture of tablets and capsules and will allow Penn Pharma to build on its heritage and varied services. The marketplace has seen growth in the number of highly potent compounds requiring solid dosage development and with this new facility, Penn Pharma is ideally positioned to address the formulation and both clinical and

commercial manufacturing needs of its clients. Richard Yarwood, Penn Pharma Chief Executive Officer, said: “It is a monumental day for Penn Pharma. In less than one year, we have built a world-class facility for contained manufacturing and produced our first batch of coated tablets. This gives our customers even greater confidence that Penn Pharma can meet the challenging timelines they require to get their products to market.” Mark Dean-Netscher, Penn Pharma Chief Operating Officer, said: “This success is the result of hard work and determination to get us to this stage in such a short space of time. A facility of this complex nature was a tight build in

the timeframe, but we have demonstrated that when Penn Pharma commits to something, we always deliver.”

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Penn Pharma +44 1495 711 222 www.pennpharm.com

INGREDIENTS & CONTRACT SERVICES ROUNDUP Sterile Products Manufacturer Appoints Director SCM Pharma has strengthened its senior management team by recruiting a highprofile director. Paul Bradley joins the award-winning CDMO as Operations Director and will also sit on the company’s board. Formally of Hospira Aseptic Services, he will now be responsible for all operational activities at SCM Pharma, including production, warehouse and facilities. In keeping with the company’s core area of competence, Bradley brings exceptional experience of clinical trial and commercial manufacturing involving sterile products. He is the latest in a string of new senior appointments by the organisation, which added quality professional Mark Edwards as Quality Assurance Director earlier this year. Dianne Sharp, Managing Director at

SCM Pharma, said: “As the company continues to grow and handle more and more products, it is vital we are reliably planning, manufacturing and delivering drugs to our clients whether they are for clinical trials or commercial market supply. Paul will no doubt be a great addition to the team and will play a significant role in overseeing and supporting client projects across both of our sites.” With over 15 years’ experience of research, development and manufacturing, Bradley moved into the sterile manufacturing area in 2007. With a BSc (Hons) in Chemistry from Durham University and a Management Diploma at Loughborough College, he will play a pivotal role in developing robust and efficient processes and systems at SCM

Pharma on technically challenging products. He said: “As soon as I became aware of the opportunity at SCM Pharma, I was immediately interested as I’d heard very good things about the company’s setup, vision and its willingness to invest in people, technology and facilities. I am very excited by the prospect of working closely with the team and clients to develop and deliver technically challenging products that will benefit all stakeholders and improve patient health.” SCM Pharma specialises in the sterile production of products for clinical trials along with the supply of licensed drugs in niche markets. It will soon open the doors of its new commercial facility, which will reinforce its expertise in vial,

ampoule and syringe filling, particularly when dealing with potent products requiring high containment. SCM Pharma Ltd +44 1661 833 693 info@scmpharma.com www.scmpharma.com

API Provider Recruits Well-Known Solubisation Expert to Lead Particle Design Team Hovione has appointed Dr. Justin Hughey to lead the Particle Design sciences at its site in New Jersey, US. With over 30 publications, posters and book chapters, Dr. Hughey is an acknowledged expert in the field of solubilisation, including the creation of amorphous solid dispersions with emphasis on hot melt extrusion (HME). Dr. Hughey most recently served as the Director of Research for Enavail. To complement its spray drying capabilities and other technologies to

improve bioavailability, Hovione is investing in both laboratory- and midscale hot melt extruders to enable the efficient development of particles with improved solubility for seamless scale up and transfer to clinical manufacture. “I have always admired Hovione’s capabilities in the area of spray drying and was pleased to hear that they were adding hot melt extrusion to their portfolio. I am looking forward to making significant contributions to this

area and offering customers a range of solubility enhancement options,” said Dr. Hughey. Dr. Hughey earned his Ph.D. in Pharmaceutics from The University of Texas at Austin, US, and also holds B.S. degrees in Chemical Engineering and Chemistry. His pharmaceutical development experience extends to particle engineering technologies for pulmonary delivery as well as controlled and immediate release solid oral dosage forms.

