EPM May 2015 by EPM Magazine

PRESSING AHEAD

COVER STORY: PRESSING AHEAD NATOLI outlines its tablet tooling expertise at Achema Hall 3.1 F15 MAY 2015

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Contents May 2015 | Volume 15 Issue 3

Regulars

Features

COMMENT

A PROBLEM SHARED

How the pharma sector is getting up close and personal

I Holland helps with the most common tablet compression tooling problems

NEWS ANALYSIS

THE CURE

How students from the University of York have helped with new pain relief method

OPINION

Lu Rahman looks at some of the latest drug developments for curing disease

MANAGEMENT SKILLS

This issue’s Q&A features David Hinds, I Holland

LIMS expertise form Thermo Fisher Scientific

REGULATORY AFFAIRS

LABELLED WITH LOVE

Owne Mumford in the spotlight

The latest from the packaging & bottling sector including Faubel, Essentra and Nolato.

CHEMICAL REACTION

TRANSFER WINDOW

COVER STORY: PRESSING AHEAD Natoli outlines its tablet tooling expertise

Getinge discusses containment

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from the editor Gene genie From number plates to drug development, the personal is big business and the individual has never been more important. Precision medicine is gaining ground with clinical trials centred around one person, not overall average results, becoming increasingly significant. Last month Nature, ran an article highlighting how everyday millions of drugs are taken that have no effect on the patient. The piece stated: “The top ten highest grossing drugs in the United States help between 1 and 25 and 1 and 4 of the people who take them. For some drugs, such as statins – routinely used to lower cholestrol – as few as 1 in 50 may benefit. There are even drugs that are harmful to certain ethnic groups because of the bias towards white Western participants in classic clinical trials.” In the US, the move towards a more personal and precise approach has seen Obama announce a $215 million Precision Medicine initiative and the ‘one size fits all’ approach is becoming less relevant for the treatment of certain illnesses such as cancer. Using genetic information to treat disease enables professionals to gain increased knowledge about tumours, for example, and the way in which tumours may exhibit their own set of genetic changes. By getting to grips with the changes taking place within cancer cells in one individual’s body, it is becoming possible to create more effective treatments targeted at that patient’s genetic profile.

And on a more general scale, the link up of Apple and IBM is being hailed as potentially offering major implication for the growing number of people using wearable tech to monitor their health. The partnership will see the two companies and other medical device manufacturers make the data available to doctors. One consequence of this could be more personalised treatment for illness such as diabetes. It’s all exciting stuff and the possibility of more targeted therapies and medicines has to be welcomed. At last the time has come to get up close and personal with the pharmaceutical sector.

Lu Rahman

An example of the advancement of personalised medicine has taken a step forward through a UK-US life science collaboration involving Cambridge-based Horizon Discovery. Nebraskabased Transgenomic has evaluated Horizon’s gene editing technology and has been so impressed it has strengthened the alliance to use Horizon’s human genomic reference standards to assure the quality and performance of its own technology. Transgenomic’s expertise crosses multi-disease areas including cancer, cardiology and inherited diseases where gene editing is critical to finding therapies tailored to an individual’s genetic make-up.

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NEWS ANALYSIS

Student helps discover new pain relief delivery method

University of York chemistry undergraduate has helped develop a drug release gel, which may help avoid some of the side effects of painkillers such as ibuprofen and naproxen. In a final year project, MChem undergraduate student Edward Howe, working in professor David Smith's research team in the department of chemistry looked for a way of eliminating the adverse side-effects associated painkilling drugs, particularly in the stomach,

and the problems, such as ulceration, this could cause patients. Supervised by PhD student Babatunde Okesola, whose research is supported by The Wild Chemistry Scholars Fund, Howe hoped to create gels which could interact with drugs such as naproxen and release them at the slightly alkaline pH values found in the intestine rather than the acidic conditions in the stomach. His aim was to both protect the pain-killing drugs and help limit some of the side effects they can cause.

The researchers created a new gel, based on small molecules which self-assemble into nanofibres which could interact with a variety of anti-inflammatory, painkiller drugs, including iburofen and naproxen. The research is published in Chemical Communications. Specific interactions between the gel nanofibres and the drugs meant that high loadings could be achieved, and more importantly, the release of the drug could be precisely controlled. The gels were able to release naproxen at pH 8

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Professor Smith said: “Although researchers have used gels before to try and improve the formulation of naproxen, this is the first time that a self-assembling system has been used for the job, with the advantages of directed interactions between the nanoscale delivery scaffold and the drug. As such, this is the first time that such precise control has been achieved.” Howe said: "The research really fascinated me. The prospect of being involved in developing a method to reduce the pain of others filled me with great pride. Understanding the interactions between the gel and the painkillers was very interesting and improved my knowledge of supramolecular chemistry." The next step for Professor Smith's team will involve stabilising the gel drug delivery systems in the very acidic, low pH, conditions found in the stomach so that they can transit safely to the intestine before delivering naproxen just where it is needed.

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Professor Smith added: “Perhaps this is something that one of next year's undergraduate project students might solve. As a research-intensive institution, York is committed to its undergraduates carrying out cutting-edge research such as this.” Soft touch: Edward Howe undergraduate has helped develop a drug release gel which may help avoid side effects of painkillers such as ibuprofen

NEWS ANALYSIS

Quality counts: According to Chris Wilkinson, Siemens Financial Services, labs need to acquire the ability to improve the quality of lab testing services

Financial management – making it pay Chris Wilkinson, head of sales for healthcare and public sector for Siemens Financial Services in the UK looks at making financial management effective

he UK medical laboratory sector is operating under mounting pressure as budget constraints and requirements to drive efficiency savings within the NHS have led to shrinking financial allowances for lab testing services. In an effort to cut costs, many hospital laboratories are being asked to consolidate into a single regional lab organisation. The search for competitive prices has also resulted in primary care trusts tendering for pathology testing services, further exacerbating the financial pressure already confronting the laboratory industry. To defend medical test budgets, laboratories must demonstrate the value they can provide to physicians, patients and the healthcare system. Studies have shown that a more effective use of laboratory tests can directly improve patient outcomes and thus significantly reduces the final cost of care. In order to navigate themselves in the new economic reality, medical laboratories need to acquire the ability to continuously improve the quality of lab testing services as well as to offer a more sophisticated menu of medical tests. This much needed competence is particularly crucial in helping diagnose and treat patients effectively as demographic changes and an increase in chronic illnesses further strain the healthcare system. This requirement, however, necessitates access to upto-date equipment and technologies that allow medical laboratory professionals to deliver speedy, efficient and accurate diagnoses and analyses to physicians and patients. Medical laboratories are particularly vulnerable to the pitfalls of retaining outdated technology, with its potential to negatively impact

capability, productivity and efficiency. The acquisition of modern lab equipment can offer advantages such as expanded test capabilities and optimal sample processing, thereby enhancing customer service, boosting competitiveness and ultimately improving patient care. Nevertheless, medical laboratory technology is often costly to replace and upgrade. Keeping pace with technological advancements also requires considerable capital expenditure. The spill over effect of a constrained budget within the health system is making it even harder for medical laboratories to contemplate such investment. In short, the medical laboratory sector is caught in a predicament where budget limitations are hampering its ability to make essential investments which play a key role in increasing the value of testing services. In this light, asset financing solutions such as leasing and renting are emerging as increasingly popular financing tools. Such financing techniques spread the cost of the equipment over an agreed financing period, with the ability to align monthly finance payments with the expected efficiency gains enabled by the use of the latest equipment. This removes the need for a large initial outlay and allows laboratories access to the latest technologies, without having to commit scarce capital or use traditional lines of credit. Financing arrangements can also cover other costs such as installation, maintenance, service and some consumables, as well as introduce the flexibility of future technology upgrade in line with future technology developments.

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Such tailored, all-encompassing financing packages tend to be offered by specialist financiers who have an in-depth understanding of medical technology and its applications. They are therefore more predisposed and more able to create customised financing packages that fit the specific requirements of each particular organisation – for instance, flexing the financing period to suit the customer’s cash flow. This contrasts with the standard financing terms usually available from generalist financiers. In today’s economic climate, medical laboratories that want to remain at the vanguard of their field need to be able to bring high value to the broader healthcare system. The deployment of the latest technology and equipment can help the medical laboratory sector realise this aim through improving diagnostic accuracy while maximising productivity. Medical technology investment, however, must be undertaken under the premise of sustainable and affordable financing. Forward-looking medical laboratories are therefore increasingly turning to alternative financing techniques, with which they can overcome affordability issues, as well as devise a much more transparent and sustainable financing strategy in equipment investment. More importantly, instead of tying up precious capital in equipment, medical laboratories can more effectively deploy available financial resources in other areas, such as staffing, training, and research and development – key areas that underpin the sector’s ability to make a vital contribution to raising healthcare service quality.

NEWS ANALYSIS

Consulting room B J Richards, Source, provides a buyer’s guide to management consulting

On the up: According to BJ Richards use of management consulting is on the rise in pharma

ith pharmaceutical companies facing challenges ranging from regulatory compliance to post-merger integration, it’s no wonder their use of management consulting is on the rise. Our research shows that the pharma and life sciences industry’s consulting use grew 11% in the UK last year and shows no sign of slowing down. But the pharma sector has tended to be a reluctant user of consultants in the past, which means that many executives will be wondering both if it’s the right thing to do now, and how to get the most out of their investment if it is. If these questions are top of your mind, here are a few things to consider.

Why use consultants? The single most common reason for hiring management consultants is to gain access to a particular set of skills. In broadest terms, specialist skills are of two types: Issue-specific skills are those that relate to the particular problem you face (say, regulatory compliance) while industry-specific skills are those relating specifically

to pharma – they mean speaking your language and knowing the industry (including your competition) inside-out. Ideally, you’ll want someone with a healthy mix of both issue and industry expertise, but identifying the right balance will mean thinking hard about the nature of your project, its complexity, and how important it is that someone ‘gets’ your industry before they can help you achieve your objective. Whatever a consultant’s skill set, the goal, of course, is to apply those skills to a particular project or problem. There are nearly as many reasons for using consultants as there are individual consulting engagements, but perhaps the most clear-cut case for using them (and the easiest to justify to the board) is when there’s a big project to be done and you know your team doesn’t have the time, people, or expertise to do it, do it well, or do it fast enough alone. In this instance, there are many ways quality consulting can smooth the path. Perhaps you have a project in mind and a good idea of what the end result should look like – a more resilient

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supply chain or a cost-cutting target – but you’re less clear on how to get there. In this case, a consultant with experience helping similarly situated clients accomplish similar goals – and with a tried-and-tested methodology for going from concept through to completion – can prove invaluable. Other times, there’s a battle plan but not enough soldiers to take the field: in this case, consulting firms can providing bright, energetic people ready to take charge, roll up their sleeves, and get your initiative running – without having to free up scarce resources in house. Sometimes what you need is less concrete – you have a difficult decision to make and a need to get your colleagues on board once it’s made. Here, a consultant can prove invaluable simply by virtue of bringing a fresh perspective and a dispassionate assessment of your situation and your options. A good consultant can also bring innovation, finding solutions that turn problems into opportunities to differentiate you organisation.

While there are many things you can do to ensure the success of your project once it begins, always remember that much of a project’s success is determined before you even start talking to consultants. If you’re able to identify the exact reasons why you’re hiring a consultant, what you hope to get out of the engagement, and you’re able to get your internal team on board in advance – you’ll be half way to victory before you even start.

How do I make the most of my consulting engagement? The most effective consulting projects are those in which the client and the consultant work together as a team, and as with any team, communication, and a willingness to cooperate are vital. •R emember that providing your consultants with too much information is always better than providing too little. •C onsultants should receive a briefing on the project, the people involved, and the criteria on which they were chosen. ake sure expected outputs and budget limits are understood. •M •M ake sure you have written agreement as to how the project will be conducted, including the project plan, deliverables, expectations, and who will be responsible for which risks. • I dentify problems early so they can be addressed. •H old regular progress reviews and get any agreed-upon action points in writing.

“

The most effective consulting projects are those in which the client and the consultant work together as a team.

• P romptly provide any resources and information you’re agreed to provide. t the project’s end, you should •A hold a joint project review to discuss outcomes and lessons learned.

HEADSPACE GAS ANALYSIS

“

If you’re able to identify the exact reasons why you’re hiring a consultant, what you hope to get out of the engagement, and you’re able to get your internal team on board in advance – you’ll be half way to victory before you even start.

”

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NEWS PROFILE

Need for change in pharma says industry

eakdale Molecular, a UK-based provider of drug discovery services to the pharmaceutical, biotech, diagnostics and materials sciences, has told EPM that the country’s leading authorities in research and development believe that as the pharmaceutical sector is constantly changing, there should be pre-competitive focus on areas fundamental to the research industry bedrock. An event, hosted by Peakdale Molecular, challenged its delegates with focusing efforts and driving change in order to address the key problems within the pharmaceutical sector. “We’ve seen huge changes within the pharmaceutical industry over the past number of years, and with that a shift in the type of drugs research undertaken,” said Paul Doyle, COO at Peakdale. “It’s no longer just about the science, it’s about wider issues. There are also problems surrounding the changing demographics, the threat of pandemics, and the increasing risk of the global population becoming resistant to antibiotics. All of these are very real threats, and the event presented a great opportunity to not only discuss these problems, but to plant the seed within each of the delegates about how to action change for the better.” The event brought together industry leaders from Pfizer, GSK, AZ, Sanofi, Eli Lilly, Novartis, Orion, Takeda, UCB and leading heads across academia to anticipate the future in drug discovery strategy. One of the focal points of the day’s discussion centred on the need for pre-competitive focus within early discovery.

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“If we are to progress and move forward as an industry, we need to make some changes to the way that we work,” said Prof. Trevor Jones. “If we are to progress research and look to provide solutions to meet the changing population’s problems, we need to work collectively as a sector. The consensus yesterday was clear, we need greater collaboration on a pre-competitive basis in order to meet the problems of tomorrow.” Discussions also focused on the role that university academics should play in drugs research. With a 2010 study showing that nearly a quarter of 252 FDA approved drugs produced in the US between 1997 – 2005 had their origins in US universities, one of the keynote addressed the steps that UK universities could take to emulate the success of this model.

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Speakers also addressed the topic of personalised medicine – looking at the increases in screening for genetic markers. The session raised important questions around the economic criteria for introducing treatments, particularly in light of a constrained health service burdened with increasing health care costs. It also questioned the impact that lifestyle changes would have on the key diseases that any future government would consider to be beneficial/cost effective. “We hope this event and its surrounding discussions act as catalyst for change,” said Doyle. “We wanted all parties to come out of the session with something to focus on, drive forward and to commit to actions that we can initiate and really make a difference. With the calibre of people that were in attendance yesterday, I really feel we achieved that and we will hopefully see the results of our efforts come to fruition over the coming year.”

NEWS ANALYSIS

Shetland pony midge secret to curbing allergies?

hetland ponies’ immune response to insect bites is helping scientists understand how people could be prevented from developing allergies.

The horse immune system can respond to midge bites in a way that prevents – rather than triggers – allergic reactions, researchers say. The ponies’ immune response to midge bites is similar to what happens in people with allergies, the team says. Understanding what triggers allergic reactions could help researchers come up with ways to stop people developing sensitivities. It was previously thought that ponies which do not suffer an allergic reaction to bites do so because their immune system does not recognise allergens carried by the insects, and as a result does not respond. However, researchers at the University of Edinburgh have shown for the first time that all horses respond and that their immune system can act in two different ways in response to the irritants in midge bites. One of these responses produces allergy symptoms – such as itching and inflammation – while the other prevents an allergic reaction, researchers say. The team found that after being exposed to midges, the horse immune system can release various types of factors – known as cytokines – which affect the behaviour of other cells.

Ponies that react to midge bites release cytokines – known as IL-4 – which trigger v symptoms. In ponies not sensitive to bites, another cytokine – INF-γ – is released, which blocks different immune cells that would otherwise trigger allergic reactions, researchers say. By priming the human immune system to respond to allergens in a way that does not trigger reactions, it could be possible to prevent people developing sensitivities, the team says. Allergies are caused by a complex interaction between genetic and environmental factors. Researchers say the reason why some individuals develop sensitivities to certain substances, while others do not, is not fully understood. It is unclear what causes the immune system to activate a protective response over an allergic one, the team says. The study, published in the journal PLOS ONE, was funded by the Dutch Foundation for Technical Sciences (STW) and was carried out in collaboration with researchers in the Netherlands. Dr Dietmar Zaiss, of the University of Edinburgh’s School of Biological Sciences, who led the study, said: “To our knowledge, this is the very first study of a natural allergic disease in which we can show that immune responses to allergens can take two directions, either leading to allergy or to tolerance. We believe this finding could have direct practical implications, for example by helping immune responses to choose the “right” direction in individuals who we would like to protect from developing occupation-associated allergies.”

