Pharma May 2011

w w w. p h a r m a - m a g . c o m May/June 2011 ISSN 1746-174X

Volume 7 Number 3

The global magazine for the pharmaceutical and biopharmaceutical industry

Processes & Automation

Continuous Production

PAT/QbD

Slow Progress?

Supply Chain Management Opportunities for Improvement

Green Pharma Losing Steam?

PACKAGING LABELLING Trends, Innovation and Regulation

© 2011 Thermo Fisher Scientific Inc. All rights reserved. PB AD 2011 03.

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Moving science forward

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May/June 2011

CONTENTS For up-to-date news follow us on Twitter (PharmaMag) and join our Pharma group discussions on LinkedIn

Contents FOCUS TOPICS

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Packaging & Labelling

Contributing Companies: Optima Group

Pharma GmbH, Burgopak, MWV Healthcare, Avery Dennison, IHMA, Rieke Dispensing, Thermo Fisher Scientific, Catalent Pharma Solutions and Domino.

Industry experts highlight a range of current issues and technologies shaping the sector.

20

Processes & Automation

Contributing Companies: Gebr. Lödige

Maschinenbau GmbH, Siemens IT Solutions & Services

MAY/JUNE 2011

44

Supply Chain Management: Technology Replaces the Pen

Tim Mohn — Sparta Systems

The author explains why manufacturers are turning to enterprise quality management solutions.

Supply Chain Management: Falsified Medicines Directive: An Opportunity to Enhance the Pharma Supply Chain

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Pvt. Ltd, Thermo Fisher Scientific and Pfaudler.

Pascal Durdu — Zetes

Advice on continuous production processes;

Incoming legislation to increase patient safety also offers a number of

information technologies; mixing and transporting solids in glasslined rectors; and production-scale cell manufacturing.

FEATURES

28

PAT/QbD: A Pharmaceutical Field of Dreams?

Wes Wheeler — WPWheeler LLC and Ken Somers — JK Somers and Associates

A provocative study regarding the industry’s slow implementation of PAT.

32

Green Pharma: Wasting Energy Through Steam Loss

Grant Bailey — Thermal Energy International Inc.

Installing venturi orifice steam traps can save money and reduce CO2 emissions.

34

Green Pharma: More the Merely Green

Leon Wyszkowski — Fisher Clinical Services

Customers and the environment can benefit from paperless operations.

36

Green Pharma: Actions Speak Louder than Words

Yukio Matsui — Astellas Pharma Europe Ltd

Setting ambitious targets for environmental impact reduction can mobilize organizations to make changes happen.

38

Analytical: Feature Films Jo Smewing — Stable Micro Systems

New methods to help pharma manufacturers quantify and analyse the performance characteristics of pharmaceutical film applications.

42

Supply Chain Management: Successful Supply Chains for the Future

Jonathan Betts — Science Warehouse Ltd

The modern supply chain can be a key means of differentiation in today’s challenging pharma marketplace.

May/June 2011

real business benefits.

48

Litigation: Reformulating Intellectual Property Litigation

Claire Bennett and Kokyee Ng — DLA Piper

How will the new IPCC regime affect the pharma industry?

50

R&D: Precompetative Collaboration

R. Arun Kumar — Pistoia Alliance

The author talks to Pharma about the Pistoia Alliance and its aims to improve R&D business processes.

56

Marketing: Managing Events and Meetings Spend

Mark Harris — The TIN/Grass Roots

Managing the meetings and events supply chain in a strictly regulated environment.

REGULARS

05

From the Editor: Have You Got the X Factor?

Corrine Lawrence

The European Outsourcing Awards 2011 — are you a potential winner?

06

Comment: Is Complexity Killing Pharma Profits?

Melvin Jay — Simplicity and Simon Collinson — Warwick Business School

Complexity is an inevitable part of the industry and pharma firms need to view it more holistically.

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Nostrapharmus: Keeping the Supply Chain Agile

Nostrapharmus

Agile techniques may be more appropriate and promising than Lean thinking for the industry’s uncertain future.

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STAFF

Contributors

Innovative

Filtration...

Editor Corrine Lawrence +44 (0) 771 517 7767 corrine.lawrence@via-medialtd.com

Publisher/Sales Director Fred Winsor +44 (0) 1372 364 125 fred.winsor@via-medialtd.com

Editorial Director Kevin Robinson +44 (0) 1392 202 591 kevin.robinson@via-medialtd.com

Financial Controller Catherine Swainson +44 (0) 1372 364 122

Art Director/Production Paul Andrews Tel. +44 (0) 1372 364 126 paul.andrews@via-medialtd.com

General Manager Miranda Docherty +44 (0) 1372 364 125

3M Purification’s new easy to use, disposable, ergonomically designed system for the bio processing industry has been designed for upstream clarification and downstream applications where impurity removal is essential.

• • • • •

Editorial Advisory Board

The Editorial Advisory Board of Pharma comprises a distinguished panel of experts from various parts of the pharmaceutical industry. They review technical manuscripts, suggest topics for inclusion, recommend subject matter and potential authors, and act as the quality control department for the magazine’s editorial content and direction.

Patrick Crowley Vice President Product Line Extensions GSK (US) Enric Jo Plant Director Reig Jofre Group Maik W. Jornitz Senior Vice President Global Product Management, Bioprocess Sartorius North America Inc.

Carlos Lopez Relationship Director Healthcare & Pharmaceuticals Lloyds TSB Corporate Markets

Harald Stahl Senior Pharmaceutical Technologist GEA Pharma Systems

Kurt Speckhals Gino Martini Director, Strategic Technologies Senior Director, Supply Chain Pfizer Inc. GSK (UK) Jim McKiernan Chief Executive Officer McKiernan Associates GmbH Maireadh Pedersen Head of Business Development Quay Pharma

Geoff Tovey Visiting Professor Dept of Pharmacy King’s College Wes Wheeler President, WPWheeler LLC

Ray Rowe Chief Scientist/Prof of Industrial Pharmaceutics Intelligensys/Uni of Bradford

To subscribe

Professionals working within the industries we cover may receive Pharma free of charge on completion of a registration card. Individuals in other industries or countries may purchase a year’s subscription by sending a cheque for £100 made payable to : Via Media UK Ltd by post to: Via Media UK Ltd, Wesley House, Bull Hill, Leatherhead, Surrey, KT22 7AH, UK.

Reduced machine Downtime Ease of Use Minimal product loss Low cleaning costs Reduced operator exposure

Registered Office:

Reduce total filtration costs without compromising quality To find out more about 3M Purification and any of our products, call us or visit us online 0845 602 5237 www.3M.co.uk/filtration 4 www.pharma-mag.com

miranda.docherty@via-medialtd.com

Content/Marketing Manager Claire Day Tel. +44 (0) 1372 364 129 claire.day@via-medialtd.com

Rory Budihandojo Director, Quality Systems Audit Boehringer Ingelheim Shanghai Pharmaceuticals Co., Ltd

The ZetaPlus Encapsulated System

catherine.swainson@via-medialtd.com

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Via Media UK Ltd, 22 Highacre, Dorking, Surrey RH4 3BF, UK. The publisher endeavours to collect and include complete, correct and current information in Pharma but does not warrant that any or all such information is complete, correct or current.

The publisher does not assume, and hereby disclaims, any liability to any person or entity for any loss or damage caused by errors or omissions of any kind, whether resulting from negligence, accident or any other cause. Pharma does not verify any claims or other information appearing in any of the advertisements contained in the publication, and cannot take any responsibility for any losses or other damages incurred by readers in reliance on such content.

Copyright © 2011, Via Media UK Ltd All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical including by photocopy, recording or information storage and retrieval system, without permission in writing from the publisher.

Send permission request in writing to Permissions Department, Pharma, Fax +44 870 487 3469.

Authorisation to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted for libraries and other users registered with the Copyright Licensing Agency, 90 Tottenham Court Road, London W1P 0LP, UK (ISSN: 1742-447X).

May/June 2011

Have You Got the

I

ndulge me as I stray beyond my editorial boundaries into the territory of sales. I may not be able to sell a chicken to a fox, but I will endeavour to show you the chicken, describe its redeeming qualities and suggest that you need it (how am I doing so far?). The chicken, in this case is the 2011 European Outsourcing Awards (EOA), organized

by Via Connect.

As an editor, I receive many press releases, the majority of which tell me — within the first sentence — that the company in question is ‘the world leader’ or ‘a leading xxx’ in its given field. Is this you? It really is astounding, and indeed encouraging, to read daily of the impressive and innovative advances being made in the pharma industry, particularly with partnerships, where limits are pushed to find solutions.

As competition in the outsourcing arena grows stronger, so too does the number and calibre of the EOA nominations.

This, along with the credibility of the judging procedure and the rigorous process of assessing the submissions, has fortified the EOA making it an unmissable opportunity to be recognized and to stand out.

X

FROM THE EDITOR

Factor?

So, who is eligible? Clearly, from the press releases I receive, many of you! Any company involved in marketing, business and technology across the pharmaceutical outsourcing, biopharmaceutical and clinical trial industries can enter. This year, we are delighted to introduce two new categories to the EOA: Most Effective Drug Discovery/ Development Programme; and Outsourcing Executive of the Year. These will replace the Nutraceutical award (The NBT Awards has been launched as a stand‑alone event this year) and the Supply Chain award. The full list of categories can be found at www.europeanoutsourcingawards.com Once you have selected the category(ies) you wish to enter, request an entry pack online or by contacting Miranda Docherty (miranda.docherty@via-medialtd. com). The closing date for receiving nominations is 5 August. You have plenty of time to put your submission together, so I expect you to join us for the EOA gala diner on 26 October, during the week of CPhI/ICSE/P-MEC in Frankfurt… though not wearing a chicken outfit!

Corrine Lawrence Editor, Pharma corrine.lawrence@via-medialtd.com

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8833

COMMENT

IS COMPLEXITY KILLING PHARMA PROFITS? The authors consider whether the pharmaceutical industry needs to radically rethink its approach to complexity.

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For more information

Melvin Jay Founder Simplicity Tel. +44 203 178 3185 melvin.jay@ simplicitypartnership.com Professor Simon Collinson International Business and Innovation Warwick Business School

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harmaceutical giant Novartis dealt a fresh blow to the UK pharmaceutical industry last month when it announced it was likely to close its West Sussex factory. Similarly, Pfizer, AstraZeneca and GlaxoSmithKline have all closed offices or factories during the past few months. These closures can be seen as an attempt by these companies to reduce complexity within their operations.

The Global Simplicity Index (GSI), which was published March 2011, highlights that the pharmaceutical industry is the second most complicated industries in the world. It also demonstrates that geographical diversity is just one of many drivers of complexity and addressing this in isolation will do little to attack the overall problem of complexity in this industry. A more rigorous and concerted attack on harmful complexity is needed.

The GSI is a study of the 200 largest companies in the world, which found these companies are wasting on average 10.2% of their annual profits (EBITDA) each year because of bad complexity.

Developed by Simplicity and Warwick Business School, the study also found that many companies are now too complex to perform at their best and are becoming slower to react to changing economic and competitive forces.

Initially, complexity is no bad thing. As a business grows, it will develop more formal methods for managing people, or add divisions, new processes and strategic initiatives to grow. But, left unchecked, these systems can proliferate and become over‑engineered.

This is what we call the ‘Complexity Curve’ — an inverted U‑shape graph that shows how complexity naturally reaches a tipping point, after which any benefits are outweighed by costs.

With highly technical R&D programmes, strict regulation and sophisticated products it is tempting to argue that complexity is an inevitable consequence of operating in the pharma industry. But if this were true, all pharma companies would have similar levels of complexity. Our study shows a wide variation in the level of complexity between pharma companies, with some of the pharmaceutical giants managing complexity far more effectively than others.

We split the pharma companies into four main typologies depending on their levels of complexity and

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performance: performers, complicators, simplifiers and strugglers (companies failing to cope with complexity). Novartis, Johnson & Johnson, Pfizer and Roche are all ‘complicators’ — identified as companies that have higher levels of value‑destructive complexity than their rivals. Bayer was identified as a struggler, with excessive complexity having a major impact on their profitability.

So why aren’t these companies doing something about it? Perhaps complexity has been placed on the ‘too difficult’ pile. Identifying all of the sources of complexity within a business is not easy (our survey found more than 100!), and knowing how to make the necessary changes to eradicate complexity is even more difficult.

So, how should the pharmaceutical industry address this problem? First, managers need to identify and weed out the value‑destructive complexity in their departments. This requires a better understanding of the processes and activities that add value and those that do not. Benchmarking against competitors can quickly show the company where complexity is highest and most damaging. Once you identify where the harmful complexity is hiding, action plans can be developed to simplify the company.

Second, the management behaviours that cause complexity need to be addressed. People create all complexity in business. Managers need to see how their decisions create complexity and be trained on how to simplify their businesses. Managers should also avoid new sources of complexity from springing up by establishing an evaluation process to test the complexity impact of new initiatives. Finally, managers should identify and nurture the kinds of complexity that add value.

It is important for pharmaceutical firms to view complexity more holistically. Although closing factories and R&D centres will reduce operating costs, it will not be enough to reduce the stifling levels of complexity within the industry. This requires complexity to be reduced in strategy, organizational structure, process and many other areas of business.

Most importantly, it requires a shift in mindset from regarding complexity as an inevitable part of the industry, to seeing it as a major burden on patients, on physicians, on employees and on shareholders that can no longer be ignored.

May/June 2011

May/June 2011

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packaging & Labelling

PACKAGING DIAGNOSTIC REAGENTS WITH CONFIDENCE

As a seemingly inconsequential part of the shipping and storage process, the material used for packaging diagnostic reagents can have a significant impact upon quality. As a commonly used material, glass can pose a significant hazard because it cracks and shatters easily. Plastic has, therefore, been introduced as a viable and safe alternative. When selecting a plastic, it is essential to realize the differences between resin types and the impact that these can have on the purity of the contained reagent. Here, we discuss these different properties and the potential implications that these could have on resulting downstream data.

D

iagnostic companies are facing ever‑increasing pressures to deliver new products safely and efficiently.

With diagnostic reagents as the basis of any experimental protocol, it is essential that they remain highly pure and that the potential for any contamination is minimized. Reagent packaging has commonly taken the form of glass bottles and containers, which have a well‑known mode of failure: they break and shatter. This poses a significant hazard in terms of spilled reagents and exposed sharp edges. More recently, plastic has been introduced as a safer packaging material — it’s resistant to breakage, and plastic bottles are lighter and more durable, making them an ideal alternative to glass.

Plastic Properties

The properties of any plastic used for packaging will affect the type of reagent that can be stored safely. There is a wide range of commercially available plastics and they vary in terms of their chemical composition. The molecular weight of a plastic can range from 40,000 to ≥100,000 kDa. As molecular weight increases, so do the physical (temperature resistance, surface hardness) and chemical resistance properties of the plastic.

Manufacturing plastic bottles and containers from

high molecular weight materials, however, is more challenging. In addition, intramolecular forces can also affect the resulting plastic properties: • S trong intramolecular forces tend to form more crystalline materials, where there is a higher level of order and structure, producing an opaque plastic with good temperature and chemical resistance.

• Weaker intramolecular bonds produce more amorphous materials with less molecular order. These tend to have better clarity, but lower temperature and chemical resistance.

Selecting the Best Plastic

Different plastic resins have varying physical and chemical properties and it is, therefore, important that the correct plastic packaging is used to maintain purity.

Diagnostic reagent packaging is commonly made from three different polymers: • P olyethylene terephthalate (PET) has thin walls, providing a flexible material with an effective O2 and CO 2 barrier. It has a relatively poor water barrier and poor chemical resistance to most solvents and virtually all aromatic solvents. Strong bases will also depolymerize it.

• P olyethylene terephthalate glycol modified (PETG) is noncytotoxic and makes excellent radiation

Figure1: The life cycle inventory of PET in comparison to glass.

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May/June 2011

packaging & Labelling Table 1: Hydrophobic proteins will be more likely to bind to HDPE than PET/PETG, but can adhere to most surfaces in the absence of surfactants.

sterilizable containers. It is clear with thick walls, moderately flexible, and provides an effective CO2 and O 2 barrier. It has greater temperature resistance than PET, but still has relatively poor chemical resistance to most solvents and virtually all aromatic solvents.

• H igh density polyethylene (HDPE) is translucent with an excellent water barrier and is usable across a broad temperature range. It has a relatively poor O 2 and CO 2 barrier, but very good chemical resistance.

Solvents can cause permeation and softening, which is reversible, but oxidizers (nitric acid, perchloric acid, sodium peroxide) will result in degradation of the polymer following extending exposure.

Reduced Environmental Impact

With an increasing concern to maintain a ‘green’ laboratory, more and more users are taking into account the environmental impact of their purchasing decisions.

A 2009 study demonstrates the environmentally friendly aspects of plastic through a representation of the life cycle inventory, from raw material procurement to delivery of the container to the filling line. 1 It includes the amount of energy needed to produce, ship and dispose of the materials, as well as the impact in terms of CO 2 generated, water consumed and weight/volume of waste generated at the end of the packaging’s usable lifespan. In this comparison of PET and glass, plastic requires less energy in the production process than glass, because of the lower temperatures required to process the raw materials (Figure 1). Plastic is also significantly lighter to ship and, therefore, saves on vehicle emissions to provide a more cost‑effective and environmentally friendly method of delivery. The methods used in this study are consistent with those for Life Cycle Inventory as described in the ISO 14040 and 14044 standards. 2

The Importance of Purity

When packaged for shipping or storage, it is essential that the composition of the reagents remains unchanged and highly pure. Any decrease in purity can have a detrimental effect on resulting downstream data,

May/June 2011

potentially rendering results unusable. Once packaged, the reagents are in constant close contact with the surrounding material and the most common factors to decrease purity are, therefore, leachables and extractables. Because all plastic packaging essentially looks the same, it can be easy to overlook their differing chemical composition. Factors such as ash and metal content, and protein binding can also have a detrimental impact on the resulting purity of the contained liquid.

Extractables and Leachables Extractables are released from the plastic into stored liquids following exposure to high temperatures or strong solvents, which can alter its chemical composition and, therefore, represent a “worst case.” Leachables are those chemicals being released under the normal use conditions of the plastic. Furthermore, to help prevent degradation of the plastic from heat, oxygen or radiation, for example, resin manufacturers can use additives.

Bottle grades of HDPE typically include antioxidants and heat stabilizers, whereas PET and PETG contain few, if any. All three resins have an innate resistance to radiation.

Ash Content Ash represents a mixture of inorganic materials trapped in the polymer matrix. To define the ash content of a variety of plastics, the polymer is burned away under controlled conditions, leaving behind any inorganic residue. Metals can be present in the plastic from a number of different sources as a result of catalyst residue in the resin, such as tin and silicon, slip agents (zinc, calcium or magnesium stearate) or the molding and molding machine, which use aluminium, nickel, iron, cobalt or chromium.

Protein Binding Diagnostic reagents commonly contain proteins; it is essential, therefore, to understand the interactions between the stored reagent proteins and the packaging materials. Numerous factors affect protein binding, including pH and protein isoelectric point; temperature; salts; surfactants; and other proteins, and hydrophobicity/hydrophilicity of those proteins.