Hovione +351 21 982 9362 ipina@hovione.com www.hovione.com

Developability Assessment Platform Reduces Attrition Rates and Improves Predictability of Clinical Safety Early risk assessment has become a critical factor in biopharmaceutical drug development programmes. To address this growing market need, Lonza has announced the launch of its new Developability Assessment Platform. This platform is designed to reduce attrition rates and improve the ranking of early drug candidates. The prediction tools include a suite of in silico based

services, which assess candidates for: fitness for large-scale manufacture (manufacturability) and immunogenicity profiles in humans (safety). One of the main challenges for companies today is the increasing R&D costs due in part to high attrition rates of therapeutic candidates. R&D organisations need to rapidly screen out inferior candidates with a potential low probability of clinical and commercial success. Being able to assess the manufacturability and safety at the pre-clinical stage, before large investments are made, allows companies to focus on the most promising candidate and maximise R&D spending. Lonza is uniquely positioned to offer customers a complete Developability Assessment Platform Bioinformatic assessment of possible immunogenic peptide that consists of both sequences via in silico screening.

in silico tools and protein structure expertise. The Platform includes Manufacturability Assessment and Safety Assessment Services applicable to customers in both discovery and early stage biological drug development. The Manufacturability Assessment Service analyses chemical degradation pathways and post translational modifications, including deamidation, oxidation and glycosylation, as well as potential physical stability issues, most notably, protein aggregation. The Safety Assessment Service uses Lonza’s proprietary Epibase in silico screening tool to identify potential T-cell epitopes in target proteins that may trigger potential immune reactions in human studies. “The costs associated with late-stage clinical failure is an increasing area of concern for our emerging and established biopharmaceutical customers,” said Janet White, Head of

Lonza’s Custom Development Services Organization. “This combination of manufacturability and safety assessment allows our customers to de-risk their candidates, supporting the ‘fail fast, fail early’ mantra.” All Developability Assessment Services include a full data report, including interpretation by Lonza’s structural bioinformaticians. In addition, risk mitigation recommendations will be given, including the option of protein engineering followed by expression and validation of variants using Lonza’s Light Path Custom Material Supply Service. The movement toward early risk assessment and streamlined development processes will greatly impact the timeline of biotherapeutics to first in human studies. Lonza Group Ltd +44 1753 504383 shiva.khalafpour@lonza.com www.lonza.com/developability

Injectables for Clinical Trials Specialist Appoints Business Development Manager Symbiosis Pharmaceutical Services has announced the arrival of Business Development Manager Joanne Anderson, who possesses a background in programme management that has seen her responsible for an R&D portfolio that afforded experience of taking products from research through to commercialisation. Having worked in analytical chemistry and biomedical analysis roles, Anderson first entered the pharmaceutical industry over 12 years ago with an API manufacturer and was more recently with a fill/finish service provider. Having

previously set up a client account management function, she moved into the sales arena while completing a Master’s in Business Administration at Newcastle University Business School. Anderson will be responsible for securing target sales for new and existing clients through developing relationships and industry networks for penetration of new and existing markets along with representing Symbiosis at trade exhibitions, conferences and partnering events to identify potential new clients and partners. Colin Mackay, Symbiosis CEO, said: “Joanne’s energy and experience aligns

with the ambitions of the company and strengthens our ability to tailor our services to our clients’ specific sterile manufacturing needs.” Anderson said: “The Symbiosis focus on the creation of long-term mutually beneficial relationships aligns strongly with my belief of how service providers can integrate seamlessly as a preferred outsourcing partner.” Symbiosis Pharmaceutical Services specialises in the GMP manufacture of liquid, lyophilised, cytotoxic, conventional and biological pharmaceuticals for Phase I and Phase II clinical trials.

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Symbiosis Pharmaceutical Services +44 1786 220000 enquiries@symbiosis-pharma.com www.symbiosis-pharma.com

ARTICLE Increased Bioavailability Using New Formulation Technology

Industry/academic partnerships — a proven model for driving process development innovation In today’s demanding pharmaceutical formulation market place, innovation and entrepreneurship are key drivers essential to generating new approaches that add value for customers. However, this is only part of the battle. It is essential to consider how to create sustainable competitive advantage from the start of the invention process. This involves a focus primarily on the task of invention and their competitive advantages.