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OPINION

Perfect partners Mike Straw, Achieve Breakthrough offers advice on why pharma procurement functions need to get hitched with the business

Money matters: According to Mike Straw, pharmaceutical companies are under increasing pressure from investors to improve financial returns and procurement functions have a role to play

harmaceutical companies are under increasing pressure from investors to improve financial returns. Coming at the same time as healthcare providers around the world try to rein in drug prices, the need to cut out waste and improve efficiencies has never been greater. Undoubtedly, procurement functions have a role to play here. Better aligned and more effective procurement processes can help the whole business to improve performance.

Procurement needs to stand up as an equal within the organisation. They have hugely important roles and until they respect that themselves the rest of the company will never ask them to the dance.

Shift perceptions

Despite this, the 2015 ProcureCon Healthcare benchmarking survey found that less than half (48%) of the pharmaceutical professionals surveyed saw procurement as a strategic partner in their organisation. This follows a recent Deloitte survey that declared only 28% of CPOs felt their procurement function was highly regarded internally and seen as a key business partner.

The procurement team needs to start challenging the status quo, not just accepting things because “that is the way they have always been”. Their perceptions need to be shifted just as the organisation also needs to shift its own perception to give procurement the respect it deserves.

In the current climate, pharma big and small need every part of the business to play a maximum part in value creation – and procurement is no exception. Procurement functions really need to prove their worth and show that they can be a real partner to the business – not just an administrative backwater.

Through more strategic thinking and being organisationally savvy, the procurement team can start to contribute more to leading the agenda, instead of just following it. This occurs when you start thinking big and can switch between modes: facilitator (simply helping to get contracts in place), expert (a source of knowledge to be consulted by the business) and coach (helping the business to improve by offering advice and guidance based on previous learnings).

A key issue for pharma procurement professionals is that 58% of CPOs feel their team does not have the skills required to deliver their procurement strategy. As a client once told us “procurement professionals are hired for their procurement skills and fired for their behavioural skills”. This lack of love for pharmaceutical procurement functions and the wider procurement industry has resulted in a lack of confidence in themselves. While speaking at a recent conference I found that procurement professionals often under-valued themselves and, you might say, saw themselves as the “ugly-stepsister” of the organisation. Perhaps they need to take some advice from Will Smith’s character, Alex Hitchens in the 2005 film Hitch in which he professes that to be loved you have to “leap and hope to God you can fly! Because otherwise, we just drop like a rock... wondering the whole way down...’why in the hell did I jump?’" Procurement functions need to take this leap and start seeing themselves as the prettiest girl at the party. To do this they need to shift their thinking. I believe that to shift perceptions four key changes need to be made:

Permission and confidence

Leading the agenda

Executing the agenda Whenever you look to strive for more there are always pitfalls. The more ambitious you are the more pitfalls you are bound to encounter. So procurement teams should not become dispirited if, in making the three changes above, they experience setbacks. That’s an inevitable part of the process. The key to executing the agenda is navigating such roadblocks and turning resistance into momentum. Don’t take the path of least resistance and revert back to old ways at the first sight of trouble. Instead, expect some setbacks and look for solutions so that you can execute what you are trying to achieve. Working with a number of large procurement functions in the pharma sector, we have seen ROI of as much as 60:1 through programmes that have helped transform how they partner with the business. If procurement implements these changes, they can start to achieve breakthroughs – and just maybe, get asked to the prom.

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OPINION

Planning ahead I Holland’s director, David Hinds reveals the company’s focus for the rest of the year to EPM

EPM: What’s I Holland’s focus for the rest of the year? DH: I Holland currently exports to 97 countries worldwide with a global network of agents and distributors enabling a local presence in most markets and areas of the world.

Our focus for this year is to continue to deliver the highest quality tooling and technical service to our customers. We will also continue to offer first class lead times, and value for money tooling to fit all types of press. We are also concentrating efforts in agent and market visits to ensure we understand what the industry requires and provide advice and information to answer any requirements. We will also continue to innovate and offer new solutions to tackle common tabletting problems within the industry. This will be achieved by continuing Research and Development into tablet sticking problems via our TSAR initiative, and by looking at increasing our range of coatings to deal with both sticking and wear issues which we commonly come across. 2015 has already been a very busy year for I Holland and this will continue with a number of exhibitions planned, including ACHEMA in June where we will be introducing some new additions to the portfolio. We will also continue to share our expertise with customers with troubleshooting courses planned to take place this year. This support continues with technical support available worldwide for our customers through meetings, conference calls and site visits. We will also be expanding our PharmaCare product portfolio and we are looking forward to introducing customers to new initiatives later in the year which will benefit manufacturing capacity. As a part of this will are continuing to focus on the 7 Step SOP programme which helps to promote tooling care and longevity. The future of growth of I Holland is important so we can provide an unparalleled service and support system. As a part of this focus we will be upgrading all internal computer systems to further improve processes and reporting. It is important that we offer the best possible service and products and our focus will always be to the market leading provider of innovative tablet tooling and complimentary equipment, underpinned by our understanding of tabletting science. This approach will always be at the heart of our future plans.

EPM: How do you see the pharma sector at the moment its strengths and weaknesses? DH: The pharmaceutical market is still very strong and continuing to grow and many areas are consolidating to reinforce the market. Another strength is the continuation for product transfers from one market to another within the major global pharmaceutical market. We are continuing to see a great demand to reduce pricing and lead times to get products to market so companies have to ensure they are competitive and use their knowledge and expertise to provide the service that the industry demands. This may be seen as a weakness but it does help to push innovation, with companies having to have advanced processes in place to meet demand.

EPM: With the first six months behind you, what’s going particularly well for the business? DH: We have already had a very successful year and have seen growth within the company with new agents in Mexico, Turkey and Peru. We have also expanded our market reach, which in turn has resulted in a healthy order intake. We have introduced new systems allowing us to improve quote conversion, order intakes and due date performance to ensure our service is unsurpassed.

EPM: Which exhibitions are you attending this year and what will your focus be? DH: We will be attending Ipack IMA in Italy in May, Achema in June and be exhibiting at Interphex Japan in August. We will also be in Columbia at Andina Pack at the start of November.

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REGULATORY AFFAIRS

Strategic thinking Vikash Patel, ELC Group outlines how EU regulators launch five-year strategy On 27 March 2015, the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) launched a draft paper for consultation outlining their strategic direction for the next five years. This is the first time that both agencies have aligned themselves under one banner in a coordinated approach and is a significant step in the acknowledgment of a rapidly developing regulatory landscape.

Key areas The agencies state that the new strategic document will help to strengthen collaboration across the network as well as meet the demands being faced by challenges in public health. In order to deliver on this they have focused on four main themes: Contributing to human health; contributing to animal health and human health in relation to veterinary medicines; optimising the operation of the network; contributing to the global regulatory environment. In each of these themes the agencies have identified four key objectives to work towards over the five year period.

Conclusion The emergence of this draft paper for consultation has helped to bridge the gap between innovation and regulation within a global landscape. It shows that the agencies are keen to be more collaborative and transparent, thus acknowledging the change in the scientific landscape. This paper is a step in the right direction and we look forward to its development and implementation over the next five years. The door has now been opened, so companies should be encouraged to take advantage of the proposed changes to the regulatory landscape and maximise their growth potential.

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These areas of focus provide companies both small and large with a golden opportunity to align their regulatory strategies to the proposed changes in the agencies focus in the following ways:

• Human health The agencies are targeting areas such as product availability and antimicrobial resistance as well as more flexible but robust regulatory pathways to support growing capabilities. This allows companies to help leverage disease areas where time-to-approval is key for patient welfare (such as dementia, for example). • Veterinary medicines The agencies are targeting a much more efficient regulatory framework thus allowing greater transparency in the approvals of veterinary medicines, as well as a more robust internal market for movement of approved products across Europe. • Network optimisation The agencies are focusing on strengthening global networks, such as those with pricing and reimbursement bodies, thus potentially facilitating quicker access to medicines. They are also focusing on greater collaboration with medical devices and therefore a greater opportunity to help steer regulation in this rapidly developing growth area. • Global environment The network will be taking a lead role in the convergence of global standards in close association with WHO. This will include integrated cooperation with emerging markets such as China and India, providing a more harmonized global framework.

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COVER STORY

Pressing ahead Natoli outlines its tablet tooling expertise and reveals its line-up for this year’s Achema

Member’s club: The NP-400 tablet press is a new addition to the Natoli portfolio

lthough the general process of solid dosage tablet compression has not significantly changed in more than 100 years, advances in tablet manufacture and quality continue to be made by forwardthinking companies in the industry. Tablet presses are becoming faster, more efficient, and more automated. Gone are the days when tablets could only be tested following a batch run. Tablet properties can now be monitored throughout the compression cycle to ensure conformity and quality. Automated testing and analysis can now be run during tablet manufacture to improve quality by identifying if problems such as inconsistent weight or dimensional non-uniformity arise during a batch. Using new available technology to monitor tablet production allows manufacturers to address such issues immediately, rather than waiting for testing and/or wasting product and technicians’ time. Batch records captured using new technology can also assist in process improvement and support the release of lots. The pharmaceutical industry is going to continue to look for ways to produce tablets more efficiently and at a level of quality that meets consumers’ expectations. Natoli Engineering Company, has partnered with leading solid dosage technology providers to provide innovative solutions the industry needs to ensure quality tablets. Natoli will debut its new tablet press, the NP-400, which has been designed to enable Process Analytical Technology (PAT) solutions, at the ACHEMA exhibition in Germany, June 15-19, 2015.

Powder Components are Integral to Tablet Quality The physical properties of a tablet are determined when the drug product formulation encounters the compression tools in the tablet press. The correct active pharmaceutical ingredient dose is brought to this point by a properly prepared recipe of powder components which have been appropriately granulated and/or blended. This formulation is delivered as a stable homogeneous mixture to be placed on to the die table of the press via a gravity or power feeder. The compression of that proper dose will determine the physical properties of the tablet and thus determine proper delivery of the medicine to the patient through specified tablet disintegration and dissolution performance. These physical qualities are arguably the most important to a product’s success. Warnings, recalls and loss of consumer trust can result from inadequate tablet analysis and failure to deliver proper dose in the tablet. Most modern tablet presses offer automation systems that provide system control and data acquisition during the manufacture of tablets. These systems are used to ensure conformity of the physical properties of tablets to their specified parameters. Some pharmaceutical manufacturers have found a need to use more advanced methods to ensure their tablets adhere to such standards.

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and utilizes a multivariate calibration model to determine whether the tablet is within the specification range. In the event that tablets are out of specification, the NIR controller will communicate with the NP-400â&#x20AC;&#x2122;s on-machine SCADA system and the tablets will be directed to the reject chute of the tablet press for later evaluation. This capability will enable customers to generate a data rich batch record that can be used for lot release support and process improvement options for the drug product manufacturing process.

Hourly rate: Inside the NP-400. According to Natoli, this machine can produce up to 180,000 tablets per hour

Natoli Engineering will also demonstrate an additional tablet testing and analysis system at the ACHEMA exhibition. The Kraemer Tablet Testing System complements the monitoring and control systems provided by the NP-400 data acquisition system and can be integrated with an on board NIR to assess content uniformity. This system can be used to test sample tablets taken from the tablet press at predetermined intervals so that the manufacturing batch can be characterized from the beginning to the end. The system tests the tablets for weight, thickness, diameter, hardness and content uniformity. Content uniformity is determined by utilizing an integrated NIR system. A combination of the real time tablet press monitoring systems with the offline tablet testing data delivers a comprehensive assessment of tablet compression performance. The data package provided could be a significant chapter in a real time release testing protocol that will offer Natoliâ&#x20AC;&#x2122;s customers the opportunity to realize significant cost savings through reduced laboratory testing and faster lot release of the tablets to the packaging department and on to the patient.

Partnerships Provide Solutions The use of process analytical technology (PAT) to monitor the critical process parameters of oral solid dosage processes has been adopted by some of these manufacturers to understand and control the processes involved in formulation preparation and tablet compression. Near infrared spectroscopy (NIR) has been utilized as a method to monitor product formulation blend uniformity as it comes on to the tablet press either at the exit of the powder chute or in the feed frame. NIR has also been utilized to monitor tablet properties immediately after compression. Either measurement location is capable of recognizing tablet content uniformity or physical property anomalies so that suspect tablets can be rejected and the integrity of the rest of the manufacturing lot retained.

The future of innovation in tablet manufacturing will require cooperation and partnerships among vendors in order to continue to advance solid oral dosage manufacturing practices for batch manufacturing as well as in the up and coming world of continuous manufacturing. The implementation of on-line and at-line PAT techniques will require a complimentary dossier of research and development work that validates the measurement and control techniques in order to achieve the utility and value of the installed analyzers and control system. Natoli is positioning its tablet press offerings to allow the smaller scale pharmaceutical company or contract manufacturer to implement and realize the economic value of this approach to modernization. These solutions provide economical opportunities to companies looking to improve tablet quality and improve manufacturing efficiency.

Testing and rejecting nonconforming tablets immediately after compression can present significant advantages to manufacturers employing the technology. In addition to producing consistently higher quality tablets, they also can improve efficiency and reduce costs by identifying nonconforming tablets during production. The opportunity to correct issues during lot manufacture saves time and prevents formulation waste.

Presses and Product Advances International tooling manufacturer Natoli Engineering Company is working with instrument manufacturers to add this technology to Natoliâ&#x20AC;&#x2122;s tablet press offerings. Natoli recently introduced a new tablet press, the NP-400. The NP-400 is a medium output workhorse capable of running around the clock, producing up to 180,000 tablets per hour. The NP-400 utilizes a supervisory control and data acquisition system (SCADA) to continuously monitor the tablet precompression and main compression forces, the tablet ejection force, tablet take off force, press temperature and humidity as well as the lubrication and utilities of the press operation. Its single footprint, off-shelf-controls, and selflubricated turret provide an efficient and simple operational setup. In the way that features such as auto-lubrication have become indispensible on tablet presses, spectroscopy is set to become an important option for tablet analysis during manufacture. Natoli has worked in cooperation with its instrumentation partners to integrate an NIR system onto its newest press. A design to implement a NIR probe to examine tablets post compression, on the die tablet, has been designed into the frame of the tablet press. Such a probe can take the NIR spectrum of each tablet after compression

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Pass the test: The Kraemer Tablet Testing System complements the monitoring and control systems of the NP-400

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• Validated Pharmaceutical production at rates of 78 tablets per second. • High speed/high force production with longevity, for abrasive compounds. • New & Intuitive touch screen software developed in house. • Automatic product recall, so set up is a button push away. • Soft starting to protect tooling during acceleration and deceleration. • Quick change turrets with perfect repeatablility every changeover. • Temperature management features and continuous sensor monitoring. • Hopper and feeder geometries to handle poor flow powders. • Lights-out capability & OEE monitoring within PTK’s software platform.

See our range of Tablet Presses, Capsule Fillers, Coating Systems, Granulators, Fluid Bed Dryers, Laboratory Equipment at www.ptk4u.com / www.ptk-gb.com

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TABLET PRODUCTION

A problem shared Problems with tablet compression tooling? I Holland gets to grips with the five most common issues

ablet tooling is subjected to a highly demanding process and this everyday use can lead to a number of problems during tablet manufacture. I Holland has developed answers to all tablet tooling problems by supporting tablet manufacturers with simple solutions to combat daily issues. Here are the five most common problems experienced by tablet manufacturers.

Handling damage One of the most common issues experienced is handling damage. There are several stages of the tablet manufacturing process where damage can take place, including unpacking the tooling, loading/unloading the tools in or out of the tablet press, during tool cleaning/maintenance procedures and storage/transportation. If damage occurs it can lead to the production of poor quality tablets, and even further damage to both the tooling and the tablet press. It is important to understand the delicate nature of the tooling and operate good tool care, maintenance, storage and handling procedures, to keep this problem to a minimum.

