As I strolled through Times Square, famous brand coffee cup in hand, towards the Jacob K. Javits Convention Center in New York, my thoughts were entirely focused on Interphex. As I sit here, typing this, I realise that the Interpack event in Dusseldorf looms large. And I am constantly aware of the fact that we are interconnected at all times thanks to the interweb (as my father says). "Inter" has become an important word for us, but what does it mean? 

At Interphex, so much valuable information and intelligence was divulged to expectant delegates. One particular stand out for me was a unified message from not one but two officials that the FDA fully supports continuous manufacturing. Watch this space for forthcoming articles on this very topic. It seems that 'missing out' on this sort of information is what drives our thirst to visit such exhibitions, make new contacts and join salient groups on LinkedIn (other networking tools are available!).  

What can be shared and, thus, what can be learned?  

No doubt Interpack will provide enormous amounts of potential in this vein, spanning multiple industries as it does. I hope to share the experience with some of our readers—you know who you are! 

, sharing is becoming more and more important for us. Peer reviews are a staple of our publication and within these covers you will find three such articles, all delivering strong insight on diverse topics. This has only been made possible by working more closely with 

 in North America. And I would like to take this opportunity to thank them for their continued support and ethic of sharing. 

What this means to you, dear reader, is that our scope for sharing industry knowledge has widened significantly. All peer reviewed articles will now be published simultaneously in both 

 — especially great if you happen to be the author. Our hope is that this move will aid the pharma industry by connecting you, the people in that industry, to what's happening on a scientific level around the world. 

Please feel free to share your thoughts directly with me at 

 or with other likeminded readers on LinkedIn (

Articles

As I strolled through Times Square, famous brand coffee cup in hand, towards the Jacob K. Javits Convention Center in New York, my thoughts were entirely focused on Interphex.

Inter city tales

Extending a drug product's shelf life while maintaining its strength, quality, and purity is a challenge for pharma companies. Using an optimised sorbent formulation, however, can significantly reduce chemical and physical degradation caused by free-moisture, oxygen, and hydrocarbons in the drug product and its packaging. This results in sustained drug product quality, stability, shelf-life, safety and efficacy. 

 Adrian Possumato, global director, healthcare packaging at Multisorb Technologies.   

The process for assuring that a packaged drug will remain stable throughout its expected shelf life is long and difficult. Sometimes a pharma company will have comprehensive knowledge of the mechanisms of degradation for the drug substance or drug product, and will be able to surmise whether a sorbent is required. However, forced degradation studies are often performed to determine whether or not a sorbent is required. Either way, the exact type and quantity of sorbent is often unknown by the company, which leads to the need for sorbent-ranging studies to optimise the sorbent type and quantity. 

If empirically-derived data on the drug product is readily available, modelling can be performed to assist with sorbent selection in a given packaging presentation, which can save time and money. 

Sorbent selection is often an afterthought in the development process; however, it is beneficial to incorporate the correct sorbent in the early stages of the process. Pseudo-empirical modeling provides the means to accomplish this because it can provide an analytical model of the permeation and adsorption of moisture, which can be used to determine the proper sorbent type and capacity needed to achieve the targeted shelf life of a given drug product or drug–device combination product.  

Formulation chemists and packaging engineers must work together in this effort because the drug product, container and sorbent function together as a system. The sorbent will reduce or otherwise manage the Equilibrium Relative Humidity (ERH) and/or oxygen in the packaging headspace, but it will also manage free-moisture in the drug product; thus, managing molecular mobility and chemical degradation. The sorbent must also compensate for the increased rate of ingress of moisture or oxygen through permeable packaging brought on by its use. Modeling simulates how all the interdependent variables will affect one another over time.  

This Quality by Design approach allows manufacturers to quickly determine which sorbent solutions are required. This eliminates the need for sorbent ranging studies and, ultimately, expedites the commencement of registration stability testing and regulatory submission. 

Traditionally, a desiccant packet placed in the drug product packaging would be sufficient to protect the product from moisture. But with today's new drug formulations and progressive packaging configurations companies need the sorbent to fill the role of an intelligent environmental manager. Multiple undesirable environmental conditions can present within the package headspace, such as free-moisture, oxygen and volatiles, which must all be successfully managed. 

Intelligent sorbents are specifically formulated to achieve a desired outcome. Maintaining specific ERH within the packaging presentation is required for the stability of some drug products; for example, amorphous drug substances that undergo oxidation can improve their chemical stability upon hydration. Though aggressive management of moisture in solid state is suitable for moisture-mediated oxidation for most drug substances, doing so with amorphous substances would result in decreased stability. In such cases, the use of an intelligent sorbent formulation combining oxygen management with moisture regulation in the package headspace provides an optimised chemical and physical stability profile of the final drug product. 

In another scenario, a pharmaceutical formulation may need a sorbent to remove volatilised hydrocarbons. All of these cases require an optimised sorbent formulation that can intelligently manage the packaging or device headspace by reacting to environmental changes. 

Some drugs have multiple conditions that must be managed. For instance, moisture and oxygen may need to be removed while allowing a specific hydrocarbon to remain. Another example is a combination drug product where two drug substances are combined into a single dose. These formulations can require complex, multifunctional, intelligent sorbents.  

