EPM Jan/Feb 2015 by EPM Magazine

COVER STORY: Getting the point Schott demonstrates its expertise in glass pre-filled syringes

JANUARY/FEBRUARY 2015

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Contents

head office

January/February 2015 | Volume 15 Issue 1

Carlton House, Sandpiper Way, Chester Business Park, Chester, CH4 9QE.

Regulars

Features

NEWS ANALYSIS What does the Xceleron / Molecular Profiles union mean for pharma?

NEWS

LOOK & LEARN Industry predictions – what’s ahead for pharma in 2015

TIPPING POINT Tabletting & encapsulation expertise from I Holland and Bosch

Antibiotics discovery in focus

NEWS PROFILE

GET CONNECTED

Injectable 3D vaccines fight cancer & how to drive innovation in pharma

Agilent looks at achieving an inert gas chromatography flow path through better GC connections

19 28

OPINION Including how to stay safe in pharma from Casella Solutions

FRENCH CONNECTION

A run-down of what to expect at this year’s Pharmapack event

CHEMICAL REACTION Telstar in the sp spoltlight

COVER STORY: GETTING THE POINT Schott demonstrates its expertise in glass pre-filled syringes

SAFETY FIRST A look at some of the packaging solutions on offer

SOLO PERFORMANCE Solo Containment reveals the expertise behind its engineered acrylic containment system

Tel. +44 (0) 1244 680222 Fax. +44 (0) 1244 671074 Web: www.epmmagazine.com

editorial group editor lu rahman, lu.rahman@rapidnews.com associate editor dave gray david.g@rapidnews.com contributing editor aleksandra jones, ola@rapidnews.com publishers mark blezard, duncan wood

production art robert wood

advertising robert anderton tel: +44 (0) 1244 680222, rob@rapidnews.com jacqui priestley tel: +44 (0)7907 361588 jacqui.priestley@rapidnews.com

subscriptions subscriptions@rapidnews.com qualifying readers Europe - Free, ROW - £115 outside qualifying criteria UK - £80, ROW - £115 please subscribe online at www.epmmagazine.com Address changes should be emailed to subscriptions@rapidnews.com. European Pharmaceutical Manufacturer is published by Rapid Life Sciences Ltd. European Pharmaceutical Manufacturer is distributed in electronic and print formats to a combined readership of 14,000 pharmaceutical manufacturing professionals. Volume 15 Issue 1 © June 2014. While every attempt has been made to ensure that the information contained within European Pharmaceutical Manufacturer is accurate, the publisher accepts no liability for information published in error, or for views expressed. All rights for European Pharmaceutical Manufacturer are reserved and reproduction in part or whole without written permission is strictly prohibited.

Erratum: The caption on page 23 of the October issue of EPM should have referred to the GEA Pharma Systems’ equipment, not Diosna’s

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from the editor Sharing economy In 2007 23andMe began selling its $99 genetic testing kit in the US. It was a simple and easy concept – spit into a pot, send it back to the company and it would analyse your DNA, providing you with a little insight into your make-up and ancestry. Many of us are curious about our genealogy – why do we do the things we do, what’s the reason behind our particular traits – so of course, the appeal of this natty little kit was understandable. As it was, the FDA didn’t have a problem with what was on offer from 23andMe, until that is, the company began to market its offering as a way of highlighting an individual’s chances of befalling certain illnesses or diseases. According to the FDA, the kit now fell under the medical device category and as such, need to be approved. Initially agreeing to the FDA approval process, 23andMe then decided to terminate its relationship with the body and began a full-on campaign to sell the kit as a means of discovering more about your health and the likelihood of contracting particular diseases. Last year the company announced its arrival in the UK. What is possibly more interesting than the u-turn of 23andMe, or the fact that we have the ability to potentially discover what our chances of contracting certain illnesses are, is the fact that more recently, it has been reported that Roche-owned biotech firm, Genentech has paid $10 million to back the company and that this is just one of ten deals reported to be coming from big players in pharma. There has been much talk about 23andMe and the fact that the agreements with pharma companies will see customer-donated DNA data being sold to them for research purposes – according to reports Genentech will use the data to develop drugs for Parkinson’s. The moved hasn’t been helped by the fact that 23andMe founder Anne Wojcicki was married to Sergei Brin, founder of Google. With Google’s ability to track and monitor our online activity, parallels are of course being drawn to this now happening in the pharma sector.

But is this really the case? Are we right to be suspicious of the way this data is being used? And should we be wary of the way the company initially presented its service? Did it reel the public in or was it more just a natural progression as a consequence of the data it received? Is this a legitimate way for pharma companies to gather information and use it to further the development of drugs and medicine? Or should we be wary of the lack of protection we have when we fall for something that we think will offer up an insight into our behaviour and make up. It’s an interesting situation. If pharma firms need more data, where do they get it from and if we expect new drugs to be developed, should we be more willing to help with that process? The fact that 23andMe has a connection to Google has of course, added fuel to the fire but if the result of its actions and its links with big pharma is the development of drugs, who are we to argue? It’s interesting that Johnson & Johnson recently agreed to also make some of its clinical trial data available to outside researchers via a link up with Yale University. The Institute of Medicine, of the National Academy of Sciences in the US has also called on all sponsors of clinical trails to share their data. We’re talking medical device data here but how soon before this approach is recommended in the pharmaceutical sector? In an era where innovation is coupled with keeping a close eye on spend, doesn’t it make sense that we look to ways of sharing information or should we hold tight to our right for privacy, even in drug development?

Lu Rahman

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NEWS ANALYSIS

Xceleron and Molecular Profiles collaboration – what does it mean for pharma? Molecular Profiles and Maryland-based Xceleron recently announced a collaboration to assist drug developers with improved efficiency during clinical development. In an exclusive interview with EPM, we found out why this partnership will have an impact on the sector in 2015

ichael Butler, chief executive officer at Maryland-based Xceleron, explained: “We believe that the Molecular Profiles-Xceleron partnership is very well positioned to add value to the pharmaceutical sector because it directly addresses the industry’s macro-need for improved efficiency (cost to market) and its micro-need to develop poorly soluble small molecule drugs. Both companies have grown by helping their customers to substantially improve upon (disrupt) the status quo and to do so with technology and a problem-solving scientific approach. By combining their expertise, the partnership promises to improve drug efficacy by properly characterizing drug disposition in preclinical and clinical development.” Over the last 15 years, UK-based Molecular Profiles, a subsidiary of Columbia Laboratories, has established itself as a science-led leader in asset characterisation, formulation development and clinical trial manufacturing. Central to the CDMO’s approach, for more challenging to deliver drugs, is the application of a range of enabling technologies and characterization tools to explore nanomilling, solid dispersions and lipid-based formulation routes. These are deployed through Molecular Profiles’ Enabling Technologies Rapid Screen platform, designed to quickly and robustly identify the best formulation approach. Using a combination of its consulting and clinical trial manufacture, it is unique in the world of formulation development and clinical production. Talking about Xceleron’s role, Butler said: “Xceleron has similarly established itself as a technology leader. The company uses an analytical technology platform called Accelerator Mass Spectrometry (AMS) and combines that technology with proprietary analytical protocols. Their application in clinical development has produced a clinical pharmacology protocol that is demonstrably quicker (50%) and cheaper (75%) for the determination of drug disposition than has historically been the case. AMS is a highly sensitive, mediumthroughput platform which is uniquely unaffected by matrix effects or by chemical classes. It is ideally suited to the elucidation of disposition of the most insoluble drugs in a range of tissue types for any class of drug molecule, irrespective of the formulation approach taken.” The combination of Molecular Profiles and Xceleron can be viewed in the context of a Molecular Profiles’ ROADMAP to Clinical Trials platform,

which it launched in 2014. This scientific approach and application of stage gating and screening technologies was designed with the aim of assisting clients in choosing a development pathway that will be the most time, cost and volume efficient route forward. Xceleron is presented here as enabling efficient clinical pharmacology investigations, although it can also support preclinical studies. Claire Madden-Smith (pictured), VP of commercial services at Molecular Profiles added: “A more granular view of the partnership is presented in the second schematic. Here we are highlighting a number of preclinical and clinical interactions. By working with Xceleron at the preclinical stages we can accelerate in vivo assessment through the ability to dose at low levels equivalent to as low as 5µg/mL without any risk on nondetection, thus helping to gain valuable data for poorly solubility drugs.” Clinically, there are two broad scenarios in which the partnership can deliver. “Firstly, as Molecular Profiles approaches the need to investigate the clinical impact of its formulation efforts, Xceleron can deploy its network of partners and analytical approach to secure human drug disposition information, including absolute bioavailability, within six months. This approach can be taken as a one-off or can be used iteratively as part of ongoing formulation improvement. “The second broad clinical interaction arises when Xceleron has helped a customer to understand its drug’s disposition and those results indicate low bioavailability for which formulation improvement may represent a solution. In such cases, Molecular Profiles’ scientists review the available information and recommend an efficient formulation approach. The improved formulation can be investigated using the same efficient clinical protocol by the team at Xceleron.” It is hoped that the collaboration will appeal to drug developers in the US and Europe looking to improve efficiency during clinical development. Butler concluded: “I believe our alliance with Molecular Profiles is firmly at the centre of a current opportunity and market need relating to a greater role for science and technology in early biopharmaceutics. Working within Molecular Profiles’ ROADMAP to Clinical Trials platform, we will give clients the option to investigate the impact of solid state and formulations on human disposition at a very early stage.”

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NEWS

Pan-European HTA necessary, says pharma chief

Antibiotic Research UK welcomes finding of new antibiotic

Richard Bergström, director general, European Federation of Pharmaceutical Industries and Associations (EFPIA) argued in favour of the homogenisation of European Health Technology Agency regulation, during an interview with Paul Simms, chairman, Eyeforpharma. Asserting that harmonisation would be the only way for market access to make a step improvement, Bergström explained that it was in everyone’s interests, not just those of pharmaceutical companies.

The publication of a scientific paper by a group of American and European researchers announcing the identification of a new antibiotic with the potential to treat MRSA is fantastic news, says Professor Colin Garner, chief executive of Antibiotic Research UK (ANTRUK).

All stakeholders need to invest in more wide-ranging data collection and analysis. That includes pharma companies themselves: “You better make sure you spend wisely, because if you are going to pour in billions into Real World Data systems, they need to deliver. They must be sustainable and sustained over time, because we can’t, for each individual, country and product go in and do a bolt-on data capture and then after one year close it down.

It is thought that the novel strategy used by the researchers could lead to the identification of many more novel antibiotics. The new antibiotic has been named teixobactin and was discovered in the back garden soil at the home of one of the American researchers, Dr Ling using a new device called the iChip. (The discovery was reported in the journal Nature.)

“As an industry, we can’t have a Slovenian Real World data system; we can’t have a separate one for Austria, etc. We need to build a pan-European standardised model and for that to happen you need to have an agreement,” he said.