Protein binding may be greater in solutions of higher

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packaging & Labelling

References

1. w ww.container-recycling. org/assets/pdfs/LCASodaContainers2009.pdf 2. w ww.iso.org/iso/catalogue_ detail?csnumber=38498

For more information

Dan Dwyer Product Development Technical Manager Thermo Fisher Scientific www.thermoscientific.com

ionic strength or with pH levels below the isoelectric point of the protein. Hydrophobic proteins, such as integral membrane proteins or lipoproteins, will be more likely to bind to HDPE than PET/PETG, but can adhere to most surfaces in the absence of surfactants (Table I).

Although glass and plastic surfaces exhibit a similar level of protein binding, there are a number of important differences in the binding mechanism. Protein binding to the borosilicate glass is highly unstable, making it inconsistent and difficult to predict the resulting purity of the reagent. As the protein molecules adsorb and detach from the surface, denaturation of the proteins can occur. Protein binding to the plastic surfaces is more stable, reducing the cycle of adsorption and detachment and thus minimizing the occurrence of protein denaturation.

Conclusion

As demonstrated in this article, plastics are a viable and effective alternative to glass for the packaging of in vitro diagnostic reagents. When selecting a plastic, it is essential to realize the differences between resin types and the impact that these can have on the purity of the contained reagent. Although no plastic will be 100% free from leachables, products from different bottle manufacturers can have dramatically different levels present and it is key that users are aware of which extractables and leachables will be the most problematic to their application. One should only purchase plastics from a reputable source; look for products tested for biological toxicity or made from ISO 10993‑6/10993‑11 or USP <88> Class VI compliant resins; and look for suppliers who use pharmaceutical/medical- and food‑grade resins containing minimal additives.

DISPOSABLES IN PHARMACEUTICAL FILLING AND PACKAGING APPLICATIONS

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For more information

Jürgen Schäfer Managing Director Optima Group Pharma GmbH www.optima-packaging-group.de

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isposable systems are playing an increasingly important role in aseptic pharmaceutical production, and this trend extends to liquid product filling and packaging. There are a number of reasons why this is the case. Biopharmaceuticals have ushered in a number of changes to the filling and packaging process.

Batch sizes are often very small, but the financial value can be very significant. Many of the products are highly toxic, creating the need for maximum operator protection. Any risk of cross‑contamination must be eliminated.

In response to the revolutionary developments in the industry, most systems must be designed to handle a certain variety of products. Cleaning and subsequent system validation can take up to several days. A disproportionate amount of time is spent on cleaning at the expense of system utilization. Single‑use items provide a way of reducing the amount of time and effort spent on cleaning.

On filling systems, disposables are normally used in combination with peristaltic pumps. Disposable tubes are routed through the peristaltic pumps to the filling nozzles, which can also be made of single‑use materials. With this solution, the pumps do not contact the product and do not require time‑consuming cleaning. Elimination of clean‑in‑place (CIP) and steam‑in‑place (SIP) systems also reduces capital investment costs.

In deciding on whether or not to use disposables, system designers assess the trade off between greater flexibility and the long‑term cost of disposables, which can be a significant factor if large quantities are used. Moreover, the filling accuracy of today’s peristaltic pumps cannot match that of time/pressure systems. This may be a significant factor in the

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cost/benefit equation depending on the value of the product being handled.

Peristaltic pumps have a reputation for being very gentle on the product. This is a welcome feature for many delicate, large‑molecule biopharmaceuticals. The effectiveness of APIs remains unaltered following dosing with peristaltic pumps. As well as greater system flexibility, this can be a major factor in the decision to take the disposable option.

Disposable systems normally have interfaces that are bridged with plug‑in connectors. The interfaces must be carefully configured to eliminate potential sources of impurity and contamination.

Disposable technologies are also used in filling and packaging systems to introduce materials via sterile transfer into isolator‑protected areas. The items involved can include syringe plungers transferred in bulk or pharmaceuticals in powder form. The sterile path is created with foil liners and bags that contain the sterile material and are welded together for transfer using a special welding process (Stericon). A welding unit can be a worthwhile investment even in applications where transfer frequency is in the low to medium range, because the familiar Alpha/Beta systems are substantially more expensive than the bag/liner solution. When environmental considerations play a role in the decision, waste accumulation and disposal versus cleaning agent consumption and CIP/SIP energy costs are factors to consider.

In conclusion, even on biopharmaceutical filling and packaging projects, the parameters to consider are too specific to make a general statement about the use of disposables. There can be no doubt, however, that single‑use solutions extend the range of options available for providing solutions that are tailored to the varied needs of the industry.

May/June 2011

GE Healthcare Life Science

Confidence comes with the right interactions.

Join leading scientists from academia and industry at Developments in Protein Interaction Analysis (DiPIA), November 12-15, Boston, Massachusetts, USA. This scientific conference offers opportunities to meet and discuss the latest developments in label-free interaction and stability analysis using Biacore™ Surface Plasmon Resonance (SPR) and MicroCal™ microcalorimetry systems.

Register at www.gelifesciences.com/dipia

© 2011 General Electric Company – All rights reserved.

GE Healthcare Bio-Sciences AB, Björkgatan 30, 751 84 Uppsala, Sweden K11074. First published May 2011.

imagination at work May/June 2011

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packaging & Labelling

PUMP IT UP

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or the effective dispensing of creams and lotions, the pump has provided the ideal solution. Product can be carefully metered and measured to a specific dose; this is more hygienic, less messy and provides accurate control.

More recently, however, the introduction of new formulations has increasingly challenged the traditional pump format. A major requirement for many of these formulations is the need to keep them free from oxygen contact and this has led to a growing requirement for airless dispensing. A noticeable example has been the introduction of sophisticated dermatological emollient creams for a variety of skin conditions.

Such creams are also usually extremely thick and viscous and for this reason unable to self level. With conventional pump systems, product is drawn from the centre of the container, leaving residue clinging to the side that cannot be accessed and is therefore wasted.

Dispenser manufacturers have been seeking to develop new technologies to tackle these issues.

Some systems, such as Airless HVDS (high viscosity dispensing system), use a combination of airless and piston‑up technology to push product up from the bottom of the container. This ensures an orderly and complete evacuation of product, delivering a superior performance compared with standard pumps or follower‑plate‑down systems.

Typically, these systems can achieve particularly high evacuation rates of product — as much as 98%. This offers a vital consumer benefit as the avoidance of excessive product waste presents a better value proposition and a higher likelihood of repeat purchases.

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Serving the pharmaceutical industry with confidence With over 30 years’ experience of providing the highest quality in commercial packaging and clinical trials services, Brecon is acknowledged as one of the leading outsource service providers in the global pharmaceutical industry.

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May/June 2011

packaging & Labelling Indeed, consumer concerns have been the driving force behind other dispenser innovations during recent years. Notable examples include shippable pumps that can be locked in the down position for ease of transport and, once opened, relocked in the up position to avoid a final unwanted dose when locking; ‘Suckback’ systems that pull product back into the nozzle after dispensing to provide a consistently clean and hygienic operation and avoid mess and waste; and tamper-evident and child-resistant options.

For manufacturers, a universal closure or large lid adaptor can be specified to allow pumps to be

used with a variety of container sizes and designs.

Dispensers have also been created to handle many other product types. Ball, poppet valve and wide bore designs are available for liquids of different viscosities, whereas no metal contact dispensers are ideal for alcohol‑based products. A shower proof construction prevents water ingress.

To the untrained eye, today’s pumps and dispensers may look remarkably similar to those that have gone before. The technology behind them, however, continues to be developed and enhanced to meet new product challenges.

For more information

Mark Box Managing Director Rieke Dispensing Tel. +44 116 233 1100 Fax +44 116 231 2077 sales@riekedispensing.co.uk http://riekepackaging.com

HOW INNOVATIVE PACKAGING SOLUTIONS HELP WITH PATIENT COMPLIANCE

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oncompliance is a major obstacle in the delivery of effective healthcare, as well as being a major waste of time for healthcare professionals when patients remain ill because of noncompliance. A patient’s initial interaction with their medication is the packaging; so packaging providers must constantly consider how the design of the pack can affect a patient’s impression of taking their medication and how to ensure patients adhere to the prescribed course.

A major issue with traditional medical packaging is that the patient information leaflet, medicine and outer carton are separate components. Patient information leaflets are regularly discarded leaving the patient no reference point if they have any concerns regarding the prescribed medication.

This can result in the patient taking the medication incorrectly and prolonging their illness. Intelligent packaging design can be effective in ensuring these three components remain connected at all times,

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which is essential to help support compliance.

The aesthetics — design, functionality and portability — of medical packaging are key contributing factors in helping patients interact with their medication. Packaging that distracts the patient from thinking about their illness, but focuses on the benefits of taking the medication is key. Simple and clear communication using reassuring, engaging colours and images on the pack will support this. Playful, user‑friendly packaging design will further ensure the patient enjoys interacting with their medication. Offering design solutions that are discreet, easily portable and designed to promote health rather than being ill will encourage regular daily compliance.

As packaging suppliers we need to put ourselves in the shoes of the consumer. By delivering innovative packaging solutions that focus on the packaging as part of the treatment, not just a container for medicine, will help overcome the ongoing issue of noncompliance.

For more information

Tim Clarke CEO Burgopak Tel. +44 207 089 1950 pharma@burgopak.com www.burgopakhealthcare.com

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■ Analytical services ■ QP release of non-EU products ■ Encapsulation & Powder Filling

growth through excellence

Brecon Pharmaceuticals Ltd, Wye Valley Business Park, Hay-on-Wye, Hereford, HR3 5PG, UK ■ T:+44 (0) 1497 820829 ■ E sales@breconpharm.com May/June 2011 www.pharma-mag.com

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packaging & Labelling

GOING HOLISTIC IN COMPLEX CODING

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For more information

Craig Stobie Global Life Sciences Sector Manager Domino Printing Sciences plc Craig.Stobie@domino-uk.com www.domino-printing.com

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he CIP-13 legislation that came into force in France at the start of the year requires external packaging of every pharmaceutical product to carry more information than before: namely, a Datamatrix bar code made up of the 13‑digit CIP‑13 code plus three lines of human‑readable text — the CIP‑13 code in numeric format, batch number and expiration date. In addition, prescribed drugs must carry a preprinted vignette sticker to facilitate reimbursements.

CIP-13 is a sign of things to come. In future we will see more similar legislation, as a glance at other markets illustrates: Turkey’s ITS scheme (already in force) and the proposed pan‑European EFPIA scheme both combine a Datamatrix code with four lines of human‑readable text. In each case, the fourth line is a unique pack identifier: for ITS, this is based on simple (predictive) serialization, whereas the EFPIA model is based on complex (nonpredictive) serialization. The recently ratified EU Falsified Medicines Directive also points in this direction, decreeing that within 3 years, all pharmaceutical packaging must incorporate a unique pack identifier.

A significant proportion of currently installed coding devices is not compatible with the new legislation, so for manufacturers who have not yet updated their lines to meet French or Turkish requirements, the clock is ticking.

Updating packaging lines to conform to new regulations calls for close co‑operation between the end user and the equipment suppliers to ensure compliance, performance and a long service life. When equipment is supplied under an original equipment manufacturer (OEM) agreement — as is generally the case for new lines — the relationship between the manufacturers of all equipment (host machine, coding and inspection devices) and the end user makes managing the project even more important. So what should you bear in mind to guarantee a smooth transition and minimal downtime?

Reassuringly, the first thing to realize is that the coding and packaging industries have considerable experience of OEM relationships and know the “Dos and Don’ts.” As integration between packaging and coding specializations has become more technically sophisticated, OEM agreements enable companies to incorporate the best technology into their solutions without developing it themselves from the ground up. Unlike OEM deals involving off‑the‑shelf products — a rebadging agreement between two PC suppliers, for example — all parties recognize that the OEM arrangement is more than simply a channel to market, with a simple buyer/seller dynamic, but a three‑way relationship in which a third party — the end user — produces the profits.

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This makes understanding and co‑ordinating the interests and capabilities of the three parties fundamental to the health of an OEM relationship, so from the outset you need to establish who’s in charge. (I’ve heard it called the “Ghostbuster Question” — “Who you gonna call” if problems arise?) It is particularly important when the project involves installing a whole new solution rather than simply retrofitting a system enhancement. Will the OEM partner take full responsibility for specifying and delivering a fully functioning solution? Or will they sub‑contract validation and installation to the manufacturer of the equipment, who will take responsibility for key stages such as Factory Acceptance Testing (at the OEM) and Site Acceptance Testing (at the customer)?

Whoever takes ultimate responsibility must appreciate the holistic nature of a complex project. The importance of this was brought home to Domino recently during a thorough evaluation of exactly what services the company provides.

The exercise — which gave rise, among other things, to our new initiative “Do more” — confirmed that complex integration and technical expertise is at least as important as product installation and maintenance, and that much of our role involves “innovating at the customer interface,” engineering local solutions on site.

In practice, this means identifying the different factors that influence a project and understanding how they interact. Taking the CIP‑13 regulations as an example, it brings together IT, materials science, packaging design and coding technology.

Where serialization is required, a unique tracking number needs not only to be generated and printed on each pack, but also scanned to verify that it is readable. The information is more comprehensive and its presentation more sophisticated, which affects the physical design of the label, the choice of coding technology and its suitability for the packaging materials involved. Even in less complex applications, several factors must be taken into account to ensure that the packaging performs its dual role of physically protecting the product, through the right choice of materials, and protecting the brand itself, through measures to prevent counterfeiting or increase shelf appeal.

The holistic approach involves, and is itself the product of, other factors that make for a successful OEM relationship.

Experience is crucial, of course, because the more experience each party has, both as individual companies and as a partnership, the more likely they are to have encountered and solved any problems. Technical resources likewise — you need to be confident that they possess the expertise and have the engineers to apply it. Training is also important — a major change to production such as CIP‑13 calls for the workforce to gain new skills.

May/June 2011

Process automation just got easier.

Again.

The DeltaV™ S-Series consists of a collection of new technologies, including a range of Human Centered Design improvements, all aimed at giving you the greatest degree of flexibility in your control decisions with the least amount of effort and risk. From I/O on Demand, to embedded intelligent control, to ultimate scalability, to ease of integration – the re-designed DeltaV system brings a new level to the now-familiar DeltaV standard: Easy. www.EmersonProcess.com/DeltaV

The Emerson logo is a trademark and a service mark of Emerson Electric Co. ©2011 Emerson Electric Company.

May/June 2011

www.pharma-mag.com

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packaging & Labelling

COMMERCIAL PACKAGING

KEY INDUSTRY TRENDS

References

1. Prescription Solutions and National Council on Patient Information and Education, “New Survey: More Than Half Of Americans Do Not Take Prescription Medicines As Instructed, Pointing To Growing Public Health Problem,” 2009.

2. www.healthtransformation. net/galleries/wp-HIT/ White%20Paper%20 on%20Medication%20 Adherence.pdf

For more information

Aileen Ruff Group Product Manager Medication Delivery Solutions Catalent Pharma Solutions Aileen.ruff@catalent.com www.catalent.com/adherence

C

ustomers are being more strategic — thinking less about procurement and more about total supply chain solutions.

An integrated supply chain solution can provide cycle time and working capital benefits, whilst reducing the risk and complexity that comes from relying on multiple suppliers. Given the increased focus on costs, these solutions can be a key advantage for customers looking to improve efficiencies.

Packaging of injectables is another area of interest, because of the significant growth projected in that space.

Injectable technology itself is also changing, moving from multidose to single‑dose delivery solutions. To support increased demand, customers are increasingly looking for the specialized capabilities — such as cold chain storage and kitting capacity — needed to handle and package injectables.

Emphasis on patient adherence is also a key trend; ensuring that patients take and refill medications is a global concern. It is estimated that half of prescriptions dispensed in the US are not taken as prescribed and more than 30% of prescriptions for chronic conditions are not refilled.1 This puts a heavy burden on the healthcare

system and represents nearly $300 million of unnecessary hospitalization, medical procedures and physician treatments each year.1 An equally staggering number in a report by the Center for Health Transformation is that approximately 120,000 people die every year in the US from not taking their medication as prescribed.2 These trends apply worldwide and many players in the healthcare system are actively pursuing effective programmes to drive patient adherence.

Finally, serialization is another trend we are seeing.

Although the topic has been a bit of moving target, increased incidents of counterfeiting and other supply chain concerns are starting to motivate action. California regulations for drug pedigree have been set and January 2015 is soon approaching, whereas other countries, such as Turkey, Italy and Brazil, are already starting to implement some of the principles of serialization. Expertise in supply chain management and serialization can offer increased visibility, generate efficiencies, and guard against anticounterfeiting and divergence. Companies are looking for partners who understand global regulations and have the flexibility to handle different requirements.

ADHERENCE PACKAGING

T

References

1. B CC Research, “Global Pharmaceutical Markets,” 2008.

2. w ww.nehi.net/ publications/48/ medication_adherence_ and_care_teams_a_call_ for_demonstration_projects

For more information

Ted Lithgow, PhD Chief Science Officer MWV Healthcare www.meadwestvaco.com

16

he strategic business focus of MWV Healthcare is to help patients take their medication correctly, fully obtain the benefits of their medication and achieve better health. We take a science‑based approach to identifying the unmet needs of patients treated with our customers’ products. By developing innovative packaging solutions and services that address those needs, we help our customers optimize the performance of their products.

During the past few years, pharmaceutical product packaging has become an integral part of health management. Pharmaceutical packaging companies must now support and help brand and market products by improving patient experience. This functional role is likely to continue to evolve to address future healthcare reform demands for overall cost reduction. More significant expectations are likely to include reducing medication error, assisting pharmacists with inventory management, improving patient adherence and helping the industry to keep healthcare costs in check.

Following relatively flat performance since 2008, the pharmaceutical industry is recovering from its longstanding inertia and returning to former profitable growth and stability. In fact, the global market for pharmaceuticals

www.pharma-mag.com

is expected to surpass $1 trillion by 2013.1 Healthcare packaging will be critical component of the pharmaceutical industry growth and innovation plan.

According to a New England Healthcare Institute study, otherwise avoidable medical spending resulting directly from nonadherence accounts for up to $290 billion per year, or 13% of total health care expenditures.2 Adherence packaging — packaging that helps patients to adhere to their medication regimen as prescribed — is a highly scalable intervention that has been proven to generate increased value and enhance efficiencies, revenue and profitability.

Adherence packaging has also been shown to yield tangible patient health benefits and corresponding benefits for healthcare professionals, manufacturers and retailers.

In addition to adherence packaging, preservative‑free formulations for primary dispensing solutions represent a growing trend in prescription and over‑the‑counter nasal spray medications. To address this trend, we’ve developed PFP N — a preservative‑free nasal pump that eliminates the preservatives that may cause nasal sensitization. PFP N also protects the integrity and purity of the pharmaceutical solution, preventing contamination whilst allowing patients to achieve the intended therapeutic effect without unintended preservative side effects.

May/June 2011

NEW HP Thermal Inkjet Printers from Xact Xact’s range of HSA thermal inkjet printers operate using the reliable HP TIJ 2.5 technology, delivering high resolution, cost effective print to the pharmaceutical industry and increase security of pharmaceutical products.