Figure 1: Example of damage to punch tip land area caused by poor handling

continued overleaf>

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Inappropriate operating conditions

Figure 2: Example of punch tip edges showing cracking and removal from the punch

The punch tip, or ‘cup’, forms the profile of the tablet, which can contain detail such as embossing or break-lines. These effectively reduce the strength of the punch tips. Problems can occur with small difficult to detect cracks, chipping of the punch tip edges, or even a full piece of the tip edge breaking away. Because high cyclic loading is applied to the cup many thousands of times per running hour, the tip edge is flexing and bending within the clearance between the punch tip and die bore. If operating conditions are not optimised, this can eventually lead to fatigue or brittle fracture, causing the punch tip to fail.

These types of failure can be avoided by careful punch and tablet design, correct metallurgical specification and conditioning and using the appropriate compaction force for the tool design.

Aggressive formulations Some formulations can cause adverse effects on the punch tips when under compression, such as abrasion, pitting or corrosion. Although tools are manufactured from hardened and tempered tool steel, the demanding processes involved can lead to deterioration if the tool material is not optimised to suit the formulation being compressed. Some granules are extremely hard and abrasive and can scratch, wear and impregnate the steel surface. Other granules can contain corrosive elements which react with the steel.

Figure 3: Pitting and abrasion caused by aggressive granules

These effects can be reduced by understanding the nature of the formulation to be compressed and carefully selecting a material or tool coating and condition to resist this.

Die wear

Figure 4: Examples of die bore wear, otherwise known as ‘Ringing’

This occurs especially when compressing hard, abrasive granules and powders. Die wear, or ‘die ringing’, takes place in the area of the die bore where the tablet is compacted. The wear appears as a double ring due the upper and lower punch tips flexing and bending within the clearance between the tips and the die bores during full compaction. The granule reacts between these surfaces leading to compressive and abrasive wear. Once wear becomes considerable it leads to problems such as tablet capping or delamination and increased tablet ejection forces.

This type of wear can be reduced by the selection of a harder more wear resistant die material such as tungsten carbide or utilising different zones in the die bore by turning the die or changing compression area.

Incompatibility between punches and the tablet press The punch heads are subjected to high cyclic loadings, typically 20 kN to 50 kN, many thousands of times per hour of running. If the punches are running tight for any reason there will be resistance between the punch heads and the cams and rollers, adding in high frictional force. This will lead to premature wearing of the heads and eventual fatigue and total breakdown of the metal. This in turn will cause contamination in the tablet press due to metal particles and expensive damage to tooling, press cams and compression rollers.

Figure 5: Wear to punch heads

This can be avoided by close recording, monitoring and management of the tooling condition and good tooling and tablet press maintenance procedures.

I Holland has first-hand experience in combating the problems of damage and wear to tooling. These challenges can result in costly downtime for the tablet manufacturer and the knowledge to help to solve any tabletting issues that can occur during production is a valuable resource that should be supplied by any quality tooling manufacturer.

With the right procedures in place at the beginning of the process and by employing good handling, operating, care and maintenance practices for both the tooling and the tablet press, common problems seen in today’s tablet tooling manufacture can be prevented.

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CURING DISEASE

The cure Society has come to expect a cure for every illness. But who’s behind some of the latest drug developments and where do these breakthroughs begin? Lu Rahman takes a look at some of the latest cures that will no doubt prove to be significant in the coming years

s a society we automatically think about seeking help and advice from our doctor when we think about curing disease. But behind the headlines for wonder drugs and the latest breakthroughs available to the healthcare sector, there is a variety of pharmaceutical companies and research establishments pushing the boundaries of drug development for the improvement of the health and well-being of us all. In recent months the disease that has arguably stolen the majority of column inches has of course been Ebola. Last month it was announced that one injection will now immunise against this illness. The first case of Ebola was reported in West Africa around 15 months ago. According to estimates, around 25,000 people have been infected by the virus, with more than 10,000 of them having died since as a result of this serious illness A live vaccine based on the ‘Vesicular Stomatitis Virus’ (VSV) has yielded highly promising results for the rapid development of an effective vaccine against the Ebola virus. This vaccine would only need to be injected once for long-lasting immunoprotection. These are the key findings of an international study coordinated by the World Health Organisation (WHO) in which the MedUni Vienna played an important role. “An Ebola glycoprotein from the Ebola strain in Zaire is inserted into the VSV live vaccine," explains Michael Ramharter, University Department of Internal Medicine I at the MedUni Vienna, co-author of the study published in the New England Journal of Medicine.

"While VSV only causes mild symptoms in humans, the protein acts as an Ebola antigen and triggers the formation of antibodies against the disease in the immune system."

In what seems a strange and bizarre link, research suggests that herds of African cattle could hold the secret to fighting parasitic diseases – such as malaria – in people.

These antibodies hide, almost like a ‘Trojan horse’, in the body in order to successfully fight the Ebola virus if the individual becomes infected.

A study has found that cows are protected from a parasite that causes deadly East Coast Fever if they have been infected with a closely related but milder species of the parasite in early life.

"Just one vaccine has conferred one hundred per cent protection against Ebola in the initial trials on primates,” says Ramharter. As part of the phase I study which is now complete and the results of which were published in the New England Journal of Medicine,138 test subjects – healthy adults – were vaccinated with various doses of the live vaccine. The results are highly promising. “The vaccine response is very reliable, the vaccine itself is safe and its tolerability is acceptable,” says Ramharter. The most significant side-effect was found to be temporary joint pain and inflammation reported among a small group of test subjects, particularly in the European centres.

The findings could help develop new strategies to prevent parasitic diseases, including severe malaria infection in people, researchers say. A team led by the University of Edinburgh tracked the health of 500 Kenyan calves from birth to one year old. They built up a set of data on the cattle’s survival, growth, health and infection with viruses, bacteria, worms and tick-borne parasites. Deaths caused by East Coast Fever – the biggest killer of East African cattle – dropped 89% among calves also infected with other species of parasites that do not cause disease, the researchers found.

In the phase II studies that are now starting, the vaccine will be used in patients living in the areas currently most badly affected by Ebola – especially Guinea and Sierra Leone but also in Liberia.

They say a similar situation may occur when humans are infected with the parasite that causes severe malaria – Plasmodium falciparum – at the same time as a less aggressive species – Plasmodium vivax – making people more likely to survive the disease.

Malaria rarely leaves the headlines. And in the West we are rightly reminded of the unnecessary death toll attached to this disease.

The findings, published in the journal Science Advances, helps explain how African cattle survive in a region where European cattle quickly succumb to East Coast Fever. continued overleaf>

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Controlling East Coast Fever would benefit an estimated 30 million cattle in sub-Saharan Africa, which would have a tremendous economic and health impact on farmers living in these areas. Vaccinating calves with benign parasite species could give them time to develop immunity to more aggressive species, the researchers suggest. Professor Mark Woolhouse, of the University of Edinburgh’s Centre for Immunity, Infection and Evolution, said: “This discovery suggests a completely new way to control a devastating disease in cattle, while reducing the use of antibiotics and environmentally damaging pesticides at the same time. It may also provide clues to new ways of combatting human diseases such as malaria.” The study was funded by the Wellcome Trust and involved researchers from the University of Edinburgh, the International Livestock Research Institute, the Roslin Institute, the University of Nottingham, University of Glasgow and the University of Pretoria. In a similar vein, Biotech Company, ExpreS2ion Biotechnologies, announced the release of a vaccine by its partners at University of Copenhagen, against the form of malaria that strikes pregnant women, for testing in humans. The vaccine candidate contains a malaria antigen made with ExpreS2ion’s proprietary protein expression technology, ExpreS2. This vaccine candidate is the result of years of research carried out by Professor Ali Salanti and his team at the Department of Immunology and Microbiology at the University of Copenhagen.

“

It is the first time that a university in Denmark has conceived and produced a vaccine.

”

Dr. Charlotte Dyring, CEO of ExpreS2ion Biotechnologies, said: “This is a very important milestone for our company. The ExpreS2 system solved the protein expression challenge for this antigen that had failed to be expressed in alternative systems. More than 30 variants of the complex malaria antigen that forms part of this vaccine were produced by ExpreS2ion to enable Professor Salanti’s team to perform tests to select the most promising vaccine candidate. A very robust production process for the antigen was developed by ExpreS2ion and transferred to a manufacturer for production of a batch performed under conditions necessary for human testing. We consider the collaboration with the University of Copenhagen an important success for ExpreS2ion: we have delivered on the needs of the project, and demonstrated again the power of our protein expression system ExpreS2 to deliver results seamlessly through development, from research to manufacturing under the stringent regulatory needs of Good Manufacturing Practice (GMP) “It is the first time that a university in Denmark has conceived and produced a vaccine, and this has only been achieved because of the very close cooperation within the consortium that includes ExpreS2ion and the University,” commented Professor Salanti.

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A common treatment for diabetes – liraglutide – may now also hold a cure for Alzheimer’s. Human trials have already begun following tests on mice – and it is thought that in just a matter of years, the medication will be widely available leading to a cure in the fight against this disease. The early findings have led to the Alzheimer’s Society heading up a £5 million research trial in involving over 200 patients. It is hoped that tests on individuals showing early stages of the disease will help improve brain function, quality of life and slow down the progression of the disease. Current evidence suggests that patients with Alzheimer’s have insulin resistance similar to that seen in diabetes patients. According Dr Paul Edison, brain scientist at Imperial College, London, there was a 70-80% increased risk in people with diabetes getting Alzheimer’s with experts adding that this breakthrough could indeed be a game-changer in the way dementia is eventually treated. Of course, these examples are the tip of a pharmaceutical iceberg. Every week we are made aware of the ongoing breakthroughs that R&D teams and pharmaceutical establishments across the globe are working on in order to improve the well-being of us all. From time to time, it’s important to remind ourselves of the medical advancement taking place as well as the way in which these drugs and cures are discovered. It’s an evolving process but one which is always relevant and crucial to society as a whole.

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engineering for a better world

LIMS

Management skills Trish Meek, Thermo Fisher Scientific offers the case for user-friendly informatics in the pharmaceutical QA/QC lab

oday, lab software productivity is less about computing power and more about user-friendliness and integration. As Moore’s Law predicted, our computers can process orders of magnitude more than even a decade ago. But putting more transistors on a chip isn’t all that’s making modern lab workers more productive: new business models, system architectures and software delivery models play major roles too. Cloud computing and infrastructure-as-a-service (IaaS) have lowered the costs of accessing computing power so today it’s more about the idea, not the infrastructure to operationalise it. These days we are much more discerning about user interfaces and usability: we expect our laboratory software to behave as intuitively as our smartphones. Intuitive software is useful software and users will require little encouragement to make it central to their daily regimen. Equally important, well-designed software is a stabilising constant in a workplace that is increasingly marked by turnover and change. Staff may leave and projects may transition but an informatics system never loses track – from workflows to SOPs, it helps new staff adapt and ensures people and processes achieve maximum productivity. How can more user-friendly software find its way to the pharmaceutical QA/QC lab and what role do today’s integrated informatics solutions play to help move this process along? What should an informatics system offer its users in a pharma QA/QC setting? First, it is important that we differentiate the system users and how the software can provide the most value. The first group is scientists and technicians who are documenting their day to day activities. Lab informatics software should walk these users through common tasks and automate their SOPs; the ability to record, transcribe and manage all data digitally; prevent them or warn them about instruments requiring system maintenance or calibration and expired solutions or reagents and user-friendly functionality for reporting data. The second group is lab managers and directors who need to manage day to day laboratory operations and make it run efficiently. For them, the first and perhaps most critical step is that this information is captured in the system. The system needs to ensure that SOPs and regulations are followed ensuring good scientific process and valid results. Once the process is executed and the data captured, they need sophisticated data analytics to monitor data trends and stop nonconformance before it occurs. Intuitive software is also integrated software. Many laboratories today operate with disparate systems that could – but don’t – share interrelated data that if combined would reduce complexity and workload. The ability to network systems is critically important to modern labs – silos are not conducive to productivity. An integrated informatics system eliminates silos, combining the complementary capabilities of a laboratory information management system (LIMS), scientific data management system (SDMS), laboratory

execution system (LES) and an electronic laboratory notebook (ELN). It’s not enough to have each of these systems – they must be integrated and the communication among them must be rationalised and automated. Labs that manually share data between systems are not only sacrificing productivity, they are introducing risk. The single-system requirement leaves only two real options – either buy the entire system from a single vendor or ensure that all systems can share data via digital interfaces or utilise integration tools that can translate and communicate data. The system must enable bidirectional data flow, including the ability to acquire and assimilate data directly from all laboratory instruments, regardless of vendor or format. This means that data must be assimilated from the most complex laboratory instruments, like mass spectrometers or chromatographs, as well as basic lab essentials like Ph meters, balances and scales. While productivity has always been important to pharma QA/QC labs, greater complexity and more onerous regulation is sharpening the focus on productivity-enabling systems and tools. Take large molecule drug production, where complex production processes and evolving regulatory oversight are data dependent. Large molecules can be more difficult to characterise during production and this requires greater vigilance and reporting. The environment is significantly more dynamic so too must be the approaches to QA/QC. It would be impossible to manage today’s dynamic production environment with data in silos. The data must be integrated and it must be actionable at all times. Consider Quality by Design (QbD) principles introduced by the FDA in 2004. How can a manufacturer monitor quality at every stage of the production process if that data isn’t readily accessible and easy to manage? The answer is that they cannot, and this means that an integrated informatics system, combining a LIMS, SDMS, LES/ELN functionality, as well as full integration capabilities with the full complement of lab equipment and enterprise systems, isn’t a luxury, it’s a necessity. The key to highly functioning QA/QC is a system that is designed for how today’s laboratory staff work. The necessary computing power will be there but not all software is created alike. It must have an interface that adapts to users, end-to-end automation that mitigates risk and integration enables a comprehensive approach to production quality and compliance. Intuitive software is both useful and integrated. Seems simple but many manufacturers struggle with interfaces that neither match how they work nor pull in data from all the systems on which they rely. By focusing on the users, making the system friendly to the way QA/ QC is done today, integrated informatics systems can be drivers of greater productivity as production and regulatory environments become more challenging and complex.

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PACKAGING & BOTTLING

Positive approach: An index gives a user-friendly structure to any booklet label and high compliance has a positive impact on the validity of the studies.

Labelled with love When is a label not just a label? When it’s a multifunctional tool relaying a range data in a variety of languages, says Faubel

eciding which label is best for a particular trial project is not always easy. Labels have become multifunctional tools which are able to convey variable data in different languages indicate first opening, support ease of use or blind study drugs. They are no longer used as mere carriers of specified contents. Every clinical trial has its own specific requirements concerning the labelling of investigational products. However, they have one thing in common: trials taking place within the European Union have to comply with the EU Guidelines to Good Manufacturing Practice while those conducted in the US have to meet the requirements of the Code of Federal Regulations. In the European Union, label contents are still specified in Annex 13. Other aspects such as structure, layout, font size and symbols are defined in the Guideline on Readability.

Several countries, different languages Clinical trials are not usually limited to a single participating country but conducted in several countries. The labelling of investigational medicinal products has to accommodate an increasing number of languages. Labels may have to be printed in up to 40 different versions. Another option is to integrate several languages into a single product. This can be achieved by using booklet labels, now available in up to 113 pages. These provide an all-purpose solution that can be applied in every participating country. In addition to tables of contents, thumb indexes can help users find their way through booklets. Direct access to user-specific data is to be facilitated by intuitive handling, which enhances patient compliance durably.

“

Printing variable data and blinding clinical trials

Product labelling must be capable of withstanding temperatures as low as -196°C.

Personalised data is, however, not specified until very shortly before drug labelling takes place. This is why some label manufacturers tend to offer variable data printing at short notice.

Regardless of whether complete marking is achieved by means of one-layer, multilayer or booklet labels, labels should always match the shape of primary packaging. Unusual shapes or additional functions like an integrated hoop for hanging a bottle tend to require a high level of creativity, know-how and experience from label manufacturers. Labels are developed individually and tested for criteria such as adhesion and adaptability as well as user-friendliness. Label performance during application can be simulated at label supplier or tested at the investigational drug manufacturer's facilities.