About the Author: Professor Anant Paradkar holds an Interdisciplinary Chair in Pharmaceutical Engineering Science and is Director of the Centre for Pharmaceutical Engineering Science (CPES), University of Bradford. He completed his PhD in Pharmaceutics from Nagpur University and joined Bradford following a 20-year academic career in India. He has worked on various interdisciplinary collaborative research projects in the areas of product and process development. Paradkar has a strong background in crystal and particle engineering. Major crystallisation technologies being developed at his laboratory include HME, spherical crystallisation, microwave and ultrasound assisted processing. Paradkar has received Research and Knowledge Transfer grants totalling more than £1 million pounds from agencies including the Engineering and Physical Sciences Research Council (EPSRC), the Technology Strategy Board (TSB) and small and big pharma companies. He has been awarded a Yorkshire Enterprise Fellowship to strengthen exploitation and impact of his research work. To date, Paradkar has supervised 15 PhD and 50 MPharm candidates and published over 100 research papers. Since its formation in April 2010, a key focus of the Centre for Pharmaceutical Engineering Science (CPES) has been novel green technologies for pharmaceutical and biopharmaceutical processing. Examples of these technologies include hot melt extrusion (HME), spray drying, ultrasound, injection moulding, milling and microwave assisted synthesis. The CPES has a significant interest in improving the physicochemical properties of poorly soluble drugs by using the aforementioned green technologies. Background: The model that has brought Hot Melt Extrusion innovation to life The CPES is an interdisciplinary research centre at the University of Bradford, UK. The University’s engineering laboratories have over 20 years of experience in polymer and reactive extrusion. Indeed, CPES covers

the pharmaceutical sciences and polymer and process engineering disciplines with expertise in pharmaceutical materials, drug delivery systems, process development, material characterisation and process analytical technology (PAT). The state-of-the-art pharmaceutical extrusion laboratories at CPES are located within the Interdisciplinary Research Centre (IRC) in Polymer Engineering. CPES also has pharmaceutical formulation laboratories within the School of Pharmacy and access to characterisation facilities run by the University’s Analytical Centre. The University of Bradford partners with companies such as Aesica Pharmaceuticals to meet the full expectations and needs of the market when utilising innovation like HME in pharmaceutical formulation, namely a complete solution from bench-scale work at the CPES to generating clinical trial and commercial products at Aesica Pharmaceuticals’s cGMP site in Nottingham, UK. Funded research projects at the CPES fall into two categories: industrial cooperation and core scientific. Industrial cooperation projects include partnerships such as the one with Aesica Pharmaceuticals while the core scientific ones focus on research that may be relevant to future industry partners and allow the centre to build up a solid scientific base. Knowledge transfer partnerships with relevant companies also aid technological innovation. Hot melt extrusion — innovation in processing technology A key focus of the Centre is to understand the process of HME and explore its novel pharmaceutical applications. Extrusion is a process that involves forcing raw material or a mixture through a die or orifice under set conditions such as temperature, pressure, rate of mixing and feed rate for the purpose of producing a stable product of uniform composition. HME is one of the most commonly used processing technologies in the plastic, polymer, rubber and food industries. The pharmaceutical industry has shown an increased interest in HME due to the many advantages it has over conventional technologies. This technology has been shown to be extremely robust and a viable method of producing various drug delivery systems such as tablets, capsules, pellets, films and implants. Extrusion involves one or two corotating screws that convey material along an enclosed barrel and consists of

Figure 1. Applications of hot melt extrusion. Features and benefits of hot melt extrusion. Features

Benefits

Solvent free.

Environmentally friendly, economical and no residue in final product.

Continuous Process.

Fewer unit batches required and efficient scale-up from laboratory-to large-scale production.

Intense mixing and agitation achieved.

Improved content uniformity.

Compressibility not required.

Useful for powder with low compressibility index.

Polymers serve multiple purposes.

Less number of excipients required and cost effective.