• Complete solutions - with full print & camera verification control for pharmaceutical industry • Anti-counterfeiting - Datamatrix barcodes, UV & Infrared printing • Compliance with GAMP and other regulations • Touch or key based interface - for fast, easy message creation at exceptional value • Prints up to 600x600 dpi • Print speeds up to 300 meters/min • Product identification, 1D & 2D barcodes, expiry codes, graphics, date & time, batch numbers • Clean/Maintenance free - Easy to change cartridges in same way as your desktop printer • Bulk ink system - for all surface types • Compact - with flexible print head mounting for down and side printing • Multiple cartridge mounting - for increased print height, up to 50mm print height • Database integration - and custom software solutions

t: 0800 112 3620 May/June 2011

e: info@xactpack.co.uk

www.xactpack.co.uk

www.pharma-mag.com

17

packaging & Labelling

PACKAGING WITH VISiBILITY AND CONTROL

R For more information

Pascal Wopperer Pharmaceutical Supply Chain EMEA Avery Dennison pascal.wopperer@ eu.averydennison.com www.rbis.averydennison.com

egulations concerning the supply of medical products, such as the new traceability regulation created by the French Agency of Sanitary Safety and Health Products, have been effective in France since January this year and are becoming much more evident worldwide. Pharmaceutical manufacturers are under great pressure to develop packaging systems that can offer complete visibility throughout the entire supply chain.

Companies that produce and distribute medicines need to apply effective and reliable manufacturing technology that is able to increase both visibility and control within the pharmaceutical supply chain, and also help fight against issues such as counterfeiting and grey markets. Avery Dennison suggests the first step to combat counterfeiting in this industry includes a Datamatrix system, which is designed to ensure the quality and integrity of medicines with customer safety remaining a priority consideration.

T

All pharmaceutical manufacturers who wish to distribute medicines within the French market have equipped their production lines with this solution to meet France’s new regulation. The second step of this regulation is called serialization, which means the addition of a serial number within the packaging of a product and will take effect within the next 3 years.

The new directive, which was recently approved by the European Parliament, advocates the introduction of mandatory safety features, such as seals or serial numbers, for prescription medicines — and there is a possibility that this obligation could be extended to generic medicines within the next 4 years. Once this regulation is enforced as a law, Member States will have 18 months to make adjustments to their national legislation.

The Datamatrix solution is a global software solution designed to improve the tracking and traceability of medicines. It also limits counterfeit medicine sales and as a result, it is perfectly in line with the European Parliament’s recent approval.

HOLOGR APHIC SECURITY TECHNOLOGY

For more information Glen Wood US Media Representative IHMA www.ihma.org

18

he EU Falsified Medicines Directive, welcomed by the International Hologram Manufacturers Association (IHMA), is designed to strengthen pan-European anticounterfeiting laws, ensuring that a definition of ‘falsified medicinal product’ is provided to clearly distinguish falsified medicinal products from other illegal products, as well as from infringements of intellectual property rights. Furthermore, it will distinguish clearly those products with unintentional quality defects resulting from manufacturing or distribution errors from ones that have been deliberately falsified.

As concern grows for counterfeit products stealing brand identity and diverted product undermining legitimate distribution channels, so the need for security labels and seals also grows. The label is the most convenient and cost effective way of delivering holographic security technology — overt, covert, forensic and track and trace, all in a single hit.

Compared with foiling techniques, label applicators are relatively inexpensive and operators require far less training than their foiling counterparts; therefore, the barriers to entry with customers are far lower for label suppliers. Moreover, tamper evidence can be incorporated into holographic labels making them ideal for closure seals for cartons, thus another important functionality can be added in addition authentication and tracking.

There are many security technologies, but holographic — or optically variable security features, as we prefer

www.pharma-mag.com

to call them — remains one of the most tried and tested technologies endorsed, and used by some of the world’s most prestigious brand owners. Many multinationals use holograms on their packaging — for example, GlaxoSmithKline, Pfizer and Dr Reddy’s (India) — but often these are brand and territory specific.

Many branded medicines have a hologram on the pack or in the blister pack including in Malaysia where the Meditag serialized hologram label found on all registered medicines — traditional and western — has helped the Ministry of Health inspectors to detect unauthorized and counterfeit product. Everything and anything can be copied, including holograms, well enough to pass the inspection of most members of the public. To date, however, we have found that copy holograms can be detected by an expert with the right training and equipment.

The evolving anticounterfeiting role of holograms lies in their ability to combine authentication with detection and sometimes pack enhancement, as Rodotex GmbH has shown with its packaging for Vitamin C+Kollagen in Indonesia. This is why the more enlightened pharmaceuticals companies and enforcement agencies continue to make them an integral part of modern anticounterfeiting strategies.

The pharma industry is moving towards the use of serialization encoded in to things such as 2D barcodes (or Datamatrix codes), to allow the tracking of medicines through the supply chain. But this will be used in conjunction with overt authenticators such as holograms.

May/June 2011

packaging & Labelling

PACKAGING WITH VISABILITY AND CONTROL

R

For more information

Pascal Wopperer Pharmaceutical Supply Chain EMEA Avery Dennison pascal.wopperer@ eu.averydennison.com www.rbis.averydennison.com

egulations concerning the supply of medical products, such as the new traceability regulation created by the French Agency of Sanitary Safety and Health Products, have been effective in France since January this year and are becoming much more evident worldwide. Pharmaceutical manufacturers are under great pressure to develop packaging systems that can offer complete visibility throughout the entire supply chain.

Companies that produce and distribute medicines need to apply effective and reliable manufacturing technology that is able to increase both visibility and control within the pharmaceutical supply chain, and also help fight against issues such as counterfeiting and grey markets. Avery Dennison suggests the first step to combat counterfeiting in this industry includes a Datamatrix system, which is designed to ensure the quality and integrity of medicines with customer safety remaining a priority consideration.

T

All pharmaceutical manufacturers who wish to distribute medicines within the French market have equipped their production lines with this solution to meet France’s new regulation. The second step of this regulation is called serialization, which means the addition of a serial number within the packaging of a product and will take effect within the next 3 years.

The new directive, which was recently approved by the European Parliament, advocates the introduction of mandatory safety features, such as seals or serial numbers, for prescription medicines — and there is a possibility that this obligation could be extended to generic medicines within the next 4 years. Once this regulation is enforced as a law, Member States will have 18 months to make adjustments to their national legislation.

The Datamatrix solution is a global software solution designed to improve the tracking and traceability of medicines. It also limits counterfeit medicine sales and as a result, it is perfectly in line with the European Parliament’s recent approval.

HOLOGRAPHIC SECURITY TECHNOLOGY

For more information Glen Wood US Media Representative IHMA www.ihma.org

18

he EU Falsified Medicines Directive, welcomed by the International Hologram Manufacturers Association (IHMA), is designed to strengthen pan-European anticounterfeiting laws, ensuring that a definition of ‘falsified medicinal product’ is provided to clearly distinguish falsified medicinal products from other illegal products, as well as from infringements of intellectual property rights. Furthermore, it will distinguish clearly those products with unintentional quality defects resulting from manufacturing or distribution errors from ones that have been deliberately falsified.

As concern grows for counterfeit products stealing brand identity and diverted product undermining legitimate distribution channels, so the need for security labels and seals also grows. The label is the most convenient and cost effective way of delivering holographic security technology — overt, covert, forensic and track and trace, all in a single hit.

Compared with foiling techniques, label applicators are relatively inexpensive and operators require far less training than their foiling counterparts; therefore, the barriers to entry with customers are far lower for label suppliers. Moreover, tamper evidence can be incorporated into holographic labels making them ideal for closure seals for cartons, thus another important functionality can be added in addition authentication and tracking.

There are many security technologies, but holographic — or optically variable security features, as we prefer

www.pharma-mag.com

to call them — remains one of the most tried and tested technologies endorsed, and used by some of the world’s most prestigious brand owners. Many multinationals use holograms on their packaging — for example, GlaxoSmithKline, Pfizer and Dr Reddy’s (India) — but often these are brand and territory specific.

Many branded medicines have a hologram on the pack or in the blister pack including in Malaysia where the Meditag serialized hologram label found on all registered medicines — traditional and western — has helped the Ministry of Health inspectors to detect unauthorized and counterfeit product. Everything and anything can be copied, including holograms, well enough to pass the inspection of most members of the public. To date, however, we have found that copy holograms can be detected by an expert with the right training and equipment.

The evolving anticounterfeiting role of holograms lies in their ability to combine authentication with detection and sometimes pack enhancement, as Rodotex GmbH has shown with its packaging for Vitamin C+Kollagen in Indonesia. This is why the more enlightened pharmaceuticals companies and enforcement agencies continue to make them an integral part of modern anticounterfeiting strategies.

The pharma industry is moving towards the use of serialization encoded in to things such as 2D barcodes (or Datamatrix codes), to allow the tracking of medicines through the supply chain. But this will be used in conjunction with overt authenticators such as holograms.

May/June 2011

Lödige Systems are the produce of decades of broad experience in the construction of process units for the pharmaceutical industry.

Practice-proven applications and trials in our own Test Centre make our process know-how the best experience.

Our customers are well-known producers of the pharmaceutical industry worldwide.

Mixing, granulating, drying, coating and emulsifying Lödige Systems are in compliance with international norms and standards with highest quality.

Please contact us: Tel. +49 5251 309-147 More information under www.loedige.de

From powder to granules ready for compression – Your partner www.loedige.de May/June 2011

www.pharma-mag.com 19 LÖDIGE – ALWAYS THE RIGHT MIX

PROCESSES & AUTOMATION

ADVANTAGES AND REQUIREMENTS OF CONTINUOUS PRODUCTION PROCESSES

N

early every industry uses continuous processes thanks to their numerous advantages. Yet, the pharmaceutical industry remains an exception, in which even large quantities are usually produced in batches. It is slow to take up continuous processes because of the presumed difficulty of traceability. FDA’s “Process Analytical Technology” (PAT) initiative, however, encourages the industry to benefit from the excellence of continuous units in the production of pharmaceuticals.

The highest quality and safety standards are a foregone conclusion in the pharmaceutical production.

International Good Manufacturing Practice (GMP) directives promote these standards are met and maintained. It takes time, therefore, for technical innovations to become accepted in this particularly demanding field. The “Quality by Design” initiative started by FDA concerning the PAT focus, lends more importance to a precise knowledge of each process and thereby facilitates more flexibility in producing pharmaceuticals. The original skepticism towards continuous processes has given way to high interest since then.

Advantages of Continuous Process

Figure 1: In principle, all continuous machines and units can be used in the pharmaceutical industry provided that they comply with all GMP requirements.

(Source: Lödige)

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Economical production of larger product quantities has, until now, always been the main argument for so‑called continuous processes. There are, however, numerous further advantages that have even greater weighting in the pharmaceutical industry and make smaller volumes lucrative, including • Constant product quality — the continuous process ensures constant product quality during the whole production period.

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Figure 1

• Production quantity controlled by operating time — the process is completed when the required production quantity has been reached.

• Smaller machines — as there is less of the product in a continuous machine than in a batch machine. A smaller drum and drive are needed for the same throughput.

• Less manual product handling — continuous machines can be easily integrated in comprehensive units with automatic feeding. This makes some working steps redundant and reduces the risk of accidental contamination.

• Operational safety — less manual product handling means that the operators are less exposed to the product, which also ensures safety at work.

• Less manpower — fewer operators are required.

• Less cleaning — cleaning frequencies of batch machines can be quite high. In extreme cases cleaning will be required after each batch. Continuous units only require cleaning when the product is changed.

• Lower product cost — compared with a batch process, a continuous process reduces the production cost whilst achieving the same or better product quality.

Continuous Mixing and Related Processes

In principle, all continuous machines and units can be used in the pharmaceutical industry as long as they comply with all GMP requirements (Figure 1). This means, for example, that they have to meet the specific demands of hygienic design.

Technical and process areas must be strictly separated from each other. An integrated wash‑in‑place cleaning function and an easy access for inspection are also required.

Today, companies can be supplied with a complete continuous process for tablet production — transforming raw materials to granules ready for compression — by performing three steps: mixing, granulating and drying.

May/June 2011

PROCESSES & AUTOMATION Mixer The continuous mixer operates according to the ploughshare principle.1 Mixing tools welded to a horizontal main shaft generate intensive and reliable mixing of raw products.

The products are introduced at the one end of the mixer and are conveyed during mixing to the other end where the mix is discharged through an outlet door in the bottom of the drum. The mixer design ensures the required mixing quality before the mixture is discharged. The continuous mixer achieves the same high quality as the batch mixer.

The mixer is fed by gravimetric dosing (loss‑in‑weight).

Components are exactly added according to their weight, which means that one dosing system is required for each component. Big bag stations or containers are installed upstream to ensure feeding of the dosing systems.

All of this minimizes the handling whilst feeding the complete unit. Individual weighing of the components prior to each batch is unnecessary. Depending on the application, the product is discharged in a wet granulator (wet granulation) or in a compactor/tablet press (direct compression).

Granulator The continuous granulator has a horizontal drum equipped with a horizontal main shaft.2 The main shaft is designed according to the application to ensure high‑shear granulation; that is, it is fitted with a number of mixing tools.

The granulation liquid is introduced into the machine via a dosing pump. The intensive mixing and high shear effect of the mixing tools create granules. As for the mixer, the feeding is done at the one end of the mixer and the product is conveyed during granulation to the other end where it is discharged. The continuous process generates a very tight, uniform and reproducible particle size distribution.

As a result of the high‑shear granulation, the properties of the granules are comparable to those obtained in batch high‑shear mixers. The mixed product is discharged either into a dryer or via a continuous conical wet sieve.

Dryer The dryer operates according to fluid bed technology.

Heated air is introduced through the specially designed

continuous processes are gaining increasing importance in pharmaceutical production fluidization bottom plate of the machines. The airflow keeps the product in suspension, where it is fluidized, and dried gently and effectively. The dryer has a square shape and the wet granules are introduced at one end to be transported across the complete length of the machine to the opposite end, whilst being dried. Here again, the product is discharged at the end of the dryer and dried parallel to motion through the machine.

The configuration of the bottom additionally ensures a slight horizontal motion of the granules towards the discharge. As the continuous fluid bed technology is practically identical to the batch fluid bed technology, the results are typically equivalent.

If the mixer, granulator and dryer are arranged in a vertical line (Figure 2), the product transport between the machines will be gravimetric. If the line is horizontal, product transport will be pneumatic. The continuous machines described here are designed for throughputs of 5–500 kg/h.

This allows both continuous production of small quantities up to so‑called high‑volume drugs and the development of new recipes. Because operating time is a decisive factor in continuous production, small quantities can be produced within a couple of minutes and larger quantities within a couple of hours, some days or even weeks.

Conclusion

Figure 2

May/June 2011

Figure 2: If the mixer, granulator and dryer are arranged in a vertical line, the product transport between the machines will be gravimetric.

Given the wide range of advantages, continuous processes are gaining increasing importance in pharmaceutical production provided that the machines can combine this innovation with the practice‑proven GMP standards. Machines for mixing, granulating and drying must conform to legal requirements for hygiene. If batch processes are to be replaced by continuous processes, new and individually developed system concepts will be required. A key aspect in the implementation of such concepts will be the precise definition and description of the individual phases.

Notes

1. P atented by Lödige.

2. T he Ploughshare mixer.

For more information Reiner Lemperle Manager Life Science Technology Gebr. Lödige Maschinenbau GmbH Tel. +49 5251 309 371 Fax +49 5251 309 123 lemperle@loedige.de www.loedige.de

www.pharma-mag.com

21

PROCESSES & AUTOMATION

ENHANCING PROCESS AUTOMATION THROUGH INFORMATION TECHNOLOGIES

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harmaceutical companies are spending vast sums of money to bring drugs to market; even incremental improvements can make a huge difference to the bottom line. Yet, cost‑cutting measures can’t come at the expense of quality. Fortunately, companies can embed quality into their processes to improve productivity, reduce overall supply chain costs, mitigate risks and ease regulatory review.

Declining market share and margins are being experienced for the first time in many years, primarily because of the increased competition from generics.

Price pressures, shortened new drug exclusivity periods, mergers, acquisitions, consolidation and escalating R&D costs also play significant roles.

Positioning products globally is making regulatory compliance more complex. The supply chain continues to experience restructuring.

Business Drivers

Maintain profitability — establish first‑to‑market price premiums: • Innovation regarding getting a ‘first time’ product in the market — a pharma company’s ability to innovate and develop new products/methods is critical to its success.

• It calls for an accelerating rate of effective innovation.

Merge and integrate supply chains — create safe and secure supply chains. By using state‑of‑the‑art technologies, pharma companies can optimize their supply chain, including reverse logistics; for example, ePedigree and track & trace solutions, which provide alerts to stakeholders in supply chain regarding, for example, drug shelf life.

Pharmaceutical Supply Chain Challenges

• Growing complexities in a heterogeneous business environment (for example, mergers, acquisitions): • The challenge for the supply chain is both the marriage of information technologies and the union of the people/stakeholders within supply chain.

• Recently a big global pharma company faced a supply chain challenge whereby the parent company was unable to manage the business of the acquired company. It struggled for almost a year to align their IT infrastructure, business processes and stakeholders, such as distributors and sales agents. This affected the launching of new products across regions.

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www.pharma-mag.com

• Increasing compliance requirements and regulations.

• Serialization and ePedigree for medication to combat counterfeiting and comply with regulatory requirements.

• Optimization and harmonization of processes across global entities.

• Increasing requirements with regard to business transparency and global regulation.

• Pressures on R&D to reduce innovation cycle times and shorten the time‑to‑market.

• Focus on core business whilst managing inorganic growth.

Solutions

• Focus the entire value chain — value chain automation using IT, plays an important role in business and process consulting, solution design and implementation to outsourcing and other support processes.

• Information sharing across supply chain — use of IT in general and enterprise resource planning (ERP) in particular helps to understand the following: • Point‑of‑sale data to reduce forecast errors is helping firms to schedule their lines for the requirements.

• Use of an electronic data interface to capture online sales orders, which reduces data errors and improves planning.

• Information sharing is facilitated by IT across the manufacturing locations. Because this information flow is on a real time basis supply chain stakeholders can use it to make correct decisions for planning, scheduling and accommodating demand fluctuations.

• Automation can convert intercompany purchase orders into sales orders. Alternately, the delivery orders raised to intercompany plants, for example, can be converted to invoices, thereby reducing manual human intervention.

• IT enhances regulatory compliance for master data that reside centrally across the organization. Automation is possible in areas triggering workflow for creation, change and approval of key master data, such as material master data. This reduces data duplication and provides change control traceability. Workflow can be automated with a unique system‑generated change control number for each change, with time and date stamping.

• Engage comprehensive expertise in resolving process challenges through innovative IT solutions; for example, sending alerts to distributors or retailers to advise of products/batches nearing the end of their shelf life.

Technologies are also rapidly evolving so ensure you

May/June 2011

PROCESSES & AUTOMATION engage experts to keep you informed of the latest available technology for possible automation.

• I mplement industry‑specific IT solutions: • Industry‑specific IT (for example, SAP‑ERP for pharmaceuticals) solutions help to automate supply chain processes across the organization.

• Vendor selection and evaluation processes can be automated, which can record the samples analysed, results obtained and work.