In addition to sorbent chemistry, the sorbent device configuration must continually evolve with the demands of the changing market. In many applications, a drop-in solution such as a sachet or canister will work well. With some drug delivery systems, this is not a feasible approach and a fit-in solution is required where sorbent is compressed and shaped to fit into an available space in the packaging or drug device. A third option is a built-in solution where a desiccant-loaded polymer is used to make a component of the packaging or device.  

The commercial success of a pharmaceutical is dependent upon protecting the drug from degradation. The important thing to remember is that sorbent selection is a complex process that involves many interdependent variables and nothing should be left to chance. 

Special Feature

Extending a drug product's shelf life while maintaining its strength, quality and purity is a challenge for pharma companies.

Extending Shelf-Life With Sorbents

Editor's Note: This article is part of a special feature on packaging that was published in the May issue of PTE Digital.

There are a number of points to consider where secondary packaging is concerned. In most cases, the secondary pack has to fulfil dual roles of product protection and product information; both of which are arguably more important in pharma compared with other industries because of the nature of the product. 

Product protection falls into two categories. The first is physical protection. Will the carton withstand physical shocks? Is it substantial enough to maintain integrity throughout the supply chain? The second category is brand protection, which has been at the top of the pharma industry's agenda for years. Anti-counterfeiting strategies, which may involve both covert and overt features, as well as item-level serialisation, can also influence many aspects of the packaging. 

On-pack product information strategies are often influenced by the category of the product (e.g., prescription only, OTC) and the relative importance of product branding. Needless to say, on-shelf appeal has a significant impact on the design of every aspect of OTC packaging! 

Common to all pharma products is the requirement for variable data, including batch/lot codes and expiry dates. Some countries also operate reimbursement schemes that require a specific label or vignette to be applied. Most legislation require variable data in human-readable format, but in future, as a result of the EU's Falsified Medicines Directive, data will also need to be incorporated in Data Matrix format for products to be sold within EU markets covered by the directive. 

Pharma manufacturers and their suppliers are used to complying with regulations, but this doesn't mean that regulations don't present challenges. One recent example is the need to incorporate Braille onto packaging, which became mandatory for new Marketing Authorisations in 2005. Since 30 October 2010, it has been mandatory for all packs to bear the product name and strength in Braille. Some manufacturers also use accessible media packaging that assists the visually impaired by speaking product information aloud. 

The Falsified Medicines Directive will also present challenges, with the industry potentially having to re-evaluate every stockkeeping unit to ensure that there is adequate space and an appropriate surface to apply the new information. 

Last but not least, child-resistant and senior-friendly strategies are increasingly in the spotlight. The ideal pack is one that, through a combination of cognitive and physical capabilities, allows ease of access for adults, but remains strictly off-limits for minors. 

A number of innovations can be seen in pharma packaging. Some boost brand profile or protect the brand by frustrating the counterfeiters. Others can boost product protection or enhance patient compliance. One example of a novel pack with multiple benefits is the walletstyle packs. In the competitive OTC arena, such packs are popular for their portability and branding opportunities. Many also offer high childresistant and seniorfriendly properties. Some innovations respond to more than one of these objectives. The Burgopak sliding blister pack, for example, was originally developed for its marketing appeal, but has subsequently proved to have substantial benefits in terms of improved patient compliance and child-resistant and senior-friendly properties. 

Environmental responsibility is also high on the list of pharma's priorities and often forms part of the supplier qualification process where new contracts are concerned. While regulations governing pharmaceutical packaging may seem to militate against radical changes, major steps have been taken in the area of greener packaging. For example, pharmaceuticals are required by law to accommodate certain patient information. Traditionally, this has been in the form of a leaflet that is folded and inserted into the carton. However, the use of leaflet labels means that for some presentations (notably bottles), the product information can actually be applied directly to the product, which makes the carton superfluous. This can radically reduce a product's carbon footprint. 

Another notable trend is the move away from recycled materials to virgin board. While this might seem counter-intuitive, virgin board has a significantly improved environmental impact compared with recycled materials because of improved handling and lower ink absorption. 

Pharmaceutical packaging is positive proof that regulation doesn't necessarily stifle innovation! 

 is business development director at Brecon Pharmaceuticals.

There are a number of points to consider where secondary packaging is concerned.

Packaging Considerations

Editor's note: This article is part of a special feature on packaging that was published in the May issue of PTE Digital.

Legislation has prompted the pharma industry to seek technologies that can be used alone or in combination to secure a product throughout the supply chain. Some markets, including France, Italy and Turkey, have specific guidelines about identification solutions that must be applied to packaging to help solve counterfeiting and reimbursement challenges.  

In February this year, members of the European Parliament approved a new law to help prevent fake medicines from entering the supply chain by mandating the use of technologies that enable pharmacists and patients to check whether the outer packaging has been tampered with. One solution could be to include a serialisation number that can be 'read' by the pharmacy to ascertain whether the pack is authentic. The European Parliament has also recognised that outer packaging needs to be made secure with tamper-evident labelling or similar measures. In this respect, a combination of overt and covert measures may provide optimal security because they help prevent counterfeiting and reassure end-users. For example, the packaging could use a holographic label containing a random code that is repeated in the serialisation number or even on the tablet or medication itself. 

Currently available solutions vary from the straightforward application of labels to far more complex solutions, such as serialisation, which requires a significant supporting infrastructure to gather data at various points of the supply chain. To protect a product, it is important to use a multilevel approach that combats the counterfeiters at as many stages of the supply chain as possible.  