Greater thermodynamic stability than that Less tendency towards recrystallisation. produced by other hot melt methods. three main parts: an opening through which material is fed, the barrel and the die. A variety of extruders are utilised at the Centre, including a Thermo Scientific HAAKE MiniLab (5–10 gm) micro compounder and 16 mm co-rotating twin screw extruder. The CPES has expertise in pharmaceutical product development through its links with the School of Pharmacy at the University of Bradford. Major targets in product development include: • poorly soluble drugs: solid dispersions, co-crystals and polymorphs • controlled release systems • moulded products: tablets and implants • transdermal drug delivery technologies and mucoadhesive films • inhaled drug delivery systems • novel drug delivery systems to address needs of elderly care. At present, nearly 40% of the new

chemical entities (NCEs) being discovered have poor water solubility (Biopharmaceutics Classification System (BCS) Class 2 and 4, with particular emphasis on Class 2). This is a serious drawback for drug formulation and as a consequence, many new potential drugs fail in the formulation stages. More than 80% of drugs are marketed as solid formulations and 90% of them are crystalline in nature. Active Pharmaceutical Ingredients (APIs) can exist in various solid forms, such as polymorphs, pseudopolymorphs (solvates and hydrates), salts, cocrystals and amorphous solids. Each form may possess its own unique mechanical, thermal, physical and chemical properties that can have a significant effect on the solubility, bioavailability, hygroscopicity, melting point, stability, compressibility and other performance characteristics of the drug. Continued on page 32

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INGREDIENTS & CONTRACT SERVICES ARTICLE HME has been applied in the pharmaceutical industry for preparing solid dispersions to improve the solubility of poor water soluble drugs. Solid dispersions prepared by HME can exhibit controlled drug release and provide improvements in dissolution. The CPES has developed mini tablets that have fast dissolution rates for a small dose drug using HME technology. This technology avoids the many unit operations encountered in conventional tablet processing and can be easily scaled-up for mass manufacturing purposes. Differential scanning calorimetry (DSC), shear cell, rotational rheometer, capillary rheometer and hot stage microscopy are used as screening techniques by the CPES to optimise HME processing. In recent years, another alternative to polymorphs and salts has emerged in the form of pharmaceutical co-crystals. Pharmaceutical co-crystals have two components: an API and a co-former. The API is usually selected because of its poor solubility, and it is matched with a co-former to improve its solubility. To synthesise a pharmaceutical co-crystal, one has to select an API and co-former that can potentially form hydrogen bonds with each other. Once chosen, there are several methods that can be used for their synthesis, however at the CPES, HME is the preferred choice. The CPES was successful in obtaining a £500k research grant from the Engineering and Physical Sciences

Research Council (EPSRC) in March 2012, to explore the underpinning science behind the formation of cocrystals in this innovative process. The findings of this project will significantly improve the potential for use of cocrystals in commercial drug delivery. Understanding the fundamental mechanisms behind co-crystal formation and the subsequent optimisation of this process will accelerate industrial interest in this field, providing direct benefits to the UK pharmaceutical sector and wider long-term benefits to public health through the availability of otherwise unusable drugs. Using HME, the API and co-former are usually fed into the extruder in a 1:1 or 2:1 ratio, depending on the specific cocrystal to be made. Parameters such as temperature, residence time and shear are critical during this process because it is thought that the mixture must undergo good mixing and be allowed to partially melt to allow co-crystals to form. Studies carried out by the students at the CPES have adjusted the parameters to achieve a good co-crystal yield for several different API-co-former systems. The CPES has successfully generated ibuprofen-nicotinamide, carbamazepinenicotinamide, caffeine-malic acid, salicylic acid-nicotinamide and itraconazole-malic acid co-crystals using HME. Rheological studies are also underway in the department to help understand the effect of shear force on polymorph and

Polymer IRC laboratories where CPES’s cleanroom facilities are located.

Thermo Scientific Pharmalab, 16 mm twin screw hot melt extruder.