Teixobactin was particularly active against against Gram-positive bacteria such as Staph. aureus, Bacillus anthracis and Clostridium difficile. It is early days in the development of teixobactin and it could be between 10-15 years before the drug might become available for use in the clinic. There are many steps between discovery of a new antibiotic and its eventual approval as a drug. Interestingly the researchers found it impossible to produce bacterial resistance against teixobactin in contrast to other antibiotics. The new antibiotic targets the cell wall of the sensitive bacteria and this might explain why it is not as effective against Gram-negative bacteria. Its mechanism of action is similar to another antibiotic in use today called vancomycin which is used as a last resort antibiotic because of its toxicity to the kidney. It remains to be seen if teixobactin demonstrates similar toxicity.

Bergström believes that pharma companies have now largely worked out how to cope with understanding patient need and remodelling their company around that need, albeit admitting there was still a lot more urgent work to be done to see out existing plans. When pushed on where the next frontier lies for pharma executives, Bergström states: “What the industry really needs next is to understand healthcare systems – especially where access is concerned. Pharma hasn’t really figured out how to engage the healthcare system. The skillset needed is a further understanding of healthcare, how it works, who does what, and who makes decisions. We need to understand how these people budget, how they forecast a budget for a product two years from launch. The industry and the payer come from two different worlds, but their conversation needs to move far beyond price negotiations.”

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NEWS PROFILE

Injectable 3D vaccines could fight cancer Researchers at the Wyss Institute have created 3D structures using minimally–invasive delivery to enrich and activate a host's immune cells to target and attack harmful cells in vivo "Although right now we are focusing on developing a cancer vaccine, in the future we could be able to manipulate which type of dendritic cells or other types of immune cells are recruited to the 3D scaffold by using different kinds of cytokines released from the MSRs," said Aileen Li, a graduate student in bioengineering at Harvard SEAS. "By tuning the surface properties and pore size of the MSRs, and therefore controlling the introduction and release of various proteins and drugs, we can manipulate the immune system to treat multiple diseases."

Mesoporous silica rods (MSRs) spontaneously assemble to form a porous 3D scaffold, as seen in this SEM image. The 3D scaffold has many nooks and crannies and is large enough to house tens of millions of recruited immune cells. Credit: Wyss Institute at Harvard University

ne of the reasons cancer is so deadly is that it can evade attack from the body's immune system, which allows tumours to flourish and spread. Scientists can try to induce the immune system, known as immunotherapy, to go into attack mode to fight cancer and to build long lasting immune resistance to cancer cells. Now, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard's School of Engineering and Applied Sciences (SEAS) show a non–surgical injection of programmable biomaterial that spontaneously assembles in vivo into a 3D structure could fight and even help prevent cancer and also infectious disease such as HIV. Their findings are reported in Nature Biotechnology. "We can create 3D structures using minimally–invasive delivery to enrich and activate a host's immune cells to target and attack harmful cells in vivo," said the study's senior author David Mooney, a Wyss Institute core faculty member and the Robert Pinkas professor of bioengineering at Harvard SEAS. Tiny biodegradable rod–like structures made from silica, known as mesoporous silica rods (MSRs), can be loaded 8

with biological and chemical drug components and then delivered by needle just underneath the skin. The rods spontaneously assemble at the vaccination site to form a three–dimensional scaffold, like pouring a box of matchsticks into a pile on a table. The porous spaces in the stack of MSRs are large enough to recruit and fill up with dendritic cells, which are "surveillance" cells that monitor the body and trigger an immune response when a harmful presence is detected.

Once the 3D scaffold has recruited dendritic cells from the body, the drugs contained in the MSRs are released, which trips their "surveillance" trigger and initiates an immune response. The activated dendritic cells leave the scaffold and travel to the lymph nodes, where they raise alarm and direct the body's immune system to attack specific cells, such as cancerous cells. At the site of the injection, the MSRs biodegrade and dissolve naturally within a few months. So far, the researchers have only tested the 3D vaccine in mice, but have found that it is highly effective. An experiment showed that the injectable 3D scaffold recruited and attracted millions of dendritic cells in a host mouse, before dispersing the cells to the lymph nodes and triggering a powerful immune response.

The vaccines are easily and rapidly manufactured so that they could potentially be widely available very quickly in the face of an emerging infectious disease. "We anticipate 3D vaccines could be broadly useful for many settings, and their injectable nature would also make them easy to administer both inside and outside a clinic," said Mooney. Since the vaccine works by triggering an immune response, the method could even be used preventatively by building the body's immune resistance prior to infection. "Injectable immunotherapies that use programmable biomaterials as a powerful vehicle to deliver targeted treatment and preventative care could help fight a whole range of deadly infections, including common worldwide killers like HIV and Ebola, as well as cancer," said Wyss Institute founding director Donald Ingber. "These injectable 3D vaccines offer a minimally invasive and scalable way to deliver therapies that work by mimicking the body’s own powerful immune– response in diseases that have previously been able to skirt immune detection."

"Nano–sized mesoporous silica particles have already been established as useful for manipulating individual cells from the inside, but this is the first time that larger particles, in the micron–sized range, are used to create a 3D in vivo scaffold that can recruit and attract tens of millions of immune cells," said Jaeyun Kim, assistant professor of Chemical Engineering at Sungkyunkwan University and a former Wyss Institute postdoctoral fellow. Synthesized in the lab, the MSRs are built with small holes, known as nanopores, inside. The nanopores can be filled with specific cytokines, oligonucleotides, large protein antigens, or any variety of drugs of interest to allow a vast number of possible combinations to treat a range of infections.

A microscope image shows many of the immune system's dendritic cells that were collected from a 3D scaffold three days after in vivo injection. The 3D scaffold effectively recruits and activates the dendritic cells to trigger an immune response against specific cells, such as cancerous cells. Credit: Wyss Institute at Harvard University

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NEWS PROFILE

Man in the middle David Straw, from consultancy Achieve Breakthrough, looks at unlocking the frozen middle to drive innovation in pharma

<< Shock tactics: If senior leadership can create the right environment, it could be genuinely astonished at the results it can achieve by unlocking the potential of its mighty middle

he pressure that the pharma industry is under is clear to see. We need only look at the amount of actual or attempted deals activity to see that market players – even the largest – are desperate to find ways to build value and profitability.

How can they do this? In my experience, there are four key steps:

Last year, we saw a host of deals announced or rumoured in just one week. Pfizer attempted to acquire AstraZeneca for somewhere in the region of £69 bn; AbbVie abandoned a £32bn takeover of Shire; Actavis emerged as the successful buyer, ahead of Valeant and hedge fund billionaire William Ackman, of Botox maker Allergen in a $66bn deal; while Reckitt Benckiser announced its intention to spin off its pharmaceutical division at the end of the year.

Help them blow up conventional wisdom and assumptions. • By encouraging open discussion, in which anything can be challenged, the middle layers can start to look with fresh eyes at new ways of working

New breakthrough drugs are few and far between, while an influx of generics has hit the market. Meanwhile, health services around the world are having to work to tighter budgets and are not prepared to pay the kind of premiums for new products that they did in the past. The net effect is that the pharma industry is having to reduce fixed costs as never before. It needs to get more for less. And one of the biggest areas that this applies to is – its own people. It desperately needs to create a more innovative, creative and free-flowing culture where people feel empowered to work to their full potential. However, in a new cost-cutting environment where ROI is everything, its people are having to get used to a very different climate from years gone by. Middle managers are reluctant to take risks as they are constantly adapting to change rather than driving it and capitalising on it. Recently, it was reported that a lack of risk appetite is undermining European life sciences. This at a time when they most need to successfully take risks. In addition, pharmaceuticals are finding it hard to attract the new talent needed. A recent study found that pharma topped a ‘talent challenge poll’ with 51% of respondents reporting it was becoming more difficult to attract and hire the right people. I believe that boards and senior management within pharma companies are missing a trick. The talent they need is there all around them – but they need to unlock it from what I call the ‘frozen’ middle. The task for senior leadership is to find ways to enable the layers of their middle management to work to its full potential – and indeed, to reach new heights of productivity.

• Retrain the senior leadership and middle management on what they believe it is possible to accomplish. By raising aspirations and inspiring them to be bolder, a new mind-set can start to be born

• Help them see that they can be accountable for delivering on things that are missing and essential. By giving them a sense of empowerment to change things, they will feel a new level of engagement and commitment to the business • Open conversations about the future they want to build. Encourage discussion of the place everyone wants to get to and help to create the future they want This is not something that can happen overnight and it is not straightforward. It takes genuine commitment and an investment of time and energy. It requires much of senior leadership. They must be as committed to the process as anyone, and it requires them to believe that what they are really there for is to unblock potential and creativity - rather than simply to control and manage. If senior leadership can create the right environment, it could be genuinely astonished at the results it can achieve by unlocking the potential of its mighty middle. It can create an environment characterised by genuine innovation, the constant and productive challenging of the status quo, and collaborations across all the different elements of the pharma pathway. We have seen employee engagement shift from 60% to 85% at one global pharmaceutical company we worked with, with absolute savings of $95 million. At another, there was tangible ROI of 60:1 with an 80% over-achievement of target improvements. In a corporate world that is more unpredictable than ever, the pharma companies that are agile and super-responsive, powered by an inspired middle management layer, will be the successful organisations of the future.

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REGULATORY AFFAIRS

Global scale Lini Subin, senior manager, regulatory affairs, ELC Group, discusses how EMA opens doors for global biosimilar development Talking point: Lini Subin, ELC Group, explains how the EMA has taken initiatives that will lead to the global development of biosimilar drugs >>

he biosimilar regulatory framework in Europe is the most advanced in the world. The European Medicines Agency (EMA) has now taken initiatives that will lead to the global development of biosimilar drugs.

