EPM March/April 2014

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IN THIS ISSUE: interpack 2014 Preview Cleanrooms Sample Preparation Drug Delivery

European Pharmaceutical Manufacturer March/April 2014

Volume 14 | Issue 02

Specialization drives innovation. Since 1918, KORSCH has focused on its core competency of tablet presses and today, KORSCH offers the most innovative line of tablet compression equipment. At INTERPACK 2014, KORSCH will launch our latest innovation, a new machine model which has been developed in response to a clear market demand. Please visit The Specialist at Booth B51 in Hall 17 and see the very latest in tablet compression technology.

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ellie@rapidnews.com publishers mark blezard,

IN THIS ISSUE INTERPACK 2014 PREVIEW

duncan wood

production art samantha hamlyn production peter bartley

pages 5–16

advertising robert anderton tel: +44 (0) 1244 680222,

Exhibitor News

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MANUFACTURING PRODUCTS

pages 17–38

Industry News

17–18

Product News

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Buyers’ Guide — Granulation & Milling Buyers’ Guide — Mixing & Blending

31 32

In the Spotlight — TSAR Predict service solves sticking conundrum in hours With I Holland’s research, development & quality systems manager Rob Blanchard

33–34

Article — Busting the myths of chlorine disinfection

By Karen Rossington, marketing consultant to Contec Inc.

36–37

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Showcase — Cleanrooms

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LABORATORY PRODUCTS

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Industry News

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Product News

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Showcase — Sample Preparation

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INGREDIENTS & CONTRACT SERVICES

pages 47–57

News

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Opinion — Choosing a lab services partner

By Jane Sanderson, executive director global laboratory services, Packaging Coordinators, Inc.

54–55

Regulatory Affairs — Harmonisation challenges in the EU

By Dr. Parvinder Puna, a senior regulatory affairs manager at ELC Group.

Showcase — Drug Delivery

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European Pharmaceutical Manufacturer is published by Rapid Life Sciences Ltd. European Pharmaceutical Manufacturer is distributed in electronic and print formats to a combined readership of 14,000 pharmaceutical manufacturing professionals.

Volume 14 Issue 2 © April 2014.

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ISSN No - 2052-4811

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FROM THE EDITOR

New look EPM, Early Access to Medicines Scheme and I Holland’s new anti-sticking tablet tooling service ‘TSAR Predict’

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You have no doubt noticed that this issue looks different; in fact, as you scan though, you will realise it has been given something of an overhaul. This marks a turning point not only aesthetically but also in terms of future content, meaning more articles, comment from industry experts and new columns. So watch this mag! As always, I look forward to receiving readers’ comments and suggestions.

A ‘big’ mainstream media pharma headline is that the Early Access to Medicines Scheme (EAMS) is to launch this month, enabling severely ill patients to be given promising new medicines before they are licenced; this will be after they have passed the clinical trials stage and are waiting for marketing approval.

Health secretary Jeremy Hunt has fully endorsed the scheme, saying: “What patients want is sometimes to be able to try medicines that may not be clinically proven to be effective but are clinically safe.”

It is of course anticipated that the EAMS will be advantageous for the pharma and biotech industry as well as the NHS. The MHRA, which will be overseeing the scheme, estimates that one or two products a year might qualify, although it could be more.

These medicines will be fast-tracked for patients with serious conditions such as cancer and muscular dystrophy and

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for whom there are no other treatment options.

However, there is some controversy surrounding the EAMS. Whereas Cancer UK has welcomed the new regulations from the standpoint that it could mean the difference between life and death for some patients, there are doctors who have expressed concern that these drugs could do more harm than good. A discussion surrounding this has been started on the LinkedIn EPM Magazine Group page — http://linkd.in/1j3EinP — and your viewpoint is welcomed.

Now you may recall that in our May 2013 issue, I spoke to tablet tooling manufacturer I Holland Ltd’s research, development and quality systems manager Rob Blanchard about the TSAR (Tabletting Science and Anti-Stick Research) project — a collaboration between I Holland and the University of Nottingham’s School of Pharmacy. The goal of the project has been to offer a service whereby I Holland is able to recommend the ‘right’ anti-stick tooling for customers’ formulations in significantly less time than previously — hours as oppose to months — and without disruption to their busy production schedules. The project took two years and on 6 February, I Holland announced this new capability, aptly called TSAR Predict. On pages 33–34, I learn from Rob how effective TSAR Predict has proved thus far and how close the company is to achieving its goal of eliminating the ‘sticking’ issue altogether.

And that is all from me until the May issue. In the meantime, please join the LinkedIn EPM Magazine Group and get involved in our EAMS debate.

Elizabeth Valero, Editor

INTERPACK PREVIEW 2014 Düsseldorf trade fair centre in Germany. This year, about 2,700 exhibitors are expected from industries ranging from food and beverages, confectionary and baked goods to pharmaceuticals and cosmetics, non-food consumer goods, industrial goods and related services.

interpack is one of the world’s most important trade fairs for the packaging sector and related processing industries. The last interpack, held in May 2011, attracted 165,000 professionals from all over the world. The next interpack will take place on 8–14 May 2014 at the

Vacuum mixer dryer with conical floor boasts complete self-discharge With the AMT series, amixon presents a new generation of vacuum mixer dryers.

The main difference between the AMT style and previous models is their conical floor form. This floor offers the decisive advantage that complete and automatic self-discharging is achieved with freeflowing material.

A further benefit is that even mixing is also achieved in the cone. This is the result of a patented, helical ribbon mixing tool, which creates a three-dimensional movement of the mixing-goods. The helical spring gathers the mixing materials at the periphery of the mixing chamber and transports them upwards. Once it reaches the top, the mixture flows downwards in the centre of the container.

The mixing effect essentially takes place at the interfaces between the two macrocurrents.

Not only the mixer itself, but also the helical ribbon, mixing arms and mixing shaft are completely heated. Drying is said to be extremely fast, gentle and even. The patented mixing tool is only fixed and driven at the top. The tanks are vacuum- and pressure-proof, which means that pressure-dependent reactions can also be managed. For example, an inert carrier gas can be used for subsequent drying.

The AMT mixer dryer reactor is suitable for drying powders, suspensions, pastes and dough. Cutting rotors can accelerate the mixing and drying process and at the

same time carry out de-agglomeration; as a further option, the tanks can be provided with a heated inspection door without dead space.

The amixon mixers and dryers are developed to fulfil the highest hygiene requirements. They can be used as sterile equipment in compliance with FDA regulations, EHEDG (European Hygienic Engineering and Design Group) requirements and the 3a sanitary standards.

Each amixon vacuum mixer-dryer and reactor is individually adapted to the respective customer’s requirements and process parameters. The mixers and dryers as well as all components are manufactured exclusively in Germany.

The processes within the drying procedure can be determined at the amixon test centres at Paderborn, Germany, Memphis, US, Osaka, Japan, Bangkok, Thailand or Satara, India, where all the relevant parameters are recorded in real time.

Hall 1/Stand F23 amixon GmbH www.amixon.com

Particle coating method guarantees precise and uniform results with minimal losses With the development of the new Bohle Uni Cone BUC, it is claimed that customers now have a precise method for coating particles as a utility model.

“We have shown that our new method works much more accurately and evenly than the conventional Wurster process,” said managing director Lorenz Bohle.

The Wurster process is used in the pharmaceutical industry when coating small particles, so called pellets. Most coating systems used today are still based on this method, which was developed in 1959.

For L.B. Bohle, the biggest weaknesses of the Wurster process are

the calculation of scale-up parameters and the location of the spray nozzles inside the product bowl. The scale-up parameters must be verified in multiple and lengthy tests for each product, resulting in a loss of production time and large fluctuations in coating uniformity.

L.B. Bohle developed two major changes to solve both problems of the Wurster process. A sloping floor and a conical tip in the centre aims to provide a uniform movement of product.

Simultaneously, the coating substance is delivered from nozzles located tangentially to the product vortex and accessible from outside the product bowl

during the process. “Therefore, we achieve the best possible coating uniformity. With this process, customers can use active substances with the highest precision,” explained Bohle.

“Even in a very complex process, the losses are under 1%.”

In addition, the tangential nozzles have enhanced quality advantages in handling. If a nozzle is blocked, it can be cleaned with an aqueous solution during the current process. “Because of the tremendous benefits, we can secure a patent protection for the process and protect the Bohle Uni Cone BUC as a European brand,” concluded Bohle.

Hall 3/Stand D27 L.B. Bohle Maschinen + Verfahren GmbH www.lbbohle.de

German pharma plant invests in 750 l tablet coater to perform complex task Gebr. Lödige Maschinenbau has received the first order for large-scale implementation of the latest LC coater series; a major German pharmaceutical manufacturer will be using coating system model LC 150 with a useable volume of 750 l for the organic coating of tablets. Commissioning/start-up is scheduled for April 2015.

The LC coater series was specially developed for coating tablets. The top priority in its conception was optimum process management, in addition to ease of operation and ease of cleaning.

According to Lödige, all three sub-processes, which are relevant for film coating, were optimised: spraying the coating solution, mixing the tablets and drying them.

At the same time, this development distinguishes itself with a new design for spraying on the coating solution with a high number of jets, which the company says enables a perfect fit with the tablet bed. The technology makes it possible to easily set and automatically control the correct spraying distance and angle at any time to achieve an outstanding result. At the same time, the arrangement and number of jets accelerates the process in comparison with similar coaters.

The recently commissioned coating system is extraordinarily complex; the task requires complex gas preparation technology, especially after a large amount of drying gas is used. In addition, the system is equipped with a

specially designed and extensive highpressure jet assembly. This enables short processing times as well as coating homogeneity.

To guard against explosions, the entire process takes place in a nitrogen circulation system. Nitrogen blocks atmospheric oxygen. The oxygen concentration in the unit is monitored continually. The solvent is condensed during the process.

The LC coater series will be highlighted on Lödige’s interpack stand. In addition, emphasis will be on continuous production processes in the pharmaceutical industry. As a supplier of both batch and continuous systems, Lödige actively supports the trend towards exploiting the characteristic

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strengths of continuous processes for the manufacture of pharmaceutical products.

Hall 3/Stand F22 Gebr.Lödige Maschinenbau GmbH www.loedige.de

INTERPACK

News

Three-in-one modular milling system drives process and cost efficiency gains People talk about modular systems in the automobile industry often and correctly as a model for efficiency and quality, and it is often cited in software development as the preferred basis for today’s automation. Frewitt began developing modular systems six years ago with the introduction of the ConiWitt conical sieve mill. The mill head on the ConiWitt-150, which was designed for a maximum throughput of 1,500 kg/hour, could be exchanged with the mill head of a ConiWitt-200, giving a maximum throughput of 2,200 kg/hour, without having to change the system’s platform.

Since this first approach, Frewitt’s development department has worked intensively to create a modular system that not only brings together the conical reduction of powders and granulates

but also the control screening and fine grinding in one machine.

The concept was to put together a conical sieve mill with a rotor at medium revolutions per minute (RPM) with a cylindrical sieve mill with a turning stator with lower RPM and a hammer mill with high RPMs in one modular system. The interface was the drive arm, which connects the entire drive and control system with the milling system electronically and mechanically. The control and operator interface design was completely reworked in order to increase the degree of automation and to be able to integrate the PLC of the sieve mill into the higher level system.

This field-proven functionality of the three milling processes — collectively known as FreDrive — was not altered.

The design of the hammer mill did receive a new mono-block housing and internal cabling.

Thanks to the three, easily interchangeable mill heads, a customer should be able to quickly convert to a new process. Three different grinding methods can be used for grinding, fine grinding or controlled screening of powders and granules. This modular system is not only intended to be ergonomically friendly but also very cost-effective. In the past, a customer was forced to invest in three mills.

Today, the customer has the option of a drive and control system with three milling heads, capable of reducing investment by 50%.

Faster product cycles, easier assembly/disassembly of

screening/rotors, increased process reliability, low maintenance and easy scale-up from laboratory to production lots are additional benefits of its modular construction, says Frewitt.

Hall 4/Stand C39 Frewitt fabrique de machines SA www.frewitt.com

Systech presents permeation analysis range for reliable testing of packaging At this year’s interpack, Systech Illinois will be exhibiting its range of water vapour permeation and oxygen permeation analysers, for testing in many different packaging applications.

According to Systech, these oxygen permeation analysers offer reliable and versatile testing for bottles, packages and films with the company’s bestselling

instruments, delivering fast permeation results. It is claimed they provide extremely fast purge down time and accurate readings at the lowest levels.

Systech’s water vapour permeation analysers utilise the Proprietary Coulometric P2O5 sensor for absolute moisture measurement of films and packages.

Also on display will be the company’s range of oxygen and carbon dioxide headspace gas analysers for the food and pharmaceutical packaging industry and oxygen analysers for process applications.

Hall 5/Stand A29 Systech Illinois www.systechillinois.com

Videojet showcases print and apply labelling, thermal-ink jet, CO2 laser marking and code detection solutions Addressing packaging, food and pharmaceutical manufacturers’ coding and marking needs, Videojet Technologies will showcase its latest technologies at interpack.

Videojet will launch the latest LPA print and apply labelling solution for outer case and bundle packaging, intelligently designed to remove the mechanisms that frequently cause everyday operational problems such as label jams. The event will also see the official launch of three other developments. For high-resolution coding on non-porous packaging, Videojet has designed a print solution that combines the highresolution and simplicity of thermal ink jet (TIJ) technology with methyl ethyl ketone (MEK) industrial ink performance.

In addition, Videojet will present its

advanced range of CO2 laser marking systems, engineered to extend marking speeds. Also being unveiled is a code detection system that verifies the presence of ink jet printed codes, providing an advantage over manual sampling by increasing the number of products that can be inspected.

The design of the new LPA system removes the mechanical adjustments, wear parts and failure points that cause operational problems and downtime.

Labels can be applied directly onto outer case and bundle packaging without the need for an applicator, claimed to result in higher throughput and elimination of label jams.

The TIJ solution utilises fast-drying inks such as MEK-based fluids to provide high-resolution print on non-

porous packaging materials. According to Videojet, it offers resolutions up to four times greater than continuous ink jet technology.

The advanced range of CO2 laser marking systems aims to deliver outstanding code quality across a range of marking speeds. The laser solutions offer over 20,000 configuration options for easy integration into virtually any application.

Ideal for flat and light-coloured packaging, the code detection system provides an enhanced level of assurance by helping detect common printing issues including missing, mispositioned and clipped codes. The system offers a simple, three-step set-up process that minimises changeover time.

Videojet will host ‘by invitation only’ seminars and expert sessions aimed at sharing the very latest trends and issues surrounding coding and marking.

Hall 6/Stand A01 Videojet Technologies Inc. www.videojet.com

Bosch exhibits modular filling and packaging machines for diverse requirements At interpack, Bosch Packaging Technology will introduce numerous developments for the pharmaceutical industry. Thanks to their modular design, all machines can be adapted to current and future market requirements and integrated into line concepts.

The new FXS Combi — a filling and closing machine for pre-sterilised nested syringes, vials and cartridges, featuring an integrated capping station — will be presented. It can be flexibly integrated into existing line concepts, allowing for significant space savings. The FXS Combi is designed for low and medium output and can be combined with the proven bag and tub opening machines from Bosch. The presentation of an entire high-performance syringe line, consisting of the filling and closing machine FXS 5100 for pre-sterilised nested syringes, an ABO bag opener and an ATO tub opener, will further

underline the company’s competence in the processing of pre-filled syringes.

Bosch Inspection Technology will provide an overview of its product portfolio, ranging from manual to fully automated inspection machines for the detection of particles in pharmaceutical liquids and cosmetic container inspection.

A highlight will be the reveal of the AIM 8 series, the new generation of fully automated inspection machines. From its portfolio of manual inspection devices, Bosch will showcase the tabletop device MIH-LX and the camera-based ETAC Easy View, which are, amongst others, used for laboratory analysis.

A new tablet press from the product brand Manesty will be displayed. It is cliamed that the newly developed filling shoe as well as fast product and format changeover enhance the tablet press’s output, making it especially suitable for customers with flexible requirements.

The flexible application of Bosch’s capsule filling machines will be demonstrated. The GKF 702 is suited for small and medium batches and all standard filling technologies. The GKF Capsylon 3005 focuses on a reliable output of up to 175,000 capsules per hour. It meets the demands of nutraceutical manufacturers for high Bosch will present an entire high-performance syringe efficiency, easy maintenance line, consisting of the filling and closing machine FXS and operation.

5100, an ABO bag opener and an ATO tub opener.

Finally, Bosch will showcase its after-sales services portfolio, offering part in the ‘OEE Challenge’, a contest solutions that aim to improve packaging that tests participants’ speed, feeding flexibility, machine efficiency and accuracy and productivity on an productivity. Machine upgrades and overhauled horizontal wrapper. modernisations should enable customers Hall 6/Stand A31–C58 to flexibly adapt their existing equipment to new market requirements. During live Bosch Packaging Technology presentations, visitors will be able to take www.boschpackaging.com

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INTERPACK

News

215+ Rockwell Automation equipped machines to showcase worldwide potential At this year’s interpack, OEMs will showcase over 215 new and enhanced machines running on Rockwell Automation-based automation, motion, process and safety solutions. With interpack being a world leading event for the launch of new and innovative packaging technology, Rockwell Automation says it should come as no surprise to learn that such a large number of machines at the show will be running discrete and integrated automation, motion, process and safety solutions based on its Allen-Bradley products.

In today’s competitive environment, the packaging industry is demanding machines that easily integrate into plantwide infrastructures. It needs flexible and efficient equipment that increases business agility, optimises productivity and helps end users to achieve sustainability objectives — all while lowering total cost of ownership.

At this year's event, Rockwell Automation says it will be helping to foster and formalise relationships between machine builders and manufacturers by acting as a conduit to match customer needs with new and proven, high-performing solutions from a variety of established machine builders.

In addition, the Rockwell Automation stand will showcase the latest technology the company has to offer along with multimedia presentations showing this technology in action across the globe. Industry specialists will also be on hand to discuss customer needs at all stages in the production chain.

Rockwell Automation company specialists will be on hand to illustrate

how the company has catered for the varied and demanding needs of the industry and then introduce visitors to leading machine and equipment builders. For those with limited time on their hands, a literature suite will be available as will the ability to arrange follow ups and site visits.

The company’s website will help visitors plan their visit and identify key priorities so that, as an end user, they can connect with leading OEMs. This approach from Rockwell Automation mirrors the official objective of this year’s event — covering the entire value creation chain; from production and refinement of packaging products and packaging materials, through packaging and distribution, up to quality assurance and consumer protection.

Rockwell Automation has products, solutions, capabilities and examples of OEM successes and can illustrate this with multiple success stories.

Hall 6/Stand A61 Rockwell Automation Ltd www.rockwellautomation.com

OYSTAR A+F showcases recently launched packer and palletiser Specialist in final packaging OYSTAR A+F will present a newly developed packer with flexible application at the forthcoming interpack.

The machine uses a fouraxis Delta 3 robot to group portion cups, thermoformed trays, pouches and blister packs into cartons. It is also the perfect packing solution for products in secondary packaging. The packer can handle trays and wraparound cartons as well as cases with lids and two-piece trays. Depending on the box type, the packer can provide an output up to 40 cartons per minute in single lane and 70 in dual lane.

In addition, OYSTAR A+F will be presenting a new, modular palletiser, a loader for the lower- and mid-level output range. The standard version of the machine loads and unloads the pallets manually, but there is an automated solution available as well. It is still possible to integrate layer sheet processing and packaging rotation equipment into the machine.

With a servo-driven container feeder that needs no spacing devices, this machine can handle layers with great flexibility. It can feed folding cartons,

Palletiser. wraparound cartons and cartons with loose lids as well as trays with and without lids. Depending on the type of layers and the machine equipment, the palletiser can provide an output up to 150 layers or 1,400 containers per hour.

The palletiser’s drive is run by a servomotor using a flat or a toothed belt. This is said to guarantee the best possible service lifetime and simplified maintenance. Furthermore, the linear actuators feature a clamping device to prevent falls and therefore enhance the protection of the machine and its operators.

Hall 6/Stand B73 OYSTAR Group www.oystar-group.com EPM 7

INTERPACK

News

Optical carton tester quickly assesses multi-layer construction of carton board

Cerulean is introducing its handheld OCT optical carton tester at interpack.

The OCT optically measures and records dimensions, angles and symmetry of carton crease, bead and formed box. It is said to quickly assess the multi-layer construction of all types of printed or non-printed carton board, paperboard and waxed carton products. The system can also test complex embossing and multi-folded corners.

Utilising a full HD handheld camera, the OCT is connected to a laptop via a simple USB cable and is intended to be easy to use. The system comes pre-programmed with analysis and reporting software.

Available in two versions, the OCT provides simple measurement for quality control with results in PDF

Dosator for customised handling of capsule powders

format and the OCT Plus is suited to production and incorporates sophisticated measurement software for coordinating the various matrices that influence carton quality. After assessment is complete, certification can be printed for quality assurance purposes.

The new OCT follows the recent introduction of the PCT portable carton tester and the launch of the LCT laboratory carton tester in 2013.

The LCT has already been installed in 50 locations worldwide and is one of a series of new products being developed by Cerulean for the carton industry.

Hall 6/Stand C43 Cerulean www.cerulean.com

A new dosator powder filling system has been developed

by Dott Bonapace for its In-Cap fully automatic benchtop capsule filling machine, to compliment the existing dosing disc filling system currently available.

As an R&D machine, the In-Cap is frequently used to formulate and refine products that are to be transferred to production units.

This new system should enable powders to be developed for all types of production equipment as well as allow different types of product to be handled in the way best suited to their characteristics.

The unit has been designed so that not only can it be fitted to new machines but also installed on all existing Bonapace In-Cap units with a simple modification of the machine.

The system consists of two dosator tubes, each with an internal pin which forms the chamber. The length of this chamber is centrally adjustable to suit the filling requirements. The dosators are raised and lowered each cycle, while being rotated as the machine

indexes. The tubes are lowered in the powder bed of the hopper, with an adjustable tamping facility if required for forming a slug of product. They run until located over the open body of the capsule when the dosator pin is used to push the powder out of the chamber and into the capsule.

The hopper consists of an annular ring to minimise the amount of product needed to allow the unit to run. The depth of the powder bed is adjustable while the residual product is agitated after the dosing station. A bulk hopper feeds powder to this device and has been designed to lessen the problems of bridging experienced with some products.

The dosator system is interchangeable with the existing tamping system so that, according to powder type, the customer can use the most suitable one for obtaining the best performance.

This new system marks a major step forward for the In-Cap machine, which has proved successful in many locations throughout the world, says Bonapace.

Hall 6/Stand D30 Dott. Bonapace & C. srl www.dottbonapace.com EPM 8

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INTERPACK

News

Travtec demonstrates FMD-ready coding solutions A variety of equipment will be showcased by Travtec at this year’s interpack, including its FMD-ready solutions to help pharmaceutical manufacturers prepare for the requirements of the forthcoming EC Falsified Medicines Directive (FMD).

Highlights include the Lixis PVS vision system and the Wolke m600 Advanced thermal inkjet printer for printing and checking serialised 2D codes, while models from the company’s portfolio will also be demonstrated.

The Lixis PVS is a high-end OCR/OCV imaging system that Travtec claims offers reliability, accuracy and speed for a wide variety of inspection requirements throughout the packaging process. Its character recognition software reads both pre-printed and inline 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 set-up 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 Wolke m600 Advanced uses HP technology and water-based inks to deliver clean and maintenance-free realtime coding onto a wide range of substrates, producing characters and barcodes up to 600 dpi. The printer can also be specified with an ink for non-

porous surfaces such as blister foil packs, while Travtec’s special traversing unit enables the printer to be integrated into existing blister lines with multiple head configurations.

The m600’s ability to print variable Datamatrix codes to ECC 200 makes it suitable for track and trace requirements, particularly where products are exported worldwide. Data for the bar codes is transferred to the printer via a built-in Ethernet port and the m600 Advanced also features a USB port as standard.