Figure 2. Solid state classification. co-crystal formation. This is an important study because the mixing intensity and shear can be changed when designing the screws used for HME. The screw configuration can have a significant effect on the co-crystal yield achieved and it is thought that shear force plays a vital role. A polymorph is a solid crystalline phase of a given compound resulting from the possibility of at least two different arrangements of the molecules of that compound in the solid form. The CPES has patented a solvent-free technology to generate and stabilise metastable polymorphs without the need of any additional stabilisers (patent application number: GB 1208489.3). This method involves processing the marketed available form of artemisinin in a hot screw extruder at a temperature below the melting point of the drug; the resultant product is a more soluble form of artemisinin. Artemisinin can exist in two structural forms: orthorhombic and triclinic. The orthorhombic form is the most stable and is the only form available on the market while the triclinic form possesses good water solubility and has shown four times better bioavailability compared with the marketed form. The reported methods of preparing the triclinic crystal include crystallisation involving a solvent and the addition of an anti-solvent. However, the triclinic form obtained is metastable and undergoes solvent mediated transformation to the original form. Data suggests that minor traces of solvent (1.25%) may favour solvent mediated transformation and are responsible for the formation of the other form. This is a simple, continuous, solventfree, reproducible, scalable process, with high purity and stability compared with conventional techniques. Moreover, the product obtained is in an agglomerated form that reduces several unit operations in downstream processing. The inventive process under consideration utilises the application of appropriate shear and temperature in combination by processing the material within a heated, screw-driven process, which leads to polymorphic transformation. The formation of the triclinic form is confirmed by comparing powder x-ray diffraction (PXRD) patterns of the extruded samples with

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reference patterns obtained from the Cambridge crystallographic database. Being solvent-free, the instability associated with the residual solvent is avoided. The prepared triclinic form of artemisinin showed a two-fold increase in bioavailability compared with the orthorhombic form. This method is not only specific to artemisinin but can be applied to many other pharmaceuticals. The FDA now encourages process innovation in the pharmaceutical industry through better process understanding, which is achieved by adopting quality by design (QbD) and process analytical technology (PAT). PAT allows researchers at the CPES to understand the HME process in more detail. Near-infrared spectroscopy (NIRS) and Raman spectroscopy can be used as in-line tools for monitoring polymorph/co-crystal formation during hot melt extrusion via high temperature, fibre-optic probes. The probes can be situated at different positions along the extruder barrel for quantitative analysis of the material during extrusion. Calculated purity from off-line powder Xray diffraction is used to calibrate the inline NIR and Raman measurements. PAT provides an accurate view of the processes happening during extrusion and can help locate the point at which polymorph crystals or co-crystals are formed along the barrel. In the future, this PAT method could be used as a HME quality control system. The CPES has a good infrastructure and special expertise in the area of inline process monitoring of pharmaceutical extrusion and other processes utilising: • infra-red spectroscopy • raman spectroscopy • rheology • ultrasound. It also provides expertise in the areas of: • rheological characterisation for process optimisation • real-time monitoring of biopharmaceutical aggregation • monitoring of molecular assembly. The CPES welcomes new opportunities to develop partnerships and extend its network. For more information, contact Dr. Riddhi Shukla, Business Development Manager, the CPES, University of Bradford, +44 1274 235571 r.y.shukla@bradford.ac.uk. www.pharmaceuticalengineering.brad.ac.uk

SHOWCASE EXCIPIENTS Capacity Investment Meets Growing Demand for Sugar Spheres To meet the increase in demand for Suglets sugar spheres, Colorcon is investing to increase capacity and reduce lead-time, thereby reducing customers’ supply risk while ensuring premium quality and consistent product. Suglets are uniform drug layering pellets made of sucrose and starch, for controlled release dosage forms. Colorcon is reportedly the only manufacturer dedicated to pharmaceutical excipient production of sugar spheres, providing interchangeable product from plants on two continents: Stoughton in Wisconsin, US, and Bazainville in France. Continuous supply is secured with these two interchangeable manufacturing sites. By the end of July, 2013, production capacity at the Bazainville facility will