Serialisation is certainly one of the most discussed anti-counterfeiting solutions. If it is implemented effectively then it could be possible for a patient to verify the authenticity of their medication from their mobile phone. As well as helping to secure supply chains, serialisation also offers the benefits of real-time visibility, and precise data on inventory balances, production status and other key project information across the production lifecycle. The main challenges of implementing serialisation, on the other hand, are the complexity of data that needs to be captured and tracked, and the requirement for potentially huge, multi-access databases.  

Anti-counterfeiting measures can also be incorporated through the medication itself by using intellectual property or a specific feature that is recognisable to the patient, such as a distinctive mouth feel, that makes a medicine difficult to imitate. If you can't make it, then you can't copy it! 

Packaging selection often takes place late in development programmes and cost is a key factor. If the purchasing team are not fully briefed on the adverse impact of counterfeits, then they will view any cost increases to counter this risk as unnecessary. Another risk in the implementation of anti-counterfeiting technology is that the chosen technology may be replaced if the industry veers towards a different solution. As such, for the moment at least, there is reluctance to commit to any specific coding or marking technology until regulation makes it essential. 

Legislation has prompted the pharma industry to seek technologies that can be used to secure a product throughout the supply chain.

Improving Packaging Security

How has pharma's demand for coding technologies altered recently?

More challenges face the pharma packaging industry today than ever before. According to some estimates, the market for counterfeit and illegal drugs is worth between $75 billion to $200 billion.

  Such drugs are thought to kill more than 100000 people every year — mainly in developing countries,

  but more and more cases are occurring in developed regions, necessitating the need for anti-counterfeit technologies on packaged products.  

Additionally, the industry must deal with fiscal recovery and legislative compliance programmes that oblige manufacturers to invest in and modify their existing production and packaging lines. In particular, there are a number of regulatory drivers pushing the industry to incorporate machine-readable codes, such as 2D Data Matrix codes, onto their packaging. These codes can increase patient safety by enabling product authentication, which can prevent reimbursement fraud and help identify counterfeits.  

Mass serialisation is a growing area of interest and a number of countries are changing their packaging requirements to meet new traceability initiatives. As well as increasing the use of 2D barcodes, these initiatives will involve greater use of serialised numbers and increased levels of human readable information. One example of such a legislation is France's CIP13 mandate, which came into effect on 1 January 2011. The legislation requires pharmaceutical packages to incorporate a 2D data matrix code comprising product code, batch number and expiry date, alongside human-readable information. Other countries also have proposals in place to adopt a similar code structure.  

These pieces of packaging legislation will require pharma companies to add new print and verification capabilities to their existing packaging lines. According to our research, up to 80% of currently installed coding devices within the pharmaceutical and healthcare sector cannot meet the required high speed and quality levels.  

How are new coding systems adapting to these demands?

Coding small packs with detailed information at high speed is a challenging application. High-resolution coding technologies such as thermal ink jet or scribing laser are generally best-suited to this duty. While neither technology is brand new, there is a continued emphasis on optimising the technology to deliver fast, high quality coding for optimum packaging line efficiency. Where thermal inkjet technology is concerned, matching the ink to the substrate to be coded is important to ensure a crisp, highcontrast code. With laser, higher-powered models address the need for speed. In both cases, it's important to take a holistic view of the installation, rather than looking at coding in isolation. 

Innovations in product identification are also taking place off the packaging lines. New technologies exploit the ubiquity of smart- and camera-equipped mobile phones by enabling patients to routinely capture data matrix codes of various types, which can then be cross-referenced with an online database to provide instant authentication. This is also a good way to build customer relationships. 

Which technologies are proving popular for pharma companies?

At our company, we find that the most popular coding systems in the pharma industry are thermal ink jet and laser systems. Thermal ink jet enables the printing of highquality 2D Data Matrix codes and other machine-readable formats at high speeds. Such systems also have minimal maintenance because changing the cartridge changes the whole printhead, without the need for an engineer. Scribing lasers also enable the printing of unique numbers and codes, but also eliminate the risk of ink contamination, which makes them very popular in pharma applications. These laser systems also offer clear marking and require less maintenance. Recently, a number of advances have also been made in this area. These advances includes the development of high-powered lasers for faster performance and more robust, compact systems, as well as technologies to allow for a greater linear marking area. 

Existing technologies are already well-suited to meet the current needs of the pharma industry in terms of legislation and traceability requirements. However, the challenge is to optimise these technologies to ensure that packaging and production lines are as lean and efficient as possible. 

1. All News Wire, "Fake Drug Rings on the Rise" (September 2010). 

2. The Economist, "Poison pills" (September 2010). 

More challenges face the pharma packaging industry today than ever before, according to Domino Printing Sciences' global life sciences sector manager.

Meeting New Packaging and Coding Requirements

This article is part of a special feature on packaging that was published in the May issue of PTE Digital, available at http://www.pharmtech.com/ptedigital0511.

In light of the challenges facing the pharma industry, such as changing patient demands and changing demographics, the relationship between the packaging, the consumer, and the product is being completely reconsidered as marketing and brand managers realise how beneficial well-designed packaging can be. For OTC products, good packaging can improve brand communication in a highly competitive market. If packaging is attractive, interactive, portable and a helpful reference, then the user is more likely to build a positive response to the product. Packaging that is not user friendly or that does not clearly communicate the added benefits of the medicine, will hold the brand back. 