On 29 October 2014, the EMA adopted the revised overarching and long-awaited guideline on biosimilars, ‘Guideline on similar biological medicinal products’. The guideline will allow marketing authorisation holders to use non-EEA authorised reference medicinal products in clinical studies, facilitating global biosimilar development. With this new development, which will grow the biosimilar industry in the early clinical trial phase, it is hoped that costs can be reduced by avoiding repeated clinical trials with different reference medicinal products. The revised guideline can currently be applied to new marketing authorisations, however, it will come into force by 30 April 2015. The EMA established the regulatory framework for similar biological products in 2005, and proposed substantial comparability studies to generate evidence for similar nature, in terms of quality, safety and efficacy, of the similar biologic medicinal product and the chosen reference medicinal product authorised in the EEA. The new guideline provides the general principles for a ‘biosimilar approach’ for similar biological medicines. This guideline reconfirms the legal basis for biosimilar applications and need for additional consideration of other guidelines and consultation regarding the document requirements. It takes into account the need for a comprehensive comparability exercise, which includes comprehensive physiochemical and biological characterisation and comparison and requires knowledge to interpret any differences between a biosimilar and its reference medicinal product. Justification and additional data are required for any deviation from reference product in strengths, pharmaceutical form, formulation, excipients or presentation. As per European regulations, a reference medicinal product is a medicinal product approved in the EEA with a complete dossier, in accordance with the provisions of Article 8 of the Directive 2001/83/ EC. In order to comply with the regulations and regulatory requirements in Europe, the biosimilar manufacturer has, until now, had to repeat the trials with EU-authorised reference medicines. With aim of facilitating a global development, the EMA is introducing the possibility of comparing a biosimilar in certain clinical studies and invivo non-clinical studies with a non-EEA-authorised comparator which is authorised by an authority with similar regulatory and scientific standard (for example, any of the ICH countries). This change could be a signal from EU regulators for the future acceptance of non-EU reference medicines in other types of

marketing authorisation applications, enabling a global development of drugs in general. Even though the EMA accepts the reference medicinal product from non-EEA regions, it will be applicant’s responsibility to demonstrate that the non-EEA reference medicine is representative of the EU reference product. The guideline insists on comparability at the quality level with the EU reference medicine. It also recommends combined use of non–EEA authorised and the EEA authorised reference medicines in development initiatives from a quality perspective. When the non–EEA product is used in the clinical/non clinical studies, it is expected to provide bridging data to the EU originator drug and this will include data from analytical studies which compares all three products (test biosimilar, EU reference drug and the non-EEA reference medicinal product) and may also include data from clinical PK and/or PD bridging studies for all three products. This approach again underlines the need for a proper scientific advice on a case-by-case basis. The revised guideline also proposes a stepwise approach throughout the development programme, starting with a comprehensive physiochemical and biological characterisation. The step-by-step approach proposes the extent and nature of the safety/efficacy studies to be decided based on the evidence obtained from previous characterisation steps. Hence the biosimilar comparability exercise should be very much sensitive to detecting any differences between the biosimilar and reference medicinal product. Apart from the above mentioned guideline, the EMA is working on the other two overarching guidelines; Guideline on similar biological medicinal products containing • biotechnology-derived proteins as active substance: quality issues (revision 1) (03/06/2014) • Draft guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues (10/06/2013) These revised guidelines will come into effect very soon, facilitating overall biosimilar development. Earlier developmental initiatives, including the establishment of regulatory framework for biosimilars and a series of other guidelines, led to approval of approximately 19 biosimilars in the European Union to date, including the first two monoclonal-antibody biosimilars. Adoption of the new guideline allowing non–EEA reference products in development will open the doors to many similar biologic drugs, facilitating global development of similar biological medicinal products.

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OPINION

Safe & Sound The pharma sector cures disease, not creates its. But what are the issues on the pharma factory floor when it comes to dust toxicity and chemical exposure? Andrea Bowen, Casella Solutions discusses

hen it comes to making headlines, it tends to be bad news that grabs the attention. And in this digital world of instant images and reporting, a photograph or tweet of a catastrophe such as the Savar building collapse in Dhaka, Bangladesh in April 2013, where more than a thousand people lost their lives, is bound to have more of a global impact than a health report full of depressing statistics, relating to events from 15 or 20 years ago. What do most people know about the ongoing well-being of the surviving workers and the dangers they face on a year-on-year basis that may lead to long-term and irreversible damage to their health? And focusing on the pharmaceutical manufacturing sector, how much do we really know about the occupational health risks facing workers, and what is being done to eradicate or at least control these risks? Employing more than 350,000 people worldwide, this sector is a significant provider of work in emerging economies and it’s the duty of employers to ensure staff are not just safeguarded from hazards but protected from conditions that can cause illness. So precaution and prevention of illness and poor health must surely be a more pragmatic approach and worthwhile investing in instead of creating a culture of cure and compensation? With workrelated disease cited as the source for around two million deaths every year, and diseases caused by occupational exposure killing six times more employees than work-related accidents, this is an epidemic that needs addressing at source rather than attempting to treat the symptom. Ironically, pharmaceutical manufacturing has been revealed as a sector with specific issues when it comes to dust toxicity and chemical

exposure. After all, this is an industry whose success lies in curing disease, rather than being a cause of it. So what are the issues on the pharma factory floor? Enclosed conditions are commonplace for the pharma factory, so installing an air quality extraction system to control and divert airborne contaminants has long been a priority. Whether that’s due to processes at high temperatures, substances being released from the reactor during cleaning and maintenance, or harmful powder escaping from tablets while on the production line, an extraction system and the level of dust in the plant needs to be closely and regularly monitored in order to ensure the system’s efficacy. Sadly, it’s usually following an actual incident that real lessons are learnt and precautionary steps are put into place. And although the assumption may be that it is only pharmaceutical factories in emerging economies where health and safety on site may not be so closely monitored that have recorded incidents, the chemical spill at Novartis’ Basel plant in 2012 proves otherwise. Although not dust-related, the caustic liquid caused damage to the mucous membranes of a number of workers, with five staff from an outside cleaning agency having to be hospitalised after they developed a severe cough. And this was only the immediate health problems. It remains to be seen whether this incident will have longterm health implications. So what is in place to limit and prevent staff from dangers? The process cycle of monitoring, measuring and analysis of dust and toxicity levels has two key purposes. To provide protection for both the workers exposed to challenging conditions and the employers who are required to ensure

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their people are operating in the healthiest environment possible. The first task in safeguarding is usually a site survey, which is carried out with a handheld device to determine how much and where the dust is. The airborne dust is graphically displayed in real time, allowing decisions to be made quickly and actions taken. Personal monitoring, however, provides the most reliable method of measuring factory workers’ exposure to dust toxicity. A sampling pump draws in a volume of air through a pre-weighed glass fibre that determines whether the particles are ‘total inhalable dust’ or ‘respirable dust’. The former is the total amount of airborne materials that can enter the respiratory system, which can be up to 100 microns in size; the largest of which can be naturally expelled by the body’s own defence system. The more troublesome particles are the smaller ones, classified as ‘respirable dust’, these are usually around 10 microns in size and can potentially cause the most damage as they can penetrate and lodge deep within the lung cavity. Once this occurs, the chances of developing a Chronic Obstructive Pulmonary Disease (COPD), or even lung cancer, significantly increase. So although it’s unlikely to grab the headlines, it’s the implementation of an effective monitoring programme to assess and deal with risk of exposure to dust that is more likely to provide healthy ending for those working on the factory floor of the pharma industry. And with the pharma companies in the emerging economies snapping at the heels of the established big names, it’s up to us in Europe to set an example and ensure our factories are fit for purpose, and our workers are fit for life.

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OPINION

The game of risk Life science start-ups are faced with a deluge of demands on limited human and financial resources, so if the insurance industry lends a hand with simple and for the most part economical one-size-fits-all package for life science companies, what’s not to like, asks life science insurance expert, Ian Thomson, RKH Healthcare

<< Loss leader: Insurance losses should be seen as an inevitable cost of doing business in life science industries and companies should get to grips with issues they may face

nsurance packages offer an easy and straightforward option, designed to be hassle-free. For small businesses and startups they are often an efficient and effective solution. Package policies save time, but for life science companies they’re rarely the right answer for long. I would argue that insurance losses should be seen as an inevitable cost of doing business in pharmaceutical and life science industries and companies need to start getting to grips with the issues they are likely to face, the earlier the better. Once a business has matured beyond pure product development, begun commercialising its first product or is expanding its territorial footprint, these are the signs that a different approach is required. It’s obvious really, insurance needs to grow in step with the business and insurance cover need to provide the support that best aligns to the business and its direction, but in reality this rarely happens and this is also when the limitations of package policies become more obvious. The effects of an ill-fitting insurance package policy will be magnified as soon as a company expands beyond its home country and seeks to establish roots in other territories – in life sciences particularly, no company is safe from litigation. Legal costs and expenses can eat into the low limits under package policies leaving very little left for payment of actual claims: legal defence costs are often a silent drain

that can leave a business unprotected when a claim needs to be paid. Going international uncovers numerous other risks not protected by package policies such as political risks, trade credit and environmental liabilities. Just at the same point when flexibility of policy wordings such as definition of reinstatement begin to matter much more, package policies find it difficult to deliver. In my experience, there are also common issues around supplier or customer coverage, limits associated with bottlenecks and constraints that need to be targeted through contingent business interruption cover limits that match the revenue dependency on those key suppliers. Growing complexity is an inevitable part of a growing business, but it’s unlikely that the problems companies face haven’t been faced and solved by others. That’s where a specialist can add real value. Up to a certain stage in a company’s development, insurance can and should have a relatively low profile. But as a business grows the benefits of a close relationship with a specialist insurer, one with an in-depth knowledge of the life science industry, become evident. These relationships are developed over years and enable future-planned protection of the business through special wordings tailored, not only to the life science arena but also to particular companies’ plans and product portfolios. Insurance limits accurately reflect

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the company’s exposures as well as expertise in local compliance and technical support to risk management are features of a more specialist approach. I have over 27 years experience in life sciences and now work as a specialist insurance intermediary advising life science companies. I get really excited about meeting a prospect or client because of what I learn about their business. Their ambition and their anxieties around risk all set my creative juices running! Unless you are prepared to listen and learn, how can you identify the right insurance arrangements, ones that will fit into their business plans and will provide pro-active support and protection to them as they grow? For some companies, having such relationships with an insurer can seem out of reach as they have neither the will nor resource of an internal life science sector insurance expert. Such hurdles can be overcome by experts who act as ‘virtual’ insurance and risk managers and provide consultancy services on renewals, insurance procurement exercises and reviews. They use their knowledge and expertise to ensure businesses are adequately covered against risk, both immediate and future. For growing life science companies insurance and risk management cannot be an afterthought, or even a one-size-fits-all package solution - they are an integral part of operations and planning.

COVER STORY

<< Turning point: Schott’s syriQ InJentle pre-filled syringes have been designed to offer a safer, more effective packaging option for many sensitive drugs

Getting the point Designing safer, more comfortable, and more effective glass pre-filled syringes, by Anil-Kumar Busimi, head of global product management for the syringe business, Schott

re-filled syringes (PFS) make injection easier and safer for both doctors and patients. But that’s just one reason why the pharmaceutical industry is increasingly adopting and demanding them. This demand will only continue to accelerate in coming years, as more than half of all drug candidates in development are biotech based drugs and are generally only administered by injection. Yet some of these complex and sensitive pharmaceutical formulations can cause issues when coming into direct contact with the materials/components of a PFS. Packaging manufacturers have taken on the challenges the pharmaceutical market is facing with pre-filled syringes and are developing new solutions—like Schott’s syriQ InJentle pre-filled syringe — which offers a safer, more effective packaging option for many sensitive drugs in development.

A growing need for pre-filled syringes The error-prone procedure of drawing the medication out of a glass vial or ampoule into the syringe is replaced for many drugs with more accurate and cost-effective prefilled syringes. This way, it is ensured that the patient always receives the right dosage and pharmaceutical companies can benefit from less overfill in PFS compared to vials, an important advantage, particularly with costly biopharmaceuticals. Last but not least, pre-filled syringes work well with increasingly popular safety devices and auto-injection systems. All of these properties combined in a syringe that meets FDA and other drug authorities’ guidelines for minimising the risk of error while operating medical technology devices. From a manufacturer’s perspective, prefilled syringes also open up new marketing opportunities because more and more pharmaceutical companies—generic drug manufacturers in particular—believe that packaging enables them to stand out from the competition.