have increased by more than 25%. The investment in the Bazainville site will help to fulfill the growing demand from customers around the world and ensure the shortest possible lead times for Suglets products. For even more immediate availability of product, Suglets sourced from the Stoughton facility are a viable alternative. The Stoughton facility holds stock for many of the popular line items, available to ship within 10 working days from order. Studies demonstrate the interchangeability of quality and performance, regardless of the site of manufacture. All manufacturing equipment, methods and raw materials are interchangeable, and both sites are certified to ISO9001 standards. An equivalency report is

available upon request. With manufacturing sites dedicated to pharmaceutical production, customers can be confident that Suglets meet the high standards expected from a highly reputable supplier of pharmaceutical excipients. Colorcon is committed to reducing supply risk, providing flexibility and supporting solid oral dose development. For new product development or equivalency testing,

samples and technical support are available. Colorcon Ltd +44 1322 293000 www.colorcon.com

Taste-Masking Excipient to Target Paediatric and Nutraceutical Markets Roquette has launched KLEPTOSE LINECAPS, a new excipient for tastemasking. Based on special food grade maltodextrin, the product is capable of masking the taste of drugs by decreasing the overall amount of drug particles exposed to the taste buds. Suitable for many oral dosage forms, KLEPTOSE LINECAPS is ideal for paediatric and nutraceutical use. APIs’ undesirable taste is one of the most challenging parameters when addressing patient compliance for oral drug delivery systems. This issue is even more critical in the case of paediatric and geriatric populations. The

ability to mask taste impacts the commercial success of the final product by increasing patient compliance and business profitability. To address this issue, Roquette Pharma has developed KLEPTOSE LINECAPS 17, a new excipient for tastemasking. This particular maltodextrin contains linear amylose in significant amounts, making it easy to form the inclusion compounds with APIs, flavours or nutraceutical ingredients needed for taste-masking. As soluble amylose, it is a realistic alternative for both food and pharmaceutical preparations.

KLEPTOSE LINECAPS 17 also serves as a flavour encapsulation matrix, protecting against oxidation and preserving original flavours. KLEPTOSE LINECAPS 17 is suitable for many oral dosage forms, e.g., liquid and solid formulations intended for liquid reconstitution. Its food grade acceptability is particularly appropriate for the paediatric and nutraceutical markets. Roquette Pharma +33 3 21 63 36 00 pharma.business.unit@roquette.com www.roquette-pharma.com

International GMP and GDP Certification Scheme for Pharma Excipients Launches in US IPEC-Americas has announced the successful US launch of EXCiPACT, a voluntary international certification scheme designed and developed to assure cGMP and cGDP standards are being used in the manufacture and supply of pharmaceutical excipients. Approximately 100 stakeholders, representing designers, manufacturers, suppliers, distributors and users of pharmaceutical excipients, plus regulatory bodies and academia,

gathered in Maryland on 29 April for the launch event during ExcipientFest. They heard and interacted with speakers from the FDA, J.M. Huber Corporation and Hedinger GmbH & Co., who discussed the reasons for creating EXCiPACT and the benefits it can bring to supply chain security and patient safety. Much emphasis has been placed on the training and certification of third party auditors to deliver the scheme.

A website, www.excipact.org, is available to assist the pharmaceutical supply chain to learn more about the use and value of EXCiPACT. In addition to useful background information, the website provides access to the EXCiPACT standards, information and guidance on the certification process, plus auditor training requirements, training sessions and qualifications. Lists of approved third party audit organisations, approved auditors and

certified organisations will be added as they become available. IPEC Federation EXCiPACT Association +44 1786 220000 info@exipact.org www.exipact.org

Excipients Supplier Presents ‘Effect of Loaded Dose on Delivered Dose in Dry Powder Inhalers’ Poster at RDD Europe On 22–24 May, DFE Pharma shared its inhalation expertise at the RDD (Respiratory Drug Delivery) Europe event in Berlin to major global stakeholders in the inhalation industry. DFE Pharma presented a poster promoting the latest state of expertise in the field of inhalation lactose. RDD events are considered leading forums for the global inhalation industry, with participants from multinationals and

suppliers to the industry. The presence at RDD Europe provided an excellent opportunity to promote DFE Pharma as a leading inhalation excipient provider and expand both customer base and industrial network. DFE Pharma expertise was highlighted with a poster titled ‘Effect of Loaded Dose on Delivered Dose in Dry Powder Inhalers’, describing a study done in collaboration with the University of Bath,