• Document management systems keep track and version control of various documents created by quality assurance functions.

• The main challenge for procurement and manufacturing is to ensure they use the current version of printed packaging items. This is possible through the ERP system.

• Material issue/dispensing is an important and high risk starting activity in product manufacturing.

This can be automated by interfacing weighing balances and the system. The interface will enable the recording of the correct material quantity to be issued in the process order. The system provides the material selection based on FEFO (First Expiry First Out). Other material parameters, such as, material

May/June 2011

code, analytical report number, can be captured by using a barcode reader. This is a crucial input in the batch manufacturing record because it removes errors that are the result of manual intervention.

• Using an E‑BPR tool, wherein process parameters, such as temperature and pressure can be in real time, can create electronic batch processing records.

• D uring in‑process quality checks, results can be recorded via a laboratory information management system.

• Importantly, ERP provides authorization/access to responsible, qualified staff in areas such as manufacturing and quality control with built‑in double‑checking of important inputs.

• T he SAP‑ERP system also has control checks built within, such as FEFO for issuing material to manufacturing, recoding changes in data and audit trails.

• Process harmonization and IT standardization • Optimal alignment of the entire application environment ensures the lowest cost of automation.

• The standardization of business processes ensures easy operational change control management across the plants.

Shrinivas Inamdar

For more information Shrinivas Inamdar Senior Consultant Pharmaceutical Solutions Siemens IT Solutions & Services Pvt. Ltd

Inamdar.shrinivas@siemens.com shrini01@gmail.com www.siemens.co.in

www.pharma-mag.com

23

PROCESSES & AUTOMATION

OVERCOMING THE PROBLEMS WHEN MIXING AND TRANSPORTING SOLIDS IN GLASS-LINED REACTORS The author discusses a system that offers a complete solution for powder charging and for cleaning the charging apparatus.

T

ransporting solids and mixing them with liquids in glass‑lined reactors always bears tough challenges, particularly when handing large quantities. Many powders and granules readily absorb moisture from the atmosphere, and some solids also have hazardous properties that affect transport, including the risk of a dust explosion.

A new powerful pneumatic conveyor system that can be utilized to manage many different challenges associated with the transport of dry bulk goods. The PCC Conveyor (HECHT Technologie GmbH, Germany) has the same operating principle of any vacuum conveyor; a vacuum pump produces a vacuum in a pipeline or hose system to aspirate the product from a fixed or flexible bulk material container. The system operates in an externally closed configuration, allowing the vacuum to be maintained. This results in an oxygen‑free (inert) atmosphere for particle transportation (Figure 1).

The product–gas mixture enters the separating tank through the charging gate. The ring filter precipitates the fine dust particles to separate the product from the gas in the mixture. Because of natural gravity, the product accumulates in the container and gradually fills it. When the aspiration cycle is complete, the pneumatic control system starts the filter cleaning cycle. Instead of a vacuum, compressed air is applied to reverse the direction of gas flow. The fine particles accumulated on the filter are removed, leaving the ring filter clean for the next aspiration cycle.

When the separating tank of the PCC is full, the product is discharged. The tank can also be emptied by connecting the product discharge gate of the PCC to the nozzle of a C baffle to mix the product with the contents of a reactor.

The distinguishing element of the PCC is its special filter head — the heart of any vacuum conveyor —, which has no connection ports and contains a novel ring filter system. This has a large surface area and offers low resistance when the product is aspirated to ensure a high transport capacity. In addition, the ring filter is durable, robust against filter breakdowns, and available in different designs and materials.

24

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This provides a more flexible response to different requirements when seeking to achieve optimal capacity for transporting different products.

The system can also be extended to accommodate a double filter. In this configuration, two ring filters are placed on top of each other. While product is aspirated through one filter, the other can be cleaned.

The cleaning gas is extracted directly through the double filter without being discharged into the downstream container. As a result, dust generation in the container is lower, thereby removing the requirement for additional dust removal equipment.

Depending on the application, both dilute phase conveying and safe, gentle plug conveying

Figure 1

May/June 2011

PROCESSES & AUTOMATION are enabled. The plug conveying method can be particularly effective in preventing product from becoming unmixed … and it can prevent destruction of the product structure during the preliminary stages.

The vacuum and compressed air unit are attached laterally to the enclosure and do not need to be removed to replace filters or for product chamber inspection. This can be achieved even faster and with less effort if a design with hasp screws and a hinge is chosen. Installing a sight glass in the cover is another option as it allows visual monitoring of the product flow. As a result, the conveyor cycles can be fine‑tuned for optimization. An integrated nozzle and a liner connection system (mini‑LAS; HECHT Technologie GmbH) means that additional small quantities can be added to the unit from top, without contamination.

Compliance with the highest demands on hygiene and safety for staff and product can be guaranteed using the PCC concept. Strict containment requirements can be satisfied, ensuring that employees are not in contact with the product (contamination‑free), and that their health is protected. The requirement for protective gear is removed. Based on the continuously smooth, cylindrical inner shape, extremely small product residues remain in the separating tank during the normal conveying cycles. Washing and cleaning

The C baffle offers reduced mixing times and improvements when mixing liquids and solids.

May/June 2011

Figure 1: PCC assembled on a C-Baffle.

Figure 2: PCC with DN100 sightglass.

Figure 2

can be performed reliably and automatically. For this purpose, a PCC is equipped with a cleaning‑in‑place (CIP) or washing‑in‑place (WIP) unit. If the PCC is connected to a C baffle, there is an added benefit: the emerging cleaning liquid will also clean the baffle … and the tangential cleaning nozzle on the PCC ensures efficient, gentle cleaning of the filter.

A further issue can arise when solids are introduced into and mixed with the contents of a reactor. The particles can float and may not be drawn into the liquid. Large quantities of low‑weight solids added too quickly or solids that are difficult to moisten typically result in thick particle lumps floating on the surface. These can form agglomerates that can be difficult to dissolve as they slowly sink.

For optimal mixing effect it is recommended that solids are added in front of the C baffle — by simply attaching the PCC to the nozzle (Figure 2) that supplies the product to a reactor. The effect of the C baffle is enhanced by a PCC as the downward flow occurring in front of the baffle results in efficient drawing‑in of the medium added into the liquid receiving tank.

The C baffle offers reduced mixing times and improvements when mixing liquids and solids.

Chemical processes can be accelerated, and in many cases the quality and yield can be improved.

Coupled with the C baffle, the PCC’s highly efficient conveying capacity, flexible application, quality and safe operation provide an efficient link for conveying and adding solids to reactors.

Kerry Clunie

For more information Kerry Clunie Pfaudler

sales@pfaudlerbalfour.co.uk www.robn.com

www.pharma-mag.com

25

PROCESSES & AUTOMATION

A

STREAMLINING THE BIOPRODUCTION PROCESS

For more information Jill Staggert Product Market Manager Bioproduction Thermo Fisher Scientific

www.thermoscientific.com/easyfill

s the number of biologicals being developed and approved for therapeutic use continues to increase, it is vital that consistent delivery of high quality products for bioproduction is effectively maintained. Although increasing product yield is important, streamlining the aseptic process itself is the main priority.

Purity is a key issue in the production of any biologics. Manual processes and sample handling needs to be removed from the process as much as possible. Modifications can be made to reduce the number of operators and intervention frequency, as well as the proportion of components that require manual cleaning, which will undoubtedly improve the sterility of cell cultures and subsequently, the final product. Increasing the use of automation and replacing components such as traditional glassware or stainless steel with single‑use disposable products can significantly reduce the risk of contamination, in particular, the risks associated with cleaning, storage and re‑use.

More recently, organizations are looking for alternatives that improve their economies of scale. They also require a level of assurance that the products maintain their integrity and efficacy, whilst ensuring the sterility and efficiency of upstream processing, as well as resulting downstream data. Single‑use culturing systems, can provide a validated sterile solution that negates the need for steam/water sterilization and its associated

cleaning validation. This presents obvious cost and time benefits.

Furthermore, automated modular cell culture systems that assist in the filling, incubation, transport, storage and harvesting of cultures reduce the risks of contamination. Ideally, successfully optimized processes will need to be scaled‑up and validated for high volume production. The incorporation of instrumentation and consumables that can rapidly facilitate this process and reduce revalidation where possible, is therefore of extremely high value; for example, systems that use the same culture surface areas in small‑scale development and large‑scale production can simplify the transfer process.

The wealth of equipment and consumables available to the bioproduction industry to produce a fully automated workflow is ever expanding. The opportunity to source all materials such as instrumentation (shakers, incubators, rack systems), automation, culture ware, fluid transfer and containment solutions from a single source can be highly advantageous and efficient. In addition, the ability to provide customized solutions and innovative designs whilst addressing the ever‑changing regulatory requirements is of increasing importance. Consequently, vendors utilize their knowledge of disposable technologies and automation to bring projects from research to commercial production faster and cost-efficiently, thereby ensuring they continuously stay ahead of evolving industry demands.

We’ve moulded our packaging for you 1 Extensive choice of designs, sizes, materials and necks 1 Wide range of closures including tamper evident and child resistant 1 Small production and/or print runs 1 Customised blow and injection moulding projects 1 50 years manufacturing experience ensures superior quality and service Sterilin Limited.

Parkway, Pen-y-Fan Industrial Estate, Newport, NP11 3EF Tel: +44 (0) 844 844 3737 PACKAGING PRODUCTS Fax: +44 (0) 1495 242 242 www.pharma-mag.come-mail:packagingproducts@sterilin.co.uk www.sterilin.co.uk

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May/June 2011

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PAT/QbD

PAT: A PHARMACEUTICAL FIELD OF DREAMS?

The authors take a provocative look at Process Analytical Technology (PAT) that challenges the slow industry implementation of this advanced technique.

I

s PAT the pharmaceutical Field of Dreams? In case you missed it, Field of Dreams is a Kevin Costner film about an Iowa farmer who heard voices, and interpreted them as a command to build a baseball diamond in his cornfield. Costner’s character built it and the ghosts of the Chicago Black Sox came to play, led by Shoeless Joe Jackson.

A tortured analogy, maybe, but 12 years ago, FDA advocated PAT in the Guidance for Industry document “PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance.” We wonder, is PAT the pharma equivalent of a baseball diamond in a cornfield?

Similar to a Field of Dreams, we all hear the voices, but unlike the movie, we aren’t sure that any baseball fields are being built — perhaps a few infields, but not enough for a game.

What is PAT?

Clearly, FDA had good intentions when it wrote the original guidance document. They were true to form, reiterating the concept that “quality cannot be tested into products; it should be built‑in or should be by design.”1 PAT is a method of active control for monitoring a pharma process in real time, and adjusting inputs in situ to control the outcome.

“PAT is a system for designing, analysing and controlling manufacturing through timely measurements (that is, during processing) of critical quality and performance attributes of raw materials and in‑process materials and processes with the goal of ensuring final product quality.”1 PAT is based on the principle that quality happens real-time versus being inspected in. It assumes that product and process variables are so well understood that it is possible to make near‑instantaneous adjustments to ensure in‑specification outcomes. Even if the in-, at- or near‑process instrumentation is in place, PAT still needs to work for products that have been designed for manufacturability.

That implies the concept of Quality by Design (QbD), using tools such as Design of Experiments (DoE) and Design for Six Sigma (DfSS) in the design of a process. Failing early QbD, PAT is still possible for existing products provided we can correlate known product parameters and process behaviours with the original submission.

FDA was clear with its original challenge. The Guidance document states: “The agency is encouraging manufacturers to use the PAT framework . . . to develop and implement effective, efficient, innovative approaches in pharmaceutical development, manufacturing and quality assurance.”1 The approach is right, but where we currently stand as an industry seems to fall short of expectations.

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Why aren’t we making more progress? FDA wanted a win–win with their 2004 guidance. FDA wins because commercial drug product will be better controlled, with less variability and, therefore, more reproducible results.

Better in‑process, active control produces better results and should ease the burden on inspections. The industry wins when there are fewer batch failures, shorter cycle times and lower costs.

It all sounds perfect. FDA even acknowledged early on that there might be a regulatory barrier because of the “fixed” nature of new drug application (NDA) submissions.

They seemed to contemplate that industry would expect new hurdles in the development, approval and post‑marketing inspection of drug product. To deal with these issues, FDA created a PAT team, which survives today. But have the barriers — real or perceived — been removed? FDA did implement a protocol (FDA5427) to enable the validation of active control (PAT) results to known standards, but was this enough? Industry appears to be skeptical. It seems that the major real life implementation of PAT is still concentrated in the development phase, not in commercial manufacturing where the true benefits will accrue. Furthermore, according to our sources, it seems that the majority of PAT equipment is being sold to manufacturers primarily for the development of APIs rather than drug product.

Ultimately, industry must be satisfied that the additional expense will yield real benefits. That requires experimentation time in pilot plants to prove, which means buying equipment. Stalemate?

Of Course, Cost Matters

Active control is a great concept; coupled with continuous processing, it may well be the Holy Grail of pharmaceutical manufacturing. Given the economics, however, it is a daunting challenge. Consider a major manufacturer with 100 dedicated drug product manufacturing lines.

Multiply that by an approximate $150,000–500,000 capital investment per line to monitor the critical parameters, such as chemical composition, size, shape and crystallinity. Such a $15–50 million investment would demand a huge leap of faith, even for Big Pharma, and out of the question for most of the rest of the industry. This is particularly true as cash flow, margins and capital expenditures (CAPEX) come under increasing scrutiny.

Continuing with the cost problem, consider PAT in the contract manufacturing segment. Most contract manufacturing organizations (CMOs) aren’t making the margins necessary for the capital investment required to

May/June 2011

PAT/QbD

Anonymous Quotes

We interviewed several people from various parts of the industry and received a few interesting observations; some were positive, some negative and all anonymous for this article.

“We’re using QbD with all new products from one of our major customers, and we are actively pursuing PAT applications, with their support.” VP Operations, CMO. “We don’t pursue PAT or DfSS because our clients don’t ask for it or want it. If we suggest it, they won’t pay a premium for it.” CMO Product Development VP. “It is too expensive to convert our current manufacturing methods and equipment. It really is cost prohibitive, and besides, where do we start?”

VP Operations.

“Who’d try to get PAT past the FDA? Do they have the experience to back up their guidance papers?”

Product Development Scientist.

“The regulatory environment is still seen as a barrier to adoption.” CEO of PAT equipment supplier.

“We are seeing adoption mainly in the API side, and even that is concentrated in development, not necessarily in commercial manufacture.” Major PAT equipment supplier.

“We missed the boat on PAT — got involved, then CAPEX killed us. But we’re making a comeback, starting with development designs. We’ll get there.”

Chief Scientist. exploit PAT. One scientist we talked to said: “Whenever there’s a CAPEX decision to use traditional or leading‑edge methods, old school always wins.”

It is ironic, as the CMOs know that to not invest in PAT means to be considered “traditional pharma” by their customers — customers who can afford to experiment with and implement PAT at some or all of their sites. Sooner or later, old school will have to step aside as new methods come on line. There is always the tension between the forward‑looking scientists and the accountants. And even bulletproof return on investments can get kicked back if there isn’t a capital budget to support moving ahead.

Real‑Time Quality and Culture Change

Consider quality in real time. Culture being what it is, how likely is it that our industry will suddenly change course and accept that “we don’t inspect quality in?” But that is, of course, what we do most of the time. What is the probability that an industry that uses state‑of‑the‑art laboratory information management systems and still hand‑writes in lab notebooks will ever adopt “real‑time quality?” It isn’t a

May/June 2011

far leap to envision real‑time monitoring and active control, plus the same lab testing done today. It’s a belt‑and‑braces scenario that we’ve seen all too often in many sites with other technologies, and one that would cripple the early adopter unwilling to commit fully to PAT. Frequently, in the pharmaceutical world, we simply accept, overlook or are unaware of the time and effort we waste. Converting to real‑time quality will be a giant step for our industry. In fact, other industries that run 24/7 processing plants such as oil, gas and chemicals companies are critically dependent upon in‑process analysers.

QbD

QbD is core to the implementation of PAT. Simply put, no amount of real‑time process variable adjustment can overcome a poorly conceived, non‑robust process. Designed experiments are core to a robust process, and DfSS is core for manufacturability. Both must be the cornerstones of any effective PAT installation, as knowledge of the design space and critical performance variables is absolutely required.

Unfortunately, our industry is not adopting these powerful tools quickly enough. Other industries (automotive, aerospace, electronics, chemicals, petroleum refining) use these advanced statistical methods to identify the performance parameters for both new products and manufacturing processes. It is often the pharma standard, however, to follow the approach of “we did it this way before, maybe it’ll work again.” This mindset will not thrive in a neo‑PAT world.

Giving credit where it’s due, QbD is beginning to make inroads in development. But when we review the Guideline, it applies to commercial products and not just API or formulation development. Is this a disconnect or simply the first stages of adoption?

Regardless, we need to acknowledge the industry “as is.”

Many of our products are manufactured based on historical knowledge, and we are wont to change. And of course, we might admit that we are resistant to NDA supplemental filings that incorporate PAT, for fear of introducing new parameters that might expose our product and delay approval. Again, FDA seemed to contemplate this in the original Guidance: “Our new strategy is intended to alleviate concern among manufacturers that innovation in manufacturing and quality assurance will result in regulatory impasse.”1 Are we slaves to our current processes, our current thinking and self‑imposed restrictions?

What do you think?

Here’s the challenge to our readers. Tell us what you think. To take the survey, click on the address below or copy the link and paste it into your web browser and complete the survey about your company’s use of PAT and DfSS. We’ll get back to you with results in a future article. www.surveymonkey.com/s/3VXKVJQ

Wes Wheeler

Ken Somers

Reference

1. P AT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance.

For more information Wes Wheeler President WPWheeler LLC Pharma Editorial Advisory Board member Tel. +1 919 606 5575 Wes@WPWheeler.com Ken Somers President JK Somers & Associates Tel. +1 713 838 1815 kensomers@aol.com

www.pharma-mag.com

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GREEN PHARMA

WASTING ENERGY THROUGH STEAM LOSS Thermal Energy International discusses how installing venturi orifice steam traps can save companies money and reduce CO2 emissions.

I

n the past, energy management was not a core function for many processing and manufacturing companies. The continuing and unwavering increase in energy prices together with ongoing legislation regarding carbon emissions has, however, put energy management on the boardroom agenda. The Carbon Trust has recently ascertained that UK companies waste £1 billion a year on energy largely because of energy plant optimization issues, energy wastage and inefficient energy usage across the manufacturing site.1 In an announcement late last year, the Carbon Trust stated that last summer alone, businesses were emitting over 8 million tonnes of CO2. 2 Across manufacturing, including the food, drink and chemical sectors the amount of energy spent is £1.8 billion, of which 12% (£226 million) is wasted.2 Steam has been a popular mode of conveying energy since the industrial revolution. It is used extensively in industry for generating power and is also utilized within process industries including chemicals. As a heat transfer medium, steam has an advantage compared with fluids, such as hot water and oil, as it is able to store very large quantities of heat, which can be given up at constant temperature as the steam condenses. Unfortunately, more energy is lost in industry through steam wastage than through any other medium. Research studies by industry experts suggest that losses from steam systems make up approximately 35% of all identified potential energy savings. 3,4 The purpose of installing steam traps is to obtain fast heating of the product and equipment by keeping the steam lines and equipment free from condensate, air and noncondensable gases. A steam trap is a device that discharges condensate and air from the line or piece of equipment without discharging the steam. The three important functions of a steam trap are • To discharge condensate as soon as it is formed.