Focus on potentially harmful interactions But along with the advantages of pre-filled syringes have come several challenges. Pharmaceutical companies must be able to ensure patient safety by demonstrating that no component or material including any extractables and leachables (E&L) of the primary packaging has an adverse interaction with the drugs. Some of the extractables and leachables can interfere with the drug molecules and could compromise the effectiveness of a drug. In a worst-case scenario, this can have detrimental effects on a patient’s health. In ampoules and vials the drug is in contact with only glass and rubber, whereas in PFS the drug is in contact with more materials and components, creating additional opportunities for interactions and E&L. Hence the design, manufacturing, quality and choice of PFS - suitable for a specific therapeutic area - is critical.

Tungsten For example, a potential cause of interactions between glass syringes and medications are the tungsten pins that syringe manufacturers are using during the production process. Heat-resistant tungsten pins are commonly used to form the fluid path (luer channel) in syringe barrels. Numerous studies have shown that tungsten residues could interact with sensitive biological drugs leading to protein aggregation. This not only destabilizes the pharmaceutical formulation, but also possibly causes an undesirable immune response from the patient after the injection.

Adhesive Another potential cause of interactions between glass syringes with needle and medications is the adhesive (glue) used to bond the needle with the glass barrel. The adhesive is a possible source of E&L in pre-filled syringes. The adhesive is designed to be safe, usually consisting of organic polymers and cured using UV light. Many acrylate bonds and other substances of concern commonly used by the adhesive industry have been removed from the pre-fillable syringes that many manufacturers offer. Nevertheless, the adhesive formulation isn't the only potential risk of E&L. The way in which the syringe manufacturer has applied, activated, and cured the adhesive is also important. If it hasn't been processed properly or doesn't suit the medication in terms of its chemical composition, the adhesive could interact with the drug and impact the efficacy of the drug.

Silicone oil Silicone oil used to lubricate the inner surface of glass PFS is seen as an ‘essential evil’ which cannot be avoided. On one hand silicone is needed to ensure functionality, ie. make sure the plunger can be pressed down more easily and smoothly. Silicone oil ensures that the syringe continues to work even after it has been stored for a longer period of time. But, silicone can be a source of E&L or particles which could alter sensitive proteins under certain conditions, causing them to aggregate or change their form. Quite a few studies have been published on this since the 1980s. For pharmaceutical manufacturers, silicone oil in pre-filled syringes also presents a different problem. If the oil migrates into the pharmaceutical formulation, it can form particles inside the drug. Typically, these subvisible particles are smaller than 100 micrometers in size, and cannot be seen by the naked eye, but ‘invisible’ does not mean ‘harmless’. For this reason, regulatory authorities expect pharmaceutical manufacturers to monitor the number and size of these particles as a quality criterion.

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Needles There are many critical components in a PFS, but the needle requires special attention as it is in contact with the drug during storage (in staked in needle PFS) and is the only component which is in contact with the patient during drug administration. The right choice of the needle material, needle size and design is very critical for optimal drug delivery and patient safety. There are various aspects to be considered for a needle design for example the outer / inner diameter, bevel design, length and siliconization for the intended use. The viscosity of the drug and injection time also influence the choice of needle. To make the injections more comfortable for the patient thin needles are used.

1) Understand the requirements of the pharma companies and end users. Include human factors into the PFS design at an early stage. 2) Fewer contact materials or materials with low E&L profile to ensure drug stability 3) Tight dimensional tolerances are required for a. Optimal processing on filling lines b. Assembly of components like finger flange or backstop c. I f PFS is combined with devices like safety devices and auto-injectors to avoid device failure d. For lower residual volume especially for expensive biotech drugs

There are several quality criteria for the design of pre-filled syringes that make injections more comfortable and effective for the patient, below are some key factors:

4) For staked in needle syringes: selection of needles which are sharp and make injections more comfortable for patients 5) Uniform siliconization of the syringe barrels which results in best functionality with no drug interaction. 6) The quality of the glass is, of course, paramount. Manufacturers must avoid breakage, scratches, cracks, particles, and other cosmetic defects in the glass which could impair the functionality or use of the PFS.

Consult the packaging manufacturer By considering these factors, pharmaceutical companies can find the right type of packaging for their products, especially for sensitive biopharmaceuticals. In response to these challenges, Schott has combined the quality characteristics mentioned here and others in designing its product syriQ InJentle. This pre-filled syringe meets the growing demand for systems that offer improved stability of sensitive drugs, safer and more comfortable injections. InJentle's design, employing a ‘pinch seal’ closure, ensures that the drug is not in contact with the metal needle or the adhesive of the syringe during storage, preventing sensitive drugs from interacting with these potential contaminants. The special geometry of the glass barrel does not require the use of tungsten pins during the glass forming process, making the syringe completely tungstenfree. In addition, the syringe barrel is offered with baked-on silicone. This results in less free silicone and significantly lower particles without compromising the functionality of PFS. The needle shield has a robust tamper-evident closure. This enables physicians or patients to determine easily if the syringe is still unused. Due to the design of InJentle, the needle is not in contact with the needle shield and this minimises the risk from the occurrence of ‘hooks’. Sharper ‘virgin’ needles make the injection less painful for patients. In addition, InJentle can be combined with particularly thin needles potentially up to 32 gauge - which are also siliconised, contributing to improved comfort for patients.

Team up with your packaging supplier Packaging manufacturer’s expertise is just as important as the packaging design. Involving a packaging manufacturer in the project at an early stage can reduce the development time, approval processes and ultimately time to market. The question of whether to use syringes made of glass or those made of polymers like cyclo olefin copolymers (COC) is just one example.

Singled out: From a manufacturer’s perspective, pre-filled syringes open up marketing opportunities

The properties that the respective drug formulation possesses and the special demands it places on production and drug delivery can determine the most optimal packaging. For this reason, pharmaceutical companies are well advised to contact a syringe manufacturer that offers both glass and polymer when they first begin developing a drug in order to obtain neutral advice and benefit from a wealth of application-related expertise. As the demand for pre-fillable syringes continues to grow, pharmaceutical companies that partner with a syringe manufacturer from day one can ensure the primary packaging is ideal for their formulation and produce a safer, more comfortable, and more effective treatment for patients.

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ADVERTORIAL

Controlling temperature BioPharma Dynamics discusses the importance of controlling parameters in your process. Temperature monitoring and control devices are an integral part of any process within the life sciences sector. Having a quality temperature control system in place can impact the safety and effectiveness of an end product, along with minimising energy consumption and avoiding process control issues. However, many people still underestimate the importance of having adequate control and monitoring in place, and when looking to replace chillers in a system, simply replace the old temperature control unit with the same size and type, or for new applications, utilise existing equipment on site – this can lead to unnecessarily high running costs and reduced equipment life cycle. When it comes to replacing a unit, there are some factors to be considered: •H ave the process parameters changed? • Has the process itself changed? New equipment and pipe lengths added or valves fitted can have an impact. • Was the original chiller sized to the specification of the process at the time it was fitted? • Can new technologies offer me more precise and/or more energy efficient temperature control? • Would more automation and monitoring in our process improve results and free up time? • Can my supplier offer a scalable solution from lab through to pilot scale and full production?

As a company focused on providing complete, cost effective results with market leading technologies, BioPharma Dynamics is pleased to be able to offer the most popular product ranges and market leading technologies. By controlling the automation of a process through SciLog systems and pumps with the temperature control units of SMC, a complete control solution is delivered including valves, pumps and chillers. This type of solution would give temperature, pressure, flow, and diagnostic control to your process at various scales. The HRS series temperature controller range gives some excellent features to the end user with real benefits without the large cost implications. We often hear that space is at a premium in many laboratories; the compact footprint, lightweight design and the ability to site the unit close to side panels and walls minimizes the floor space taken by the HRS, leaving valuable space for other processes. The units are available in air cooled and water cooled options with temperature stability of +/0.1˚C and a temperature range from 5˚C to 40˚C, ensuring processes are maintained within tight parameters and the same unit can be used on different applications. Thanks to the HRS thermo chiller’s advanced control functions, abnormalities and errors are quickly detected before any real danger or process spoiling can occur. When used in conjunction with other innovative products from the SMC range – such as our unique digital flow switch with integrated temperature sensor from Series PF3W or our high performance Series VX fluid valve range – we can provide the right solution to help you automate your process. Support of the SMC temperature control product range can be guaranteed globally with 400 sales offices across 82 countries worldwide, which allows for easy tech transfer for end users or simple product support on OEM packages. With a strong background in automation and partnerships with world leading innovative manufacturers, BioPharma Dynamics are able to work with you to specify the best temperature control unit to meet your process requirements. If you are looking for a no obligation survey of your systems, an informal discussion on temperature control requirements or to trial a temperature control unit in your process, then contact BioPharma Dynamics today.

In the life sciences industry, small fluctuations in process temperature can make a large difference to results. The sizing of the correct temperature control equipment in your process can help in quality by design systems by firstly ensuring the controls maintain process quality, and secondly by highlighting any areas where there may be a process problem. Even with accurate control your system may see temperatures outside of the determined parameters due to other equipment failure; in this case, the temperature control unit can be used to sound alarms for manual intervention or feed out to other equipment for automatic adjustments. Temperature control is not just about cooling. Some applications such as maintaining process parameters in a bio-reactor may need cooling and heating capabilities within the same batch, and so some temperature control units are available to cover heat loads of exothermic and endothermic requirements.

BioPharma Dynamics is a provider of solutions for traditional and single-use processes within the Life Sciences Industry. The company sees partnership with its suppliers and customers as the best way to help enhance process innovations and challenges in a positive way. Enjoying partnerships with world leading companies such as Saint Gobain Performance Plastics, SMC Pneumatics, Colder Products, Parker SciLog and Quattrowflow Pumps allows BioPharma Dynamics to offer radical solutions with products ranging from single-use tube and sampling sets through to full process control, integrating pumps, sensors, chillers and valves.

For more information, contact BioPharma Dynamics on 01235 750690 or email info@biopharmadynamics.com

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INDUSTRY PREDICTIONS

Future proofing What’s next for pharmaceutical companies in an increasingly complex industry? Asks Peter Sheppard, Europe life sciences leader, Genpact

s I look back at the last decade, I’m struck by how the pace of change in the pharmaceutical industry has accelerated, but also, looking forward by how the industry’s winners will be defined by an ability to rapidly re-allocate resources to take advantage of new opportunities. A decade ago the combination of a steep decline in R&D productivity coupled with a wave of patent expiries provided the initial impetus to seek new market opportunities and to challenge cost structure. The ‘coming of age’ of large molecule therapies and the push into emerging markets then drove a significant refocus of resources taking the pace of change up another gear. Today, a fundamental change in market opportunity, driven by the need to impact patient outcomes, is causing pharmaceutical companies to reconsider their core mission and the capabilities required to succeed. Recently, we have seen health outcomes benefit from new therapeutic options and greater collaboration between payers, providers and pharmaceutical companies. The result is that healthcare practitioners expect to reduce total costs by providing more customised care with the ability to closely measure patient outcomes. Pharmaceutical companies are reconsidering their value proposition in this context, based on a better understanding of patient needs and sharing responsibility for overall patient outcomes. As companies look to respond to this situation, I believe that the answer lies in the adoption of new business models that are sufficiently flexible and adapted to meet the ‘new normal’. There are a number of major areas that pharmaceutical companies need to focus on in 2015.