To further ensure clear and accurate coding for FMD requirements, the Travtec Pharmacarton Elite and TR-760TT offer online and offline handling respectively for full and accurate control of cartons and packs during printing.

Both machines are fully adjustable to suit a range of carton sizes. The Pharmacarton Elite features a new compact design with an enclosed operating unit. The TR-760-TT can

handle cartons, boards, sheets, blister and credit cards and can also be used in conjunction with labellers and print and apply labellers.

Hall 7A/Stand C31-5 (Lixis stand) and Hall 8A/Stand E17 (King stand) Travtec Ltd www.travtec.co.uk

Single dose counter allows PDMI users to keep track of medication As one of the major global packaging exhibitions, interpack provides the ideal platform to demonstrate the diversity of the RPC Group, with its extensive choice of manufacturing processes and polymers that enable the company to tailor a pack to the requirements of each customer.

According to RPC Formatec, it has introduced a cost-effective system for pharmaceutical markets that enables

users of pressurised metered dose inhalers (PDMIs) to easily count down the number of doses taken from their inhalers. The single dose counter allows users to keep track of their medication and alerts them when the inhaler needs replacing.

RPC will also underline how it uses the same design and manufacturing expertise to help customers create product differentiation and on-shelf

impact throughout its comprehensive standard ranges.

Equally important, the company’s many initiatives in weight and energy savings during manufacture help to deliver carbon reductions and valuable sustainability benefits.

Hall 10/Stand D21 RPC Group www.rpc-group.com

Mettler-Toledo displays latest product inspection and track and trace solutions To address the quality and process control needs of food and pharmaceutical manufacturers, the product inspection and industrial weighing divisions of Mettler-Toledo will present their comprehensive portfolio of product inspection, QA and track and trace solutions at interpack. The guiding theme for this year’s exhibition is effective process data collection and management information systems.

Mettler-Toledo will showcase its new generation of Garvens checkweighers, which the company says ensures precise weighing results regardless of production environments and supports manufacturers in continually improving product quality and safety. The new generation is built to enhance performance by up to 33% through total design customisation.

For the first time, the company will present its latest generation of Safeline x-

ray inspection systems. The X36 Series is designed for monitoring a range of products and deploys advanced imaging technology to deliver competitive efficiency on processing lines.

Mettler-Toledo will demonstrate a full range of complete track and trace and serialisation solutions for labelling, controlling and verifying pharmaceutical packaging from Pharmacontrol Electronic GmbH. The company’s vision inspection systems verify correct labelling and package integrity in order to achieve perfect product presentation in line with compliance needs. Visitors to the stand can view a demonstration of the CI Vision V6300 system. The modular design can support up to five cameras and can be integrated into existing production lines.

The data management software ProdX 1.2 for integrated management of x-ray inspection, metal detection and

checkweighing technologies will be presented. The software connects data from multiple systems and enables central monitoring from any location for improved process efficiency.

Mettler-Toledo offers the networkbased software solution FreeWeigh.Net, a configurable, standardised software system for statistic quality control of filling and packaging processes. With the FreeWeigh.Net device integration module, a wide variety of devices can be connected to the system without additional programming. FreeWeigh.Net evaluates the data from many measuring devices and instruments such as checkweighers and static scales in order to comply with fill quantity control.

Pilot Site Manager software for integrated track and trace line management provides enterprise-wide high visibility of data for the

pharmaceutical industry. The software is a global solution and can be fully accessed by production managers from any location to enable compliance with a range of regional requirements as well as allow flexibility to meet future regulations.

Hall 11/Stand B55 Mettler-Toledo Product Inspection www.mt.com/pi

Affordable labeller guarantees reliability and precision at affordable price With an entirely new labeller bearing the name ‘basic’ for reliable and economical applications, HERMA is staging a world premiere at the forthcoming interpack.

The HERMA basic model is designed to ensure reliability and precision in a broad variety of standard applications at a price that is affordable. It is built on the same line in Deizisau, near Stuttgart, Germany, as the much higher-spec HERMA 400 labellers. Users can benefit

from connectors on the new labeller that are identical to those of the HERMA 400. Customers requiring significantly higher performance and greater functionality as time progresses can therefore easily exchange a HERMA basic labeller for a more versatile model. “Thanks to this new model, even users with modest budgets now have access to cutting-edge HERMA technology,” said Martin Kühl,

head of HERMA’s Labelling Machines division.

The HERMA basic offers a speed of up to 25 m/min, which is adjustable by way of the keypad with integral display. By integrating the control in the machine, HERMA has been able to dispense with a separate switch cabinet. The compatible label size extends from 12 x 12 mm to 160 x 400 mm.

Hall 12/Stand B24

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HERMA GmbH www.herma.com/en

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INTERPACK

News

Packaging machine without switch cabinet makes debut Gerhard Schubert is again boosting the capacity of its extremely flexible TLM transmodule packaging technology. The latest TLM generation will premiere at interpack. According to Schubert, a prototype of the world’s first packaging machine without a switch cabinet for the processing of infusion bags will be among the innovations presented. The company claims to already achieve higher efficiency in manufacturing and configuring the lines in the current stage of development and that customers benefit from lower maintenance expenditures.

The new 3D scanners from Schubert realise spatial perception. The resulting

height profile reflects the threedimensional shape of the product to be packaged. This technology reportedly exceeds quality assurance requirements with attractive control parameters such as volume, weight and stack height.

Both the housing and the inner workings of the transmodules have been updated. The transport carriage has been shortened and equipped with an LED display for the operating status. The maximum acceleration and speed have been significantly increased. The transport robot assumes diverse jobs such as transporting products and boxes in TLM picker lines.

Schubert will also exhibit a packaging line that utilises automatic tool change to produce shelf-ready cartons of aerosol cans. The line comprises just four submachines. It processes aerosol cans of four different sizes and makes shelfready cartons in four different dimensions (cardboard tray plus lid).

The output is 320 products per minute.

Members of the new Schubert Pharma expert team will be available for pharmaceutical customers to consult.

Hall 14/Stand A06 Gerhard Schubert GmbH www.gerhard-schubert.com

The automatic tool change enables sizes to be changed at the press of a button. While doing so, tools are packed in tool cabinets automatically and neatly.

Aseptic BFS system fills 9,000 ampoules per hr

bottelpack 321M aseptic machine for filling of unit dose ampoules.

Blow-fill-seal (BFS) technology expert rommelag will exhibit the following developments at the forthcoming interpack: • The bottelpack 321M aseptic system, complete with electric servo drives and including the internal ampoule punch — entirely without hydraulics — for the filling of unit dose ampoules made from LDPE plastic, with an output of approximately 9,000 ampoules per hour in 3 x 10 ampoule blocks. The system is equipped with dark/white side separation, a remote maintenance modem and ROVIS. • The VIM942 ampoule test system for the fully automated in-process control of ampoule blocks with manual or automatic infeed directly from the bottelpack systems. The container engravings for LOT/EXP, ampoule separation and twistoff torque, empty container and product bottling weights and the wall thickness measurements in the container body are tested. The measurement data stored in long-term memory is displayed as tables of value and trend curves and also stored as an electronic log and printed out. The filling volume of each cavity of the bottelpack system can be automatically corrected using this information. A system can test various types of ampoules if it has the corresponding qualifications and validations.

• A head camera system with eye monitor with image and audio transmission system in a vest, batteryoperated with WiFi VPN connection for the online support of operating and service personnel at the customer site, directly at the bottelpack system. The system makes it possible to communicate with the rommelag service personnel at the manufacturing plant and to display information on an eye monitor.

Hall 14/Stand C29 rommelag ag www.rommelag.com EPM 12

INTERPACK

News

Newman Labelling Systems highlights track and trace capabilities Moving to a new hall and stand location for the first time in many years for improved visibility, Newman Labelling Systems’ top of the range S350 fully automatic, versatile labelling system will take pride of place at interpack.

The S350 has been designed to operate 24/7 at a true production rate of up to 300 containers per minute with high levels of efficiency according to DIN 8743. It is capable of applying both paper and clear plastic labels to cylindrical products in glass, plastic, metal and composite materials. Both label and container size changes can be rapidly achieved without the use of

tools, and digital scales provide repeatable container changeover in minutes.

A compact cGMP design, manufactured in stainless steel 304 finish, the S350 comes with a range of features as standard, such as autoteach label length facility, a positive accept security system and in-process control.

The latest data-bus technology has been utilised to simplify the integration of security and ancillary devices such as vision systems to allow the latest track and trace applications to be accommodated.

A further enhancement to meet track and trace requirements comes in the form of Newman’s FLR faulty label removal system, with its automatic controlling of reject labels, which will also be demonstrated at interpack. In operation, should the FLR system not receive good signals from the scanning/security devices in use (including barcode reader, missing overprint detector, OCV camera and 2D matrix code reader), the faulty label is securely removed from the label web prior to application onto the container. These faulty labels are then transferred to a paper roll for batch reconciliation and inspection.

Newman Labelling Systems’ customer base includes the world’s top ten pharmaceutical companies. All purposebuilt systems are fully compliant with FDA cGMP requirements.

Hall 15/Stand E19 Newman Labelling Systems Ltd www.newman.co.uk

Software facilitates safe and simple serialisation with existing machinery The pharmaceutical industry is contemplating the implications of the likely introduction of an EU-wide serialisation requirement for drug packages by 2017. Small- and mid-size pharmaceutical manufacturers in particular, but also their packaging service providers, are facing massive challenges in the search for suitable software solutions: how are existing hardware components to be integrated?, how can maximum data security be ensured?, can a fast-growing and currently inestimable data volume be feasibly managed? and what action is being taken to accommodate future requirements efficiently? Atlantic Zeiser is presenting a modular, easy-to-implement software solution for the forthcoming range of tasks at interpack.

MEDTRACKER is a flexible solution for generating, distributing, printing, aggregating and tracking codes for all international regulations and includes a full track and trace capability for e-pedigree applications. Atlantic Zeiser has developed the architecture of MEDTRACKER to be fully compatible with existing, even heterogeneous, thirdparty hardware. Thanks to an extensive interface library, MEDTRACKER can be integrated in all conventional business and process management solutions. If required, it can even take charge of all process management tasks. The modularity achieved by the flexible architecture, moreover, is said to facilitate seamless expansion.

The modular design also allows the implementation of track and trace for parts of a line, entire lines, production sites or whole enterprises with a single product. Unlike conventional software, MEDTRACKER is a generic database application in which all functionalities are dynamically programmed. Not only can this software solution collect and aggregate data on the usual three levels of the packaging hierarchy (individual product, secondary packaging and pallet) but the customer can also simply Continued on page 15 EPM 14

INTERPACK

News Avery Dennison exhibits latest printing and labelling products

insert any number of additional levels such as bundles, containers, etc.

MEDTRACKER integrates the new processes of serialisation and verification into users’ existing and often fully automated workflows. This functionality can be combined with manual handling routines, including aggregation and reaggregation, typically in the shipping warehouse.

Atlantic Zeiser has been integrating many of the software solution’s fundamental components in securityconscious industrial sectors for more than ten years and is now making an extended suite of applications available to the pharmaceutical segment for the first time.

MEDTRACKER embraces effective, continuously refined defense measures against criminal hacking by outsiders. In addition, data are exchanged between

production operations and facilities in an encrypted format as a general rule. All product and logistic information is collected and stored for each individual medicine package. Proven and defined access mechanisms ensure the system’s auditability. Thanks to its real-time capability, MEDTRACKER is also able to comply with the extremely short response times demanded by packaging lines, which reportedly sets it apart from classic database applications.

Hall 16/Stand A47 Atlantic Zeiser www.atlanticzeiser.com

Marking systems Trace-it software. provider Avery Dennison RBIS will present its comprehensive product portfolio — encompassing printers, industrial print and apply solutions, labelling machines, portable labellers and software solutions — at the upcoming interpack exhibition.

The backing paperfree print and apply solution LPA 81x, powered by Avery Dennison LightSmart technology, will be demonstrated.

Eliminating the backing paper, it serves to increase production line uptime and productivity. In addition, the LPA 81x offers maximised material use and flexible label formats that traditional systems are not able to offer, says Avery Dennison.

The company’s data management software Trace-it will drive the print and apply machines on the stand. Trace-it is claimed to allow precise production and smooth distribution and ensure reduced costs and compliance with global regulations.

Hall 16/Stand C38

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LPA 81x powered by Avery Dennison LightSmart Technology.

Avery Dennison RBIS www.monarch.averydennison.com

INTERPACK

News

Non-destructive inspection, blister recovery and packaging technologies launch Sepha is to launch a series of new products across each of its divisions at interpack.

BottleScan is claimed to be the world’s first tool-less, non-destructive leak detection instrument for testing multiple induction-sealed bottles simultaneously.

It incorporates force decay technology to test induction-sealed bottles for holes and weak seals without destroying the contents. Ahead of its interpack launch, Bottlescan has already had orders from Asia and North America.

Press Out Universal Mini is a lowvolume, rapid product changeover deblistering unit that enables product to

be recovered from all blister pack types, particularly child-resistant, peelable and senior-friendly packs. The unit has been developed to reflect changes in the pharmaceutical manufacturing market, where manufacturers are focusing on shorter runs of more bespoke, highvalue drugs in child resistant/senior friendly blister packs.

EZ MedPak extends Sepha’s EZ range of low-volume package development units into the wider medical packaging market. It is aimed specifically at medical device and packaging development teams who want to take control of their own pack designs and develop bespoke

packs for small devices and pre-filled syringes.

Commenting on the launches, Paul Kelly, Sepha head of sales and marketing, said: “Sepha are focused on innovation, investing in new technologies and developing our product offering in line with market demand. Our new equipment extends our range into new markets and will meet the changing demands of our global pharma clients. We are excited at these additions and look forward to a successful interpack.”

The three new machines will be showcased at the show alongside

existing technologies such as the VisionScan and PakScan.

Hall 16/Stand F23 Sepha Ltd www.sepha.com

OPTIMA pharma demonstrates flexible and diverse packaging solutions Intelligent process and packaging solutions will be exhibited by OPTIMA packaging at the interpack trade fair, where the focus will be on flexibility, high outputs and line solutions.

On display will be the INOVA SV125, a proven, modular filling and closing machine that is suitable for pilot testing to medium outputs. A maximum output of 18,000 containers per hour is achieved via ten filling points, with a dosing range of 0.1 to 50 ml. The operator can implement up to three different filling systems in a single machine while also processing three different container types: nested syringes, carpules and vials.

Numerous additional modules and functions can be integrated, including filling under vacuum, pre- and postflushing with gas and up to 100% inprocess control. Upstream, the presterilised containers are manually to fully automatically unpacked and fed to

the process. The post-processing section features such modules as backstop locks and safety devices, optical and sensor controls, labellers and track and trace systems. RAB systems and isolators can be deployed for containment.

The company will also present the KUGLER LINOLINE, a monoblock filling and closing machine with an extended format range of 5 to 1,000 ml dosed via a peristaltic pump system, allowing for a high output of up to 7,200 products per hour. Up to 4,800 containers per hour can be processed in the 500 ml format.

The compact machine also comes equipped with a sophisticated closing system consisting of a stopper insertion station, a sealing station, a screw capper with a final torquing station and a station for attaching a secondary cap and a measuring cup. Optical inspections and integrated in-process control with tendency control

of dosing ensure outstanding product quality and filling accuracy, says OPTIMA. The Klee freeze dryer, a pilot unit capable of being retrofitted for production as needed, will be demonstrated. It can be manually loaded and unloaded under an isolator with VHP-sterilisation. A special stopper closure mechanism on the back of the machine makes it possible to close individual vials of a test batch in order to assess how the process is progressing. Klee offers a comprehensive portfolio of freeze drying technologies in all capacity ranges, including with automatic loading and unloading.

Metall + Plastic will exhibit one of its models to highlight the advantages of its isolator technology, including pneumatic sealing systems and catalytic aeration techniques that aim to massively reduce cycle times. Metall +

INOVA SV125.

Plastic will also present e-beam decontamination tunnels and isolators for specific requirements.

In addition to its filling and closing technologies, OPTIMA pharma will be showing the rest of its product range, including washing machines, sterilisation tunnels, containment and process technologies and robotics.

Hall 16/Stand F25–26 OPTIMA packaging group GmbH www.optima-ger.com

IMA displays latest processing and packaging machines and complete lines At around 3,000 m2, the IMA Group’s interpack stand will present new machines and complete lines for the processing and packaging of pharmaceuticals, cosmetics, tea, coffee and food. IMA staff will be on hand to demonstrate the company’s range of new offerings. IMA Pharma designs and manufactures automatic machines for the processing and packaging of pharmaceutical products and has the technological expertise to provide bespoke solutions that meet the requirements of the market. IMA Pharma includes the divisions: IMA Active, IMA Life and IMA Safe.

IMA Active division will show the new ADAPTA 200 capsule filler, which boasts exceptional flexibility, says the company.

Its dosing units can be easily removed and are reversible/interchangeable, giving the possibility of a plug and play shift between different machine configurations and filling combinations.

ADAPTA is designed to dose three products into the same capsule (up to five upon request), without affecting the production speed of 200,000 capsules per hour. ADAPTA reportedly has an indisputable efficiency as far as inprocess control is concerned; total production control can be achieved — even with product combinations — for each single product dosage, including possible self-adjustment of machine working parameters.

IMA Life division produces a full range of proven systems for fully automatic

loading and unloading vials into industrial freeze dryers and will present its latest DA VINCI loading/unloading system at this year’s event. This new generation of loading systems is designed according to the latest international guidelines and can be installed under RABS or barrier isolation technology.

Finally, IMA Safe division will launch the new SWIFTPACK SP 2-4 multi-channel electronic counter for tablets and capsules. With the experience gained from having supplied over 80 SWIFTPHARM machines throughout the world, IMA Safe has now developed the SWIFTPACK SP 2-4, which along with a smaller footprint and increased output,

has a single HMI for control of both its counter and integrated conveyor. Quick changeover components and the tabletop design further improve the machine’s ease of cleanability.

Hall 17/Stands A20, A30 and B03 IMA S.p.A. / IMA Pharma www.ima.it / www.ima-pharma.com

Pharma and food inspection trailblazers unveil next generation inspection systems Loma Systems and Lock Inspection will showcase why they are deserving champions of the EEF Future Manufacturing Awards 2013 ‘Innovative Operating Practices and Processes Award’. The detection and inspection specialists will present the largest display to date of combined Loma and Lock systems, including a new portfolio of pharmaceutical and food metal detection, checkweighing and x-ray inspection systems.

The team will unveil three new inspection systems at interpack, including Lock’s next generation pharmaceutical metal detector, the INSIGHT PH. Already highly acclaimed by industry experts, the improved INSIGHT PH has a new easy-clean polished frame that resolves potential stability issues caused by noisy processing environments. A hectic exhibition provides the perfect opportunity for users to test this out.

Hygienic according to FDA standards, the

frame is height adjustable and comes with a robust clamping sleeve, removing the need for resin assembly. For ease of installation, there are 200 product presets and the permanent memory stores up to 8,000 data events, even during a power interruption or disconnect.

In total, seven flagship systems will be on the stand, including Lock’s compact INSIGHT VF vertical fall metal detector, which is created specifically for the pharmaceutical industry to inspect

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incoming raw materials in powder and granular form and comply with 21 CFR Parts 210 and 211.

Live testing is fully encouraged, with visitors openly invited to bring along samples of shelf-ready products to run through the systems.

Hall 17/Stand B52 Loma Systems and Lock Inspection www.loma.com / www.lockinspection.com

MANUFACTURING PRODUCTS Denny Bros event addresses labelling challenges for healthcare sector Manufacturer of the multi-page Fix-aForm label Denny Bros is staging a pharmaceutical open day entitled ‘Pharmaceutical Packaging and Labelling — putting the patient first’ at its Suffolk headquarters on 14 May. Keynote speaker is the BBC’s Dr. Rosemary Leonard and invitations are being extended to delegates from the pharmaceutical arena to examine the packaging and labelling challenges now facing the healthcare sector. The day will include a mix of formal presentations and a tour of the key areas of Denny Bros’ pharmaceuticallyaccredited facility. The event promises to be an education and will make clear requirements to help comply with global legislation, improve patient safety and streamline logistics.

Dr. Leonard will be speaking from a GP perspective and will be highlighting the importance of patient and medicine safety. Her work as a consultant to the national television, radio and newspapers makes her one of the country’s best known doctors. She is the resident doctor on BBC Breakfast and also writes and broadcasts on behalf of various other media.

Supporting speakers will include

Omar Ali, an NHS educational consultant, who will look at packaging information from an enduser perspective, and Jim Kaye from Atlantic Zeiser, who will discuss serialisation and product coding. Denny Bros has now invested in this technology for Fix-a-Form multi-page labels and will be demonstrating how to add characters, barcodes, 2D codes, graphics and even doctors’ signatures in variable, sequential and alpha numeric formats to various on-pack media concepts.

Paul Beamish, from linerless-labelling specialist Ravenwood Packaging, will explain the green advantages of labels with no backing paper and how this will work for manufacturers within the pharmaceutical and healthcare sectors.

Stephen Jarrold, sales and marketing director at Denny Bros, completes the line-up of speakers with an overview of the use of Fix-a-Form worldwide as a pharmaceutical packaging solution. His presentation is entitled ‘A Cure for the Information Headache.’

Commenting on the programme for

the event, Jarrold said: “We have recently exhibited at both Pharmapack Europe and Packaging Innovations where we found that the need to comply with global legislation and the mission to improve patient safety were still high priority for suppliers to the pharmaceutical and healthcare sectors.

This has assisted in our decision to hold an open day to cover these matters and more.”

To book a place at ‘Pharmaceutical Packaging and Labelling — putting the patient first’, call +44 (0)1284 701381 or visit the Denny Bros website.

Denny Bros www.dennybros.com

ISPE launches Europe Annual Conference ISPE (the International Society for Pharmaceutical Engineering) has announced its first Europe Annual Conference — Driving Effectiveness in Pharmaceutical Operations within the New Quality Culture, 28–30 April 2014, Sheraton Frankfurt Airport Hotel & Conference Centre, Frankfurt, Germany.

This two-and-half-day event will bring together pharmaceutical, regulatory and technology experts from locations around the world.

The conference will consist of an executive forum, keynote sessions and three different tracks to assess how senior management, operational challenges, quality system effectiveness and regulatory changes can be brought into a new pharmaceutical paradigm to exploit opportunities like QbD, continuous manufacturing and science and risk-based regulations in daily operations. Additionally, the conference will discuss QRM in the industry as it relates to drug shortages as well as exploring technical advancements.

“One key benefit of this conference is the attendance of several regulators from various European authorities,” said

conference chair Jean-Francois Duliere, pharmaceutical process technologist, Technip Life Sciences, France. “Regulators are involved in nearly all stages of this conference, from providing input on track content to presenting during the conference and participating in each of the question and answer panels. Their involvement will provide valuable insights to conference delegates.”

Keynote speakers from industry and regulatory authorities will define the ‘New Quality Culture’ and share their perspectives on: • the future of biopharmaceutical operations in a stronger competitive market • current and future regulatory challenges, while ensuring control over manufacturing cost • the most effective principles of managing quality and compliance and how they can be employed in the pharmaceutical industry • the latest regulatory perspectives on the implementation of the new regulations, how regulators continue to

EPM 17

work with the industry and the current changes to the regulatory framework.

The executive forum will offer pharmaceutical executives, senior experts and future decision makers a platform to interactively examine the current challenges in technical operations and dominant factors to achieving successful pharmaceutical manufacturing, namely safety, efficiency and compliance during development, transfer, production and distribution.

ISPE www.ispe.org/2014-europe-annualconference

MANUFACTURING

Industry News

PSL extends partnership network to meet global demand for high containment products At least 90% of Powder Systems Ltd’s (PSL’s) business is now overseas. To meet this demand, the company has launched the PSL Plus scheme for international partnerships. Already appointing 10 partners around the world, including Sigma Aldrich, Austar in China and recently Mason Technology in Ireland. PSL’s ambition is to triple this number while maintaining the existing high level of support to all its representatives around the globe.