• To stop steam escaping.

• To be capable of discharging air and other condensable gases.

Yet, approximately 10% of mechanical steam traps will fail each year. Traps that fail ‘open’ (the steam trap stops working in the open position and, therefore, lets steam escape) result in a loss of steam and its

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energy; where condensate is not returned, the water is lost as well. The result is significant economic loss, directly via increased boiler plant costs and potentially indirectly via decreased steam heat capacity. Steam leakage is a visible indicator of waste and accounts for up to 11% of steam consumption in a small- or medium‑scale industry rising up to an astonishing 55% in high usage processing industries.5 Steam traps need to be working at optimum efficiency with a minimum impact on the environment; for example, for each litre of heavy fuel oil burned unnecessarily to compensate for a steam leak, approximately 3 kg of CO 2 are emitted to the atmosphere. Steam traps can have different sized orifices to suit different conditions. If a trap leaks steam, the amount wasted will depend on the size of the trap and the steam pressure. The cost of waste will also depend on the number of traps and the operating time. For example, a process plant with 200 traps based on an average trap size of DN20 and a stream pressure of 14 barg with 10% failing annually will have steam wastage of 8900 tonnes.

If the overall cost of steam for this plant were £20/tonne, the direct cost of ignoring these leaking steam traps would be £178,000 each year, which is equivalent to nearly 1 million litres of fuel oil. The cost to the environment would be 3000 tonnes of CO 2 dumped into the atmosphere.

UK manufacturers are looking for ways of reducing overheads and many are cutting maintenance budgets and staff. The consequence is a spiral of ever‑increasing steam loss and escalating fuel bills as mechanical steam traps fail open. This has lead management with two options: either minimal maintenance and watch the steam plume from the condensate receiver rise along with the fuel, water and chemical treatment costs or regularly test, repair and replace faulty mechanical traps at considerable ongoing cost.

What to Look for in a Steam Trap

To be efficient and economical, a steam trap has to • M inimize the loss of steam.

• P rovide long lasting and dependable service by minimizing trap testing, repair, cleaning, downtime and other associated losses.

• B e corrosion resistant to prevent the damaging effects of acidic or oxygen‑laden condensate.

May/June 2011

GREEN PHARMA

• Ventilate air for efficient heat transfer and to prevent system binding.

• R emove CO 2 to prevent the formation of carbonic acid — the steam trap must function at or near steam temperature because CO 2 dissolves in condensate that has cooled below steam temperature.

• O perate against the actual backpressure build‑up in the return lines.

• B e free of the dirt collected by the condensate as it travels through the distribution piping and on to the boiler. Even particles passing through strainer

Case Study

Aesica, a leading supplier of APIs to the global pharmaceutical industry, has saved more than £67,000 a year in energy costs at its Ponders End site following the installation of Thermal Energy International’s GEM steam traps. Thermal Energy International has installed a total of 200 steam traps throughout the process plant achieving a 28% energy saving in just 12 months.

Purchased from Merck Sharp & Dohme (MSD) in 2006, Aesica’s Ponders End site is a hi‑tech manufacturing facility with a capacity to produce 300 tonnes of products per year. It has potent compound and bulk manufacturing facilities producing active potent ingredients for MSD products.

When MSD recruited Phil Page as Utilities Engineer & Energy Manager, he was given special responsibility for saving energy. Having previously installed GEM steam traps when employed at GlaxoSmithKline, he was aware of the energy savings that could be made using the patented venturi orifice design and therefore called in Thermal Energy International to conduct a full survey of the steam system.

The report from Thermal Energy International showed that approximately 10% of the steam traps on the site were failing open resulting in 8900 tonnes of steam being lost each year at a cost of £67,200. This was increasing energy and maintenance costs, reducing production time and having an environmental impact by creating 3000 tonnes of CO2 emissions each year.

By replacing the existing traps with the GEM venturi orifice design, blocked steam traps could be prevented from impacting on production and by efficiently returning condensate back to the boilers energy saving would be made. During the following 12 months all 200 mechanical traps were replaced with appropriately sized GEM steam traps.

The company’s US headquarters had set the site an energy reduction target of 25% during a 3‑year period. By installing the GEM steam traps, the company achieved its target in less than 12 months. Such was the site’s accomplishment that a senior executive visited from the US to see how the energy savings had been achieved.

“Mechanical traps fail and this has an effect on production times and costs as well as energy, maintenance and the environment”, says Phil Page. “Fixed orifice steam traps do not fail open. Because of the success of the GEM steam traps, Aesica has decided to complete those final areas not previously converted to GEM traps to benefit from additional energy savings.”

screens are erosive and, therefore, the steam trap must be able to function in the presence of dirt.

There are numerous steam traps available and selecting the correct type of steam trap is an important element of any steam system. Whilst Thermostatic, Thermodynamic and Mechanical are extensively used, the Fixed Orifice Condense Discharge Trap is now becoming the steam trap of choice. Instead of utilizing a valve mechanism to close off steam for maximum energy and water conservation, the venturi orifice design effectively drains condensate from the steam system. As these steam traps have no moving parts to wedge open or fail, they provide the ultimate in reliability necessitating only minimal maintenance and requiring no spares, testing or monitoring equipment. They are available in a range of options for specific applications, manufactured from corrosion‑resistant stainless steel and are performance guaranteed for 10 years, obviating the need for repair or replacement.

Unfortunately, steam traps are often ignored. This complacency is costing steam users much more than they realize. The hard reality of a plant maintaining its boiler and forgetting about the rest of the steam system can be a horribly wasteful proposition. Losses can include not only wasted energy, but also the replacement of damaged equipment and misuse of man‑hours. Fortunately, installing low maintenance orifice venturi steam traps can avert much of these potential losses.

Unfortunately, steam traps are often ignored. This complacency is costing steam users much more than they realize.

May/June 2011

Grant Bailey

References

1. w ww.carbontrust.co.uk/ news/news/newsletter/ pages/2010-12-energyefficiency.aspx 2. w ww.envirovaluation. org/blogs/index.php/ the_carbon_trust_www_ carbontrust_co_uk 3. w ww.swagelokenergy. com/download/BONZ.pdf 4. w ww.uniongas. com/largebusiness/ customerinformation/ presentations/2007/ Spirax_Sarco_ Presentation.pdf 5. w ww.enerchecksystems. com/steamcht.html

For more information

Grant Bailey Sales & Marketing Director Thermal Energy International Inc. www.gemtrap.com

www.pharma-mag.com

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GREEN PHARMA

MORE THAN MERELY GREEN

T

Paperless operations can benefit customers and the environment. he mantra of doing more with less recently assumed new meaning for the clinical supply chain industry and the timing couldn’t be more appropriate. In this case, ‘less’ refers to paper — at least 4 tons annually — that will be saved, thanks to new paperless operations at all of Fisher Clinical Services’ (FCS) facilities. Two years in the making, the move is initially expected to reduce paper consumption across worldwide locations by as much as 70%.

Of course, ‘green’ initiatives are hardly new; they’ve been embraced by virtually every major pharmaceutical company, often with a high degree of visibility. Corporate responsibility reports are brimming with features and glossy photos about the replacement of older work systems with modern, environmentally friendly technology.

Although the transformation of a highly paper‑intensive process into a paperless one certainly qualifies as another ‘green’ initiative worth highlighting, the implementation of paperless operations in the clinical supply chain industry is a great deal more than that.

Our discipline has been under increasing pressure to reduce cycle times and increase productivity without compromising quality. To achieve all of these goals, we must find more innovative ways to deploy technology.

Information technology (IT) systems are among the critical tools that will make it possible for us to be successful under this new paradigm. That’s why an investment in paperless operations is really an investment in sustainability — and not merely sustainability of the environmental kind.

In this case, we’re defining sustainability as the deployment of consistent processes that generate durable improvements in operational efficiency and quality.

Everyone recognizes that improved efficiency and quality translate into reduced cycle times — the Holy Grail of a pharmaceutical industry that has never been under greater productivity pressures.

For more information Leon Wyszkowski Vice President and General Manager Fisher Clinical Services North America leon.wyszkowski@ thermofisher.com

www.fisherclinicalservices.com

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Benefits

As drug companies become increasingly global in their quest to drive productivity, paperless operations inject much‑needed consistency into multinational clinical trials. Using electronic systems instead of emails or paper reports to communicate across countries and continents establishes a tightly integrated supply chain.

Another key benefit of paperless systems is reduced error rates. It’s easy to understand why: manual processes are

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by their nature vulnerable to human error. Unfortunately, misplaced or mixed‑up paperwork, illegible handwriting and steps taken without rigorously following proper procedures are all too commonplace across the industry.

Broadly speaking, our collective approach in the past has been to pile additional forms or rigorous checks into the process. That’s no longer a viable approach.

Paperless operations work by distilling the variability from processes and replacing it with predictable quality controls. There are no papers to lose, electronic approvals replace indecipherable handwriting and preprogrammed forms compel work teams to comply with prescribed procedures each and every time — no shortcuts permitted. Unwieldy paper jackets give way to online work queues, eliminating the need for batteries of file cabinets that consume crucial real estate in global facilities.

Customers of FCS’s Bristol (PA, USA) facility, where paperless operations were pioneered 6 years ago, immediately realized tangible benefits. They quickly came to appreciate the simplicity of the system, including more organized, easy‑to‑review batch records and a reduction in time‑consuming steps. Importantly, the use of paperless operations to remove complexity from work processes empowers customers to accomplish more in less time, supporting their efforts to achieve that most elusive of goals, work–life balance: • Clean, online reports replace marked‑up, multipage documents that formerly required hours of review.

• Reconciling a job electronically takes 70% less time than it does with a paper process.

• Electronic control gates replace extensive, frequent human checks across the process, thus shrinking postproduction review cycle times by as much as 50%.

• Project approvals proceed immediately into queue, instead of taking as much as a day to make their way to the production floor.

Two years of meticulous planning preceded FCS’s global adoption of paperless operations in April. Eventually, up to 90% of operations — including every activity that encompasses packaging or packaging support — will go paperless.

Maximizing paperless operations in this way requires the clinical supply chain industry to partner with customers on technology that delivers new solutions. Although more work lies ahead, it’s fair to say that the industry and its customers are already off to a most productive start.

May/June 2011

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ACTIONS SPEAK LOUDER THAN WORDS

The pharmaceutical industry has an opportunity to lead the way in positive environmental change by demonstrating what can be achieved and sharing the knowledge we have gained along the way.

C

Yukio Matsui

For more information

Yukio Matsui Senior Vice President, Chief Strategy Officer Astellas Pharma Europe Ltd Tel. +44 0784 419 400 astellas.european. communications@eu.astellas.com www.astellas.eu

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ompanies in all industries are coming under increasing pressure to reduce their negative impact and enhance their positive impact on the environment. Ten years ago, improving our environmental profile was a second or third factor to influence our business decisions; now, it has become a key driver. Many of us are making significant progress in this despite the numerous challenges we’re facing in today’s business environment.

By setting ourselves ambitious targets for environmental impact reduction we mobilize our organizations to make changes happen. As a part of our mid‑term management plan, which specifies targets to be achieved by fiscal year 2014, we have set targets for reducing greenhouse gas emissions, water consumption and energy consumption. By making these reductions a core part of our overarching business strategy, we have ensured that they are prioritized throughout the Astellas Group.

So how are we doing so far? Based on our last audit, on a global basis, our greenhouse gas emissions have fallen by 17.7% since 2005. Our water use in 2009 for example was 15.3% less than in 2005. We are well on our way to a 20% reduction in global water consumption by 2015. In addition, we are making significant progress in making our car fleets as green as possible.

In Europe, we are implementing specific energy efficient measures across our offices and manufacturing plants. To better position this overarching strategy, we have devised a range of projects that span our network.

One such example is ‘Project Ozone,’ through which we will introduce a greener fleet of cars and reduce both our CO2 emissions and running costs for approximately 2000 cars in 34 countries across Europe. The environmental performance will be balanced alongside the culture, operational needs and taxation in each location, and will ultimately benefit employees in our European network.

We know from experience that green measures are most effective when they take into account the unique needs and opportunities of the community in which they are based. I would like to share two other initiatives that meet the global need for a better environment through addressing needs and leveraging opportunities in the local environment, namely the energy resource we use for a manufacturing plant in Ireland and the construction of our new building in The Netherlands.

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Ireland and The Netherlands

In Kerry (Ireland), we’ve spent the previous 4 years devising energy efficiency improvements at our manufacturing plant. Originally, a million units packaged required 2.96 million kWh of electricity; that has now been reduced to 1.92 million kWh. Last year, we packaged 8.4 million units; these energy efficiencies translate into an enormous annual saving of 8.7 million kWh. In terms of annual CO2 reductions, these measures are equivalent to taking 850 cars off the road. Moreover, this initiative alone has saved the company more than €1.4 million in energy bills, which makes a strong business case for far‑reaching green measures.

In addition, the wind turbine under construction at our Kerry plant will save 1000 tonnes of CO2 annually and provide 20% of the site’s electricity, which is equivalent to running more than 1.4 million computers a year.

Furthermore, the plant will be installing a biomass boiler, which will be a carbon neutral system that generates heat energy from renewable sources and reduces our use of oil for energy. Both of these projects are partially funded by the Irish Industrial Development Authority and are scheduled to begin construction in September 2011.

In Leiden (The Netherlands), we are building a new plant to join a cluster of other companies at the Leiden Bio Science Park. The architect who has designed the new building has adhered to the BREEAM standard — an international standard for sustainability. As a result, approximately 40% less CO2 greenhouse gas will be emitted during construction than would normally have been the case.

Summary

Although big changes are important, we must never underestimate the cumulative effect of smaller actions. We make it easy for employees to recycle, to reduce waste and to minimize the impact of their daily work on the environment as much as possible. While it is less easy for us to measure the differences made by these small changes, we know that they are better for health and for our planet.

Our journey towards a better environmental profile isn’t going to end in 2015 or 2020. In fact, it is only just the beginning — as an industry, our focus on environmental efficiency is set to grow rather than to diminish. Going green is good for the environment, good for employees and good for the company.

May/June 2011

Epichem Supplies API Degradants & Impurities for QA/QC & Product Development

A

nalytical Standards

Epichem’s range of standards includes impurities, degradants and metabolites of active ingredients and excipients. The range is continually expanding in response to customer requests and developments in the industry. Our current catalogue can be viewed at www.epichem.com.au We also supply hard-to-find degradant standards for a number of OTC and generic drugs, and we have considerable experience in the synthesis of deuterated and 13C labelled standards.

Epichem’s Range of API Degradants & Impurities ¥ Benzydamine ¥ Bromhexine ¥ Carbocysteine ¥ Cetirizine ¥ Chlorpheniramine

Bulk Quantities Bulk quantities of degradants and impurities can be supplied for your toxicity testing and product development requirements.

¥ Cinchocaine/ Dibucaine

¥ Guaifenesin ¥ Ibuprofen ¥ Loperamide

¥ Codeine

¥ Mebendazole

Quality & Reliability

¥ Dextromethorphan

¥ Minoxidil

Epichem understands the industry’s need for quality and reliability.

We stock a wide range of standards for quick and reliable supply. Our analytical standards are thoroughly characterised and prepared in accordance with a robust quality system. Our laboratory and quality systems have successfully passed audits by four of the world’s largest pharmaceutical companies.

¥ Diphenhydramine

¥ Oxycodone

¥ Diphenoxylate

¥ Phenylephrine

¥ Domperidone

¥ Propofol

¥ Doxylamine

¥ Ranitidine

¥ Dropropizine

¥ Tretinoin

¥ Flecainide

¥ and more...

We regularly ship to customers throughout the world. Our standards are shipped with full documentation, including a Certificate of Analysis and MSDS, to ensure smooth customs clearance.

Problem Solving, Identification and Synthesis of Degradants and Impurities Epichem has considerable expertise in the identification and synthesis of new and challenging degradants and impurities. We have provided expert advice on the mechanism of degradant formation and advised of modifications to formulations which have reduced their levels. We have a track record of solving difficult problems for our customers, saving time and money in new product development.

Custom Synthesis & Drug Discovery Epichem also provides world-class products and services in synthetic and medicinal chemistry to both the drug discovery and pharmaceutical industries. Further details can be found on our website.

Visit Epichem online to browse our catalogue or call today!

www.epichem.com.au sales@epichem.com.au Phone +61 8 9360 7696 Fax +61 8 9360 7699 Epichem Pty Ltd, Murdoch University Campus, South Street, Murdoch WA 6150, Australia

May/June 2011

molecules made to order www.pharma-mag.com

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ANALYTICAL

FEATURE FILMS Jo Smewing of Stable Micro Systems explores new methods to help pharmaceutical manufacturers quantify and analyse the performance characteristics of pharmaceutical film applications.

D Figure 1: 90 degree peel rig.

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evelopments in oral and transdermal drug delivery methods are paving the way to the future of systemic drug administration. Films have long been recognized as ideal carriers for products that require ultrahigh barrier properties in a transparent, small footprint package for pharmaceutical and nutraceutical applications. But with the advent of controlled release (CR) pharmaceutical dosage forms that release active ingredients gradually and predictably, films are increasingly finding their way into new drug applications. For an effective clinical performance films must adhere reliably to the target organ and withstand daily wear without compromising their functionality.

Automated texture analysis (TA) allows CR films to be tested in objectively controlled conditions that closely simulate real applications. TA via a TA.XTplus texture analyser, for instance, allows manufacturers to assess and fineâ&#x20AC;&#x2018;tune the mechanical characteristics

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May/June 2011

Developed by:

First ever KAM specific pharma conference in North America STRAP

Key Account Management USA 2011 Two-day pharmaceutical conference - September 13th-14th, Philadelphia

Use KAM to revolutionize your pharma sales strategies and maximize profitability Implement KAM to achieve: Increased market share and access: Exploit the multiple benefits of KAM to escalate your market share and access while providing a better customer experience A positive return on investments and objectives: Learn from experts how to set your company’s key account goals and execute them effectively Improved stakeholder management: Find out how you can effectively enhance stakeholder relationships and increase customer retention through best practices

Benchmark your KAM strategies against our expert speakers: Juan Orriols Regional Director, SFE Johnson & Johnson Joe Coffey VP Sales Baxter

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Higher retention of top sales talent: Examine ways to retain your best talent by training them to be effective KAM enforcers

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Dramatic sales growth: Boost your sales figures like never before with a dynamic KAM model

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PLUS KAM in action: Hear successful case studies from companies leading the field in KAM and how it has positively affected sales

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“eyeforpharma always deliver cutting-edge, concise conferences on a global scale. I am proud to be associated with them and see them as a key player in delivering up-to-date intelligence to the industry”

Media Partners:

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Len Strarnes, Bayer - Schering

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THE FULL SPECTRUM OF PRODUCT MANAGEMENT

Visit www.eyeforpharma.com/kamusa/ for the latest speaker line up, www.pharma-mag.com agenda, free podcasts and easy registeration!