Flexible operating models Companies that evolve their business architecture in order to innovate and execute with speed and at scale will out-compete the rest. Many organisations have outsourced capabilities in whole or in part for cost advantage, but have not considered how these services need to integrate to enable business agility. In fact, this approach may inhibit competitive advantage. The need to drive operational effectiveness is already top of mind for many company executives who declared in a recent Genpact survey that operational initiatives are a key current priority. In response to this, pharmaceutical companies are beginning to adopt advanced operating models, drawing on experiences of other industries. Much of the recent growth in advanced operating models, such as integrated business services, has been focused on finance and accounting, human resources, and IT. As these operating models mature across other industries, pharmaceutical companies are now accelerating their adoption to free-up resources and to deliver agility. In particular, pharmaceutical companies need to rapidly evolve their business architecture and be able to deliver change without compromising on execution. In addition to back-office opportunities, advanced operating models are increasingly relevant to core business processes. Change must be driven across marketing and sales, medical, and supply chain operations in order to compete in an environment where patient outcomes are the priority. This comes with a number of challenges such as breaking down barriers between internal functions. To achieve this will require tighter internal integration and an overhaul of existing processes.

Partnership and control Effective market access is a crucial area which requires integration of business processes and data across the value chain, while simultaneously driving the need to be flexible in delivering a market-specific effect. Companies need to leverage external partners for capability, cost and flexibility. For instance, the time and investment risk in installing the infrastructure, staffing and local capabilities often cannot meet commercial time-lines. In this way, partners can bring local presence and knowledge while minimising overheads. Building the capability to establish and integrate services across a network of such partnerships is the key to remaining flexible and scalable, especially where they help bring global reach with locally relevant capability. Partners are increasingly capable of delivering core capabilities on a flexible basis, however, maintaining transparency and control while managing integration are key to delivering the required business outcomes. In addition, the co-ordination of enterprise-wide data management and process orchestration are required to handle a larger numbers of products, tracking regulatory licencing and supporting a highly complex distribution network.

The path forward The pharmaceutical sector can gain significantly by continuing to seek knowledge accumulated in other industries where operational transformation has been in practice for many years. This experience can help define a business strategy that uses agility as a source of competitive advantage and allocates resources to where they can deliver maximum impact on patient outcomes. This is a business critical issue and one that must be at the top of pharmaceutical business leader’s agenda as they look to next year and beyond.

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INDUSTRY PREDICTIONS

Look and learn It’s good to keep on top of industry trends and the pharma sector is no exception. Lu Rahman looks at some of the key trends likely to be feature significantly in 2015

014 in the pharma sector was dominated by mergers & acquisitions – actual and speculative. Heading into 2015, it looks likely that trend will continue to dominate the pharma space. Add to this the need for the industry to continue its push on innovation and the picture for the year ahead looks very interesting indeed.

One company that is embracing the digital future is Novartis which has launched the ‘Trials of the Future’ initiative to digitally connect and aggregate medical device data during clinical trials.

Jen Goldsmith, VP of Veeva Vault, Veeva Systems comments: “There seems no end to the cloud’s ability to enable progress, and content management is no exception. For decades, life sciences companies have been struggling to establish a single source of the truth – the Holy Grail of content management – across all functional areas including therapeutic areas, regional affiliates, and investigator sites worldwide. Though many have tried, no technology provider has been able to fully deliver on this promise without sacrificing business efficiency or compliance. Instead, diverse teams were historically served by isolated solutions that didn’t interact, forcing manual document handoffs that created gross inefficiencies and compliance risk.”

Teaming up with Qualcomm Life, the pharma group says it aims to “leverage health care technology to improve the experience of clinical trial participants and patients using Novartis products, and provide connectivity with future products marketed by Novartis”.

According to Goldsmith, the cloud, in contrast, has the power to unite these groups without a single compromise – regulatory teams share content with marketing; Europe with North America; investigator sites with clinical departments.

As always, innovation is key and 2015 looks likely to continue this trend which is vital to the sector. There has been much discussion of late of the role that digital health, the cloud and digital medicine have to bring to the sector and many pharma companies are exploring the benefits this can bring.

Clouded house: Jen Goldsmith, Veeva Vault, says the clould will become increasingly significant in pharma in the year ahead

Novartis is just one example of the pharma sector exploring digital possibilities as it opens up ways to potentially revolutionise the way many businesses operate internally and with external partners and customers.

“In the cloud, it’s no longer an ‘either/or’ decision – as in either a centralised content repository that supports content sharing and corporate control but adds enormous complexity or a decentralised solution that meets local or department requirements but limits content reuse and collaboration. The cloud bridges content gaps across all linesof-business and geographic regions to balance global harmonisation with local autonomy. In the near future, a reliable, single source of the truth will live in the cloud for universal sharing, yet also reflect unique business processes and compliance requirements for the best of both worlds,” she says.

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INDUSTRY PREDICTIONS While pharma explores new ways of working, accessing and recording information, there are some trends from 2014 that look likely to remain going forward. Innovation is of course crucial but 2015 looks set to marry this with financial caution as companies look to keep a close eye on spend. At the start of the year, Flemming Ornskov, chief executive of Shire, told the Financial Times that 2015 is likely to see more dealmaking as pharma companies increase their efforts to find growth and efficiency savings. “I think you are going to continue to see consolidation” he told the newspaper, highlighting the continued need for scale, efficiency and innovation that is driving current “deal frenzy”. Last year Shire made an attempt to buy US firm AbbVie for £32 billion but the deal fell through. More recently, the company has been in the news for its decision to purchase US group NPS Pharmaceuticals for £4 billion in a bid to strengthen its position in the rare disease medicine field. According to Ornskov, it will be the companies whose treatments are able to ‘change the trajectory of diseases’ that will be able to flourish going forward.

Come together: Adam Moorhouse, Onyx Scientific, believes that on the CRO side, we will see the consolidation of the past few years across the industry Adam Moorhouse, director of US business development, West Coast at Onyx Scientific, says there are some trends that look likely to continue into 2015. He believes that on the CRO side, we will see the consolidation of the past few years across the industry. “In large pharma and the larger biotechs, there is a move towards re-evaluation of current CRO/CMO partnership, or a more strategic organisation of CRO/CMO partnerships respectively. Circumstantial evidence of this includes the attendance at numerous outsourcing shows of increasing numbers of representatives from said companies. Easy to spot as those companies which were previously closed shops find their employees swamped by eager CRO/CMO staffers… Given the often protracted nature of the evaluation, short-listing and due diligence applied to the assessment of new suppliers, it seems likely that this process (and the new partnerships formed as a result of it) will be of significance in 2015. Perhaps the time is right for CRO/CMOs to poach a new big player before they cosy up into hibernation with their new strategic partners,” he says.

View point: According to Sven Stegemann, Capsugel, quality will be crucial in 2015 Sven Stegemann, director of pharmaceutical development at Capsugel, is looking at quality during 2015 and believes this will be have a significant contribution to play. “A decade of cost-cutting in pharmaceutical development and manufacturing yielded some unintended consequences for many companies in 2014, as the quality of their products failed to meet established standards,” he says. According to Stegemann, some of these consequences resulted in manufacturing sites being shuttered or banned from import into the US by the Food and Drug Administration (FDA) due to serious violations in Good Manufacturing Practices (GMP). “For example, high levels of chromium were found in gelatin capsules, jeopardising product safety and creating detrimental legal issues for companies. And, just recently, hundreds of product licenses were withdrawn by European regulators due to falsified clinical trial data generated by a contractor. Aside from the direct legal and financial impact for the companies involved, the damage to the reputation of the overall pharmaceutical industry is potentially enormous,” he adds. Stegemann says that as every customer is also a vendor, just looking at costs at the supply level is no longer a sustainable approach, without seriously addressing product quality and supply chain security. “Future enhancements in manufacturing efficiency designed to manage overall costs require a combination of innovative formulation, lean manufacturing platforms and high-performance components utilising the opportunities derived from QbD, PAT, six sigma and continuous manufacturing. The industry has to increasingly recognise that credible and trusted suppliers are essential partners to achieving these objectives and that quality is a ‘value’ rather than a ‘cost’” he says.

Moorhouse says it seems safe to assume that the consolidation in the CRO/CMO space will continue, given the continued perceived importance by much of the industry of suppliers providing increased integration of services. “This pattern matches the movements within big pharma of a move towards forming more strategic partnerships with CRO/CMOs, vendor consolidation and also the trend of pharma reducing fixed assets and peering outward for approaches to finding innovation (biotechs and partnerships) and maximising profits (increased mergers & acquisitions), in the face of the patent cliff free-fall, from which no-one has yet landed,” he adds.

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3 370 international suppliers in packaging and advanced drug delivery technologies

3 3,300 senior level managers from pharma companies expected

EXHIBITION & CONFERENCE 11&12 FEBRUARY 2015 PARIS EXPO, PORTE DE VERSAILLES, HALL 5

Innovation, Networking & Education in Pharmaceutical Packaging and Drug Delivery Technologies

ED th FEA ITION TUR ING :

3 2 day conference to hear about the latest market trends for packaging developments and new drug delivery systems

3 1 day Technical Symposium dedicated to Serialisation, Track & Trace

3 Workshops allowing an in-depth discussion in 360° on specific technical issues

3 NEW! A learning lab to enable visitors to learn how to apply new concepts or tools to their projects

3 NEW! 2 networking breakfasts on the North American and Chinese markets

3 Innovation Gallery showcasing recently launched products, organised by product category

3 The Pharmapack Awards ceremony rewarding the most innovative solutions

#pharmapackeu

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PharmapackEu Ad 220x156mm.indd 1

20/10/2014 13:40

GENDERLESS SIMPLIFIES MODULAR SYSTEM DESIGN Interchangeability maximizes process flexibility Robust AseptiQuik® sterile connectors deliver reliable, repeatable performance in 9.5mm to 19.0mm applications. • Simplify process integration • Minimize risk of operator error • Streamline supply chain Read the “Single-use Connections” white paper at cpcworldwide.com/bio

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TABLETTING & ENCAPSULATION

Tipping point Steve Osborn, I Hollandâ&#x20AC;&#x2122;s tablet design and multi-tipped tooling expert looks at increasing tablet production and efficiency using multi-tip tooling Growing demands: Improved productivity within modern tablet production is growing and so is the need to increase tablet output in an economical way

s the demand for improved productivity within modern tablet production grows, the need to increase tablet output in an economical way is a key factor to consider. The most effective way to fulfil this requirement is through multi-tip tooling which offers a number of benefits, including greater productivity and a reduction in run-time per output of tablets. Multi-tip tooling also reduces the press set up time for the quantity of tablets produced and can exclude the requirement to purchase a new tablet press to increase production. Here we look at the benefits of multitip tooling: What is a multi-tipped punch and how can it benefit production? Multi-tipped punches are conceptually as simple as they sound, punches with more than one tip. This can range from a simple two tip punch to a punch with often up to somewhere in the region of 26 tips per punch face. Depending on tablet design it may be more than this. Multi-tip tooling has transformed the way tablets are produced and it is now considered the most productive form of tablet manufacture. Successful implementation of multi-tipped tooling can eliminate the need to invest in expensive tablet presses, therefore reducing the overall capital spend. The number of tool set-ups required per production batch can also be reduced and product batches are completed quickly decreasing the overall time required to produce the product.