Four years ago, PSL launched the GFD (Glass Filter Dryer) and simplefilter for applications in the chemical and pharmaceutical industries; the GFD is a laboratory glassware for small-scale synthesis of intermediates and APIs, and the simplefilter is a vacuum filter plate for pilot plants.

Having recently refined the designs of the GFD and simplefilter — which has resulted in significant sales increases

in Europe, Asia and the US — PSL aims to expand the market still further by establishing additional partnerships with local specialists all around the world, continuing to meet and exceed its customers expectations. With the opening of PSL’s Australia office in February, the company can now support every continent.

Powder Systems Ltd www.powdersystems.com

GEA Pharma Systems supports pharma research at SKKU in South Korea GEA Pharma Systems has provided solid dose processing technology for a new Pharmaceutical Process Research Centre (PPRC) at South Korea’s Sungkyunkwan University (SKKU). The new centre will provide academic and commercial research facilities for under graduate, post graduate, post doctorate students and the wider pharmaceutical industry in South Korea and underlines GEA’s longterm commitment to the South Korean market. The GEA-SKKU, as it is now known, was opened by professor Hyuck Chung, dean of the university’s School of Pharmacy, on 17 December 2013.

SKKU is one of Asia’s oldest universities, founded in 1398. It has gained a reputation for nurturing global leaders and as a driver in the global technology revolution. SKKU is located in the centre of the Gyeonggi province, with 40% of the South Korean pharmaceutical industry within a 100 km radius. The PPRC project has established a

processing research centre to service and support the Korean pharmaceutical industry. It focuses on product R&D, process support, trials and training.

Research conducted at the centre will include tablet formulation, particle coating and sustained release delivery products.

The GEA-SKKU was the brainchild of Professor Eun-Seok Park, head of the university’s School of Pharmacy. He was introduced to GEA by professor Paul Heng of the National University of Singapore with whom GEA had worked on a similar, successful project called GEANUS. During a visit to GEANUS in 2010, professor Park was inspired to create a similar facility at SKKU. Over the last three years, GEA has supplied a range of equipment, including an MP1 laboratory-scale fluid bed processor, PMA 10 granulator, IBC blender and NICA IPS5 extrusion and spheronisation pelletising modules linked through the GEA PharmaConnect that

brings together GEA processing equipment behind a single control system. The facility also has a Niro Mobile Minor spray dryer. All the equipment is designed to handle laboratory batch sizes from 0.5 to 5 kg of material. GEA–SKKU also has plans to install a ConsiGma 1 continuous processing line and a Courtoy MODUL P tablet press in the near future.

Professor Park’s vision for the facility is to deliver an industrial pharmacy degree course for undergraduates to a high, internationally-renowned standard, undertake research by doctorate and post doctorate students and provide a product development facility and training courses for the pharmaceutical industry in South Korea.

The research centre is part of a longterm memorandum of understanding between SKKU and GEA Process Engineering. GEA Pharma Systems has also agreed to take part in a regular

programme of seminars at the university to provide advice and guidance on solid dose pharmaceutical processing.

The School of Pharmacy has received funding from the Korean government for pharmaceutical research and from Gyeonggi province for the purchase of equipment.

GEA Pharma Systems www.gea-ps.com

Freeman Technology and GEA Pharma Systems partner to progress continuous manufacturing Freeman Technology, a global provider of powder testing instruments, and GEA Pharma Systems, a company that specialises in design and development of processing solutions for the pharmaceutical industry, are collaborating to advance the application of continuous wet granulation and drying technology in the pharmaceutical industry.

The work involves Freeman Technology’s FT4 powder rheometer and GEA Pharma Systems’s ConsiGma 1 continuous granulation unit. Data from the FT4 are being used to quantify the influence of the operating conditions of the ConsiGma 1 on the bulk characteristics of the granules being manufactured. These data are then correlated to attributes of the tablets, providing the link between granule and tablet properties. An application note detailing the study can be can be accessed online at http://bit.ly/FTGEA.

Pharmaceutical manufacturers frequently utilise wet granulation as a precursor to tabletting, with the current trend moving from traditional batch manufacturing towards integrated continuous processing. Consequently, there is a requirement for continuous wet granulation technology. The ConsiGma 1 is a laboratory-scale version of GEA Pharma Systems’s ConsiGma concept, incorporating a patented, continuous high-shear granulator and small batch dryer, which has been developed specifically to meet this continuous wet granulation need.

The FT4 powder rheometer enables the measurement of bulk, shear and dynamic powder properties that can be correlated directly with process performance and product quality. It is therefore a powerful tool for scoping the design space for powder processes, as advocated by QbD. Identification of the operating envelope that results in

product with the defined critical quality attributes (CQAs) is a central strategy for ensuring consistent clinical efficacy. This operating envelope is the design space for the process.

In this study, dynamic properties were measured to quantify the impact of granulation process variables on the quality of granules produced.

Paracetamol (APAP) and dicalcium phosphate (DCP) blends were used in the work. These dynamic properties

Pharma production line specialist joins Travtec Jake Barnes has been appointed technical sales manager to strengthen Travtec’s sales and technical support service, developing tailored coding and verification solutions utilising the company’s product portfolio, which has recently been expanded with the introduction of the Lixis range of systems, including blister vision, pin hole detection, OCR/OCV, code reading and grading.

A trained mechanical biased engineer, Jake has experience of the pharmaceutical sector, including the design, installation and validation of new production and packing lines, having spent over 12 years with Catalent Pharma Solutions and Cardinal Health in a variety of engineering and project roles.

“We are delighted to welcome Jake to Travtec,” commented managing director Harry Thomason. “His in-depth

knowledge in areas such as track and trace and validation will be invaluable to help develop systems to meet the specific needs of our pharmaceutical customers, and this has particular relevance with the requirements of the forthcoming Falsified Medicines Directive.”

Travtec Ltd www.travtec.co.uk

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were also successfully correlated with the CQAs of finished tablets such as hardness.

The study rigorously investigated the impact of changes in water addition level, granulator screw speed and powder feed rate. The results show how it is possible to produce granules of closely defined quality using a series of different operating conditions and demonstrate how the design space for the ConsiGma can be mapped efficiently for a given tabletting blend.

Dynamic powder measurements provide the information needed to effectively specify optimal operating conditions.

Within a commercial manufacturing environment, they would also provide the information needed for operational decision making within the design space.

Freeman Technology Ltd www.freemantech.co.uk

MANUFACTURING

Product News

Case Study: ALLERGY LABS PUTS PERISTALTIC PUMP TO THE TEST While primarily used for developmental purposes, peristaltic pump technology today offers a safe, clean and flexible alternative to conventional filling systems.

Allergy Laboratories, Inc. has been successfully working with this technology for just over two years and reports some very positive user experiences.

Allergy Laboratories, Inc. was established in 1929 in Oklahoma City for the manufacture of allergenic extracts needed to support the growing immunotherapy practice of founder Dr. Raymond Balyeat. Allergy Labs, as the company is more widely known, has since evolved into an FDA-licenced pharmaceutical manufacturer of over 500 different biological extracts for the diagnostic testing and therapeutic treatment of allergies. Additional manufacturing and supply capabilities have been added over the years, including a parenteral production facility for contract manufacturing.

In 2010, Allergy Labs acquired a new filling and closing machine for vials and infusion bottles from Bosch. Two main requirements had to be fulfilled: the line needed to operate with peristaltic pump technology, and it had to fit exactly into the space that had become available by discarding an old machine. “We work with piston pump technology on another line, which can lead to cleaning and maintenance difficulties, so we started looking for a filling and closing machine that operates with peristaltic pump technology,” explained Lee Beaver, director of manufacturing at Allergy Laboratories, Inc. “We checked the market, and Bosch has a good reputation for this kind of technology.

The open communication and expertise of our contacts at Bosch facilitated our decision. They were always quick in responding to our queries and requests, which enabled a quick turnaround time for the project.”

Traditional concept revisited Six years ago, Bosch started to develop its own peristaltic pumps to supply the growing needs of its pharmaceutical customers. They combine the advantages of the traditional peristaltic concept with optimised dosing accuracy and a very flexible operating concept.

The new tubing makes the technology suitable for all kinds of filling operations, from development purposes to production-scale filling operations. The offset alignment of the rollers reduces mechanical strain on the tubing and permits longer periods of use. Product and batch changeovers are easier, faster and safer.

The pump can be opened and closed in two simple steps without removing any parts, saving time and increasing safety, especially for isolator applications. With the exception of the tubing, the system completely eliminates product contact. This ensures high product quality by reducing the risk of cross contamination and minimises the potential downtime associated with product changeovers.

The low pulsation volumetric flow ensures very precise filling tolerances.

Allergy Labs mainly uses the Bosch

filling and closing line for waterbased, easily soluble products such as injectable, sterile generic drugs.

The peristaltic pump is suited for filling volumes of 0.1 to 30 ml. The pump can also be modified to handle even smaller sizes, flexibly adjusting to each manufacturer’s requirements.

“Allergy Labs operates with 2 ml fills, so filling accuracy was a big concern for us, but Bosch met all of our specifications,” added Beaver. “Filling operations are drip-free, and the single-use components significantly contribute to clean handling.”

Pretty much maintenance-free Along with the peristaltic pump, Allergy Labs opted for a new filling and closing line from the FLC series. The FLC 3080 filling and closing machine is designed to fill, sample check-weigh and stopper vials in a continuous motion process.

The FLC 3080 uses a vacuum star wheel to accurately position each vial for capping. Additional features include a V-cleat conveyor system that enables users to conveniently run different size vials without changing parts. The containers are carried freely in the laminar-flow stream in an upright

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position. “The FLC line not only provides the cleanliness we require for our filling operations, it also handles the vials very gently,” summarised Beaver.

The peristaltic pumps and a disposable tubing system are fully integrated with the machine’s control system, drive and controllers. An integrated touchscreen ensures easy and automated operations.

Beaver concluded: “At first, we were skeptical about the degree of automation of the FLC, but its set-up was easy; our operators quickly adapted to it and it’s pretty much maintenancefree. The line has been in operation for over two years now, but it didn’t take us that long to recognise the key benefits for us — safe and reliable vial handling, filling accuracy of the peristaltic pump technology and the cleanliness of the entire process.”

Bosch Packaging Technology www.boschpackaging.com

MANUFACTURING

Product News

Case Study: DISCHARGE AIDS OVERCOME BRIDGING ISSUES AT BIG PHARMA COMPANY A large multi-national pharmaceutical organisation in the North East of England asked Mucon to ascertain whether intermittent bridging/ rat-holing issues within its stainless steel cones could be resolved using the Mucon Promoflow range of discharge aids.

The pharmaceutical company has several small asymmetrical and symmetrical stainless steel cones that on occasion experience intermittent bridging issues when processing powders. The production staff has been known to bang the sides of the cones in an attempt to keep the flow of powders moving, but this has only served to damage them and to further consolidate material inside them, making it even more difficult for the powders to flow. Banging on the cones not only resulted in lost productivity but also tied up engineering resources that could have been better utilised elsewhere in the plant.

Mucon staff visited the manufacturing site and measured the cones and also took note of the material being handled, such as bulk density, particle size, etc.

The pharmaceutical organisation was eager to point out that the stainless steel cones were steam cleaned with purified water and then either oven or vacuum dried. Mucon engineers were informed that as the cones were located in a clean environment, any pneumatically operated device must not use a lubricated air supply so hygiene levels could be maintained.

The customer’s engineers also specified that they did not want a discharge aid with any internal fixings to ensure that nothing could work loose over time and damage other equipment in the manufacturing process such as a tablet press.

Rib cage screen fitted internally to the stainless steel cone.

Requirements The customer’s demands were very specific in that any equipment chosen must satisfy the following criteria: • cleaning regime — steam cleaning of the cones using purified water • no material hang up • easy to clean and maintain • discharge aid to function using only a non-lubricated air supply • no fixings on the inside of the vessel • manual control mechanism was requested for operators to easily utilise.

Solution Once the customer’s needs were identified and confirmed, Process Components Ltd (manufacturer of the

Mucon product range) set about designing a system that would adhere to these.

Rib cage screens in 316L mirror polished stainless steel was decided on to meet with the customer’s cleaning requirements and minimise product hang up.

Control of the discharge aid was important. A variety of options was on offer, but the end-user preferred a manual toggle switch instead of automatic actuation.

Fixing and fastening of the MiniPromoflow was made on the outside of the cone to ensure that nothing could work itself loose and provide easy access for cleaning and maintenance if required.

Nanomilling achieves more targeted drug delivery More than 90% of drugs approved since 1995 have poor solubility, poor permeability or both. Drug performance can be improved by reducing the particle size and at the same time increasing the specific surface area of the APIs. Therefore, however an API is administered — in tablet, capsule, powder or liquid form — small particle sizes offer exciting advantages for pharmaceuticals. Known benefits include improved dissolution rate, increased bioavailability and higher activity, leading to lower dosages and a lower risk of side effects for the patient.

The NETZSCH DELTAVITA mill has been specially designed to efficiently increase solubility of APIs, thereby enhancing their efficacy. DELTAVITA mills achieve excellent repeatability as well as homogeneous dispersion and produce a very narrow range of ultra fine particles in a homogeneous formulation.

Stainless steel cone with Mucon Mini-Promoflow discharge aid.

With the DELTAVITA, users can achieve consistent particle size distributions below 100 µm. With nanometer-scale particles, gene and vaccine delivery becomes more targeted, as does the development of particles that cross the blood brain barrier. Nanoparticles can enhance the properties of time-release molecules and nano-receptors can be added to drug surfaces to release drugs exactly where needed.

As for different models, the DELTAVITA is designed with flexibility in mind with several available chamber sizes in stainless steel and ceramic construction.

The laboratory series sizes range from 15 to 300 ml chamber volumes and the pilot series offers 600 ml chamber volume. In the production series, NETZSCH offers models from 2,000 to 60,000 ml.

NETZSCH-Feinmahltechnik GmbH www.netzsch.com/deltavita EPM 22

Result The end-user decided to send one of the stainless steel cones to Process Components to have the Mini-Promoflow installed and then sent back, so that an initial trial could be undertaken to assess how effective the equipment was.

They were very methodical and cautious in their testing of the Mini-Promoflow.

Consequently, after several months of testing the Mucon Mini-Promoflow, the end-user was delighted with their findings and the customer decided to order several more discharge aids to solve bridging issues elsewhere in the plant.

Mucon www.mucon.com

MANUFACTURING

Product News

Case Study: EPIDEMIOLOGY INSTITUTE UPSCALES WITH THREE AUTOMATIC LIQUID FILLING MACHINES A leading epidemiology research institute based in Moscow, Russia, has ordered three Flexicon FMB210 fully automatic filling and capping systems from WatsonMarlow Pumps Group.The new machines are at the forefront of providing antiepidemic arrangements for communicable and parasite-born diseases. The move follows years of success using Flexicon semi-automatic equipment.

Traditionally, the institute’s laboratories performed simple manual filling and capping of bottles and micro-tubes.

However, keen to advance, the organisation purchased its first Flexicon PF6 dispensing pump, a semi-automatic FF20 bottle handling system and FC10 crimp capper in 2006. In subsequent years, satisfied with the quality and reliability of Flexicon equipment as well as the support provided by the local Flexicon distributor — Pharmintec/Interpharm Technology — several more FF20, PF6 and FC10 units were purchased for the institute’s research.

Automated concept In 2013, the institute wanted to take the step into fully automatic filling and capping operations, opting for a trio of high-specification Flexicon FMB210 machines. The FMB210 is a complete concept for fully automated production based on a design featuring modular tool blocks on a central tool platform for different applications.

Microtubes, vials and bottles are processed by means of a 10-slot star wheel, which positions the vials with great stability and accuracy in the

different working stations. The star wheel indexing system has been developed to meet the demand for accurate positioning and gentle handling.

Furthermore, FMB210 is equipped with a number of sensors to facilitate correct operation and ensure that a missing bottle does not result in subsequent filling/capping.

Precision assured Two of the FMB210 machines are used to fill 1.5 and 2 ml microtubes and vials with a maximum 1.3 ml of test substance. Up to 38 microtubes per minute are filled with accuracy better than ±1%. After filling, the machine applies screw caps by deploying Flexicon’s highly accurate, servo-driven screwdriver with torque control.

The third FMB features a BU12 bottle unscrambling unit for bigger plastic bottles with screw caps. The bottles used are 20–100 ml, with filling volumes from 8–100 ml. The output of the machine depends on the size of bottle and filling volume, but it will be up to approximately 30 bottles per minute. Typical batch size is circa 1,500 bottles. After the filling and capping process, the microtubes, vials and bottles are used for in-vitro testing.

Busy future Each FMB210 machine is used for around four hours per day initially, although production is set to ramp up in the near future. The three machines are

located in different laboratories over the company’s facility.

Watson-Marlow Pumps Group www.wmpg.co.uk

No more breakage with latest vial loading and unloading systems Telstar has introduced a new generation of vial loading and unloading systems that can be integrated into freeze dryers and that offer greater robustness, efficiency, reliability and accuracy in the vial transport and transfer process, in addition to easier cleaning and simplified maintenance. The improvements are mainly concentrated in the transport conveyor transition modules and the vial alignment systems, which offer increased security of vial transport in loading and unloading processes, resulting in elimination of breakage and significant reduction in rejects. Telstar has also developed a pusher-type loading mechanism with a 40% shorter length than conventional systems, which reduces the footprint required in the aseptic area and increases the size range of shelves that can be automatically loaded.

A standard range of modules combine easy installation and accurate alignment between conveyor systems, ensuring that the vials move smoothly and

continuously between the modules and makes the vial transition process more robust and reliable. Designed to be applied to any vial loading system, this system provides greater efficiency in the transition process and reduces vial losses during transport owing to breakages or falls.

Telstar has developed and tested longitudinal transitions, sliding longitudinal transitions, active and passive 90˚rotations, transitions with curved belts and T-shaped belts and various other geometrical arrangements required to accommodate the configuration of loading systems. By combining modules, the transport system can be readily configured to any layout.

The vial single-lining system is a complex element for accepting vials unloaded from the freeze dryer in random packets and aligning them at high speed so that they can be transferred in a single line towards the capping machine. Since there are many applications that involve unloading vials

onto a rotary accumulation module, Telstar has developed an alternative based on different single-liner system configurations that enable unloading the shelves of the freeze dryer while preserving as much as possible the row order followed during the loading process. The new Telstar vial descrambling modules are suitable for unloading processes at up to 400 per minute with a typical rejection rate of 0.01%. Telstar has come up with a range of single-liner modules to address the various speed and layout requirements of specific clients.

The loading mechanism with a 40% shorter length than conventional systems is primarily intended for installation in freeze dryers which, owing to cleanroom space constraints, need to have a fixed loading system with a compact footprint.

The new design also features a built-in HMI screen that offers improved ergonomics and cleaner construction compared with screens supported on floating columns. Owing to its compact

EPM 24

and robust makeup, the mechanism can be integrated with freeze drying equipment that has shelf widths of up to 1,500 mm, thereby increasing the loading capacity per row by 25% over earlier designs.

Telstar www.telstar.com

MANUFACTURING

Product News

Roller compaction technology delivers precise process control Pharmaceutical manufacturers are constantly striving to develop new methods of reducing costs and environmental impact by using the dry compaction method to produce granules from powdered and micronised products. The control of the compaction and granulation process is of vital importance and cooperates with the need for the highest process stability.

Gerteis equipment can maintain a maximum measure of process stability and reproducibility throughout its full range of compaction force. To achieve this, Gerteis developed the Pactor highperformance line. A fully computerised, sensor controlled unit with solid design and exceptional solutions help the customer attain the best granulating results, stable processing sequences and complete validation and replication.

During new product development, this unit will adapt to all requirements, enabling the customer to tailor processes and reduce start-up time.

With worldwide patented construction, the Pactor line provides optimal conditions to precisely process products with a great range of density and best flow characteristics.

From R&D to mass production, high containment or CIP, Gerteis roller compactors can process powders that have extreme physical properties, with no application of vacuum or roller cooling. The Pactor line of machines is ideal when launching a QbD programme, covering linear scale-up from R&D to high-volume production. As

One-nut design and electronic rupture protection secure 3-A accreditation for AODD pump Macro Pactor.

Micro Pactor. well as technical support, Gerteis provides formulation support to its customers.

Gerteis Maschinen + Processengineering AG www.gerteis.com

Flotronic Pumps has secured 3-A accreditation for its new H series airoperated double-diaphragm pump.

Among a number of critical design features, Flotronic’s one-nut design, which allows rapid pump disassembly and straightforward CIP, was crucial to the success of the H series pump’s application. Its electronic rather than pneumatic rupture protection system was also a deciding factor.

3-A Sanitary Standards Inc is an independent not-for-profit corporation dedicated to advancing hygienic equipment design for the food, beverage and pharmaceutical industries. It sets high standards for cleanability of equipment as well as for the provenance of the parts and raw materials used and the pump’s ability to shut down immediately to avoid contamination in the event of a problem. “Ease of cleaning and robust rupture protection and associated alarm systems are vital for 3-A accreditation,” said Peter Wheal, Flotronic’s chief engineer. “We were confident that our one-nut design would completely satisfy 3-A cleaning and maintenance demands. One nut means that the pump can be maintained in minutes, with cleaning made easier by a specially designed support stand that allows full rotation for draining. Wetted surfaces polished to 32 µin Ra maximum and an electro-polished overall finish also make cleaning effective.

We also knew that we needed to find a cost-effective alternative to our pneumatic rupture protection system

and the solution is an electrical unit connected to sensors in the pump’s air domes. The presence of any leakage is immediately detected, avoiding the need for any secondary chamber, with a control unit shutting the pump down when activated.”

Flotronic designed the H series not only to meet 3-A’s stringent criteria but also with the US market in mind.

Meeting the high standards demanded by 3-A is a requirement of many US companies. “While 3-A is not a statutory requirement, it is a standard increasingly required by the sanitary industry and particularly in the US,” said Jane Waite, Flotronic’s managing director. “Being authorised to display the 3-A symbol ensures credibility of the new H series, at home and abroad.”

Flotronic Pumps Ltd www.flotronicpumps.co.uk

Roller compactor customers reap benefits of high throughput and batch size flexibility For over 125 years, Alexanderwerk has been improving its machines. Based on the expertise of its employees and longterm success in the area of roller compactors, the company is a reliable partner for the pharmaceutical, chemical and primary industries.

Alexanderwerk provides different solutions to support customers in producing a large range of products, including textile dyes, battery compounds, fertiliser, silicic acid, feedstuffs and additives as well as tablets, capsules, life science products, flavours and many more.

Alexanderwerk machines are designed to enable customers to work as efficiently as possible, offering: • vertical arrangement of the rollers for better control of feed flow • the patented Combi-Vent-Feeder system with two chambers for a better compaction process • two-stage granulation in DiagonalDesign, which increases throughput by up to 100%.

For example, the WP 200 Pharma can be used for the production of a large range of products in small batches as well as for the compaction and

granulation of single products in a continuous operation. Owing to its modular design, the WP 200 Pharma can be almost completely disassembled without special tools.

Beginning with the machine’s manufacture, followed by delivery, installation supervision, commissioning, maintenance and on-site assistance, Alexanderwerk endeavours to provide a comprehensive and bespoke service offering.

Alexanderwerk GmbH www.alexanderwerk.com

Stainless steel connectors meet stringent demands of pharma The Stäubli Connectors division has introduced a range of stainless steel, full flow fluid connectors that are suitable for applications where cleanliness is paramount.