Furthermore, pharmaceutical manufacturers sometimes face the challenge of having to blind their study drugs adequately to make sure that trial investigators, nursing staff, participating patients as well as the persons in charge of handling the data are unaware of the treatment administered to individual patients. Unwanted biases can only be avoided in this manner. Some blinding solutions can only be used for single-blind trials, some others for double-blind trials.

”

Security features and material properties In order for trial subjects and staff to be able to assess the integrity of investigational products, it is advisable to choose labels with tamper-evident features. The area around the mouth of the container is fully or partly covered by the label. Opening the product will damage the label badly and make tampering clearly visible. So staff or customers are able to assess the integrity of trial products. Often investigational products are stored in cool places or even temporarily frozen. As a result, product labelling must be capable of withstanding temperatures as low as -196°C. To exclude label deterioration caused by water, grease or chemicals right from the start, it is recommended that synthetic materials be used to manufacture labels.

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For example, vials can be blinded by using boxes made of opaque and robust cardboard. As a result, the volume and the height of the containers as well as the colour of the contents are entirely masked and therefore unidentifiable. Habitually pharmacists and contract packagers use labels to blind tubes, jars or pots. If trial-specific data needs additional masking, printable laser fields, scratch areas and sections with code-break function can be subsequently incorporated into the secondary packaging.

Custom-made solutions Labels traditionally used as secondary packaging for trial products have changed into flexible, though compact, multifunctional tools. Increasing demands on quality and user friendliness, shorter lead times in development and production describe the significantly general conditions of clinical trial labelling.

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VISITUS USAT ATACHEMA THE INTERPHEX 2015 IN NEW YORK, USA VISIT 2015 IN FRANKFURT, GERMANY FROM 15. 21.--19. 23.JUNE APRIL 2015, BOOTH 2035 FROM 2015, HALL 3.1 F3

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PACKAGING & BOTTLING

Keeping it real Ian Lemon from Essentra offers valuable advice on how to tackle counterfeiting, a global public health issue

oday, counterfeit products can be found in every country and every sector of the global economy. According to international organisations like the WHO, counterfeiting concerns approximately between 5 and 9% of global trade and 10% of the global pharmaceutical market. It is estimated that 50% of drugs available on the internet are counterfeit, while this figure can reach up to 70% in some African or Eastern European countries. The MHRA also recently announced that UK customs officials have seized counterfeit drugs estimated to be worth £3 million.

Counterfeit sophistication The discrepancy between the potential profit from counterfeiting and the relatively low risk of legal punishment encourages criminals to invest their resources and cash flow into making their products look as similar as possible to authentic goods. Working with companies to help them develop cutting edge covert technologies such as infra-red (IR) and ultra-violet (UV) inks, microtext, and microscopic tagging, both invisible and difficult to detect and replicate without specialist detection equipment, is part of the solution.

Patients and pharmaceutical brands are in danger

Lack of coordinated enforcement capacity

Criminals who trade in fake medicines are finding sophisticated ways to infiltrate legitimate supply chains. The high demand for specific drugs works as an incentive for them to take advantage of consumers who cannot afford the cost of authentic products. Price differences fixed by national governments or multinational companies drives parallel trade, which then grows in high correlation with counterfeit trade. According to Interpol, patients across the world put their health, even life, at risk by unknowingly consuming fake drugs or genuine drugs that have been doctored, badly stored or that have expired. On the other side of the spectrum, counterfeit products can also affect a brand’s reputation.

There is currently no effective regulation or sufficiently strong enforcement capacity across the industry to tackle counterfeiting. Putting the topic on governments’ agenda and setting it as a top priority for businesses will be essential for the industry to help enforcement agencies develop a coordinated initiative that will make the fight simpler and less time consuming. It is today impossible for governments to monitor all exports and imports of goods; only a joint effort between industry and governments will enable a realistic solution.

Serialisation alone is not a panacea Serialisation, as promoted in the EU Falsified Medicines Directive, is not a panacea, as coding alone is not authentication. Training and enforcement methods have not yet been addressed. Coding initiatives have focused exclusively on digital methods, with under-exploitation of physical protection opportunities. However, in the pharmaceutical industry, the consumer, whose life could be endangered, should be able to check on their own if a product is counterfeited or authentic. By giving more responsibility to the patient, the industry could help raise awareness on the issue.

Taking action to tackle the issue What are the drivers of counterfeit growth and how can private actors like Essentra help international and national regulators tackle this global issue? As a packaging specialist with more than 30 years of experience on the healthcare market, Essentra has identified four drivers of counterfeit growth: the supply chain complexity; the development of e-commerce; the increasing sophistication of counterfeiters and the lack of coordinated enforcement capacity.

Supply chain complexity The supply chain for pharmaceuticals is now global. This means increasingly complex supply chains, supported by multiple opportunities for significant cost savings, but also unfortunately increased opportunity for illegal activity. The focus should therefore be on monitoring and maintaining the integrity of the supply chain by paying more attention to details and having proper protocols in place. Tamper evidence technologies introduced in the shipping process can also give a clear indication to the consumer if tampering has occurred.

Web of lies: The internet has given counterfeiters a direct and easy access to the consumers says Essentra

Development of e-commerce Many legitimate platforms exist, but the internet has given counterfeiters a direct and easy access to the consumers. As a result, rogue internet pharmacy sites are proliferating and it becomes harder to track the criminals and their products down.

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Only allowing companies to choose a “layered” combination of physical and digital attributes will deliver enhanced protection. That is why companies such as Essentra, packaging specialist, has developed technologies to integrate security within a product packaging. These solutions include technologies that can allow instant authentication, but also solutions that are more complicated to detect or replicate without specialist detection equipment, as well as tamper-evidence, tear tape and integrated design.

Milling & Mixing Equipment for Pharmaceutical Applications The NETZSCH VITA line of mills, mixers and dispersers are customengineered for your specific application. With scalability in mind, every solution we engineer is easily sized for production capacity.

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15 - 19 Ju ne 2015 Frankfurt am Main, Germany Hall 6.0 B ooth B6

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PACKAGING & BOTTLING

Stick with it Justin Schroeder from PCI explains the role of packaging in improving adherence

ith recent governmental reforms in healthcare across the US, Europe, and extending into other developed countries there is more accountability for stakeholders to demonstrate the effectiveness of treatments in driving improved health outcomes. Staggering statistics demonstrate that adherence to some medication regiments can fall as low as 30% for some grave disease states. As such, across the pharmaceutical and healthcare spectrum, industry professionals are working diligently and investing significant resources to solve the enduring challenge of patient compliance and positively affect patient behaviors.

is based on the true impact of their medication on patient health.

Patient compliance and adherence is drawing significant attention in the clinical healthcare community because of its impact on the ultimate success of demonstrating investigational drug effectiveness in clinical studies. Sponsors simply cannot afford to waste the time, cost and associated resources when studies are undermined by non-adherence.

Patient non-compliance in the general population is a multifaceted issue and rarely does a single remedy fully address the cause or significantly affect the health outcome. Non-compliance is driven by conscious and unconscious behaviours, and those behaviors and factors may vary significantly from one disease state to the next.

Techniques designed to monitor patient adherence can provide widely differing results in patient behaviors and realised patient health outcomes for the study medication. The traditional method of studying adherence is to pill count returned study medications however, published studies have proved that patients ‘pill dump’ rather than reporting their inconsistencies in dosing. This creates unreliable data for monitoring true compliance and adherence. These inconsistencies may occur over the course of several days masking lengthier drug holidays where the patient is off therapy. This variable cycle reduces the medication’s therapeutic effect for the patient and hampers the sponsor’s expected study outcomes.

Stakeholders look to address patient behaviors and their causes at various patient touch points. This may include doctor/nurse interventions, pharmacist counseling or third party clinical counseling, gadgets such as electronic reminders, text messaging, phone or email prompts may also be considered. Other adherence strategies include predictive modeling to identify at-risk patients, goal setting programs and incentivizing patients for positive behaviors.

To ensure a more accurate view of patient behaviours sponsors are utilising innovative electronic compliance monitoring technologies, allowing study administrators to identify non-adherent study subjects. As such analysis

Monitoring patient behavior in clinical studies is less complicated; patients have opted into study participation and are typically receiving therapy free of cost. This patient population is motivated to try a new therapy that may provide hope in addressing their disease state. By contrast, analysing patient behaviour for commercially available medications ushers in many other considerations and environmental influences, most notably cost.

Experts agree finding synergies and addressing the root cause for the specific patient population and disease state delivers the most effective results. Published studies demonstrate that the most effective singular strategy is providing medication in unit dose calendarised formats. This is proven to increase patient compliance and adherence, i.e. taking product as prescribed, as well as medication persistence. In 2011

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Designs on you: Effective package design is proven to deliver tangible results and adherence gains, translating into improved health outcomes for patients

the Clinical Therapeutics journal published a study of 3 million users of generic medicines. The study highlighted the use of calenderised packaging demonstrated a 17 day increase in persistence compared to using traditional vials whilst patients receiving a calendarised blister design also realized up to 37% increase in proportion of days covered (PDC). A second study in the journal Dove Press analyzed the effect of calendarized packaging for the drug Diovan HCT. This study affirmed the findings in the generic study, demonstrating up to 44 days increased length of therapy for users of calendarized unit dose formats. These results demonstrate that simple packaging interventions realize modest gains in addressing patient health outcomes. Even more encouraging is the use of compliance prompting packaging in conjunction with other adherence methods. Increasingly calendarized formats in concert with other adherence tools are being used to address conscious and unconscious patient behaviors at the point of administration. These tools may include co-pay cards or instructions for medication reimbursement, education tools about the drug or disease state, enrollment tools for integrated health programs, lifestyle tips and guides, specific dosing guides for complicated drug regimens, patient diaries and goal setting tools. Integrated directly in the packaging, these tools can yield tremendous results. Utilizing packaging as part of a broader adherence strategy is best achieved with collaborative goal setting and specific measures for Return on Investment. Effective package design is proven to deliver tangible results and adherence gains, translating into improved health outcomes for patients. The rise in prominence of compliance prompting packaging in the competitive landscape underscores its role in the new healthcare paradigm – proven effectiveness in better patient health as a competitive necessity. 33

A & Q PACKAGING & BOTTLING

Signed and sealed

Sylvia Marzotko, West Pharmaceutical Services, explains how to increase patient safety through clean sealing

Fitting news: The choice of seal can help create operational efficiency and eliminate potential sources of bioburden and particulates

What role do caps and seals play in terms of high-quality in pharmaceutical manufacturing? Many pharmaceutical and packaging manufacturers have placed emphasis on materials in direct contact with the drug product itself, such as the glass vial, plastic syringe, and elastomeric stopper or plunger. Additional packaging elements, such as caps and seals, were little thought of. However, in recent years, regulatory guidelines have influenced the requirements for crimping processes significantly. What regulatory guidelines do pharmaceutical and packaging manufacturers have to take into consideration? The European Medicines Agency (EMA) Annex 1 “Manufacture of Sterile Medicinal Products” specifies that the manufacturing of sterile products is subject to “special requirements in order to minimize risks of microbiological contamination.” When it comes to processing, precautions must be taken to minimize contamination during all stages before sterilization, and the EMA refers in particular to two processes in the fill-finish area of those manufacturing plants that also perform aseptic filling: Aseptic Crimping and Clean Crimping. What are the specifics for aseptic crimping? Aseptic crimping requires the use of sterile seals. A drug product’s biological and particulate cleanliness is best assured using aseptic crimping processes and pre-sterilized components. For aseptic crimping processes, as well as for reflecting the trend toward controlling particulate cleanliness, knowledge about particle specification limits may be requested.

In order to meet aseptic crimping requirements there are high-quality sterile seals available that have a specified bioburden level prior to sterilization (as referred to in EMA Annex 1 Clause 80) as well as a specified particulate level. How does clean crimping differ from this? For the clean crimping process, capping and crimping is performed in a non-aseptic environment under Grade A (Class 100/ISO 5) air supply. EMA Annex 1, Clause 120 notes that when vial capping is undertaken outside of the aseptic core, “vials should be protected by Grade A conditions up to the point of leaving the aseptic processing area, and thereafter stoppered vials should be protected with a Grade A air supply until the cap has been crimped.” Although for clean crimping processes the use of unsterile seals is not excluded by the EMA Annex 1, there is a growing uncertainty regarding the introduction of potentially biological contaminated components into the clean crimping area and the effects on operational efficiency that this might cause. In order to meet regulatory requirements and ensure clean crimping procedures, pharmaceutical and biopharmaceutical companies increasingly have turned towards ready-to-sterilize and ready-to-use sterile packaging components and product qualities. Are there any sealing components which meet especially the needs of pharmaceutical companies performing clean crimping? Yes, there are high-quality seals available that meet the needs of companies performing clean crimping. These seals have a bioburden level controlled and specified before sterilization and are developed for clean crimping under grade A air supply.

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Using high-quality packaging components ensures a stable crimping performance, which minimizes the risk for introduction of external contamination, line stoppages and equipment down-time. What do drug manufacturers have to keep in mind when choosing the right seals? Just as different drug products may require different primary containers (i.e., those with a high pH level may require a polymer container to ensure efficacy), secondary packaging also maintains a variety of levels to ensure that the right quality is provided for the drug product and the manufacturing process. For many, a high-quality sealing component that is vision controlled, consistent and reliable during the capping process is an excellent choice. In particular, this type of seal can be a cost-effective method for clean crimping processes. Increasing quality levels for seals would include sterile, ready-to-use components that have specified and controlled bioburden levels before sterilisation. It is expected that this type of seal will become the future standard for clean crimping under Grade A air supply. Whether a manufacturer decides to use aseptic crimping or clean crimping, the choice of seal can aid in the process by helping to create operational efficiency and eliminate potential sources of bioburden and particulates. High-quality seals are intended to meet operational and regulatory challenges and consistently achieve reproducible and safe container integrity for the drug product. Use of such a seal will increase filling line efficiency and drug product safety, helping to meet the regulations and expectations of an industry for which quality is an evergrowing concern.

PACKAGING & BOTTLING

The printed word Contract packer Millmount Healthcare gives Domino its mark of approval

Pharmaceutical contract packaging provider Millmount Healthcare has enjoyed reduced downtime and achieved cost savings following the installation of Domino’s V230i thermal transfer printer as part of a compliance upgrade. Based in Stamullen Ireland, Millmount specialises in pharmaceutical and healthcare blister packaging and bottle/tub contract packing, handling solid and semi-solid dosage forms. With an annual capacity of 150 million blisters and over 30 million bottles, tubs and containers across three sites, the equipment and technology Millmount installs is required to keep pace with the high quality, efficient and compliant outsourcing packaging service the company provides. In preparation for a specific packaging project in 2014 Millmount decided on an equipment upgrade, undertaking a market survey to establish which printer and supplier would be best suited to their requirement of high-resolution primary coding onto labels that are then applied to vials. Pascal Keogh, managing director at Millmount, said: “We had previously been using hot foil coding to apply variable data, but we needed to upgrade to equipment compatible with upcoming legislation and we felt that thermal transfer printing was the best option. A market survey was important in order for us to gauge what equipment was available to ensure we were making the right decision, not just for our immediate requirements, but for all future projects.” A Domino’s V230i thermal transfer printer was identified as the most suitable technology for the project and was fitted as an entirely new line. “The fast pace of our packaging halls means simple installation of new equipment is integral so that lines can be up and running as soon as possible,” said Keogh. “The V230i was in place and functioning in good time ready for our packaging project to begin.” Since installing the Domino V230i earlier this year as a new line, Millmount has seen lower total cost of ownership and reduced

downtime in comparison to the technology used previously. Domino’s i-Tech ribbon drive aims to eliminate the downtime associated with ribbon break, while ribbon economy means less ribbon is consumed per print, reducing both the cost of consumables and the number of ribbon changeovers. “We have seen a marked reduction in downtime which is vital in maintaining an efficient packaging facility,” said Keogh. “Lower consumables use creates savings we can pass on to our customers.” With an impeccable compliance record, Millmount ensures that all upgrades and developments are made to comply with global legislation. The impending EU Falsified Medicines Directive (FMD) mandates a change from batch to item-level serialisation and will impact on European pharmaceutical manufacturing throughout the supply chain. “Domino’s V230i printer encompasses 2D coding support, ensuring we are compliant as the industry moves from batch to item-level serialisation,” explained Keogh. “As the FMD mandates that much larger amounts of data must be processed in packaging lines, our equipment must be able to produce durable codes and handle unique numbers at speed. The V230i is a key part of this upgrade as we edge closer to the FMD deadline. The V230i is one of numerous serialisation-capable printers in the Domino range, which also includes thermal ink jet, laser, continuous ink jet and print and apply labelling solutions for coding from product to pallet. Craig Stobie, head of global life sciences team at Domino said: “Millmount’s decision to implement the V230i was a great choice for them considering their particular production requirements; for others, ink jet or laser might be most appropriate. At Domino, we pride ourselves on the extent of our product range, which includes technologies appropriate for every current or emerging serialisation and aggregation requirement.”