May/June 2011

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ANALYTICAL of these products, thereby optimizing their acceptability and efficacy. Accurate and consistent quality control (QC) tests enable pharmaceutical manufacturers to develop films that combine optimal therapeutic efficacy with user‑friendliness: less frequent administration, improved convenience and greater patient compliance. TA provides a rapid and simple technique for measuring the adhesiveness, rupture, burst strength, resilience and relaxation properties of pharmaceutical films.

Transdermal Applications

Transdermal CR films usually combine a therapeutic component with an adhesive formulation that ensures a continuous delivery of the active ingredient through unbroken skin at a constant absorption rate. Skin adhesion and drug compatibility determine the efficacy of transdermal applications. Adhesive properties are critical because the amount of medication delivered is directly proportional to the skin contact area. Transdermal systems need to cause minimum skin disruption, be easy to handle and be equally effective for the infinite variations in human skin. In vitro tests are commonly used to determine and compare tack, peel adhesion, tensile and shear characteristics of film samples.

Polymeric films are typical examples of dermal delivery drugs. Various shearing forces, such as breathing, swallowing and flexing of the skin, challenge their retention on the affected area. Their performance depends on bioadhesion and good drug release.

Moisture-Activated Polymers Adhesive film patches are widely used in highly targeted and custom‑designed applications. Bioadhesive polymer composition is combined with the moisture‑activated drug release system to provide effective localized treatment that is simple to produce and easy to use. The efficacy of topical films is dependent on correct application to the skin

and the retention of the product on the body for a sustained period. Incorrect application can result in inconsistent results from the same medication so new moisture‑activated patch applications have been developed to overcome these issues. In contrast to topical creams, the fixed dimensions of transdermal patches ensure better coverage of the affected area and control the release of active ingredients, as well as their retention. Clinically relevant product groups include hydrocolloids and hydropolymers, semipermeable films, gelatine films and calcium alginates.

In a test to measure the bioadhesion of topical films, an adhesive sample is attached to a cylinder probe, which is then lowered onto a neonate porcine skin sample (which closely resembles the human epidermis). The texture analyser then measures the force required to remove the probe from the skin surface. To tailor the test conditions to the specific requirements of hydrogel films, a flexible substrate clamp can be used to secure both the sample and the skin in place.

The device consists of a multislot plate and a clamp fixture, and works in conjunction with an adhesive indexing system.

The skin sample is held under the plate and the upper fixture lowers the sample down into each slot. The texture analyser then records the force required to withdraw after adhesive bonds have been formed.

Peel Profiles To assess the peel strength of a typical bilaminar patch formulation, a cyanoacrylate adhesive is used to attach wetted neonate porcine skin to the sliding platform of a 90 Degree Peel Rig (Figure 1). A sample of the patch is secured vertically; held at the top with a clamp, and at the bottom attached to the skin. As the clamp moves upwards, the sliding section of the rig moves horizontally, forming a 90° angle between the interface of the skin sample and the adhesive patch. A texture analyser records the force required to peel the patch off the skin sample.

Figure 2: Tablet coating adhesion fixture.

Figure 3: Film Support Rig.

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Figure 2

Figure 3

May/June 2011

ANALYTICAL Oral Applications

Oral delivery accounts for 90% of all medicines prescribed.

Yet, degradation of the drug by the stomach’s enzymes and acids, as well as liver metabolism and absorption, challenge the efficacy of many oral dosage forms. New developments taking place in this area include delivering medication through fast‑dissolving tablets and films designed to manipulate biological barriers and deliver required absorption rates.

Cracking Coatings Film tablet coatings are popular because of their multiple roles: from aesthetics and masking taste and odour to eased ingestion and prolonged product shelf life. Problematically, aqueous film coatings tend to act as local stress concentrators, promoting cracking, edge splitting and peeling. To assess these risks accurately, Stable Micro Systems developed the Tablet Coating Adhesion Fixture (Figure 2), which calculates the force required to separate a tablet from its coating. The coating is removed from around the circumference of the tablet using a scalpel, leaving it present only on the upper and lower surfaces. Lower and upper fixture cavities are covered with double‑sided foam tape, and the prepared tablet is then positioned in the lower cavity. As the test starts, the upper fixture descends onto the tablet at a specific force for a defined time. Once the sample has been fully compressed into both cavities, ensuring full coating contact with the adhesive, the upper fixture is withdrawn, either removing the upper coating or leaving the lower one in the stationary fixture.

The maximum force required to separate the tablet from its coating is known as the “tablet coating adhesion force.”

Mucosal Delivery

Mucosal delivery requires a drug delivery system to be attached to a target area of mucous membrane, such as a part of the gut, for a predefined length of time. Its success depends on the strength of the product’s mucoadhesive bonds, which

can be measured using, for example, the TA.XTplus.

Simple adhesive tests, similar to the ones described above, provide details of the mucoadhesive properties of films, powders, gastrospheres or polymers. Developed by Stable Micro Systems and the University of Strathclyde, the Mucoadhesion Rig, closely replicates in vivo conditions with a porcine membrane sample positioned in a fixed volume of temperature‑regulated gastric fluid. A cylinder probe, with sample attached, descends into the vessel until the sample is in contact with the tissue. The texture analyser controls the force and time of contact between the two surfaces and records the force required to separate the surfaces, thereby measuring the mucoadhesion strength.

Figure 4: Burst strength of two types of film.

Under the Tensile Stress

Theapplicationofpolymericfilmsdependsontheirmechanical, electrical, thermal and bonding properties, which can be assessed by using tensile, shear and compression techniques.

Subjecting films to tensile stress is a fast and accurate method of defining whether the material is strong and flexible enough for transdermal pharmaceutical applications. Tensile grips allow manufacturers to optimize the balance between drug loading and plasticizer content to ensure the required clinical performance. Attached to the base plate and the cross head of the texture analyser, tensile grips firmly hold the film sample from both ends. A test is then performed at a predetermined speed and the results, such as tensile strength, work of failure, elastic modulus and extension, or elongation to break, are calculated from load‑extension curves. Pneumatic grips are often a preferred means of holding a sample for tensile testing because the gripping pressure can be controlled precisely as it is not affected by the deformation of the sample.

Although tensile or pneumatic grips are traditionally used to assess the tensile properties of polymeric films, the reproducibility of results can be compromised if the pressure is unevenly distributed across the sample’s surface area. By comparison, the film support rig (Figure 3) can hold small sections of film in a drum configuration, which means the pressure is evenly distributed around the circumference of the sample. A puncture test performed by a spherical probe determines the film’s burst strength (Figure 4), as well as resilience, stiffness and relaxation.

Summary

Figure 4

May/June 2011

Pharmaceutical films are becoming increasingly prevalent among over the counter pharmaceutical products, ranging from tablet coatings to fast‑dissolving film wafers and transdermal patches. Because of their optimal physical structure, films are discreet, have good adhesion and peel profiles, and do not interfere with daily activities. Facilitating repeatable and reliable testing of various mechanical properties of film applications, TA enables pharmaceutical manufacturers to evaluate and evolve their products. Extensive tests help to identify optimal material and drug dosage formulations that promote stability and long‑term performance of a product.

For more information Jo Smewing Applications Manager Stable Micro Systems Tel. +44 1483 427 345 Fax +44 1483 427 600

sales@stablemicrosystems.com www.stablemicrosystems.com

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SUPPLY CHAIN MANAGEMENT

SUCCESSFUL SUPPLY CHAINS FOR THE FUTURE Dr Jonathan Betts of Science Warehouse discusses the modern supply chain and offers views on how it can be a key means of differentiation in today’s challenging pharma marketplace.

T

here are signs globally that the economy is moving out of recession, but the recovery is still fragile. The key to continued recovery is two fold: consumer confidence and the financial ability to purchase.

With economies carrying major structural deficits and governments pushing through spending cuts and tax rises combined with inflationary pressures, finance ministers have a recovery tight rope to negotiate.

Whilst subject to different market forces, the pharmaceutical industry is not immune to economic conditions, particularly at a time when the healthcare system it serves is undergoing unprecedented change globally. Shifting demographics, shrinking budgets, greater complexity and personalization, and an increasing focus on healthcare costs all contribute to pressure on the sector.

A Vulnerable Sector

Dr Jonathan Betts

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Effective procurement, where optimized correctly, can increase the competitive advantage of key players within the sector. Additional investment in procurement is increasingly important as the wider economy readjusts to tighter market conditions and the government cuts come into play.

During the last few years, companies in the pharmaceutical industry have taken several approaches to prepare themselves for a projected reduction of $250 billion in sales, between now and 2015.1 Sales growth is expected to slow with businesses set to face a challenging year ahead. This is leading many in the sector to rethink cost structures, and use outsourcing and process standardization as a key business strategy to improve efficiency and provide quality real-time information to effectively manage costs.

Driven by the desire for expertise, IT outsourcing is expected to account for a large proportion of the overall IT services spend in 2011.2 This is supported by the fact that a large majority of pharmaceutical companies are already outsourcing certain aspects of the supply chain, but can they do more and which strategies will yield the best results?

Although the sector is focused on implementing cost savings, this has to be balanced with a duty of care for patients, both in product and service. Key issues influencing the sector’s strategic approach to outsourcing include privacy, regulatory and intellectual property issues. Cost savings may be the current prime driver, but quality, improvement and innovation of business processes will also be part of any well‑thought out outsourcing decision process.

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Patent Cliff

Faced with an impending ‘patent cliff,’ pharma companies have focused on bolstering R&D productivity, looking increasingly to biotech as a cost‑effective innovation engine.

At the same time, restructuring has resulted in a large numbers of layoffs — topping 50,000 in 2010.3 Amongst this, supply chain transformation has played second fiddle and yet offers significant opportunities as an area for development.

A strong supply chain management function encompasses the planning and management of all activities involved in sourcing and procurement. Adaptability is a key component of any successful supply chain function enabling access to new channels quickly and efficiently using innovative, bespoke procurement solutions.

Importantly, it also includes co‑ordination and collaboration with channel partners, which can be suppliers, intermediaries, third‑party service providers and customers.

In essence, supply chain management allows integration of supply and demand management within and across companies, both national and international. Successful supply chains are all about effectively responding to demand, but at the same time introducing initiatives to drive down costs, whilst maintaining quality.

Modern Supply Chains

Currently, supply chains are complex, but are not structured to meet the future needs of the pharmaceutical industry.

Whereas most innovation has been at the R&D end of things, supply chains for most pharma companies don’t compare with best‑in‑class from other sectors (such as, Apple, P&G, Cisco, Wal‑Mart); for example, most organizations are unable to produce on demand, but instead rely on producing large inventories — an approach that is massively inefficient and costly.

I believe the future market will be made up of more complex therapeutics targeting the smaller, more fragmented markets. This requires more dynamic and flexible supply chains with a focus on margin at each stage. With the end of the blockbuster era, product life cycles are likely to become shorter with incremental product launches slowing the rate of revenue growth. This will not only reduce the period of market exclusivity that conventional drugs have enjoyed, but will also require fine‑tuning of the supply chain to cope with the different stages of development.

Coupled with this, financial constraints mean developed nations are becoming less willing, or able, to pump ever‑increasing amounts of cash into a seemingly bottomless healthcare pit. The healthcare industry is, therefore, being

May/June 2011

SUPPLY CHAIN MANAGEMENT increasingly driven by cost reduction options, plus demands to improve their patient outcomes — effectively value for money in procurement terms.

New Approaches

Other than developments in formulation and manufacture, including approaches such as transgenic production methods, new distribution technologies will also play a part in the supply chain. Cloud computing has an important role to play by improving management and sharing of data securely and economically.

Significant value can be lost at the final step in the supply chain — the self‑administration of medicines by patients.

Currently, it is very difficult to know whether a patient is taking their doses correctly, but new ‘patient interface’ technologies will allow compliance to be monitored and the results used to ensure value.

Greater supply chain integration will also be important for efficient output. In many organizations today there are separate supply chains for design, manufacture and distribution of pharmaceuticals; design, manufacture and distribution of devices; and provision of healthcare services.

Improved integration across these areas is key and will drive greater visibility and improve demand management.

Sharing Services

There are many opportunities for improving shared services across pharma companies in manufacturing and distribution.

Given that competitiveness will be derived in a large part from speed‑to‑market and flexibility of the supply chain, it makes sense for companies to utilize pre‑existing assets where those assets in themselves do not form the basis of sustained competitive advantage. Indeed, the approach of outsourcing key processes, such as manufacturing and clinical research is well established; so why not maximize value from R&D to deliver to market?

2011 is a challenging year for every sector; as economic factors squeeze margins, investment in supply chain and procurement will be essential to drive innovation within the market and service delivery. During 2011, the industry needs to drive efficiency and adopt new capabilities and skills via a new breed of pharmaceutical professionals that contribute to the future prosperity of the sector.

The supply chain is becoming increasingly important as a value driver as medicines become more complex and markets more fragmented. These factors reduce returns, whilst healthcare buyers are also becoming focused on value for money and patient outcomes. The opportunity exists to drive value without compromising quality and security of supply.

References

1. www.fiercepharma. com/story/patent-cliffjeapordizes-250b-salesthrough-2015/2011-03-04 2. www.pwc.com/en_GX/ gx/pharma-life-sciences/ pharma-2020/pharma2020-supplying-thefuture.jhtml 3. www.fiercepharma.com/ story/2010-pharmajob-cuts-cross-50kmark/2010-12-01

For more information

Dr Jonathan Betts Sales & Marketing Director Science Warehouse Ltd www.sci-ware.com

Products, Project Management and Services for the Healthcare Industry B. Braun OEM Division - System-built Solutions As one of the leading companies in the healthcare market, B. Braun is your professional and reliable outsourcing partner for pharmaceutical contract manufacturing and customized product variation and combination. Rely on our expertise in infusion therapy and project management and contact us for your system-built outsourcing solution.

B. Braun Melsungen AG | 34209 Melsungen | Germany Tel +49 (0) 566171 2826 | service_oem@bbraun.com | www.bbraunoem.com May/June 2011

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SUPPLY CHAIN MANAGEMENT

TECHNOLOGY REPLACES THE PEN Tim Mohn of Sparta Systems explains why manufacturers are turning to enterprise quality management solutions (EQMS) to ensure that supplier quality and production processes meet the exacting quality requirements of consumer health agencies and the compliance requirements of the highly regulated, consumer-facing pharmaceutical industry.

M

anufacturers in highly regulated industries struggle between two opposing forces — supply chain efficiency and supplier quality.

The board drives for optimum efficiency and profitability, whilst the quality managers want component, production and end product quality.

This doesn’t mean the board is not concerned about product quality or that quality managers have no commercial understanding, it simply means their objectives are conflicting and, as a result, quality can be overridden in favour of production efficiency and revenue increases.

The irony is that poor quality can devastate share prices and destroy brands. Quality issues tend to stem from substandard ingredients, inferior packaging or contamination on the production line, all of which can be prevented if supplier and production quality is consistently monitored and if any issues are reported on in real-time and put right before there is any cost or consumer impact.

Traditionally, manufacturers have been “pen and paper” driven. With no central processes, policies or reporting procedures in place quality management becomes a local concern and at the discretion of site management. Quality, therefore, becomes inconsistent between plants and/or countries and major issues arise when regulatory reporting is required. This can result in compliance failures, leading to fines and the revoking of licences if reporting errors are continually repeated.

It is impossible to achieve customer key performance indicators and to meet the reporting requirements of regulatory authorities using manual processes. Interim steps have included Excel reports and database entries, but these remain disparate.

To effectively monitor quality across multiple sites and suppliers, extensive tracking and management of supplier qualifications, audits, nonconformance, corrective actions and other processes is required.

The best way is to introduce an EQMS. This can be a standalone application or used as a bolt‑on to an enterprise resource planning system.

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Managing

supply quality effectively drives compliance and reduces the cost of poor quality Benefits

An EQMS brings supply chain quality into the overall quality control processes of the business operations. It •P rovides efficient, consistent, centralized reporting — tracks, analyses and reports on supplier activities globally. It collates feedback from the customers, highlights issues and records how these were put right.

• Involves the board in quality management decisions — moves quality management from a departmental concern to an operational process, which impacts profitability.

• Introduces risk-based analysis for supplier quality — removes the time and cost of supplier reassessments, thereby releasing valuable resources.

• Reduces global pressures — sets-up standard, global processes for managing supplier audits, organizational efficiency and supply quality, whilst still driving profitability.

May/June 2011

SUPPLY CHAIN MANAGEMENT • Increases visibility into potential supplier problems — a global view of all quality issues and supplier scorecards ensures • Regulatory compliance, good manufacturing practices and ISO standards.

• The high costs of scrap, rework and delays caused by quality issues are eliminated.

• Repeat problems are anticipated and eliminated through experience learning.

Critical Components for Supplier Quality Management

An enterprise-wide centralized process needs to encompass quality management and compliance components including • Supplier qualification, including all qualification steps based on the supplier’s risk assessment.

• Supplier audits based on the risk level, audit frequency and the supplier rating or score, highlighting trends in quality issues.

• Incoming material inspections, including all incoming materials and components, and detailing inspection type and results, received date, material information and quantity‑related information.

mAnuFActuRing

www.ngpsummit.eu.com

May/June 2011

• Approved supplier lists and scorecards — maintaining and monitoring approved or preferred supplier lists.

• Supplier nonconformance generating nonconforming material reports from the inspection record or when below quality control standards.

• Supplier CAPAs — tracking all supplier corrective and preventive actions (CAPAs) through to completion.

•S upplier documentation — containing important specifications, including inspection plans, delivery windows and acceptance sampling for received items.

Tim Mohn

Conclusion

Managing supply quality effectively drives compliance and reduces the cost of poor quality, which, with both tangible and intangible ramifications (costs of product recalls, tarnished reputations or brand image), can be detrimental to any business. Without a supply quality management initiative a business’s bottom‑line objectives will be undermined, thus eroding previous organizational successes.

For more information

Tim Mohn Industry Principal Sparta Systems www.spartasystems.com

The FairmonT Le monTreux PaLace, SwiTzerLand

7Th - 9Th June 2011

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SUPPLY CHAIN MANAGEMENT

Falsified Medicines Directive

An Opportunity to Enhance the Pharma Supply Chain

Consumer protection and an ever-increasing concern for health and safety have become central issues in the pharmaceutical supply chain as a result of the need to track medicines moving from manufacturer to dispensing pharmacy.

O

n 16 February 2011, the European Parliament voted in favour of an amendment to the existing (2001/83/EC) Falsified Medicines Directive concerning the threat of falsified medicinal products for human use. Once enforced, this Directive will ensure all prescription medicine products sold in Europe are uniquely identifiable and can be traced throughout the supply chain to ensure authenticity. We believe this agreement brings welcome reassurance. The industry has 3 years to comply once the delegated acts within the Directive are published, by introducing unique labelling to authenticate products.

A variety of solutions already exist to enable manufacturers to achieve compliance as cost effectively as possible; for instance, high-speed print and apply marking systems that allow secure identification and serialization of the secondary packaging of medicines and medical goods at the production line. These work by applying a unique Datamatrix code that includes information such as expiry date, lot number, product number and a serialization code.

Combined, this data helps combat counterfeiting or theft and facilitates fast resolution of claims and recalls because products can be checked for authenticity and tracked throughout their life cycle.