UPA connectors are suitable for all fluids and are ideal for applications in the pharmaceutical, medical and food processing industries where frequent cleaning is required. The stainless steel body of the connector provides excellent corrosion resistance and is finished to a high standard with a surface texture of Ra 0.8 in the fluid stream, allowing for easy and efficient cleaning. Seals can also be replaced quickly and easily, minimising any disruption to production. The connectors comply fully with the FDA and USP Class VI requirements for the

agri-foods and pharmaceutical industries.

Safety has been designed into the connector with two simultaneous opposing movements (pushing the plug into the socket while pulling back on the locking ring) being necessary to disconnect. This eliminates any chance of accidental disconnection; the socket cannot be disconnected simply by pulling on the locking ring or hose.

UPB connectors feature a robust automatic locking system using multiple ball bearings, ensuring strength and long-term reliability. Made entirely from stainless steel, the connectors have been designed to perform well under high pressure and are capable of withstanding up to 20 bar. Automatic connection is said to make this

connector easy to use while the optional safety pin prevents accidental disconnection. Similar to the UPA connector, the finish is to a high standard (Ra 0.8 in the fluid stream) and complies fully with FDA and USP Class VI standards.

UPC stainless steel connectors are designed for sampling applications and loading, unloading, filling and drainage of process equipment in the pharmaceutical, medical and food industries.

The design eliminates any retention areas in the bore, allowing the connectors to be cleaned or sterilised efficiently. Seals can be easily removed and replaced. A bayonet locking system

EPM 26

provides safe and reliable connection.

Stäubli stainless steel connectors have a range of applications across the pharmaceutical, medical and food processing industries. Their design makes them ideal for the tasks where cleanliness is paramount and their safety features ensure that any chance of accidental disconnection is eliminated.

Stäubli (UK) Ltd www.staubli.com

MANUFACTURING

Product News

Websites provide richer insight into sieving and filtration products Russell Finex has launched websites that boast a cleaner design, streamlined content and enhanced navigation, providing users with quick and easy access to the information they require.

Key features of the websites are: • enhanced navigation, providing users with the quickest path to the information they require and machine recommendations based on their individual requirements • improved visuals; product photos, demonstration videos and product animations provide a greater understanding of how each product works

• extended product and after-sales information, providing detailed information on the range of aftermarket products including spare parts, meshing and other services • clearer access to contact information and an interactive map showing local representation.

Available in 13 languages, the launch of the multi-lingual website reflects the importance of Russell Finex’s growing global customer base. Ray Singh, managing director, commented: “The new websites reflect our international growth strategy as we continue to increase our market presence. It is

important for our customers, no matter where they are, to be able to readily access information on our products and services in their local language.”

The websites will be updated on a regular basis with news of new product launches, case studies, demonstration videos, events and business activity, ensuring users are constantly kept up to date.

Russell Finex Ltd www.russellfinex.com

Multi-page wraparound label offers quantity flexibility and more space

Wraptac, the multi-page wraparound product label from Denny Bros, allows for the printing of as many or as few labels as needed as well as offering much more space than a conventional label and being suitable for most container types.

The space comes from one of Wraptac’s core features — it is several times longer than the original label that might be being used but wraps around itself, seals and can be opened and closed as often as required.

Wraptac comes on an A4 sheet of toughened paper that can be printed on virtually any machine — a desktop or office printer and even commercial printing machines. Also, one sheet can be printed at a time, resulting in a multipage label quickly available at very low cost. This makes it suitable for low volumes of print or even labelling for product trials and testing.

Depending on the finished label size needed, three sizes are currently being produced with a choice of three, four or five labels included on any one A4 sheet.

They are micro-perforated so each label can be easily removed. The clever addition of pre-applied self-adhesive strips fixes Wraptac to the container and allows easy opening and closing, ideal for repeated reference.

In addition, because both sides of the patented Wraptac label can be printed, leaflets that become separated from the product will no longer be needed; there should be more than enough space.

Denny Bros created the original multipage leaflet label Fix-a-Form but is now adding Wraptac to a growing range of digitally printable media where the customer decides how many, how often and when.

Denny Bros invites readers to request some free samples to realise how simple and quick it is to create wraparound product labelling with Wraptac.

Denny Bros Ltd www.dennybros.com EPM 28

MANUFACTURING

Product News

Belt conveyor checkweigher ensures ATEX protection Manufacturers and production lines for food, pharmaceuticals, cosmetics and fast-moving consumer goods can now benefit from improved safety protection in explosive manufacturing environments with a new ATEX-certified checkweigher designed by MettlerToledo Garvens. The XS3 checkweigher offers exceptional weighing sensitivity to minimise costly product giveaway and an advanced design to comply with European ATEX safety requirements for devices used in areas at risk of explosion. Featuring an anti-static belt conveyor, the checkweigher is also said to be ideal for the inspection of small, lightweight products.

The European Union Directive 94/9/EC (ATEX 95) stipulates essential safety requirements for equipment used in explosion hazard zones, such as those involved in the production of dusty, powdered products or flammable gases and aerosols. These materials can, in the right quantities and with an appropriate source of ignition, cause an explosion, with serious implications for employee safety and damage to production line equipment. ATEX standards classify such production lines into zones according to the nature and gravity of the explosion risk to specify appropriate devices. Prior to selecting equipment for the line, manufacturers must also ensure they acquire zone confirmation documentation, including all the information necessary to enable

suppliers to offer the most appropriate solutions for compliance.

In addition to offering exceptional levels of weighing sensitivity, the XS3 checkweigher has been certified by ATEX assessors as a Category 3 device, making it suitable for use in Zone 2 gassy environments (Category 3G) and Zone 22 dusty atmospheres (Category 3D).

The system’s conveyor belt, designed for the transport of lightweight products, is made from antistatic plastic that, combined with the conductive stainless steel shell, encasing the conveyor motor and weigh cells, minimises the risk of sparks caused by the build-up of static charge.

The control cabinet has been designed as a hermetically sealed enclosure to avoid any contact of the ambient, potentially explosive atmosphere with the electronic and electric elements protected inside the cabinet. Antistatic materials have also been used in the construction of the operating terminal to further reduce the risk of electrical sparks that could be an ignition source. What is more, special connector feeds for cabling as well as energy limitation features for switches and sensors have been developed to help maximise explosion protection.

The HMI and control cabinet can be built to ATEX 3 specifications for use on production lines where the explosion

Steam water mixer provides safe washdown

hazard zone cannot be easily isolated.

The XS3 checkweigher comes with ATEX documentation, containing a certificate of conformity as well as advice regarding maintenance and requirements for safe machine operation.

A number of additional features can be customised on the XS3 checkweigher to meet the individual needs of the production line and to comply with similar safety guidelines in nonEuropean markets. These include China’s National Supervision and Inspection Centre for Explosion Protection and Safety of Instrumentation (NEPSI), the Korean Occupational Safety and Health Agency (KOSHA) in Korea, and the guidelines of the Factory Mutual Insurance Company (FM Global) in the US.

Providing a reliable source of hot water, delivered at the correct temperature and pressure, makes the CSF steam water mixer a safe and easy-to-use device of choice for most cleaning or washdown applications in just about every industry.

Available through Pump Engineering, the steam water mixer is said to be versatile, effective and very simple to use in most industrial and process environments. These rugged and reliable mixers are constructed from stainless steel and are capable of delivering water up to a maximum temperature of 95˚C at volumes up to 10,000 l per hour.

They are simple to install because existing steam and cold water supplies can be utilised. Also, running costs are minimal because the design of the mixer ensures that all the heat energy in the steam is transferred to the water.

Mettler-Toledo Garvens GmbH www.mt.com/garvens-atex

Pump Engineering Ltd www.pumpeng.co.uk

EPM 29

MANUFACTURING

Product News

Lab paddle blender and sponge swab combo prove worth in production hygiene

Single-use functionalised media provides scalable purification performance in cell culture

Seward has highlighted the effective use of its Stomacher technology in combination with sponge swabs for hygiene monitoring and biosecurity applications.

Hygiene monitoring in food and pharmaceutical production facilities and clinical environments requires simple sampling techniques with excellent microbial recovery rates across a spectrum of different species. A recent study1 has confirmed the effectiveness of the combined sponge swab and Stomacher sampling methodology for sampling a large surface area.

This popular sampling method utilises sponge swabs pre-dosed with buffer to swab a surface and then, to recover the micro flora, the sponge swabs are processed in the Stomacher 400 circulator. Some suppliers such as 3M and Technical Services Consultants Ltd offer pre-manufactured devices, which work effectively in Stomacher products.

Various different approaches can be applied, processing either pooled samples in the Stomacher 400 or individual swabs in the Stomacher 80 Biomaster.

Owing to the efficacy of the Stomacher and sponge swab combination, it has also been adopted in more critical fields such as biosecurity. Security services on both sides of the Atlantic have recently adopted the technique to detect and monitor the potential spread of

3M has introduced a new purification and separation product for biopharmaceutical processes. The Emphaze AEX hybrid purifier encapsulates an anionic exchange (AEX) media with a downstream microporous membrane for single-use manufacturing. The scalable range is suitable for process development through to large-scale cell culture.

Emphaze AEX hybrid purifiers address the requirement for high purity as early as possible in the manufacturing process. Using anionic ligand technology, the purifier delivers chromatographic adsorption capabilities to reduce soluble and insoluble contaminants that are typically removed by Protein A columns and subsequent purification stages such as host cell proteins, host cell DNA and endotoxin. Rapid pressure

Stomacher 400 circulator. weaponised bacterial contaminates such as Bacillus anthracis.

The effectiveness of the sponge and Stomacher technique over the swab technique for sample collection is demonstrated in a recent paper1 concerning the clinical environment and the monitoring of Acinetobacter baumannii. The sponge and Stomacher technique allow for a greater surface area to be tested than achievable with a swab head. This also means that the sponge method delivers greater sensitivity.

1Thom K.A.etal.C om parison ofsw ab and sponge m ethodologies for identification ofAcinetobacterbaum annii from the hospitalenvironm ent.Journalof C linicalM icrobiology 2012,50(6):2140.

Seward Ltd www.seward.co.uk

EPM 30

build on the 0.2 Âľm bioburden membrane downstream of the functionalised media signals when ion exchange capacity is saturated, helping to protect against breakthrough of impurities. Early removal of soluble impurities lessens the impact on expensive downstream purification technologies such as the Protein A column.

Emphaze AEX hybrid purifiers are designed to be easy to use, scalable and offer reproducible performance as there is no scope for channelling or mixing as seen with mobile media. The range is disposable, eliminating the need for cleaning validation, and can be retrofitted into existing hardware platforms.

3M Purification Division www.3m.co.uk

Alexanderwerk GmbH +49 2191 795 0 contact@alexanderwerk.com www.alexanderwerk.com amixon GmbH +49 5251 688888 0 info@amixon.com www.amixon.com Dec Group +41 21 694 20 59 info@dec-group.net www.dec-group.net Frewitt SA +41 26 460 74 00 r.herzog@frewitt.com www.frewitt.com GEA Pharma Systems +32 3 350 12 11 pharma@gea.com www.gea-ps.com Gebrüder Lödige Maschinenbau GmbH +49 5251 309 208 spittka@loedige.de www.loedige.de Hosokawa Micron Ltd +44 1928 755100 info@hmluk.hosokawa.com www.hosokawa.co.uk IMA S.p.A. - IMA Active Division +39 051 6514111 tenorec@ima.it www.ima-pharma.com Kek-Gardner Ltd +44 1625 665 999 sales@kekgardner.com www.kekgardner.com NETZSCH Premier Technologies, LLC +1 484 879 2020 stephen.miranda@netzsch.com www.netzsch.com/gd Powder Systems Ltd +44 151 448 7700 info@powdersystems.com www.powdersystems.com Process Components Ltd +44 1625 412000 james.atkins@pro-components.com www.pro-components.com The Fitzpatrick Company +1 630 530 3333 fitzinfo@idexcorp.com www.quadro.com Willy A. Bachofen +44 1707 327777 t.mangan@wab.uk.com www.wab.uk.com

5

25

Size Reduction — Parts & Accessories

Size Reduction Equipment

Crushers

Containment Solutions

Compactors

Mills — Sanitary

Mills — Pelletising

Mills — Homogenising

Mills — High-Shear

Mills — Hammer

Mills — Granulating

Mills — Fluid Energy

Mills — Fine Grinding

Mills — Dispersion

Mills — Cone

Mills — Continuous

Mills — Colloid

Mills — Attrition

Kneading Mills

Grinders

Pelletisers

Comminutors

Granulators — High-Shear

Granulators — Size Reduction

Granulators — Vacuum Dryers

Granulators — Centrifugal

Granulators — Fluid Bed

Granulators — Particle Enlargers

Granulation & Milling

Granulators — Rotary

BUYERS’ GUIDE

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

OTHER

27

Mixers, blenders and dryers.

1

6 7 8

17 18

2

5

1

3

1

3

1

10

3

17

19 20 21 22

28 29

26 27 28 29

6 7 8

26

Solutions for mixing, coating, reacting, drying and emulsifying.

5 6 7

5 6

1

14 15

26

9 10

12

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5 6 7 8

14 15

25 26 27 28 29

19

21 22

24

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21 22

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26 27 28 29

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Exclusive supplier of genuine Premier Mill parts, upgrades and service.

28 29

Air jet mill, dust collectors, micronisers, integrated feeder, and CIP system.

Pin mills and pre-breakers.

2

5

7

10

12

10

5 6

14 15

13

17

15 16 17

15

19

22

26

29

5

9 10

1 2

17

15

EPM 31

20

24 25 26

28 29

24

28

Spare parts for centrifugal sifters, mixers and milling machines as well as contract and bespoke maintenance.

Ajax Equipment Ltd +44 1204 386723 sales@ajax.co.uk www.ajax.co.uk amixon GmbH +49 5251 68 88 88 0 info@amixon.com www.amixon.com Charles Ross & Son Company +1 631 234 0500 cross@mixers.com www.mixers.com Chemineer UK Ltd +44 1332 363 175 chemineeruk@nov.com www.chemineer.com Dec Group +41 21 694 20 40 info@dec-group.net www.dec-group.net Diosna Dierks & SĂśhne GmbH +49 541 33 104 810 dietzmann@diosna.de www.diosna.com Hosokawa Micron Ltd +44 1928 755100 info@hmluk.hosokawa.com www.hosokawa.co.uk L.B. Bohle Maschinen + Verfahren GmbH +49 2524 9323 0 t.remmert@lbbohle.de www.lbbohle.com Pharmatech +44 1675 467 636 info@pharmatech.co.uk www.pharmatech.co.uk

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

1 2 3 4 5

Ribbon Gravity Column Homogenising Pneumatic Portable Hoppers

Mixing & Blending

1

2

3

4

5

6

7

8

Blenders

Aerators Ball Mills Conical Continuous Cooker Dispersion Fluid Bed High Shear Homogenising Hydraulic Mill In-Line Jacketed Kneading Low Shear Paddle Planetary Pneumatic Portable Roll Mills Roller Sanitary Screw Self-Cleaning Tumble Ultrasonic Vacuum Vibratory

BUYERS’ GUIDE

Mixers

3

4

12

3

4

6

8

9

3

4

6

8

9

8

22

12

14 15

18

21 22

26

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26

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17 18

21

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9

7 8

2 3

4

6

8

1

14

19

5

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Devices for complete discharge.

Static, multi-shaft and ultrahigh shear mixers and paddle, vertical cone screw and cylindrical blenders.

1

12 13

11 12

Additional

23

26

23

26

22

26

3 4

Dense phase conveying mixer.

1

Bin blender.

8

14

24

Change shell blenders.

14

EPM 32

18

21

24

MANUFACTURING

In the Spotlight

TSAR Predict service solves

AGE-OLD ‘STICKING’ CONUNDRUM IN HOURS It is a year since EPM’s editor Elizabeth Valero first spoke to I Holland Ltd’s research, development & quality systems manager Rob Blanchard about I Holland and the University of Nottingham’s School of Pharmacy’s TSAR (Tabletting Science and Anti-Stick Research) project, the sole aim of which has been to solve the most prevalent tabletting issue of formulation ‘sticking’ to the punch tip face. As forecast, TSAR Predict — the resulting and much-hyped solution that aims to put an end to sticking by straightaway providing a right-firsttime answer as to the ideal PharmaCote tooling coating for any formulation — is finally here.

Elizabeth recently spoke to Rob again to learn how TSAR Predict works and what it means for I Holland customers now and in the future.

On 6 February 2014 — two years since I Holland and the University of Nottingham’s School of Pharmacy embarked on this mammoth project, headed up by Rob and chair of pharmaceutical nanotechnology at the University of Nottingham professor Clive Roberts — TSAR Predict was launched by way of a webinar entitled ‘Solving Your Sticking Problems with Tabletting Science’, available on the I Holland website (http://bit.ly/1k6Cf6i). Hosted by Rob and Professor Roberts, the webinar culminated in an explanation of how two years’ research findings had been incorporated into the mathematical model TSAR Predict, helping to speed up the process of selecting the most suitable of I Holland’s PharmaCote anti-stick punch coatings for any sticky formulation.

So how does TSAR Predict actually work? It is really very simple with I Holland requiring only the name of the API and or excipients to make a prediction. The key parameters are then entered into TSAR Predict to obtain the predicted particle adhesion force against each of the nine PharmaCote anti-stick coatings in I Holland’s range. “This gives a strong indication as to whether the formulation will adhere to our anti-stick solutions,” affirmed Rob. “The mathematical model is a combination of different formulas — based on a multitude of Van der Waals, capillary and electrostatic calculations obtained during the project — which directly correlate with each of our PharmaCote coatings, providing the predicted particle adhesion force that will be experienced with each.”

Obviously, the lower the force, the more suitable that coating is going to be.

In instances where the product is in development and ingredient information is classified — as is often the case in the pharmaceutical industry — I Holland EPM 33

is still able to use to use the model to suggest a suitable solution going on the basic characteristic information of a formulation’s key physical properties.

As the nature of each sticky formulation differs, it is impossible to suggest that one single coating could solve a multitude of sticking problems, so what was needed was a way of recommending the right PharmaCote coating for each sticky formulation as efficiently and as accurately as possible.

Prior to the introduction of TSAR Predict, selecting the right coating was a lengthy process that involved extensive in-the-field testing, taking up valuable production time for I Holland’s customers. I Holland would manufacture several tooling stations with different coatings, which would be taken to the customer’s facility and tested in situ with the product. Through trial and error, I Holland was then able to recommend the most appropriate anti-stick solution for that formulation. From start to finish, this process could take up to six months, whereas with TSAR Predict, providing I Holland has the aforementioned information, a highly accurate recommendation can be made within just hours or days.

With its highly skilled engineers, I Holland already possessed eight years’ experience in the provision of effective anti-stick solutions at the start of the project and had kept a record of which ones were likely to work for a number of APIs and formulations. Although, as Rob has been keen to stress, simply looking at historical data was insufficient: “More advanced scientific research needed to be applied, formulaic chemistry backing if you like,” a role that was fulfilled by Professor Roberts and the School of Pharmacy team.

There is of course always the possibility that sticking is caused by

MANUFACTURING something other than particle adhesion but — now possessing an impressive 10 years’ anti-sticking expertise — I Holland has a thorough understanding of all the parameters that could be responsible and takes these into account whilst using the mathematical model. “TSAR Predict is only as powerful as it is because of all the knowledge and data that’s gone into it and the scientific development of our PharmaCote coatings over the years,” stressed Rob. “It’s about interpreting the data that we get out of the model to make the right recommendation.”

The TSAR project staff studied and created data for numerous customers’ formulations, taking into consideration key factors attributable to sticking such as Van der Waals forces or molecular attraction, capillary action linked to high moisture content and static electricity as well as other parameters such as roughness of the punch tips, different materials/chemistries on the punch tips and deformation mechanics of the granules. The mathematical model was thoroughly tested by matching predictions with compression trials on an R&D press.

At the end of the project, I Holland ran blind trials, inviting customers to send formulations that had not been used in the initial compression trials. “One of these blind trials moved quickly to production and the customer’s sticking issues are no more, it’s a big success,” enthused Rob. “We saw it all the way through, getting a prediction and carrying out our own compression trials

In the Spotlight

on an R&D press as part of the project, and now the customer’s tried the final solution in production and it works.”

Although it has only been a couple of months, TSAR Predict is already very much in demand. Since the webinar, I Holland has been inundated with prediction requests from potential as well as existing customers, running data through the model numerous times on a daily basis. According to Rob, TSAR Predict has quickly integrated into the day-to-day running of the business leaving little time for allimportant R&D work, hence its planned adoption by the company’s CSG (Customer Support Group) over the coming months will be a welcome relief. “Our CSG stretches right across the business,” he proudly stated. “The team offers pre- and post-sale technical support, advising customers on coating selection, tabletting issues, tooling problems, maintenance processes, etc. A number of CSG staff will soon have access to the TSAR Predict model and be able to run adhoc predictions.”

As the service is so new, it is impossible to definitively judge/accurately assess its success rate. Once a prediction has been made, the process that normally follows is receipt of the order, manufacture of the tooling, delivery to the customer, before it being run through production and prompting a verdict. There are a number of orders to be manufactured and there are some tooling sets that have been

delivered and customers are waiting to use them, although as Rob keenly pointed out: “Where they have been put to the test so far, we’ve had great feedback.”

An additional highlight of the TSAR project is that through the knowledge gained on the causes of sticking, another PharmaCote coating — PharmaCote CT — has been developed. Rob described it as “unique” owing to the fact that it works very differently to the other anti-stick coatings in the range. “It’s all in the manufacturing technique; we’ve surface engineered the actual punch tip face in conjunction with the coating to almost provide a two-in-one solution,” he said.

“We tested a very early prototype as part of the TSAR project and were pleasantly surprised to learn it offered exceptionally low adhesion forces for the majority of formulations in the project’s compression trials.”

Looking as always to the future, I Holland intends to develop further anti-

EPM 34

stick solutions that will be added to the model. As outlined by Rob, the TSAR project has paved the way for improving and extending the PharmaCote range to accommodate additional parameters.

“The two-year project has taught us an enormous amount about particle adhesion, which will help us focus our development in the future,” he said. “We want to be recognised as a company dedicated to tabletting science, driving the development of advanced solutions in a direction that suits our customers.”

MANUFACTURING

Article

Busting the myths of

CHLORINE DISINFECTION A successful cleanroom disinfectant needs to meet many criteria, not only in terms of its efficaciousness but also in terms of packaging, ease of use, operator acceptability, etc.

Many articles have been written on how to specify and select a cleanroom disinfectant, but this is not the main focus of this article. However, a brief summary of requirements helps when comparing available chlorine chemistries.

The ideal cleanroom disinfectant Obviously, the ideal cleanroom disinfectant should have good broad spectrum efficacy including highly resistant bacterial spores but additional requirements include: a sterile option for grade A and B environments1, nonflammable so it can be used over large areas with no health and safety concerns, also fast drying with short contact times to reduce the time taken for biodecontamination. However, in an ideal world, this cannot be traded for any problems with either equipment or operators and the wider environment in terms of disposal. Another requirement

ABOUT THE AUTHOR: Karen Rossington, marketing consultant to Contec Inc. Rossington works as an independent consultant to companies in the pharmaceutical contamination control sector. She represents Contec Inc., a manufacturer of contamination control products for lifescience cleanrooms. Having previously worked with isolator and cleanroom design, Rossington has spent the last 14 years in both the marketing and development of cleanroom disinfectants and has written and presented many papers on cleanroom disinfection and biodecontamination.

that shortens the decontamination process is if the disinfectant has no residue that needs to be removed or as a minimum is free rinsing.

The product will need to have in excess of a 12-month unopened shelf life and in excess of a three-month inuse shelf life to be practical to store and use. This ideal disinfectant would then need to be manufactured to the requirements of cGMP, be notified to the BPR2 and provided in cleanroom compatible packaging in a variety of formats so it was suitable for use in all areas of the cleanroom. It goes without saying that this all needs to be achieved in a cost-effective formulation.

Many people believe that this ideal sporicide does not exist and that a compromise must be made.