 Tim Clarke, CEO, healthcare and technology, at Burgopak Ltd. 

First impressions are crucial. When a consumer receives a product, their first interaction before taking the medicine is the packaging. Packaging that distracts the patient from thinking about their illness, but focuses them on the benefits of taking the medication is key. Think like a patient. What does the packaging say to them? Is it easy to use? Environmentally friendly? Well designed with clear communication? These are a few of thoughts that take place before the medicine has even been used. Smart packaging can help to make the patient feel more secure and well informed, and this can help improve compliance, which is a big issue in the pharma industry. 

One problem with traditional medical packaging is that the leaflet, medicine and outer carton are separate components. Patient information leaflets are usually large once opened up and are almost impossible to reassemble back into the outer carton! Leaflets may then be discarded, leaving the patient with no reference point if they have any concerns regarding the medication they are taking. This can result in the patient not taking the medication correctly and prolonging their illness. Intelligent packaging design that is user friendly, functional and influences the patient to interact with the packaging helps support compliance.  

One big issue for the pharma industry is general regulation, which is ever changing and becoming more stringent. In the area of packaging, however, the regulatory requirements for text and graphics have remained largely unchanged for many years, with the one notable exception of the mandate to include Braille on the outer carton. In the highly competitive market of OTC packaging, regulators, such as the UK's Medicines and Healthcare products Regulatory Agency, do appear to be getting stricter about not over-emphasising a product's benefits through claims such as "Max. Strength" and "Faster Acting". 

Another problem in the industry is counterfeiting. Most pharma companies have adopted covert solutions to tackle this problem. However, packaging differentiation can also play a role. If a package is innovative and more difficult to produce than traditional packets and cartons, it may discourage counterfeiting.  

Some packaging solutions are available that address all of these issues in a single pack; ultimately, improving patient compliance, discouraging counterfeiting and keeping the manufacturer's brand in front of the patient. 

In light of the challenges facing the pharma industry, such as changing patient demands and changing demographics, the relationship between the packaging, the consumer and the product is being completely reconsidered.

The Relationship Between Packaging And The Patient

How do you measure innovation in outsourcing? 

Outsourcing can have its benefits, but how often do we bother to measure the actual value of our outsourcing relationships? Or the innovation they deliver? In Europe, at least, the answer is: not very often. 

According to a study conducted by business consultancy services provider, Cognizant and the UK's Warwick Business School, about two-thirds of companies don't attempt to measure the value of innovation gained 

outsourcing. The study encompassed 250 chief innovation officers (CIOs) and chief financial officers (CFOs) in Europe, and examined their attitudes about outsourcing for innovation. 

Ironically, most CIOs and CFOs seem fully aware of the benefits that outsourcing brings. More than 60% of CIOs turn to outsourcing companies for innovation and 50% said they would be willing to pay more for an outsourced service that enables them to maintain innovation within their industry. Threequarters of respondents (70%) also believe that innovation achieved through outsourcing contributes to their organisation's financial performance. The study also notes that more is being spent on outsourcing now than at any other point during the past.  

 in an interview, Sanjiv Gossain, UK MD of Cognizant, explained the problem in greater detail. "While businesses are clearly turning to outsourcers to aid and deliver innovation within their organisations, many are missing a major opportunity to demonstrate the successful impact that this innovation is having within the organisation. This can only mean that money is being wasted by investment into innovation initiatives that are not delivering tangible results." 

So why are so few companies actually measuring the value and innovation that they get from their investment? 

One major hurdle lies in actually finding a method to successfully measure the value of outsourcing and the innovation it delivers. "The problem comes with defining innovation and educating businesses on how to successfully measure it to prove its impact on the company's bottom line," Gossain told 

Ilan Oshri from Warwick Business School explained that the management of innovation is a key weakness in many businesses. However, Warwick Business School is now in the process of conducting qualitative research among C-level executives in more detail to put a figure on the value of innovation and further investigate the links between outsourcing and client organisations. The final findings will be available in a report later this year, available for download at 

This isn't the first time that Cognizant and Warwick Business School have examined outsourcing issues. In 2009, they conducted a study about the benefits of outsourcing beyond the one-time cost saving. The results revealed that less than half of CIOs and CFOs try to calculate the impact of outsourcing on their business. If you missed out on this then you can catch up in the October and November 2009 issues of

"This new research into innovation, and the accompanying academic report due later this year, is a natural extension of our former study," said Gossain. "Modern outsourcing relationships now offer and deliver far more than just cost savings. Clients are now looking for more value from their outsourcing partnerships and innovation is a big part of this. This is a shift we are seeing across the industry." 

Modern outsourcing relationships should help a business to innovate, and metrics should be established at the very beginning. It is also important to appraise any financial benefits that outsourcing for innovation offers.   

"In order to drive repeatable innovation, companies need to establish a framework with their outsourcing partners to determine their objectives and formalise the innovation achieved," said Gossain. "Developing metrics will also help the C-level share the results and prove the worth of outsourcing-led innovation." 

Pfizer has sold Capsugel to Kohlberg Kravis Roberts & Co L.P for approximately $2.4 billion. Capsugel's headquarters will remain in New Jersey and any Pfizer staff dedicated to the business will be transferred to Capsugel. 

Sanofi-aventis has, at last, gained full control over Genzyme, bringing the much talkedabout acquisition deal between the two companies to a close. The deal, which has been under negotiation since August 2010, will give sanofi an extended presence in the field of biotechnology and, in particular, rare diseases.  