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CheQ this out: Travtec’s CheQAssure system automatically checks the details held in individual bar codes

PACKAGING & BOTTLING

Future proof

Companies need to look further than 2017 when considering the best anti-counterfeiting solution to meet their needs, says Harry Thomason of Travtec

f there is one thing we can be certain of in life, it is that nothing is certain! So although pharmaceutical companies are currently focused on ensuring they are able to meet the coding requirements of the Falsified Medicines Directive (FMD) by its 2017 deadline, most commentators would acknowledge that this will not be the end of the matter. Regulations and legislation in any industry are constantly changing and being updated or refined. Implementing them across more than one country only adds to the complexity. And of course, while the FMD covers the European Union, today’s global market often means companies have to be aware of more than one set of regulations and adapt their systems and procedures accordingly. Even while the requirements for the FMD were being discussed, some countries were already implementing their own regulations. Turkey for example was the first in Europe to introduce Track & Trace into the pharmaceutical industry in 2010. And a 2D coding system with the CIP 13 coding requirement was implemented in France from January 2011. Further afield, California is now in the process of introducing an E-pedigree for prescription drugs. The new Electronic Product Code Information Services (EPCIS) for pedigree track and trace requires a record, in electronic form, containing information regarding each transaction that results in a change of ownership of a given drug - from sale by a manufacturer, through acquisition and sale by one or more wholesalers, manufacturers, or pharmacies, to the final sale to a pharmacy or other person furnishing, administering, or dispensing the drug. This has to be created and maintained in an interoperable electronic system, ensuring compatibility throughout all stages of distribution. The Californian model could become worldwide in the coming years. This means it is essential that companies currently seeking to invest in equipment to meet the FMD think carefully only about their immediate requirements and what they may need – and where they may be supplying – in the future. Future-proofing will be a key consideration in any anti-counterfeiting system – but the more practical criteria should not be ignored either.

Selecting the right printer is only the start of finding an appropriate coding solution. While today’s high resolution printing technologies can deliver the quality of bar code necessary for the automated serialisation and verification systems, it has to be recognised that they will not always be printing in ideal conditions. Substrate, line speed and factory environment also need to be taken into account. And for a system to work effectively, it will be necessary not only to have an easily readable code but also ensure that it is placed correctly on the pack. What is equally important is for the pack to be completely controlled during the printing process. This requires an appropriate feeding and handling system. And for efficient quality control purposes, a vision system needs to be incorporated as well. And since none of these pieces of equipment work in isolation, it is vital that they are fully integrated and able to communicate with each other as part of seamless operation. In other words, the effective coding of the pack becomes part of a specialised product handling solution comprising all these elements along with a fail to safety reject system. This means that an anti-counterfeiting system should not be regarded purely as an IT issue. Installing equipment is not as simple as merely placing it on the line and expecting it to work first time. Equal attention has to be paid to the engineering aspect; otherwise there is the risk that problems will continue to arise in the supply chains. However, pharmaceutical manufacturers also need to ensure that they have the flexibility and freedom to continue to choose the appropriate equipment that is right for their business. The focus on the need for integration means many suppliers are now offering ‘complete’ solutions comprising not just the various pieces of equipment but also the software systems and packages that allow them to work together. This may be a very tempting offer at first glance but there is a danger of companies then being ‘tied’ to one particular manufacturer or system and this can have a detrimental effect as markets develop and business focus and requirements change. All of which means companies must choose carefully – not just the equipment but a collaborative partner who can offer the appropriate advice and guidance at every stage. In this way, their operations will be properly future-proofed.

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LAB.line

By Kraemer & Ischi

FOLIO

P-Series The New Stars of the LAB.line

The P-Series sets new standards for laboratory tablet testing technology Kraemer and Ischi, specialists for pharmaceutical testing equipment are launching new products at the ACHEMA Exhibition: The P-Series are the innovative stars of the new LAB.line product range specifically for laboratories. The compact, space-saving testers determine the physical composition of tablets. Thanks to a modular construction, the standard basis version (P2-P5) can be upgraded with additional modules into a fully integrated automated testing line. The new design of the LAB.line testers also offers numerous practical advantages. Cleaning is easy due to the rounded corners and smooth surfaces.

With the P5 version all 5 parameters are checked automatically:

HARDNESS

WEIGHT

THICKNESS

LENGTH

WIDTH

Discover the New Stars:

Modular. Precise. High quality. The right solution for every application.

15 - 19 June 2015 Frankfurt am Main, Germany Hall 4.1, Stand J80

More information:

www.labline.info info@kraemer-elektronik.com

info@ischi.ch

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Qualicaps® New Imprinting Equipment has Laser Focus Introducing the LIS-250 UV Laser Imprinting System for Tablets, Softgels and Capsules

Why Laser?

Visit Qualicaps at ACHEMA 15 - 19 June 2015 in Frankfurt, Germany to see the LIS-250 Hall Forum 0/Stand C1 Qualicaps.com Follow Us: @Qualicaps

• Defects caused by ink (double print, ink spots, missing print, etc.) are eliminated • CAD design allows for flexible imprinting options • Eliminates the need for print rolls, ink and extra storage, reducing the run cost of imprinting • No cleaning necessary due to the lack of ink • Larger printable surface than ink printing • Potential for the prevention of counterfeiting • Non-thermal effects of UV laser allow marking without resulting in thermal denaturation on tablets

PACKAGING & BOTTLING

Easy option: Patients, especially those who have difficulty using their hands, are wanting more easy-to-open packaging for their medication

Designs on you When specific factors are required, developing packaging can become a challenge, keeping the end-user in mind throughout the process, whether young or old, says Nolato When developing pharmaceutical packaging, several considerations need to be accounted for. Whether it’s child-resistance, tamperproofing, stability, ease of use or efficiency for filling lines, packaging suppliers have to be one step ahead with meeting these requirements. But further to these factors, there is a more important element to look at – understanding the customers’ and end customers’ needs. The key is to develop and maintain long-term and consistent client relationships, becoming an extension to the product development team. With the end-user in mind though, two major requirements are seniorfriendliness and child-resistance. Patients, especially those who have difficulty using their hands, are wanting more easy-to-open packaging for their medication, but yet there are more stringent regulations being enforced for child-resistance. When developing the packaging of a product, the focus of seniorfriendliness and child-resistance depends on the treatment area and target patient group, as well as the geographical areas. For instance, US legislation has driven the use of child-resistant closures. But legislation in Europe is expected to increase, considering both factors. Senior-friendliness and child-resistance is a balancing act for the packaging industry. There are a number of solutions on the market that satisfy each requirement, but the perfect solution that incorporates both does not yet

exist. Optimising one factor will decrease the effectiveness of the other, which leaves packaging companies to prioritise on just one feature. Not only do companies have to meet the specific end-user requirements, such as child-resistance; there are other factors that need to be considered, such as cost-effectiveness and stability. In particular, a package needs to provide a tight seal with high repeat usage and low failure rate. A unique shape or design is also important in some instances, to make a product stand out on the shelf, especially so in the OTC and nutraceuticals market. It is certainly challenging to be able to meet all the requirements on a client’s ‘wish list’, but the ideal way to work, is to have the flexibility to meet as many different needs as possible. It is advantageous to standardise a product portfolio, this can drive high-volume synergies. In general, pharma companies and regulatory agencies are not keen to change the way they do things because they see it increases work, cost and risk, especially in an industry that has such a big impact on health. Consequently, innovation is driven more by OTC and nutraceuticals companies, mainly for their marketing purposes and the need to attract end consumers. Continued pressure for change in the area of seniorfriendliness and child-resistance also comes from patient groups, such as rheumatism associations – companies in the industry would do well to take this factor on board, but the ultimate key is to be flexible.

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CONTAINMENT

Transfer window Wenceslas Daniel, Thierry Girard, Chloé Guilmet and Jean-Luc Schneider, Getinge–La Calhène outline an evolution in rapid transfer ports and offer an innovative DPTE system to revolutionise safer transfer Figure 1: DPTE-XO connected to a DPTE-BetaBag for sterile transfer

he pharmaceutical industry has new challenges to face in terms of ergonomics, productivity and ever more stringent safety concerns. One area of concern is the safe (ie contaminantfree) insertion of pre-sterilised products eg components and cleaning materials into the production line. Removal of toxic substances is another instance where maintaining containment is essential. Technology is evolving to respond to these concerns, bringing major improvements in transfer security. Getinge – La Calhène is an expert in the science of containment technologies. After the launch of the DPTE-S in 1993 and the DPTE-XS in 2012, the new DPTE-XO ultra-clean transfer system from Getinge La Calhène is a new step in this technological revolution.

“

One area of concern is the safe (ie contaminant-free) insertion of pre-sterilised products eg components and cleaning materials into the production line.

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Greater safety The DPTE-XO, like all classic transfer systems whose purpose is to maintain containment, is based on the interaction of two separate units, each comprising a door and a flange: • The Alpha part fixed on an isolator wall • The Beta part: a DPTE container or DPTE BetaBag In order to preserve the containment between the two sterile volumes (isolator and container) after docking, both their doors are fixed together to form a single unit. To date this has been achieved by rotation which causes issues frequently encountered in the industry when heavy or bulky Beta parts have to be manually rotated and when fragile components are being transferred1. The functioning principle of the DPTE-XO Alpha port ensures that there is no rotation, either of the Alpha flange or the Beta part, when the two doors are linked together as one. The absence of rotation also reduces the risk of creating particles by rubbing when the two units are connected and/or disconnected. Contamination-free transfers can be done. The activating mechanism of the new DPTE-XO port is located outside the isolator on the edge of the Alpha part. There is no longer a requirement for a glove system to be positioned next to the port in order to activate it, so risk is further reduced because this contributes to minimizing operator intervention, probably the biggest potential source of contamination in the industry2. Depending on the application, the activating mechanism may be remote and/or motorised. This single activating mechanism drives the entire sequence of actions involved in the transfer operation: locking the Beta flange, unlocking the Beta port, connecting both doors, unlocking and opening the Alpha door with the Beta door fixed onto it. With its single command, the system reduces risks of faulty manipulation on the part of the operator. Functional security is further improved by integration of a lock which prevents the double door unit from separating when the transfer is under way. When the doors are connected together the interlock is automatically activated, without any operator intervention, ruling out any risks of omission or manipulation errors.

Productivity gains With its modular, upgradable design, the DPTE-XO is available in a variety of models so end-users can define the solution best suited to their requirements in terms of layout and applications. The motorised version, for example, is particularly useful for high throughput production lines. The model that is motorised and remote is highly suited to layouts where it is difficult to manually actuate a transfer from outside the isolator, near the transfer system, eg in facilities with RTP systems positioned at a very high level. From the start of the design process, all the relevant industrial rules and regulations were integrated making the DPTE-XO compatible with validation and qualification requirements. Particular attention was paid to cleanability and reliability, taking a GMP approach. Simplified shapes have been used to make the new port easy to clean and the DPTE-XO was designed to minimise surfaces not directly accessible for cleaning with wipes. In terms of durability the DPTE-XO was developed to be extra long-lasting and has undergone rigorous mechanical testing.

Figure 2: DPTE-XO port view inside isolator and outside isolator

“

With its modular, upgradable design, the DPTE-XO is available in a variety of models so end-users can define the solution best suited to their requirements in terms of layout and applications.

”

Conclusion The DPTE-XO joins the DPTE-XS among the range of solutions provided by Getinge La Calhène for leak-tight safe transfers. It provides an extra degree of security while being backwards compatible with the entire DPTE range of products already installed on production lines. Together with the various accessories and control systems available for Beta parts, the DPTE-XO is the foundation stone of the DPTE transfer system, paving the way to carry out ultra-clean transfers with better efficiency and productivity.

1. Gladd, T, “Getting Particular About Particulates: How Can You Avoid Becoming The Next Recall?” Pharmaceutical Online and BioProcess Online, Accessed 17 March 2015 2. Dufour, C. and Guilmet, C, “Ensuring Ergonomic Design in Sterile Transfer Ports”. In: Pharmaceutical Technology e-Newsletter, http://www.pharmtech.com/enews. Accessed 15 July 2014

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FOLIO

It’s safer InsIde

mo d e l 6 4 0

We took a cue from Mother Nature. At Weiler Engineering, our ASEP-TECH® Blow/Fill/Seal packaging machines deliver sterile, aseptic liquid packaging solutions using proprietary technology that ensures safe, tamper-evident environments for your company’s most sensitive assets.

What else would you expect from the world’s most advanced aseptic liquid packaging system? Our Blow/Fill/Seal machines integrate blow molding, sterile filling, and hermetic sealing in one uninterrupted operation— a hands-free manufacturing process that ensures your company’s parenterals, ophthalmic solutions, respiratory drugs, and other pharmaceutical liquids reach the marketplace in the most cost-effective manner possible—every time. For more than 40 years, we have set the industry standard for sterile processing development with a continuous commitment to quality and innovation for aseptic technology. We will work with your company to develop a customized approach for each

of your products.

See ASEP-TECH® systems in action, visit www.asep-tech.com/epm

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Safeguarding solutions through innovative packaging

BLOW-FILL-SEAL

Filling station Bill Hartzel, Catalent outlines the advantages of its Blow-Fill-Seal aseptic filling technique for injectable drugs

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The QbD principles behind the technology aim to eliminate the root cause of the contamination issues that are being seen in the injectables market today.

”

In recent years, the growing number of drug shortages for injectable drugs has highlighted some of the challenges of traditional aseptic manufacturing of injectable products in glass vials, including the ingress of foreign or glass particulates, and microbial contamination. With the increasing number of biologic based drug products advancing through the clinic and to the market, the number of injectable doses is increasing, leading to a strain on traditional manufacturing processes and further highlighting these manufacturing challenges. There is a growing need to look for innovative solutions to address these issues. One such alternative to traditional aseptic glass vial filling is Blow-Fill-Seal (BFS), an automated aseptic filling technique based on the principles and practices of Quality by Design (QbD), and that addresses the main issues of contamination in aseptic manufacturing. The very nature of the technology eliminates the sources by removing people and glass management from the process. The BFS technology creates, fills and seals the primary sterile container in less than 15 seconds. The aseptic filling machine effectively contains and maintains a class A filling zone within the machine, reducing the amount of controlled space required and minimising process variables whilst simultaneously eliminating human intervention. The BFS process is wholly automated and starts with virgin plastic pellets that are fed into a hot melt extruder, where the polymer is melted at high temperature and pressure. These extreme physical conditions act as an effective barrier because they can inactivate microbial contaminants. Additionally, the process creates the primary container before immediately filling the body of the vial and sealing it. The container therefore is only exposed to the class A environment for a few seconds; drastically reducing the risk of foreign particulate contamination. This is in contrast to a glass vial filling line, where the vials are loaded, undergo multiple washing, treatment and depyrogenating steps. After filling, the stoppers are introduced and capped by crimping. The majority of the stages take place in barrier-control conditions and then all products are inspected, labelled and contained in secondary packaging. Human intervention is required throughout, and with it, the risks of microbial contamination, regardless of how much care and training is undertaken. Additionally, the time during which the components and products are exposed to the environment, potentially for hours prior to filling, increases the risk of contamination.