On first reflection, a chlorinebased disinfectant would not necessarily spring to mind as the disinfectant that meets all of these ideal needs. Sodium hypochlorite is the most widely used chlorine-based surface disinfectant but has some known drawbacks, notably it is inactive in organic matter, corrosive to some metals and will leave a particulate residue. However, all chlorine disinfectants are not the same.

Advances in production methodologies have allowed the creation of a disinfectant that meets all of the aforementioned requirements.

History of chlorine disinfection One of the first known uses of chlorine for disinfection was in the form of

hypochlorite known as chloride of lime.

John Snow used it in 18543, after an outbreak of cholera to attempt to disinfect the Broad Street pump water supply in London. Claude-Louis Berthollet, in 1785, prepared a bleaching agent by dissolving Scheele’s gas in water and in 1789 improved it by mixing it with a solution of caustic potash (KOH); this was carried out in a French chemical plant in Javel and was known and remains known today as Javelle water. A short while later, AntoineGermain Labarraque replaced the expensive potassium hydroxide with caustic soda, resulting in what was probably the first use of sodium hypochlorite as bleach.

Chlorine first began to be used as a disinfectant in the late 1800s, early 1900s. Liquid bleach, sodium hypochlorite, came into widespread use

EPM 36

in the 1930s and today it is the most widely used of all the chlorinated bleaches.

Hypochlorite solutions were used for the treatment of open wounds during World War I and led to the use of onsite generation of hypochlorite in hospitals.

These disappeared out of favour until the 1990s, which saw a great surge in the interest of onsite generation of chlorine. These onsite generators provide a solution containing only 0.8% chlorine, which is non-hazardous, however hazardous hydrogen gas is produced as a by-product. Onsite generation is also quite inefficient compared with bulk production because of associated electricity costs.

Dry calcium hypochlorite appeared on the US market in 1928. This bleaching agent contains up to 70% active chlorine and is also known as high-test

EPM_14_2_Progress_Layout 1 04/04/2014 11:19 Page 37

MANUFACTURING hypochlorite (HTH). It is available in a variety of forms including powder, granules, briquettes and tablets. Calcium hypochlorite systems tend to be used for small water treatment plants and well systems. Calcium hypochlorite has a very strong oxidising potential and consequently is very dangerous to store and use. Calcium hypochlorite dissolved in water generates 2 mols of hypochlorous acid for every 1 mol of calcium hypochlorite.

Chlorine as a disinfectant Not all chlorine species are equally effective as disinfectants. Many studies have explored the mechanism of chlorine disinfection and although it is not possible to precisely explain how each particular chlorine species works, current theory4 states that inactivation occurs by means of one or more of the following mechanisms: inactivation of the key enzymes, disruption of nucleic acids rendering them non-functional and oxidative damage to cell walls or other vital cell components. For each of the mechanisms above, the effectiveness of each disinfecting agent is a function of both its rate of diffusion through the cell wall and its reactivity with the cell wall, proteins and nucleic acid.

Hypochlorous acid (HOCL) is the most effective disinfectant in the chlorine family available in dilute solution. It is suggested that HOCL is 80 to 120 times5 more efficacious than sodium hypochlorite. Owing to the fact that HOCL has no charge and has a relatively low molecular weight, it is better than the other chlorine-based disinfectants at penetrating the cell walls.

It also reacts more rapidly than other chlorine-based disinfectants to oxidation reactions with organic matter, i.e. the critical components of microbial cells.

Conversely, the hypochlorite ion is a relatively poor disinfectant because of its inability to diffuse through the cell wall.

Since it is negatively charged, it is electrostatically repelled from the cell walls, which are also negatively charged.

It is much larger in size than an HOCL molecule so it also diffuses more slowly.

Chlorine chemistry Chlorine is added to water in one of three forms: elemental chlorine (chlorine gas), sodium hypochlorite solution or calcium hypochlorite powder (high-test hypochlorite). Chlorine gas reacts rapidly with water to form two compounds: hypochlorous acid (HOCl) and hydrochloric acid (HCl).

Cl2 + H2O ↔ chlorine water acid hydrochloric

HOCl + hydrochloric acid

HCl hypochlorous acid

HOCl is a weak acid that further dissociates into the hydrogen ion (H+) and hypochlorite ion (OCl-) according to the following equation: HOCl

⇔ H+ + OCL- (hypochlorite ion)

These three species exist in an equilibrium that is both pH and temperature dependent; the sum of these is referred to as the total available chlorine. At 25 ˚C and a pH of 7.5, half of the total chlorine is present as HOCl and the other half as OCl-. The dissociated hypochlorite ion (OCl-) predominates at higher pH values, above 7.5 pH, whilst the undissociated hypochlorous acid (HOCl) predominates

Article

at lower pH values. At pH 5, nearly all the chlorine is present as HOCl, while a pH value of 10 drives nearly all the chlorine to be present as OCl-.

Efficacy data for 2,000 ppm hypochlorous acid.

At low pH and high chlorine concentrations, the hydrolysis is not complete and a significant fraction remains in the form of molecular chlorine Cl2.

In a sodium hypochlorite solution that normally sits at a pH of 11–13, all available chlorine is in a form of hypochlorite ions, which as previously discussed is far less efficacious than hypochlorous acid. Until recently, it has not been possible to create hypochlorous acid in a stable solution with a usable shelf life. Hypochlorous acid generated from dissolving dry calcium hypochlorite has a shelf life of approximately four hours and therefore has not been suitable for use in pharmaceutical or healthcare environments. Advances in chlorine chemistry have made it possible for contamination control products manufacturer Contec Inc. to stabilise a solution based on calcium hypochlorite at a pH of 3.5 to 5.5, so all available chlorine is in the form of hypochlorous acid as a ready-to-use product with a shelf life of 18 months.

Stabilised hypochlorous acid efficacy If the science was correct, this hypochlorous acid-based disinfectant should be more efficacious and faster acting than the equivalent sodium hypochlorite product. Contec’s solution of 2,000 ppm hypochlorous acid was therefore tested against the standard EN panel of tests for disinfectant efficacy; the table (top of page) shows a summary of these results. Complete kill against spores was achieved in both clean and dirty conditions against a modified EN 13697 surface test in 1 minute. This is a significant increase in both log reduction achieved and kill rate over sodium hypochlorite. Various microorganisms were tested, including a particular resistant house isolate, which was typed as P. glucanolyticus. Test work was also repeated against the newest version of EN 16506 for fungi and moulds, which has a requirement for >75% of the A niger (now A brasiliensis) spores to be in the form of spiny spores, which are more resistant.

It is not sufficient though for a cleanroom disinfectant to only have powerful activity, as invariably this activity comes at a cost. Either the product is unpleasant for operators to handle because of smell or toxicity or powerful sporicides very often require specialised PPE or costly disposal consideration. Hypochlorous acid at low concentrations is non-hazardous and requires no specialised disposal process or operators to wear any PPE other than standard cleanroom gloves.

Very often, fast-acting and efficacious sporicides are detrimental to the environment they are used in. At

concentrations of 2,000 ppm, hypochlorous acid is non-corrosive, so when used in a controlled manner will be compatible with cleanroom materials.

Although not residue free, as hypochlorous acid does leave a very low level of calcium salt on the surface — 1,200 ppm per 100 ml on a residue on evaporation test — it compares favourably with other well-used disinfectants such as quaternary ammonium compounds that give results of 4,500 ppm per 100 ml and 21,000 ppm for hypochlorite solutions.

To conclude, it would seem that stabilised hypochlorous acid challenges some of the commonly held beliefs about chlorine disinfection as it meets most, if not all, of the ideal cleanroom disinfectant functional requirements.

References 1EudraLex. The Rules Governing Medicinal Products in the European Union

EPM 37

Volume 4 EU Guidelines to Good Manufacturing Practices for Medicinal Products for Human and Veterinary Use. Annexe 1.

2EU Biocides Regulation (528/2012).

3White’s Handbook of Chlorination and Alternative Disinfectants, Black and Veatech Corporation, Wiley Publishing.

4GM Fair, et al. The dynamics of water chlorination, Journal of the New England Water Works Association, 1947 61 285–391.

5GM Fair, et al. The behaviour of chlorine as a water disinfectant. Journal of the American Water Works Association. 1948 40 1051–1061.

6BS EN1650:2008 +A1:2013 Chemical disinfectants and antiseptics — Quantitative suspension test for the evaluation of fungicidal or yeasticidal activity of chemical disinfectants and antiseptics used in food, industrial, domestic and institutional areas — Test method and requirements (phase 2, step 1).

MANUFACTURING

Showcase

CLEANROOMS Isolators prove worth over cleanrooms Isolators are a common means for protecting operators when handling highly potent compounds, although this practice is used less for aseptic applications where the use of cleanrooms are more common as the only protection barrier.

However, owing to increased regulatory requirements, open systems have their limits in terms of the risks inherent with human intervention and therefore the need to implement closed systems has become a logical answer.

It is still widely believed in the industry that the cost of installing closed systems such as RABS or isolators will increase the cost of the plant, but there are many

examples of well-designed, closed systems that substantially decrease the costs of operation and validation compared with traditional cleanrooms and ensure pay back in a very short period of time.

Some of the major advantages of using closed systems versus open operation in cleanrooms are: • smaller workspace; isolator-based aseptic facilities are 30–50% smaller than standard cleanrooms • decrease of cleanroom classification • reduced costs owing to less gowning, cleaning and staffing requirements • less product waste and risk of cross contamination

• reduced monitoring costs • quicker turnaround of product change.

Dec Group has developed isolator systems combined with its powder handling technology, allowing an interface of the processes and therefore removing the need for separated process rooms and intermediate containers. The productivity of such isolators is largely increased as they are fully automated with limited staff requirement and can be CIP and SIP, allowing a very fast changeover of product.

Dec’s isolators, whether standard or customised complex systems, enable ergonomic and flexible working in a safe environment.

Diaphragm quick release valve makes mark in Russia Russia’s International Biotechnology Center Generium carries out its research and development of molecular and cell biology in the most stringent of cleanrooms. The company had a requirement to temporarily pass pipes through the walls of its cleanrooms to help formulate its research. Initially, a multitude of seals were used to gland around the pipes. However, as these seals needed to be replaced every time a pipe was put through or removed from the cleanroom walls, it was soon realised that valuable hours were being

wasted every time this procedure needed to be carried out.

Generium required a device that would quickly seal around any pipe diameter, reducing downtime and increasing productivity. In addition, when the pipe was removed, the gap in the wall needed to be closed off, keeping the room clean and dust free.

The Mucon Series K Iris diaphragm, quick release valve quickly proved to be a major improvement. This is because the Iris valve can quickly and easily control the seal and tightly gland around

any pipe diameter. No time is lost changing individual seals and should the company wish to remove a pipe to close off the hole in the wall, the valve can be simply shut off, thereby preventing any ingress into the cleanroom. As a result, the task of installing and removing utility pipes in the cleanrooms has been made quick and easy and hours that were previously wasted have become increased hours of productivity.

Mucon www.mucon.com

Contamination control flooring reduces environmental impact Dycem has released CleanZone-Flexi, a flexible new flooring solution offering end-users a high-performance alternative to peel-off mats, without impacting on daily waste volumes.

CleanZone Flexi is a one to six month replacement system, proven to prevent up to 99.9% of foot, wheel and airborne contaminants. The high surface energy of the polymeric flooring attracts, collects and retains dirt, dust and bacteria between cleaning, preventing particulate from entering critical environments.

According to a scientific study conducted by Gerry Prout, managing director at Kennet Bioservices Ltd, the use of polymeric flooring can save approximately 18 tonnes of raw material over a period of two years compared with the disposal of peel-off mats.

At the end of its lifecycle, the CleanZone-Flexi system can be disposed of normally or readily recycled into less critical applications.

Peel-off mats however, which are heavily laden with hazardous

contaminants after use, present a more costly disposal procedure.

Available in a range of contract lengths, the flooring solution presents an ideal solution for shortterm projects and can be easily integrated into individual SOPs. Dycem considers the environment at each stage of its operations, which is recognised by its ISO:14001 certification.

Dycem Ltd www.dycem-cc.com

Stainless steel floor divides and protects wet and dry environments When maintaining a hygienic environment is priority, ASPEN products are ideal. All ASPEN stainless steel drainage, kerbing, protection and other bespoke products are British engineered with a lifetime guarantee.

ASPEN was recently approached by a company in need of stainless steel protection in its building for smoother operations. In particular, the chilled environment on the ground floor directly

affected the dry environment on the first floor above, creating a moist working environment. ASPEN designed and manufactured a fully welded, stainless steel floor for the first floor. Along with appropriate insulation, the stainless steel floor was installed, creating a sealed environment from the ground floor and keeping the conditions dry.

Other areas of the building also benefited from ASPEN stainless steel

bollards, kerbing and wall cladding for protection against daily operations.

With the increasing demands for hygienic plants and equipment in and around the pharmaceutical industry, ASPEN has provided product engineering solutions to meet specialist requirements year on year.

Canal Engineering Ltd www.aspen.eu.com

EPM 38

Dec Group www.dec-group.net

LABORATORY PRODUCTS Automated pipetting device wins Red Dot Design Award INTEGRA Biosciences has received a Red Dot Design Award for its VIAFLO ASSIST, a new laboratory device that, in combination with a VIAFLO II electronic handheld pipette, enables the pipette’s protocols to be performed automatically. With its origins dating back to 1955, the Red Dot Design Award ranks among the most renowned design competitions in the world.

INTEGRA received the prestigious Red Dot Design Award for the design and function of its VIAFLO ASSIST pipetting assistant, which reduces the need for traditional handheld pipetting to a minimum, relieving laboratory personnel from activities that may cause repetitive stress injuries.

The VIAFLO ASSIST met the Red Dot Design Award jury’s criteria of degree of innovation, functionality, formal quality, ergonomics, durability, symbolic and emotional content, product periphery, self-explanatory quality and ecological compatibility. Some 4,815 products were submitted in 23 main categories and have been evaluated by the international jury comprising 40 renowned designers. Following the

award announcement, the VIAFLO ASSIST will be put on display in the Red Dot Design Museum in Essen, Germany.

“Handheld pipetting requires practice to achieve steady reproducible pipetting results,” said Juerg Bass, marketing and communications manager for INTEGRA. “Typical parameters influencing performance are tip immersion depth and pipetting angle. The automated pipetting capability of VIAFLO ASSIST ensures these parameters are always the same, resulting in increased reproducibility and thus better results. This award underlines how INTEGRA strives to provide ergonomic laboratory tools that help improve the ease with which customers can undertake their working practices and that also increase productivity.”

The VIAFLO ASSIST works with all VIAFLO II multichannel pipettes, enabling precision pipetting throughout the volume range of 0.5–1,250 µl. To use the VIAFLO ASSIST, the user simply mounts a VIAFLO II electronic pipette onto the pipette adapter, chooses a protocol and presses the run button.

VIAFLO ASSIST will then obtain the protocol via Bluetooth from the VIAFLO II electronic pipette and automatically execute it.

INTEGRA Biosciences AG www.integra-biosciences.com

Syrris celebrates record flow chemistry product sales Increasing profits by over 50% year-onyear have been announced by Syrris.

The company achieved record returns in 2013, shipping products to over 50 countries worldwide and significantly increasing its global customer base.

This includes the top 20 pharmaceutical companies, leading universities and government institutes, plus companies working in fields such as food, flavour and fragrance, petrochemicals, nanoparticles and fine chemical synthesis.

Highlights of 2013 included a global series of workshops — enabling chemists to discover the advantages of flow and automated process chemistry — and the launch of an exclusive Customer Club, offering members easy access to a variety of select benefits and additional information. Syrris also committed to a three-year, multi-million pound R&D programme, part funded by EU and Technology Strategy Board grants, which were awarded in recognition of the company’s ability to develop user-friendly and commercially successful products for chemists and

chemical engineers. The programme will allow existing award-winning products, including Asia and Atlas reactors, to be further enhanced and batch and flow chemistry products to be developed.

CEO Mike Hawes commented: “This is a really exciting time in Syrris’ history. Our most successful year ever has established Syrris as the market leader in flow chemistry products. The launch of our R&D programme will deliver further worldclass products offering the greatest control and ultimate ease of use to our customers, enabling a broader array of

EPM 39

chemistry on a wider scale than ever before.”

Syrris Ltd www.syrris.com

LABORATORY

Industry News

PANalytical participates in International Year of Crystallography 2014 with OpenLab events The United Nations Educational, Scientific and Cultural Organization (UNESCO) has declared 2014 to be the International Year of Crystallography (IYCr2014). Throughout this year, UNESCO, with the support of the International Union of Crystallography (IUCr), will be working on raising awareness of the importance of crystallography in daily life. This year, a large number of events around the world will aim to spread crystallographic knowledge, inspire young people and promote education and research in crystallography.

PANalytical attended the IYCr2014 opening ceremony on 20–21 January 2014, at the UNESCO building in Paris, France, with a lecture on ‘The importance of crystallography in our daily

lives, held by Martijn Fransen, product marketing manager X-ray diffraction. The company’s ongoing support of IYCr2014 includes the organisation of a number of educational OpenLab events worldwide, consisting of schools and workshops on crystallography, aiming to raise awareness and understanding of this powerful science, responsible for 29 Nobel Prizes.

Crystallography is the basis of a wide range of applications throughout industry, from geological investigation (mineralogical exploration) and pharmaceutical development to research into novel materials for renewable energy. In addition to day-to-day routine use, crystallography is emerging as an essential tool in tackling some of the world's most pressing contemporary

issues such as finding innovative solutions for dealing with the scarcity of natural resources, managing global population growth and addressing climate change.

Fransen said: “At PANalytical, we believe that access to education in crystallography on a global scale is the key to finding solutions to these issues.

Through our support and participation in the 2014 International Year of Crystallography we hope to attract the interest of young people and those working in research and industry worldwide and inspire the next generation of crystallographers.”

For more information on PANalytical’s participation in IYCr2014 and the upcoming OpenLab events, visit www.panalytical.com/IYCr2014.

PANalytical’s product marketing manager XRD Martijn Fransen talking about ‘crystallography in our daily lives’ at the IYCr2014 opening ceremony in Paris.

PANalytical www.panalytical.com

Avestin chooses BPS to sell high-pressure homogenisers in UK and Ireland Biopharma Process Systems (BPS) is representing Avestin high-pressure homogenisers in the UK and Ireland.

These homogenisers are suitable for high-pressure applications such as pharmaceuticals and biotechnology.

Their design eliminates all o-rings and gaskets in the product path, resulting in less risk of contamination, easier cleaning and no risk of leakage.

Avestin’s laboratory homogenisers are capable of processing samples as small as 3 ml, with both electrically-powered

and pneumatically-driven models available. The dynamic homogenising value is used in all the systems from laboratory- to production-scale so that research results can be easily scaled up.

All Avestin’s systems are capable of achieving controllable pressures up to 30,000 psi, ideal for processing tough samples such as E. coli or yeast cells.

Avestin’s dynamic homogenising valve is proven on over 2,000

installations worldwide and selfregulates once set.

Avestin systems are suitable for a range of cell disruption, emulsification, homogenising and particle size reduction applications.

They are also fully supported for service and spares in the UK and Ireland by BPS’ in-house service department.

Biopharma Process Systems www.biopharma.co.uk

Popularity of NMR spectrometers prompts Magritek to expand sales and marketing team Magritek has announced further expansion in company activities worldwide. With offices now in the US, Germany and New Zealand and increased growth in worldwide markets for benchtop-sized analytical techniques, Magritek made the decision to appoint two experienced industry professionals to its sales and marketing team.

Silverio Iacono is to head up the company’s sales operations worldwide.

Iacono has spent his career leading sales and marketing teams for analytical tools, most recently as vice president and general manager of PerkinElmer’s mass spectrometry business. With nearly 25 years’ working in the scientific community, he arrives at Magritek with the aim of further building the company into a world-leading business.

Joining him is another spectroscopy veteran. John Paul Cerroti has worked

in analytical instrumentation for nearly 30 years. With a background in materials science, Cerroti has held senior sales and marketing roles for many of the leading spectroscopy tools specialists, including PerkinElmer, Renishaw and Oxford Instruments. Cerroti is based at Magritek European headquarters in Aachen, Germany.

Magritek CEO Andrew Coy commented: “Since we launched the Spinsolve family of NMR spectrometers, we have seen a large increase in the interest for instruments that fit into educational programmes where the system delivers rapid, repeatable results with minimal operator interaction. With operations on three continents and further expansion in the pipeline, we are confident that Silverio and John Paul will make vital contributions to Magritek.”

Magritek’s latest Spinsolve system is used to conduct carbon-13 NMR spectroscopy experiments, delivering

more detail in its spectra than with the use of the more basic 1H nucleus.

Carbon has a large chemical shift range of approximately 250 ppm and using composite pulse decoupling there is usually a single peak per carbon atom in the molecule, making carbon spectra much more New arrivals at Magritek — John Paul Cerroti will lead marketing informative than efforts out of Aachen while Silverio Iacono heads up sales proton spectra. operations worldwide from his East Coast US base.

Furthermore, resolve isomers that are often confused multinuclear and multidimensional with other analytical methods. experiments reveal additional structural information such as how carbon and Magritek proton atoms in the molecule are www.magritek.com connected. This enables NMR to easily

Sartorius appoints internationally experienced lab manager On 1 April 2014, Michael Melingo headed-up marketing, sales and services of the Lab Products & Services division at Sartorius. He succeeds Dominique Baly, who has retired from the company.

Melingo will report to CEO and executive board chairman Dr. Joachim Kreuzburg and be a member of the group executive committee, the highest operational management level of the Sartorius Group.

Melingo, who brings more than 30 years of experience in the industry as a

sales and marketing executive, will be joining Sartorius from Metrohm, the Swiss manufacturer of analytical instruments, where he was CEO of its US subsidiary. Before that, he had worked for Baxter, Bio-Rad, Millipore and Waters in Europe and Asia. Melingo is of Austrian nationality and a bioengineer who specialises in biochemistry and food technology.

“With Michael, we have found an exceptionally experienced manager to join our team, who has successfully EPM 40

managed international laboratory businesses,” said Sartorius CEO and executive board chairman Joachim Kreuzburg. “In his new role at Sartorius, he will focus on further developing the global sales, marketing and service organisation of our laboratory division business and strengthen its strategic positioning.”

Sartorius Corporate Administration GmbH www.sartorius.com

LABORATORY

Product News

Infrared and Raman spectroscopy technologies deliver accurate ID of unknown compounds

Website’s product finder enables easy selection of right autoclave

Bio-Rad Laboratories has released KnowItAll ATR/IR ID Expert and Raman ID Expert solutions for spectral identification, technologies that combine Bio-Rad’s knowledge in spectroscopy with advanced computational power to provide scientists identifying unknown infrared and Raman spectra with fast and accurate answers.

“The spectral intelligence built into KnowItAll ATR/IR ID Expert combined with the world’s largest spectral reference collection provides the highest level of expertise to any scientist, whether a novice or power user,” said Gregory Banik, Ph.D., BioRad general manager, informatics.

Scientists often employ multiple software tools to identify a spectrum depending on its chemical composition and the availability of reference spectra.

Even experienced researchers can misinterpret results, particularly if they choose the wrong software tool.

With ATR/IR ID Expert and Raman ID Expert, the user opens an unknown spectrum and the software automatically performs single and multiple component searches as well as functional group analyses simultaneously, summarising

Priorclave’s new website went live in March and reflects the company’s upfront policy of providing would-be autoclave purchasers with facts and figures that will steer them easily to identify the best possible steam steriliser for their application. The selection process begins on the home page where answering a few key questions on the product finder guides the user to the most appropriate Priorclave product available within their given budget.

Priorclave is firmly established as a global autoclave supplier to a range of industrial sectors that includes food and dairy, pharmaceutical, microbiology and healthcare. The company’s success is built around its in-house assets of strong design credentials and modern manufacturing facility coupled with rigorous test and calibration centre.