Of course this reduction leads to other benefits from the reduction in energy consumption due to the press running for shorter periods of time, to reduced man hours req uired per press. The cost to maintain the machine is also reduced, whilst overall press availability will be increased making time for additional production. Another less obvious benefit is in the production of tablets which need to be compressed within a very short time of the formulation being prepared. The use of multi-tips enables the formulation to be processed quickly with optimum conditions. Why are multi-tips the best option for improving tablet productivity?

An example of the benefits gained from multi-tips in production I Holland was approached by a customer who required increased tablet output, but without incurring costly expenditure on additional tablet presses. The machine being utilised for production of this particular tablet was a Korsch PH800, 77 Station Press. Single tip punches were being used initially, which gave a theoretical maximum tablet output of approximately 831,000 tablets per hour.

If your requirement for tablet manufacture is to increase production capacity within a short time frame, multi-tips are considered to be the best solution. They can eliminate the expense and time delay that can be experienced waiting for new capital projects to be approved and implemented. They can also drive a reduction in plant running costs without decreasing output and reduce the time required to get them to market.

In reality, the machine was running at 80% of maximum speed (which is quite typical) and actual tablet output was around 665,000 tablets per hour.

With the combination of correctly designed tablets and well manufactured multi-tip tooling, using the correct raw material and coatings, the use of multi-tips is the obvious answer to greater productivity, and a reduction in run-time per output of tablets, leading to less maintenance per batch and reduced press set-up time, which in turn reduces costs.

Another example of the successful implementation of multi-tip tooling was with the installation of monoblock multi-two tooling onto a high speed Fette press with a segmented die table. Initially running at 900 RPM with a single tip, resulting in 900,000 tablets being produced per hour. The customer required a greater output so I Holland increased the machine speed to 1200 RPMMP using monoblock multi two tooling and increased tablet output to 2.4 million tablets per hour.

In order to increase tablet output I Holland suggested using multi-two tooling. During trials, tablet output was increased to 1 million tablets per hour at a press speed of 60% resulting in a 66% increase in productivity. But there was further potential for increased productivity, so I Holland provided multi-three tooling. This reached an output of nearly 1.5 million tablets per hour, which was an impressive 125% improvement on the original numbers. In this instance, production time per batch reduced from 14.5 to 8.5 hours which represents a significant improvement for the customer.

By simply adding multi-tip tooling, both of these companies increased tablet output without the need for expensive machine replacement, therefore providing significant gains to the tablet manufacturers.

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TABLETTING & ENCAPSULATION

hen expanding its analytical capabilities, the pharmaceutical services supplier Almac required a flexible machine to address the growing demand for clinical trial studies. Bosch supplied Almac’s site in Pennsylvania with a GKF 702 capsule filling machine and further equipment, built around a new concept focusing on research and development. Almac provides a product and services range from research to pharmaceutical and clinical development to commercialisation of products. The company has its global headquarters in Northern Ireland, and extensive facilities in the UK and the US. Target customers include the top multinational pharmaceutical manufacturers in the clinical trial supply industry down to smaller biotech companies. Half of Almac’s clinical supply business is primary and secondary clinical packaging. “Our operational team decided to expand our analytical capabilities,” said Dan Megill, director of operations at Almac. For that purpose, the facility in Pennsylvania needed equipment that could handle higher volumes. In order to analyse the effect of tablets, Almac was looking for a flexible and modular machine that is able to fill different tablets into capsules. At the same time, the capsules should be filled with powder and blended for clinical analyses. 24

Flexible friend Almac opts for capsule filling line from Bosch Packaging Technology

No influence through placebo effect For its customer’s efficacy studies, it was important to Almac that the encapsulation equipment was able to produce DB-AA and DB-AAel capsules for double-blind clinical trials. Using these special capsule formats, it is virtually impossible to open the capsule without causing visible damage. This way, the service provider can blend capsules for medical comparisons and test persons from being influenced by the so-called placebo effect. Comparator products can be discreetly enclosed to improve patient compliance, while the tamper-evident design prevents bias. Almac’s new capsule filling line includes the GKF 702 capsule filler, a capsule deduster, a metal detector and the KKE 1700 checkweigher. The integration of the checkweigher ensures 100% control of filled capsules. A feedback loop from the checkweigher to the machine determines whether capsules are under- or overfilled. The KKE

1700 checkweigher comprehensively documents all production batches. “Our team toured Europe and looked at the different machines that vendors were offering. We determined very quickly that the Bosch equipment met all of our requirements. The equipment provides optimal pharmaceutical security, achieves an appropriate level of blindness, and is fully cGMP compliant. Out of all the options we evaluated, the Bosch machinery was the obvious choice,” Megill explained. This specific machine was the first GKF 702 that Bosch sold to the US market. “In the view of Bosch, the GKF 702 is probably a mid-output machine. For us it really stands for high volumes,” Megill added. The purchase of the capsule filling machine created a balance between Almac’s European and American sites by providing paralleled capacity to handle large and smaller scale projects simultaneously.

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‘A real showpiece’ In this particular project, the challenge was to fill capsules with different tablet sizes which were originally not developed to be filled into capsules. “The Bosch team helped us with their overall knowledge base, which they have never stopped improving,” Megill said. “It also gave our technicians and operators very extensive training on the machine including trouble-shooting matters.” Megill sees the key benefits of the equipment in its tooling for filling and easy-to-clean configuration. Another aspect is the enormous flexibility. While Almac utilises the equipment’s capability to fill capsules with powder, tablets, and pellets, the GKF 702 also allows for liquid and combination fills, in case a pharmaceutical producer requests these features. Moreover, a vacuum dosing wheel enables a gentle and accurate filling of very small quantities of powder. Filling weights can be easily adjusted during the set-up phase and throughout the production process. “We now have a real showpiece here,” Megill said. “Customers who visit our facility are happy to see the new equipment available for their overencapsulation needs.”

TESTING Frankfurt am Main · 15 – 19 June 2015

SGS completes analytical validation

GS Life Science Services, pharmaceutical clinical and bioanalytical contract solutions provider, has successfully completed a full analytical validation of the novel Meso Scale Discovery (MSD) V-PLEX 10-plex Proinflammatory Panel I, for use with human plasma samples at its laboratory in Poitiers, France. The validation included measurement of accuracy, recovery, dilutional linearity, and stability, using a set of in-house, as well as the manufacturer’s surrogate validation quality controls. This new service offering, complementing SGS’ existing biomarker portfolio, will enable the laboratory to generate more information by quantification of multiple biomarkers, and as 10 assays can be conducted in parallel, save on the volume of clinical samples required, while reducing turnaround time and cost for customers.

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The Panel measures 10 cytokines that are important in inflammatory response and immune system regulation, as well as numerous other biological processes. These assays can detect biomarkers produced in a variety of tissues and body fluids, where over- or under-expression may indicate a shift in biological equilibrium. It also includes assays for many of the Th1/Th2 pathway biomarkers and measures biomarkers that are implicated in various disorders, including rheumatoid arthritis, Alzheimer’s disease, asthma, atherosclerosis, allergies, systemic lupus erythematosus, obesity, cancer, depression, multiple sclerosis, diabetes, psoriasis, and Crohn’s disease.

Be informed. Be inspired. Be there.

“We have deep understanding and expertise in the use of multiplex platforms as one of the routine bioanalytical procedures for clinical testing,” commented Dr Rabia Hidi, SGS Life Science services director of biomarkers & biopharmaceutical testing. She added: “We can produce robust data and fully validate multiplexing methods to offer both quality of data and cost convenience, while using the minimum sample volumes. Where SGS differentiates itself in this space, is that our multiplexing methods can be fully validated and used in decision making studies.”

www.achema.de

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CHROMATOGRAPHY

Get connected Lindy Miller, Agilent Technologies takes a look at achieving an inert gas chromatography flow path through better GC connections

Column selection in particular is a key consideration for an inert GC flowpath as column bleed can cause baseline noise and interference. Poor GC column performance can also affect productivity and data quality. The use of high-performance GC columns delivers better results when it comes to inertness and column bleed. Figure 1 shows a comparison between two competitive GC columns for the recovery of active compounds.

as chromatography (GC) and GC/MS are powerful techniques for trace level analysis across a range of applications. Regulatory agencies are increasingly pushing for lower levels of detection of active compounds. At the same time, sample matrices are becoming more complex. Balancing these trends is a challenge for analysts who need to maximize sample throughput, while keeping systems within calibration. To avoid re-runs and improve productivity, analysts seek tools that help systems hold calibration, even after injection of samples with difficult matrices. An inert GC flowpath has been shown to extend the time and number of samples between calibration. Flow path inertness is at the cutting edge of GC and by optimising the transfer of analytes from the injector through the GC flowpath the signal can be increased. This allows the analyst to extend the calibration range. This optimization can now be achieved by considering all the components of the GC flowpath, in particular ensuring robust and leakfree GC connections.

Improving GC sensitivity through an inert flow path In gas chromatography, inert surfaces in the flow path from the inlet through the column to the detector are essential for achieving good peak shapes, low levels of detection and accurate results for active analytes. Active sites along a non-inert GC flow path (such as injector, column, liner and detector) can latch onto active analytes and degrade peak shapes, or can absorb trace analytes completely. Lower limits of detection, less tailing, and more reliable results are now available even for difficult analytes. Active sites in an improperly deactivated liner or glass wool, such as silanol groups present on the glass surface, can cause the degradation or adsorption of sensitive compounds. This can result in loss of analytes before even reaching the GC column. A lack of inertness can negatively impact GC sensitivity but by following these five steps you can achieve an inert GC flow path for optimum GC sensitivity: 4M aintain the inlet to help ensure peak instrument performance and productivity 4 P revent sample loss at injection by using a deactivated liner suited to your injection technique 4 S elect a column with optimized inertness to minimize compound loss and degradation for more accurate quantitation of active analytes, especially at trace levels emember your detector for mass spec systems, use an inert source 4R to ensure accurate quantification and high sensitivity se a gas purifier to provide a clean, high quality gas supply that 4U is free of oxygen and contaminants

Better GC connections Ever since the techniqueâ&#x20AC;&#x2122;s invention, leaking GC column connections have been a source of frustration and wasted time in GC laboratories. Time is often spent troubleshooting and manually re-tightening column, retention gap and transfer line connections using a wrench â&#x20AC;&#x201C; time which could otherwise be spent analysing results or running more investigations. Due to this time impact, as well as the critical impact on results and instrumentation, preventing GC leaks becomes a priority for those looking to achieve an inert flowpath. GC column connections leak because capillary column ferrules made of graphite-polyimide blends loosen after repeated heating cycles, creating gaps in the mechanical fitting. This can lead to instability of detector baseline, noise and questionable results. On top of this, leaks at the GC column fitting can also cause significant losses of expensive high quality gas, shorten equipment lifetimes, and destroy columns. Furthermore, some detectors can be damaged by exposure due to high column bleed caused when oxygen diffuses into the flowpath from leaking column connections resulting in inaccurate results and costly instrument downtime. New GC supplies have been developed to help ensure column connections are secure by offering a tight, consistent seal without the need for expensive system upgrades or adaptors. One such development is the Self Tightening column nut from Agilent.