AstraZeneca has paid $1.1 billion to settle a dispute with UK and US tax authorities concerning transferpricing arrangements for the company's US business. The amount, however, is lower than the company had anticipated. As a result, AstraZeneca will add $500 million to its first-quarter earnings for 2011. 

The global market for biosimilars is set to grow from $243 million in 2010 to $3.7 billion in 2015, according to Datamonitor. One of the key drivers for growth will be the loss of patent exclusivity for many branded products. More than 30 branded biologics with sales of $51 billion will lose patent exclusivity by 2015.  

News

Outsourcing can have its benefits, but how often do we bother to measure the actual value of our outsourcing relationships?

Editor's Note: This article is part of a special feature on packaging that was published in the May issue of PTE Digital. 

Research conducted in the UK by the University of Leeds and Luto Research shows that many commonly-used phrases on medicine labels are easily misunderstood, which is why the latest version of the UK's British National Formulary (a drugs bible used by doctors, nurses, pharmacists and other health professionals) will feature revised, simplified language and phrases. 

 caught up with DK Theo Raynor in an interview to find out more... 

What labelling changes are being recommended in the UK?

The labelling changes being recommended relate to the 30 or so "cautionary and advisory labels" that pharmacists use when labelling prescription medicines. These include wordings such as "Avoid alcoholic drink" and "This may cause drowsiness", which have remained unchanged for 30 years. The BNF asked Luto Research and the University of Leeds to user test the labels with members of the public to determine whether they were understandable.  

We used nearly 200 people in three rounds of testing. In one-to-one interviews, people were asked to explain, in their own words, the meaning of each label's wording. After each round, the performance of each label was assessed and if there were problems, the label was re-written and re-tested. A number of labels were re-written in this way. For instance, "Avoid alcoholic drink" became " Do not drink alcohol while taking this medicine"; "Take with or after food" became "Take with or just after food or a meal"; and "May cause drowsiness" became "This medicine may make you sleepy".  

The philosophy behind this testing and the changes is that many of the wordings used technical language rather than everyday language, which can be confusing. It is important to take into account everyone who takes medicines, including those who are not proficient readers. 

On-package instructions are often more widely read then leaflets accompanying a medicinal product. Do you think that there is more that pharmaceutical manufacturers should do in the area of on-package labelling?

This research related to the labels that pharmacists prepare and apply to prescribed medicines whenever they are dispensed. One key issues for pharmacists, however, is where do they apply the label on the original pack? There needs to be a space large enough to accommodate the label without obscuring information that is on the pack. In particular, the label should not be placed over a barcode because this often shows through the label and makes it more difficult to read. 

For OTC medicines, pharmacists usually don't apply a label. In these instances, branding and marketing can adversely affect the information on a pack. This is especially important when the need for a leaflet is waived because all the information is already present on the package. 

Why do you think many patients overlook product leaflets?

Many patients do fail to take notice of the leaflet. This is partly because of the nature of the leaflet: thin paper folded multiple times inside the box. The new EU-wide legal requirement for user testing of packaged leaflets, however, means that the content and layout of leaflets, as well as the print size, is now much improved. We hope, these changes will mean that people will start to take more notice of the leaflets. 

For the record, our research in the UK, which was conducted in the early 2000s before user testing was in place, showed that around 70% of people read some or all of the package leaflet when they received a medicine for the first time. For a long-term medicines, however, 60% of people said they never or rarely looked at the leaflet after the first time. Health professionals play an important role in drawing people's attention to the package leaflet and the important information that it contains. 

The labelling changes have been proposed to clarify important information. Do you think there is any benefit in doing the same for leaflets provided by pharmaceutical manufacturers?

In fact, the process we've applied to label wordings actually brings them up to speed with package leaflets, which have already been user tested — rather than the other way round. The UK is one of the few EU countries that have retrospectively applied legislation mandating leaflet user-testing. New leaflets have been tested since 2005, but the UK also implemented a requirement for user-testing of older leaflets, completed in 2008. 

Some packaging companies have devised packaging that displays essential information on the outer packaging and ensures that product leaflets cannot be separated and lost. Do you think is a positive development?

There are advantages and disadvantages. You are right that leaflets may be lost or discarded, but incorporating the information into the packaging itself can lead to compromises in terms of how the information is laid out, as well as print size. Our testing has shown that in some cases, people aren't even aware of leaflets that can be opened up from the pack; for instance, some labels can be peeled back to reveal the leaflet, but some people don't realise this. Additionally, people who have problems manipulating things, typically older people, can find it difficult to actually open these leaflets and read all of the information while it is attached to the packaging. 

The bottom line is that the information with a medicine pack can make the difference between a medicine being used safely and effectively, and a medicine that does not work to best effect or even causes harm. The only way of ensuring if the information works is to test it with real people – such as through user testing. Can people find and understand the key information for safe and effective use? 

Research conducted in the UK by the University of Leeds and Luto Research shows that many commonly-used phrases on medicine labels are easily misunderstood.

Is Pharma's Language Too Confusing?

When Pfizer decided to close its R&D site in Sandwich it renewed concerns over the UK's attractiveness to the pharma industry. The site employs 2400 people and although Pfizer has stated that some positions will be transferred to other sites or to other companies working with Pfizer, it is expected that most staff will be made redundant over the next two years (1).