With over 50 standard autoclaves — including front and top loading sterilisers with cylindrical or rectangular stainless steel chambers and with capacities from 40 to 700 l — Priorclave aims to make the task of searching for the most suitable autoclave much easier. In addition to the product finder on the home page, every product range incorporates a quick-selection guide to help locate the most appropriate autoclave for the laboratory application.

This comprehensive selection of autoclaves includes a variety of styles such as benchtop and floor-standing

the results on a single screen to give a complete view of all possibilities for the unknown spectrum.

If there are problems with the user’s query spectrum, ID Expert has the spectral intelligence to identify these issues and suggest ways to fix them.

Once the user has identified the unknown spectrum, a PDF report can be generated with a single click.

Bio-Rad claims that this combination of spectral software combined with highquality spectral reference data gives ID Expert users the most advanced technology now available for IR and Raman spectral identification.

Bio-Rad Laboratories, Inc. www.knowitall.com/contactus

Label-free cell-based assay forecast to take big slice of drug discovery market Symcel has announced the commercial readiness of its calScreener system, which has spent over 10 years in development.

Since the technology has moved from its prototype into a fully functional commercial platform, three units have been installed at leading international research institutions with exponential growth predicted over the next few years.

The calScreener is a drug discovery tool enabling continuous monitoring of energy release from biological systems regardless of morphology. The label-free detection system aims to provide significant cost advantages and is predicted to revolutionise drug discovery techniques. The last few years has seen a drive in drug discovery for technologies that enable more in vivo like environments. By measuring the total energy released, the calScreener system actively measures the true phenotype effect and gives a more accurate indication of pharmacodynamics, regardless of pathway or mechanism involved. As the measurement is noninvasive and non-destructive, it also enables post experimental analysis of cellular contents and metabolites.

What is said to be remarkable about this system is its flexibility of experiments, with parameters such as toxic effects, bioavailability, stability of tested compound and, ultimately, drug efficacy. Current technologies are

focused on genotype performance testing, whereas calScreener enables a true phenotype screen says Symcel.

The company has predicted significant sales across Europe in 2014, with the US market launch forecast within the next year. “Already we have seen a huge demand for the calScreener as pharmaceutical companies search for more predictive models to drug discovery,” commented Christer Wallin, president and CEO at SymCel. “The technology is the closest to in vivo testing of any commercially available product and provides far better clinical predictability in drug development. The system is adapted for 3D cell cultures and monitors tissue-like behaviour and can also be used for bacteria, yeast and parasites.”

Having successfully proved the commercial viability at three sites, the company is now actively looking for partners across Europe and will design bespoke systems and installations for each customer.

SymCel Sverige AB www.symcel.se EPM 41

designs for mid- and high-capacity applications, power-door as well as double-door versions and a choice of steam generation.

There will be an autoclave to meet most requirements, however should a bespoke build be required, this can be undertaken since Priorclave has total control over design and production at its British manufacturing centre.

Visitors to the new Priorclave website should find it much easier to navigate, plus helpful information on topics such as what to consider when selecting an autoclave and information on the company’s extensive pre- and after sales support.

Priorclave Ltd www.priorclave.co.uk

LABORATORY

Product News

Added QC automation capabilities enhance LIMS solution

Fully integrated gel electrophoresis system saves space and time

Autoscribe has added a facility for the automation of QC samples and how they are grouped together to its Matrix Gemini LIMS. Accessed through either Matrix Gemini’s web or Windows interface, this is an enhancement of the existing runsheet function and provides the ability to create runsheet templates and automatically build runsheets from those templates as well as performing standard QC calculations.

Since laboratories typically perform the same type of QC over and over again based on the type of test being performed, Matrix Gemini now offers the flexibility to select the type of test, select a runsheet template, select a set of unknowns and have the LIMS build the run list and related QC samples automatically. This could include QC samples such as spikes, duplicates, replicates, spike duplicates, etc. Export of run lists to the appropriate analytical instruments has also been simplified.

In addition, different types of runsheet can be defined, for example, a

The VS20 WAVE is a complete electrophoresis system that provides a fully integrated solution using one gel tank and lid for vertical PAGE, tube gel IEF and electro blotting. Available from Cleaver Scientific Ltd (CSL), the VS20 Wave is designed to perform a variety of separations, ranging from first and second dimension SDS-PAGE to capillary tube gel IEF and electroblotting.

Unlike other systems whose traditional clamping configurations require adjustment of as many as 24 screws to secure just two glass plates, the VS20 WAVE insert utilises only four screws to secure as many 20 x 20 cm gels. The vertical screw-clamp technology ensures not only much faster set-up speed, it also exerts uniform pressure along the height of the glass plates to facilitate a leak-free seal without gel compression and bowing to provide even migration.

The ergonomic WAVE-like design of the PAGE insert aids both handling and set-up, while its built-in inner buffer chamber allows set-up to be completed without the inclusion of a top tank or

‘preparation batch’ and an ‘analytical batch’. Sample tests can also be added to multiple runsheets since a particular sample test may be associated with more than one type of run list.

Standard QC calculations such as percentage recovery or relative percentage difference can now be automatically calculated within the test grids. In addition, the capability to select sets of results and mark them as nonreportable has been added to accommodate the possibility that certain results are not appropriate for some reason such as the sample needing to be diluted.

Autoscribe Ltd www.autoscribe.co.uk

upper buffer chamber. A detachable cooling coil is supplied, enabling the WAVE to be connected to a recirculating chiller for uniform, trouble-free electrophoresis, and this also permits runs to be performed faster at higher voltage.

The WAVE is also said to benefit from a high-specification injection-moulded construction, while its modular design and optional conversion kit allow blotting and isoelectric focusing techniques to be undertaken in the same all-purpose tank.

Cleaver Scientific Ltd www.cleaverscientific.com

Lightweight electronic pipettes enable fast and accurate working According to INTEGRA, the new VIAFLO II multichannel electronic pipette range combines ultra lightweight design and operation comfort, enabling users to improve efficiency in their working environment.

VIAFLO II electronic pipettes together with INTEGRA’s range of GripTip pipette tips aim to form a perfect pipetting system. GripTips snap into place with minimal tip loading effort, providing a secure connection.

GripTips are designed to never fall off and be perfectly aligned, resulting in high precision.

The integral colour screen together with the easy to navigate touch wheel user interface promote ease of set up

and operation. All VIAFLO II pipettes offer a choice of up to 10 predefined pipetting modes (including repeat dispense, serial dilute and manual pipette), enabling users to quickly perform typical pipetting operations. For more demanding pipetting routines, up to 20 personalised custom programmes can be created using the following steps: aspirate, dispense, mix, purge and prompt.

The ergonomic design of VIAFLO II electronic pipettes facilitates hours of tireless pipetting. With just one light press of the run button, a VIAFLO II electronic pipette can perform many procedures, eliminating the timeconsuming repetitive plunger motion

required of manual pipettes.

Available in 8-, 12and 16-channel versions, VIAFLO II electronic pipettes offer an optimised precision pipetting solution from 0.5–1,250 µl.

For laboratories looking for further gains in productivity, VIAFLO II electronic pipettes are compatible with the INTEGRA VIAFLO Assist, enabling easy and affordable automation of these handheld devices.

INTEGRA Biosciences AG www.integra-biosciences.com

Robert Gordon University uses temperature-controlled stages to advance knowledge of pharma processes Temperature controlled microscopy specialist Linkam Scientific Instruments has reported on the use of its stages in the study of pharmaceutical processes at the Robert Gordon University.

The School of Pharmacy and Life Sciences has been using Linkam systems to look at the behaviour of drugs at varying temperatures. This relatively young university was awarded The Sunday Times Best Modern University in the UK in 2012, with the School of Pharmacy and Life Sciences being one of the key factors contributing to this recognition.

Dr. Kerr Mathews, a lecturer in pharmaceutics at the university since 2004, has focused a lot of time and effort in key interests in the area of drug delivery and formulation science.

The research and development of solid and liquid drug delivery systems have been extensively undertaken.

Dr. Matthews has used both a Linkam

LTS stage and FDCS stage to study the phase transitions of drugs, excipients and delivery systems as a function of temperature. He has found the equipment to be integral to his work. “We find this classic technique of qualitative analysis invaluable when used in conjunction with differential scanning calorimetry or thermogravimetry, especially to corroborate assignment of phase transitions in solids or liquids,” he said.

He added that the ability to study the samples under polarised light is also of vital importance. “We also use the capabilities of a materials microscope fitted with cross-polarising filters in both transmitted and reflected light modes to assess the degree of anisotropy in solid solutions, polymers and assorted dosage forms.”

Lyophilisation is of particular interest to Dr. Matthews and his team. They

have used the Linkam FDCS 196 stage to recreate low temperature conditions that are encountered during the pharmaceutical freeze drying process.

With the ever increasing cost of pharmaceutical products, the importance of research into the formulation and stability of drugs has never been higher. World-renowned companies from all over the globe use such research to optimise the synthesis and storage of their products.

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Linkam Scientific Instruments Ltd www.linkam.co.uk

LABORATORY

Product News

Paper shows component-specific characterisation of pharma cream The application of morphologically directed Raman spectroscopy in characterising the component-specific particulate properties of the active components in a topical pharmaceutical cream is described in an application note from Malvern Instruments.

While it is relatively straightforward to determine the particle size distributions of the individual components of a drug formulation before they are formulated as a blend, doing so post-blending is more challenging. Now, the Morphologi G3-ID, which combines automated image analysis with Raman spectroscopy in a single instrument, enables component-specific particle size and shape distributions to be obtained from a blend. The results of this analysis can provide information about the homogeneity and potency of individual components. Such insight is helpful in

improving product understanding and can be applied from a regulatory perspective right through to troubleshooting and optimising manufacturing processes.

‘Component specific particle characterization of active component(s) in topical cream products’ is freely downloadable from the Malvern website.

It details the analysis of a commercially available topical cream containing two active ingredients. These two morphologically similar actives could not be differentiated by image analysis alone, however the combination of image analysis with Raman spectroscopy allowed the unambiguous determination of particle size distribution for each component. To download the application note, go to www.malvern.com/topicalformulations-g3id.

The Morphologi G3-ID provides size, shape and chemical analysis information for particles in the size range 0.5–1000 µm for a variety of sample types, including dry powders, liquids and creams. It operates by scanning a particle dispersion and using advanced optics to capture images of individual particles. The system then automatically selects particles within the dispersion and collects a Raman spectrum from each one, allowing them to be classified and grouped in terms of discrete component populations. Designed for operational ease of use, the fully automated

instrument enables particle characterisation scientists with even limited spectroscopic experience to gain an in-depth understanding of their particulate samples.

Malvern Instruments Ltd www.malvern.com

Overhead stirrer performs three blending experiments in parallel Asynt has developed a new adaption of its Vortex overhead stirrer, called the Vortex Blend, specifically to cater for the requirement of scientists to test new formulations and blends in parallel.

Many scientists have established methods for blending and formulation development based upon mixing materials in standard laboratory beakers.

These protocols often require heating and powerful mixing to ensure blend/formulation homogeneity. To accelerate formulation development, it is

advantageous to perform multiple blending experiments in parallel.

Traditionally, conducting multiple heating and overhead stirring experiments in parallel has taken up a lot of valuable fume hood space. Also, when working in parallel, it is important identical conditions are created in each beaker, which is difficult when using multiple heater stirrer set-ups where motor speeds and heating rates may vary.

Developed in conjunction with a leading industrial formulation

development group, the Vortex Blend should offer scientists an efficient, space saving way of performing three blending experiments in parallel. Benefiting from a three-way gearbox and integral heating plate, the Vortex Blend economises laboratory space and ensures that parallel experiments have identical stirring rate and heating rate/temperature conditions, improving result reliability.

Asynt Ltd www.asynt.com

Midatech Biogune rates reactor system for gold nanoparticle scale up Spanish biotechnology company Midatech Biogune is using Syrris Atlas Potassium reactor systems to produce custom-made functionalised gold nanoparticles for medicinal use.

Midatech’s CEO Justin Barry explained: “Midatech is a clinical stage biotechnology company focused on translating its proprietary gold nanoparticle drug delivery platform into effective nanomedicines targeting currently unmet medical needs. We begin by producing functionalised gold nanoparticles on a bench scale, then

move to larger scale manufacturing processes, where it makes sense to use a reactor system. Our Atlas Potassium reactors, with pH control and an Atlas Syringe Pump XL, have allowed us to scale up production, enabling variables such as pH and temperature to be tightly controlled.

“The Atlas Potassium was the only logical way to move from manufacturing nanoparticles on a laboratory scale to a mini-production environment. It is a reliable and reproducible reactor system that is well-assembled, compact and

portable and performs exactly as we were told it would. Atlas Potassium is also very flexible, accommodating volumes ranging from 50 ml to 2 l, and its operating software works well, enabling a series of validation runs to be performed quickly and easily. The Atlas reactors were easy to implement in the laboratory, and it took just six to eight months to establish a validated process.

We are very happy with them.”

allow the Model 440 to deliver some of the lowest operating costs of any CHN elemental analyser. Intuitive Windowsbased operating software is designed to reduce human errors through incorporation of automation, comprehensive customer help and diagnostic facilities. Most parts on the Model 440 are user replaceable, further reducing operating costs and downtime.

GE Healthcare’s newly-launched Amersham Imager 600 series is designed to enable capture and analysis of high-resolution digital images of protein and DNA samples in gels and membranes. These multipurpose imagers deliver highperformance imaging to chemiluminescence, fluorescence and colourimetric applications and the dynamic range allows weak and strong signals to be quantitated accurately at the same time.

Full system automation means that after startup, there is no need for focusing, insertion of light sources, changing of filters, calibrations or other adjustments. In each capture mode, images are automatically corrected for both geometric and intensity distortion to minimise the hassle of post-processing for publication.

The seamless workflow allows users to readily detect and quantitate bands, determine molecular weight and perform normalisation. With integrated analysis software controllable via a touchscreen device, the results are presented in both tabular and graphical formats, enabling quick and easy generation and analysis of data.

Exeter Analytical Inc. www.eai1.com

GE Healthcare Life Sciences www.gelifesciences.com

Syrris Ltd www.syrris.com

CHN analyser popular with CROs and service labs The Model 440 CHN analyser, says Exeter Analytical, has become the system of choice for many CROs and service laboratories because of its ability to accurately analyse a range of sample types quickly, easily and reliably.

Operating across a wide linear range, the Model 440 can routinely determine percentage carbon, hydrogen and nitrogen levels in almost any sample type, including organic compounds, pharmaceuticals, petrochemicals, polymers and refractory, environmental or natural materials (soil, plants or insects).

The Model 440 has a furnace design that prevents cross contamination and allows for the running of a greater number of samples between combustion tube changes.

Based upon a combined static/dynamic combustion technology,

the Model 440 is said to precisely analyse a range of sample types from volatile to difficult-to-combust materials, including nitrides, graphite fibres, ceramics and even carbides with melting points of over 2,000˚C. Offering outstanding operating accuracy and precision, the fully automated Model 440 delivers simultaneous CHN analysis in less than five minutes, says Exeter Analytical.

Low gas and reagent consumption combined with high reduction tube life

Imaging system spans chemiluminescence, fluorescence and colourimetric applications

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LABORATORY

Product News

Immunoassay kits help scientists get results faster Gyros has announced that EMD Millipore, Life Science division of Merck KGaA, has released five new immunoassay kits designed specifically for use on the Gyrolab xP workstation.

The fully qualified GyroMark HT kits from EMD Millipore should enable clinical researchers and drug developers to generate research data much faster than typical ELISA kits.

Traditional ELISAs can consume significant time, sample and reagents.

With the fully automated, walk-away system from Gyros, up to 480 data points can be generated in a run.

The initial launch includes five assays for important metabolic and toxicity biomarkers such as GLP-1, insulin, clusterin and KIM-1. EMD Millipore plans to release additional kits this year and is offering custom kits that have specific needs or unique or novel antibodies.

Because the Gyrolab platform employs microfluidic technology with parallel processing, it offers many advantages over traditional assays in addition to reagent and time savings.

GyroMark HT assays provide: • accuracy over a four-log dynamic range (compared with two logs for ELISAs) • elimination of cross-talk and plate position artifacts • simplified sample prep (only 1:2 dilution necessary) with reduced matrix interference.

Drug discovery software users benefit from Pilot Pipeline tools for SAR data analysis and 3D-QSAR modelling

Gyros’ global marketing director Maria Hjortsmark commented: “Gyrolab revolutionises immunoassays, enabling scientists to analyse large numbers of samples in parallel, at nanolitre scale and using a fully automated system. We are delighted that EMD Millipore has now chosen to work with us to develop off-the-shelf kits to further reduce time to results, freeing up analyst time and offering an easier route to robust, reproducible data.”

EMD Millipore www.emdmillipore.com Gyros AB www.gyros.com

Cresset has released its latest set of Pipeline Pilot components V2.0.0, including new tools for SAR (structure activity relationship) data analysis and 3DQSAR (quantitative structure–activity relationship) modelling. “Chemists can now access even more of Cresset’s advanced technology through Pipeline Pilot,” said Dr. Tim Cheeseright, director of products at Cresset. “This release gives the benefit of new ideas and insight for their drug discovery projects within a familiar interface. All of Cresset’s Pipeline Pilot components are free for existing users of Cresset’s software.”

The new Activity Miner component (pictured) finds activity cliffs in SAR data.

It uses the disparity between two molecules to highlight where small changes in structure result in disproportionately large changes in activity. Activity Miner operates using both 3D and 2D similarity metrics to assess the change in a structure, enabling a better understanding of the reasons for the change in activity.

Pipeline Pilot’s advanced reporting and visualisation capabilities can be used to

view this data, as heat maps for example, so users can quickly focus on the most important regions of SAR in their data sets.

New 3D-QSAR components bring a combined alignment and 3D-QSAR capability based on accurate molecular electrostatics, something previously unavailable in Pipeline Pilot. Users can generate 3D-QSAR models, view the models to gain information about the field patterns required for activity in their data set and predict the activity of new compounds.

Also, new XedeX and XedMin components simplify access to Cresset’s advanced XED force field minimisation and conformation searching engine, allowing the user to use their force field anywhere along an existing protocol.

Cresset www.cresset-group.com

Advanced CSP screening set performs high-efficiency separations Chiral Technologies Worldwide has announced the availability of i-CHIRAL 6, a set of six Daicel 3-µm immobilised chiral stationary phases (CSPs) packed in columns of 4.6 mm internal diameter and 150 mm long. This combination of columns, which includes CHIRALPAK IA, IB, IC, ID, IE and IF, raises method

development success rates to greater than 93%.

“This advanced screening set will further equip pharmaceutical scientists in identifying and developing separation protocols using our state-of-the-art immobilised chiral stationary phases,” said Brian Freer, business manager for

Temperature control hoses reduce heating and cooling times Huber Kältemaschinenbau’s product portfolio includes special temperature control hoses with smooth internal wall that improve flow characteristics and thermal transfer. Compared with traditional hoses with fluted internal wall, these hoses aim to accelerate the heating and cooling processes.

Tests with different reactor systems at Unistats have shown a reduction of the heating and cooling times of up to 30%, depending on the application. The insulated hoses can be used with operating temperatures of -60 to +260˚C. They are available in lengths of

Chiral Technologies Europe. “Similar to iCHIRAL 4, the tool set is value-priced to meet the most stringent research budgets.”

The i-CHIRAL 6 set, which complements the i-CHIRAL 4 set released in late 2013, is designed for high-speed, high-efficiency separations

Chiral Technologies Europe www.chiral.fr

Microbiological product guide available as digital flip book or pdf download

100, 150, 200 and 300 cm. By means of connecting threads on both ends, the hoses can be coupled directly to reactor systems, autoclaves, synthesiser or distillation units.

Lab M has made its comprehensive Product Guide available as a digital flip book or a pdf download as well as offering printed versions for those who prefer to access a hard copy in the laboratory. The flip book and pdf download can be accessed at www.bit.ly/LABMPG14 or a print copy can be requested from info@labm.com.

The latest additions to Lab M’s portfolio are featured in the guide. These include the new µPREP buffered peptone water (ISO), the first in a line of bagged, sterile dehydrated culture media that are made ready to use simply by adding water.

Peter Huber Kältemaschinenbau GmbH www.huber-online.com

Compact oil-free compressor boasts super-quiet operation Gast Group — a member of the IDEX Corporation’s health and science division — has introduced the oil-free JUN-AIR 85R-4P compact compressor system with a maximum working pressure of 7 bar and flow rates to 55 l/min.

The small footprint, plug and play capability and quiet operation (only 50 decibels) of the 85R-4P make it easy-touse and ideal for point-of-use laboratory, medical and test equipment applications

of enantiomers. It is the complementarity nature of the added CHIRALPAK IE and IF that allows scientists to achieve resolution of the most difficult-toseparate target compounds.

or where a clean and quiet source of compressed air is required.

It features a 100% continuous duty cycle and comes equipped with a 5 µm filter regulator, automatic drain system with evaporation tray, hour run meter and a choice of castors or vibration isolation pads. Optional higher grade filtration and air dryers are available.

Featuring Gast’s latest rocking piston technology, the JUN-AIR compact

compressor is designed with long life and minimum maintenance in mind, requiring a filter replacement every 2,000 hours and compressor service every 8,000 hours. The system has a two-year warranty as standard and the internallycoated 4 l receiver tank is covered by a five-year warranty.

Gast Group Ltd www.jun-air.com

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Designed for high throughput laboratories where speed, convenience and costeffectiveness are paramount and where storage space is at a premium, µPREP media are reconstituted and ready for use in minutes.

The expanding range of Captivate immunomagnetic separation (IMS) products also features as IMS continues to play an increasing role in the detection and isolation of Verocytoxin producing E. coli (VTEC)/Shiga Toxigenic E. coli (STEC).

Lab M Ltd www.labm.com

LABORATORY

Showcase

SAMPLE PREPARATION Rotor mill delivers fine grinding in short times Fritsch’s variable speed rotor mill, the PULVERISETTE 14, rapidly grinds soft to medium-hard and brittle as well as fibrous samples. Comminution of samples that are difficult to grind or temperature-sensitive samples like tablets, dragées and pharmaceuticals are no problem for the PULVERISETTE 14 because of its efficient air cooling.

The PULVERISETTE 14 also features newly developed impact blades, which together with a sieve ring, allow for a very gentle grinding of the sample. This quick and effective grinding action where the heat load is minimised is an ideal solution for temperature-sensitive materials such as powder coatings or plastics as well as for smooth pre- and fine grinding of hard and brittle to soft, fatty samples or samples with a residual moisture.

With a top speed of 20,000 rpm, the PULVERISETTE 14 is capable of rapid sample throughput. Its feed particle size

of <10 mm means a final fineness of up to 40 µm can be achieved. The throughput depends on the material and lies between 0.05 and 5 l per hour.

Rotors, sieve rings and collecting vessels made of different materials and in different sizes enable flexible adjustment of the instrument to the application.

Advantages of the PULVERISETTE 14 are: • rapid sample throughput as a result of high-speed grinding and simple cleaning

• simple and easy changeover of all grinding parts without tools • simple, contamination-free cleaning and assembly of all grinding parts outside the instrument • variable speed adjustment from 6,000 to 20,000 rpm • automatic speed following system for constant grinding • efficient air cooling of the rotor, all motor components and the grinding material owing to a sophisticated routing of the air flow

• grinding parts made of stainless steel, pure titanium, TiN-coated and WCcoated • rapid-action clamping lock.

A range of accessories is available for the PULVERISETTE 14 so it can be configured to the customer’s application.

Fritsch offers a complimentary sample grinding and invites readers to send in their most difficult sample.

Fritsch GmbH www.fritsch.de/en

Agilent Technologies and CambTEK co-market LC sample preparation solution

Big pharma chooses protein precipitation kit for simpler and faster procedure

CambTEK and Agilent Technologies are offering CambTEK’s Rapid Extraction System (RES) automated sample preparation system with an assortment of Agilent’s liquid-phase separation, life science and chemical analysis instruments and software.