Whilst the technology to do this exists already, implementing the Directive properly will also require the co-operation of all stakeholders — manufacturers, pharmacists, wholesalers and the patients themselves — to create a system that can assign and store unique ID numbers for all products. A central repository such as this will most likely be managed on a country-by-country level to ensure product serial numbers can be checked against the items having been previously dispensed and thereby prevent the possibility of counterfeiting.

In addition to compliance with new smart legislation, other voluntary improvements to data capture and traceability made by pharma manufacturers can bring considerable competitive advantage through better product quality, improved reputation and longer term profitability. Here, there is an opportunity for the industry to learn from the ultra-competitive food and fast moving consumer goods sectors to achieve faster, more accurate order preparation with advanced stock picking strategies, greater shipment accuracy, improved product quality and all round greater safety through better cold chain management. The increased visibility such systems deliver

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Pascal Durdu

will also improve customer intimacy levels by allowing a greater understanding of consumption patterns.

Enhanced Order Preparation

Manufacturers need to supply pharmacies with the right order in a timely manner, often many times daily and at short notice. Pharmaceutical wholesalers/distributors and logistics companies can quickly optimize order preparation processes by applying voice directed picking techniques adopted by food retailers in particular. ‘Pick to voice’ as it is known, has been proven to cut costs and improve operational efficiency by up to 40% depending on existing processes. Most recently, Merck implemented voice picking and the company saw improvements across all areas of the warehouse with just eight pickers using the technology.

The results are faster, more flexible stock picking, fewer mistakes, lower labour and training costs and workforces that can be managed flexibly around peak times. It is also possible to combine voice picking with either manual or automated scanning systems to eliminate the requirement for any pre-dispatch verification.

Shipment Accuracy and Supply Chain Visibility

Next generation automatic shipment verification solutions, such as Visidot (Zetes), use image-based technology to ensure the right medicines are sent to the right pharmacy

May/June 2011

SUPPLY CHAIN MANAGEMENT or hospital. These systems have been employed by manufacturers supplying the major supermarkets to avoid penalties by ensuring 100% accuracy of the shipped pallets and improved supply chain visibility. Using this technique it is also straightforward to inspect items when preparing boxes or crates on the production line, manage returns from pharmacies and create a log of all unique identifiers placed on crates and cartons to maintain a record of products shipped.

Improved Cold Chain Management

RFID technology offers significant advantages for cold chain management and ensures that certain medicines such as vaccines and antibiotics are stored at a constant temperature along the supply chain. In a temperature-controlled environment, the entire operation is only as strong as its weakest link, with every negative impact having a cumulative effect on product quality, including point of sale. Using special RFID tags, it is possible for pharmaceutical companies to monitor temperature levels, ensure that information about any inappropriate events are being escalated and to maintain optimal product quality from the moment medicines are produced to the time they are2dispensed to patients.

Y23_210x140_colad_1:Layout 10/5/11 16:52 Page

Summary

Although there is a range of technology to help manufacturers comply with the Falsified Medicines Directive, its implementation will also require the co-operation of all stakeholders. A collective responsibility exists for all stakeholders within the pharmaceutical supply chain to inform the competent authority if any medicinal products are suspected of being falsified, irrespective of whether those products were distributed by legal or illegal means.

In practice, we believe it will be necessary to create a pan-European system with the support of manufacturers to assign and store unique numbers for all products. Having data in a central repository such as this will mean product serial numbers can be checked against the items having been previously dispensed to prevent the possibility of counterfeiting, but will require a significant increase in data volumes stored between partners. Incoming legislation to increase patient safety clearly creates a challenge for the entire industry, but rather than simply representing additional unnecessary ‘red tape,’ it also offers a 1number of real business benefits.

For more information

Pascal Durdu Pharmaceutical Applications Specialist Zetes pascal.durdu@zetes.com www.zetes.co.uk

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47

LITIGATION

ReFORMULATING INTELLECTUAL PROPERTY litigation the IMPLICATIONS for Pharma Intellectual property (IP) litigation in England and Wales has been re-invented with the introduction of a new, radically different, Court system. Claire Bennett and Kokyee Ng of DLA Piper explain what this means for protecting and enforcing your patent and other IP rights.

O

n 1 October 2010, the Patents County Court underwent a number of radical changes. Now known as the Intellectual Property County Court (IPCC), the IPCC has been re‑invented as a truly different forum to the High Court for resolving intellectual property disputes. So what are the main features of the new regime and what implication do these changes have for the pharma industry?

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IPCC which, despite its previous name, handles all types of IP including • Infringement or ownership disputes relating to patents, copyright and registered or unregistered trademarks and design rights.

• Actions to revoke registered rights.

• Technical trade secrets claims.

The IPCC was intended to provide an alternative forum for settling such disputes to the High Court, which historically dealt with high value, more complex and more expensive claims. In reality, however, as the same procedural rules applied there was little difference between the handling and costs of claims in either forum. By changing procedural rules and imposing monetary limitations, the reforms are designed to improve access to the courts for individuals and small- and medium‑sized enterprises (SMEs).

The New Regime

Identifying the Key Issues at the Outset Unlike in the High Court, where skeletal formulaic statements of case are the norm, in the IPCC both the claimant and the defendant are required to set out their cases in full from the outset in their written statements of case. The idea is to encourage early settlement, and the upfront disclosure of each party’s case should enable a better assessment of the strengths and weaknesses of each party’s case. As a result, however, a claimant will need to do more work preparing its case before issuing proceedings and overall, despite an extended period for putting in its defence, a defendant may well have less opportunity to prepare its case.

Stricter and More Active Case Management by the Judge The Judge is expected to take a more interventionist approach in managing cases. Also, the Case Management Conference (CMC) held after the statements of case are exchanged assumes greater importance.

Transfer to the High Court A party may ask for the case to be transferred to the High Court (or vice versa), but the application must be made before or at the CMC. In deciding whether to transfer the case the Judge will consider whether a party can only afford to use the IPCC and whether the claim is an appropriate one for the IPCC to determine (considering among other matters the claim’s value and complexity of the issues). This is likely to make it difficult for larger businesses to ‘forum shop’ for tactical purposses; for example, forcing a case issued by an

May/June 2011

R&D

PRECOMPETiTIVE COLLABORATION R. Arun Kumar, Board Member of the Pistoia Alliance talks to Pharma about the Alliance and its aims to improve R&D business processes.

What is the Pistoia Alliance?

The Pistoia Alliance is a global, not‑for‑profit, precompetitive alliance of life science companies, vendors, publishers and academics that aims to lower barriers to innovation by improving the interoperability of R&D business processes. We differ from standards groups because we bring together the key constituents to identify the root causes that lead to R&D inefficiencies and develop best practices and short‑term technology pilots to overcome common obstacles.

Who is in it?

The Pistoia Alliance uniquely brings together key players in life science R&D. The more than 45 member organizations in the Alliance include seven of the top 10 pharmaceutical companies, as well as smaller pharmaceutical and biotech businesses such as UCB; service organizations such as Infosys, Cognizant and HCL; and vendors in R&D informatics and publishing, including CambridgeSoft, Accelrys, ChemAxon and Thomson Reuters. We are also reaching out to academics, as we know academic collaboration is increasingly important to R&D research programmes. We believe a solid working relationship among these constituents is essential to resolving many of the emerging issues in the precompetitive domains of R&D.

spans a broad range of companies, including pharmaceutical and other life science companies, technology suppliers and academic research groups.

Members team together in working groups to identify business process impediments, define use cases and implement technology solutions; so we encourage a broad cross‑section of industry experts to join and share their expertise.

What are the current hot topics in drug discovery and how is the Alliance addressing each of these?

Precompetitive collaboration is a critical issue for pharmaceutical and life science companies as they restructure for competitiveness in a tough business climate. The global economic crisis came at a hard time for this industry. Prior to the crisis, pharmaceutical companies had already been struggling with the

Why was it formed?

Informatics experts at AstraZeneca, GSK, Novartis, and Pfizer, who were together attending a meeting in Pistoia (Italy), first conceived the Pistoia Alliance in 2007. During their conversations at the meeting, Pistoia’s founders realized that their organizations were struggling to solve many of the same problems. How could they integrate access to proprietary and public data sources? Was the cloud a viable option for R&D informatics? They agreed that by working together to solve these common problems in an alliance including companies, vendors and academics, they would be able to spend more time on innovation and direct their resources to projects with more strategic impact.

Who is eligible to join?

The Pistoia Alliance is open to individuals and organizations engaged in R&D life science. This

50

www.pharma-mag.com

R. Arun Kumar

impending expiration of several major patents. The age of the blockbuster drug was coming to an end, and companies were concerned with how to re-invent themselves and regain profitability. Then the economic crisis hit, putting further pressure on organizations to “do more with less.”

This is why precompetitive issues are so important.

Organizations aren’t set apart in the marketplace by how they run a centrifuge or access public and private sources of sequence data or configure their electronic laboratory notebook (ELN) so that information can be shared with outsourced partners. Innovation rests in what they do next — the decisions that are enabled by

May/June 2011

LITIGATION individual to be transferred to the High Court with the aim of putting financial pressure on that individual.

No Automatic Right to Disclosure or to Put in Further Evidence or Written Arguments In contrast to the High Court there is no automatic right to put forward any further facts or arguments as these are supposed to be put in the statements of case. The idea is that where possible the Judge will decide a case based on the statements of case and oral submissions at trial alone, thus significantly reducing costs. A party may apply for • Specific disclosure of documents held by the other party.

• A description of the alleged infringing product and/or process.

• The submission of further evidence of fact or expert evidence, and/or skeleton arguments.

• To cross–examine the other party’s witnesses or expert at trial.

The above, however, will only be permitted if they each satisfy a strict cost‑benefit analysis, and will be limited to specific identifiable issues.

Shorter Trials and Paper‑Based Decisions The trial will generally be limited to 1–2 days (compared with a more typical 3–5 days, or longer, in the High Court) thus significantly reducing trial‑related costs. The parties can also elect for a decision to be made without a hearing based on the materials submitted.

Limits on the Recovery of Legal Costs In England and Wales, the loser generally pays the winner’s legal costs. The indeterminate potential cost liability if they should lose can deter individuals and SMEs from bringing a claim. Under the new system, the costs recoverable at each stage are capped (amounting to a total potential liability of £50,000 if the case goes to trial and a further £25,000 cap for any subsequent enquiry as to damages), providing certainty.

Limits on the Recovery of Damages The winner is limited to recovering a maximum of £500,000 in damages.1

The New System in Practice

So what do these changes mean in practice for a pharma business — in which situations might the IPCC prove useful?

Preventing Infringement of Patent and Other IP Rights With the cap on recoverable damages awards, where infringement has been going on for a while, a patent holder may prefer to bring proceedings before the High Court to be able to recover a suitable level of damages. When an infringer is unlikely in practice to be able pay more than £500,000, or when obtaining an injunction is of primary importance, as is often the case (for example, where aiming to prevent the launch of a competing product or use of trade secrets), the IPCC offers a lower cost alternative to the High Court.

Clearing the Way The IPCC would be a suitable forum for attempting to revoke a patent in simple cases, for example, where the

May/June 2011

technology is not complex or there is clear evidence that a patent is invalid. As much of the case preparation is done in advance and the scope for putting in further evidence is limited; a business is likely to be able to obtain a quick result and can put pressure on the patent holder as, overall, the patent holder has a more limited opportunity to gather together its defence.

Testing the Validity of a Patent On the flip side, when England and Wales are not key markets a patent holder could use the IPCC as a forum to test the validity of its patent before proceeding to enforce its patent in other territories — the patent holder should be able to obtain a quick decision with a low cost risk, and with up-front case disclosure may obtain information that it can use to shape its approach in other territories. Overall, the infringer will have a more limited opportunity to put its invalidity attack together.

Nonpatent IP Rights and SMEs The IPCC is likely to be particularly advantageous and cost effective in cases involving IP rights other than patents as, in many cases, it may be possible for the matter to be determined on the papers with little, if any, further documents, evidence or arguments. By lowering costs and enhancing visibility of the strength of the party’s respective cases and predictability of potential costs liabilities, the reforms open up access to the courts for individuals and SMEs. Although the opposing party can still spend us much as it chooses in pursing its case (it is only the amount of costs that may be recovered that it is limited), the new regime goes some way to levelling the playing field.

Conclusion

Overall, the reforms introduce a forum where the requirement for more up-front preparation will impose a greater management burden before commencing a claim, but the early disclosure of a party’s case should enhance visibility of a party’s true commercial position. Cases should be cheaper and quicker whilst retaining the quality of judgement for which England and Wales is renowned (the IPCC Judge is a specialist IP practitioner experienced in dealing with technical subject matter).

For larger pharma businesses, the reforms have extended the range of litigation options available in England and Wales that can be exploited. Saying that, given the aim of the reforms the Judge may be reluctant to allow cases between two large pharma companies to proceed in the IPCC and a large pharma company may more typically find itself in the IPCC only when an individual or SME is involved, or in less complex nonpatent‑related matters.

It remains to be seen whether the re-invented IPCC will better enable individuals and smaller businesses to enforce those rights that are at the heart of their business. At the time of writing, the first new cases under the new regime are due to be heard.

Claire Bennett

Note

1. This limit is due to come into effect on 14 June 2011 for patent- and registered design right‑related actions, and is intended to be extended to all IP actions later in the year.

For more information

Claire Bennett Lead Lawyer Intellectual Property and Technology DLA Piper +44 207 796 6992 claire.bennett@dlapiper.com Kokyee Ng Trainee DLA Piper

www.pharma-mag.com

49

R&D

PRECOMPETATIVE

COLLABORATION

R. Arun Kumar, Board Member of the Pistoia Alliance talks to Pharma about the Alliance and its aims to improve R&D business processes.

What is the Pistoia Alliance?

The Pistoia Alliance is a global, not‑for‑profit, precompetitive alliance of life science companies, vendors, publishers and academics that aims to lower barriers to innovation by improving the interoperability of R&D business processes. We differ from standards groups because we bring together the key constituents to identify the root causes that lead to R&D inefficiencies and develop best practices and short‑term technology pilots to overcome common obstacles.

Who is in it?

The Pistoia Alliance uniquely brings together key players in life science R&D. The more than 45 member organizations in the Alliance include seven of the top 10 pharmaceutical companies, as well as smaller pharmaceutical and biotech businesses such as UCB; service organizations such as Infosys, Cognizant and HCL; and vendors in R&D informatics and publishing, including CambridgeSoft, Accelrys, ChemAxon and Thomson Reuters. We are also reaching out to academics, as we know academic collaboration is increasingly important to R&D research programmes. We believe a solid working relationship among these constituents is essential to resolving many of the emerging issues in the precompetitive domains of R&D.

spans a broad range of companies, including pharmaceutical and other life science companies, technology suppliers and academic research groups.

Members team together in working groups to identify business process impediments, define use cases and implement technology solutions; so we encourage a broad cross‑section of industry experts to join and share their expertise.

What are the current hot topics in drug discovery and how is the Alliance addressing each of these?

Precompetitive collaboration is a critical issue for pharmaceutical and life science companies as they restructure for competitiveness in a tough business climate. The global economic crisis came at a hard time for this industry. Prior to the crisis, pharmaceutical companies had already been struggling with the

Why was it formed?

Informatics experts at AstraZeneca, GSK, Novartis, and Pfizer, who were together attending a meeting in Pistoia (Italy), first conceived the Pistoia Alliance in 2007. During their conversations at the meeting, Pistoia’s founders realized that their organizations were struggling to solve many of the same problems. How could they integrate access to proprietary and public data sources? Was the cloud a viable option for R&D informatics? They agreed that by working together to solve these common problems in an alliance including companies, vendors and academics, they would be able to spend more time on innovation and direct their resources to projects with more strategic impact.

Who is eligible to join?

The Pistoia Alliance is open to individuals and organizations engaged in R&D life science. This

50

www.pharma-mag.com

R. Arun Kumar

impending expiration of several major patents. The age of the blockbuster drug was coming to an end, and companies were concerned with how to re-invent themselves and regain profitability. Then the economic crisis hit, putting further pressure on organizations to “do more with less.”

This is why precompetitive issues are so important.

Organizations aren’t set apart in the marketplace by how they run a centrifuge or access public and private sources of sequence data or configure their electronic laboratory notebook (ELN) so that information can be shared with outsourced partners. Innovation rests in what they do next — the decisions that are enabled by

May/June 2011

R&D the workflows they establish and the data they access.

By working together in an alliance such as the Pistoia Alliance, organizations go farther. Use cases are more accurate, problems are better defined and solutions are easier to achieve quickly.

Another hot topic is how the pharmaceutical industry can tackle the challenge of handling the huge amount of sequence data that is hosted on public databases and how to analyse and query this data for gene evaluation purposes both securely and confidentially. From a company perspective, Infosys is interested in understanding the challenges and market needs in R&D so that it can better contribute to appropriate solutions and services. By participating in the Pistoia Alliance, Infosys can be closely involved with its various initiatives and help direct the industry to focus more on enterprise‑class solutions. Infosys believes that by 2015, R&D initiatives will involve externalization (collaborating with external partners, sometimes even competitors) in a much more significant manner than now. The technologies around cloud‑based computing, social networking, mobility, analytics and interoperability will form the foundation around which this will happen. By participating in

May/June 2011

working groups, Infosys is also gaining exposure and insights into the real‑life challenges and innovative solutions being considered by the industry and hence is in a better position to contribute to its evolution.

What are the Alliance’s plans for the next 5 years?

Many of the Alliance’s initial projects will be coming to fruition this year. We have completed two feasibility studies: the first aimed at defining and documenting an externally hosted service for securely storing and mining both proprietary derived gene/sequence information and public domain gene databases; and a second one focused on the feasibility of providing an Amazon‑like “brokering service” that scientists can use to rapidly gather information on disease‑causing genes. We are also sponsoring initiatives to define better vocabularies to support data exchange and overcome obstacles to hosting ELNs in the cloud.

Our aim during the next 5 years is to work within the broadly defined biology and chemistry domains to identify and resolve some of the roadblocks that keep organizations from thinking broadly and creatively about R&D problems.

For more information

R. Arun Kumar Vice President and Head of the Global Life Sciences Infosys Board Member of Pistoia Alliance http://pistoiaalliance.org

www.pharma-mag.com

51

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Astra Biotech manufacture high quality reagents, allergens, antibodies, recombinant proteins and assays for the determination of hormones including fertility, allergies, genetic related diseases and tumour markers plus are able to supply component materials for existing products. Astra Biotech GmbH is known for producing superior products by incorporating only certified high purity reagents and by rigorous quality control procedures in their manufacturing facilities thus enabling clear tracking of all component materials.

Astra Biotech is able to supply complete ranges of IVD compliant assays down to individual components so that partner organisations may fill gaps in their present portfolio without the expense of further research and development costs.

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Micronic Europe has announced a new 1.4ml amber polypropylene storage tube that, used in conjunction with a secure screw cap, ensures the integrity of light sensitive biological samples even over long-term storage periods.

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Micronic has introduced a new version of its Roborack 96-position sample tube storage rack.

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provide a stark contrast thereby providing excellent bar coding readability and minimising the risk of incorrect sample identification.