EPM 33

on how DFE Pharma is investigating the fundamental properties of lactose affecting end product performance. The poster can be viewed online at: bit.ly/EffectofLoadedDoseonDeliveredDo seinDPIs. DFE Pharma +49 2823 9288 770 pharma@dfepharma.com www.dfepharma.com

Events

Pharma Integrates Organiser Releases 2013 Programme

REGULATORY AFFAIRS Regulatory Affairs Vs Regulatory Sciences

This issue’s contribution comes from Dr. Paolo Biffignandi’s colleague Dr. Parvinder Punia, Senior Regulatory Affairs Manager at ELC Group. With a scientific background, Dr. Punia has nine years of regulatory experience, which includes three years from within two EU health agencies (the National Authority of Medicines and Health Products (INFARMED, I.P.) in Portugal and the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK). She has represented the UK agency at the European Medicines Agency (EMEA) level. Her key expertise is in strategy, budgeting, preparation, co-ordination and review of a variety of scientific and regulatory documents for European and experience in non-European countries. Dr. Punia has extensive knowledge of the development cycle and internal knowledge of the EU and other regulated region procedures and has worked in a business development capacity.

Regulatory affairs is a comparatively new profession that developed from the desire of governments to protect public health by controlling the safety and efficacy of products in areas including pharmaceuticals, veterinary medicines, medical devices, pesticides, agrochemicals, cosmetics and complementary medicines. The regulatory professional should have a mix of scientific knowledge, negotiation skills and business intelligence, which is a science in itself and can be applied to the industry, the academy and the authorities. But how much of it is really science, and how much of it is affairs? The answer could be simple, as suggested by the EMA: ‘Regulatory science is defined as a range of scientific disciplines that are applied to the quality, safety and efficacy assessment of medicinal products and that inform regulatory decision-making throughout the lifecycle of a medicine. It encompasses basic and applied medicinal science and social sciences, and contributes to the development of regulatory standards and tools’. So, a scientific discipline, but one conducted within a legal framework. Since the entire development pipeline must be within regulatory boundaries, where one’s particular professional skills are being applied can also influence how one views the profession. A formulation developer solely concerned with reverse technology of a reference product may only be applying scientific knowledge. The same would be applicable for a principal investigator of a clinical trial. However, in the background, there are the monitors of compliance, who ensure that the standards required are adhered to. These are the negotiators of the regulation. At the opposite end of the spectrum are the professionals solely concerned with management of submissions to agencies. The majority of the work is administrative and project management-based, with the minimum of science involved. These industry professionals would be engaged in persuading regulators to review material from not only a scientific perspective but possibly also from a patient and commercial perspective. The basis of pharmaceutical developments is always attributed to science. However, with the reduction of novel drug research and the expansion of innovation based on old discoveries, it is difficult to avoid the ‘affairs’ side of the profession. Nowadays, regulators are constantly required to answer deep questions as to why such guidelines or requirements exist. Although steeped in scientific history, many of the guidelines are open for discussion in regard to any single development. This is the crossover line between science and negotiation. However, the individuals engaged in such discussions must understand the technicalities of development sciences. This is not a general discipline, so such professionals may need to be qualified in one of the following: chemistry, pharmacology, toxicology, genetics, clinical trial expertise and biostatistics, amongst many other disciplines. Additionally, such discussions would require experts familiar with legislation, negotiation, budgeting, risk management and general compliance issues. In essence, even the most skilled regulatory scientist must work in a team of professionals with different backgrounds and knowledge to ensure a positive outcome and a scientific approach to regulatory intelligence. This, ultimately, is the key for success. Dr. Parvinder Punia parvinder.punia@elc-group.com