Maintain, prevent, protect Increasingly stringent demands on GC systems for sensitivity, accuracy and reproducibility means that analysts need access to the tools to create an inert GC flowpath. By investing in the right chromatography supplies, researchers carrying out trace-level analysis can discover how the right GC connections really do make all the difference.

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PHARMAPACK

French connection This year’s Pharmapack Europe promises innovation, networking and education for anyone seeking pharmaceutical packaging and drug delivery solutions

ore than 380 leading suppliers (including 80 new companies) in pharmaceutical packaging and drug delivery technologies will be exhibiting at Pharmapack Europe, which takes place on the 11-12 February 2015 in Paris Expo, Porte de Versailles. For pharmaceutical buyers and R&D managers, Pharmapack Europe is an ideal showcase for technological innovations, especially those presented in the Innovation Gallery and the Pharmapack Awards. Reflecting market trends, the international theme of the event is shown through more than 65% of international exhibitors and 45% of international visitors. According to the show organiser, what makes Pharmapack Europe different is its content programme, which deals with industrial issues. The main topics this year will be focused on regulation updates, new packaging materials, patient adherence & compliance, what’s new in injectables, oncology drug delivery & packaging, emerging technologies & innovation forecast and finally animal health packaging & drug delivery.

New features The Learning Lab area on the exhibition floor will provide 12 free conference presentations and the possibility for the exhibitors to talk about their latest innovations for 30 minutes. This open area will enable visitors to directly interact and share knowledge with exhibitors. Fast-growing markets will be discussed through networking breakfasts (North America & China) and a special workshop on “Pharmaceutical Packaging Materials Registration in China”. A dedicated workshop will be held on 12th February and hosted by Voisin Consulting Life Sciences who will address “Combination products: CMC and human factors/user tests for regulatory compliance & market success”. The organiser is also offering a new service to help visitors optimise their time and their visit. The International Meetings Programme will enable visitors to have private meetings with exhibitors based on their requirements. An area on the exhibition floor will be dedicated to networking to favour a performing business environment. The event also boasts an award ceremony with two distinctive product categories: Health Products: This award category will reward • pharmaceutical companies and suppliers they have worked with to develop a health product. It can be a new health product launch or improvement of an existing product which packaging has been improved. • Best innovative exhibitor. • Both ceremonies will be held on the Innovation Gallery at 12.30 on both days.

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Pharmapack North America relaunched Pharmapack North America (PPNA) will be relaunched, June 9-10, 2015, at the Jacob K Javits Convention Centre, New York. PPNA will follow the Pharmapack Europe model, bringing its highly successful European format to the North American audience. Featuring a special conference venue and a networking area directly on the show floor, PPNA is designed to be the must-attend event for pharmaceutical packaging suppliers and buyers in 2015. "Building on its success in Europe, we are delighted to bring an expanded Pharmapack event to New York. It sits at the heart of the US advanced drug producing market and will serve the largest market for pharmaceutical packaging in the world" said UBM Canon's medical portfolio director, Stephen Corrick. "The expanded educational and networking opportunities will provide a great opportunity for attendees and exhibitors."

PHARMAPACK

PREMIER EVENT Baltimore Innovations – exhibiting for the first time at Pharmapack Europe – will be showcasing its new proprietary Moisture Budget technical service, which evaluates humidity and desiccant behaviour within a product’s protective packaging. The analysis carried out is based on computer models developed by the company’s R & D director, Dr Mark Valentine, who will also be presenting at the event.

PERFECTLY PACKAGED

Visitors to this stand will see Baltimore’s FDA-approved desiccants and foil products. This include silica gel and molecular sieve sachets, together with and Activ-Strip films on a roll; barrier foil bags, zip lock pouches with SuperDryFoil patented proprietary packaging technology; desiccated flip-top vials with integral molecular sieve sleeve; and humidity indicator cards.

The pharmaceutical industry is awaiting the implementation of the EU Falsified Medicines Directive 2011/62/EU which includes identification and authentication features on the medicine packaging. August Faller, will be presenting various solutions for the tamper-proof protection of medicines at Pharmapack. Faller offers solutions for the tamper-proof protection of packaging. These include adhesive labels (closure labels) on the folding carton, structural tamper-evident closures, self-destructing engaging flaps and glued flaps.

Stand 318 Protected species: August Faller, will be presenting various solutions for the tamperproof protection of medicines at Pharmapack

Stand 442

SANNER AT PHARMAPACK 2015 IN PARIS Sanner, manufacturer of plastic packaging for pharmaceutical, medical and healthcare products, will be showcasing three product launches at Pharmapack. This will include the Brilliance tube for effervescent tablets and solid pharmaceuticals with IML technology, as well as two drop-in solutions for pharmaceutical packaging. The company also offers AdCap capsules and the AdPack pillow packs, for desiccant packaging. “After our very positive trading results from the preceding year, we have invested a considerable amount of energy into product development and have expanded our portfolio, especially in the categories of effervescent packaging and pharma desiccant packaging,” says Sanner CEO Holger Frank. “Pharmapack is the ideal platform to present our clients and prospects all three launches at a glance.”

Stand 904

Take the tube: Head to the Sanner stand to see the Brilliance tube for effervescent tablets and solid pharmaceuticals with IML technology

DELIVERY SERVICE Gerresheimer will be exhibiting a range of glass and plastic packaging products and systems for the pharmaceutical industry and healthcare sector at Pharmapack. The product highlights at the event will be MultiShell vials and the Clearject syringes made of COP, for parenteral medications, biopharmaceuticals and oncological drugs. “We’re fully focused on our customers in the pharmaceutical industry and committed to offering them custom solutions in excellent quality,” said Andreas Schütte, board member with responsibility for the medical systems division.

Stand 802

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Meeting point: MultiShell vials and the Clearject syringes made of COP will be among the exhibits on the Gerresheimer stand at Pharmapack

PACKAGING

Safety first Christina Desirée Holder and Marek Miszczak at Gerresheimer discuss the case for stronger laws for child-resistant packaging

hese days, child-resistant packaging is mandatory for many household chemicals and prescription drugs. There is also an evident trend of similar regulations being introduced for non-prescription drugs and food supplements.

A survey by the US Consumer Product Safety Commission (CPSC) shows, for example, that over 85,000 children were treated at public hospitals in 2004 due to poisoning. That corresponds to almost 430 cases of poisoning per 100,000 children. In just under 60% of cases, the children had consumed oral prescription drugs, oral over-thecounter medications or food supplements. When medications for external application are also taken into account, the figures are even higher.

CR packaging for PD High-risk household chemicals such as drain pipe cleaners, oven cleaners and methylated spirit, which often come in bright coloured packaging that appeals to children, have long had child-resistant closures as standard. These drugs generally have packaging closures that require specific action sequences to open which small children, in particular, are unable to perform. To open the packaging, a combination of simultaneous or sequential actions is generally necessary. The popular squeeze and turn closures have to be squeezed and turned simultaneously in order to open them. Pressing the cap at defined positions distorts its shape so that the locking elements are released. In addition to the combination of two actions, packagings often have large sized caps which hinder small children’s hands from pressing the two diametrically opposed release points at the same time. Push and turn closures have to be simultaneously pushed and turned before they can be screwed off. Packaging products with flip-top lids or pump sprays incorporate other safety features relating to the opening or trigger mechanism.

Health service: 85,000 children were treated at public hospitals in 2004 due to poisoning

The future: CR packaging for supplements In the future, the use of child resistant packaging will probably be extended beyond prescription and OTC drugs to food supplements such as vitamins and minerals. Overdoses of food supplements can also lead to serious health problems and they pose a particular risk because they are often stored in the kitchen rather than the medicine cabinet, where children have easy access to them. In light of this, primary packaging manufacturers will play a pioneering role in bringing about greater child safety. In addition to obligatory compliance with regulatory requirements, it is in their interest to develop efficient solutions for patient health and product safety – firstly because it is also in the interest of patients - as end-users of their products - and secondly because this will provide them with a means of differentiating themselves from competitors.

Innovative solutions

CR packaging for OTC

Government authorities are well aware that although these safety measures improve the child safety situation, they don’t guarantee it. The CPSC has emphasised that there is no such thing as child-resistant packaging. It therefore recommends that the packaging - including child resistant packaging - is not viewed as the primary protective measure but as the last line of defense. There is another problem associated with ‘child’-resistant packaging, namely that it often less effectively withstands the energetic efforts of a four year old than attempts by elderly citizens or people with limited motor skills to open it. The trend of tighter regulatory requirements for childresistant packaging therefore collides with the requirement of senior citizen-friendly packaging, a requirement which is becoming increasingly relevant due to the aging population. Associations which work in the field of anti-age-related discrimination are demanding ergonomic packaging that facilitates patient adherence and in some cases they oppose child protection association demands to optimize the efficiency of child resistant mechanisms.

The CPSC is currently drafting a guideline according to which all prescription and OTC drugs with more than 0.08mg of imidazolines must have child resistant packaging. Imidazolines (tetrahydrozoline, naphazoline, oxymetazoline and xylometazoline) are vasoconstrictors indicated for ophthalmic irritation or nasal congestion. Accidental ingestion by children can cause serious adverse reactions, such as central nervous system depression, decreased heart rate and depressed ventilation. From 1997 through 2009, according to CPSC 5,675 children younger than five years suffered injuries after ingesting products containing imidazolines, especially eye drops.