When measuring foreign particulates, BFS technology can provide a drastic reduction in particulates compared to both the industry standards measured by USP <788>1 and the reported industry average. In 2004, a study was conducted and published2 indicating that the acceptable levels within USP <788> were too high and needed to be tightened. This study reviewed 406 drug lots across 295 ANDAs, and the average numbers across these lots were 219 particles greater than 10µm, and 15 greater than 25µm.This is in contrast to Catalent’s patent-pending BFS filling technology, ADVASEPT. When an experiment was conducted to review the specific processing conditions within its BFS process, it reviewed 32 different conditions within the process and yielded an average of 5.0 particles greater than 10µm, and just 0.9 greater than 25µm on average. This represented a reduction of more than 95% in foreign particulates compared to the industry average. The QbD principles behind the technology aim to eliminate the root cause of the contamination issues that are being seen in the injectables market today. The reduction of variables, automation of the process, and elimination of human intervention, can provide a more robust supply of products, based on the reduction of risk in the manufacturing process. BFS technology is used widely in the sterile manufacturing of respiratory and ophthalmic products where the sectors were early adopters of the technology and have benefited from innovative primary packaging solutions. Because of the challenges with traditional glass vial manufacturing, more companies are being exposed to the benefits that BFS advanced aseptic processing can have on production, and an extensive compendium of data has been generated to support the use of BFS for biologics products. Safety and quality are still the most important factors in drug product manufacture and with more data available on the reliability of BFS, this innovative technology may help provide more reliable supply of products for the injectable drugs market.

References: 1. U nited States Pharmacopeial Convention. (2014).General Chapter <788>, Particulate Matter in Injections. In USP 37, pp. 398-401. 2. P resenter Shabushnig, John. (November, 2010).Regulatory and Compendial Considerations for Particles in Parenteral Products. Presented at AAPS, New Orleans, LA.

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THEY SAID IT COULDN’T BE DONE.

FOLIO

running the Four minute mile

6 May 1954

man landing on the moon

20 July 1969

birth of the first test tube baby

Irradiation of H2 02

25 July 1978

29 august 2013

CONTEC HYDROPURE THE WORLD’S FIRST IRRADIATED H202 PRODUCT. Contec are delighted to introduce Sterile HydroPure, a 6% stabilised hydrogen peroxide solution blended with Water for Injection (EP). With a guaranteed low level of endotoxins, 0.25 EU/ml, Contec HydroPure is the only hydrogen peroxide solution to be terminally sterilised. Triple bagged and manufactured using the highest grade of hydrogen peroxide, HydroPure leaves no residue so is especially suitable for product contact areas. To find out more about Contec HydroPure and other exciting developments in the Contec range;

contact Contec at infoeu@contecinc.com or by calling 0845 652 2582 to request a sample. www.contecinc.com Use biocides safely. Always read the label and product information before use.

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SPECTROSCOPY

Critical analysis Thermo Scientific Portable Analytical Instruments describes its fast, cost-effective material verification

eveloped with in-depth pharmaceutical industry experience, Thermo Scientific handheld analysers provide manufacturers with a portable solution to achieve quality initiatives throughout the manufacturing process. Installed in more than 900 GMP facilities worldwide, these Raman and NIR analysers are designed to enable pharmaceutical companies to quickly and effectively identify most any pharmaceutical material from receipt to release.

Handheld solutions Thermo Scientific TruScan RM and microPHAZIR RX, handheld Raman and NIR spectrometers, aim to offer pharmaceutical manufacturers fast, accurate material identity verification in less than 30 seconds. These solutions should allow users to quickly develop methods, enabling immediate release of raw materials into production. Both analysers were designed to meet the stringent requirements of current good manufacturing practices (cGMP) and 21 CFR Part 11-compliant environments

In hand: The microPHAZIR RX analyzer is a lightweight, handheld point-and-shoot instrument

Ease of use: Easily operated by non-technical staff, the analysers perform nondestructive analysis

microPHAZIR RX

TruScan RM The Thermo Scientific TruScan RM analyser is the companyâ&#x20AC;&#x2122;s lightest, fastest and most portable handheld instrument for rapid authentication of pharmaceutical raw materials and finished products. Featuring the specificity of Raman, it allows operators with minimal training to perform highly-reliable analysis wherever pharmaceuticals are manufactured or distributed.

Intuitive operation This next generation Raman spectrometer for raw material identification and finished product inspection is highly specific and performs rapid material identification at the point of need to decrease sampling costs and increase inventory turns. Designed for intuitive operation, its non-destructive point and shoot sampling principle facilitates rapid verification of a broad range of chemical compounds, both solid and liquid, through sealed packaging to minimise the risk of contamination and exposure.

The microPHAZIR RX is a handheld Near-Infrared (NIR) instrument designed for rapid on-site pharmaceutical material identification and analysis. This analyser takes the power of NIR out of the laboratory and into the warehouse to cut costs, ensure product quality through increased testing frequency, and reduce supply chain risk. Eliminates exposure The microPHAZIR RX measures directly through transparent plastic drum liners and glass containers to minimize the risk of contamination and exposure. By enabling manufacturers to meet global cGMP requirements, it also improves inventory management and reduces raw material supply risks.

Field-ready The microPHAZIR RX is suitable for applications including incoming raw material identification, quality control and assurance, counterfeit product screening, process troubleshooting and quantitative analysis.

The TruScan RM analyser builds on the proven capability of the flagship TruScan analyser which is now used in hundreds of pharmaceutical manufacturing sites globally to deliver a modern optical platform paired with an embedded analysis package. The analyser also offers enhanced compliance features, as well as software and data management functions designed to facilitate workflow and optimise efficiency in tightly regulated environments.

Seeing is believing: With the TruScan RM, pharmaceutical manufacturers can conduct rapid raw material identification at the point of receipt

Counterfeit detection Using Raman spectroscopy, TruScan RM examines the chemical composition of all components of a pharmaceutical dosage, including APIs, excipients, fillers, dyes, and coatings to create a unique spectral fingerprint representing the authentic medicine. Deviation from the original formulation will lead to a detectable change in the measured spectrum, making TruScan ideal for rapid detection of counterfeit pharmaceuticals in the field.

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SPECTROSCOPY

Lean work Bruker explains how its FT-NIR technology can help to increase manufacturing efficiency

“

Manufacturing pharmaceutical products is a very complex task.

”

oday quality control is the major issue in pharmaceutical manufacturing. With the PAT initiative, the FDA is striving for greater efficiency and cost reduction.

Manufacturing pharmaceutical products is a very complex task – from controlling the raw materials to the release analysis of finished products, there are numerous sources of error. The FDA has laid the cornerstone for an intense discussion as part of its PAT (Process Analytical Technology) initiative for a better understanding of the process and increased product and security at lower cost. The FDA sees process analysis technology as a key to monitor the Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs) of pharmaceutical manufacturing processes. The aim is to increase the robustness of the processes by defining the CPPs and their timely control – preferably in-line or on-line. This can improve product quality, reduce reject and rework rates and minimise the number of release analyses. Even an on-line release of the products is possible. The implementation of other initiatives such as QbD (Quality by Design) and RTRT (Real Time Release Testing) in the course of the control strategy are useful particularly for continuous manufacturing. The automatic interpretation of reliable on-line analysis values for use in control loops plays a crucial role. Only an error-free flow of the individual production steps, as well as their understanding guarantee a product of the desired quality. Classic process variables such as pressure, temperature, pH or other physical parameters are often not specific enough to adequately characterize the processes and the relevant properties of the product. In addition to other analytical methods the optical spectroscopy (UV, VIS, IR, NIR, Raman) is here of particular interest. These methods are • non-destructive • free of sample preparation and • process-suited for on-line or in-line applications. Bruker’s Matrix-F FT-NIR spectrometer allows the direct measurement in process reactors and pipelines, leading to a better understanding and control of the process.

Conventional spectrometers can only be installed close to the process that they are monitoring, which exposes the analyser to a hostile environment, like drastic temperature changes and exposure to dust and dirt. Furthermore, the instrument needs to be positioned in hard-to-access and often ex-protected area. By using fibre optics technology, the difficult-to-reach measurement points can be accessed by industry hardened fibre optic probes, while the Matrix-F is positioned, eg in an analysis house. Bruker Optics offers complete solutions for various on-line analysis tasks.

Manifold applications Since the NIR technology permits a quantitative analysis of organic molecules in small concentrations, a monitoring of most pharmaceutical production processes is possible. In many areas, even the direct control of processes as demanded by the PAT initiative.

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Applications include: • Quality control of incoming goods: During the goods in control the identity of the raw materials is checked. Only if they are within the specified quality, is the consignment accepted and forwarded to the process. Hierarchical identification libraries based on NIR spectra allow real identification of all substances and not only checks of similarity. • Formulation and reaction control: As each molecule has a characteristic NIR spectrum, formulations can be directly examined in-line. This also applies if the contents change with time, for example, during a synthesis, fermentation or an extraction process. In this way it is possible to determine the optimum reaction end point and to document the process has succeeded in the defined design space. • Mixing: Producing homogeneous mixtures that are suitable for the tabletting is usually difficult. The homogeneity of pharmaceutical mixtures can be measured with the NIR technology, if a probe records spectra continuously during the mixing process or the complete spectrometer is rotating with the blend container. At the beginning of the blend process large differences between the spectra will be measured, since the individual materials are not yet homogeneously distributed. With increasing homogenisation the spectra become more similar. Since NIR probes can have very small measurement spots, the homogeneity of smallest volumes can be supervised. • Granulation and drying process: More than 60% of all pharmaceuticals are solids. The individual powder substances are in most cases granulated and dried before tabletting. Both processes can be monitored with NIR technology. Here the exact end point determination of the time consuming drying process in fluid bed dryers is of special interest, since suitable in-line measurements can reduce the drying times considerably. •T ablet coating: Coating procedures in a drum coater or a vertical centrifugal coater can be monitored by means of NIR spectroscopy. The correlation of NIR spectra to eg spray rate and coating thickness helps to produce in specification. abletting and packing: Thickness, hardness, dimensions, and active ingredient content are relevant quality •T parameters of tablets. Their automatic measurement directly off the machine offers large advantages compared to the classical laboratory analysis. Especially when producing tablets, which do not correspond to the specifications, it must be recognised immediately. Otherwise thousands of tablets must be rejected and disposed of, leading to high economical damage.

Final product testing and release analytics There is no doubt that the cardinal task of the PAT initiative is to avoid time-consuming release analytics in the laboratory. Nevertheless: If in-line monitoring does not seem suitable, NIR technology can still be beneficial. In the QA/QC laboratory NIR can be used for release analytics, because the advantages of a fast and non-destructive measurement are also available off-line. With the FT-NIR laboratory spectrometer MPA all kind of samples (liquids, solids, pastes, foils) can be analysed quickly and reliably. The NIR spectroscopy allows in many areas the direct control of processes as demanded by the PAT initiative. Shorter cycle times, higher product quality and the avoidance of non-specification grade batches are the result. Furthermore, with real-time analysis, many system parameters can be monitored and their meaning better understood. Today, many users say that the PAT initiative represents a paradigm shift in pharmaceutical analytics, meaning that the current ‘testing to document quality’ paradigm is shifted to a ‘continuous quality assurance’ paradigm. So the analytics get a complete new relevance: it does not only serve for the examination, but it is tool for the control. And in this context the NIR technology represents the most valuable tool at present.

“

Conventional spectrometers can only be installed close to the process that they are monitoring.

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” 47

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Uncompromising QA/QC Portable, rugged and proven, the Thermo Scientific TM TruScanTM RM analyzer uses a 785nm wavelength for maximum coverage-without compromising resolution or selectivity. TruScan RM employs a multivariate residual algorithm that eliminates the need for manual threshold setting or method maintenance.

Only with the TruScan RM

â&#x20AC;˘ Protect your brand at thermoscientific.com/quality

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LOGISTICS & DISTRIBUTION

RD Centre Prague: Engineering & Technology Centre: To confirm that the refrigerated equipment is performing to specification, tests have been conducted in a temperature-controlled chamber of the industry-certified Ingersoll Rand Engineering and Technology Centre (IRETC) in Prague.

Safe cargo Thermo King explains how it protects patient safety by maintaining the quality and integrity of medical products

t Thermo King we understand that if the quality of pharmaceutical product shipments is compromised, the risk is more than the loss of cargo – it can compromise the health of patients.

Industry statistics indicate that 25% of vaccines reach their destination in a degraded state because of incorrect shipping, and approximately 30% of scrapped sales at pharmaceutical companies can be attributed to logistics issues – Thermo King has been working to decrease these percentages to ensure top quality medical products for patients worldwide. PharmaSolutions, a comprehensive and dedicated expertise platform from Thermo King, addresses the precise needs of the pharmaceutical industry by delivering applications, advice and a broad spectrum of services.

This solutions package purposefully covers the four stages outlined in the European Commission’s Good Distributions Practice Guidelines (GDP Guidelines) of Medicinal Products for Human Use to include: • Design Qualification (DQ) • Installation Qualification (IQ) • Operations Qualification (OQ) • Performance Qualification (PQ)

Design and installation qualification PharmaSolutions offers a range of equipment for temperature-controlled transportation, from trailer to pulley-motor truck, as well as ColdCube thermo King containers. All equipment has been tested to conform with GDP guidelines: • At temperatures of +15°C to +25°C; +2°C to +8°C; at -20°C to suit different cargo, as well as an annual three-temperature calibration check

VP Truck and Trailer monitor your vehicle: PharmaSolutions offers 24/7 fleet monitoring services for end-to-end management of any refrigerated vehicle fleet.

Under extreme ambient temperatures • from -30°C to +40°C to assure you of your cargo’s safety in extremes of climate • Test of door openings, failure mode as a reference for customer’s risk management analysis. The validation protocol has been supervised and validated by an independent pharmaceutical company specialised in regulatory affairs of the healthcare industry, with qualified responsible personnel and pharmacists highly-experienced in the design and implementation of pharmaceutical related Quality Systems (eg ISO13485, GDP and GMP). continued overleaf>

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FOLIO

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To confirm that the refrigerated equipment is performing to specification, tests have been conducted in a temperature-controlled chamber of the industry-certified Ingersoll Rand Engineering and Technology Centre (IRETC) in Prague. This R&D facility is certified ISO 9001: 2000; ISO 14001 and ISO 18000 and authorized for ATP certification.

Operations and performance qualification The PharmaSolutions service range can be delivered as a complete package, individually, or as a selection of services combined into a PharmaAssist service contract. The service range includes: • Product application expertise and training services • 24/7 fleet monitoring services • Real-time tracking and monitoring

Thanks to a strong dealer network, PharmaSolutions helps you to minimize the risk of load-loss in case of breakage, with about 2,000 Europe-wide technicians highly trained to Thermo King standards as well as to GDP standards. The Dealer Locator App can help you identify the nearest service points when evaluating the points of risk along the delivery route.

Real-time tracking and monitoring With regard to transportation temperatures, the GDP guidelines say that medicines requiring controlled temperature storage should be transported by appropriately specialised means. PharmaSolutions recommends the use of remote monitoring systems such as Thermo King's TracKing to reduce the risk of damage, loss of quality and wastage of high value medical and biological products.

Proactive maintenance

• Full service history and proactive maintenance

Product application expertise and training PharmaSolutions delivers product application expertise covering refrigeration system set-up, risk mitigation and operating guidelines that are critical to know for any transportation partner. Pharmaceutical transporters can rely on the Thermo King dealer network for guidance on installation and use of refrigeration systems. Customised training services can also be offered based on the customer’s operations and needs in relationship to the new requirements of the GDP guidelines.

This PharmaSolution can offer the option of storing a full service history over the complete life of your refrigerated vehicles, with an online database recording of all your repairs, maintenance and calibration activities conducted on your equipment to ensure data management for audit and inspection. A planned maintenance schedule for your equipment that proactively notifies you when you need a service is also an option. (Source: World Health Organization (WHO), Parenteral Drug Association (PDA) and other industry estimates

24/7 fleet monitoring services PharmaSolutions offers 24/7 fleet monitoring services for end-to-end management of any refrigerated vehicle fleet. It is a powerful tool to improve operational efficiency of the pharmaceutical supply chain and enable connectivity to manufacturers’ goals.

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Weighing tabs track your temperature: PharmaSolutions recommends the use of remote monitoring systems such as Thermo King’s TracKing to reduce the risk of damage, loss of quality and wastage of high value medical and biological products.

FOLIO

VITAL EXPERTISE.