At this year’s Pharma Integrates — 26–27 November, Park Plaza Riverbank, London, UK — over 200 strategy level pharmaceutical executives from big pharma, SMEs, CMOs, CROs, generics, specialty and virtual pharma will gather to debate ‘Strategically transforming pharma business relationships’, examining how such collaborations are evolving and supporting innovation, productivity, differentiation and profitable growth. Many critical topics steered by a select pharma steering committee will be addressed over one-and-a-half days with a series of keynotes and highly interactive panel discussions to stimulate organic, honest discussion and open information exchange. Dispersed throughout the conference programme will be a variety of informal networking opportunities to encourage one-to-one meetings with industry peers. The Pharma Integrates programme is as follows: Day One • Chairman and Keynote Speaker Professor Trevor Jones CBE, Director at Allergan and President of Sigma-Tau Glenn Crocker, Chief Pharmaceuticals, Executive Officer, BioCity to open Pharma Nottingham, and Integrates with a Director, Mobius Life state of the Sciences Fund. nation opening address. • Exclusive Preview of 2013 UK Life Sciences Start-Up Report from Dr. Glenn Crocker, Chief Executive Officer of Biocity Nottingham. • ‘Building a Resilient Supply Chain’. Panellists include Dr. Peter Comes, Corporate Vice President End-to-End Supply Network Strategy, Boehringer

Ingelheim, Dr. Sven Remmerbach, Director Business Development & Contract Manufacturing, Baxter, and Arjan Adegeest, Executive Director Supply Chain, Alexion Pharmaceuticals. • ‘The Increasing Role of Collaboration — The Key to Success in the Pharma Industry?’. Panellists include David Roblin, Chief Medical Officer, Creabilis Biotech, and Bio-Industry Advisor, NOCRI, Ian Muir, President Modified Release Technologies, Catalent Pharma Solutions, and Alex Robertson, Director Sourcing R&D Pharmaceutical Development, AstraZeneca. • Champagne and canapé networking reception. Day Two • ‘Increasing Pricing Pressure: Partnerships and Strategies to Compete’, facilitated by Ewan Livesey, Senior Vice President Corporate Development, Lupin. Panellists include Guy Clark, Strategic Development Director, Amdipharm Mercury Company, Richard Learwood, Global Director Brand Strategy & Innovation, PGT Healthcare, and Douglas Andrews, Director Planning & Business Development, Stravencon. • ‘Beyond Account Management’, focused on leveraging pharma supplybase capabilities to co-create value in the broader healthcare sector. Panellists include Sammy Rashed, Global Head of Productivity & Sourcing Strategy, Novartis Pharma, Detlef Behrens, Vice President Business Development Formulations, Piramal Healthcare, and Giles Breault, Global Head of Productivity & Business Services, Novartis Pharma. • Networking luncheon. Life Sciences Index +44 20 8667 2117 miranda.zouheir@lsi-uk.com www.lifesciencesindex.com

Forum for Improving Biological Production Performance to Overcome Biomanufacturing Challenges The Biological Production Forum 2013, running for the 12th year, welcomes senior biotechnology professionals working within biological manufacturing, bioprocess development and product operations. Join experts to learn and find out about the latest industry news, benchmark against the competition and network during the pre-arranged one-toone meetings. This leading event is taking place on 23–25 September 2013, at the Swissôtel, Düsseldorf, Germany, and features speakers from a variety of organisations, including Shire, GSK, Roche, Novartis, Pfizer and UCB. The agenda features case studies that cover topics such as single-use facilities, viral clearance and closed systems. This summit will also host interactive workshops on topics such as tech transfer and human error reduction. Programme highlights include: • Building a sustainable operation for the pharmaceutical business or ‘go with the flow’, by Kim Sandell, Director, EPM 34

Operations Management & Operational Excellence, Pfizer • Successfully developing a seasonal influenza vaccine, by Karsten Kattmann, Plant Manager, Novartis • Overcoming regulatory challenges with raw material contamination, presented by Lada Ivana Laenen Horvat, Managing Principal Scientist, Genzyme • Improving productivity during the lifecycle of biopharma products, led by Torsten Schmidt, Head of R&D Operations, Lonza. View the full programme and read about the leading speakers at www.biologicalproduction.com/program me. World Trade Group +44 207 202 7690 michaela.melcher@wtgevents.com www.biologicalproduction.com

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