Historically, the UK has been one of the leading forces in the world of pharmaceuticals. The pharma industry is also a major contributor to the country's economy. The job losses at Pfizer have come at an unfortunate time with the UK economy still emerging from recession and unemployment remaining high. According to the European Federation of Pharmaceutical Industries and Associations (EFPIA), the innovative pharmaceutical industry is an "important engine of economic recovery", which means that the UK can ill afford to lose investment from a company of Pfizer's size and stature (2). It's not just Pfizer either; a number of other companies have announced cuts in the UK, including AstraZeneca, GSK and Novartis. 

The pharma industry's economic importance to the UK is illustrated by figures from the Association of the British Pharmaceutical Industry (ABPI), which show that the industry has been a net earner for the country for the past 30 years (3). In 2009, the pharmaceutical industry invested £4.4 billion (€5 billion) in UK R&D and employed 72?000 staff. For a number of years, however, EFPIA has been concerned about a drift in investment away from Europe to the US and to the fast-growing economies of Brazil, China and India (2). According to EFPIA, excessive interventions by European national governments to control healthcare expenditure have dented multinational pharma companies' confidence to invest in the region. The organisation will, no doubt, be alarmed by Pfizer's decision to downgrade its investment in the UK, and the fact that it may prompt other large companies to reconsider their presence in the country. 

The irony for the UK is that there are a number of longstanding initiatives in place to help strengthen its position in both traditional pharma and biotech R&D. Despite opposing views over pharmaceutical pricing, government and industry representatives often have joint discussions on issues of common concern. 

Indeed, in November 1999, the UK government, together with representatives of the domestic pharma industry, set up the Pharmaceutical Industry Competitiveness Task Force (PICTF) to identify steps that could be taken to make the UK more attractive for R&D investment (4). The PICTF team met in April 2000 and published its final recommendations in March 2001. Industry representatives were of the opinion that despite the UK's historically strong performance, traditional factors that had contributed to success in the past, such as established academic excellence in life sciences, could not be relied upon to maintain competitiveness in the future. Factors such as market access and intellectual property protection would gauge how the UK was viewed relative to the rest of the world — particularly the US. 

PICTF focused on six areas of UK competitiveness (market developments, intellectual property rights, regulation of medicines licensing, science base and biopharmaceuticals, clinical research and wider economic climate) considered vital for future performance, and established working groups to examine them. Reliable competitiveness indicators were identified, with the intention of reviewing them annually. A quick look at the DoH site notes that reviews were not published for 2006–2008, though 2009 is available, so perhaps they are back on track (5). 

The pharmaceutical industry representatives also used the PICTF initiative as an opportunity to gain commitment from the government to explore some of the industry's concerns. One particular worry at this time was the role that NICE would play in the future UK market (something which continues to trouble the industry today). They sought clarification on the timing of the body's decisions in relation to the availability of data, the limitations of modelling with reference to particular case studies, and how topics were selected for NICE appraisal. Separately, the industry representatives also had helpful discussions with the treasury on a range of fiscal and taxation issues. 

PICTF was considered a success in that it established a framework for dialogue on issues over which the government and the pharma industry might differ. However, it also represented high-level recognition from the government that it valued the industry's contribution to the UK economy. The value of PICTF was also recognised by other countries, as well as by the European Commission (EC), and has shaped their own approaches to boosting national and regional R&D. In 2004, for example, the French government launched a similar exercise called PharmaFrance and even sent representatives to the UK to seek company viewpoints on the R&D environment.  

Another pharmaceutical R&D initiative that featured UK pharma industry participation was conducted at an overall EU level by the EC's G10 Medicines Group (6). In 2002, the group brought together top European industry and public health decision makers to consider ways of improving competitiveness in line with social and public health objectives. In a similar fashion to PICTF, the G10 group set up a system of EU indicators to allow comparisons to be made between the EU and its major competitors as a basis for establishing best practice within the EU and uptake in each member state. The group also published a report on its findings for the EC, outlining proposals for concrete action to be taken (7).Out of the 14 or so G10 recommendations, perhaps the most one important was to set benchmarks by which Europe could measure its industry productivity against the US. More information was also to be made available regarding disease statistics, as there was an incomplete picture across Europe. 

Recognising the growing importance of biotech R&D to the future of new drug development, in 2003, the UK Government launched the Bioscience Innovation and Growth Team (BIGT), which was led by the BioIndustry Association (BIA) in conjunction with the Departments of Trade & Industry and Health. Like PICTF, the BIGT issued a report, following consultation with more than 70 industry experts. Its recommendations included programmes to increase the scientific and managerial talent base available to the biotech sector, with the hope of emulating the leading position of the US in the field of biotech drug development. Many of the recommendations recognised the need for a long-term vision for the industry and reached as far as 2015. Unfortunately, such goals make monitoring its ongoing success difficult. 

A much more recent initiative is "Lifescience UK". Launched in January 2011, four key members, the Association of British Healthcare Industries (ABHI), the Association of the British Pharmaceutical Industry (ABPI), the BioIndustry Association (BIA) and the British In Vitro Diagnostics Association (BIVDA), will all represent their own sector interests and work with the government to help strengthen and grow the UK's life sciences environment. Watch this space. 