Vital expertise for safe and secure pharmaceutical transportation Pharmaceutical products require precise handling at every stage of transport to ensure patient protection. Thatâ&#x20AC;&#x2122;s why Thermo King PharmaSolutions offers precise temperature control and air distribution throughout the supply chain, and a wide range of GDP-validated equipment and services to enhance your quality system. Easy access to service history, advanced monitoring, 24/7 assistance, and training are also available.

europe.thermoking.com 52

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LOGISTICS & DISTRIBUTION

Chain reaction What’s your business supply chain strategy? If you’re not quite sure, then you probably don’t have one! Professor Richard Wilding OBE, Cranfield School of Management discusses building a firm foundation for the pharmaceutical supply chain Supply and demand: Professor Richard Wilding finds that when working with organisations’ supply chains it is possible to identify useful areas of focus

be sold in a less well-developed nation, the competitive strategy might be focused around affordability, and on how to make and distribute the product as cheaply as possible.

So if its supply chains are so different, how can one make recommendations on how to improve them? A useful analogy is that of a medical doctor. All patients are different, but at the same time there is commonality: they all have a heart, lungs and brain and we are all told certain things to do to keep healthy. The same is the case with supply chains: although all are different, there are commonalities, and all have customers and suppliers and resources are moved. Keeping the supply chain healthy requires certain issues to be addressed.

This then requires us to define the supply chain strategy, which in turn defines how ’demand is fulfilled’. And clearly, the supply chain strategy needs to align with the competitive strategy if we are to deliver value in full. So, logically enough, the supply chain strategy considers and impacts on four main elements: the supply chain process design, the supply chain network and infrastructure design, the supply chain information system design and finally, the supply chain organisation design. All of these elements need to be tailored to the products and organisational specifics that are involved, in order to enable the desired value to be created in the marketplace—a task that is complicated by the fact that each of these four elements interacts with the others. Moreover, it also needs to be recognised that if we do not have the relevant infrastructure, then we may not be able to support the desired competitive strategy. And so, each of these elements needs to be fed back to those involved in the competitive strategy development process, to provide opportunities to adjust the strategy accordingly.

ost industry sectors consider themselves to be unique. But in truth, the pharmaceutical industry has a better claim than most to that distinction. And quite apart from the rigorous quality and traceability standards that apply, the very diversity and complexity of pharmaceutical supply chains means very clearly that ‘one size does not fit all’. More than most, there are no supply chain ’magic solutions’ for the pharmaceutical industry, and many of its supply chains are different.

So as a ‘doctor’, I find that when working with organisations’ supply chains it is possible to very quickly identify potentially useful areas of focus. A good starting point for all businesses is ‘Does a supply chain strategy exist?’ And is it written down and readily communicated across the organisation? Understanding the development of an effective supply chain strategy is critical to success. This needs to start with the corporate strategy of an organisation, which then helps to define the competitive strategy for different products in different markets. The competitive strategy in simple terms gives direction as to how value is going to be created in the market place. Consequently, it is very much focused on how ’demand is created’ for the product or services in question, and involves understanding in detail what it is that actually creates ’value’ in the final market place for the various stakeholders that the product or service impacts upon. Taking a simplistic example, the competitive strategy behind a commodity pharmaceutical product for a European market might be focused on high levels of availability and innovation in the packaging design. In contrast, if the product were to

Which then raises the next important question: “Who is responsible for developing the competitive strategy, and who is responsible for developing the supply chain strategy?” and perhaps more importantly, “Do they actually talk to each other and collaborate in the development of each element?” In short, collaboration is critical within the organisation if we are to ensure the successful execution of our supply chain strategy. Importantly, it also requires individuals to occasionally be prepared to take time away from the daily pressure of running the business in order to reflect on the strategy. And that’s because what creates value today is not necessarily what creates value tomorrow. We define supply chain management at Cranfield as “the management of upstream and downstream relationships with all stakeholders, in order to achieve greater final customer value-added at less cost to the supply chain as a whole.” Managing relationships and relational intelligence both internally and externally to the organisation is clearly critical to the success of this.

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ACHEMA

Get appy at Achema This year’s Achema offers a plethora of exhibitors as well as providing a focus for those interested in bio trends From 15 to 19 June 2015 ACHEMA 2015 takes place in Frankfurt. Over 3,100 exhibitors have already registered. A range of themes will emerge at this year’s event including energy efficiency, materials and materials testing, and safety technology. The number of papers submitted for the congress in these areas has been high to meet the unprecedented demand, additional space has already had to be created for the pharmaceutical and packaging sectors. ACHEMA aims to reflect the overall trends in its core sectors such as machinery and plant engineering and the chemical industry which, despite a turbulent international business environment, are proving to be surprisingly resilient.

The organiser of the event has created an app to help make the exhibition experience event smoother. This features hall and stand numbers, interactive hall plans for orientation on the exhibition grounds, simple search functions covering all product categories, exhibition groups and halls, short company profiles of exhibitors with business fields and products as well as contact data for getting in touch directly. The app also offers the ‘My ACHEMA’ feature to list your favourites and will provide daily updates of the congress progamme with all lectures and speakers. Users will be able to create a personal show schedule plus share interesting information on exhibition stands and lectures via Twitter. The ACHEMA app will be available at official app stores from mid-May 2015 free of charge.

BiobasedWorld at ACHEMA will highlight where bioeconomy becomes visible and tangible. This will include a session on specialty chemicals, pharma intermediates and food ingredients.

On with the new

Driving ahead

Holland will be exhibiting some of it most innovative products at ACHEMA, and will showcase a number of new products, which will be launched exclusively at the show.

The company’s innovative products and solutions will also extend into the general conference programme, where Rob Blanchard, research, development and quality systems manager will talk through the reasons why tablet formulations stick to punch tip faces and how to overcome sticking issues by using the TSAR-Predict model, which calculates particle adhesion levels and which coating would help in solving sticking problems. Andy Dumelow, I Holland’s PharmaCare product manager said: “ACHEMA is a very important exhibition for us and it will give us the opportunity to not only showcase new products, but also engage with the audience through Rob’s presentation on one of I Holland’s most innovative projects, TSAR-Predict. “As well the new product launches we will also be introducing the European market to I Holland’s new MF80 automated punch polisher, which offers a large capacity for increased polishing per cycle.”

coording to Frewitt, its FreDrive makes possible what many operators can only dream of –adjusting production levels and requirement via different milling processes with changeovers in record time.

FreDrive, the new universal platform for special applications can be used in the pharmaceutical industry for the size reduction or sifting of solids. Frewitt describes FreDrive as a revolutionary milling platform concept. Up to five different grinding heads can be attached in five minutes, either for primary crushing, deagglomeration, granulation, fine grinding or control screening on the universal platform, which combines the control and drive units. Changeover to a new grinding process takes a few minutes; loosen the Tri-Clamp, change the milling head, and reattach the Tri-Clamp. Frewitt has created the ability with FreDrive to mill sticky, hard, or crystalline powder with widely varying product characteristics gently and problem-free, providing requirement satisfying, flowing powder to processes. All applications that require a mill with screen calibration (including ATEX zones 0/20 and 1/21) are suitable. Solid work: Frewitt’s FreDrive can be used in the pharmaceutical industry for the size reduction or sifting of solids

Speaker’s corner: Rob Blanchard, I Holland will be presenting at the show on one of I Holland’s most innovative projects, TSAR-Predict

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ACHEMA

Labeling by Faubel.

CONVINCING QUALITY. www.faubel.de

Going green Extract Technology will be launching GreenLine at ACHEMA – an ECO efficient containment booth The pharmaceutical industry is faced with an increasing competitive environment, resulting in manufacturers looking for opportunities to reduce production costs without affecting the quality of products. Extract Technology has put ECO efficiency at the heart of developments and will unveil its latest standard product GreenLine – a low energy, low noise Downflow Booth at this year’s show. GreenLine aims to offer energy savings of up to 70% compared with that of conventional systems and is “set to deliver best global practice” according to Rob Wallace, energy efficiency consultant of EECO2 – a specialist company that provide monitoring and reporting services to ensure system efficiency.

Warm front DIR Technologies, a provider of pharmaceutical primary packaging, will showcase its pioneering application of thermal imaging solutions for induction and heat sealing integrity assurance during ACHEMA. DIR Technologies’ Induction Integrity Verification System (I2VS) provides induction sealing integrity analysis for 100% of bottles without packaging line slowdown. The company has also developed the Sachet Full Monitoring System (SFM) to provide 100% in-line inspection of sachets and pouches. Both DIR systems are either in use or in trials on packaging lines for several leading pharmaceutical packaging companies. Both the I²VS and SFM systems provide real-time quality control solutions that improve overall production workflow.

Booklet labels for automatic application Multi-layer labels up to 9 pages Single-layer labels from small lots to high volumes Tamper-evident solutions 56 Entwurf FPS.indd 1

Show and tell: Innovation on show from DIR Technologies at Achema include the Induction Integrity Verification System (I2VS)

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ACHEMA

Print works Qualicaps will be showing its LIS-250 laser imprinting machine at ACHEMA. The LIS-250 UV imprints tablets, softgels and capsules at a speed up to 250,000 per hour. Laser imprinting has many benefits, including the elimination of defects caused by ink, flexible printing options, a larger printable surface than ink, and no cleaning due to ink. Other benefits include the potential to help with counterfeiting and printing on tables without resulting in thermal denaturation. Speed star: The LIS-250 UV imprints tablets, softgels and capsules at a speed up to 250,000 per hour

For the first time

Premier event According to Sepha, the world’s first automated, tool-less and nondestructive leak-detection device for pharmaceutical blister packs will make its global debut at ACHEMA. By offering the capability to leak test full production batches of blister-packs with minimal operator input, the launch of the new VisionScan Max gives pharmaceutical manufacturers the ability to deliver significant quality improvements and cost savings during production.

ACHEMA will be the first major European outing for the latest additions to Malvern Instrument’s recently acquired MicroCal microcalorimetry range and for the OMNISEC GPC/SEC platform.

VisonScan Max can test over 600 packs per hour at accuracy levels of 12 micron with minimal operator input or requirements and giving repeatable objective pass and fail results. VisionScan Max has been designed to integrate with blister production lines via automated ‘pick and place’ technologies to further enhance automation on production lines and minimize operator requirements, or operate as a stand-alone unit.

Malvern’s products for life scientists provide information to drive drug discovery and development. Centre stage will be the recently launched Malvern performance and enhanced functionality for the study of biomolecular interactions. Alongside will be the new Viscosizer TD, for automated ultra low volume particle and molecular sizing via Taylor Dispersion Analysis.

New Vision: Sepha’s VisionScan Max gives pharma manufacturers the ability to deliver quality improvements and cost savings

Stick with it Self-adhesive technology specialist Herma will premiere the 132M HC at ACHEMA. This is a wrap-around labelling machine that is fully equipped for serialisation tasks. The equipment includes a Videojet printer and a Laetus camera system that monitors the print quality. This is of particular interest for pharmaceutical companies and packaging specialists in search of a track & trace solution for pharmaceuticals as serialisation is expected to become mandatory in the European Union in 2017 / 2018. The 132M HC’s controller, which can be chosen according to customer preference, is another exhibition highlight: Users now have the choice between Allen-Bradley and Siemens. “With the HERMA 132M HC, we now offer another machine platform with an Allen-Bradley option,” says Martin Kühl, head of the Herma labelling machines division. “We thereby continue our company’s internationalisation strategy, and accommodate especially multinational companies that opt for globally universal machine standards in their individual plants.” First view: Self-adhesive technology specialist Herma will premiere the 132M HC at Achema

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Introducing the Ezi-Flow™ CSV4 All Plastic High Containment Transfer System The New All Plastic Ezi-Flow™ CSV4 High Containment Transfer System provides a highly effective but simple to use solution for the Pharma and Biopharma industries.

Ezi-Flow™ CSV4 All Plastic OEB5 Containment Level of <1μg/m3 (task based) Fast, Full-Bore Discharge Liquid Tight Zero Maintenance Fully Disposable Many times cheaper than “Old Style” Split Butterfly Valves Fast, Trouble-Free Supply

World Class Industrial Packaging Solutions

Manufacturers & Suppliers of World Class Industrial Packaging Solutions.

The low cost system can be used as a batch/campaign solution, or even as a single use system for contained powder addition.

Tel: +44 870 041 0326 Email: sales@ezidock.com

Visit us at www.ezidock.com

Visit us at Achema 2015 Hall 3.1 Stand A71 Ezidock 220 x156 ad.v7.indd 1

5/7/2015 6:10:55 PM

Visit us at ACHEMA in Hall 3.0, Booth C24 and in Hall 4.1, Booth H77 15 – 19 June 2015

Fast. Simple. Precise. The new MultiTest 50 tablet hardness tester The new generation MultiTest 50 sets new standards in testing up to 5 physical parameters of virtually all tablet shapes with one single unit. In full compliance with current Pharmacopeia requirements, the system offers highest precision, flexibility and exceptional user-friendliness. Next to fast and efficient operation, the MultiTest 50 provides accurate and highly reliable test data, resulting in increased productivity and ease of regulatory compliance. www.pharmatron.com/MT50 Dr. Schleuniger ® Pharmatron is a brand of

Quality matters.

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ACHEMA

Lean and mean

On a plate

At this year’s ACHEMA, Bosch Packaging Technology will present a new granulation unit GranuLean for the first time. Developed by the Bosch subsidiary Hüttlin, this combines the process steps of mixing, granulating and drying for the manufacturing of pharmaceutical granules.

Visitors to ACHEMA are invited by Porvair Sciences’ stand to see its range of application optimised microplates and microplate equipment. For labs involved with fraction collecting, compound storage, plate replication and mixing applications – Porvair has developed a genuine 2.00 ml 96 round well deep well plate that enables scientists to use the full 2.00 ml well capacity. Manufactured under class 10,000 conditions from ultra-pure grade polypropylene the 2.00ml 96 round well deep well plates are certified as RNase / DNase free and contain no measurable contaminants that could otherwise leach out and affect the sample.

“The name GranuLean stands for a lean and compact machine, which can be easily integrated into production rooms and focuses on the basic requirements of pharmaceutical producers,” Fritz-Martin Scholz, product manager at Bosch Packaging Technology, explains. “By concentrating on the essential basic functions within fixed dimensions, we have developed an especially efficient granulation solution.” The GranuLean exhibited at ACHEMA, says the company, saves valuable production room with its 6m length and 3.4m height. The new development is available for three different batch sizes and is based on Hüttlin’s process technology experience.

Also, the company will be exclusively previewing the Ultravap Levant at ACHEMA. This is the latest in Porvair Sciences’ series of nitrogen blow-down sample concentrators and evaporators. On show: Visitors to ACHEMA should head to Porvair Sciences’ stand to see its range of application optimised microplates and microplate equipment

Making a splash Purite will be exhibiting its water purification solutions at ACHEMA 2015. At the show, the company will present its Integra HP and Select Fusion water purification solutions. The Integra HP is a compact and mobile water purification and distribution unit, which incorporates reverse osmosis, ion-exchange, carbon dioxide, membrane degassing, UV irradiation and bacterial filtration technologies and provides purified water that meets the requirement of laboratory grade water. The Select Fusion is a self-contained unit for laboratory use, which integrates pretreatment, reverse osmosis, UV photo-oxidation, ion exchange and sub-micron filtration technology in a robust and compact enclosure. Water purification experts will be on hand to discuss the water purification needs of visitors, covering of topics, including types of water purification technology; achieving high purity water for applications such as healthcare and pharmaceutical and how to specify water purification systems for water reuse.

Pure and simple: At the show, the company will present its Integra HP and Select Fusion water purification solutions

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Process Analytical Technology

Pumps for FT-NIR Spectrometer

Today, many companies are not only striving to manufacture high quality products, but also to increase production efficiency by installing the analytical systems directly into their production plants. This improves process verifiability and process understanding and gives the company the opportunity to optimize material use, run-time of machines and product quality up to real-time-release.

Allows in-line measurements e.g. in blender, granulators, dryers, and coaters leading to a tighter control of processes and products.

Bruker´s spectroscopical technology based on modern FT spectrometers can be implemented in different process steps and offers high amount of information to gain better process understanding. The robust design of all spectrometers enables usage in tough conditions in production plants with very low maintenance costs and downtimes.

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MAoth H50 E H AC 4.2, Bo Hal

Quattroflow™ quaternary diaphragm pumps deliver high-value solutions for your applications. Depending on your requirements, Multiple-Use and Single-Use models are available.

• • • •

FT-IR Spectrometer Development/process spectrometer ideal for realtime monitoring and analysis of chemical, biological and fermentation reactions.