Society of Biomolecular Screening (SBS) standard footprint, Micronic’s 1.4ml amber storage

The white Roborack-96 incorporates a wealth of novel features enabling turn-key integration

tubes are compatible with almost all automated sample handling systems. Manufactured to strict

into almost any laboratory automation systems. An enclosed wall design allows robotic grippers

tolerances, the precision and consistency of Micronic amber storage tubes maximises operational

to access the rack from any height allowing easy rack manipulation and movement. Contoured

uptime when used with automated cherry picking and other sample handling systems.

Sure-Shot™ well tops on the Roborack-96 help guide tubes that are incorrectly delivered by

Produced from high-quality, FDA-approved polypropylene, in a class 7 automated

automated equipment. The design allows robotic grippers to access the rack from any height for

manufacturing facility, Micronic amber storage tubes resist most organic solvents and are

easy rack manipulation. The wells have an open airflow design for faster freezing and thawing.

To ensure sample integrity during transport or storage each Roborack-96 is supplied with an easy-to-operate lockable lid. All Micronic racks are manufactured under US Federal Standard 209E Class 10,000 clean room conditions. www.micronic.com

supplied ‘sample safe’, free from additives or leachates. Micronic amber storage tubes are also fully validated RNase / DNase and pyrogen free, meaning they can be used to store the most sensitive biological samples. www.micronic.com

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This clean/maintenance free system’s cartridges are easy to change in the same way as your desktop printer, printing at speeds up to 300 meters/min. Printing up to 600x600dpi, typical applications include 1D & 2D barcodes, expiry codes, graphics, product identification, date & time and batch numbers. Furthermore its use of Datamatrix barcodes and UV & Infrared printing increases security, ensuring traceability and prevention of counterfeiting of pharmaceutical products, thus helping manufacturers comply with requirements within GAMP and other regulations such as 21 CFR Part 11 and e-pedigree.

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Co-located with CPhI Worldwide for pharma ingredients, P-MEC Europe for pharma machinery, equipment and technology and InnoPack for pharma packaging, ICSE is the must attend networking event for any business or individual in the contract services sector.

Dedicated Zones and Pavilions for Easy Navigation CRO & Clinical Trial Zone: a dedicated area where you can find companies offering Clinical Trials, Pre-Clinical, Clinical Research, Phase 1-4 Clinical Trials and Contract Research services New Exhibitor Zone: a zone where you can find first-time exhibitors at ICSE; companies that might offer just what you need USA Zone: a dedicated zone where you’ll find Outsourcing service providers from the USA Logistics and Supply Chain Zone: a zone where you find the right partners for logistics, distribution and supply chain management solutions General Floor: here you can build partnerships with companies that provide a wide range of contract services BioPh Pavilion: a dedicated area where you can find companies providing bio-solutions for pharma

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53

Case study

Chr Olesen Pharmaceuticals builds stronger relationships at CPhI China Danish API distributor Chr Olesen Pharmaceuticals uses CPhI China as a means to visit new and existing suppliers, build relationships and gauge the state of the Chinese pharma manufacturing industry.

Chr Olesen Pharmaceuticals A/S was founded in 2009 and is part of the Chr Olesen Group. Chr Olesen Pharmaceuticals focuses on the supply of Active Pharmaceutical Ingredients (APIs) to the pharmaceutical industry.

Carsten Machholdt, Head of Global Sales, explains the company’s focus in more detail. ‘Our main business in Chr Olesen Pharmaceuticals is APIs for the generic industry,’ he says. ‘Our principal customers are in the generic industry worldwide, particularly in South America, Africa and Europe.’

Meeting manufacturers With 22 years’ professional experience in APIs, Carsten has attended quite a few CPhI exhibitions; today, he attends CPhI China as a visitor to meet up with suppliers in China. ‘We outsource around 80% of our products from Chinese manufacturers,’ he explains.

‘So for me, attending CPhI China is more about meeting manufacturers than meeting customers. As well as progressing our current sourcing projects, we

54

© 2011 UBM Live. All rights reserved. All brands, product names, company names, www.pharma-mag.com trademarks and service marks are the properties of their respective owners.

also want to meet new manufacturers. We want to discover new sources and talk to the people who are new to the API scene in China.’

Building relationships With such strong links to the Chinese pharma manufacturing industry, Chr Olesen’s key priority is forging stronger alliances with its suppliers in China.

‘For us, the most valuable part of attending CPhI is building relationships,’ affirms Carsten. ‘If you’re looking to break new ground and source new products, it’s ideal.’

‘If you’re looking to break new ground and source new products, it’s ideal.’

Chr Olesen Pharmaceuticals travels to see its Chinese suppliers independently, but CPhI still plays an important role. ‘Once a supplier reaches a certain size, you will obviously want to visit them in any case, and that’s why we visit our manufacturers throughout the year,’ says Carsten. ‘But CPhI is still an important meeting-place for us. On a recent trip to see a manufacturer in China, for example, we agreed that the follow-up to our meeting would take place at CPhI China.’

May/June 2011

CPhI also offers a valuable opportunity to meet several suppliers under one roof, saving time, cost and hassle.

‘It’s a forum where you can save a lot of money in terms of travel costs, by meeting several new suppliers all in one place.’ agrees Carsten.

However, it’s not all business. CPhI is also a chance to chat and relax with suppliers and get to know them as people. ‘It’s great for me to meet with our manufacturers in China,’ says Carsten. ‘It’s a big social event, and a great way to break the ice with new suppliers. I really enjoy it.’

Understanding trends Another important benefit for Chr Olesen Pharmaceuticals is the opportunity to see first-hand how their particular branch of the pharma industry is developing in China. ‘The Chinese API business is developing fast,’ says Carsten. ‘Certain companies are on the verge of beginning to export their finished products into the European market. I’ve been doing business with Chinese manufacturers for 20 years, and the changes over the last 10 years or so have been significant.

Right balance Many factors have to come together to make an exhibition work: the organization, the environment, the exhibitors and the visitors. In Carsten’s view, CPhI is a good example of how to get everything right. ‘With so many exhibitors taking part in CPhI exhibitions, you really have to be very targeted in terms of setting your priorities. CPhI China offers just the right balance: a decent number of stands to visit, good accessibility and the right level of visitor numbers for the event to be truly enjoyable.’

Summing, up, Carsten expresses the key benefits of CPhI China in a nutshell. ‘For us, it’s a great tool for breaking new ground, finding new products and speaking with suppliers – and customers too. We’re very happy with it.’

For additional CPhI China case studies, success stories and customer quotes, please visit: www.cphi-china.com/success

‘We’ve seen rapid development in terms of intellectual property, documentation and product quality.’

‘We’ve seen rapid development in terms of intellectual property, documentation and product quality. Also, many Chinese factories have been upgraded over the last 15 years. Finally, the Chinese government has imposed many more requirements on pharma manufacturers in terms of the environment, which is a positive development – from our point of view, at least.’

Is CPhI helpful in terms of understanding these industry trends? ‘Absolutely,’ replies Carsten. ‘It’s a great forum, particularly for meeting new suppliers with whom we’re hoping to establish a connection.’

© 2011 UBM Live. All rights reserved. All brands, product names, company names, May/June 2011 marks are the properties of their respective owners. trademarks and service

Chr Olesen Pharmaceuticals has its headquarters in Copenhagen, Denmark, and also has three warehouses across the EU, from which it offers just-in-time deliveries to customers around the world. The firm is certified under the ISO 9001:2008 standard, and describes its corporate philosophy as being a reliable partner and supplier, always ready to supply customers with the right product. The company’s stated mission is to be a key worldwide distributor of APIs for the pharmaceutical industry.

www.pharma-mag.com

55

MARKETING

MANAGING MEETINGS AND EVENTS SPEND

The demands of managing the meeting and events supply chain vary dramatically between organizations. Operating in a strictly regulated environment, the healthcare sector was an early adopter of strategic meeting management, but how does the sector’s approach differ from other markets? How do organizations in this industry manage expenditure?

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n 2010, the sector was labelled “about as recession proof as you can get.”1 This year saw a reversal of the slump on new pharmaceutical products coming onto the market that had accounted for a sharp fall in the number of product launches and large meetings organized in 2009.

PricewaterhouseCooper’s (PwC) Pharma 2020 report The vision: Which path will you take? shows that the global pharmaceutical industry would be worth $825 billion by 2013 and almost triple in value to $1.3 trillion by 2020, with much of that growth coming from developing countries.2,3 Yet, PwC predicts that European and US markets are likely to shrink in value, with commentators identifying three influences: “the global economy, the changing mix of new and mature products and the rising influence of healthcare access and funding.”4 The meetings spend of any healthcare organization is substantial. Pharma companies are not allowed to advertise directly to patients outside the US, thus making face-to-face activities highly important in marketing and clinical plans as they enable companies to fully explain their products to desired audiences. Events are proven to deliver measurable results around message retention, as Mark Handforth, former Head of Global Event Management at Roche, affirms: “We tracked through message retention from our events using a marketing research firm, during both our internal and customer face-to-face communications, and confirmed they were proven to deliver strong results against objectives. This data provided evidence to the business case for continuing and often investing more in face-to-face activities.”

According to Nick Bender at Grass Roots, a global meetings, events and communications agency, with big spend comes big expectations to see both cost management and high quality results. “Every pharma company is facing pressure on existing revenues and with a shortage of blockbuster drugs coming through the pipeline they want to cut out areas of waste in big spend. Events usually represent 40% of a healthcare marketing budget and being the biggest line item, this brings close scrutiny.”

“The key lies in having a detailed and credible business model for events including a 3-year view guiding how

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the meetings and events category will be delivered.

With this clarity comes the transparency of spend, opportunities for consolidation and the best operational formats to deliver successful events.” Nick adds: “You don’t manage big spend without change in the healthcare sector because you are consolidating across a broad range of daily activities that touch to some extent everyone in the organization. For example, turning occasional contact with multiple suppliers into approved vendor relationships with possibly new vendors, clearing out bad historical practices, improving approvals processes, evaluating which types of events are optimal in certain circumstances and allocating spend accordingly.”

Grass Roots estimates that 20% of meetings and events programmes within the top 20 healthcare companies are operating reasonably cost efficiently; 50% are generally working towards best practice and 30% are just getting into the process, having implemented a level of structure, but not yet driving best value. The challenge for most procurement departments is that budgets are not held above market and, therefore, managing cash flow from central departments to the supply chain often proves a barrier to successful consolidation.

The sector is pioneering the global consolidation of meetings spend and this reflects how healthcare uses events. A large part of activity is integrated between territories because the science and message is created in a global or regional location and cascaded locally.

Strategic Meeting Management Programme Pioneers

Healthcare has led the trend towards centralized procurement of meetings. In Europe, Pfizer announced achieved savings of 19% in meetings spend by consolidating its meetings spend data.5 Other sectors have reported achieved savings of around 25%.6 Without a Strategic Meetings Management Programme (SMMP) in place, companies can underestimate their meetings spend by up to 60%, according to Kari Kesler, principal developer of the National Business Travel Association’s Strategic Meetings Management Certification. Although the pharma sector has pioneered the concept, the truism remains that companies without control of spend do

May/June 2011

MARKETING not have clear plans in place to manage their meetings and events expenditure. Those falling into this category don’t know what they are spending and where. Their systems don’t allow transparency so they can’t make informed decisions. Procurement and event decision makers recognize there is a problem and want to change, which is fundamental to best practice. Yet, as Nick says: “The problem is that the people specifying the systems aren’t the event owners. Companies have to go down to the individual budget holder level to get an accurate picture of what is happening.”

Compliance

One advantage of a regulated environment is that it makes driving compliance easier. If a healthcare company is not compliant, it could be fined substantial sums by regulatory bodies. There can, however, be a lack of clarity surrounding this, so breaches such as delegations staying in 5-star hotels do happen. As Christian Roth of Novartis puts it: “Compliance and a regulated environment are closely related, although we have to deal with congress and event regulatory compliance, as well as compliance with sourcing and purchasing principles. On top of this there are the various data protection laws in different countries, nonaligned definitions and a lack of awareness in our industry of what’s necessary.”

By 2013, under US law, healthcare companies will be required to track all event spend on a guest doctor including expenses, speaker’s honorarium, meetings they attend and so forth. It’s therefore clear a complete and efficient means of data collection will be essential for pharma meetings that include healthcare professionals.

Effect of Regulation

Every healthcare business is regulated on what it can spend on marketing. This presents an administrative burden to ensure the appropriate decisions are made internally. External agencies can help with this.

In-house event teams are much smaller these days so it is crucial that the agency is on top of compliance requirements. Healthcare businesses often struggle to define regulatory issues, so it goes from being specific to becoming more nebulous. Regulatory bodies are trying to encourage healthcare companies to self-regulate, but interpretation is becoming more prevalent.

Culture and Practices

Dealing with local culture and ingrained practices is another challenge. Meeting programmes must reflect the business needs of the local market and mould regional solutions to meet those needs.

Greater compliance comes from a clear and proper explanation of a strategy that is moulded to local conditions. Change takes time and demands a ‘hearts

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and minds’ approach, as Nick explains: “Implementation of best practices varies between healthcare companies because local needs have to be taken seriously and there are also differing levels of stakeholder understanding of company-wide decisions and their interpretation. In addition, there will always be different ways of looking at the solution and varying levels of control being exerted.”

The results achieved by healthcare companies through consolidation also vary between each other and with other sectors. This is partly because of a greater focus on events in the sector and it is driving best practice in this area of spend consolidation. Nick believes that global strategies with regional variations will be the winning solution for healthcare: “There has to be global strategies for meetings and events spend in the same way as there are global strategies for market research, clinical trials services and manufacturing.”

Best Practice

There is consensus that any organization seeking to achieve procedural or cultural change must have senior level sponsorship for the initiative or process change.

Five ‘must haves’ to achieve best practice are • Deep buy-in to event strategies, particularly in defining what the business model should be, before embarking on the request for proposal process.

• Clear event strategies all the way down the structural chain, providing clear benefits to all stakeholders.

• Stakeholder understanding that robust implementation of a full consolidation process takes 2–3 years.

• Keeping stakeholders informed about successes that are relevant to the individual • Picking the right agency partners to deliver the strategy; those that understand what best practice is, particularly in healthcare.

The Meetings Horizon

National meetings activity will continue to rise, as hospitality rules tighten, co-payment bites and the effort it takes to host a group to an international congress becomes questionable. The role of national cascade and physician-to-physician events will become more important. Medical association meetings will become less attractive, even if they are still perhaps seen as a necessary evil. Congress attendance will change with scientific secretariats having to adapt their events to the needs of their primary revenue drivers and audiences as they both question the relevance of association meetings.

Virtual meetings will become an accepted part of the meetings mix, blending well with face-to-face.

These will play their part in reducing costs and meeting Healthcare professionals’ preferred delivery medium for some message content. Fundamentally, events will remain a significant tool to shaping and changing views and behaviours of target groups.

References

1. h ttp://pharmtech. findpharma.com/pharmtech/ Business/ Is-Pharma-recession-proof/ ArticleStandard/Article/ detail/566721 2. w ww.pwc.com/gx/en/ pharma-life-sciences/ pharma-2020/pharma2020-vision-path.jhtml 3. w ww.bloomberg.com/apps/ news?pid=newsarchive&sid =a2Qi4a8CN.8E 4. E IBTM 2010 Industry Trends & Market Share Report.

5. w ww.btnmag.com/ businesstravelnews/ headlines/meetings_today_ display.jsp?vnu_content_ id=1002839649 6. G rass Roots research 2005–2010.

For more information Mark Harris Contributing Editor of Meetings Industry Report for Grass Roots

www.grassrootseventcom.uk.com A full version of this article, Managing

Big Spend can be downloaded from the White Papers section at www.pharma-mag.com To request a copy of Grass Roots Meetings Industry Report 2011, please email

lisa.maddix@grg.com

www.pharma-mag.com

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NOSTRAPHARMUS

KEEPING THE SUPPLY CHAIN AGILE

Lean thinking works well for the automotive industry, but is it really suitable for pharma supply chains? ‘Agile’ techniques may be more appropriate and promising for the industry’s uncertain future.

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For more information nostrapharmus@wcigroup.com

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n the wake of cost pressures, Lean thinking has made its appearance within the pharmaceutical industry. Nostrapharmus notes that we were asked to look at, and learn from, other industries that have been under cost pressure for decades.

Lean seemed the answer to all our questions; it focuses on eliminating all forms of waste in the supply chain, including spare resources such as inventory and equipment. This works very well in an environment where demand is stable and product variety is low…in fact the very environment in which Toyota developed Lean thinking.

But, does this really work for us? Eliminating waste and, thus, fat from the supply chain does cut costs, but with it also comes risk: it makes the supply chain increasingly vulnerable to disruptions and unpredictable events as there is no slack to fall back on. In the car industry that may not be such a problem — all it means is the customer will just have to wait a little bit longer until the car is ready. Patients, on the other hand, have to take their medication immediately; sometimes their life depends on having the product available day to day. We have the moral obligation to guarantee the best possible treatment to the patients and, consequently, securing the supply of medication.

So, if Lean makes the supply chain vulnerable, does this mean it is unsuitable?

Nostrapharmus says: “We have to apply Lean techniques to cut costs whilst, at the same time, gain supply chain resilience through Agility.” Agile supply chains are, in contrast to Lean, able to respond rapidly to changes and events. Agile supply chains put risk management at the centre of supply chain strategy — buffers removed by Lean are replaced to mitigate or eliminate the risk of out of stocks through change and events. This could be in the form of spare capacity or inventory, depending on the risk to mitigate. The likelihood of occurrence and the financial impact of the risk can be used to calculate the expected cost of recovery from the event. The additional cost of Agility can be compared against this expected cost of risk recovery to come to

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an optimum solution. Yet, if we have learned anything from recent catastrophic events triggered by nature, it is that the cost of risk recovery for certain risks is meaningless. The equation no longer works if likelihood is low, but impact extremely high. Risk management, therefore, should clearly differentiate between more manageable and calculable risks and events that put the overall company at stake. For the latter, the cost of risk recovery should only look at the overall impact, regardless of the likelihood of occurrence.

Agile Supply Chains: Two Key Features First and, perhaps most importantly, is the statistical approach to inventory setting. To create the ability to respond to a sudden or significant shift in demand or supply, the likelihood of such events is statistically calculated through by analysing demand and supply variability. Inventory levels are calculated to buffer confidently against the event. The prerequisite for such methodology is that pharmaceutical companies move away from the more traditional, but uncertain, forecast driven materials requirements planning, to a more controllable demand driven approach.

Second, it requires close supplier collaboration, as often it is the lead time and quality of inbound suppliers that limit the ability to respond. This becomes particularly important with the increased outsourcing we see within our industry. The supplier base needs to be rationalized because it’s just not possible to create close working relationships with many suppliers. Strategic partnerships should be formed with linked processes and systems at multiple levels in the organization. The supplier does not feed into, but becomes part of the overall supply chain.

Nostrapharmus predicts: “In 10 years’ time, risk management will not only take place on a strategic level, but it will have penetrated day-to-day supply chain operations. We will see a comeback of operations research, not to cut costs, but to calculate and balance the likelihood and impact of risks against the cost of mitigation. Agility will become a feature of the industry, and the organizations that succeed in implementing this most successfully are best equipped for survival in an uncertain 21st century.”

May/June 2011

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May/June 2011