The UK's Ministerial Industry Strategy Group (MISG) continues to meet twice a year as part of the follow-up to the implementation of the PICTF recommendations. The latest review available from PICTF is for 2009, and it paints an optimistic view for the UK (8). Key highlights include the fact that the UK's corporate taxation rates are more favourable than those of the US and Japan, and that there is an upward trend in annual numbers of new graduates in subjects considered relevant to the UK pharma industry. The report also focused on the fact that 16 of the world's top-selling 75 medicines were discovered and developed in the UK — more than any other country except for the US. In light of the closure of Pfizer's Sandwich facility, which was often considered the jewel in the crown of UK R&D because of its role in development of a certain Pfizer blockbuster, it will be interesting to see what the next PICTF report contains. 

The reaction of the government to Pfizer's decision will beimportant for a number of reasons. A primary concern is the economic impact that the closure will have on the local economy in Kent. Not only is the company a major employer in the area, but many other local businesses supplying goods and services depend on its presence for their own viability. Initial estimates suggest that outside Pfizer, 3000 extra jobs could be lost when contractors and other small businesses lose a major source of their revenue (9). The government has said that it will seek to preserve R&D activity in the area through discussions with other firms in the pharmaceutical sector, but it is difficult to see why such companies would commit themselves to high level investment in Sandwich, given that Pfizer has exited despite its long association with the area (10). 

Other multinational pharmaceutical companies will be watching closely as they weigh up decisions to streamline their own operations. Although GSK's CEO, Andrew Witty, recently stated that Pfizer's decision had nothing to do with the UK business environment, there must be considerable unease over what lies ahead for the domestic industry (11). The UK Government's efforts to implement costcontainment measures have tended to be more direct in recent years, such as price cuts, which have angered companies. In 2008,the ABPI warned that the pharma industry had cut UK jobs by 10% over the previous three years because of the pricing environment, and claimed that there was a "direct link between job cuts and changes to the pricing mechanism" (12). 

It certainly seems as though pharma companies are not happy with the UK at the moment and, as with most things, the likes of Pfizer will vote with their feet. 

1. BBC, Pfizer to close UK research site (2011). 

2. EFPIA, The Pharmaceutical Industry in Figures (2010). 

3. ABPI, The pharmaceutical industry in the UK (2011). 

4. UK Department of Health, "Pharmaceutical Industry Competitiveness Task Force" (2001). 

5. Department of Health, "Pharmaceutical industry competitiveness and performance indicators" (2010). 

6. EurActiv, "G10 Medicines Group makes recommendations to enhance pharmaceutical competitiveness" (2002). 

7. European Commission, "High Level Group on innovation and provision of medicines" (2002). 

8. Bioscience Innovation and Growth Team, "Bioscience 2015" (2004). 

9. Business For Kent, "Shockwaves of Pfizer closure will be felt across Kent" (2011). 

10. InPharm, "Pfizer's CRO plans for Sandwich will have limited impact" (2011). 

11. Sky News, "Glaxo Backs UK After Rival's Plant Closure" (2011). 

, "UK Drug firms to slash workforce by 10pc" (2008). 

Industry Insider

Despite initiatives to encourage multinational pharma companies to conduct R&D in the UK, the country may be losing its edge; is Pfizer's decision to exit a key site earlier this year the beginning of a mass exodus?

Could The UK Be Losing Its Pharma Luster?

You have opted to drop the sub brands of Pharma, Supply Solutions and Biosciences and are rebranding as SAFC. What is the rationale behind this decision? 

We found that our customers wanted to interact with one SAFC. Although our brand segments helped us to build awareness in the different markets we are active in, they were also somewhat confusing to our audience. We wanted to build clarity around our business model under a single umbrella.

In light of the changing landscape, how have pharma/biopharma companies’ changing strategies affected your business? 

Bio/pharma companies are continuing to reduce costs and there is increasing pressure for their respective supply chains to comply. As a consequence, we have seen more outsourcing of manufacturing and minimised investment in fixed costs, such as plant costs. Pharma is also looking for greater supply chain flexibility, and is seeking to reduce working capital while still being able to respond to demand fluctuation, so outsourcing is becoming more and more relevant. Of course, quality levels at outsourcing companies need to be at the same level that a pharma company would have at their captive facility. Currently, many plants can also only manufacture a limited number of products, but both the pharma and biopharma industries are demanding contract manufacturing partners who have the ability and resources to switch between a diverse range of products every few months.

Another trend we are witnessing from major pharma is a move towards ‘preferred vendor’ strategies to consolidate outsourcing requirements from a single supplier. As such, we have built up SAFC’s image as a solution provider for early-stage drug discovery through to bulk API manufacture, where clients and partners come to us with an issue and we then work alongside them to determine the best course of action. We then help to implement it from the ground up. 

As an industry, contract manufacturers need to move away from the old ways of doing business and improve the entire value chain, rather than just a few convenient elements. This means being proactive in anticipating client needs before they arise. At our company, for instance, we anticipated that there would be increased interest from clients for high potency API (HPAPI) manufacture. We invested in this area so that these capabilities were already online when the demand arose, rather than waiting until clients requested these facilities. 

What investments has SAFC made in HPAPI manufacturing technology and facilities? 

In 2010, we added a second HPAPI facility in Wisconsin (USA) to complement our kilo and pilot labs already in place. This second facility has two large commercial trains, as well as an additional pilot plant, and enabled us to increase our manufacturing capacity by 24000 L. 