CambTEK's Rapid Extraction System (RES) is designed for rapid extraction of a range of sample types, including tablets, capsules, gels/pastes and beads, with important applications in the pharmaceutical, chemical and food science industries. The RES quickly breaks apart up to 30 samples at a time for subsequent analysis by liquid chromatography (LC) and other liquidbased techniques.

“Continuing advancements in analytical technology are enabling faster, more robust analysis capabilities in the laboratory, but work is getting trapped in the bottleneck of the sample preparation workflow,” said Christian Gotenfels, Agilent’s senior product manager for liquid chromatography. “By offering a combined solution for liquid chromatography sample preparation,

The Combipack from Porvair Sciences has been introduced for laboratories tasked with protein precipitation sample preparation.

Comprising five colourcoded Porvair P3 protein precipitation plates and five 1 ml deep well collection plates, the Combipack contains all the elements required to accelerate the traditionally troublesome procedure at a budget price.

Biological samples commonly contain proteins that interfere with downstream applications. The P3 protein precipitation plate uses the crash method, in which the protein is denatured with acetronitrile and the flocculant filtered out, allowing 96 samples to be handled at one time. The P3 is based on the industry standard MicroLute format but without the chromatographic sorbent. Protein crashes out of solution and precipitates directly in each well when acetonitrile is added, thus solving all common

our complementary technologies will enable analytical researchers to access faster and more robust workflow solutions to achieve higher productivity and data quality.”

“We are delighted to partner with Agilent to co-market our solutions for the preparation and analysis of solid dosage forms,” said CambTEK CEO Dr. Hugh Malkin. “Used together, these technologies will deliver significant benefits to our customers.”

CambTEK Ltd www.cambtek.com Agilent Technologies www.agilent.com

problems associated with the crash technique of protein clean-up. The dual frit, hydrophobically treated matrix means that there is no wetting out and leakage of the sample through the plate before the application of vacuum.

The P3 is now commonly used as the protein precipitation plate of choice by many major pharmaceutical companies.

Optional drain cap and top cap mats are available for those wishing to use vortex sample mixing.

Manufactured to the standard ANSI/SBS 96-well format footprint, all plates in the Combipack are fully automation compatible.

Porvair Sciences Ltd www.porvair-sciences.com

Non-destructive evaporation improves crystallisation control Genevac has launched eXalt, a technology developed with partners in the field of pharmaceutical small molecule crystallisation. eXalt has found application in laboratories that perform tasks including first-time crystallisation of amorphous forms, recrystallisation of samples that have only a few known forms, removing a hydrate, solvent screening studies to find the most suitable conditions to take

forward in development, high-throughput co-crystallisation screens and studies to confirm stable isoforms. eXalt enables a range of solvents and multiple actives to be evaporated all at the same slow rate, under the same conditions, giving the user outstanding control of the crystallisation process.

This is achieved using a special holder that can be configured to slow the evaporation rate of each solvent, i.e. the

more volatile solvents are impeded more and some solvents such as water need no restriction. The holder is then placed in the controlled conditions of a Genevac HT Series evaporator, which cycles the pressure over the samples to create a draw, achieving controlled, even evaporation. eXalt holders can accept up to 24 different samples, and 4, 8 or 12 holders can be placed in the evaporator, depending on size.

EPM 46

Genevac Ltd www.genevac.com

INGREDIENTS & CONTRACT SERVICES Ready-to-use components prove beneficial in primary packaging systems for parenteral drugs

The selection of primary packaging components as well as proper preparation before use by the pharmaceutical manufacturer are increasingly important. Primary packaging systems are considered an integral part of the drug product since the drug is in direct contact with packaging components throughout its shelf life.

High-quality elastomeric components deliver: • high performance on drug filling lines for operational efficiency • clean leachable profiles for drug protection • low particle contamination level for patient protection • excellent insertion penetrability and low fragmentation for safe drug application.

Modern elastomer formulations from West meet these requirements. To maintain cleanliness and physical

functionality, component preparation steps such as sterilisation and drying require well-controlled processes.

To support science-based decision making in the effective pre-treatment of elastomeric components, West conducted a study to determine the effects of steam and high-gamma sterilisation methods on the physical and chemical properties of elastomeric closures. The study found that key features of elastomers can be affected by the method of sterilisation.

After gamma irradiation, elastomer material became significantly harder, which can lead to lower performance on filling lines, higher penetrability forces and increased fragmentation risk, plus more potential extractables were found during testing, which may result in increased risk of drug product interactions.

After steam sterilisation and optimised drying, no significant changes were

observed in physical elastomer properties that could affect stopper performance, plus lower number of potential extractables was observed compared with pre-sterilisation levels.

West strongly recommends the use of steam sterilisation for elastomeric components. Westar ready-to-use (RU) steam sterilised components undergo a fully validated washing, sterilisation and drying process to ensure superior functionality from filling line to final drug application.

Westar RU steam-sterilised components may help to: • eliminate capital investments and maintenance costs for stopper washing, sterilisation and drying equipment • minimise preparation time and effort • increase operational efficiency • improve total cost of ownership.

West Pharmaceutical Services, Inc. www.westpharma.com

Harlan CRS and Bertin Pharma sign early drug development agreement Harlan Contract Research Services (CRS) and Bertin Pharma have announced a strategic partnership to offer a comprehensive package for early drug development. Under the agreement, the companies will offer a wider range of drug discovery and translational medicine services, including expanded profiling and molecule testing, especially in the context of regulatory studies.

Through the alliance, Harlan CRS will strengthen its drug discovery and translational medicine offerings utilising Bertin Pharma’s expertise in immunology and biomarkers.

“The new agreement benefits us both strategically and scientifically,” said Ciriaco Maraschiello, director of strategic initiatives and director of drug discovery and translational medicine at Harlan CRS. “Working together, we will provide the pharmaceutical industry with the best team of scientists to increase the likelihood of success for new generation drugs.”

“PharmImmune, our joint offer with the French Alternative Energies and Atomic Energy Commission (CEA), is the perfect example of an innovative tool that we will be able to better utilise through our agreement with Harlan CRS,” said

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Pascal Clayette, head of the ImmunoPharmacology department at Bertin Pharma.

Harlan Contract Research Services www.harlan.com/crs Bertin Pharma www.bertinpharma.com

INGREDIENTS

News

Biotec elects replacement CEO Dr. Fiona Withey has been promoted to the position of CEO at Biotec Services International. Dr. Withey joined Biotec’s business development team in 2007 after gaining a PhD in Biochemical Engineering from Swansea University, which was followed by 12 years working in the pharmaceutical outsourcing sector.

In 2008, Dr. Withey was appointed to the main board of directors as business development director. She played an instrumental role in the company’s management buyout in 2010 and since February 2012, she has headed up the operations team as operations director during a period of very strong growth in the business.

Dr. Withey will be responsible for starting a new stage of Biotec’s international development plan, which includes expanding its US operation, continuing to develop its client base internationally and to build further on its position as a leading worldwide provider of temperature controlled pharmaceutical services.

Dr. Withey replaces Keren Winmill who, after four years as CEO of Biotec, is moving to the role of non-executive director and advisory board chair.

On her appointment, Dr. Withey said: “I’m delighted to be taking over the reins as CEO. Keren has been an exceptional leader during the past four years; under her direction, Biotec has become a world-renowned name for quality and flexibility in our industry.

Today, our business supports more than 100 clinical and commercial projects for over 75 customers, across 60 countries. I’m very keen to build on this by continuing to develop the services for our existing customers and to grow more and more partnerships worldwide.”

Headquartered in South Wales, UK, Biotec Services International delivers efficient solutions for the packaging, distribution, transport and storage of temperature controlled pharmaceutical products, including regenerative and cell-based therapies, in over 60 countries, working with virtual right through to blue chip international pharmaceutical companies.

In recent years, Biotec has achieved international growth in both the US and Israel. It has opened a new processcentric operations facility and the company was awarded the ‘Best International Business in the UK’ by the British Chamber of Commerce.

Biotec Services International Ltd www.biotec-uk.com

Almac expands Asia Pacific operations to cater for trials of any size or complexity Clinical services and technologies capabilities have been expanded by Almac to include on-the-ground leadership as well as technical, project and operational resources in Asia. The company has established regional hubs in Singapore and Japan to better enable the industry’s growing need to conduct clinical trials in Asia and/or manage global trials from the region. Local teams apply insights gained from Almac’s experience managing more than 10,000 trials around the world to design, implement and manage drug supply strategies and efficient technology solutions throughout the life of the study.

“From protocol to patient to kit destruction, Almac delivers high quality, flexible and cost-effective solutions that enable a more comprehensive approach to trial supply management,” said Alan Armstrong, CEO, Almac. “No one else can provide the global scale, scope and reach required to optimise sponsors’ R&D investments across every facet of the supply chain within Asia or around the world.”

Providing expert and responsive service is essential for all trials but particularly those managed from or within Asia. Sponsors must be able to navigate technical, logistical and clinical complexities from trial start-up through to supply and patient management.

Almac’s local teams support studies of all sizes and degrees of complexity, helping sponsors to achieve time-saving efficiencies, reduce costs and improve trial outcomes. Services are augmented

by a secure, web-based interface to monitor trial execution anywhere in the world, multi-lingual technical and project teams and an in-house 24 x 7 x 365 hotline connecting site staff to on-call clinicians and unblinding specialists. By positioning operational resources within the same time zones as where trials are executed, Almac is able to resolve issues in less than 24 hours, which in turn eliminates communications delays and improves patient care.

Almac is strengthening its Asia Pacific offerings by establishing a new secondary packaging facility in Singapore that will open by the end of 2014. Through this facility, the company will better enable just-in-time supply management and support drug pooling strategies, which further optimise the supply chain, minimise wastage and reduce costs.

“With 15% of all clinical trials conducted in Asia, it’s imperative that we provide localised service and support to our clients,” continued Armstrong.

“We’ve long managed clinical trials on a global basis, but there’s now sufficient critical mass that requires we establish dedicated resources in the region. I’m pleased that our international expertise and global capabilities are now even more accessible to sponsors in this critically important part of the world and look forward to opening our new packaging facility later this year.”

Almac Group www.almacgroup.com

US packaging site expands Packaging Coordinators, Inc. (PCI) has completed the planned expansion of its packaging facilities in Rockford, Illinois, US. The Rockford site is one of three locations in the US and the facilities expansion was designed to accommodate continued business development in its contract packaging services.

PCI converted underutilised space to further support its expanding packaging operations, adding 1,858 m2 for secondary and tertiary packaging. The additional production capacity will enable continued growth in operations such as cartoning, overwrapping, heat seal carding and compliance prompting packaging as well as supporting packaging for biotech delivery forms such as secondary packaging for injectable vials, syringes, devices and transdermal products. The packaging operations support both commercial operations as well as large-scale clinical studies.

In addition to packaging of commercial medicines, PCI provides clinical packaging services for investigational medicines at the Rockford location, supported by on-site storage and distribution services, facilitating global logistics for clinical studies. In December 2013, PCI announced a new 8,640 m2 storage and EPM 48

distribution site for investigational medicines, currently forecast to be in operation in August of this year. The clinical services expansion complements investments in PCI’s UK operations, most recently construction of a storage and distribution facility near Cardiff, Wales.

“The facilities expansion we have undertaken in Rockford is the latest in a series of investments we have made to enable continued growth and at the same time continued provision of the extraordinary service our customers have come to expect from PCI,” stated Bill Mitchell, president and CEO at PCI. “We are committed to providing an unparalleled customer experience with our clinical and commercial services and those services require world-class facilities.”

Packaging Coordinators Inc. www.pciservices.com

INGREDIENTS

News

UK high capacity manufacturing facility ready for action following successful validation Aesica’s high capacity manufacturing facility has been validated for commercial production; $45 million (€32.4/£27 million) has been invested at its Queenborough, UK, site.

With the completion of this new facility, Aesica has expanded the commercial production of a solid dose medication used in treating one of the world’s most common lifestyle diseases — Type 2 diabetes in adults. The solid dose product has global sales and is set for worldwide export.

The purpose-built facility is capable of producing in excess of 1 billion tablets per annum and, designed with future

expansion in mind, it is expected the facility will more than double its current capacity to produce over 2.5 billion tablets a year on expansion.

The facility provides a 929 m2 expansion to the existing Queenborough site and has a dedicated workforce of 55 technicians. This will increase to 100 when expansion plans are completed.

The new facility is an advanced unit that contains highly technical and specialist equipment including spray granulators, coaters, tablet presses, powder handling systems and large capacity blenders.

Dr. Robert Hardy, CEO of Aesica Pharmaceuticals, commented: “The validation of this facility for commercial production is a major milestone for the company and brings to fruition what has been a significant investment. Aesica is

already a major exporter of finished dose products and the investment in this facility reflects the continued growth in export demand. This state-of-the-art facility will allow us to manufacture a high quality product used to treat one of the world’s most prevalent diseases and has the capability to double its capacity in the future, representing an expanding revenue stream for Aesica.”

Aesica Pharmaceuticals Ltd www.aesica-pharma.com

Croda celebrates EXCiPACT double Two achievements in relation to EXCiPACT — the voluntary scheme that reduces the audit burden in the pharmaceutical industry by providing independent third party certification of manufacturers, suppliers and distributors of excipients — are being celebrated

by Croda.

In the same month in which Croda joined the first few companies to be awarded the prestigious EXCiPACT Certificate, Croda’s head of global quality assurance Iain Moore was singled out as a “leading light” in driving EXCiPACT forward in a speech by Frank Milek, chair of The International Pharmaceutical Excipients Council Europe at its annual seminar in Cannes. “Iain has been involved right from the beginning,” said Milek. “The time and the empathy Iain invested into this project was a major contribution to make it work. I do not think to exaggerate Iain’s merits when I say that EXCiPACT would not have happened or would have established much, much later without his engagement into this project.”

Croda’s first EXCiPACT certification covers ingredients manufactured at Rawcliffe Bridge in the UK. This achievement is part of a global programme to gain accreditation at the six Croda sites that supply pharmaceutical excipients. “This achievement is a real win-win for Croda and our customers,” commented Sandra Breene, president of Croda’s Consumer Care business in Europe. “It reduces the audit burden on both sides whilst maintaining confidence in Croda’s compliance to the demanding standards of the pharmaceutical industry.

The certificate assures our customers that Croda manufactures and distributes pharmaceutical excipients to EXCiPACT GMP standards. It is a measure of excellence in quality and an assurance for our customers that they are always in receipt of material of the highest standards.”

Croda says its proactive commitment to EXCiPACT provides a reinforcement of the company’s dedication to quality and customer support.

Croda www.croda.com/healthcare EPM 50

INGREDIENTS

News

Cobra Biologics and BioCancell to manufacture promising cancer therapy drug Cobra Biologics and BioCancell have announced an agreement to manufacture BioCancell’s BC-821 cancer drug for clinical trials.

BioCancell’s Phase I clinical trial for BC-821, scheduled to commence in 2015, is a continuity of the success of pre-clinical studies that examined the use of BC-821 as a treatment for several cancer indications such as non-smallcell lung carcinoma, ovarian cancer, glioblastoma (brain tumour) and liver metastasis.

Cobra Biologics will provide GMP manufacture of BC-821 plasmid DNA and fill and finish the product in

accordance with aseptic manufacturing procedures before releasing it for clinical trials. Cobra Biologics experienced and expert team has a strong track record for producing high-quality non-GMP and GMP plasmid DNA for preclinical, clinical and commercial supply, operating efficiently and consistently through a platform DNA process. Cobra’s DNA programmes have full regulatory support from a dedicated QA team.

BC-821 is a potential therapeutic product that penetrates cancerous cells and activates the synthesis of DTA under the control of H19 and/or P4 promoter of the target gene IGF2. Both H19 and P4-

IGF2 transcription factors are expressed only in cancerous cells. This doublepromoter method has the potential to reach a large patient population, as patients expressing either of the target genes will be treatable. An international patent application (PCT) for this product was filed by BioCancell in 2008.

Peter Coleman, CEO of Cobra Biologics, commented: “Cobra has been manufacturing plasmid therapeutics and DNA vaccines for more than 16 years and I am delighted that we are able to announce this partnership with BioCancell. Our DNA platform process is based on Cobra’s pioneering heritage in

Biopta first in vitro human tissue assays catalogue

A major development in discovery research has been claimed by Biopta with the launch of a catalogue of assays based on human functional tissues. The catalogue serves to provide the scientific community with ready access to assays that improve the prediction of safety, absorption and efficacy of drug candidates in humans.

Ex vivo human tissue studies play a key part in drug development, providing pharmaceutical and biotechnology companies with a more predictive human model earlier in the development process. Many pharmaceutical and biotechnology companies have, up until now, depended solely on animal models; however, Biopta’s access to fresh functional human biomaterials means that early human tissue testing is increasingly becoming a routine part of preclinical drug discovery.

Biopta has announced that its research has generated a database of over 60 assays in a range of human fresh tissues. Biopta’s database is claimed to be the first to build an in vitro library of human functional pharmacology using intact tissues. Biopta aims to fill the knowledge gap in preclinical testing by providing phenotypically-accurate assays that measure drug responses from healthy and diseased human tissue.

Dr. David Bunton, Biopta’s CEO, said: “The literature on human preclinical pharmacology is unacceptably sparse and too many decisions on early-stage compounds are made without considering translation to human biology. By illustrating the wide range of tissues and functional endpoints that are possible in human functional tissues, we hope to raise awareness that drug discovery can be de-risked at an early stage.”

Biopta Ltd www.biopta.com EPM 51

gene therapy manufacturing and technology development.”

Cobra Biologics www.cobrabio.com

INGREDIENTS

News

Reach Separations collaborates with Evotec on chiral analysis and purification projects A strategic alliance with Evotec will see UK-based Reach Separations provide additional purification and analytical capability to support Evotec’s pharmaceutical and biotech clients worldwide. As part of the deal, the purification specialist will become a technology partner to Evotec and be responsible for providing expertise in small molecule chromatography.

The two companies have developed a working partnership since 2012, which has provided a solid foundation for this official agreement.

The move was initiated by Evotec in a bid to support its expanded chemistry group by further improving the turnaround of chiral analysis and purification on client projects, without needing to make significant investment in additional equipment and facilities.

Located in BioCity in Nottingham, Reach Separations is capable of purifying from mg scale to in excess of 250 g. It will now look after all chiral purification above 0.3 g and 50% of all chiral analysis and purification under 0.3 g for Evotec.

Reach Separations’ technical group is led by technical director Phil Abbott, who

has worked in the pharmaceutical industry for almost 20 years, including several years at AstraZeneca as a separation science group leader.

Peter Ridgway, business development director at Reach Separations, said: “We are delighted to have collaborated with one of the world’s leading drug discovery research organisations. Given the existing scientific knowledge available within the team at Evotec, this deal demonstrates the high level of purification and analytical expertise we are able to bring to such projects.

“To support the increasing workload this new partnership brings, we have invested in expanded laboratory space, taken on more scientists and increased our instrumentation capability, ensuring we are consistently able to deliver not only for Evotec and its clients but for our developing client base as a whole.”

Evotec is a drug discovery and development expert focused on rapidly progressing product approaches with pharmaceutical and biotechnology companies worldwide. Headquartered in Hamburg, Germany, the company has major operations in Abingdon, UK,

Göttingen, Munich, Germany, San Francisco, and Branford, US. Dr. David Hallett, executive vice president of discovery chemistry at Evotec, said: “The team at Reach Separations has considerable expertise in the fields of chiral, reverse phase and normal phase chromatography that will help our in-house team with added expertise and resource.

Evotec’s Dr. David Hallett with Reach Separations’ Peter “By adding Reach Ridgway at Evotec’s UK labs.

Separations to our has a strong track record in the exclusive portfolio of technology pharmaceutical outsourcing sector. The partners, it will allow us to streamline our company already works closely with processes to meet clients’ project chemistry expert Onyx Scientific, milestones even quicker.” providing custom separation for The partnership is well under way with companies in drug discovery and Reach Separations collecting and intermediate environments. delivering samples at least twice weekly to support the Evotec chemistry group.

Reach Separations Ltd This is the latest strategic alliance for www.reachseparations.com the team at Reach Separations, which

Ashfield Commercial & Medical Services redefines healthcare outsourcing to meet challenges UDG Healthcare plc (formerly United Drug plc) has integrated its sales, marketing and medical service offerings within one division to better meet the needs of pharmaceutical clients. The new division, Ashfield Commercial and Medical Services, combines eight service areas under the Ashfield division umbrella, allowing the newly created cross-functional business approach to enhance future client engagements.

The global healthcare environment is increasingly complex and characterised by: an increase in speciality products; greater regulatory control; reimbursement difficulties; healthcare professional access challenges; better informed patients; increased use of technology and media influence and continued pressure on pharmaceutical companies to demonstrate real world patient benefits to justify treatment costs.

Ashfield, as a leading international outsourced service provider for the pharmaceutical industry, is responding to these needs by utilising a partnership approach to bring greater insight, more

flexibility and ingenuity to its services for global clients.

Bringing together highly successful individual business brands including Ashfield In2Focus, Business Edge, Pharmexx, InforMed, Watermeadow Medical, Pharma Marketing Academy and Universal World Events under the Ashfield brand provides even more value to clients through a cross-functional business approach. This enables Ashfield to develop solutions that harness excellence across their areas of expertise and work in partnership with clients to ensure impact, effectiveness and efficiency.

Ashfield’s eight areas of expertise are: Ashfield Commercial; Ashfield Clinical; Ashfield Healthcare Communications; Ashfield Insight and Performance; Ashfield Market Access; Ashfield Meetings and Events; Ashfield Pharmacovigilance; Ashfield Medical Information.

The Ashfield portfolio provides solutions throughout the product lifecycle. In the pre-launch phase,

services include managing investigator meetings and developing scientific communications, through to organising advisory boards and conducting the market research required to develop brand strategy. Once products are approved, Ashfield provides marketing consultancy, designs and organises launch conferences and implements sales force effectiveness programmes to ensure launch success, then delivers sales Chris Corbin, managing director of Ashfield Commercial solutions via Ashfield’s multi& Medical Services. channel field and call centre the industry, healthcare professionals services. In addition, Ashfield provides and patients through our combined the clinical education, patient support expertise and insight, whilst retaining the programmes and medical information ingenuity and energy that our services to ensure patients and companies are known for.” healthcare professionals receive the information and support they need.

Ashfield Commercial & Medical Chris Corbin, managing director of Ashfield Commercial & Medical Services, Services www.ashfieldhealthcare.com / commented: “This transformation of our www.udghealthcare.com business allows us to deliver more for

Seasoned life science industry expert joins Avantor’s board of directors Avantor Performance Materials has announced the appointment of JeanPaul Mangeolle to its board of directors.

Mangeolle’s extensive experience includes a long career with Millipore, a global supplier of materials for the life science industry. Mangeolle served in various executive leadership roles within Millipore prior to and following its acquisition by Merck KGaA. Most recently, Mangeolle oversaw Merck Millipore’s $1.3 billion (€0.95/£0.78 billion) Process Solutions business. Prior to that time, he served as president of the $1 billion (€0.73/£0.6 billion) Bioprocess division of Millipore and at various times held senior roles within the company’s sales, marketing and supply chain functions.

Mangeolle also served as vice president of worldwide operations for Mykrolis, a developer, manufacturer and supplier of liquid and gas delivery systems, components and consumables, which has since merged with Entegris.

“Jean-Paul offers a wealth of experience in the life science and speciality chemicals space,” said Richard White, COO and interim CEO of Avantor. “Our management team will benefit greatly from the unique insight that Jean-Paul has developed over his long career.”

“We are committed to finding the best and brightest minds to advise us as we further establish Avantor as a global leader in performance materials and chemistries,” said Raj Gupta, chairman

of Avantor. “In Jean-Paul, we have found an ideal partner, with the industry knowledge and business acumen needed to support us as we pursue our aggressive growth objectives.”