Robert L. Franklin, MS, Gregory B. Rodgers, PhD: Unintentional Child Poisonings Treated in United States Hospital Emergency Departments: National Estimates of Incident Cases, Population-Based Poisoning Rates, and Product Involvement. Directorate for Economic Analysis, US Consumer Product Safety Commission, Bethesda, Maryland. Pediatrics 2008;122;1244

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PACKAGING

Eye line How an eye drop manufacturer accelerated production with help from Bosch Packaging Systems

Specialising in sterile manufacturing, Excelvision, based in Annonay, France, provides contract manufacturing services for liquid eye drop plastic vials to numerous companies. However, to increase production and capitalise on additional contract manufacturing opportunities, Excelvision enlisted Bosch Packaging Systems to install a fully automated packaging line. With significantly higher output capabilities, Excelvision expects to increase production by nearly five-fold. The new line also gives the company greater flexibility to meet the diverse requirements of its customers. Excelvision manufactures vial cards in bulk, each hold five blow-fill-sealed single-use vials. Because the company produces different product shapes and configurations for its customers, it faced a logistical challenge in rapidly packaging the diverse products. Prior to working with Bosch, Excelvision relied on individual vertical form, fill and seal (VFFS) machines to package each vial card. However, this approach required vial cards to be manually fed into the system. At peak capacity, production only reached approximately 60 cards per minute, not fast enough to keep up with current demand, let alone plan for new market expansion. “We found ourselves at a crossroads,” says Philippe Pensuet, head of engineering and EHS at Excelvision. “Our operations were not flexible enough to react to our customers’ demands, and it was taking too much time and effort to win new contracts.” Purchasing multiple storage trays dedicated to each product format size would have been too costly. However, Bosch’s complete line solution allowed the company to use one storage tray type for all product formats. The line provided the necessary flexibility to separate the vial cards and then package them appropriately for each customer.

“Also, as demand increases for single-dosage packaging, the new line gives us the flexibility to adapt production in the future,” adds Philippe Pensuet. “This was a challenging project for us because we’ve always used stand-alone machines,” Pierre Laissy, project manager at Excelvision explains. “Bosch provided the consultation we needed for a successful upgrade to our first highly automated, complete line solution.” The project also involved a lengthy approval process with Excelvision’s customers as they needed to verify that the new packaging solution would meet market needs and regulations. During this vetting process, Bosch regularly consulted with Excelvision about different packaging styles and materials. Because of the many parties involved, the project took two years to come to fruition, during which time the company developed a close partnership with Bosch. Laissy notes that two advantages offered by Bosch were flexibility and modularity. To meet different customer needs, Excelvision required equipment that could be easily adapted to meet specific demands. This modular approach, allowing for quick and tool-less changeovers, was critical for Excelvision. In addition, the new line requires only three operators, letting Excelvision redirect labor to higher-skilled positions. The bulk vial cards are first manually loaded into an intelligent feeding unit, which unscrambles and separates them equidistantly. It then aligns the individual vial cards before transferring them onto a conveyor. The intelligent feeding unit operates at adjustable speeds, with an output of up to 300 pieces per minute. The vial cards then travel to the Sigpack LDF feed placer, which features delta robots that pick and place individual cards into an infeed wrapper chain. The Sigpack LDF is equipped with a vision detection system that ensures

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quality control of the products. It also communicates with the robot to ensure correct product orientation. Products then move along to the Bosch Sigpack HSL horizontal flow wrapper, which features a long dwell sealing unit for extended sealing time. This ensures that the aluminum-laminated film is hermetically sealed, which is critical to protecting the blow-fill-sealed products against water evaporation and light effects. In addition to automatic film splicing, the flow wrapper features printing and vision inspection of various data. “We decided to overwrap each vial card with PE plasticaluminum laminated film. This material significantly extends product shelf life by providing the highest protection from oxygen and humidity,” remarks Philippe Pensuet. The longer shelf life benefits Excelvision’s customers, as well as retailers and consumers. Bosch also subjected the wrapped cards to various tests, such as vacuum pressure and under water submersion, to verify that packs have an air-tight seal. For cartoning Excelvision installed Bosch’s Sigpack TTM topload cartoner. The Sigpack TTM picks flow-wrapped products out of a grouping chain and places them into cartons via a robotic top loader arm with gripper unit. The unit operates at speeds up to 70 cartons per minute, and the topload carton former has up to four lanes available for production. A key advantage of the Sigpack TTM is the ability to make quick and tool-less changeovers for up to four different carton formats, giving Excelvision the flexibility to accommodate diverse customer needs. “Depending on the market sector we are serving, the system allows us to produce different configurations, including four-, five-, and six-counts,” Laissey explains.

CONTAINMENT

Solo performance Solo Containment reveals the expertise behind its engineered acrylic containment system Harmful API particle escape from uncoated tablets during bottling or blister pack operations is a growing threat in many pharma packaging facilities.

unacceptable 16 micrograms /M3 with the un contained process to levels below 10 nanogram / M3 with the containment isolator in place.

Looking for an alternative to conventional hard shell isolator technology Solo Containment has developed an engineered acrylic containment system that combines total process visibility with what it calls exceptional API containment.

The Solo system has already been applied to high speed blister lines, large-scale micro tablet cassette fillers and conventional tablet bottling lines. In all cases, says Solo Containment, the clients have enjoyed significantly lower construction costs as well as faster delivery cycles than would be the case with conventional isolator technology.

The company says that occupational exposure data from recent installations proves that the Solo system attains OEB 5 containment standards during tablet bulk loading , vibratory feed and final fill / packing operations. Using multi-stage HEPA filter exhaust airflow the Solo packing line isolators create a safe negative pressure airflow around all API exposed parts of the packing operation. Visibility through the cast acrylic isolator walls is unrestricted and operator access to load hoppers and set up stations are contained by full arm length glove access developed from ergonomic trials at the design phase. Recognising that one of the major particulate escape sources is tablet hopper loading Solo has developed solutions for contained tablet in feed using both the EziDock CSV systems as well as RTP canister technology. These systems permit routine replenishment of bulk tablets with close-to-zero aerosol escape. In a recent SMEPAC test with a US client, the Solo system registered a reduction in operator exposure from an

Well kept: Solo Containment has developed an engineered acrylic containment system that combines total process visibility with what it calls exceptional API containment One to bottle: The Solo system has already been applied to high speed blister lines, large-scale micro tablet cassette fillers and conventional tablet bottling lines

While the engineered acrylic solutions Solo provides are ideal for high volume lines operated on a bulk campaign basis, clients in the CRO or clinical trials sector seek a single campaign duration system that avoids any risk of batch-to-batch API cross contamination. At the CTS facilities, the Solo team has harnessed the same total transparency, negative pressure and multi HEPA filter airflow principles and constructed the containment from flexible film complete with welded in glove access sleeves, load airlocks and waste disposal sleeves. Solo’s flexible film filling line isolators are constructed from FDA compatible anti static films that may be attached around the filling machine, capsule filler or blister machine in minutes, giving a fast track change over at each campaign change. The engineered acrylic and soft wall packaging isolators are subjected to design review, ergonomic and task efficiency verification and detailed operator training.

TIME’S UP

SERIALISE NOW ! In many markets, serialisation of pharmaceutical products is imminent or already compulsory. Isn’t it time to get started?

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MedTracker

: Discover the future-proof software solution for pharmaceutical serialisation and T&T

Genderless AseptiQuik sterile connectors from CPC simplify single-use systems design and process integration. The interchangeable connectors support modular system design, reduce system complexity and help streamline the supply chain.

For your demonstration, meet us at Packaging Innovations, stand K3!

These genderless connectors are available in a range of interchangeable 6.4 mm to 19.0 mm flow solutions, in both gamma and high-temperature versions. For flexibility in hybrid processing applications, AseptiQuik G STC connectors integrate a genderless AseptiQuik sterile connector and the Steam-Thru II SIP connector. This integrated combination connector increases flexibility in process design and plant configuration, simplifies systems integration, and reduces both overall production costs and time to market. AseptiQuik G STC connectors enable manufacturers to steamin-place CPC’s AseptiQuik G connector directly to stainless processing equipment. Steam-Thru technology allows the SIP process to be completed in advance of the final connection, without having to wait up to 60 minutes for SIP prior to harvest or feed. After the SIP cycle, the genderless AspetiQuik G allows a sterile connection to a range of single-use systems, driving down cost by allowing the same bag system and tubing manifold SKUs s to be used on both hybrid and complete single-use systems.

25/26 February 2015 – NEC Birmingham

Come and meet us at stand K3

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Atlantic Zeiser Ltd 53 Central Way – Andover Hampshire – SP10 5AN – UK Tel: +44 (0) 1264 324222 www.atlanticzeiser.com

CHEMICAL REACTION It’s important to keep on top of the latest services, companies and individuals. EPM’s Chemical Reaction highlights a technology or business we think would be worth your while keeping in the mix...

Problem solved Telstar offers a range of solutions for the life science sector. Jordi Serrat, Telstar, tells EPM how the company can benefit the pharmaceutical world in particular

EPM: Who are you and what do you do? JS: Telstar, part of the Azbil Group, specialises in the development of global hightechnology solutions in engineering, construction, process equipment and services for life sciences in general and for the pharmaceutical and biotechnological industry in particular.

Q & A

EPM: What have you focussed on recently? JS: The company has stepped up its activities in the development of new technologies for solutions associated with two critical pharmaceutical production fields: integrated systems applied to process equipment and modular concepts applied to the construction of facilities. Under the one-stop-shop solutions concept, the company has developed highperformance integrated systems for pharmaceutical processing using in-house sterilisation, freeze-drying, containment, water and pure steam generation and clean air technologies. It has also focused on promoting the innovative modular execution concept for pharmaceutical and biotechnological installations. Together with its sister company KeyPlants, Telstar can assist laboratories using modular concepts, especially those installations which require high containment and maximum safety specifications for handling highly active ingredients. It’s a formula which reduces time to market for lifesaving products, such as pandemic vaccines and new cancer treatment products. EPM: What is you latest service/ innovation? JS: Telstar has recently introduced the new ionHP biodecontamination system for use in pharmaceutical aseptic enclosures; an innovative technology which resolves some of the traditional difficulties associated with H2O2 biodecontamination processes. Unlike conventional systems, the ionHP technology increases the efficacy of the decontamination process and reduces degradation of construction materials. This new biodecontamination technology has been applied in aseptic isolators and sterility test isolators. The company has also developed a new generation of vial loading and unloading systems that can be integrated into freeze dryers. EPM: How can you benefit the pharmaceutical sector? JS: The main competitive value of Telstar is its capability of providing global, integrated solutions for the pharmaceutical industry, based on in-house technologies and resources of knowledge and experience from its own highly qualified workforce. We offer complete solutions that span from the design, engineering and construction through the process equipment manufacturing stage and on to start-up phases, including turnkey project management and support for critical installations.

Future plans? JS: The future short-term plans in the innovation field are targeted on increasing the added value Telstar provides in the spectrum of freeze-drying, containment, water systems and sterilization technologies. Telstar is now carrying out programs to improve productivity and efficiency in pharmaceutical process equipment, most specifically those associated with freeze-drying technologies and pharmaceutical water systems, and HVAC systems for cleanroom applications. For example, Telstar is now working on the integration of the ionHP biodecontamination system to pharmaceutical sterile cleanrooms, new methods to improve yield in lyophilization processes through time reduction of the drying phase, new flexible water for injection production systems, new systems for handling of single vials in an automatic line for loading and unloading of lyophilizers and new energy saving HVAC systems specially adapted to cleanrooms and designed to offer more efficiency and lower energy consumption.

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