While our facilities in Wisconsin are capable of supporting complex small molecules, we also recognised that there are some high potent compounds that are manufactured either completely through fermentation or in a semi-synthetic fashion. In 2010, we opened our new cGMP fermentation facility in Israel, which has a number of reactors (up to a 4000 L scale) and further expands our HPAPI offering. 

Finally, a number of these high potency products are conjugated to other biologic products, such as monoclonal antibodies and these antibody drug conjugates (ADCs) complete our high potent franchise. Collectively, these capabilities give us an extensive capability toolbox to support diverse needs in the field of HPAPIs. 

Do the absence of guidelines for the safe handling and control of HPAPIs present significant obstacles for suppliers of HPAPI equipment and the pharma/biopharma industry? 

It doesn’t necessarily present obstacles so much as potential for confusion due to the different classifications. The industry has effectively created its own standards and there are several companies who can help provide guidance in this area. Because the application and use of equipment can vary, it is imperative that companies handling HPAPIs define requirements and specifications when designing and purchasing equipment. 

In the absence of guidelines, we will continue to categorise each compound before it enters our facilities as a part of our safety and quality systems. 

What are your predictions for the demands for HPAPI services in the near future? 

A quarter of all drug candidates — from early phase to late phase — are in oncology. This is a main focus area for HPAPIs and is driving the need to identify new highly potent molecules that may be beneficial in the treatment of cancer. Of course, oncology isn’t the only use for these types of compounds, but it is a major constituent. 

Some HPAPIs are used as a final API, but there has been much interest in combining these compounds with other therapeutics. Antibody drug conjugates, for instance, offer the potential for targeting through antibodies, enabling dissociation only inside the targeted cell. 

How have you adapted to rising pressures to compete with less costly service providers? 

While there is enormous pressure on cost, there is greater pressure in terms of quality and risk mitigation throughout the supply chain, including in the components that constitute an API. Regulatory bodies are demanding increased GMP compliance and there is also increased pressure from consumers, triggered by various industry scandals over the past few years. 

Interestingly, at SAFC, we have witnessed an increasing number of late phase projects returning to the West, where the previous supplier had been located in the emerging markets. The reasons behind this shift can be attributed to quality, reliability and communication. Although cost remains important to our customers, it is more apt to focus on ‘total cost’, which factors in the cost of potential “non-quality” products. 

As with any market, we must remain competitive so we’ve been working to optimise our cost structure through process improvements. 

As the emerging markets continue to experience high growth rates, what is SAFC’s strategy with regards to these markets? 

We are currently building sales and marketing forces in China and India to sell into the emerging markets, and are actively increasing our presence in terms of sales visibility throughout Asia. We are also expanding our capabilities at facilities in Wuxi (China) and Bangalore (India), which will be completed by Q3 2011. Longer term, we will look to increase manufacturing capacity at both these locations, but while we want to be cost competitive to ensure that we are not priced out of the market, our chief differentiator will be quality. 

The other main benefit of being active in these markets is the low-cost material sourcing opportunities provided by suppliers in the region. Over the past 5 years, we have developed teams dedicated to sourcing services and products in Asia. 

What are your predictions for the future of Western contract manufacturers? 

Rising industry pressures, such as the expirations of patents, the decrease in the numbers of approvals and negative pricing pressures are all having an effect on Western contract manufacturers. I believe that the outsourcing trend will continue as pharma divests both fixed cost and research and development assets, and exits non-core activities. 

CMOs, operating with an increasing proportion of their business concentrated on niche, specialised capabilities have performed well relative to the general market. While such niche markets offer opportunities for CMOs, however, it’s also important to increase focus and resources on bringing in, or creating, experts for each technology. 

CMOs will also need to differentiate themselves through quality, security and supply chain transparency. 

With increasing pressure to reduce costs, increase efficiency and reduce the environmental impact of manufacturing processes, how has SAFC adapted? 

We will continue to improve profitability through plant process efficiency improvements, facility rationalisation and the development of our global manufacturing ‘centres of excellence,’ in which we bundle our technologies in selected locations. For example, we have a risk mitigation plan in place for both dry and liquid media capabilities in North America and Europe, and we’re also reducing our number of global facilities from five to three. We will increase our capabilities significantly at each of the remaining sites. These centres of excellence are more than just physical structures; rather, they are a coordination of intellectual resources to improve knowledge sharing, innovation management, quality and systems integration. 

Additionally, we have sought to differentiate ourselves in the market by focusing on niche areas, such as high potency, viral vaccines and fermentation, to enable us to support increasingly complex technology platforms. We have also developed our gene-editing ZFN technology for cell design and liquid and powder media. This technology has the ability to make targeted, heritable changes to genes, and will enable us and our customers to create knock-in and knock-out cell lines for drug discovery programmes, as well as more productive cell lines for manufacturing. 

What are SAFC’s key areas for future growth? Where are you currently investing and why? 

As outlined previously, we’re investing in differentiating technologies where customers are searching for high quality solutions. Specialised capabilities such as high potency, oral vaccines and ADCs have performed well relative to the general market in recent years because these capabilities pertain to drug candidates and drug platforms that have the potential to be game changers in the treatment of important diseases, such as cancer. 

We are also continuing to branch out into other practice areas to diversify our offerings. Some of the application areas in which we are growing are oncology, vaccines, RNAi, biologics and molecular diagnostics — all of which we see becoming increasingly important in the coming years. 

Interview

A large CMO explains its strategies for expanding into the emerging markets.

Pharmaceutical Technology Europe-05-03-2011