“Avantor offers proven, respected brands that make us a strong player in the pharmaceutical and laboratory markets,” said Matt Holt, managing director of New Mountain Capital, which owns Avantor. “Jean-Paul’s experience in the life sciences field will be critical as we work to enhance our presence in this area, capture market share and meet our short- and long-term growth objectives.”

Mangeolle holds a Master of Science degree in Chemical Engineering from the University of Montpellier, France.

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Avantor Performance Materials, Inc. www.avantormaterials.com

INGREDIENTS

News

Latest formulation optimisation programme accelerates timelines by 50% Quotient Clinical has commenced its 50th RapidFACT (Rapid Formulation development And Clinical Testing) programme — a significant milestone in the development of this service.

RapidFACT was first developed in 2008, with the goal of transforming the processes by which drug product formulations are optimised.

This service has now been proven to accelerate programme timelines by at least 50% and deliver significant associated cost savings.

This has been achieved by the colocation of real-time GMP manufacturing and clinical testing under Quotient’s Translational Pharmaceutics platform, which enables formulation selection to be underpinned by emerging clinical data.

RapidFACT has been successfully deployed in early development and lifecycle management programmes to develop oral, inhaled, dermal and ocular drug products. These programmes have principally focussed on optimising drug products for once- or twice-daily dosing or on addressing problems related to poor solubility. RapidFACT studies have been commissioned by customers ranging from large pharmaceutical organisations to small biotechs in the US, Europe and Japan.

Mark Egerton, CEO of Quotient Clinical, commented: “RapidFACT was launched in response to the challenges our customers told us they were confronting in their development programmes. We are pleased that the potential benefits we identified in 2008 have translated into real timeline reductions and cost savings in all of our RapidFACT programmes. Ultimately, this approach is helping our customers to address many of the R&D productivity issues prevalent in the industry today.”

Quotient Clinical www.quotientclinical.com

BioOutsource joins forces with Glythera to expand ADC characterisation capabilities Amplifying its position in antibody drug conjugates (ADCs) characterisation, BioOutsource has announced a partnership with Glythera Ltd, an emerging biotechnology company based in Newcastle-upon-Tyne, UK, which specialises in the development of next generation biotherapeutics through the application of its proprietary linker and stable glycan technologies.

BioOutsource CSO Daniel Galbraith commented: “Building on our position as a leader in biological characterisation of monoclonal antibodies, ADCs represent an exciting development that will enhance the performance of a wide range of therapeutic products. We are delighted to partner with Glythera to characterise their ADC product in development as we believe it holds considerable promise.”

Glythera COO, Dr. David Simpson, highlighted the value of the collaboration: “We are delighted to have the opportunity to work with BioOutsource on their ADCs characterisation as it is an area where our linker technologies offer significant benefits. This partnership demonstrates recognition of these powerful capabilities and we look forward to working with BioOutsource on this exciting project.”

BioOutsource Ltd www.biooutsource.com EPM 53

INGREDIENTS

CHOOSING A LAB SERVICES PARTNER In today’s dynamically changing environment, innovation and cost efficiency in drug development is crucial; costs of R&D are growing aggressively with an average investment of $1.3 billion required to successfully initiate a new drug to market1 and an average 12 years to bring a new molecule from laboratory to approval. Furthermore, approximately 1 in 5,000 candidates entering preclinical testing make it to market2. Drug development timelines are under constant attack with speed to market paramount to success. Continual internal and external pressures mean traditional approaches to drug development are difficult to sustain and more and more pharmaceutical companies are relying on outsourcing to achieve their goals.

Analytical testing is one area where pharmaceutical companies look for expert support from a third party. The process of testing and packaging is a niche, technically specialist service, requiring state-of-the-art equipment, quality assurance and extensive expertise. When selecting an outsourcing partner, a company must conduct extensive research to ascertain that their chosen partner has the expertise and experience to support their drug development requirements and meets the appropriate regulatory obligations.

ABOUT THE AUTHOR: Jane Sanderson, executive director global laboratory services, Packaging Coordinators, Inc. Sanderson serves as the director of laboratory services for PCI’s North American site located in Rockford, Illinois, after relocating from PCI's UK site located in Hay-on-Wye, Wales. She previously headed up AndersonBrecon’s European laboratory services and offers extensive experience in laboratory services and analytical development.

Prior to her tenure with PCI, Sanderson served as laboratory operations manager for the UK laboratory services of Cardinal Health (Catalent).

Selecting the optimal outsourcing laboratory can provide benefit both in expediting the development process as well as reducing potential risk to the overall development timeline. In selecting a partner laboratory, the drug company needs to qualify the laboratory’s breadth of services, experience and expertise. High performance laboratories can bring significant insight and knowledge from their collective experiences to benefit the drug company’s specific programme.

These insights are invaluable in overcoming the hurdles common to drug development. Laboratories physically located adjacent to other services, such as manufacturing or packaging sites, can provide additional benefit in reducing risks inherent in shipping test samples around the globe.

Outsourcing to offsite laboratories is often the chosen method; however, with shipping costs rising as well as drug transportation regulations becoming more stringent, the conveying of drug samples can present unnecessary risk. Not only is there a potential timelines extension to account for transit time, there is also the risk that samples are not representative of the batch owing to differences in shipping and storage conditions. As a result, outsourcing to offsite analytical laboratories can increase both cost and lengthen project timelines.

Many of the challenges encountered during this outsourcing process can be alleviated by the selection of a partner

that can manage the entire continuum, from analytical and clinical packaging to commercial packaging requirements, under one roof.

Choosing the right supplier is about more than comparing product and services or price.

Ensuring that business needs and project objectives are met is vital and therefore selection of one, carefully targeted partner can deliver a wealth of benefits.

Trust and expertise The relationship built during a strategic partnership benefits both sides.

Outsourcing partners work hard to become an extension of your own team, utilising experience and drawing on

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learned best practices to deliver the optimal results for both businesses. The experience gained working with a variety of clients and projects ensures a consultative approach to developing customised solutions, working together to alleviate risk and adding value across the whole project lifecycle.

Opinion

Regulatory Affairs HARMONISATION CHALLENGES IN THE EU This issue’s contribution comes from Dr. Paolo Biffignandi’s colleague Dr. Parvinder Punia, a senior regulatory affairs manager at pan-European regulatory affairs organisation 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 (EMA) 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.

Speed to market When using a supplier with these extensive capabilities, speed to market is greatly accelerated. Turnaround times are reduced as there is no need to factor transportation time for offsite analytical testing into the project.

It is not only in transportation that efficiencies can be made. Qualifying a new supplier can be time-consuming; carrying out site visits and audits can add delays to already tight project timelines. Using one pre-approved facility for regular projects promises accredited facilities that are trusted and maintained to an agreed standard.

By using one expert team, complexities can be speedily identified and resolved and adaptations that may be required to the project design can be expedited quickly and at a lower cost. Using one supplier will also guarantee the consistency and accuracy of analytical methods and results, meaning that further delays are avoided by transference from another party.

Leveraging costs and expertise In order to retain competitive advantage in the aggressive pharmaceutical market, companies need to address their strategic direction. Outsourcing has the potential to deliver extraordinary business value and additional operational efficiencies above and beyond cost savings.

Utilising a company that has laboratories in different geographical locations can be beneficial when looking to enter several markets. Choosing a partner with knowledge and experience of a chosen region as well as the ability to easily manage the internal transfer of drug product and analytical methods can ensure significant savings.

Costs are also lowered in areas such as shipping, staffing and other business

overheads; more and more companies are realising exceptional benefits from leveraging global expertise and talent in all areas of their projects.

Reducing risk The integrity of a drug is paramount throughout all stages of a project.

Reducing risk in all areas is vital to maintain the quality and success of the drug development process. By utilising one supplier, risks are significantly mitigated through fewer opportunities for error and variation during transportation, document and method transfer and communication. Furthermore, having one supplier ensures continuity across the project with one dedicated project manager and team.

Conclusion With pharmaceutical companies increasingly looking to improve their time to market while reducing costs and maintaining their competitive advantage, outsourcing enables companies to leverage the global marketplace and drive the greatest profit.

The success of a project and the level of benefit achieved are highly dependent on the outsourcing partner’s ability to continually deliver at a high level and maintain the trust of its stakeholders, placing their interests first and offering quality advice, unrivalled expertise and measurable added value.

Choose a partner carefully and you will realise faster and more cost-effective time to market.

References 2 Oct 2012: Matthew Herpers 2012, The Truly Staggering Cost of Inventing New Drugs.

2 www.medicinenet.com, Drug Approvals — From Invention to Market ... A 12-Year Trip.

1 Forbes

The EU directive, as updated in 2005, had many objectives and one of them was to ensure that the agencies harmonised medicines from one county to another. Harmonisation can be seen in several ways but is for the most part divided into two main subject areas: harmonisation of opinion and harmonisation of documentation. Both pose challenges and this is usually rooted in local requirements and culture.

From an opinion perspective, experts are drawing on experience and technical expertise that is limited to their own regulating experts. One regulatory body’s experts may not have the same experience as another. The clinical area is usually the most challenging and smaller agencies rely on external experts to fill these gaps. Furthermore, medical culture also varies significantly. One therapeutic area that has evidently differing opinions is oncology. Cancer treatments differ greatly depending on which physician you ask and what medicines are considered acceptable in first and second line therapy. The difference is so wide that some countries in the EU do not even hold active marketing authorisations (MAs) for some oncological products that may be used as standard in another. Therefore, the generic licensing of such products provides an unharmonised approach.

The challenge then, is to change the medical culture of the territory. It would not be possible to approach an agency with such generic MAs if the doctors are not habitually prescribing it. For a generic to have success, the manufacturer would have to invest heavily in marketing, which is commercially unfeasible as generics rely on an established market from the innovator. So, in theory, although a generic is licensable in a territory where the originator never was, as part of the principles of the EU harmonisation recognition, the practice is a lot more complex.

Opinions also vary with regards to quality assessment. There are many examples every month where agencies may differ in opinion on, for example, safe limits of impurities or opinions on safe processes. Although during a decentralised procedure (DCP) the reference member state (RMS) leads and most usually the concerned member states (CMS) will affirm that opinion and may or may not have additional comments, there are some recent examples where one agency

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would particularly disagree with the opinion of the RMS or vice versa. In one such extreme example, a very opinionated assessor asked the RMS to rethink its ideology of the assessment.

The principles now recognise that an agency must share data with another agency but in practice this is not happening. Some of the original data is so old and no longer available. Paper versions are not archived and the original assessments are no longer accessible. This poses a barrier for generics to bridge data where an agency never assessed the originator.

The other area of huge complexity and disharmony is the documentation. The FDA’s International Conference on Harmonisation (ICH) standardised requirements and the electronic common technical document (eCTD) standardised format but content still remains a matter of opinion. In many complex development areas, the guidelines are vague or outdated or even non-existent. This leads to different interpretations of what is a safe, efficacious medicine manufactured to the highest quality.

Lastly, intertwined with the opinion factor are the age-old disagreements on summary of product characteristics (SPCs). The harmonisation group at the EMA has worked laboriously to bridge this gap, but there are still frequent disagreements on approved indications, posology and safety statements. The generic industry suffers immensely through this discord of opinion. Old medicines were licensed nationally and one agency did not know what the other agency was approving, and now the generics suffer the consequences.

However, it can also be viewed as a tactically clever ploy by innovators.

Differing agency opinions mean that to license a generic using the correct EU approach, the harmonised procedure (i.e. DCP or mutual recognition procedure (MRP)) can be prolonged or even referred to the EMA owing to the discussion of finalising SPC texts.

Does this not lead to the sense that actually, harmonisation does not appear to be happening? The experience of two decades has been gradually catching up with the regulators and the regulated.

Harmonisation only began in the 1990s and even then the approach was rather ad-hoc. Nowadays, for a license to go into multiple EU territories, all agencies must work together towards a uniform opinion.

INGREDIENTS

Showcase

DRUG DELIVERY Phillips-Medisize wins supply contract for Sanofi injection pen components Phillips-Medisize has signed a supply agreement for insulin pen components with Sanofi, a leader for diabetes treatment. As a result, injection pen component production at the plant in Kontiolahti, Finland, has been expanded with an automated production line.

Given the successful production by Phillips-Medisize of insulin pen components for many years, this new project was assigned to the Kontiolahti plant and underlines the long-term partnership between Phillips-Medisize and Sanofi. The new pen is an easy-touse disposable pen for the administration of lixisenatide. The finished device is made for the Japanese market and meets the stringent quality demand from that country. Phillips-Medisize has fulfilled the manufacture requirements owing to its premium expertise in assembly technology. The manufacturing involves

injection moulding technology, assembly and tray handling robots, various measuring and testing systems as well as pad printing.

The complex and highly automated assembly line was planned and installed

by Phillips-Medisize and includes multiple camera inspection points in the process. The company also built the required moulds, which were principally designed and produced in the company’s in-house tool shop. PhillipsMedisize implemented the project, including all validations required, and delivered validated product in less than 12 months. The final pen assembly will be launched by Sanofi in Frankfurt, Germany.

Phillips-Medisize president and CEO Matt Jennings said: “This agreement confirms our in-house tooling and automation expertise combined with excellent project management

capabilities are highly valued by our customers. We will continue to develop our competency to offer them an even quicker service for their drug delivery device projects and are delighted to contribute to the rapid growth of the Sanofi diabetes treatment business.”

In February 2013, Phillips-Medisize added another 6,000 m² capacity to its

Finnish facility. The expansion was driven by new opportunities the company has been awarded as well as to support increased global demand for devices with precise dosage drug delivery requirements.

Phillips-Medisize Corp www.phillipsmedisize.com

Eveon and Leti mark milestone in fabrication of bolus-type micro-pump Eveon and CEA-Leti have demonstrated liquid-pumping for smart drug delivery in the bolus mode using a silicon-based micro-pump fabricated with a standard MEMS process.

This is claimed to be the first functional micro-pump integration using the MEMS standard process on Leti’s 200 mm line.

It is a result of FluMin3, Eveon and Leti’s three-year joint-development project to produce an automatic drug-delivery system integrating a MEMS micro-pump that reduces patient discomfort by delivering medicine with very high accuracy, minimal loss as well as high flow rates.

FluMin3 is a major R&D programme supported by the Rhone-Alpes competitive cluster MINALOGIC in collaboration with CEDRAT TECHNOLOGIES and IMEP-LAHC, the Institute of Microelectronics

Electromagnetism and Photonics and Microwave and Characterization Laboratory.

The micro-pump is based on core technology initiated by Eveon and IMEPLAHC. The pump demonstrator is made from silicon wafers, which include a thin deformable membrane sealed over a fluidic cavity and fluidic valves determining inlet and outlet. A dedicated electromagnetic actuator developed by CEDRAT TECHNOLOGIES shapes the membrane.

First fluidic characterisation of this device showed very promising pumping results with typical water-flow rates of 12 ml/min without any counter-pressure and up to six ml/min under 1 bar counter-pressure. These results surpass the performance of state-of-the-art commercial micro-pumps, the typical water-flow rate capacity of which is six

ml/min without any counterpressure and two ml/min under 0.5 bar counterpressure.

These encouraging results already match bolus-mode injection requirements. In addition, new designs under development by Eveon and Leti are expected to improve fluidic performances. At the same time, MEMS flow sensors designed to be finally integrated in the micro-pump have been fabricated and used to achieve an accurate liquid dosing using microdiaphragm pumps with a dosing error below 5% for different counter-pressures.

Eveon, which coordinated this project, and Leti are continuing their work to stabilise relevant MEMS processes before industrialisation and to integrate

MEMS sensors inside the micro-pump to demonstrate an automatically controlled, smart drug delivery device.

Eveon www.eveon.eu CEA-Leti www.leti.fr

West expands Dublin site after securing significant injectable device programme Tech Group Europe, a medical device manufacturer based in Mulhuddart, Dublin, Ireland, serving the pharmaceutical and medical industries, is expanding its Dublin manufacturing and development centre. The expansion is the result of securing a significant programme with a leading global pharmaceutical partner. Tech Group Europe is a subsidiary of West Pharmaceutical Services, Inc., Exton, Pennsylvania, US. The programme involves the manufacture, assembly and decoration of a complex injectable device for the diabetes market and will go into fullscale production in 2015. The device will be shipped to the customer’s European filling site for final assembly.

The new programme will require the

expansion of the existing Tech Group Dublin site by 1,115 m2.

Don O’Callaghan, vice president and general manager of Tech Group Europe, said: “This expansion reinforces the commitment to developing the Dublin capability as part of an ongoing, longterm investment plan.

“This first phase in the expansion comes about as a result of an exciting win with a leading global pharmaceutical partner in the fastgrowing diabetes market and further strengthens West’s position as one of the world’s leading manufacturers of complex medical devices for the pharmaceutical market.”

Tech Group Europe is focused on supplying engineering and manufacturing services for complex

drug delivery devices and diagnostic solutions for the pharmaceutical and healthcare sectors. The facility was established in Ireland in 1998.

West works with the leading multi-national pharmaceutical companies with products that help facilitate safe insulin administration for patients around the world. The company manufactures components for insulin pens and glucose monitoring systems at facilities in Arizona, US. In addition, West manufactures plungers and lined seals

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for insulin pen cartridges from facilities in Denmark, Germany and the US. West Pharmaceutical Services, Inc. www.westpharma.com

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Gerresheimer develops interface for integration of glass syringes in autoinjectors The development of autoinjectors generally involves the integration of a pre-filled glass syringe into a plastic drug delivery device — a major challenge owing to the different tolerances of both materials.

Gerresheimer has now filed a patent application for its Gx G-Fix standard adapter to provide precise and reliable positioning of syringes and needle shields.

Drug delivery devices play an increasingly important role in the market for pharmaceutical products. A rising number of patients suffering from chronic diseases such as rheumatism, arthritis or Parkinson’s inject their drug themselves with the help of autoinjectors. Self-administering drugs in this way obviates the need for regular visits to the doctor, is more comfortable and relieves the healthcare sector. Most autoinjectors contain two main modules: the injector itself and the prefilled syringe. Both modules are combined in one assembly, which is specified by the pharmaceutical company and supplied to the market in one piece. This approach is important as medical

technology products are subject to high quality standards and must be reliable.

In practice. However, the production of autoinjectors has to deal with the tolerance requirements of two entirely different materials: the device is made of plastic while the prefilled syringe is made of glass.

Gerresheimer developed a solution that allows an easy integration of syringes in drug delivery devices and has now applied for a patent. Andreas Schütte, member of the board of Gerresheimer and head of the company’s Plastics & Devices division, explained: “When we developed Gx GFix, we pooled our comprehensive intelligence in the area of prefilled glass syringes and polymer-based drug delivery devices and created an interface that works without complex twocomponent injection moulded parts or sophisticated assembly processes.”

Attached to the syringe shoulder, the plastic standard adapter provides a precisely defined interface to the device.

In the autoinjector, Gx G-Fix has several functions. First, the adapter connects the syringe with the device.

Before, the high-dimensional tolerance of the glass syringe allowed only marginal control of the injection needle’s position in the front opening of the autoinjector. As Gx G-Fix is specifically adapted to the autoinjector, it allows accurate needle positioning and significantly higher control of the injection process.

Second, the syringe is well protected from breaking. Conventional products coupled the syringe with the finger flange. When triggered, the structurally sensitive flange is subjected to a lot of pressure and can easily break. With Gx G-Fix, however, attaching the syringe at the sturdier shoulder has minimised the risk of breakage substantially.

Moreover, Gx G-Fix allows a precisely defined distance to the rigid needle shield (RNS). As most autoinjectors are equipped with long 1 ml syringes, tolerances often result in a repositioning of the RNS either towards the front or towards the rear, which means that RNS removal requires autoinjector caps with a complex design. This problem can be solved by using a variation of the adapter that connects with the RNS.

With a clearly defined position, RNS removal no longer requires a specific design of the injector cap.

The Gx G-Fix is assembled as part of the ready-to-fill syringe processing at the syringe manufacturer’s facility. Device integration and RNS positioning with Gx G-Fix can be used individually or in combination. Plastic syringes can also be easily fitted with the adapter.

Autoinjectors with Gx G-Fix are therefore suitable for plastic and glass syringes and can therefore be used for a variety of drugs. This does not require any changes to the customer’s filling station.

Gerresheimer AG www.gerresheimer.com

Hapten Sciences and Particle Sciences partner to bring poison ivy product to clinical trials Drug Delivery CDMO Particle Sciences has partnered with Hapten Sciences to progress Hapten’s lead product into the clinic. The product is a vaccine developed to lessen or eliminate contact dermatitis from poison ivy, oak and sumac exposure. According to Raymond Hage, CEO of Hapten Sciences: “Experts report that 50 to 85% of the population in the US is sensitive to urushiol and, when adequately exposed, will suffer an

allergic reaction. Aside from the actual physical discomfort, these reactions cost the federal government and private business millions each year in lost work days. For instance, in the western US, annually, about one third of US Forest Service firefighters will leave a fire as a result of exposure to poison ivy, oak and sumac.”

Particle Sciences will be manufacturing the Phase I/II materials of Hapten’s first

human studies scheduled for 2014.

Mark Mitchnick, CEO of Particle Sciences, said: “We have worked with Hapten in the past and are delighted to be helping them bring this important product to market. This a great use of our sterile solution manufacturing capacity: producing and filling a novel product along with providing complete analytic (service info) and release testing (service info). We have steadily

expanded or cGMP manufacturing capacity with a focus on sterile and otherwise challenging products and have several in the queue already for early 2014.”

Particle Sciences, Inc. www.particlesciences.com Hapten Sciences, Inc. www.haptensciences.com

Drinking straw avoids need to swallow bitter pills The XStraw, a new product from the company Dose Sipping Technology (DS Technology), makes taking medicine much more pleasant for children and the elderly. Many children pull a disgusted face when they have to take bitter-tasting medicine and elderly people who have trouble swallowing can find taking oral medicine a challenge. The XStraw drinking straw makes medicine taste much better.

XStraw is a drinking straw filled with pellets. The patient cannot taste the tiny balls in the straw and hardly feels them.

They can enjoy their favourite drink with the XStraw while taking the exact amount of medicine prescribed and not experience the unpleasant taste.

The drinking straw is filled with exactly the required dosage on fully automatic systems. Thanks to pre-dosing at the manufacturer, incorrect dosages are avoided. While the patient is drinking, a control filter moves upwards, which ensures that the right amount is being

taken and there is no danger of any being spilt.

With the XStraw, nobody has to sit coaxing a child into taking medicine or holding a spoon for an elderly patient.

The very simple use and individual selection of type of drink, and therefore of taste, makes the drinking straw very popular with patients. The XStraw is also available printed with brand name or dosage upon request for marketing purposes.

Thanks to perfectly matched components made of polypropylene and an air-tight packaging in an aluminium blister, special storage conditions are not required.

DS Technology is the contact partner for the issue of filling licences.

Customers receive comprehensive expertise and support for the development and manufacture of the multi-particulate dosage form (pellets), delivery of the material components, implementation of the production

process by the creation of suitable facilities, arrangement of licensing dossiers and, upon request, contract filling.

DS Technology, as system provider, offers the entire range of fully automated processing facilities for filling the XStraw and individual packaging as well as the cardboard.

DS Technology is a subsidiary of the company Harro Höfliger, an individually designed system solutions provider for the pharmaceutical industry.

Development and serial production is carried out jointly with Raumedic. The system supplier for medical and pharmaceutical polymer subassemblies owns all the necessary systems, tools

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XStraw — for the simple, safe and exact dosage of drugs in the form of pellets. and follow-up facilities for the fully automated production and packaging of the extruded drinking straw and the exactly matched injection-moulded cap.

DS Technology GmbH www.hoefliger.com

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CONTAMINATION CONTROL Helapet are a leading supplier of cleanroom disposables for hospital, pharmaceutical, electronic and laboratory cleanrooms providing solutions for contamination control in critical environments.

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