Particle generation High pulsation Lack of self priming High heat input

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Mechanical seals Product shear Burst of hoses Cleaning validation

If you use Quattroflow™ quaternary pumps, you will benefit from... • No identifiable particle generation • Low pulsation • Self priming • Low product impact • Safe dry run

• Gentle product treatment • Linear flow characteristics • Quick change over

See us at ACHEMA Hall 5.0, Stand C33 For more information, please go to: psgpumps.com/epm515q

MPA

FT-NIR Lab Spectrometer Modular, multi-channel system for your needs from raw material identification to finished product or content uniformity control.

PSG ALMATEC Maschinenbau GmbH Carl-Friedrich-Gauß-Str. 5 47475 Kamp-Lintfort, Germany P: +49/2842/961-0 info@almatec.de quattroflow.com

Innovation with Integrity

Processes

When dealing with pumps in bioprocesses, you might be faced with...

Contact us for more details: www.bruker.com/PAT Bruker Optik GmbH Rudolf-Plank-Str. 27 D-76275 Ettlingen Tel: +49 (7243) 504-2000 Fax: +49 (7243) 504-2050 E-Mail: info.bopt.de@bruker.com

Biopharmaceutical

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ACHEMA

Solid solutions

Perfectly packaged

Multivac will be presenting packaging, labelling and marking solutions for the life science and healthcare industry. Among these will be a compact thermoforming packaging machine for packing products in small batch sizes.

Marchesini Group will illustrate pharmaceutical packaging solutions at ACHEMA. The machines showcased at the stand will include the monobloc Synchro 24 for filling and counting solids and a preview of brand new units such as the robotised blister line Integra 520V and the vial filler ML 643. Altogether, there will be three complete lines and five stand-alone machines for each specific sector of the pharmaceutical packaging industry, from serialisation to aseptic packaging. The company will have information on the Stery Capsy aseptic filler and stoppering machine for injectable pharmaceuticals and the new ML 643 linear vial filler/ capper-plugger with intermittent motion. The RE 302 labeller will also be on show at the fair, set up for small eye drop containers. Other highlights will include the BL-A421 with added variables to extend the range of sizes processed. This will be showcased in line with the horizontal casepacker and palletiser MC820.

With the R 081 thermoforming packaging machine, Multivac will be showing a new entry-level model that is designed for packing products in small batches. It is also suitable for cleanoom applications and can be used for producing both vacuum packs and modified atmosphere packs with reduced residual oxygen content. Multivac will also be showing a thermoforming packaging machine in the Multivac Clean Design for the GMP-compliant packing of sterile medical products. The machine can run both flexible and rigid films as well as Tyvek and paper-based packaging materials.

Showing off: The BL-A421 with added variables will be showcased in line with the horizontal casepacker and palletiser MC820

Pharma solutions The Romaco Group will show end-to-end solutions for granulation and coating, tableting and primary and secondary packaging. The company will also unveil a blister line with an integrated anti-counterfeiting system which enables the primary packaging to be unequivocally identified. A new aseptic microdosing machine with 100% weight control and the next generation of Romaco’s Remote Assist will also be among the technological highlights. With its acquisition of Innojet Herbert Hüttlin in February 2015, the Romaco Group says it became the first supplier in the world to manage the entire process chain for manufacturing and packing pharmaceutical solids. Romaco Innojet’s high-efficiency solutions for gentle granulation and coating processes are based on the patented air flow bed technology. Originally developed by Dr. Herbert Hüttlin, this method offers linear scale-up of all process parameters and allows up to 75% shorter processing times compared with conventional technologies, says the company.

Perfect partners At ACHEMA 2015, Schubert-Pharma will be highlighting its position as a partner of the pharmaceutical industry. The innovations featured include the world’s first prototype of a packaging machine without an electrical cabinet. Another Schubert system will show flexible packaging of bags with disposable syringes, including leaflets – this will be demonstrated in different layer configurations. Schubert-Pharma will be showing its line management system (LMS) with control station, which enables the planning and documentation of efficient production line operation. Schubert-Pharma will also be presenting its consulting portfolio for the pharmaceutical industry, supports customers with engineering expertise for planning production for example.

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O’Hara Tablet Coating System Small O’Hara Laboratory Coating Systems, up to 100 kg

O’Hara Labcoat series are compact selfcontained Laboratory coating systems. Features and Benefits • Aqueous & solvent designs • Interchangeable pans • Portable & self-contained • CE declaration & conformity • Tablet pellet pans • Anti bearding spray nozzles

Medium

O’Hara Containment Coating Systems, 95 to 100 kg

The Containment Labcoat is a product line of multi-pan laboratory and production coating systems with containment for highly potent API’s. Features and Benefits • Up to OEB5 • Rigid isolator • Inflatable door seals • Reverse tablet discharge • Flex containment option

High Volume O’Hara Continuous Coaters, 30 to 1200 (kg/hr)

FastcoatTM continuous Coater is a product line of continuous/fast batch tablet coating systems. Features and Benefits • Rapid coating speeds • Wash in place (WIP) • Zero wastage • Adjustable bed depth • Anti-bearding spray nozzles • Recipe control • Less product damage

O’Hara Technologies Inc. 20 Kinnear Kinnear Court, Court, Richmond Richmond Hill Hill 20 Ontario, Canada, Canada, L4B L4B 1K8 1K8 Ontario,

Tel: +1-905-707-3286 +1-905-707-3286 Email: sales@oharatech.com Tel: Email: sales@oharatech.com Fax: +1-905-763-6749 +1-905-763-6749 Web Site: www.oharatech.com www.oharatech.com Fax: Web Please visit us at Interphex 2015 Stand #3021 in New York and at ACHEMA 2015 Hall #3 Stand # B100 in Frankfurt

Please visit us at ACHEMA 2015 Hall #3 Stand #B100 in Frankfurt 62

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ACHEMA

Prime product According to Lewa, using its Ecoprime low-pressure chromatography system, batch-tobatch reproducibility in GMP manufacturing of biopharmaceuticals can be enhanced significantly and the yield of the product can be enhanced. Due to be unveiled by the manufacturer at ACHEMA, Lewa says the system is notable for its precise flow control from 0.03 to 60 litres per minute, its unrivaled dynamic flow rate range, minimal pulsation and low holdup volume which allows better product yield, purity, and safety during purification. As a consequence, production time and the costs of validation in the entire production cycle are able to be reduced. Lewa will be unveiling its Ecoprime low-pressure chromatography system at ACHEMA

Variety show PTK says it has been building a reputation for robust, highly technical and costeffective solid dose production machinery for drug manufacturers. The company offers a range of solid dose manufacturing machinery which it says brings it shoulder to shoulder with other European brands in terms of output and quality. It will be launching its laboratory range at the show. This includes a tablet press, a lab granulator and a standalone lab scale tablet coater. All PTK machines benefit from PTK’s intuitive software, developed in-house to give batch reporting, recipe recall, rights of access management, remote support and informative diagnostics. Also on the company’s stand will be PTK’s production capsule filler and flagship tablet press, the PR2000, for high speed, high force applications.

Cover story: PTK’s stand will offer a range of the company’s products including this tablet coater

Passing the test Freeman Technology, the powder characterisation specialists, will be exhibiting the FT4 Powder Rheometer, a universal powder tester, at ACHEMA. The company will also be distributing the recently released booklet ‘The Value of Powder Testing’. Visitors will have the opportunity to discuss their individual powder processing challenges with the Freeman Technology team and the company will also be hosting a presentation where experts will discuss why powder flow is important, review traditional measurement techniques and explain how powder behaviour relates to inprocess performance. The FT4 Powder Rheometer uses a patented dynamic methodology, automated shear cells and bulk property tests, including density, compressibility and permeability, to quantify powder properties in terms of flow and processability. It delivers data that aims to maximise process and product understanding, accelerate R&D and formulation, and support process optimisation. On show: Freeman Technology will be exhibiting the FT4 Powder Rheometer at ACHEMA

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PUMP TECHNOLOGY

Pumped up Manufacturing paradigm shift for evolving disease treatments, through the perspective of advancing single-use pump and connector technologies by Wallace Wittkoff, Quattroflow Fluid Systems and John Boehm, CPC

ommon now are mainstream news reports that highlight the proliferation of more contagious and lethal diseases and their spread from continent to continent at the speed of commercial air travel. The weapons to combat these threats have been evolutionary and technological advancements that are assisting include the deployment of single-use pumps, connectors and related technologies in biopharmaceutical-manufacturing processes. Humanity is constantly being challenged at what seems to be an accelerating pace by new diseases that can be even more contagious (Bird Flu) or lethal (Ebola). In addition, certain diseases are able to gain immunity from existing treatments. The worst combination that the health-science community is preparing for is a disease that is both very contagious and extremely lethal at the same time. The foundational key to combating these diseases is faster development and the deployment of proper medical solutions. Today, needed drugs are taking too long to develop and the solutions are often too late for the first advances of new diseases. Much of this delay is regulatory in nature, but large-scale pharmaceutical processes can fall short in the ability to respond technically when rapid development and deployment of new solutions are needed.

Identifying alternatives Capable of meeting the challenge for faster development and deployment of solutions are modular processes based on single-use solutions that reduce hardware infrastructure. Over the last decade, pump technology has evolved to meet the challenge, and single-use pump technology, notably quaternary diaphragm pumps such as the Quattroflow pump, has made both the development of new drug treatments and acceleration of their production schedules possible. In its simplest form, single-use pump technology is one example of process equipment that can be used in a production run or campaign without requiring cleaning until completion. For decades, the pharmaceutical industry flourished with large, stainless-steel-laden manufacturing complexes that were used to develop the new chemical formulations that had been found to aid in the healthcare battle. Additionally, until only recently, the most prominent way to produce vaccines was by growing the viruses in eggs. However, massive research in cell biology has made it evident that cell structures can produce an infinitely greater possibility of compounds that are not possible with reactions or formulations produced by traditional chemical/pharmaceutical production processes. Looking at using cell structures as factories to create medical treatments, consider the treatments for new global threats like Ebola. Companies such as Tekmira and Medicago are using biological methods to produce remedies for this current world health crisis. Medicago, using biotechnology, is able to create virus-like particles (VLPs) to take the place of a virus (thus no use of chicken eggs). As such we are experiencing the rise of the biopharm industry. This is an industry that is producing treatments and cures using biological methods, such as ‘cell factories’ via the application of advanced science.

Single friend: A Quattroflow single-use quaternary diaphragm pump chamber coupled with a CPC AseptiQuick connector for use in sterile-manufacturing systems

Better technology A commercial biopharm facility is actually a lab that is designed to properly grow these ‘cell factories’ and then extract, filter and refine the target product, such as monoclonal antibodies, VLPs or ADCs. One main operational concern was overcoming the difficulty, cost and reliability issues associated with ensuring that permanent installations could be cleaned safely and reliably. An example of such equipment that meets biological-process requirements, as well as single-use manufacturing concepts, are the Quattroflow quaternary diaphragm pumps and CPC single-use tubing connectors, which can be a key link in the biologics-manufacturing process. The advancements that are helping single-use pumps pave the path of the future and offer many more benefits than simply the optimized cost of buying new when compared to cleaning processes are: • Speed to the challenge • Speed to market • Closed manufacturing • Geographic proximity/mobility Permanent stainless-steel process systems are inherently inflexible, but single-use components make it possible to take a ‘Lego’ approach when developing processes to meet development and production needs. This represents an accelerated ability to develop a solution to a challenge and shorten the time to market.

Conclusion Health sciences advances via biotechnology has further improved quality of life and enabled us to deal with emerging health threats. The latest chapter in this saga has been advances in processes made possible by adoption of single-use pumping solutions, connectors and associated hardware. This makes possible the implementation of closed process systems that will further expand options, capabilities and speed-to-market capabilities in the future. On the component level, single-use pumps from Quattroflow and AseptiQuik connectors from CPC can play a critical role in further advancing the future paradigm.

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CHEMICAL REACTION It’s important to stay on top of the latest services, companies and innovation. EPM’s Chemical Reaction highlights a technology, service or business we think would we worth keeping an eye on...

Take my device Cecilia Mendy, Owen Mumford, reveals the current and future initiatives at this drug delivery device business EPM: Who are you and what do you do? CM: Owen Mumford is an industry leader in medical device design and manufacturing. With a 60-year history of medical device firsts, we offer innovations for capillary blood sampling and drug delivery from a broad base of proven self-injection and blood sampling platform devices and intellectual property. These innovations help end-users and healthcare professionals deliver effective treatments for conditions such as diabetes, multiple sclerosis and a wide range of additional therapy areas. Our solutions are used as part of patient self-management plans in the home and by hospitals, doctors’ surgeries, pharmacies, care homes and clinics globally. EPM: What have you focussed on recently?

Q & A

CM: Our focus is always on making a difference. We know it is essential to design a device that meets tangible end-user needs and makes it easier for them to adhere to their self-management routines. In order to ensure we get this right every time, our human factors experts research the requirements of the end-users and health care professionals and involve them in the development process as a product is moved through the design process to industrialisation. This can include formative user studies that provide feedback on the initial design, preliminary models and soft tooled product, which mimics the final product manufacture. The key objective of user-centred healthcare is to improve the health outcomes of endusers by taking into consideration their needs, values, preferences and situation. By incorporating these requirements, our final product will not only benefit the end-user in the best way possible but also help reduce complaints, make it easier to obtain market acceptance, and increase the product lifecycle. EPM: What is your latest service / innovation? CM: Recently we were awarded the Red Dot award for Product Design for our new diabetes pen needle with built in remover, Unifine Pentips Plus. Unifine Pentips Plus is the world’s first pen needle with built in remover, developed for endusers with diabetes who are self-injecting insulin or glucagon-like peptide-1 analogues. Unifine Pentips Plus is designed to encourage adherence to a good injection routine and is proven to increase the rate of pen needle change among end-users. A study observing the impact of Unifine Pentips Plus on pen needle changing behaviour amongst people with diabetes, showed that when using Unifine Pentips Plus, the rate of pen needle change increased by 61% compared to their current pen needle. With analysis from 2012 estimating that more than half of the 100 million people in the world who use insulin, use a pen device, this product is an example of our focus on making life simpler for the end user. The major negative outcomes that can arise when not adhering to a good injection routine, including frequent change of the pen needle, can consist of infection, dose inaccuracy and bruising. EPM: How can you benefit the pharmaceutical sector? CM: In addition to end-users needs and adherence issues, we understand the complexities of creating medical devices for partners with complex requirements and international markets. We develop medical device solutions both for our own Owen Mumford brand and for some of the world’s leading pharmaceutical and diagnostic companies. We understand the importance of bringing a product to market on time and on budget. Our in-house research, design and engineering expertise are able to offer advanced concept to supply services, reducing the industrialisation risks associated with new product development.

EPM: Future plans? CM: The medical device market continues to grow and innovate and we continue to ensure that we invest in new resources to enable our research and design team to design, develop and industrialise all of our new concepts into final product, as rapidly and smoothly as possible. With advanced 3D printing capabilities we are able to effectively prototype our products early in the development stage and iterate rapidly as we amend and adapt the design to deliver the required end user outcomes. This allows the team to evaluate any potential issues with components, without having to go through lengthy and costly tooling activities. It also enables them to check how mechanisms work and how they look and feel, before committing to tooling. This allows us to ensure the product is suitable for the end-user as well as fit for industrialisation and manufacture. As we look ahead, our focus is on designing and manufacturing high quality products that meet and fulfil regulatory requirements and the end-user and healthcare provider industry’s needs. Our motivation is to make lives easier. As the market changes, we continue to innovate by bringing together world-class research, design and engineering expertise to create products that improve lives and reduce healthcare costs.

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Meet Q, MODUL Q

Discover the next generation of tableting technology Taking the concept of Infinite Possibilities one step further, GEA is pleased to announce the global launch of the MODUL Q rotary tablet press at this yearâ&#x20AC;&#x2122;s ACHEMA trade show. Where: ACHEMA 2015 Frankfurt am Main Germany Hall 4.0 Stand F46 When: Monday 15th June, 11am Tel: +32 2 363 8300

Email: pharma@gea.com

engineering for a better world

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NATOLI leads the industry in tablet compression tooling.

At Natoli Engineering Co., weâ&#x20AC;&#x2122;re proud to engineer punches and dies of superior quality. We use the highest quality steel paired with the latest manufacturing innovations, and all of our materials are tested for quality by our in-house metallurgist and an independent lab. Can your tooling supplier document steel quality like Natoli can? Find out at natoli.com. 68